Background and Objectives: There is no consensus regarding the surface treatment method for achieving optimal bonding strength between zirconia and resin cements. We evaluated the effect of hot-etching with 9% hydrofluoric acid (HF) gel using the Zirconia Etchant Cloud System on zirconia surfaces and the consequent shear bond strength (SBS) of different resin cements to such surface-treated zirconia ceramics. Materials and Methods: Forty-five zirconia specimens were randomly assigned to surface-treatment groups (n = 15/group): no treatment ; sandblasting with 110-μm Al2O3 at an air pressure of 1 bar for 10 s (SB); hot-etching with 9% HF gel (HE). Post-treatment, specimens were examined using scanning electron microscopy (SEM) and surface roughness (SR) analysis. After treatment, self-adhesive resin cements  were bonded to zirconia specimens, which were stored in distilled water at 37 °C for 24 h. All specimens were then subjected to SBS testing, using a universal testing machine, until failure. Data were analyzed using one-way analysis of variance and Tukey’s post hoc test (α = 0.05). Results: In the SEM images, roughness was greater in SB than in HE specimens. Ra and Rt values were highest in SB, followed by HE, and CT specimens. HE specimens showed significantly higher SBS values than CT or SB specimens (p < 0.05). MAZIC Cem cement, with 10-methacryloyloxydcyl dihydrogen phosphate yielded the highest SBS values. Conclusions: Hot-etching with 9% HF gel in a safe shell formed uniformly small, defined holes on the zirconia surface and achieved significantly higher SBS values than sandblasting (p < 0.05). Zirconia prostheses can be bonded micromechanically with resin cement, without the deterioration of properties due to t-m transformation, using chemical acid etching with the Zirconia Etchant Cloud System. Due to high gold prices, and aided by advances in dental computer-aided design and computer-aided manufacturing (CAD/CAM) systems, the clinical use of zirconia in dentistry has increased exponentially, with zirconia ceramics now rapidly replacing gold and metal restorations ,2. DentaVarious mechanical and chemical surface treatment methods have been applied to increase the adhesive area and enhance the bond strength of zirconia ceramic and resin cement ,9,10,11.Several other methods for achieving roughness of the zirconia surface have been recommended ,22,23. AOn the other hand, HF gel does not flow easily and can be applied to a small area; therefore, it is relatively safer than the HF solution. This study therefore aimed to evaluate the effect of hot-etching with 9% hydrofluoric acid (HF) gel on zirconia surfaces and the consequent shear bond strength (SBS) of different resin cements to such surface-treated zirconia ceramics. Hot-etching was performed with a 9% HF gel in a safe shell with a triple-locking structure that prevented exposure to hazardous substances, such as the HF vapor. The null hypothesis was that hot-etching with 9% HF gel using the Zirconia Etchant Cloud System would have no effect on the zirconia surface and, hence, would exhibit no increase in the bonding strengths of the various resin cements.2O3  particles for sandblasting. The self-adhesive resin cements used in this study are listed in Forty-five zirconia specimens  were prepared in a rectangular block form with dimensions of 32 × 15 × 5 mm by InLab MC X5 , sintered according to the manufacturer’s guidelines, and then polished with 1000 grit silicon carbide paper. A Zirconia Etchant Cloud System  containing 9% HF gel was used, which provided a triple-locking safe shell and HF neutralizer, and a heat-generating pack. We used 110-μm AlControl (CT): No surface treatment2O3 at an air pressure of 1 bar for 10 s.Sandblasting (SB): Specimens were sandblasted with 110-μm AlHot-etching with 9% HF gel (HE): Specimens were etched using the Zirconia Etchant Cloud System in a safety shell according to the manufacturer’s recommended procedure for 10 min. The manufacturer’s recommended procedure is illustrated in Forty-five zirconia specimens were randomly assigned to three groups (n = 15/group), according to the surface treatment method used:Grouping of specimens is schematically shown in A uniformly sized cement adhesive area was obtained by attaching a 3M Scotch brand tape to a zirconia specimen. The tape had a thickness of approximately 50 μm, with three holes of 2 mm in diameter spaced at regular intervals. Then, polytetrafluoroethylene (PTFE) tubes  were placed on the adhesive area and filled with resin cement to create cement cylinders 4 mm in diameter and 5 mm in height (n = 15). All resin cement cylinders were self-cured according to the manufacturer’s guidelines, and the PTFE tube was removed after self-curing was completed. Specimens were stored in distilled water at 37 °C for 24 h. The fabrication method of the SBS specimens is shown in The SBS was measured by applying a vertical force of 2000 N at a rate of 0.8 mm/min to the specimens prepared as described above, using a universal testing machine , until failure occurred.All specimens were mounted on coded brass stubs, sputter-coated with gold for 180 s at 40 mA and examined using a scanning electron microscope , operated at 20 kV.The zirconia surface was analyzed by X-ray diffraction (XRD) . The surface roughness  and peak-to-valley roughness  were measured using a surface roughness measuring instrument .p < 0.05.All statistical analyses were performed using the IBM SPSS version 24 software . To determine the effects of surface treatment on SBS, the data were analyzed using one-way analysis of variance (ANOVA), with the Tukey post hoc test. Statistical significance was set at The SEM images of the test groups after surface treatment are shown in p < 0.05). Rt exhibited a tendency similar to that of Ra.The surface roughness values of the specimens were also measured. Values of Ra and Rt were highest in SB specimens, followed by HE and then CT specimens . SB showThe structures of the experimental zirconia specimens were also assessed . Unlike The SBS values achieved with the three types of resin cements  were higher in the HE and SB groups than in the CT group , Table 3p < 0.05) (p < 0.05). After Tukey post hoc test by rank, HE specimens showed significantly higher SBS values than CT and SB specimens (p < 0.05).One-way ANOVA revealed a significant difference in the SBS of resin cements to zirconia specimens according to the surface treatment methods ( < 0.05) . HE specp < 0.05). These results are consistent with the findings of Kang et al. [In this study, we evaluated the effect of hot-etching with 9% HF gel on the surface roughness of zirconia and on the SBS of self-adhesive resin cements  to these surface-treated zirconia ceramics. In SEM images, SB specimens showed an irregular surface that was sharply caved, while HE showed small, sharply defined, uniform holes. Surface roughness (Ra) and peak-to-valley roughness (Rt) values were highest for SB, followed by HE, and CT specimens, in descending order. XRD analysis showed that there was a transformation to the monoclinic phase in the SB specimens, as described in other studies ,30,31. Og et al. . With Mag et al. ,33. Therg et al. . A phospg et al. . The maig et al. . BecauseThe clinical success and longevity of ceramic restorations rely on a suitable bond between the ceramic and dental substrate. An adequate surface roughness is necessary for cement interlocking and enhanced bonding ,36. The The chemical surface treatment recommended for ceramics is acid etching, which enhances the bond integrity between glass or glass-ceramic restorations and resin cement. HF acid etching is a well-accepted pretreatment regimen that produces irregular surface topography. HF etching forms a porous structure on the ceramic surface by reacting with the silica matrix of the ceramic. The boundary areas of silica in the ceramic matrix dissolve at a higher rate than those within the exposed grains . HoweverIn previous investigations of the effect of various temperatures and various HF concentrations, immersion of zirconia into 9.5% HF produced similar surface roughness at 80 °C for 1 min and at 25 °C for 1 h. The surface irregularities increased with increasing immersion time and etching solution temperature . SriampoHowever, using high concentrations of HF at high temperatures is a very dangerous method, as it involves exposure to HF vapor ,46,47. TThere were some limitations to the present study. The present study did not investigate long-term water storage and thermocycling which can affect the adhesion and durability of zirconia prostheses. Future studies should include clinical studies to confirm the effect of hot-etching with 9% HF, and a study on shear bonding strength before and after thermocycling is warranted.p < 0.05). Within the limitations of the present study, we concluded that zirconia prostheses can be bonded micromechanically with resin cement, without deterioration of properties due to t-m transformation, using chemical acid etching with the Zirconia Etchant Cloud System. The long-term stability of resin cement to zirconia prostheses should be further evaluated.Zirconia ceramics are not readily etched using low-concentration HF at room temperature. However, we showed that the zirconia surface could be safely and effectively hot-etched using 9% HF gel in a safe shell. SEM and SR analyses showed that hot-etching with 9% HF distinctly affected the surface treatment of zirconia ceramics, as compared to CT specimens. XRD analysis revealed a transformation to the monoclinic phase only in the SB specimen. SBS values were significantly higher with self-adhesive resin cements  in the HE group than in the SB group (


Talisia floresii Standl) represents 80% of the total fruit weight and is obtained from trees that grow mainly in Yucatan Peninsula. The aim of this work was the physicochemical characterization from colok starch seeds as an alternative to conventional sources and to identify its characteristics for potential applications in different industrial sectors. Starch yield was 42.1% with low levels of lipids, ashes and fibers. The amylose content was 33.6 ± 1.15%. The gelatinization temperature was 85 ± 0.25 °C. Color analysis resulted in a starch with an intermediate luminosity, reflecting a dark color. Finally, in morphology, starch granule exhibited an average size of 18.7 μm, spherical, uniform and without fractures. Overall results demonstrated that isolated colok starch can be used in food products that require high processing temperatures, such as sauces, cookies, noodles, bread and food packages.Colok seed ( Musa paradisiaca), mafafa (Xanthosoma robustum), ramon  and bitter vetch (Vicia ervilia) have shown different physicochemical, structural and functional properties [Talisia floresii Standl).Nowadays, the industry has extended the use of a great diversity of materials for the production, packing, conservation and commercialization of food. Many efforts are oriented towards research and progress in food packaging, for non-polluting and biodegradable sources. Research points out starch as a material of natural origin that is used in different industrial sectors, for example, drugs, adhesives, food, and food packaging. Starch is the most popular plant polysaccharide due to its abundance, cost-effectiveness, and excellent film-forming capabilities. It is stored as semi-crystalline granules in cereals, grains, roots, tubers, leaves, seeds, fruits and pollen. It is composed of two different polysaccharides: amylose, which possesses a linear structure formed from the union of D-glucose through α 1–4 bonds, and amylopectin, where D-glucose, in addition to being joined by α 1–4 bonds, exhibits branches linked by α 1–6 bonds [operties ,3,4,5. Toperties ,8,9. HowT. floressi Stand is a tree that can reach up to 18 m in height, also known as colok in Mexico, which is distributed in the southeast, particularly in Campeche, Yucatán, Tabasco and Quintana Roo [tana Roo ,11. The tana Roo . The see®) at intervals of 10 s to be posteriorly sifted through a 100 mesh to obtain the flour. The flour obtained was stored in hermetically sealed glass containers until its use. Colok fruits were collected in the municipality of Calkiní, Campeche, México, during September 2020. Fruits were selected avoiding overripe samples, with imperfections or damage. In order to obtain seeds, colok fruit was pulped manually. The seeds were dried in a convection oven (Shell Lab 1350FX-10) for 72 h at 40 °C. Finally, the endosperm was pulverized in a commercial blender , following the procedure described by Estrada-León et al.  with modw/v) dispersion at room temperature.The proximal composition of the obtained starch was carried out according to the AOAC methods ,17 for hNative starch color was measured in triplicate using a Hunter Lab MiniScan EZ colorimeter. Parameters were estimated in the CIELAB space as L* , a*  and b*  and the final result was expressed as hue angle (h) with Equation (1) and chromaticity C* (intensity of the tone) was calculated with Equation (2) ,21:(1)h=Amylose content was determined according to Ratnayake et al. . This anTotal starch was determined using the starch assay kit , which is based on the hydrolysis of starch to glucose catalyzed by α-amylase and amyloglucosidase. Glucose is oxidized to gluconic acid and hydrogen peroxide by glucose oxidase. Hydrogen peroxide reacts with ο-dianisidine in the presence of peroxidase to form a colored product. Oxidized ο-dianisidine reacts with sulfuric acid to form a stable colored product. The intensity of the pink color measured at 540 nm is proportional to the original glucose concentration. The analyses were performed according to the instructions supplied with the kits .w/w) in the DSC pans, which were sealed and left at room temperature for 1 h. Pans were heated from 25 to 110 °C (temperature increased at a rate of 10 °C/min). The sample chamber was flushed with nitrogen to avoid moisture condensation. An empty aluminum pan was used as the reference. The onset (To), peak (Tp) and conclusion temperatures (Tc) were recorded. The enthalpy change of the thermal transition (ΔHgel) was estimated by integrating the area between the thermogram and a base line under the peak and was expressed as J/g dry weight of starch [Starch gelatinization was measured using a DSC-6  according to Estrada et al. . Approxif starch .Thermal properties of native starch (NS) were measured with a TGA Perkin Elmer 7/DX thermal analyzer. Next, 6 mg of starch was placed in a platinum pan and heated from 50 to 500 °C (rate 10 °C/min) to observe the temperature at which decomposition occurred. During the entire process, nitrogen at 3.7 bar was delivered through the system containing the sample at 20 mL/min .−1 [The FTIR spectroscopy analyses were performed on NS in order to characterize qualitatively the organic compounds of the solids by using the transmission technique. Samples were prepared by grinding 15 mg of solid powder starch with 130 mg potassium bromide (KBr) powder and then pressing the mixture into a tablet. The total mass of the solid powder was 150 mg and were recorded for 5 specimens of 30 mg of mass. The FTIR spectrum of the powder complexes was measured at room temperature with a ThermoNicolet (Nexus 670-FTIR) spectrometer in a spectral range of 4000 and 400 cm−1 .In order to analyze the X-ray diffraction, a Siemens diffractometer, model D-5000, operating at Cu-Kα radiation wavelength (λ = 1.54 Å), 40 kV, 30 mA and sampling interval of 0.02° was used. Scattered radiation was detected in the angular range of 5–35° (2θ).The morphological characteristics of NS were observed using an SEM. Starch samples were mounted on a metallic slide and the examination was performed with a scanning electron microscopy JEOL JSM 6360 LV electron probe microanalyzer at 15 kV in low vacuum. Subsequently, the starch was suspended in an appropriate volume of distilled water and placed in a Beckman Coulter LS100Q laser diffraction particle size analyzer with a precision of ±1% .The procedure of Rafiq et al.  was usedThe water absorption capacity was determined according to Delatte et al., and Torbica, Belović and Tomić ,32 with The quantitative variables of the proximal analyses and the physicochemical characteristics of the colok starch were described by estimating their mean and standard deviation (descriptive statistics). All determinations were performed in triplicate.sapindaceae [Enterolobium cyclocarpum) [At harvest time, the fruit presented an average weight of 44 ± 0.80 g and an average diameter of 44.2 ± 0.5 mm. The starch yield obtained from colok seeds was 42.1%, expressed on a dry basis. This value is slightly higher than that reported by some authors for other types of starch. Corn starch yield, extracted under conditions similar to those described in this work, was 40% . These dindaceae . Regardiocarpum)  under thocarpum) .Chenopodium quinoa Willd) [Ash content is a parameter linked to the mineral content. In starches, for example, phosphorus is a mineral that exerts a significant influence as it is responsible for the swelling and stability of the paste. Compared to some cereals, such as corn grain , and tuba Willd) .Scanning electron microscopy (SEM) analysis of starch isolated from colok fruit seeds is shown in Regarding the pH, colok starch presented a similar result to those obtained in previous investigations, for parota, a value of 6.44 ± 0.09 was observed despite the alkaline extraction method and for quinoa, a pH value of 6.45 . High pHThe color analysis  resultedThe swelling power and solubility represent evidence of interaction between the amorphous and crystalline areas. In addition, it is influenced by amylose and amylopectin characteristics . Specifigel) [o, Tp and Tc) and enthalpy of colok starch are shown in DSC technique measures the amount of heat involved in the gelatinization of starch. This property is related to various factors, such as the size, proportion and type of crystalline organization and the ultrastructure of the starch granules. Moreover, as mentioned before, starch is composed of two types of macromolecules: amylose and amylopectin. The first is related to the amorphous structure of the starch and the second to the crystalline fragment. Initially, gelatinization occurs in the amorphous part because hydrogen bonds rapidly weaken in such areas. However, amylopectin plays an important role in crystallinity. A higher content of amylopectin increases structural stability, resistance to gelatinization and the energy that initiates gelatinization, which leads to a rise in the transition temperature and enthalpy of gelatinization (ΔHgel) . DSC waso) where the beginning of the swelling of the granule due to the entry of water is identified, presumably in the amorphous structure that is related to the degree of crystallinity. When temperature is risen, the starch granules undergo fragmentation until the amylose (amorphous structure) is completely solubilized while the crystalline zone of starch remains in an aqueous solution. Under conditions of excess water, hydrogen bonds in the amorphous region of the granule are broken, allowing water to associate with the free hydroxyl groups. This is defined by the mobility of the polymer chains above the value of the glass transition temperature, causing the change from glassy to rubbery state. This change, in turn, facilitates molecular mobility in the amorphous regions, being a reversible process and allowing grain swelling. The granule expands as the polymers hydrate. Subsequently, an irreversible molecular transition occurs related to the dissociation of the double helices typical of the crystalline region. The highest value of heat absorption was observed at 85 ± 0.25 °C (Tp) in which the starch passes into a rubbery state due to the rupture of its granules. This temperature is associated with the quality of the crystalline structure, the higher it is, the more cohesive and stable the crystalline region. The process culminates at a temperature of 90 ± 0.2 °C (Tc), corresponding to the melting temperature of the strong crystal structure. High Tp values in colok starch mean that it requires more energy to produce starch gelatinization and may be influenced by its low swelling capacity, high amylose content, medium size, higher proportion of crystalline region by the interaction of starch chains and internal arrangement of starch fractions within the granule. The To, Tp, Tc values of colok starch were slightly higher than those reported by Sudheesh et al. [gel) is indicative of the loss of molecular order  which occurs in the starch granules during gelatinization. The value of ΔHgel calculated for colok starch is lower than the value reported for ramon starch [Gelatinization process begins at a temperature of 81 ± 0.5 °C  is 1.7. Other authors have reported values similar to this, such as the one obtained from ramon  seeds, which report a value of 1.6 [Melicocus bijugatus) with a value of 0.9 [In order to obtain information about the functional groups in the isolated colok starch, Fourier Transform Infrared (FTIR) spectroscopy analysis was performed. In l groups . The brol groups . Some baH groups . Likewise starch . In the ose ring . In starose ring . In thisose ring ,59,60 hae of 0.9 .Talisia floresii standl) starch is similar to that reported by other authors corresponding to ramon  [Melicoccus bijugatus) [Brosimum alicastrum) with 31.89% and 29.61% [Melicoccus bijugatus) around 31.22% [castrum)  and huayjugatus) . The perd 29.61% . For thed 29.61%  and for d 31.22% .Thermal analysis results of colok starch are shown in Physical–chemical, structural, thermal and functional properties of colok native starch were studied. Physicochemical characteristics found in colok starch could be used as a thickener in products that require high viscosity. Balance in nutritional and sensory properties in starch is a substitute for dietary fiber and used to improve properties in foods. Thus, colok starch has been used in cookies with a partial replacement for wheat starch. From a morphological point of view, granules are round and classified as medium in size. Functional properties analyzed, such as solubility, swelling power and water retention capacity, indicate it is feasible to incorporate this starch as a food additive in the preparation of sauces, cookies, bread, noodles and food packages, where these studied properties will improve the quality of the mentioned product. However, research will continue on interactions of starch with other components in a food model.


Background: Acinetobacter spp. are a potential life-threatening cause of severe meningitis noted as a nosocomial infection after neurosurgical procedures in patients admitted to neurosurgical ICUs. Community-acquired Acinetobacter meningitis is extremely rare, and only a few cases have been reported in the literature. Case presentation: In this study, we report a patient from Punjab, India, who was infected after a roadside accident in which he developed CSF otorrhea and subsequent meningitis with Acinetobacter lwoffii. The patient was managed with the cephalosporin group of antibiotics as per the sensitivity report. For the first time, we report a rare case report of community-acquired Acinetobacter meningitis from Punjab, India. Conclusions: This case report highlights the potential pathogenicity of Acinetobacter lwoffii and increases concerns that this organism might rapidly evolve into a dreadful antibiotic-resistant community pathogen. Acinetobacter meningitis of the central nervous system (CNS) is very rare [Acinetobacter spp. are Gram-negative, opportunistic coccobacilli pertaining to the ESKAPE organisms that can accumulate diverse mechanisms of resistance, leading to the emergence of strains that are resistant to most of the commercially available antibiotics [Acinetobacter spp. [Acinetobacter lwoffii.The occurrence of community-acquired ery rare ,2. Acineibiotics . Moreoveter spp. . Here, wThe patient presented was brought with an alleged history of a roadside accident. The patient was hit by a car while riding on a motorcycle on 24 October 2021. The patient was found lying unconscious at the unhygienic corner of the road and was brought for emergency management. Emergency care was provided without delay. Initial examination revealed a body temperature of 38.9 °C, a blood pressure of 150/95 mm Hg, a heart rate of 110 beats/min and a respiratory rate of 16 breaths/min. An emergency computed tomographic (CT) scan of the head was conducted, which revealed a hairline fracture involving the right petrous temporal bone, as shown in Acinetobacter lwoffii sensitive to cefoperazone sulbactam, ceftriaxone sulbactam, meropenem, colistin, etc., as shown in Acinetobacter lwoffii) sensitive to the same group of antibiotics, confirming the presence of meningitis. The identification of the strain was further confirmed by 16S rDNA sequencing using universal sets of primers as described in previous studies [Acinetobacter meningitis, as shown in The timeline of infection aggravation and subsequent management is shown in The global treatment guidelines for bacterial meningitis were followed . The patLumbar puncture of the patient was conducted after 4 days (3 November 2021) of continuous IV antibiotics. The CSF culture was found to be sterile with no growth of the organism, and also the cell count and protein level returned to normal. Intravenous (IV) antibiotics were continued for 21 days. The patient became alert, conscious and mobile, indicating complete improvement. At the follow-up, 15 days after discharge, the patient was found completely fit with no side effects.Acinetobacter meningitis is a life-threatening cause of acute pyogenic meningitis which is acquired mostly after any neurosurgical procedure and is resistant to most of the antibiotics [Acinetobacter meningitis are generally sensitive to most of the empirical antibiotics [Acinetobacter meningitis after trauma where no neurosurgical procedure was performed. To date, very few cases of Acinetobacter meningitis have been reported, and most are nosocomial infections which are acquired in the hospital ICU environment and are highly resistant to most of the commercially available antibiotics, leaving little choice of antibiotics to treat the infection [Acinetobacter meningitis by Acinetobacter lwoffii is a clear indication that the threat has moved far beyond the hospitals in India. Acinetobacter lwoffii may soon develop into a significant dreadful community pathogen in India.ibiotics ,2. Commuibiotics ,9. In thnfection ,11. ThisAcinetobacter meningitis can be community-acquired too. The unscrupulous use of antibiotics should be avoided to prevent the development of highly resistant strains of Acinetobacter spp. so that all the narrow-spectrum and commercially available antibiotics can be targeted against them.Hospital-acquired


The utilisation of mechanical circulatory support devices in patients undergoing high-risk coronary artery bypass continues to increase. The Impella is a ventricular assist device commonly used in the setting of post-cardiotomy cardiogenic shock. This device can be implanted directly into the ascending aorta during open cardiac surgery. Device fracture is a documented complication of the Impella; however, the management of device fracture during direct explantation from an aortic graft has not yet been described. We report a case of Impella device fracture during its removal from a prosthetic aortic graft and discuss the management of this complication. The Impella device  is commonly used for mechanical circulatory support in patients with post-cardiotomy cardiogenic shock , 2. DuriA 47-year-old male presented with a chief complaint of chest pain and shortness of breath consistent with acute decompensated heart failure. He was diagnosed with non-ST-segment elevation myocardial infarction and underwent left heart catheterisation, which demonstrated multivessel coronary artery disease. Echocardiogram was significant for severe global hypokinesis with an ejection fraction of 14%. Additionally, the patient was suffering from acute renal failure secondary to cardiorenal syndrome. Prior to surgery, the patient temporarily required hemodialysis and inotropic support due to his decompensated heart failure. Ultimately, the decision was made to take the patient to surgery for high-risk aortocoronary bypass.The patient underwent three-vessel coronary artery bypass without complication. After the bypasses were performed, a side-biting aortic clamp was applied approximately 7 cm from the aortic root. A 6-mm aortotomy was created. A 10-mm Dacron graft was then anastomosed to the aorta in an end-to-side fashion using a 5-0 prolene suture. The graft was tunneled to the right neck and brought out through a skin incision above the clavicle. The Impella 5.5 was inserted into the graft and advanced into the left ventricle under trans-esophageal echocardiogram (TEE) guidance. Excess graft material was trimmed and the securing device was advanced to the end of the graft. It was secured using heavy silk ties. The remaining graft was placed below the skin through the supraclavicular incision and the device was secured in place.Post-operatively, the patient had a code blue event secondary to aspiration and respiratory arrest. This ultimately resulted in a non-perfusing ventricular arrhythmia. Advanced cardiopulmonary life support protocol was initiated and he briefly underwent chest compressions. He was successfully intubated and ventricular fibrillation was noted on the cardiac monitor. The patient was subsequently defibrillated with the return of spontaneous circulation. TEE was performed showing the Impella in the correct position. There was no evidence of damage to the device.After this event, the patient’s clinical status improved and he was weaned from mechanical circulatory support. On post-operative day 7, the patient was taken back to the operating room for Impella device removal. The device and graft material were pulled from the incision to expose the excess vascular graft. The Impella was turned to the P1 setting and pulled back into the graft. As the device was being removed from the aorta, the plastic cannula broke apart from the outlet portion of the device . The remThe Impella device has demonstrated improved outcomes in the management of patients with post-cardiotomy cardiogenic shock , 2, 6. TRisks associated with Impella fracture during retrieval include massive hemorrhage and device embolisation. If device fracture occurs during direct aortic explantation, we recommend placing a heavy vascular clamp across the graft proximal to the device remnant to prevent retrograde migration into the aorta. Maintain manual control of the device until a heavy crushing clamp can be used to grasp across the device within the graft. After the device is grasped, excess graft can either be rolled down or cut in order to expose the device remnant such that it can be retrieved in its entirety. It is imperative to confirm complete retrieval of the Impella by examining the device after explantation. Evaluation with TEE is also recommended.It is important to note that our patient underwent chest compressions while the Impella device was in place. We do not suspect damage to the Impella secondary to chest compressions as the device remained functional and no abnormalities were noted on echocardiogram; however, this cannot be entirely ruled out. Post-cardiotomy patients who develop cardiac arrest with an Impella should undergo defibrillation followed by bedside sternotomy if a blood pressure cannot be obtained. In this case, chest compressions were initiated by the intensive care unit (ICU) team. Upon arrival of the cardiothoracic service, the patient was successfully defibrillated and, therefore, did not require sternotomy.Fortunately, our patient was in the operating room when this complication occurred. Although Impella explantation can be performed at the bedside in the ICU, we recommend a low threshold for performing explantation in the operating room where additional surgical instruments are readily available.Finally, we recommend maintaining enough redundant graft to apply a clamp if needed. Although current recommendations include removing excess graft prior to device retrieval, this would not have allowed us to apply a clamp and ultimately grasp the device for removal.


Journal of the International AIDS Society, 13: 7–7. https://doi.org/10.1186/1758-2652-13-7Adhikari, R. (2010), Are Nepali students at risk of HIV? A cross‐sectional study of condom use at first sexual intercourse among college students in Kathmandu. “Are Nepali students at risk of HIV? A cross‐sectional study of condom use at first sexual intercourse among college students in Kathmandu” (the “Article”) by Ramesh Adhikari (the “Author”) in the Journal of the International AIDS Society , published online on 2 March 2010 on Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the Journal's Editors, the International AIDS Society and John Wiley & Sons Ltd. This retraction has been agreed as the author did not obtain the necessary ethical approval from the Nepal Health Research Council.


Correction: International Archives of Occupational and Environmental Health 10.1007/s00420-022-01922-zhttps://legislation.wa.gov.au/.Work Health and Safety (Mines) Regulations 2022, Available online: https://www.business.qld.gov.au/industries/mining-energy-water/resources/safety-health/mining/hazards/dust/exposure-limits.Exposure limits for dust in mineral mines, Available online: Unfortunately the reference was wrongly published. The correct reference is given below.


We leverage metadata on over 36 million journal articles and reviews indexed by Scopus in order to estimate migration of scholars based on information on changes in their institutional affiliations over time. We produce a database of yearly international migration flows of scholars, for all countries from 1998 to 2017. We use the open-access database to provide descriptive evidence on the relationship between economic development and the emigration propensity of scholars. Statistical analysis using generalized additive mixed models reveals that emigration rates initially decrease as GDP per capita increases. Then, starting from around 25,000 dollars , the trend reverses and emigration propensity increases as countries get richer. This U-shaped pattern contrasts with what has been found in the literature for emigration rates for the general population and calls for theoretical frameworks to understand the heterogeneous responses of migration to development. International migration and circulation of scholars is known to enhance research performance by facilitating knowledge recombination , 2 and iRecently, the digitization of scholarly publications and their consolidation into large citation and abstract databases have opened up new opportunities for analyzing migration of scientists at scale , 5. In tAs a first step, we produced an innovative open-access database that contains counts of active academic scholars, migration flows, and migration rates for all countries that include Scopus-published scientists. This migration database, which is obtained by leveraging metadata of more than 36 million journal articles and reviews published over two decades, is a major resource to advance our understanding of migration of scholars. While the underlying data are proprietary, our approach generates anonymized aggregate-level datasets that can be shared for noncommercial purposes and that we are making publicly available for scientific purposes.After having observed substantial heterogeneity in scholarly migration rates across countries, we consider associations and descriptive trends. A central question in migration studies is how international migration responds to economic development. The answer to this question has huge implications for migration policy and for development assistance programs. From an economic point of view, income effects, as GDP per capita rises, would decrease the economic incentives to migrate. Migration theories, however, suggest an inverted U-shaped relationship, where economic development initially leads to higher international migration, which then decreases in later stages of economic development . This paMigration transition theory leaves an open door for the international migration patterns of high-skilled professionals potentially diverging from the generic pattern . HoweverSI Appendix). The U-shape pattern of the marginals shown in While it is well known that migration is a complex and heterogeneous process, the lack of high-quality data on migration flows, including for population subgroups, has hindered theoretical advances in our understanding of the heterogeneous response of different groups of migrants to both short-term shocks and long-term change. In this article, we developed a global database on international scholarly migration in order to assess emigration patterns and trends for this key group of innovators , 2.Our empirical analysis focused on the relationship between emigration and economic development, indicating that the patterns in academic settings may be widely different from the population-level ones. We do not assess the underlying mechanisms, but we hypothesize that population heterogeneity matters for migration experiences. For example, the credentials of scholars might lead to lower barriers to entering rich countries. Moreover, scholars are more likely to have enough financial resources, or enough access to credit, for an international move, than the general population in a low-income country. They are also more likely to have an international network of colleagues and have developed migration aspirations. In other words, scholars in low-income countries are, on average, more capable to move than other segments of the population , 9. In aThe academic environment in the richest countries is such that universities and research institutions that compete for top places in world rankings increasingly spur international mobility. Attracting more international members (both students and faculty) is considered a performance indicator for institutions of higher education . EmphasiThis study creates a bridge between the fields of demography and migration studies on the one hand and science of science on the other. However, it does so not without limitations. From a data perspective, the emigration counts do not necessarily refer to nationals that leave a given country . Indeed,This study does not use a causal framework. The relationships observed are relevant and robust. Nonetheless, the observed regularities remain statistical associations that cannot be interpreted in a causal way. It is beyond the scope of this article to achieve causal explanations. In the study, we focus on macrodemographic trends. However, the underlying microdata that we use is structured essentially as a repeated panel where scientists are followed throughout their careers, as long as they remain active in terms of publishing. Future studies can leverage these rich microlevel data to move toward more causal explanations of underlying mechanisms that explain observed patterns.In this study, we leveraged bibliometric data to detect migration events of published scholars, to aggregate them, and to assess the relationship between scholarly migration and economic development. We used a 2020 snapshot of Scopus data maintained by Elsevier and provided to us by the German Competence Centre for Bibliometrics via the Max Planck Digital Library. We assessed changes in residence on the basis of changes in academic affiliation on an annual basis. This approach is in accordance with the definition of long-term emigrant as a person who changes his/her country of residence for a period of at least 1 y . For eacs(year) and smooth function of log GDP s(log GDP) as fixed terms, and two terms related to the country effect: random intercept s(country) and random slope s. The model formula reads: Our GAMM includes the following terms: smooth function of year Y is the emigration count and β0 is the intercept. More detailed information on detecting migration events, the statistical analysis, and supporting sensitivity analyses, can be found in SI Appendix.where Appendix 01 (PDF)Click here for additional data file.


Whole white rice is a major staple food for human consumption, with its starch digestion rate and location in the gastrointestinal tract having a critical role for human health. Starch has a multi-scale structure, which undergoes order-disorder transitions during rice cooking, and this structure is a major determinant of its digestibility. The length distributions of amylose and amylopectin chains are important determinants of rice starch gelatinization properties. Starch chain-length and molecular-size distributions are important determinants of nucleation and crystal growth rates, as well as of intra- and intermolecular interactions during retrogradation. A number of first-order kinetics models have been developed to fit starch digestograms, producing new information on the structural basis for starch digestive characteristics of cooked whole rice. Different starch digestible fractions with distinct digestion patterns have been found for the digestion of rice starch in fully gelatinized and retrograded states, the digestion kinetics of which are largely determined by starch fine molecular structures. Current insights and future directions to better understand digestibility of starch in whole cooked rice are summarized, pointing to ways of developing whole rice into a healthier food by way of having slower starch digestibility. Whole rice is the main staple food for a significant fraction of the world’s population, especially in Asia and Africa. It supplies many nutrients, including starch, protein and lipids. Starch is the most abundant nutrient in rice, and supplies more than 40% of human daily energy world-wide. The rate and location of starch digestion in the human gastrointestinal tract is critical for human health. If starch is rapidly digested once entering the duodenum, it can cause a large fluctuation in the postprandial glycemic response, which is a risk factor for the development of many chronic diseases such as type 2 diabetes . On the Whole rice grains are almost always consumed by humans following dehulling, polishing and cooking, although a relatively small number of people consume unpolished rice (“brown rice”) in their diets. Development of whole rice or rice-based products with more slowly digestible starch and higher resistant starch content is important for the rice industry, as it would improve public health. However, cooked polished whole rice grains have undergone a high degree of starch gelatinization during cooking, and also there is the lack of a physical barrier to digestive enzymes because of what is removed or degraded by dehulling and polishing.During the cooking of rice, the starch undergoes order-disorder structural transitions due to the solvation of orthorhombic nanocrystals , which aStarch multi-scale structures, e.g., molecular fine structures (notably the chain-length distributions of both amylose and amylopectin), and, at a higher structural level, microcrystalline domains, are major controllers of starch physicochemical and digestion properties . As discThis review summarizes recent understandings on starch order-disorder structural transitions during conventional whole rice cooking, and the influence of starch fine molecular structures on these processes. Their influence on starch digestibility in cooked whole polished rice is further critically discussed. To the best of the authors’ knowledge, this is the first review to comprehensively discuss starch gelatinization, retrogradation and digestion in an integrated way for whole polished rice at the molecular level. An overview of these new insights, incorporating previous knowledge on starch structure-property relations, may aid the development of cooked whole polished rices with desirable starch digestion properties. This information indicates ways that more nutritionally beneficial cooked whole polished rice having slower starch digestibility could be developed, with potential improvements in public health.Starch has a multi-scale structure, ranging from nanometres to millimetres . Often, The first level is individual starch chain comprising glucose monomer units connected by (1→4)-α glycosidic linkages, with (1→6)-α branch points. Following enzymatic debranching of the starch sample to quantitatively break every (1→6)-α branch point, the molecular weight or number distribution of this level can be characterized by the following techniques. (a) Size-exclusion chromatography (a widely used technique in polymer characterization) with a mass-sensitive detector, e.g., a differential refractive index (DRI) detector, and a multiple-angle laser light scattering detector for weight-average molecular weight and radius of gyration. With appropriate columns, this technique can be used for any DP range A. (b) FlEach characterization method has advantages and disadvantages, as follows.SEC separates by molecular size, not by molecular weight. The column is a solid material with many channels and pores, and smaller molecules diffuse into the smaller pores as well as the larger, and thus elute more slowly than larger molecules. While SEC can characterize any DP range, it requires calibration with standards of known size to convert elution time (or elution volume) into a molecular size, if only a DRI detector is available, which is often the case. With the addition of a light-scattering detector, one has absolute size measurement, this size being the hydrodynamic radius, which is not exactly the same as the geometrical size (the radius of gyration) . It alsoFACE works by labelling the individual linear starch polymers (obtained after debranching) with a fluorophore, then separating them by mobility in an electric field; it uses a fluorescence detector. It has very high resolution, with baseline separation between individual DPs, but only works up to DP below ~180 : this coHPAEC   can be uRice can be classified into waxy (0–2%), very low (3–9%), low (10–19%), intermediate (20–25%) and high (>25%) amylose content; these classes can have distinct textural and nutritional properties .Amylopectin CLDs have distinct features, including a global maximum around DP 12 and a shoulder around DP 45, the former being chains confined to a single lamella and the latter being trans-lamellar chains. These amylopectin CLDs can be fitted by a model  that notRice amylose CLDs frequently show only a single broad peak , althoug4 (asymmetirc-flow field-flow fractionation) and by size-exclusion chromatography  and amylopectin (Rh~100 nm) molecules are typically observed for ordinary rice starches . Th. Thq powThe fifth level of rice starch structure comprises the starch granules, which can be characterized quantitatively by a variety of particle-size measuring devices for the appropriate size range, and qualitatively by scanning electron microscopy (SEM). Native rice starch has a polyhedral shape E, which The sixth level of rice starch structure is frequently referred to as the cellular or grain structure F. In theLevels 1 and 2 starch structures are normally referred to as amorphous structures, while higher levels of native starch structures (level 3 to 6) can be referred as crystalline structures, due to the presence of amylopectin double helices. Conventional cooking of whole dehusked  rice involves the cooking with certain amount of water until the disappearance of the white core in the grain, followed by cooling to various extents (depending on the culture and region) prior to human consumption. During this process, rice starch undergoes gelatinization and then retrogradation, involving starch structural order-disorder transitions, which have been shown to be critical for starch digestibility in cooked whole rice.As stated, during the cooking of whole rice, starch (mainly the amylopectin component) undergoes an order-to-disorder phase transition, which greatly disrupts starch semi-crystalline structures, the extent of which depends on the cooking method. Starch gelatinization involves disruption of the hydrogen bonding in the crystal, which can be followed by events such as starch-granule swelling and amylose leaching, as well as the disruption of amylopectin double helices . (1) At cltr chains  and Afp chains  . Lo. Locltr eratures  57,63].,63.cltr Tc − To) of rice starches  nucleation, (2) crystal growth and (3) maturation . The nucl growth . Crystall growth ,72.Rice starch fine molecular structures are the main driving factors determining the nucleation and crystal growth rate during retrogradation, when all higher levels of starch structures are destroyed during gelatinization. Amylose has a rapid retrogradation rate due to its high mobility, which can thus result in the development of the skeleton of a starch hydrogel network, within which amylopectin molecules retrograde with a much slower rate ,75,76,77Starch fine molecular structures can also determine interaction patterns  among starch molecules during retrogradation . DiffereIn vitro digestion models simulating human gastrointestinal tract are widely applied to study rice starch digestibility , as theyA sequential digestion pattern is defined as that when the digestion of a slowly digestible starch fraction (SDF) only starts when the digestion of essentially all rapidly digested fractions (RDF) are completed. Seeing more than one straight-line region in an LOS plot indicates more than one starch digestion step. For heterogenous food systems containing simultaneously digestible fractions, e.g., a partially gelatinized starch with both melted (RDF) and intact (SDF) double helices, a parallel first-order kinetics model (PK) should be applied  87]. An. An87]. The major patterns in the starch digestibility of cooked whole rice depend on whether the starch is in a raw, gelatinized or retrograded state. Raw starch is difficult to digest compared to gelatinized starch, due to the presence of crystalline and granular structures, as summarized in When completely gelatinized, all starch crystalline structures are melted, which can substantially increase the starch digestibility of cooked whole rice. Before the consumption of cooked rice, either short-term  or long-term (storage in a refrigerator overnight or for few days), retrogradation is common. Differences in starch digestibility after gelatinization are thus determined by factors relating to starch fine molecular structures and their tendency to retrograde: a higher extent of retrogradation will result in a slower starch digestion rate ,91,92.The transition from disordered to ordered starch structures during retrogradation has a critical role in determining starch digestibility in cooked whole rice. There are two simultaneous starch digestion fractions for fully gelatinized rice starches , with thThere is moderately good understanding of the effects of starch fine molecular structures on starch gelatinization, retrogradation and digestion properties in whole cooked rice, but many questions remain to be further investigated. For example, cooking conditions (including the time and storage conditions between cooking and consumption) are also important for starch digestibility in cooked whole rice . It is uFreshly cooked white rice is digested very rapidly unless protected by other food components. For example, adding red-grape polyphenols during cooking can increase the RS content in cooked whole white rice . More foMany new insights have been obtained on the importance of starch fine molecular structures in determining the starch gelatinization, retrogradation and digestibility of cooked whole rice. Starch has a complex multi-scale structure in whole rice grains, which undergoes order-disorder structural transition during rice cooking. Amylose chain-length distributions, as well as the length of amylopectin chains, are significant factors in determining rice starch gelatinization properties. Amylopectin and amylose with different CLDs and molecular size distributions are involved in determining the nucleation and crystal growth rates, as well as inter- and intramolecular interactions during retrogradation.A number of first-order kinetics models have been developed for fitting starch digestograms, which offer a powerful tool to understand the structural basis for starch digestion properties in cooked whole rice. Different numbers of starch digestible fractions with different digestion patterns have been found for the digestion of rice starch in the fully gelatinized and retrograded states, which are partly determined by starch fine molecular structure. The combined effects of starch fine molecular structures, other ingredients in whole rice  and cooking conditions on the starch digestibility of cooked whole rice should be a focus of research in the future. Considering the popularity of cooked whole rice as a staple food, the information summarized in the current review can help the food industry to develop whole rice into healthier food products with slower starch digestibility, as long as there is no significant diminution of palatability.


Dear readers,The Brazilian Journal of Otorhinolaryngology has been renewed for 2011. In this first editorial of the year, the Brazilian Association of E.N.T. and Cervicofacial Surgery announces a change in its Journal's Board. However, our Journal's fundamental characteristics will remain untouched.The main Brazilian journal of otorhinolaryngology aims at spreading knowledge and socializing experiences, research and studies, always prioritizing science in its content. Besides consolidating the progress already achieved, and very competently achieved by the previous board, we intend to adopt an editorial policy which will enhance even further our Brazilian Journal Otorhinolaryngology.The main goal of the present board is to increasingly encourage Brazilian scientific production, attracting the interest of authors from other parts of the world, in order to broaden our participation in the world scientific settings. In recent years, authors from numerous countries have sent us their papers, showing a growing interest in our journal. This is very favorable, for it leverages citations from the Brazilian Journal of Otorhinolaryngology, thus increasing the impact factor measured by the Journal Citation Report and our journal's international projection. All of this helps improve the grades of our graduate programs at CAPES.To further this evolution process, the journal's editorial board will count on new teams of coeditors and associate revisers, both made up of experienced professionals in specific fields of our specialty, with active participation in scientific research, enabling a more careful assessment of the papers sent for publication.We'd like to thank and welcome them to our team.Happy New Year to all.


Abnormal mutations in the microbial structure of early-weaning mammals are an important cause of enteritis. Based on the multiple known beneficial functions of butyrate, we hypothesized that butyrate would alleviate the imbalance of intestinal homeostasis induced by early weaning in animals. However, the mechanisms of action between butyrate and intestinal microbes are still poorly explored. In this study, we aimed to investigate whether butyrate exerts beneficial effects on the structure of the intestinal flora of weanling rabbits and their intestinal homeostasis, growth and development, and we attempted to elucidate the potential mechanisms of action through a combined omics analysis. We found that dietary butyrate upregulated the transcription of tight junction-related proteins in the epithelial barrier and improved the intestinal microbial structure by suppressing harmful bacteria and promoting beneficial ones. Intestinal and plasma metabolomes were also altered. The bile acid secretion, α-linolenic acid, apoptotic, and prostate cancer pathways responded to the positive dietary butyrate-induced metabolic changes in the weanling rabbits, resulting in the inhibition of inflammation, improved antioxidant capacity, increased rates of cell proliferation and survival, and decreased levels of apoptosis. Additionally, dietary butyrate suppressed the release of pro-inflammatory factors and enhanced positive appetite regulation, which increased the average daily gain of the rabbits. These results demonstrated that dietary butyrate can help maintain the integrity of the intestinal epithelial barrier, improve the structural composition of the intestinal microflora, enhance organismal metabolism, inhibit inflammation, reduce post-weaning anorexia, and promote growth and development in early-weaning rabbits. These positive effects of dietary butyrate were exerted via the modulation of the microbe–gut–brain axis. In modern, large-scale, intensive animal production, early weaning is used to improve economic efficiency, resulting in greater early-weaning pressure. The associated stressors lead to the loss of appetite, growth retardation, a high incidence of diarrhea, and increased risk of disease and mortality ,2. TheseThe small intestine is the main site of nutrient digestion and absorption, as well as an important defense barrier against harmful exogenous and endogenous substances or pathogens . GastroiThe gut microbiome in healthy individuals is a balanced community of a multitude of microorganisms, including bacteria, viruses, phages, archaea, and fungi . The bacNumerous studies have shown that dietary butyrate is effective at promoting intestinal development and organismal growth in weaning mammals ,24,25. AIn this study, we investigated the effect of dietary butyrate on the growth status of early-weaning rabbits (30 days old). For this, we undertook a comprehensive analysis of the effect of dietary butyrate on the microstructure of the ileal epithelium, the transcriptional levels of physical intestinal epithelium barrier regulators, the ileum microbiome, the ileum metabolome, the plasma metabolome, inflammatory responses, and appetite regulation. Our findings provide a comprehensive description of the mechanism underlying the effect of dietary butyrate on the growth of early-weaning rabbits, as well as a reference for future research on and applications of butyrate in animal health care.p < 0.05) (p < 0.05); however, dietary butyrate did not significantly affect the feed conversion ratio (p > 0.05). The analysis of the H&E-stained sections of the ileum (p < 0.05), while results of the scanning electron microscopic analysis of the ileal lumen showed that dietary butyrate significantly improved the structural integrity of the luminal epithelium of the ileum (JAM3), and zonula occludens 1 (ZO-1) (p < 0.05), but it had no significant effect on that of JAM2, as determined with RT-qPCR (p > 0.05).We analyzed rabbit growth at different growth periods and found that dietary butyrate significantly increased the average daily feed intake and average daily gain of the animals at 30–40 days of age, 40–50 days of age, and 30–60 days of age ( < 0.05) A. Meanwhhe ileum B indicathe ileum C. Furthep < 0.05) but had no significant effect on the protein expression of NF-κB p65 (p > 0.05). In the hypothalamus (p < 0.05); however, no effect on the protein expression of NF-κB p65 and TNF-ɑ was observed (p > 0.05). An ELISA for the levels of inflammatory factors in the plasma revealed that dietary butyrate significantly downregulated the level of IL-1β in rabbit plasma (p < 0.05) but had a non-significant effect on that of TNF-α or IL-6 (p > 0.05). These results suggested that dietary butyrate alleviated early-weaning-induced inflammation to varying degrees and in different tissues.To investigate whether dietary butyrate could alleviate the inflammation caused by early weaning, we examined the levels of inflammatory factors in the ileum, hypothalamus, and plasma. As shown in thalamus B, meanwhp < 0.05) (p < 0.05) (p < 0.05).ELISAs for the levels of appetite-regulating hormones demonstrated that dietary butyrate significantly decreased the levels of CCK and PYY and upregulated those of ghrelin in the mucosal surface of the ileal lumen ( < 0.05) D In plas < 0.05) E. To furp > 0.05) (p < 0.05). The top 30 most abundant phyla at the genus level among the gut microorganisms were analyzed using species hierarchical clustering. As shown in To investigate the effects of dietary butyrate on the community structure of the ileal gut microbiota and microbial functions, we performed 16S rRNA gene sequencing. As shown in  > 0.05) C. Howevep < 0.05).To determine the extent to which microorganisms contributed to the achievement of group differences between the two experimental groups, we performed a LEfSe multilevel species difference discriminant analysis. As shown in p < 0.05). We also found a significant positive correlation between the differentially dominant bacteria within the control group and g_Escherichia–Shigella, while the differentially dominant bacteria within the butyrate group showed a significant positive correlation with g_Lactobacillus (p < 0.05).To study the interactions among the main microorganisms of the rabbit gut, we performed a one-factor, genus-level network analysis of the 208 species that were enriched in the gut. As shown in p < 0.05), as well as between g__Turicibacter and the average daily gain and feed conversion rate (p < 0.05). Meanwhile, g__Terrisporobacter was significantly and positively correlated with the rate of diarrhea (p < 0.05). In the butyrate group, three differentially dominant bacteria  and g_Lactobacillus were significantly and positively correlated with the average daily feed intake of the early-weaning rabbits (p < 0.05).We constructed a correlation network by calculating the correlation between the ileal microbiome at the genus level  and the growth status of the rabbits through a two-factor network analysis. As shown in JAM3, and ZO-1, while g__Hungatella was significantly and negatively correlated with that of ZO-1 (p < 0.05). In the butyrate group, significant positive correlations were found between the differentially dominant bacterium g__Faecalibaculum and claudin-1 gene expression, between g__Coriobacteriaceae_UCG-002 and claudin-2, and between g__CAG-352 and occludin, claudin-2, and JAM3 (p < 0.05). Additionally, g_Lactobacillus was significantly and positively correlated with the gene expression of claudin-1 (p < 0.05).As shown in p < 0.05). In the butyrate group, the differentially dominant bacteria g__Faecalibaculum and g__Coriobacteriaceae_UCG-002 were significantly and negatively correlated with IL-1β and p-NF-κB p65, while g__CAG-352 was significantly and negatively correlated with IL-1β, TNF-α, and P-NF-κB p65 (p < 0.05). Meanwhile, g_Escherichia–Shigella was significantly and positively correlated with the inflammatory factors TNF-α and IL-1β, and g_Lactobacillus was significantly and negatively correlated with IL-1β and p-NF-κB p65 (p < 0.05).Similarly, a two-factor network analysis of the relationship between ileal gut microorganisms and ileal tissue inflammatory factors was undertaken in both groups D. We foup < 0.05), while g__Hungatella was positively correlated with the gut–brain hormone PYY (p < 0.05). G__Turicibacter and g__Terrisporobacter were significantly and negatively correlated with the gut–brain hormone ghrelin (p < 0.05). In the butyrate group, the differentially dominant bacteria g__CAG-352 and g__Coriobacteriaceae_UCG-002 were significantly and positively correlated with ghrelin, whereas g__CAG-352 was significantly and negatively correlated with CCK and PPY (p < 0.05).The results of the two-factor network analysis of the correlation between microorganisms and gut–brain hormones in the intestinal lumen epithelial mucosa are shown in p < 0.05). In plasma, meanwhile, seven dominant metabolites were present in the control group and 43 dominant metabolites in the butyrate group (p < 0.05).OPLS–DA results demonstrated that the ileal and plasma metabolite distributions were relatively independent between the control and butyrate groups, indicating that dietary butyrate exerted a relatively significant effect on the metabolism of the rabbits A,B. Addip-value correction. As shown in p < 0.05).To determine the relationship of the ileal metabolome with growth status, intestinal epithelial barrier development, intestinal mucosal inflammation, and intestinal hormone levels in the rabbits, we undertook a Spearman’s correlation analysis of the association between the ileal metabolome and growth status, the expression of barrier-related genes in the ileum, the levels of intestinal inflammatory factors, and the levels of brain and intestinal hormones in the intestinal mucosa. The Benjamini and Hochberg method for controlling the FDR was used for p < 0.05). Metabolites that were significantly and negatively associated with intestinal epithelial barrier development included sphingosine, simmondsin, and spermidine (p < 0.05).The analysis of the correlation between the intestinal metabolome and the expression of intestinal epithelial barrier-related genes led to the identification of metabolites that were significantly and positively correlated with intestinal epithelial barrier development. These mainly included cholestane-3,7,12,25-tetrol-3-glucuronide; 2,4,5,7α-tetrahydro-1,4,4,7a-tetramethyl-1H-inden-2-ol; 17-methyl-18-norandrosta-4,13(17)-dien-3-one; 2,4,6-undecatrienal; and -17,23-epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trione (p < 0.05). The metabolites that were negatively correlated with inflammatory factor expression included 2,4,5,7α-tetrahydro-1,4,4,7a-tetramethyl-1H-inden-2-ol; (E)-2-(2-octenyl)cyclopentanone; -ergosta-7,22-diene-2,3,9-triol; 2,4,6-undecatrienal; and -1,10-bisaboladiene-3,4-diol (p < 0.05).We further assessed the putative correlations between the ileal metabolome and inflammatory factor expression in ileal tissue. The results showed that the metabolites 3β-hydroxycinnamolide; 5β-cholestane-3α,7α,24,26-tetrol; sphingosine; simmondsin; and spermidine were positively correlated with inflammatory factor expression (p < 0.05), whereas 5β-cholestane-3α,7α,24,26-tetrol; sphingosine; D-erythro-sphingosine C-17; and 15-hydroxyicosanoic acid were significantly and negatively correlated with ghrelin (p < 0.05). The intestinal metabolites that showed a significant positive correlation with PYY included sphingosine, simmondsin, and spermidine, while those that were negatively correlated with PYY included PE(15:0/16:1(9Z)); PE(15:0/18:1(11Z)); cholestane-3,7,12,25-tetrol-3-glucuronide; (E)-2-(2-octenyl)cyclopentanone; and 2,4,5,7α-tetrahydro-1,4,4,7a-tetramethyl-1H-inden-2-ol (p < 0.05). The gut metabolites that were significantly and positively correlated with CCK included 5β-cholestane-3α,7α,24,26-tetrol; sphingosine; and D-erythro-sphingosine C-17; the metabolites that were significantly and negatively correlated with CCK included PE(15:0/18:1(11Z)); sugeonyl acetate; salbutamol 4-O-sulfate; -17,23-epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trione; and 2,4,5,7α-tetrahydro-1,4,4,7a-tetramethyl-1H-inden-2-ol (p < 0.05). The gut metabolites PE(15:0/16:1(9Z)), DG(8:0/16:0/0:0), and PE(15:0/18:1(11Z)) were significantly and negatively correlated with the gut hormone GLP-1 (p < 0.05).Finally, we undertook an analysis of the correlation between the ileal metabolome and appetite-related intestinal hormones. We found that the intestinal metabolites salbutamol 4-O-sulfate; tetradecanedioic acid; 25-acetylvulgaroside; 2,4,5,7α-tetrahydro-1,4,4,7a-tetramethyl-1H-inden-2-ol; and 2,4,6-undecatrienal, among others, were significantly and positively correlated with the intestinal hormone ghrelin (p < 0.05). The main plasma metabolites found to be significantly and negatively correlated with the average daily feed intake, average daily weight gain, and feed conversion ratio were lysoPC), 4-hydroxybenzenesulfonic acid, and lysoPC) . Furthermore, 4-hydroxybenzenesulfonic acid was significantly and positively correlated with the rate of diarrhea in the rabbits, while aflatoxin B1 dialcohol, crustecdysone, L-urobilinogen, and 5-aminosalicylic acid showed a significant negative correlation with this parameter .A Spearman’s correlation analysis was performed to investigate the relationship between the plasma metabolome and the growth status of the rabbits. As shown in p < 0.05). Meanwhile, the plasma metabolites that were significantly and positively correlated with PYY and CCK included N-fructosyl isoleucine, lysoPC, and lysoPC), and those that were significantly and negatively correlated with PYY and CCK included hexadecanedioic acid; FA(18:2(OH2)); 17-octadecene-9,11-diynoic acid; 2-pentadecylfuran; and 5a-androstan-3b-ol (p < 0.05).Regarding the association between gut–brain hormones and plasma metabolites, we found that the hormone ghrelin was significantly and positively correlated with the metabolites crustecdysone, stearidonic acid, dolichin B, trilostane, and ercalcitriol, as well as others, and it was significantly and negatively correlated with the metabolites 4-hydroxybenzenesulfonic acid and 2-ethylacrylic acid (p < 0.05); those that were significantly and negatively correlated with inflammatory factor expression in the hypothalamus included trilostane, physagulin C, ercalcitriol, hydrocortisone, and dolichin B  (p < 0.05). We further found that the plasma metabolites that showed a significant positive correlation with POMC protein expression in the hypothalamus were PC/P-18:1(11Z)), N-fructosyl isoleucine, lysoPC), and lysoPC), while those that exhibited a significant negative correlation with POMC protein expression in the hypothalamus included trilostane, dolichin B, lactupicrin, stearidonic acid, and 3-hydroxydodecanedioic acid .Next, we performed a correlation analysis to determine the relationship between the plasma metabolome and hypothalamic inflammation or the expression of hypothalamic appetite response-related proteins. For hypothalamic inflammation, the results showed that the plasma metabolites PC/P-18:1(11Z)); 3-acetyl-2,7-naphthyridine; lysoPC); and 2-ethylacrylic acid were significantly and positively correlated with inflammatory factor expression in the hypothalamus  C. RegardTo determine the relationship of the ileal metabolome with the differentially dominant microorganisms in the control and butyrate groups, as well as with g_Escherichia–Shigella and g_Lactobacillus, we performed a Spearman’s correlation analysis A. The rep < 0.05). Members of the Peptostreptococcaceae family were significantly and positively correlated with the metabolites 3β-hydroxycinnamolide and 5β-cholestane-3α,7α,24,26-tetrol and negatively correlated with deoxycholic acid, 25-acetylvulgaroside, salbutamol 4-O-sulfate, DG(8:0/16:0/0:0), and -1,10-bisaboladiene-3,4-diol . The genus Terrisporobacter showed a significant positive correlation with the metabolites 3β-hydroxycinnamolide and 5β-cholestane-3α,7α,24,26-tetrol and a negative correlation with deoxycholic acid, salbutamol 4-O-sulfate, (E)-2-(2-octenyl)cyclopentanone, DG(8:0/16:0/0:0), 25-acetylvulgaroside, and other metabolites . The genus Hungatella was significantly and negatively correlated with, among other metabolites, DG(8:0/16:0/0:0); (E)-2-(2-octenyl)cyclopentanone; 17-methyl-18-norandrosta-4,13(17)-dien-3-one; (25S)-1α,25,26-trihydroxyvitamin D3; and -ergosta-7,22-diene-2,3,9-triol . g__Jeotgalicoccus was significantly and positively correlated with simmondsin and negatively correlated with (E)-2-(2-octenyl)cyclopentanone; -ergosta-7,22-diene-2,3,9-triol; (25S)-1α,25,26-trihydroxyvitamin D3; 17-methyl-18-norandrosta-4,13(17)-dien-3-one; and -17,23-epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trione, among other metabolites . g_Escherichia–Shigella was significantly and positively correlated with 3β-hydroxycinnamolide and negatively correlated with the metabolites (E)-2-(2-octenyl)cyclopentanone; deoxycholic acid; -17,23-epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trione; DG(8:0/16:0/0:0); and sugeonyl acetate, among others .In the first microbial functional community, g__Turicibacter was significantly and positively correlated with 5β-cholestane-3α,7α,24,26-tetrol; 15-hydroxyicosanoic acid; 3β-hydroxycinnamolide; and simmondsin; it was negatively correlated with deoxycholic acid; 2,4,6-undecatrienal; tetradecanedioic acid; sugeonyl acetate; and salbutamol 4-O-sulfate, among other metabolites . The genus Faecalibaculum was significantly and positively correlated with (E)-2-(2-octenyl)cyclopentanone; -1,10-bisaboladiene-3,4-diol; (±)-enterolactone; DG(8:0/16:0/0:0); and 2,4,5,7α-tetrahydro-1,4,4,7a-tetramethyl-1H-inden-2-ol . g__CAG-352 was significantly and positively correlated with the metabolites salbutamol 4-O-sulfate; 2,4,5,7α-tetrahydro-1,4,4,7a-tetramethyl-1H-inden-2-ol; 2,4,6-undecatrienal; glutamyltryptophan; and -17,23-epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trione, among others; it was negatively correlated with the metabolites D-erythro-sphingosine C-17, sphingosine, spermidine, and simmondsin . Finally, members of the genus Lactobacillus were significantly and positively correlated with the metabolites (E)-2-(2-octenyl)cyclopentanone, (±)-enterolactone, and tetradecanedioic acid and negatively correlated with D-erythro-sphingosine C-17 and sphingosine .In the second functional community, g__Coriobacteriaceae_UCG-002 was significantly and positively correlated with the metabolites 3β-hydroxy-6β-angeloyloxy-7(11)-eremophilen-12,8β-olide; -17,23-epoxy-3,28,29-trihydroxy-27-norlanost-8-en-24-one; and salbutamol 4-O-sulfate; it was negatively correlated with D-erythro-sphingosine C-17 and sphingosine ; 5β-cholestane-3α,7α,24,26-tetrol was significantly and positively correlated with the plasma metabolites 4-hydroxybenzenesulfonic acid and negatively correlated with ercalcitriol, hydrocortisone, lactupicrin, crustecdysone, trilostane, and others ; sphingosine showed a significant positive correlation with the plasma metabolites 2-ethylacrylic acid, PC/P-18:1(11Z)), and lysoPC), and it showed a significant negative correlation with trans-dehydroandrosterone, dolichin B, stearidonic acid, ercalcitriol, and trilostane ; simmondsin showed a significant negative correlation with ercalcitriol, trilostane, hydrocortisone, stearidonic acid, and dolichin B ; finally, spermidine was significantly and positively correlated with the plasma metabolite 3-acetyl-2,7-naphthyridine and negatively correlated with dolichin B .In the first functional group, 3β-hydroxycinnamolide was significantly and positively correlated with the plasma metabolites lysoPC), 4-hydroxybenzenesulfonic acid, and lysoPC), and it was negatively correlated with hydrocortisone, lactupicrin, dolichin B, ercalcitriol, and trilostane, among others . (E)-2-(2-octenyl)cyclopentanone showed a significant positive correlation with the plasma metabolites 17-octadecene-9,11-diynoic acid; trilostane; dolichin B; hydrocortisone; and stearidonic acid, among others; it showed a significant negative correlation with the plasma metabolites lysoPC), lysoPC), PC/P-18:1(11Z)), and N-fructosyl isoleucine ; deoxycholic acid had a significant positive correlation with the plasma metabolites ganoderic acid H, hydrocortisone, ercalcitriol, medicagenic acid, and 5-aminosalicylic acid, among others, and it had a significant negative correlation with the plasma metabolites lysoPC), lysoPC), and 4-hydroxybenzenesulfonic acid ; cholestane-3,7,12,25-tetrol-3-glucuronide was negatively correlated with the plasma metabolite 3-acetyl-2,7-naphthyridine ; -17,23-epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trione was significantly and positively correlated primarily with the plasma metabolites hydrocortisone, crustecdysone, ercalcitriol, trans-dehydroandrosterone, and floionolic acid, and it was negatively correlated with the plasma metabolites lysoPC), 4-hydroxybenzenesulfonic acid, and lysoPC) ; 2,4,6-undecatrienal was significantly and positively correlated with the plasma metabolites hydrocortisone, 3-hydroxydodecanedioic acid, trilostane, lactupicrin, and dolichin B, among others, and it was negatively correlated with the plasma metabolites lysoPC), PC/P-18:1(11Z)), and lysoPC) ; trans-4-coumaric acid was significantly and positively correlated with the plasma metabolites crustecdysone, hydrocortisone, ercalcitriol, aflatoxin B1 dialcohol, and lactupicrin, and it was negatively correlated with the plasma metabolites N-fructosyl isoleucine, lysoPC), PC/P-18:1(11Z)), and lysoPC) ; finally, albutamol 4-O-sulfate had a significant positive correlation with the plasma metabolites hydrocortisone, stearidonic acid, dolichin B, crustecdysone, and trilostane, among others, and it had a significant negative correlation with the plasma metabolites 4-hydroxybenzenesulfonic acid and lysoPC) .In the second functional group of ileal metabolites, sugeonyl acetate displayed a significant positive correlation with the plasma metabolites trilostane, hydrocortisone, ercalcitriol, aflatoxin B1 dialcohol, and physagulin C, and it displayed a negative correlation with the plasma metabolites 2-ethylacrylic acid; PC/P−18:1(11Z)); and 3-acetyl-2,7-naphthyridine . In the bile acid secretion pathway, the increase in the abundance of cholestane-3,7,12,25-tetrol-3-glucuronide and deoxycholic acid in the intestinal lumen promoted the digestion and absorption of intestinal fat and the biosynthesis of secondary bile acids, activated active ileocyte transport, and finally enhanced the portal and systemic circulation of bile acids. In the apoptotic pathway, a decrease in sphingosine content in the intestine, which was regulated by a cascade in the pathway, eventually leads to a decrease in DNA fragmentation and a subsequent reduction in the levels of apoptosis. In plasma, the differential metabolites stearidonic acid, 9(S)-HOTrE, and dodecanedioic acid were significantly associated with the α-linolenic acid metabolism pathway, while trans-dehydroandrosterone and hydrocortisone were primarily associated with the prostate cancer pathway (p < 0.05). In the α-linolenic acid pathway, the levels of stearidonic acid and 9(S)-HOTrE were increased, and the production of traumatic acid was increased by dodecanedioic acid. In the prostate cancer pathway, cell proliferation and survival were affected by trans-dehydroandrosterone and hydrocortisone, while there was no effect on other metabolic mechanisms in the pathway.The KEGG pathway enrichment analysis (with Benjamini and Hochberg correction for multiple testing) of the ileal and plasma metabolite sets in the butyrate and control groups was performed to identify the major pathways associated with the differential metabolites in the metabolic sets using a hypergeometric distribution algorithm. We found that the ileal-dominant differential metabolites spermidine; cholestane-3,7,12,25-tetrol-3-glucuronide; and deoxycholic acid were significantly associated with the bile secretion pathway. We also found that sphingosine was significantly associated with the apoptosis pathway -2-(2-octenyl)cyclopentanone was negatively correlated with inflammatory factors and harmful microorganisms . In animPlasma represents a less invasive biomatrix that can reflect the dynamic changes occurring in the metabolome of the whole organism and is employed in most metabolomics studies . Here, wThe dominant differential metabolite in the butyrate group, trilostane, was shown to be a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase isoenzyme system and is often used in animals to treat metabolic disorders due to pituitary-dependent hyperaldosteronism . The dolBased on a sodium butyrate addition experiment  was fixed in a 2.5% glutaraldehyde solution, while another (1.5 cm3) was fixed in a 4% paraformaldehyde solution.On days 10, 20, and 30 of the experiment, six rabbits in each group were randomly selected for sample collection. Blood was collected from the ear marginal vein into an anticoagulant-containing (sodium heparin) blood collection tube. These were then centrifuged at 3000 rpm for 10 min, following which the supernatant was transferred to a 1.5 mL centrifuge tube and stored at −80 °C. The rabbits were euthanized using the air embolization method. Samples of rabbit hypothalamus, ileum, and ileal contents were collected and rapidly stored in liquid nitrogen. An ileal tissue sample . Immobilized samples were rinsed three times with 0.1 M PBS , 15 min each wash, and then post-fixed in a 1% starvation acid solution at room temperature for 2 h, protected from light. After rinsing three times with 0.1 M PBS, 5 min each time, the tissues were sequentially immersed in 30%, 50%, 70%, 80%, 90%, 95%, and 100% alcohol, 15 min each time, and then immersed in isoamyl acetate for 15 min. Samples were then dried in a critical point drier and fixed on the ion sputterer sample stage with double-sided conductive carbon film adhesive and sprayed with gold for 30 s. Finally, the samples were observed and imaged under a scanning electron microscope.A 3 mmp > 0.1).Total RNA extraction and RT-qPCR were performed as previously described . Exon–inTotal proteins were extracted from ileal and hypothalamic tissue using a RIPA lysis buffer containing the protease inhibitor PMSF. After centrifugation at 12,000 rpm for 15 min at 4 °C, protein concentrations were measured using the BCA Protein Assay Kit . Total proteins were separated with 4–20% sodium dodecyl sulfate–polyacrylamide gel electrophoresis , transferred to polyvinylidene fluoride membranes , blocked for 1 h, and then incubated with primary antibody overnight at 4 °C. M5 Prestained Plus Protein Ladder  was used as the protein marker. Mouse anti-β-actin monoclonal antibody  was used as a loading control. Immunoreactivity was detected using an enhanced chemiluminescence (ECL) kit  and visualized using the Fluor Chem M system. ImageJ software was used for quantitative analysis .Plasma and ileum contents were centrifuged at 3000 rpm for 30 s at 4 °C, and the supernatant was transferred to a 1.5 mL centrifuge tube. ELISAs were performed according to the instructions of the respective kits , ghrelin, GLP-1, and peptide YY (PYY)) . Absorbance was measured at 450 nm using an enzyme marker, and the contents of IL-1β, TNF-α, IL-6, CCK, ghrelin, GLP-1, and PYY in the samples were calculated using the respective standard curves.The paraffin-embedding of sections and incubation with antibodies were performed as previously described . SectionThe primer pair 338F (5′-ACTCCTACGGGAGGCAGCAG-3′) and 806R (5′-GGACTACHVGGGTWTCTAAT-3′) was used for the amplification of the V3–V4 highly variable region of the bacterial 16S rRNA gene, which was performed in an ABI GeneAmp 9700 PCR Thermal Cycler . Sample processing and assays were performed as previously described . The cluhttp://www.genome.jp/kegg/; accessed on 9 December 2022) pathway enrichment analysis of the different metabolites was also undertaken.Samples were processed and measured according to the method described by Li et al. . Metabolhttp://www.drive5.com/usearch/; accessed on 9 December 2022), Mega , and Qiime  software, respectively. The KEGG pathway enrichment (kegg_v94.2), VIP scores, and orthogonal partial least squares discriminant analysis (OPLS–DA) of the metabolomics data were performed using the KEGG NETWORK database  and R  software. Other data were analyzed using SPSS 22 software. The Student’s t-test was used to compare differences between the two groups . Figures were prepared with Adobe Illustrator 2018 and GraphPad Prism 8 software.The analysis of OUT clustering, the evolutionary tree, and microbiome diversity was performed using Usearch  was reduced while that of beneficial bacteria  was increased. The abundance of beneficial metabolites in the intestinal metabolome ((E)-2-(2-octenyl)cyclopentanone; deoxycholic acid; sugeonyl acetate; salbutamol 4-O-sulfate; cholestane-3,7,12,25-tetrol-3-glucuronide; -17,23-epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trione; and 2,4,6-undecatrienal) and the plasma metabolome -HOTrE) was increased in the butyrate group relative to that of the control group; meanwhile, the abundance of unbeneficial metabolites ), PC/P-18:1(11Z)), lysoPC), N-fructosyl isoleucine, 3-acetyl-2,7-naphthyridine, and 2-ethylacrylic acid) was decreased. The microbiome and metabolome had a positive and mutually reinforcing relationship mediated by dietary butyrate. Moreover, dietary butyrate promoted both fat digestion and absorption in the intestine and bile acid circulation by modulating the bile acid secretion pathway, enhanced anti-inflammatory and antioxidant functions via the α-linolenic acid pathway, reduced apoptosis via the apoptosis pathway, and promoted cell division and survival by modulating mechanisms related to the prostate cancer pathway. The beneficial effects exerted by dietary butyrate included the protection and maintenance of the intestinal epithelial barrier, the suppression of inflammation, and the mitigation of post-weaning anorexia in rabbits. In this study, we elucidated the mechanism of action associated with the effects of butyrate on the microbial–gut–brain axis for the first time and found that it involves a multidimensional regulatory process that effectively alleviates metabolic disorders, post-weaning anorexia, and early-weaning-related growth retardation. Our findings provide a rationale for the application of butyrate in animal production and, consequently, in the promotion of human health.


The purpose of this article is the historical survey of the foundation and development of pharmacology in Tartu (Dorpat), Estonia. Pharmacology was founded in Tartu by Naunyn, Buchheim, and Schmiedeberg. Genealogy and biographies including selected references of pharmacologists and pupils, who acted from the very beginning to today as directors of the Department of Pharmacology, as well as its successor, the Institute of Pharmacology and Toxicology, are presented and commented. This history also illustrates the conditions that are important for the development of new scientific areas. It is not a central geographical location or a formal “center of excellence” with lots of financial resources but rather brilliant researchers with the right spirit and vision and academic freedom. The implications of the early history of pharmacology for the future of science are discussed. Naunyn–Schmiedeberg’s Archives of Pharmacology celebrates its 150th anniversary. It is the oldest pharmacological journal. Naunyn–Schmiedeberg’s Archives of Pharmacology is the official journal of the Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie . The journal is a general pharmacological journal and covers all areas of pharmacology and toxicology. On its 125th anniversary in 1998, Klaus Starke wrote an excellent account on the first 125 years of the history of this journal , the first journal of pharmacology worldwide. The first issue of the journal appeared in 1873. In 1904, Bernhard Naunyn moved to Baden-Baden. He published several books about diseases such as diabetes and cholelithiasis. His collected work appeared in Würzburg  and the pathologist and bacteriologist Erwin Klebs, he founded the g Naunyn . He was g Naunyn . In BerlBernhard Naunyn died on 26 July 1925 in Baden-Baden.Rudolf Richard Buchheim Fig.  was bornBuchheim founded experimental pharmacology by introducing animal experiments and chemical analyses. For this purpose, he established the first laboratory of pharmacology worldwide in the basement of his private house, having at hand only small financial resources but many gifted students and positive scientific spirit. In his laboratory, medical students carried out pharmacological experiments on animals and chemical and biochemicals determinations for more than 20 years, until in 1860, he moved to the Department of Pharmacology at the Anatomical Theater (Theatrum Anatomicum) of the University of Tartu. During his stay in Tartu, about 90 (sic!) doctoral dissertations were accomplished; Oswald Schmiedeberg belonged to his most prominent pupils and doctoral candidates. Thus, Buchheim early on recognized that personal academic investment into gifted students  is the single most important factor for nurturing a scientific field.The focus of the research in Tartu was the replacement of speculative drug properties by experimentally based knowledge; i.e., stringent logical thinking and analysis were implemented to the field of drugs. For example, lime water  had been used to treat tuberculosis by promoting acidification of the pulmonary foci. Buchheim postulated that due to the low water solubility, it is unlikely that enough talk is taken up into the organism so that lime water is of no use to treat tuberculosis. Since then, lime water or lime milk has been used to treat gastro-intestinal or dermal infections, but not anymore tuberculosis . In 1866, he received offers for a professorship at the Universities of Giessen and Bonn. He accepted the offer of Giessen. However, in Giessen, he had again to establish a laboratory in his private house with very modest resources. In 1970, the Institut für Humanpharmakologie (Institute of Human Pharmacology) was renamed to Rudolf-Buchheim Institut für Pharmakologie. This was an initiative of the Director of the Institute of Pharmacology, Ernst Habermann  of Ludwig and Baltza is the prototype for all devices developed since then used for the continuous registration of time-dependent biological data. The kymograph consists of a writer which scratches changes of, e.g., blood pressure on blackened glossy paper. The paper is fixed on a cylinder rotating with constant speed moved by a spring. The preparation of a uniformly blackened glossy paper demanded skillfulness. Many scientists, such as O. Schmiedeberg and R. Boehm, went to Ludwig to learn working with his kymograph. This kymograph was widely used, e.g., by v. Euler, Feldberg, Gaddum, and Holtz to discover neurotransmitters and their functions. Modern kymographs with electrically moving cylinders have been used in many laboratories of pharmacology and physiology until the 1960s.In the laboratory of C. Ludwig, he met the pharmacologist Rudolf Boehm  to whom he was connected with many years of friendship Fig. .Back to Tartu, O. Schmiedeberg became first extraordinary professor of pharmacology, dietetics, and history of medicine and in 1871, as a successor of R. Buchheim, he became ordinary professor and director of the Department of Pharmacology. During the years he spent in Tartu and Leipzig, he published experimental findings concerning muscarine  very clear and pleasant.”R. Boehm retired in 1921. In 1963, under the directorship of Fritz Hauschild, the Institute of the University of Leipzig was renamed to Rudolf-Boehm-Institut für Pharmakologie und Toxikologie  influences with cultural influences from Russia and Germany provided the optimal breeding ground for the birth of a new discipline that, by its nature, is interdisciplinary and does not fit the traditional canon of medical specialties. Thus, the absence of suffocating academic traditions and preconceived opinions often found in traditional “big” universities obviously facilitated the birth of pharmacology.Naunyn–Schmiedeberg’s Archives of Pharmacology were aware of the interdisciplinary nature of the new field, being a pharmacologist (Schmiedeberg), a clinician (Naunyn), and a pathologist (Klebs). This fundamental concept of pharmacology has proven to be valid until today  grant proposals and aiming for a high ranking in excellence tables, summing up impact factors, number of publications, and the amount of third-party funding. In times when financial resources for the entire research community again become limited because “Excellence” clusters consume a big share, we must rethink how we develop science by looking back into the history. For many projects, it simply takes creativity and collaboration with gifted young people. Like pharmacology, many successful Silicon valley businesses started in private homes.Obviously, close human relationships, friendship, mutual respect, and trust (illustrated in Fig.


The aim of this study was to ascertain the correlations between patients’ views of their recovery and clinicians’ views of patients recovery, symptoms and risk, in a cohort of patients in the National Forensic Service Dundrum (NFMHS).A cross sectional study was performed of all inpatients in the NFMHS Dundrum. The self-rated Dundrum tool was offered to all 96 in-patients and completed by 64. Clinican rated measures of violence risk (HCR-20), programme completion (Dundrum-3), recovery (Dundrum-4), symptoms (PANSS) and functioning (GAF MIRECC) were rated. ANOVA and concordance ratings were calculated using SPSSA total of 64 patients agreed to participate, of whom 10 were female. The self-rated Dundrum-3 correlated with the staff rated Dundrum-3 . The self-rated Dundrum-4 correlated with the staff rated Dundrum-4 . The self-rated Dundrum-3 correlated with the HCR-20 total , HCR-C , and HCR-R . The self-rated Dundrum-3 correlated significantly with GAF occupational , symptomatic . The self-rated Dundrum-4 correlated only with the GAF symptomatic . The self-rated Dundrum-3 correlated with PANSS positive , PANSS negative , PANSS general  and PANSS total . The self-rated Dundrum-4 correlated with PANSS positive  and PANSS negative .There was good correlation between patient and clinician ratings of programme completion and recovery. Patient self-ratings of programme completion and recovery correlated with staff ratings of functioning and symptoms. The directions of agreement were correct