The os trigonum is a common cause of posterior ankle impingement in children and adults. Its incidence in the medical literature is controversial. The aim of the study is to determine the incidence of os trigonum, medullary imaging features and size in pediatric patients with suspected posterior ankle impingement.Fifty-five children  who underwent magnetic resonance ımaging (MRI) with a pre-diagnosis of posterior ankle impingement syndrome (PAIS) were included in the study. Their ankle MRI and lateral radiograms were retrospectively reviewed. The relationship between os trigonum type, size, medullary signal characteristics, and PAIS development was investigated. Skeletal maturity was graded based on the ossification pattern of the calcaneal apophysis. The possible relationship between skeletal maturity and PAIS caused by os trigonum was investigated.Among the 55 participants, there were 14 participants diagnosed with PAIS . There was no connection between the os trigonum type, its medullary signal, gender, and PAIS clinical picture (p>0.05). The os trigonum size causing PAIS was 9±3.4 mm on average. There was a statistically significant relationship between PAIS complaints and os trigonum size (p=0.04). There was no significant relationship between calcaneal stage and PAIS clinical picture (p=0.669). When the os trigonum was fused, all participants were at calcaneal stage 3 or higher.MRI is superior in detecting fusion of the os trigonum with the talus, the medullary signal of ossicle, and PAIS findings. The most important factor in the development of PAIS is the size of the os trigonum. Posterior ankle impingement syndrome (PAIS) is a range of clinical disorders characterized by posterior ankle pain during plantar flexion [ flexion . PAIS ha flexion . Osseous flexion , 4. The  flexion . Os trig flexion , 6. In a flexion . There a flexion , 8. The  flexion . This in flexion . Assessm flexion , 6. OthePAIS is manifested by posterior ankle pain that develops during plantar flexion. Repetitive plantar flexion, overuse, recurrent trauma, congenital anatomic variations lead to this syndrome . CongeniSoft tissue lesions are flexor hallux longus tenosynovitis, synovitis, joint capsule, and compression of abnormal muscles . Accesso•Posterior ankle impingement syndrome (PAIS) is a common cause of ankle dysfunctions due to physical activity in childhood and adolescence.•Os trigonum is a common variation leading to posterior ankle impingement syndrome. While types of Os trigonum do not make a significant difference for PAIS formation, ossicular size is an important factor.•MRI is the most useful imaging method in revealing PAIS and its causes.The aim of this cohort study is to determine the incidence, medullary imaging features, and size of os trigonum in pediatric patients with suspected posterior ankle impingement.Before starting to collect data for the study, local ethics committee approval  was obtained. Unilateral 360 ankle MRI examinations performed on children aged 4–16 years who were referred to the imaging department between January 2015 and June 2020 due to foot-ankle pain, trauma, and infection pathologies were re-evaluated. Children with a history of hip, knee, foot-ankle trauma or surgery were excluded from the study. Children with metabolic and endocrine system diseases were not included in the study. Thus, the number of participants examined for foot-ankle pain fell to 112. It was seen that the number of children whose etiology of posterior ankle pain was investigated from hospital information system was 75. In other 37 pediatric patients, it was observed that intra-articular foreign body, bone-bone marrow involvement due to hematological and oncological malignancies, synovial pathology, and the etiology of dorsal foot pain were investigated. Fifty-five of 75 participants who had lateral ankle-ankle radiography in 1 month in addition to MRI were included in the study. Clinical findings, treatment practices, and results of these participants were completely recorded by the clinicians in the hospital information system. Demographic characteristics of all participants were similar. There were no professional athletes and heavy laborers among the participants.MRI images were acquired using a 1.5-T unit  and standard ankle coil. Fast spin-echo T1-weighted and T2-weighted images were obtained in the routine axial plane, oblique axial-coronal plane, and oblique axial-sagittal plane. MRI parameters were listed as follows: repetition time/echo time, 400/12 ms for T1-weighted and 3600/85 ms for T2-weighted images; echo train length, 3 for T1-weighted and 20 for T2-weighted images; field of view 180 mm; slice thickness 3 mm; and interslice gap 1,5 mm. Those with protocol errors and artifacts in MRI examinations were excluded from the study.Bone age evaluations of the participants with os trigonum were performed using calcaneal epiphysis staging from lateral radiographs of the ankle and foot .All radiological reassessment was performed by a pediatric radiologist with 10 years of professional experience. MRI images were reassessed, blinded for patient characteristics for the talocalcaneal joint, the presence of medullary edema in the posterior part of the talus and calcaneus, the presence of osteophytic formation originating from the talus or calcaneus, the presence of os trigonum variation, and the presence of fluid in the paratendinous area in front of the Achilles Tendon were re-evaluated by same radiologist. These changes identified in imaging were used for the diagnosis of PAIS , 16. TheThe os trigonum was grouped into three different types in X ray, based on Zwiers et al.’s  classifiThe relationship between os trigonum and the presence of PAIS was evaluated. The possible connection between the calcaneal epiphyseal stage and os trigonum size, this osscile’s MRI signal features were investigated.st type error was 5%. Whether the continuous measurements in the study were normally distributed or not was checked with Kolmogorov-Smirnov (n>50) and Skewness-Kurtosis tests, and parametric tests were applied because the measurements were normally distributed. Descriptive statistics for continuous variables in our study; mean, standard deviation, minimum, maximum; For categorical variables, it was expressed as numbers and percentages. Independent T-test and One Way Analysis of Variance were used to compare all continuous measurements according to groups. Pearson correlation coefficients were calculated to determine the relationships between measurements. Chi-square test was used to determine the relationship between categorical variables. In the calculations, the statistical significance level was taken as (a) 5% and the SPSS  statistics package program was used for calculations.In calculating the sample size of this study, the power (power of the test) for each variable was determined as at least 80% and the 1The mean age of 55 participants  whose unilateral ankle images were selected was 13.7±0.23 years. Average age was 14±2.2 years for girls and 13.6±2.7 years for boys .When gender was ignored, 14 of the participants had type I (25%), 30 of them had type II (55%) , 11 of them had type III (20%) os trigonum. Of the 14 participants who were diagnosed with radiological PAIS, 11 had type II (78%) and 3 had type I (22%) os trigonum. There was no statistical relationship between ossicle type and gender (p=0.554). In addition, a statistically significant relationship was not observed between the development of PAIS and the os trigonum type (p=0.90).The mean age of 14 participants diagnosed with PAIS among 55 participants was 15±1.2 years. Of the 14 cases, nine were boys (64%), five were girls (36%). There was a significant statistical relationship between PAIS and os trigonum size (p=0.04). The average size according to the os trigonum measurements made in the anteroposterior direction in all participants was 7.3±2.6 mm. This size was 9±3.4 mm and significantly larger in participants with PAIS .The edema and sclerosis signal was sought by evaluating the medullary area signal in the os trigonum. When gender difference was ignored, medullary sclerosis in the ossicle of 28 participants (50.9%) and medullary edema in the ossicle of 12 participants (21.8%) was detected. Of the os trigonums detected in participants with radiological and clinical diagnosis of PAIS, 5 (36%) had medullary sclerosis and 4 (28%) had partial medullary edema. There was no change in the medullary signal in the five ossicles (36%). There was no statistical relationship between participant’s age, gender, calcaneal stage, and presence of os trigonum edema and sclerosis on MRI (respectively p=0.281–0.829).The number of participants whose os trigonum fusion was completed was 22 (40%). Of these participants, 12 were boys (55%) and ten were girls (45%). The mean age of completed os trigonum fusion was 15±1.8 years. The average age was found to be 15±0.8 years for girls and 15±1.4 years for boys. The fused os trigonum was type I in 4 (18%), type II in 14 (64%), and type III in 4 (18%) of the participants. When gender was ignored, the calcaneal ossification stage determined was on average 3.8±0.6. There was no difference in the grading of calcaneal skeletal maturity stages during fusion between boys (mean stage 3.8±0.8) and girls (mean stage 3.94±0.4) (p=0.669). When os trigonum fusion was detected, all participants were at stage 3 or higher .As the calcaneal stage increased, a higher rate of fusion was seen (p<0.001). When the relationship between os trigonum fusion and its size was evaluated, the mean size of the fused ossicles was found to be 8.7±2.7 mm. The non-fused ossicle size was on average 6.3±2.1 mm. A significant relationship was found between talar fusion and os trigonum size (p<0.001). It was seen that the possibility of talar fusion increases as the ossicle grows.The os trigonum is known as one of the most common causes of PAIS. However, there is no consensus on the definition and incidence of the os trigonum. In our study, we aimed to determine the incidence, medullary imaging characteristics, and size of os trigonum in pediatric patients with suspected posterior ankle impingement. According to our results, os trigonum type, medullary signal of the ossicles, gender were not associated with PAIS development. We found a significant correlation between PAIS complaints and os trigonum size. There was no relationship between the calcaneal stage and PAIS clinical picture.In the study of Zwiers et al. , the preThere was no difference in the grading of skeletal maturity according to calcaneal ossification stages during fusion between boys and girls (p=0.5). All participants were at stage 3 or higher during os trigonum fusion . The reaWhen os trigonum is symptomatic, primary care includes: conservative management with reducing or changing the activity, supplementary insoles, safety shoes, nonsteroidal anti-inflammatory drugs. According to the results of the studies of Knapik et al. ; conservThis cohort study is superior in that evaluation of the ossicular presence, size, medullary signal, talar fusion, and effects on surrounding tissues is done by examination on MRI images. Another advantage is that the diagnosis of PAIS can be definitively identified radiologically. This study does have a number of limitations. The number of participants who could be included in the study was low due to the small number of ankle MRI examinations performed for PAIS. Another limitation is that the side of the ankles examined could not be standardized. During reassessment, the ankles from which the images were taken were either the right or the left side. An important limitation was that all imaging was obtained from the symptomatic side and the evaluations were unilateral. When evaluating the os trigonum medullary signal change, it was not known how long after the onset of PAIS in most of the participants imaging was performed. Since there is no statistical relationship between medullar signal change and other parameters, this has a limited effect on the result.Os trigonum is among the causes of PAIS in all age groups. Os trigonum should be investigated when evaluating posterior ankle pain in children and adolescents. MRI examination is superior in detecting fusion of the os trigonum with the talus, the medullary signal of ossicular formation, and PAIS findings. While types of Os trigonum do not make a significant difference for PAIS clinic, ossicular size is an important factor. As its size increases, the fusion of the ossicle and talus increases. According to the results of the current study, it is seen that fusion develops as the age increases. It can be said that PAIS, which develops due to the os trigonum, develops more frequently in older children with larger and fused ossicles.


The aim of the present study was to identify the profile of cancer patients in need of rehabilitation with dental and/or oral-maxillofacial prostheses and evaluate possible reasons for not concluding the rehabilitation process.A retrospective observational study was conducted at the Dentistry Department of the Mato Grosso Cancer Hospital in the city of Cuiabá, Brazil, involving the analysis of the medical records of patients under care from April 2017 to November 2019.The study population comprised 256 patients who met the inclusion criteria. A total of 30.90% of the patients were older adults, 65.6% were men, 70.3% had brown skin color, 27.3% were retired, 49.2% were married and 52% resided in municipalities in the state of Mato Grosso other than the capital. A total of 67.23% reported smoking and 53.9% reported alcohol consumption. The tumor was located in the head and neck region in 57.4%. The most frequent histological type was epidermoid carcinoma (55.1%). A total of 28.9% of cases were in disease stage IV. Most patients (60.2%) completed prosthetic rehabilitation, with a predominance of total prosthesis. The main reasons for not completing rehabilitation were the patient’s death and weakness.Patients who started treatment in more advanced stages of cancer had a greater chance of not completing the prosthetic rehabilitation. The non-completion of treatment was directly related to death and the state of weakness. Key words:Cancer, dental prosthesis, epidemiology, maxillofacial prosthesis, oral rehabilitation. Cancers of the head and neck region profoundly affect the quality of life of patients due to the effect on esthetics, serving as a constant reminder of the disease. These cancers are emotionally draining for patients and their families .Indeed, the diagnosis of cancer exerts a negative impact on the patient’s life. Fear and suffering are common throughout the process, which begins with the diagnostic phase and is followed by therapy and survival ,3. Most Cancer treatment has side effects ranging from mild to severe . Large fIn the treatment of tumors of the head and neck region, patients are also often submitted to surgeries that have a serious impact on quality of life, appearance and functional characteristics . MutilatProsthetic treatment is indicated for the recovery of lost oral functions and an improvement in physical appearance, enabling patients to participate in daily activities with greater confidence . The absGiven the need for dental care among cancer patients and the positive impact of rehabilitation on their quality of life, the aim of the present study was to outline the profile of cancer patients rehabilitated with dental and/or oral-maxillofacial prostheses and investigate reasons for the non-completion of rehabilitation process.-Population Data collection involved the analysis of the medical records of patients treated at the Dentistry Department of the Cancer Hospital of Mato Grosso in the city of Cuiabá, MT, Brazil, from April 2017 to November 2019. This period was selected because the hospital currently uses a single medical record for each patient and the medical records are managed by an information system that was installed in April 2017.A search for relevant cases was performed in the Care Management System for the determination of all patients with an indication for prosthetic rehabilitation treatment in the period. Patients of both sexes and of any age were included. Patients having undergone rehabilitation but with no confirmed diagnosis of cancer and those for whom it was not possible to collect data from the respective medical records were excluded.-Data collectionInstituto Brasileiro de Geografia e Estatistica Brazilian Institute of Geography and Statistics]), place of residence , occupation, marital status, smoking habit, drinking habit, family history of cancer.Data were collected on age, sex, skin color , characteristics of prosthetic rehabilitation  and reason for not completing rehabilitation.Patients who met the inclusion criteria but whose medical records did not present information on completing rehabilitation or the installation of the prosthesis were actively contacted by telephone and asked about the reason for not completing rehabilitation treatment. The answers (provided by the patient or family member) were placed into five distinct groups: patient died before completing rehabilitation treatment; patient interrupted treatment because of weakness; patient is still undergoing rehabilitation treatment; patient completed the rehabilitation elsewhere; and no defined response (cases for which telephone contact was unsuccessful).-Data analysisp-value <0.05 were considered statistically significant.A single researcher collected and organized the data on an Excel spreadsheet. Descriptive statistical analysis was performed for the variables of interest. The data were expressed as absolute and relative frequencies. Multinominal logistic regression was performed to analyze possible associations between the independent variables and dependent variables (not completing prosthetic rehabilitation and reason for not completing rehabilitation), as described elsewhere . StatistFour hundred seventy hospital records were analyzed, 256 of which met the inclusion criteria. Exclusions were due to the non-confirmation of a diagnosis of cancer or the impossibility of collecting data from the medical record.Age in the sample ranged from 30 to over 70 years. The highest percentage of patients  was between 61 and 70 years of age. The least frequent age group was 30 to 40 years of age . Male patients predominated  over female patients . The most prevalent skin color was brown . Almost half of the patients resided in the state capital  and slightly more than half resided in other municipalities of the state . Seventy patients (27.3%) were retired; 126 patients (49.2%) were married; 172 patients reported smoking (67.2%), 138 patients (53.9%) reported alcohol consumption and 130 (50.8%) had a family history of cancer .Regarding cancer treatment, 180 patients (70.3%) underwent surgery, 182 (71.1%) underwent radiotherapy and 162 (63.3%) underwent chemotherapy. The most frequent tumor location was the head and neck region , followed by the breast . The most frequent histological type was squamous cell carcinoma . Among the patients with data on the stage of the disease when the diagnosis was made, 74 (28.9%) were in stage IV .Among the 256 medical records analyzed, 154 patients (60.2%) completed prosthetic rehabilitation and 102 (38.8%) did not complete rehabilitation at the Dentistry Department of the Mato Grosso Cancer Hospital. Among the 154 patients who completed the rehabilitation treatment, 148 (96.01%) received a maxillary prosthesis, among which 102 (68.9%) were total prostheses, 35 (23.6%) were partial prostheses, nine (6.1%) were total obturators and two (1.4%) were partial obturators. Among the 126 (81.8%) patients who received a mandibular prosthesis, 81 (64.3%) were total prostheses and 45 (35.7%) partial prostheses. Three patients received facial prostheses (1.2%). Among the 102 patients who did not complete rehabilitation, 30 (29.4%) died before completing prosthetic treatment, 26 (25.5%) were very debilitated by the disease or had health problems that prevented the continuation of rehabilitation, 18 (17.6%) were still undergoing rehabilitation, 10 (9.8%) finished treatment elsewhere and 18 (17.6%) qualified for “undefined reason for not concluding treatment”, as contact via telephone was not possible , whereas no other independent variables  were significantly associated with the completion/non-completion of prosthetic rehabilitation  and the completion/non-completion of prosthetic rehabilitation. Patients with advanced stages of cancer were less likely to complete treatment (litation .p = 0.041). A significant association was also found between cancer staging and completed treatment elsewhere (p = 0.007), as patients in more advanced stages were less likely to complete prosthetic rehabilitation at the Cancer Hospital of Mato Grosso. Place of residence and age were not significantly associated with the reason for the non-completion of prosthetic treatment  and the reason why prosthetic rehabilitation was not completed . A statistically significant association was found between the stage of cancer and not having completed prosthetic rehabilitation due to weakness , breast (12.1%) and prostate (10.3%). Breast and prostate cancer are among the most prevalent forms of cancer in Brazil . The greThe most frequent histopathological diagnosis was epidermoid carcinoma  and the most frequent disease stage was IV . Epidermoid carcinoma is the most frequent malignancy among tumors of the head and neck region and the sixth most common cancer globally .et al.  completed prosthetic rehabilitation, involving a total of three facial prostheses, 148 maxillary prostheses including 11 obturators and 126 mandibular prostheses. Quispe et al.  evaluate . A total of 28.9% of cases were in disease stage IV. The patients underwent surgery, radiotherapy and chemotherapy. Total prosthesis was the most common form of rehabilitation. Patients who started treatment in more advanced stages of cancer had a greater chance of not completing prosthetic rehabilitation and the main reasons for the non-completion of treatment were death and weakness.


Flufenamic acid (FFA) is a non-steroidal anti-inflammatory drug characterised by a low solubility and problems of variable dissolution rate and bio-inequivalence. Different FFA batches, obtained by different suppliers, showed different powder characteristics  that may affect its dissolution behaviour from solid dosage forms. Aim of this work was the improvement of FFA solubility and dissolution rate by the use of cyclodextrins (CDs) and the obtainment of an effective tablet formulation by direct compression. Several CDs have been tested, both in solution and in solid state and several binary systems drug-CDs have been obtained with different techniques, with the scope to select the most effective system. Grinding technique with randomly methylated-β-cyclodextrin (RAMEB) was the only one that allowed the complete drug amorphization, together with the highest improvement in drug dissolution rate, and was then selected for tablets formulation. Conventional and immediate release tablets were obtained and fully characterised for technological properties. In both cases an improved and well reproducible drug dissolution performance was obtained, independently from the FFA supplier and thus no more affected by the differences observed between the original FFA crystalline samples. Oral route is the main way of administration of drugs, especially by the use of tablets. The bioavailability of an orally administered drug mainly depends on its solubility in the gastrointestinal tract fluids and its permeability through the biological membranes : its disTwo different batches of flufenamic acid (2-{[3-(trifluoromethyl) phenyl] amino} benzoic acid), FFA) were used: a batch donated by S.I.M.S. (FFA SIMS)  (purity 99.97% ) and ano1:1 and the complexation efficiency (CE) of the complexes were calculated as follows [Phase solubility studies were carried out by adding an excess amount of FFA (100 mg) to 10 mL of phosphate buffer pH 6.8 containing increasing concentrations of CD (0–25 mM or 0–12.5 mM in case of βCD). The vials were sealed and electromagnetically stirred (750 rpm) at constant temperature (37 °C) until equilibrium (3 days). An aliquot of solution was then withdrawn with a filter syringe (pore size 0.45 μm) and spectrometrically assayed for drug concentration at 290.8 nm . The presence of CD did not interfere with the spectrophotometric assay of FFA. Each experiment was performed in triplicate (coefficient of variation (CV) <2.5%). The apparent 1:1 stability constant K follows :K1:1 = mv/v) solution and kneading thoroughly with a pestle to obtain a homogeneous slurry and continuing until the solvent was completely removed, and then drying the products in a vacuum desiccator for 24 h to remove traces of solvent; co-evaporated products (COE) were obtained by co-evaporation of equimolar FFA/CD ethanol–water 1:1 (v/v) solutions in a rotary evaporator at 70 °C and drying the resulting products in a vacuum desiccator for 24 h to remove traces of solvents; co-lyophilised products (COL) were prepared by freeze-drying at 50 °C and 1.3 × 10−2 mmHg equimolar drug–CD aqueous solutions .Drug–CD solid systems were prepared in equimolar ratio, based on the results of phase-solubility studies, indicative of the formation of 1:1 (mol/mol) FFA–CD complexes. Five different methods were used for their preparation. Physical mixtures (PM) were obtained by tumble mixing for 15 min equimolar amounts of the respective components (75–150 µm sieve granulometric fraction); co-ground systems (GR) were prepared by ball-milling for 30 min at 24 Hz physical mixtures in a high-energy vibrational micro-mill ; kneaded products (KN) were prepared by wetting the physical mixture with a small volume of an ethanol–water 1:1 . Briefly FFA, CDs and the obtained binary systems were weighed with a Mettler MX5 Microbalance (5–10 mg), and scanned in Al pans pierced with a perforated lid under static air with a heating rate of 10 °C/min, from 30 °C to 200 °C. The instrument was calibrated with standard Indium samples for temperature and heat flow. Drug melting enthalpy values were obtained by the area under the curve of the drug melting endotherm, calculated by the Software of the Mettler TA4000 calorimeter, and referred to the weight of FFA in each sample. Data are the mean of three determinations.Binary systems were characterised by differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD). Thermal analysis was performed with a Mettler TA4000 StarFor each sample, the percentage of residual crystallinity (% Rc) of drug was calculated as follow:®) was used as a detector, and C/Ni Goebel-Spiegel mirrors in the incident beam were used as monochromators. All samples were examined at room temperature.A Bruker D8-advance  X-ray powder diffractometer was employed for recording the diffraction patterns of drug and drug–CD binary systems. The parameters were: Cu Kα radiation = 1.54056 Å, voltage 40 kV, current 40 mA and 2θ over a 5–30° range at a scan rate of 0.05°/s with 0.02° increments and a step time= 0.8 s/step. A Si (Li) solid-state (Sol-XIn vitro dissolution studies of the prepared solid products were performed using a modified dispersed amount method . BrieflyTablets were prepared by direct compression (2.5 tons for 3 min) of the powders with a hydraulic press. The tablets were prepared using the selected drug-CD binary system FFA-RAMEB GR 1:1 mol/mol (50 mg FFA and 233 mg of RAMEB) and, as comparison, the simple PM and FFA alone, as references. For immediate release tablets (IRTs) the excipients used were spray-dried lactose (100 mg), starch (50 mg) and magnesium stearate (0.1%). For conventional tablets intended for enteric coating (CTs) a dry binder  was added to the previous formulation. Conventional tablets were prepared using both FFA SIMS and FFA TCI samples.All tablets were characterised for drug content, mean weight, diameter, thickness, friability, hardness, disaggregation time, according to official F.U. XII and Ph. Eur. X. Dissolution studies of FFA from tablets were performed as described above for FLU-CD binary systems; experiments were repeated three times (CV < 4.0%). Dissolution efficiency at 60 min (DE60) was calculated from the area under the dissolution curve at time t  and expressed as a percentage of the area of the rectangle described by 100% dissolution in the same time . ConventIn order to evaluate and compare the complexing and solubilising abilities of the different CD towards FFA, phase solubility studies have been performed in phosphate buffer (pH 6.8) with the three natural Cds, α, β and γCD and three β-derivative CDs, RAMEB, HPβCD and SBEβCD. Since no differences were previously observed in the equilibrium solubility value of FFA obtained from SIMS or TCI suppliers , phase sAs shown in Binary systems of FFA with the different examined CDs were then prepared with several methods , and carefully characterised, in order to evaluate the effect of the preparation technique on the properties and performance of the obtained products. This is particularly important in the case of FFA, since, as above discussed, it may exist in two main polymorphic Forms (I and III), enantiotropically related, being Form I the metastable one below the transition temperature (42 °C) , and polResults of DSC studies are summarised in The melting endotherm of pure FFA peaked at 135.6 °C (TCI) or at 135.5 °C (SIMS), confirming that it was provided by both suppliers in the polymorphic Form I.The drug melting peak was clearly evident in all binary systems with native crystalline βCD, even though a progressive significant decrease of fusion enthalpy indicating loss of drug crystallinity was observed when passing from the PM to KN, COE, GR and COL products .The same trend in enthalpy of fusion reduction, and then in decline of drug crystallinity was observed in the case of various FFA binary systems with the amorphous derivatives HPβCD and SBEβCD, but the effect was clearly more evident, achieving a % residual crystallinity in GR and COL products ranging from 14 to 10%. This result was considered indicative of establishing more effective drug-CD solid state interactions with such amorphous βCD-derivatives, and confirmed grinding and co-lyophilisation as the better preparation techniques to bring about their formation. On the other hand, this effect was even more marked for FFA products with RAMEB, which showed the highest complexing/amorphizing properties, giving rise to the complete disappearance of the drug melting peak in all binary systems except the simple PM.It is also interesting to point out the shift of drug melting peak from 135 to about 125 °C observed in the case of COE products with βCD, HPβCD and SBEβCD, all obtained by evaporation of a hydroalcoholic solution. An analogous shift of drug melting peak from 135 to about 125 °C was previously observed also on pure drug samples obtained by recrystallisation from hydroalcoholic solution at 78 °C, and DSC and XRPD analysis proved that it was due to the formation of its polymorphic Form III [XRPD studies have been performed to confirm these results and exclude any possible influence of the DSC technique, since the thermal energy provided to the sample during the analysis could bring about the drug amorphization process in the presence of the amorphous carrier.XRPD diffractograms of the different binary systems of FFA with SBEβCD and RAMEB are reported in The XRPD analysis of GR FFA-RAMEB repeated after 1 year from the sample preparation allowed to establish the maintenance over time of complete sample amorphization.The dissolution behaviour of all drug-CD binary samples has been evaluated and compared with that of drug alone as (Form I) . Almost In The FFA-RAMEB GR product, selected as the binary system that better improved drug solubility, was used to prepare immediate release tablets (IRT), able to give a rapid release and absorption of the drug, for the treatment of acute diseases, and conventional tablets suitable for enteric-coating (CT), more appropriate for the treatment of chronic diseases, that require prolonged drug administration and then the need of minimising the drug irritant effect towards the gastric mucosa. All tablets were prepared by direct compression, which is considered as a more advantageous process than wet granulation in terms of cost effectiveness (lesser processing steps and equipment), higher stability (for moisture- or heat-sensitive drugs), reduced transfer losses and contamination risks, and faster and more reproducible drug dissolution profiles, being this last a particularly beneficial effect for poorly soluble drugs ,27. SpecIn order to evaluate the role of the RAMEB presence and of the preparation method used for obtaining the drug-CD binary system, IRT and CT tablets containing the FFA-RAMEB system as GR product were then prepared and compared with analogous tablets containing FFA as such or as simple PM with RAMEB. The obtained tablets were characterised for drug content, mean weight, mean diameter, thickness, hardness, disaggregation time and dissolution properties. The results of these studies are summarised in As for the technological properties, all manufactured tablets showed good quality attributes, particularly in terms of weight uniformity (RSD < 1%) and drug content uniformity (RSD < 1.3%) . In all Previous studies performed on pure drug samples provided from different suppliers (SIMS and TCI) showed that contact angle values of FFA TCI compacts were significantly lower than those of FFA SIMS compacts, indicative of a better wettability of their surface, reflected in a significantly higher intrinsic dissolution rate . Since sAs shown in In order to obtain more insight about these results, the role of the tablet surface wettability in the differences observed between tablets obtained with FFA SIMS and the corresponding ones obtained with FFA TCI was then investigated.The contact angles between a water droplet and CTs containing FFA from SIMS or TCI, alone or as PM or GR with RAMEB were measured and the results are shown in p < 0.05) than those containing FFA SIMS, thus explaining the greater dissolution rate of FFA TCI than FFA SIMS when formulated in tablets. This phenomenon could be attributable to the different surface characteristics of their crystalline powders that led to a higher compactability of FFA SIMS with respect to FFA TCI, as observed in previous study [The presence of RAMEB enhanced the wettability of the tablets in any case due to the high hydrophilicity of this excipient. CTs containing FFA TCI  showed a wettability significantly better  or conventional tablets suitable for enteric coating (CTs). A comparison with the corresponding tablets containing the drug as such or as simple physical mixture (PM) with RAMEB evidenced a strong improvement of drug dissolution properties, with an increase, respectively, of 4.0 and 1.6 times (for IRT) or 5.6 and 3.0 times (for CTs) of the percent dissolved at 10 min.Moreover, in the attempt to gain insight about the unexpected difference in intrinsic dissolution rate constant presented by FFA samples from different suppliers , CTs werThe use of the amorphous co-ground product of FFA with RAMEB enabled to obtain tablets with good and well reproducible dissolution profiles, not affected by the different crystalline properties of the original FFA powder, thus resulting a useful tool for an effective oral administration of this recently rediscovered drug.


Augmented Reality (AR) is a rapidly emerging technology finding growing acceptance and application in different fields of surgery. Various studies have been performed evaluating the precision and accuracy of AR guided navigation. This study investigates the feasibility of a commercially available AR head mounted device during orthopedic surgery.Thirteen orthopedic surgeons from a Swiss university clinic performed 25 orthopedic surgical procedures wearing a holographic AR headset  providing complementary three-dimensional, patient specific anatomic information. The surgeon’s experience of using the device during surgery was recorded using a standardized 58-item questionnaire grading different aspects on a 100-point scale with anchor statements.Surgeons were generally satisfied with image quality (85 ± 17 points) and accuracy of the virtual objects (84 ± 19 point). Wearing the AR device was rated as fairly comfortable (79 ± 13 points). Functionality of voice commands (68 ± 20 points) and gestures (66 ± 20 points) provided less favorable results. The greatest potential in the use of the AR device was found for surgical correction of deformities (87 ± 15 points). Overall, surgeons were satisfied with the application of this novel technology (78 ± 20 points) and future access to it was demanded (75 ± 22 points).AR is a rapidly evolving technology with large potential in different surgical settings, offering the opportunity to provide a compact, low cost alternative requiring a minimum of infrastructure compared to conventional navigation systems. While surgeons where generally satisfied with image quality of the here tested head mounted AR device, some technical and ergonomic shortcomings were pointed out. This study serves as a proof of concept for the use of an AR head mounted device in a real-world sterile setting in orthopedic surgery.The online version contains supplementary material available at 10.1186/s12891-021-04339-w. Precise positioning of mechanical elements including screws, surgical guides, prosthetic components and anchors to restore anatomy and function remains a desirable goal in orthopedic surgery . Image-bAugmented Reality (AR) is a rapidly emerging technology providing the user with computer-generated information superimposed to real-world environment. The user’s field of view is transformed into a display where real-world objects can be complemented with virtual data. This way information including drilling axis or cutting planes can be projected directly onto the patients’ anatomy within the surgical field. Although its application in orthopedic surgery today remains limited, AR was gradually introduced in different experimental medical and surgical settings –16. ReceOrthopedic surgeons from a single Swiss university clinic where the subject of this prospective study. Surgeons were asked to wear a commercially available holographic AR headset  during surgery after receiving an introduction explaining its functionality and time to test voice commands and hand gestures.For each operation, a three-dimensional triangular surface model of the patients readily available CT data was generated using a commercial software  . Only alDuring the operation, the three-dimensional model of the patients CT-data was displayed holographically in the surgeon’s field of view in addition to routinely mounted radiological imaging on conventional screens. The displayed surface model could be moved, rotated, scaled and placed using contactless hand gestures and voice commands Fig. . The timThe device was evaluated using a standardized 58-item questionnaire administered as an electronic survey using the REDCap data capture tool . The surDescriptive analysis was performed using SPSS . Continuous variables are reported as mean ± standard deviation (SD).Thirteen orthopedic surgeons from different subspecialties  participated in this study. Four surgeons performed > 500 cases per year, 3 surgeons 251–500 and 6 surgeons 51–250 surgeries per year. Six surgeons were in the position of chief of service and 7 surgeons were attending physicians or fellows. In total, 25 surgeries  were included in this study.The general acceptance of the AR device was good Fig. . WearingConsidering usability Fig. , surgeonMost surgeons used the AR device for less than 60 min (23/25 surgeries) and no surgeon used the device for the entire surgery. All but three surgeons used the AR device only for preoperatively defined surgical steps Fig. .Fig. 7BThe most frequent reasons for early termination of use were impaired sight caused by the device (3/25) and surgical steps requiring other instruments (3/25) Fig. . HoweverThe greatest potential in the use of the AR device was found for surgical correction of deformities (87 ± 15 points), osteotomies (82 ± 17 points), revision surgery (77 ± 22 points), and tumor surgery (77 ± 21 points), whereas lowest potential was found for arthroscopic (32 ± 25 points) and reconstructive surgery (41 ± 22 points) Fig. .Fig. 9BPotential for future use within the orthopedic subspecialties was highest estimated for application in spine (86 ± 13 points) and pelvic surgery (88 ± 13 points).The greatest benefits of AR technology were expected to be increased intraoperative accuracy (78 ± 23 points), improved surgical outcome (77 ± 22 points) and reduction of exposure to radiation (72 ± 26 points) Fig. .Fig. 10Overall, surgeons were satisfied with the application of this novel technology (78 ± 20 points) and future access to it was demanded (75 ± 22 points).This prospective clinical study offers a proof of concept of the clinical feasibility of a wearable augmented reality device for using three-dimensional virtual object reconstructions of individual patients’ anatomy as an intraoperative aid during orthopedic surgical procedures. Thirteen surgeons from different orthopedic subspecialties used an AR headset as an additional display providing complementary three-dimensional, patient specific anatomic information during 25 surgical procedures. The surgeons experience with the device was recorded using a standardized questionnaire.Augmented reality is rapidly developing technology that can display a vast variety of information within the field of view of the user using a compact device with minimum infrastructure. Spatial mapping and recognition of the physical environment is a crucial difference between augmented reality and other navigations systems using conventional display methods. Projecting the required information directly into the line-of sight of the surgeon is considered the natural progression of these well-established methods mitigating the errors associated with attention shift by directly projecting the navigation guidance onto the surgical field , 23. IncThe here used iteration of the HoloLens offers a rather narrow diagonal angle of view of 34° for projection of virtual objects. However, for most surgical tasks requiring high precision, a narrow field of view is sufficient and this study, surgeons were generally satisfied with the quality of the displayed three-dimensional images.n = 2) might also be explained by the fact that participants were only supplied with supplementary information required for essential steps of the surgery. Hence, the threshold for removing the device, in particular while performing the surgical approach and during wound closure was low.The general acceptance of the device was fairly good. Considering comfort, the mostly frontloaded weight of 579 g and the size of this first iteration of the HoloLens was considered as a shortcoming. During 6 of 25 cases, the device was worn for more than 30 min, and in another 7 of 25 cases, for 15–30 min. However, despite its weight and size, most surgeons participating in this study estimated that the device could be worn for more than an hour when considering comfort. Other authors investigating the usability of the HoloLens during neurosurgical procedures graded the comfort more favorable , 26. ThiThe questionnaire also revealed technical limitations of the device, namely the voice command and gesture function. Using voice commands as a mean of interaction with the headset was less favorably graded. In most cases the recognition of voice commands was impaired by loud environment in the operation room. Other reports analyzing the usage of the HoloLens device for different surgical specialties reported more stable results using voice commands . This diSurgeons saw the biggest potential for this technology in complex surgical procedures including revision surgery, deformity correction, tumor surgery and trauma where typical anatomical landmarks are frequently not easily identifiable. However, a crucial step to provide reliable navigation in complex surgery is the registration process, the automated and precise overlay of virtual information with the real environment. Various methods of registration have been described including ultrasound-based techniques, reflective markers and non-invasive skin placed markers , 23, 27.In summary, AR is a rapidly evolving technology with large potential in different surgical settings, offering the opportunity to provide a compact, low cost alternative requiring a minimum of infrastructure compared to conventional navigation systems. While surgeons where generally satisfied with image quality of the here tested head mounted AR device, some technical and ergonomic shortcomings were pointed out. This study serves demonstrates the feasibility of the use of an AR head mounted device in a real-world sterile setting in orthopedic surgery.Additional file 1.


E/Z isomerization. Moreover, the newly formed Z isomer exhibits significantly reduced antibacterial activity, which hampers the development and biological evaluation of albicidin and potent derivatives thereof. Hence, we synthesized 13 different variants of albicidin in which the vulnerable para‐coumaric acid moiety was replaced; this yielded photostable analogues. Biological activity assays revealed that diaryl alkyne analogues exhibited virtually undiminished antibacterial efficacy. This promising scaffold will therefore serve as a blueprint for the design of a potent albicidin‐based drug.The natural product albicidin is a highly potent inhibitor of bacterial DNA gyrase. Its outstanding activity, particularly against Gram‐negative pathogens, qualifies it as a promising lead structure in the search for new antibacterial drugs. However, as we show here, the N‐terminal cinnamoyl moiety of albicidin is susceptible to photochemical  Lead optimization: The cinnamoyl residue of the antibiotic albicidin is shown to readily undergo UV‐mediated E/Z isomerization, thereby converting from the highly bioactive E form found in the natural product to the significantly less bioactive Z form. Acetylenic replacement of the susceptible methylacrylamide moiety affords a set of photochemically stable albicidin derivatives with virtually undiminished antibacterial activity. The global spread of antimicrobial resistance (AMR) increasingly renders medications used to treat life‐threatening infections ineffective and thus poses an imminent danger to millions of people.DMSO was exposed to UV light (λ=366 nm) in a time‐dependent manner and monitored by 1H NMR spectroscopy  measurements, which unambiguously confirmed the expected atomic distances in the two isomeric states . While only a small portion of the initial E state (t=0 h) was converted after t=2.5 h, an almost complete conversion to the Z isomer was detected after t=16 h. At this point, the equilibrium state had already been reached (ca. 85 % Z form) and no further conversion was observed at t=32 h . It is important to note that significant accumulation of the (Z)‐isomer also occurred when albicidin samples were exposed to sunlight  underlining the vulnerability of 1 during routine handling. These findings became even more relevant when we determined minimal inhibitory concentrations (MICs) against a panel of bacteria (Table S1). Depending on the bacterial strain, the Z isomer exhibited a five‐ to tenfold decline in antibacterial activity compared to the well‐characterized E isomer of albicidin. Accordingly, the Z isomer was incapable of inhibiting DNA gyrase when provided at the IC50 value (45 nm) of the potent E isomer . The fact, that the albicidin producer X. albilineans inhabits the xylem of sugar cane, which is exposed to sunlight, could severely impact the stability of albicidin. Given these structural and functional differences between the isomeric states that complicate SAR studies, we envisaged a photochemically more robust scaffold of albicidin without compromising its biological activity.To demonstrate the photochemical  with an alkyne, thus replacing the cinnamoyl‐pABA with diarylalkyne carboxylates. We first prepared a set of five derivatives with varying substituents in the para‐position of the aromatic ring . Based on previous findings,5 to test the effect of a heterocyclic replacement in the aromatic ring adjacent to the para‐substituent on the biological activity of these derivatives.In our initial rationale we envisioned a synthetically feasible structural modification that could be considered a surrogate for 26 was prepared from the fluoropyridine precursor 25 through a nucleophilic aromatic substitution reaction using aqueous potassium hydroxide , albicidin (1), azahistidine‐albicidin (2) and the newly synthesized derivatives 3–10 were determined for a panel of six different bacterial strains (Table 1). Cyano analogue 7 turned out to be the most active para substituent, showing low MIC values similar to those of CIP and azahistidine‐albicidin (2). Direct comparison of methoxy variant 4 and methoxypyridine variant 5 revealed that heterocyclic replacement of the aromatic ring did not have any effect on the antibacterial activity of the compound.The acetylenic A−B building blocks were prepared from commercially available aryl alkynes and aryl halides employing well‐established palladium‐mediated cross‐coupling chemistry Scheme A–E.+ 826.2467; found 826.2454 (Δm=−1.6 ppm), tR=8.38 min.Final derivative 4: Synthetic protocol analogous to compound 3. The title compound 4 was obtained as a colorless solid . 1H NMR : δ=11.54 , 11.19 , 10.55 , 9.69 , 8.95 , 8.06 , 7.97 , 7.92 , 7.75–7.84 , 7.63 , 7.56–7.61 , 7.51–7.56 , 6.98–7.04 , 4.88–4.97 , 3.91 , 3.80 , 3.78 , 3.19–3.35 . 13C NMR : δ=133.4 (Ar), 131.4 (Ar), 129.0 (Ar), 128.1 (Ar), 128.1 (Ar), 125.8 (Ar), 125.6 (Ar), 119.1 (Ar), 115.2 (Ar), 114.9 (Ar), 110.8 (Ar), 60.8 (OMe), 60.8 (OMe), 55.7 (OMe), 54.5 (α‐C), 27.6 (β‐C). HRMS (ESI): m/z calcd for C44H37N7O11 [M+H]+ 840.2624; found 840.2626 (Δm=+0.2 ppm), tR=9.38 min.Final derivative 5: Synthetic protocol analogous to compound 3. The title compound 5 was obtained as a colorless solid . 1H NMR : δ=11.56 , 11.20 , 10.56 , 9.69 , 8.98 , 8.44 , 8.06 , 7.87–8.01 , 7.76–7.84 , 7.63–7.72 , 7.60 , 7.58 , 6.91 , 4.88–4.99 , 3.91 , 3.90 , 3.78 , 3.20–3.37 . 13C NMR : δ=150.4 (Ar), 142.0 (Ar), 131.5 (Ar), 128.7 (Ar), 126.0 (Ar), 125.9 (Ar), 119.2 (Ar), 115.2 (Ar), 111.2 (Ar), 110.9 (Ar), 60.8 (OMe), 54.7 (OMe), 54.3 (α‐C), 54.0 (OMe), 27.1 (β‐C). HRMS (ESI): m/z calcd for C43H36N8O11 [M+H]+ 841.2576; found 841.2584 (Δm=+1.0 ppm), tR=8.63 min.Final derivative 6: Synthetic protocol analogous to compound 3. The title compound 6 was obtained as a colorless solid . 1H NMR : δ=11.55 , 11.19 , 10.56 , 9.69 , 8.98 , 8.06 , 7.96 , 7.76–7.85 , 7.63–7.73 , 7.59 , 7.30 , 4.88–4.99 , 3.92 , 3.78 , 3.19–3.37 . 13C NMR : δ=134.2 (Ar), 132.7 (Ar),129.4 (Ar),128.1 (Ar), 126.1 (Ar), 125.8 (Ar), 119.1 (Ar), 116.5 (Ar), 115.3 (Ar), 110.6 (Ar), 60.8 (OMe), 60.6 (OMe), 54.7 (α‐C), 27.6 (β‐C). HRMS (ESI): m/z calcd for C43H34FN7O10 [M+H]+ 828.2424; found 828.2427 (Δm=+0.4 ppm) tR=9.04 min.Final derivative 7: The tetrapeptide 43  and the active ester 33  were dissolved in a mixture of anhyd. DMF (5 mL) and triethylamine . The mixture was stirred at room temperature for 16 h. All volatiles were removed in vacuo and the crude material was dissolved in DMSO and purified by HPLC . The title compound 7  was obtained as a colorless powder. 1H NMR : δ=11.54 , 11.17 , 10.56 , 9.68 , 9.01 , 7.77–7.83 , 7.73 , 7.60 , 7.57 , 4.88–4.99 , 3.92 , 3.78 . 13C NMR : δ=132.9 (Ar), 132.7 (Ar), 132.0 (Ar), 128.8 (Ar), 126.3 (Ar), 119.1 (Ar), 115.3 (Ar), 110.3 (Ar), 60.8 (OMe), 60.5 (OMe). HRMS (ESI): m/z calcd for C44H34N8O10 [M+H]+ 835.2471; found 835.2469 (Δm=−0.2 ppm), tR=9.38 min.Final derivative 8: The tetrapeptide 42  and the active ester 38  were dissolved in a mixture of anhyd. DMF (3 mL) and triethylamine . The mixture was stirred at room temperature for 16 h. All volatiles were removed in vacuo and the residue was taken up in a mixture of THF (2 mL) and MeOH (2 mL), and 3 n KOH(aq.) (2 mL) was added dropwise at 0 °C. The ice bath was removed and after 15 min of stirring 3 n HCl(aq.) (2.1 mL) was added and the resulting suspension was concentrated under reduced pressure. The crude material was dissolved in DMSO, centrifuged, and the supernatant was purified by HPLC . The title compound 8  was obtained as a colorless powder. 1H NMR : δ=10.82 , 10.59 , 9.61 , 8.79–8.84 , 7.97 , 7.88 , 7.80 , 7.66–7.70 , 7.60–7.66 , 7.55 , 7.41–7.51 , 7.28 , 7.07 , 6.77–6.84 , 4.90–4.96 , 3.86 , 3.79 . 13C NMR : δ=130.7 (Ar‐CH), 128.9, 128.4, 128.2, 125.9, 125.2, 125.0, 124.7 (CH‐Ar), 124.4, 119.0 (Ar), 115.9 (Ar), 114.6 (Ar), 107.8 (Ar), 60.6 (OMe), 59.8 (OMe), 54.6 (α‐C), 27.5 (β‐C). HRMS (ESI): m/z calcd for C43H37N7O11 [M+H]+ 828.2624; found 828.2628 (Δm=−0.4 ppm), tR=8.11 min.Final derivative 9: Synthetic protocol analogous to compound 8. The title compound 9 was obtained as a colorless solid . 1H NMR : δ=11.54 , 11.17 , 10.58 , 9.67 , 8.86–8.91 , 8.02–8.08 , 7.97 , 7.93 , 7.77–7.87 , 7.75 , 7.69 , 7.60–7.55 , 7.51 , 4.90–4.97 , 3.91 , 3.77–3.79 , 3.77–3.79 . 13C NMR : δ=133.1, 131.2 (Ar‐CH), 129.8 (CH‐Ar), 129.6 (Ar), 128.6 (Ar), 127.4 (Ar), 127.4 (Ar), 126.1 (Ar), 119.3 (Ar), 115.3 (Ar), 110.8 (Ar), 61.1 (OMe), 61.0 (OMe), 54.8 (α‐C), 27.9 (β‐C). HRMS (ESI): m/z calcd for C44H36N8O10 [M+H]+ 837.2627; found 837.2631 (Δm=−0.4 ppm), tR=8.87 min.Final derivative 10: Synthetic protocol analogous to compound 3. The title compound 9 was obtained as a colorless solid . 1H NMR : δ=11.52 , 11.16 , 10.49 , 9.65 , 9.01–9.22 , 8.68–8.75 , 8.05 , 7.93–8.00 , 7.73–7.82 , 7.63–7.70 , 7.54–7.63 , 7.29 , 6.99 , 6.65 , 4.85–4.95 , 3.92 , 3.78 , 3.06–3.14 , 2.84–2.91 , 2.74–2.81 . 13C NMR : δ=129.8 (Ar), 129.4 (Ar), 119.2 (Ar), 127.9 (Ar), 128.8 (Ar), 115.6 (Ar), 60.5 (Ar), 60.9 (Ar), 46.1 (CH2), 37.4 (CH2), 36.1 (CH2). HRMS (ESI): m/z calcd for C43H39N7O11 [M+H]+ 830.2780; found 830.2780 (Δm=0 ppm), tR=8.23 min.Final derivative 11: Synthetic protocol analogous to compound 8. The title compound 11 was obtained as a colorless solid . 1H NMR : δ=11.54 , 11.19 , 10.55 , 10.54 , 9.69 , 8.76 , 8.06 , 7.98 , 7.85−7.94 , 7.76−7.84 , 7.62−7.72 , 7.59 , 4.88−4.98 , 4.44 , 3.92 , 3.78 , 3.18−3.38 . ‐HSQC NMR : δ=132.1 (Ar), 129.0 (Ar), 128.7 (Ar), 125.9 (Ar), 126.0 (Ar), 119.7 (Ar), 119.2 (Ar), 115.0 (Ar), 110.6 (Ar), 83.7 , 61.0 (OMe), 60.5 (OMe), 54.4 (α‐C), 27.7 (β‐C); HRMS (ESI): m/z calcd for C44H36N8O11 [M+H]+ 853.2576; found 853.2585 (Δm=+1.1 ppm), tR=8.34 min.Final derivative 12: To a solution of the alkyne derivative 11  and azidomethyl pivalate  in a mixture of THF (2 mL) and H2O (2 mL) was added CuSO4 ⋅ 5 H2O . After purging the solution with N2 for 5 min, sodium ascorbate  was added and the reaction mixture was stirred at room temperature for 16 h. MeOH (2 mL) and 3 n KOH(aq.) (2 mL) were added and the solution was stirred for another 15 min at room temperature. After adding 3 n HCl(aq.) (2.1 mL), the resulting suspension was concentrated under reduced pressure. The crude material was dissolved in DMSO, centrifuged, and the supernatant was purified by HPLC . The title compound 12  was obtained as a colorless powder. 1H NMR : δ=11.55 , 11.19 , 10.57 , 10.53 , 9.69 , 8.77 , 8.01−8.14 , 8.0 , 7.88−7.94 , 7.76–7.85 , 7.59 , 4.93 , 3.92 , 3.78 , 3.19–3.38 . ‐HSQC NMR  δ=129.1 (Ar), 128.9 (Ar), 128.7 (Ar), 126.1 (Ar), 126.0 (Ar), 125.9 (Ar), 119.8 (Ar), 118.9 (Ar), 115.1 (Ar), 110.4 (Ar), 60.8 (OMe), 60.5 (OMe), 54.7 (α‐C), 27.9 (β‐C); HRMS (ESI): m/z calcd for C44H37N11O11 [M+H]+ 896.2747; found 896.2734 (Δm=−1.5 ppm), tR=7.34 min.Final derivative 13: Synthetic protocol analogous to compound 3. The title compound 15 was obtained as a colorless solid . 1H NMR : δ=11.52 , 11.17 , 10.64 , 10.52 , 9.67 , 8.75 , 8.16–8.25 , 8.06 , 7.88–8.01 , 7.75–7.85 , 7.70 , 7.60 , 7.58 , 4.88–4.98 , 3.92 , 3.78 , 3.21–3.36 . ‐HSQC NMR : δ=129.2 (Ar), 129.1 (Ar), 128.7 (Ar), 127.2 (Ar), 126.2 (Ar), 126.0 (Ar), 119.9 (Ar), 119.2 (Ar), 115.1 (Ar), 110.6 (Ar), 60.9 (OMe), 60.5 (OMe), 54.5 (α‐C), 27.7 (β‐C); HRMS (ESI): m/z calcd for C43H36N12O11 [M+H]+ 897.2699; found 897.2725 (Δm=+2.9 ppm), tR=7.35 min.Final derivative 14: Synthetic protocol analogous to compound 3. The title compound 14 was obtained as a colorless solid . 1H NMR  δ=10.55 , 10.26 , 10.22 , 9.67 , 9.29 , 7.74–8.01 , 7.52–7.62 , 6.88 , 4.77–4.87 , 3.86–3.92 , 3.76–3.81 . HRMS (ESI): m/z calcd for C44H36N8O12 [M+H]+ 869.2525; found 869.2521 (Δm=−0.5 ppm), tR=7.82 min.Final derivative 15: Synthetic protocol analogous to compound 3. The title compound 15 was obtained as a colorless solid . 1H NMR : δ=3.06−3.25  3.78  3.81  3.92  4.81  7.03  7.52−7.62  7.67  7.76  7.81  7.97  8.06  9.23  9.69  10.53  11.19  11.55 . 13C NMR : δ=134.5 (Ar), 129.0 (Ar), 126.1 (Ar), 126.0 (Ar), 119.2 (Ar), 115.2 (Ar), 115.1 (Ar), 110.4 (Ar), 60.8 (OMe), 60.6 (OMe), 55.8 (OMe); HRMS (ESI): calcd for C38H33N7O11 [M+H]+ 764.2311; found 764.2316 (Δm=+0.7 ppm).The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


Center-surround modulation in visual processing reflects a normalization process of contrast gain control in the responsive neurons. Prior adaptation to a clockwise (CW) tilted grating, for example, leads to the percept of counterclockwise tilt in a vertical grating, referred to as the tilt-aftereffect (TAE). We previously reported that the magnitude of the TAE is modulated by adding a same-orientation annular surround to an adapter, suggesting inhibitory lateral modulation. To further examine the property of this lateral modulation effect on the perception of a central target, we here used center-surround sinusoidal patterns as adapters and varied the adapter surround and center orientations independently. The target had the same spatial extent as the adapter center with no physical overlap with the adapter surround. Participants were asked to judge the target orientation as tilted either CW or counterclockwise from vertical after adaptation. Results showed that, when the surround orientation was held constant, the TAE magnitude was determined by the adapter center, peaking between 10° and 20° of tilt. More important, the adapter surround orientation modulated the adaptation effect such that the TAE magnitude first decreased and then increased as the surround orientation became increasingly more different from that of the center, suggesting that the surround modulation effect was indeed orientation specific. Our data can be accounted for by a divisive inhibition model, in which (1) the adaptation effect is represented by increasing the normalizing constant and (2) the surround modulation is captured by two multiplicative sensitivity parameters determined by the adapter surround orientation. The concept of lateral modulation describes how the visual percept of a central stimulus can be affected by the presence of a surround pattern. Such lateral modulation of the stimulus surround on sensitivity to the stimulus center has long been recognized . ExampleThe lateral modulation effect has been the focus of numerous studies that implement various paradigms to investigate the observed phenomena. For example, in psychophysical experiments, the perceived contrast of a central stimulus can be decreased or enhanced by a surrounding pattern, and such a lateral modulation is tuned to the surround features such as luminance contrast, spatial frequency, size, and orientation , 2002. FIn addition to psychophysical experiments, single cell recording studies also provide insights into the lateral modulation effect and its properties. Many studies showed that lateral modulation from the surround depends on the spatial configuration and luminance contrast of the center and surround stimuli . Among tNeuroimaging studies have also revealed possible neural correlates of the lateral modulation effect. In one functional magnetic resonance imaging study, Several computational models have been proposed to account for the lateral modulation effect. Previous studies of center-surround modulation focused more on how the lateral interaction influences the target contrast discrimination  or perceThe tilt illusion and the tilt-aftereffect (TAE) are two visual phenomena commonly studied to understand the orientation domain of human vision . The tilIn a previous study , we seleStudying the effect of the adapter surround orientation on the adapter center allows us to observe how the TAE changed quantitatively with varying surround orientations, leading us to investigate the cross-orientation interaction of the lateral modulation effect in the orientation domain. Therefore, to further investigate the property of such a lateral modulation effect here, we manipulated the surround and center orientations independently. By doing so, we can observe how much the lateral modulation effect from the adapter surround was induced on the adapter center by measuring the changes in TAE on the subsequently presented target. In an adaptation paradigm, a center-surround adapter was presented followed by a target Gabor, about which participants were to make an orientation judgement. We measured how the TAE induced on the target depended on the adapter center and surround orientations. Because many earlier studies have shown that such lateral modulation depends on the surround features, we expect to observe an orientation-specific modulation on the TAE as the surround orientation is varied. A contrast gain control (or divisive inhibition) model has been shown to be able to explain the lateral modulation effect reported in psychophysics experiments  ThereforFour observers, aged between 20 and 30 years, including one of the authors  and three participants naïve with respect to the purpose of the experiment (P1–P3) participated in the study. All observers have normal or corrected-to-normal vision. Informed consent was acquired before participation for all participants. The study procedure and protocols were approved by the University of Regensburg ethics committee (application number: 19-1591-101) and the experiment was performed according to the Declaration of Helsinki on human experimentation. Participants (except for P0) received monetary compensation or class credits as a reward for their participation. All observers first performed a short practice session to become acquainted with the stimuli and the task before continuing the formal experiment.2. The experiment was conducted in a dimly lit room.Participants viewed stimuli on a Dell S2417DG 24-inch LED monitor with 2560 × 1440 pixel resolution and 120 Hz refresh rate in a viewing distance of 60 cm. The monitor was calibrated and gamma-corrected with a spot photometer (MINOLTA CS-100). The mean luminance was 73.8 cd/mB represents the mean luminance, C the pattern contrast, f the spatial frequency, yμ the vertical displacement of the pattern, and σ the scale parameter. θ in the second and third equations represents the pattern orientation. The center part of the adapter and the target had a 0.3° scale parameter (σ). The annular surround part of the adapter was generated by multiplying a sinusoidal grating by an annular Gabor envelope, defined by:r = (x′2 + y′2)0.5 is the radial coordinates of x′ and y′ after transformation from Cartesian coordinates to polar coordinates. Er is the eccentricity which determines the size of the annulus, whereas σr is the radial scale parameter that determines the width of the annulus. The annular surround part used in the current study was created with 3.5° eccentricity (Er) from the adapter center with a 0.9° scale parameter (σr). There was no overlap between the adapter center (where the center patch and the target locate) and the adapter surround (where the annulus is positioned) regions.The adapter was composed of two parts: a center Gabor pattern (the center patch) and a surround grating (the annulus). The stimulus orientation here was defined by a sinusoidal luminance contrast variation, with 0° corresponding to a vertical grating and CW gratings was assigned negative values whereas counterclockwise (CCW) gratings, positive values. The orientation of the center and surround gratings varied independently of each other along one of five orientations  in separate runs, resulting in 25 possible orientation combinations. x and y directions) from the central fixation point. The visual stimuli were all generated using Matlab  with PsychToolbox (http://psychtoolbox.org/).The adapter and the target were presented on the upper right quadrant of the visual display, centered at 10° eccentricity  to the combined data see  to fit aThe data  of individual participants are presented in F = 1.36, p = 0.19, was not significant, whereas the adapter center and surround main effects, F = 77.52, p < 0.01, F = 8.09, p < 0.01, To further investigate the lateral modulation effect observed in the psychophysical data where the TAE highly depended on the surround orientation, in the following section, we fitted the data with a divisive inhibition model inspired by previous studies .We implemented a divisive inhibition model in which the response to a visual stimulus is computed by dividing the excitatory component with an inhibitory component plus a normalizing constant. Researchers have long used divisive inhibition models to explain lateral modulation effects such as lateral masking  and tiltthj channel to the thi image first goes through a receptive field-like linear operator , the orientation dependent component  that can be represented by a Gaussian function  indicates the operation of choosing the larger value among a,  b.The excitatory component of channel  image i . The senfunction , and fin studies , 1999, sNote that, in the current experiment, because no terms in p, and divided by the inhibitory component, ijI, as well as the normalizing constant, z, asijI isSi the inhibitory sensitivity parameter, andcSi and sSi); the sum of the two is then multiplied by the lateral modulation parameter, Ki.Next, before adaptation, the excitation component is raised by a power, Ke and Ki are determined by two Gaussian functions of the surround orientation (θis).excitatory or θinhibitory) and standard deviation parameter (the σexcitatory or σinhibitory) to determine the center orientation and bandwidth of the function. These four center and bandwidths parameters control how the excitatory and inhibitory sensitivities vary with surround orientation.Each Gaussian function has a mean  and cSe (excitatory sensitivity to the adapter center) are set to be the same since the target has the same spatial extent as the adapter center. Likewise, Si (inhibitory sensitivity to the target) and cSi (inhibitory sensitivity to the adapter center) are set to be equal. Parameters other than z,  p,  q, m, sSi, and the two parameters determining Ki were fixed because the goodness of fit did not change empirically whether they were free or not, resulting in a total of seven free parameters. The model can explain up to 86.7% of the variance in the averaged data, with a root mean square error of 0.43. The goodness of fit ranged from 70.5% to 89.0% in the four participants. The best fitting parameters and goodness of fit of the group-averaged data and the individual data are presented in In the model, Ke, controlling how the excitatory sensitivity is modulated when a surround is added to the adapter, decreased as the surround orientation increased from 0° to 90°. In contrast, Ki, the inhibitory sensitivity modulating parameter, peaked at approximately 20° and then decreased as the surround orientation continued to increase. These results suggest that the surround interaction in the numerator terms of the normalizing process was stronger when the surround orientation was closer to 0°, whereas the surround modulation in the denominator was stronger with about 20° deviation from vertical.As demonstrated in Such orientation-specific lateral suppression that we observed has been compared to the overlay cross-orientation suppression in which a mask usually of orthogonal orientation was superimposed on the target. Se, which was most pronounced for the center, intermediately pronounced for the disk (both center and surround) and was least pronounced for the annulus (surround-only) condition in the final fitting results.To explain such orientation-specific lateral modulation effects, we modified the divisive inhibition model to account for our data. In the previous model implemented in the our earlier study , the senKe and Ki, the multiplicative sensitivity modulating parameters of the excitatory and inhibitory components, were defined as free parameters. They reported that Ke and Ki both decreased as the flanker orientation increased while the ratio between the two stayed approximately constant with flanker orientation. They fitted each of the two parameters with a linear combination of two Gaussian functions, one narrowly and one broadly tuned. In our model, Ke and Ki were each determined by a Gaussian function, representing how the excitatory and inhibitory terms change with the surround orientation, respectively  to see if we could replicate the previous lateral inhibition result and 2) to examine how introducing a gap between the center and surround could affect the lateral modulation effect. Because the surround region of the disk adapter in the 2020 study always had the same orientation as the adapter center, a fair comparison condition from the current study would be when the adapter center and surround have the same orientation. Three participants  took part in both the 2020 study and the current one; thus, we could compare their data from the two studies.We took the data of the center and the disk adaptation conditions from the 2020 study and compared these data with the conditions where the adapter center and surround were of the same orientation  after viewing a flickering sinusoidal-grating adapter with a center  and a surround  gratings in eccentric vision. Because the center and surround orientations were varied independently, we could observe how the surround feature could influence the center percept quantitatively. The results showed that the TAE induced on the target was predominantly determined by the adapter center and modulated by the adapter surround. The surround modulation effect first increased then decreased as the surround orientation deviated from the vertical orientation. Such findings demonstrate an orientation-specific interaction between the center and the surround regions in the visual field. The results aligned well with previous research on the lateral modulation effect in human vision . We fittNumerous studies have focused on the cross-orientation interactions between patterns occupying the center and surround visual fields. The results of these studies have shed light on the neural mechanisms of the long-range interactions , 2002, p


Schizophrenia, the most chronic and stigmatized form of mental illness, can be described as a brain disorder that affects an individual's cognition. Individuals with schizophrenia exhibit socially unacceptable symptoms that affect their psychosocial lives. They suffer from reduced productivity due to the debilitating effect of the illness, and the negative symptoms impede their employability; such symptoms and effects aggravate the stigma around mental illness. However, when rehabilitation is successfully achieved, so is productivity, and this decreases the associated stigma. Thus, this study describes the rehabilitation experiences and productivity of individuals with schizophrenia in South‐West Nigeria.A descriptive qualitative approach with semi‐structured interviews was used to gather information from mental health service users. The discharged users in this study received in‐hospital or outpatient rehabilitation care at four outpatient units within two specialist mental health‐care facilities in South‐West Nigeria. These facilities offer vocational training and rehabilitation services for individuals with schizophrenia. Twenty‐nine mental health service users were interviewed. The data from the interviews were independently analysed by two researchers through a content analysis approach using NVIVO version 11. The researchers compared the results of the analysis and reached an agreement on the conclusion.The rehabilitation services availed by patients in the research setting are of three types. Some attend occupational rehabilitation to learn a trade; they depend on professionals for the choice of skill but at a cost that is not affordable to many. Some stay in rehabilitation units linked to the hospital, rendering their services at a cost, and their living expenses and skill acquisition processes are based on the remuneration they get from the services rendered to the institution. Others depend on their family members' efforts to afford rehabilitation services but set up on job by family or employed in family business. The mental health service users in this study who offered their services to the institutions were able to make informed decisions and showed better performance with their chosen occupation than those who depended on their family or health professionals for the choice of rehabilitation service or vocational career. Therefore, this study concludes that prioritizing mental health facility users' preferences in terms of productive activities  or rehabilitation goals should be encouraged. It reduces disability, improves the quality of life and increases life expectancy among schizophrenic individuals.2The experiences of individuals living with schizophrenia, their rehabilitation and levels of activity and productivity were studied, including their expectations of the rehabilitation exercise, the perceived benefits, changes since they began engaging in rehabilitation, the activities they engage in, their productivity levels, their concerns about rehabilitation and suggestions for improvement. A descriptive study design was adopted with a qualitative approach to data collection, specifically using semi‐structured interviews. Purposive sampling was used to select participants who were mental health service users living with schizophrenia, discharged from hospital but receiving in‐hospital or outpatient rehabilitation care.The interviews were conducted in April–September 2019, with each interview lasting 45‐90 minutes. The researcher conducted about one to three interview sessions with each participant. The purposive sampling of mental health service users with schizophrenia was performed through record reviews and inputs from assistants of health professionals. The research setting constituted 62 patients accessing rehabilitation services, and 50 were eligible for the interview; however, 21 refused to give consent, while some withdrew their consent at the point of interview. In total, 29 mental health service users who gave their consent were interviewed. Table 2.1This study was conducted in South‐West Nigeria, which is where humanitarian psychiatric care first took off.The first institution has three units that engage in vocational and rehabilitation activities: the psychogeriatric unit ; rehabilitation wards/units (where discharged patients who cannot go home immediately or have no place to go are engaged); and the outreach clinic . Unlike the outreach clinic, the rehabilitation wards are within the hospital and have nurses as home matrons. Notably, several mental health service users who reside in rehabilitation units work as hospital cleaners and receive monthly stipends, using which they pay accommodation fees and buy medication. Some of the residents of these rehabilitation wards are retired government employees on pension. The rehabilitation units have private lodges called Hope Villas for residents who prefer, and can afford, private facilities.The second institution has only one unit that handles the rehabilitation of individuals with schizophrenia—the occupational therapy unit. Mental health service users come to this unit daily to engage in different rehabilitation services, from learning vocational skills  to behavioural habit training and psychosocial therapies (relationship and anger management).2.2Participants were purposively selected, and the prospective participants' files were sorted with the assistance of record officers before being reviewed by the investigator and nurses on duty. Inclusion criteria were that the individual had to have a diagnosis of schizophrenia and been mentally stable for not less than 3 months  at the close of the interview session; those who resided and were interviewed within the mental health facility were not given any transport fare but were thanked verbally.2.3As previously stated, all the participants gave informed consent. To ensure the appropriateness, clarity and congruence of the study content with the set objectives and interview guide, the research was presented to a peer review committee as well as an expert review committee. In addition, the interview guide was reassessed post‐validation. The fieldwork was performed by the first investigator (OO), and the co‐researcher was periodically briefed at each stage of data collection. All the interview sessions, except one, were in English, and all of them were audio‐recorded with the participants' permission and transcribed verbatim. There was a member checking with the participants after data transcription. Back translation occurred for the entire script of the one interview session conducted in the Yoruba language. Two researchers coded the data until they reached a consensus on the emerging themes. These steps, along with the efforts described below, enhance the credibility and trustworthiness of the work.2.4Data analysis was performed using NVIVO 11 and the content analysis technique.3Table 3.1The first theme generated in the description of the participants' engagement was rehabilitation approaches.This was expressed in three different perspectives which connotes, self and family initiative, hospice service and alternative/ traditional therapies.(C15Ag)I stay with my mother in her house and co‐manage her shop with her … We sell provisions, and I have financial independence through the shared gains from the products we sell. (C16Ag)I started a petty trade from capital I got from my children. I pay my house rent from it and do everything myself. They only come visiting at will, and they are always happy that I am not a burden to them. In the description of self and family initiative, some of the participants reported that, although they were receiving training in rehabilitation units, they were living within their respective communities and considered themselves productive through family/self‐initiated efforts. Their declaration of family support is expressed in the statements that;(CR12Ao)I tried going into sales and supply, but that made me anxious. Later, I tried fashion designing, with which I am coping well. Besides giving me financial independence, I do it at my convenience. On the other hand, one participant said that she faces no productivity‐related challenges as far as her illness is concerned. Her response shows self‐initiative, as she was able to understand her own capabilities and chose the activity she found the easiest:(C8Ar)We are employees of the hospital and on payroll … our employment is not from the government, but the hospital pays us. We clean and sweep every morning. Another group of participants reported another approach to rehabilitation which connotes hospital‐based/stay training, hospital‐based paid services, plus self‐services within the hospital (hospice techniques). In their description, some said that they were provided job opportunities by the institutions and that the salary they receive from the hospital is sufficient for self‐sustenance. The job description reported by one of the participants is as follows:(C13Ar)We serve as the hospital cleaners. We are trained to clean; we clean … It is this salary that we use to maintain ourselves. It's 200 naira per day (0.5 USD). Similarly, another participant talked about the supportive nature, salary and use of the job the institution provided them:(C12Ar)We live here and clean offices and the toilets on the wards. In addition, I go from bed to bed to shave the hair of patients and also sell snacks. These help me to buy my medication and pay for my accommodation. I don't depend on anybody. (C1Av)Besides the cleaning duty, I also sell sachet water using the hospital fridge. I also sell cell‐phone recharge cards to the nurses and the doctors. Two other participants stated that the scope of their work went beyond cleaning offices; they engage in some menial jobs for additional self‐support alongside their institutional jobs. They described themselves as independent and able to meet their needs without having to depend on anybody as they said;(C6L)I think they have been helping me so much in the OT that I have been attending … the kitchen rehabilitation … the salon. The catering section. I have passed through all of them. I think the way they are helping us is that they have been equipping me to be able to pick a skill. (C1L)I am into tailoring. I have learnt measurement, I have learnt to spread, but it remains to sew. I am here because they felt it's best for me. (C2L)I have learnt knitting, and I have mastered it and happy I did. What is left for me is to get materials and knitting machine. Besides job opportunities, hospice services also provide training. The participants reported going to the occupational therapy (OT) unit of the hospital for training on self‐grooming, cooking and baking, hair dressing, computer software, shoemaking and sewing. The training results, as per participant's productivity and perceived benefits, were as follows:(C12Ar)My father took me to the house of an herbalist. Though I told him to bring me to the hospital, he said I should remain there. They tied me on the floor to a tree in the bush. I was so furious and tried to run away, but the herbalist arrested me. It was during that time that I injured someone, and the person died. Apart from the self‐initiated efforts and hospice productivity techniques, some participants reported being taken to a traditional facility  against their consent because their relatives considered it their family's preferred approach of rehabilitation and or a cheaper alternative. The participants reported this as unpalatable since they were confined, and any effort to liberate themselves led to violence. The participants' descriptions of the confinement and resultant effects were as follows:(C13Ar)This is my second time here. After the first time, they had no money to bring me back to this place, so they carried me to herbalist house because my people are poor, and they tied me down there doing many things. After that, I had a misunderstanding with my father during which I mistakenly killed him. Similarly, another participant stated the following:Thus, the participants had varied experiences as far as their rehabilitation efforts are concerned.3.2(C2L)When I was diagnosed of this illness, I had to stop school and had to stay at home doing nothing … not being active is worse than the illness. I felt like dying then … but with this rehabilitation that I am undergoing, I am now in order, doing well, now at OT. I am into knitting, so as I progress further … I no longer feel idle, and I know I will be well settled after completing the training. (C8L)I have been gaining a lot because I am an introvert. So, I don't relate because I don't talk that much, but since I came in now, I have been able to come out of that attitude of being an introvert … I talk to people and relate well. No longer shy. I know I will go back fully to my work when I am very okay and can relate very well. The theme of perception emerged from the participants' view of rehabilitation exposure and the description of its impact on them. Some participants described rehabilitation as bringing hope, positive changes and improving their quality of life. They reported that their experiences help remove loneliness and boost human relations as well as enable them to see life as worth living, which they believe is vital for their productivity and effective living as they said;(C11Ar)They said we are sick and want us to believe that we are sick, so we are here now receiving treatment because they said we are sick. I was at my duty post when co‐workers took me to a health centre, and it is the nurses at the health centre that brought me here. My family came for a while, and later they stopped coming. Now, they said we are doing rehabilitation. I believe they don't know what is wrong. (C1Av)I was referred from a private hospital, where I was diagnosed of malaria. The first time I came, the referral letter was sealed, and what l was told is that where I was referred to is a specialist hospital and that I should never open the letter but give it to the health professionals there. They told me I would be better managed. However, I am here because they want me here. However, some participants expressed perceptions of having been incorrectly diagnosed and showed a lack of insight into their diagnosis. These participants perceive their rehabilitation as unnecessary and having no basis. They believe they were not provided with sufficient/appropriate information to convince them of the illness. Further, they claimed to have been productive before being admitted to the hospice by health professionals. These participants are at the rehabilitation unit of the institutions and stated the following:Some of the participants expressed anger and an acceptance of their fates. These individuals described themselves as unwanted and non‐functional due to the physical illness associated with their mental illness. They described their rehabilitation as having failed due to the belief that the illness grossly affected the extent to which they could be productive.(C4Ag)I cannot even do anything, not even clean the house, just there sitting down. … I am just there useless. A participant shook her head, hissed and said,(C3Ar)What can I do with the way I look … My mother does not want me again … she got rid of me… my mother brought me to the gate of the hospital and left me there … one of the doctor employed me as personal aid, but ejected me out of her house … since my mother rejected me, what can anyone not do to me? In such case, how is it possible for me to benefit from rehabilitation. Another participant expressed anger with a gesture of displeasure as associated not only with the disability, but also with family neglect with the way she opened her hands, like she wanted to throw something away and said:Those with physical illnesses expressed feeling incapacitated during rehabilitation, while those who engaged in vocational training and services expressed a feeling of improvement. The others had a lack of insight about their illness and diagnosis.3.3(C1Av)I wish to be back to the community. I love singing but can only do that well in the community. I have composed (songs), but I have nobody to help me. If I go back to the community, I will sing and get help … Like I composed a song which goes … There are many people in the bondage … they never wish to be in bondage. (C7Av)I manage the stock shop owned by the hospital, but I have been living here for long. I am old now, and it is not good to stay somewhere and die there. The family may not even know the person has died. It will be very unpalatable and disheartening to live forever in a place outside your home. I desire they help me go back to the community, I can also do better business and make much sales at the community. The participants' expectations were centred on what they wished to do with their lives based on what they expected from the rehabilitation programme. Some participants expressed that their utmost desire was to return to their respective homes and communities. These participants currently live within the hospital premises and guest house. Their occupational direction has been established, but they see their living within the hospital for rehabilitation as a form of bondage from which they desire freedom. Further, they recognize the fact that community life improves their chances of getting help and is best suited for them and expressed the following:(C6L)what I want is for them to help me to achieve going back to my school and graduating. I feel I will do well going back to school rather than learning a trade and wish to complete my study and work as a professional in the discipline I studied. (C9L)My aspiration in life is to become an administrative person, working for the government. I studied business administration at university and that's what I want to do. (C7L)I was in school in a university outside the country when this illness started, but I was still studying. I had not gotten my degree; I still wish to study. In contrast, the participants who live in their respective communities but visit the hospital for daily rehabilitation expressed their utmost desire to go back to the activities they had engaged in before the onset of their illness (rehabilitation to previous functioning). They believe they are doing well as far as rehabilitation is concerned and are determined to pursue their previous engagements. They believe that this will spare them the time required to venture into a new field. Excerpts from the participants' reports are given below:(C5L)I wanted computer (science) but was directed to tailoring by the HOD. There, I couldn't pass thread into the needle. I just wasted the three years. Later, the HOD agreed for me to learn computer … in this computer age, I would like to be a computer analyst. Another expectation that was different from community re‐integration and previous patterns of functioning was the participants' rehabilitation through gaining desired skills and not prescribed ones. Participants stated that they sometimes desire the acquisition of new skills and not necessarily the ones they focused on before, but they desire to choose from the available options on their own and not have the professionals decide for them. They reported experiencing frustration with skill pursuit when it was the professional's choice and not a self‐driven one. An excerpt from a participant's recount is as follows:In summary, these participants expressed a desire for acceptance of their own views on skill acquisition and rehabilitation modality in general.3.4(C7Av)I was brought back to the hospital by the social workers when the house I was to be discharged to was dilapidated. I do not even think anyone stays there anymore. This theme answers the questions on the participants' concerns about the programme and their suggestions for improvement. Some participants complained about a lack of infrastructure in the community, which impedes their functionality and rehabilitation . A participant recount goes thus:(C13Ar)I mistakenly killed my father. I have changed, but they do not want me at home. I was trained as vulcaniser here, and the institution got me equipment, but there is a challenge with going back home. There was a time I was discharged, but the family told them frankly that they can't accommodate me. If I decided to stay there by force, they could kill me. Another barrier was psychosocial in nature. Some participants revealed that there is fear and an actual expression of non‐acceptance by their family members. Social undesirability is a factor that limits their productive functioning in the community. Excerpts from a participant's statement is as follows:(C12Ar)My desire is that they should make effort to assist me to return home. But the means to using the medication is the utmost. If I go home and there is no job, getting money to buy medications for use will be difficult. So, if they can help me with getting the medications if I go home. Maybe I can sell petty things and start coming for check‐up. Further, some participants expressed financial difficulty in terms of setting up businesses and lack of financial capacity for medication and self‐upkeep. An excerpt from a participant's description is as follows:In short, these participants expressed their basic needs constituting barriers to rehabilitation.4This study revealed that individuals with schizophrenia are able to start small businesses, work in a formal setting and even learn new skills that will help them live and sustain a productive life. This is consistent with the finding that individuals with schizophrenia in paid jobs have boosted morale and increased quality of life.In terms of perception, the participants held negative and positive beliefs about themselves. Their negative beliefs evoked a feeling of worthlessness, primarily resulting from the rejection they experienced from their family. Their positive beliefs arose from being actively engaged in a vocation. This is consistent with findings that inactivity can cause mortality among schizophrenic patients.Additionally, this study revealed that individuals with schizophrenia have their own vision and expectations of life as well as the potential to live a meaningful life. Some of the participants dreamt of achieving their academic and career goals and even starting their own businesses; however, receiving suggestions for how their rehabilitation should proceed adversely affected their interests. This is consistent with a previous finding that a lack of interest results when an individual feels compelled to pursue a task, which serves as a significant constraint of the productivity of individuals with psychiatric conditions.Further, our study revealed barriers to the rehabilitation of people with schizophrenia. Resources such as housing affect the success of rehabilitation because even participants who can function independently within the community may have to remain accommodated in the hospital setting. Some of the study participants faced psychological implications due to their behaviours prior to diagnosis, leading to neglect from their family members. Such neglect impedes the success of rehabilitation. This is consistent with the finding that the public feels threatened by the presence of individuals with a history of schizophrenia coupled with violence.5This study shows that the rehabilitation programme followed by the hospitals is a good initiative and has enabled the mental health service users to regain some level of independence and productive living. However, there are still lapses and weaknesses in the execution, such as variations in the approach to rehabilitation, the lack of a unified guide to rehabilitation, and prolonged institutionalization rather than re‐integration of the service users who lacked accommodation or acceptance by their relatives. Therefore, it can be concluded that the rehabilitation of individuals with schizophrenia, though a good effort, can be improved upon through active involvement of service users in their rehabilitation decision‐making process. This can potentially help mental health professionals better serve the interest of the service users and community as a whole.6Considering the demographic profile and the participants' reports of undergoing rehabilitation and learning a trade for many years, ranging from five to 30, there seems to be no end to rehabilitation. Therefore, the setting of broad, individualized goals before the commencement of rehabilitation is recommended. Further, collaborations between different settings and other parts of the world that have recorded evidence‐based success in rehabilitation are advisable. Wide variations were also noted between the intervention approaches taken by the health professionals; therefore, a practice guide for uniformity of practice is also recommended.The full approval was secured from the first institution on the 19th October 2018 with approval number: NHREC 24/07/2013/PRO 12/18, and the second institution granted approval on the 30th October 2018 with approval number FNPH/HREC 18/10. Beneficence was promoted in this study, as there were no physical risks. Although the mental health service users are a vulnerable population, their rights were protected by strictly adhering to the enquiry on what this study is purposed. The inclusion criteria also considered mental health service users' vulnerability to determine those who were eligible to participate, part of which was clinical stability of 3 months, the evidence of which was confirmed through the follow‐up report. Co‐morbidity with an affective disorder that increases the tendency of the emotional breakdown was also excluded to minimize the emotional risk. This study posed no harm, although recounting the experience could bring about an emotional reaction in individuals with schizophrenia, despite the consideration of that for exclusion, the researcher, before the commencement of the research, liaised with the Psychology Unit of the hospitals that in the event any participant broke down emotionally during or even after the data collection would be referred at the researcher's cost; this was because mental health service users pay for this service and the section will be discontinued. The researcher developed a referral slip, and the Head of the Psychology Unit approved the referral of participants, but no participant had an emotional breakdown throughout the study.Both researchers are Mental Health Lecturers. The first researcher is a Nigerian, a PhD Candidate and a registered psychiatric lecturer, lecturing in a university about 500km from the research settings, with no connection to the facility and the participants of the research settings. This allowed participants to express themselves freely. The researcher sought consent from each participant, and participant who declined participation was excused from the study without sanction or prejudice. The other researcher is a South African and a lecturer at a South African institution with no affiliation or any form of contact with the research settings.