Molecular MRI (mMRI) is a special implementation of Molecular Imaging for the non-invasive visualisation of biological processes at the cellular and molecular level. More specifically, mMRI comprises the contrast agent-mediated alteration of tissue relaxation times for the detection and localisation of molecular disease markers , cells  or therapeutic drugs . MRI yields topographical, anatomical maps; functional MRI (fMRI) provides rendering of physiologic functions and magnetic resonance spectroscopy (MRS) reveals the distribution patterns of some specific metabolites. mMRI provides an additional level of information at the molecular or cellular level, thus extending MRI further beyond the anatomical and physiological level. These advances brought by mMRI are mandatory for MRI to be competitive in the age of molecular medicine. mMRI is already today increasingly used for research purposes, e.g. to facilitate the examination of cell migration, angiogenesis, apoptosis or gene expression in living organisms. In medical diagnostics, mMRI will pave the way toward a significant improvement in early detection of disease, therapy planning or monitoring of outcome and will therefore bring significant improvement in the medical treatment for patients.15 per ml, i.e. the concentration is in the micromole range. Many targets, however, are expressed in even considerably lower concentrations. Therefore the most sensitive modalities, namely nuclear imaging (PET and SPECT) have always been at the forefront of Molecular Imaging, and many nuclear probes in clinical use today are already designed to detect molecular mechanisms . In recent years however, Molecular Imaging has commanded attention from beyond the field of nuclear medicine. Further imaging modalities to be considered for molecular imaging primarily include optical imaging, MRI and ultrasound.In general, Molecular Imaging demands high sensitivity equipment, capable of quantitative measurements to detect probes that interact with targets at the pico- or nanomolar level. The challenge to detect such sparse targets can be exemplified with cell surface receptors, a common target for molecular imaging. At high expression levels (bigger than 106 per cell) the receptor concentration is approx. 10 The above-mentioned concentration of molecular imaging targets in the micromolar range is challenging and requires sophisticated imaging strategies. Improvements in MRI design to reduce the lower detection limit are possible only to a certain extent; hence biophysical amplification mechanisms to enhance the signal from the label are necessary.Clinical MRI scanners offer a spatial resolution of 250 µm in-plane  or in T1-weighted images . For both classes, methods for signal amplification have been developed. In general, both take advantage of either very high relaxivity probes, background reduction (SNR optimisation) via activation of low-relaxivity probes by the targeted molecular marker (induced changes in relaxivity) or pronounced tissue accumulation. The latter is possible only with a very restricted number of highly expressed molecular marker (e.g. fibrin for thrombosis imaging).-1 [For T2-contrast agents, the most prominent labels are iron-oxide nanoparticles (Superparamagnetic Iron Oxide (SPIO), Very Small Paramagnetic Iron Oxide (VSPIO) or Ultrasmall Superparamagnetic Iron Oxide (USPIO)). These particles usually consist of a crystalline iron-oxide core, surrounded by polymer coating, often dextran, polyethyleneglycol or citrate. The advantage of these preparations is that each particle contains thousands of iron atoms resulting in very high T2 relaxivities of up to 200 (mMs)in vivo (cell tracking). Using this method, the spatial distribution of immuno-competent cells into tumours over time can be studied as well as the movement of stem cells, neuronal cells or blood stem cells in vivo [et al [Specific population of cells can be labeled with magnetic nanoparticles and followed  in vivo . A widelo [et al . Key conSimilar to PET-imaging, MRI can be used to image gene expression and to assess the efficiency of gene delivery. Viral or non-viral gene therapy schemes require targeting of the gene therapy vector to the tissue or cells of interest. Delivery of a therapeutic gene can be monitored by imaging of a reporter gene, which is introduced into the gene therapy vector and expressed together with the therapeutic gene . The repin vitro method for high throughput evaluation of biological specimens.A method named “magnetic relaxation switch” facilitates the reversible activation of MR probes . Target--1 range [in vivo binding of small sized contrast agents to serum proteins [Typical T1-contrast agents are small molecular weight compounds containing a single Lanthanide chelate as contrast producing element (e.g. Gadolinium-DTPA). The tissue concentration necessary to image with these T1-contrast agents on a molecular level is considerably higher than the required concentration of iron-oxide particles, it has to be in the order of mMols, since T1 relaxivity values are usually only in the in the 5-80 (mMs)proteins . MultilaSimilar to T2 contrast agents, T1-contrast probes can be activated by different mechanisms, thus increasing the relaxivity of the agent. This target-mediated increase of relaxivity leads to an increased contrast in the presence of the target. An enzyme-mediated polymerisation (e.g. bymyeloperoxidases up-regulated in vulnerable plaques) of paramagnetic substrates into oligomers represents one possible approach. In contrast to the small monomeric substrates these polymers have a larger hydrodynamic diameter and slower rotational rate of paramagnetic metal chelates. This results in a higher longitudinal relaxivity, and since the oligomeres are eliminated much slower than the monomers all signal will come after a certain time only from the oligomere, retained at the side of the target's presence . Anotherin vivo in all organs. It furthermore allows for the measurement of the pH or the temperature. Multiparametric mMRI might become feasible as CEST agents with different absorption frequencies of the exchanging protons can be designed. The sensitivity of CEST can be improved further by incorporating larger number of exchangeable protons into a (polymeric) CEST agent. This has been accomplished by LIPOCEST agents, liposomes containing a paramagnetic shift reagent for water protons in their aqueous inner cavity [Chemical-exchange saturation transfer (CEST) agents are another emerging class of negative MRI contrast agents, which facilitate an activatable contrast. The concept of CEST can be utilised to obtain highly amplified targeted agents. The principle is based on the fact that many molecules in the body exchange protons with bulk water through the selective RF irradiation of exchanging protons. After irradiating a millimolar pool of metabolite the energy is transferred to a nearby pool of water, producing a strong increase in enhancement by means of chemical exchange. With CEST and its newer development paraCEST specific metabolites can be detected. Using this method, the concentration of metabolites such as glucose can be evaluated non-invasively r cavity .Finally an “old friend” in MRI is attracting increasing attention in the course of Molecular Imaging: Fluorine-19. Xeno-labels, i.e. elements with low physiological concentration in situ but appropriate gyro-magnetic properties proved to provide superb traceability for mMRI.To date molecular imaging is increasingly used in laboratory studies. High resolution MRI is well suited to screen mouse models for tumours and other abnormalities and can be applied to non-invasively follow up new experimental treatment strategies. While dedicated animal systems are available, clinical scanners are also very capable of obtaining high-resolution images. To further speed up translational research, a small animal MR scanner based on a clinical console has been introduced just recently . This system comes with an adapted clinical user interface and supports therefore most of the features and sequences used on clinical scanners. Standardisation of the system ensures easy protocol transfer from and to clinical scanners. Applications being developed for humans on clinical scanners will be available on ClinScan. On the other hand, any application being developed for animals can be easily transferred to human diagnostics. In addition, adaptations for clinical scanner are underway for experimental molecular imaging. These include, but are not limited to, implementing dedicated small animal protocols, (quantitative) analysis tools or dedicated small animal RF coils. In conclusion, MRI is increasingly suited to carry molecular imaging from animal models into clinical practice.When will molecular imaging enter clinical medicine? Hot (hyper-intense) spots, which add information on the molecular mechanisms underlying a disease could guide radiologist and would be highly beneficial. Hyper-intense hot spots can be caused by highly specific accumulation of paramagnetic contrast agents. Most macromolecular Gadolinium-chelates are in an early pre-clinical research stages and the time needed to reach clinical applicability is considerable. Furthermore, toxicity concerns due to the prolonged retention of heavily Gadolinium-loaded molecules within the organism must be disproved. Superparamagnetic contrast agents can give easily detectable positive signal in combination with imaging techniques such as off resonance imaging.Superparamagnetic iron-oxide based contrast agents are easily detectable on T2-weighted sequences, even better so on T2*-weighted images due to susceptibility effects. Iron-oxide particles currently in clinical use can be utilised for cellular imaging of phagocyting cells, if combined with peptides, helping to traverse the membrane; this applicability can be even expanded to any other cell type. Iron-oxide particles can furthermore be functionalised with a wide variety of biological active molecules such as targeting moieties of peptides, antibody (derivatives), nucleic acids or aptamers to increase specific binding. Therefore a wide variety of imaging agents for mMRI is emerging and can facilitate steps towards clinical mMRI. Translational research with iron-oxide particles will take advantage of a growing basis of installed high field MRI scanners, since the lower detection limit decreases with increasing field strength.Besides being a powerful tool for the acquisition of molecular information, MRI is capable to add anatomical or functional information  to molecular images acquired with other modalities such as PET, SPECT or optical imaging. Combinations of CT and PET are increasingly used in clinical diagnostics. But there are some unique advantages for MR PET. Isocentric and simultaneous measurements are possible, no re-positioning of the patient, MRI can provide navigator technique and may give attenuation correction for PET, there is a better soft tissue contrast, and lower radiation exposure enables follow up studies. The ongoing development in imaging software and computing hardware facilitates co-registration and image fusion of physically separated units without delay. But repositioning of the patient and time interval between the scans makes fusion of separately obtained images difficult and inherently imprecise. Integrated devices would clearly be preferable even for economic reasons. Simon Cherry pioneered MR PET integration.Just recently the first fully integrated experimental set-up (based on semiconductor detectors) for MR PET has been presented by Siemens . Academiin vitro diagnostics (IVD) and knowledge driven healthcare , cost-intensive (molecular) treatment schemata (such as cell- or gene therapy) or therapies of chronic diseases. In such instances, a rational therapy selection based on comprehensive diagnostic data is a decisive factor for efficient and cost sensitive patient care. One of the main cost drivers in medicine is inappropriate treatment over a prolonged time. From a medical point of view, many arising molecular therapy concepts are based on individualised drugs. These treatments must be tailored to the individual biochemical set-up or disease stage of each respective patient with the support of diagnostic data. Equipped with these patient-specific data, a therapy regime is selected, taking into account the different molecular defects for each disease as well as the particular clinical history and condition of a patient.An example of how mMRI could contribute to this scope is radiation treatment planning by semi-automated lymph nodal cancer staging using a nanoparticle-enhanced lymphotropic mMRI. Preclinical data proves that mMRI demonstrate great promise for improving quality of diagnosis in general for oncologic- (tumour angiogenesis imaging), cardiovascular- (vulnerable plaque imaging) and neurological (Alzheimer’s plaque imaging) diseases.


Background. Acne vulgaris is a disorder of sebaceous glands mainly affecting the adolescent population. There are some misconceptions about acne not only in the general population but also among the medical students. Methods. Second year medical undergraduate students attending dermatology postings for the first time were included in the study. A questionnaire (in yes or no answer format) with 20 questions on acne, each carrying one mark, was to be answered by the students. The students were categorized into 4 grades based on the marks obtained: Grade I 90% marks and above, Grade II 75%–90%, Grade III 50%–74%, and Grade IV <50% marks obtained. Results. Of the 144 students of the batch, 95 (69.5%) completed both pretest and posttest questionnaires. The average pretest score was 14.1 and that of the posttest was 16.9. The percentage of improvement in mean score from pretest to posttest was 16.5. Fischer's exact test was applied to analyze the improvement in scores between pretest and posttests which is significant at P = 0.015 (P < 0.05). In the paired t-test the improvement in mean scores between pretest and posttest was significant at P < 0.001.  What is known? It is known that the knowledge of acne among general population is low. Acne vulgaris is a disorder of sebaceous glands mainly affecting the adolescent population. Up to 91% of adolescent male and 79% of adolescent females and 3% of adult male and 12% of adult females are affected [t-test was applied to assess any significant differences in mean scores between pretest and posttest.Second year medical under graduate students attending dermatology postings for the first time and who could complete both pretest and posttest questionnaires were included in the study. The study period was from January 2008 to December 2008. The questionnaire consisting of 20 questions was designed by us to include almost all aspects of acne, such as incidence, aetiopathogenesis, exacerbating factors, role of hormonal factors, and treatment, including myths and facts. The questionnaire had a simple yes or no answer format carrying one mark each. The students were asked to answer all the questions independently on the first day of their dermatology posting and once again at the end of their postings. The students were categorized into 4 grades based on the marks they obtained: Grade I, 90% marks and above, Grade II, 75%–89%, Grade III, 50%–74%, and Grade IV, <50% marks obtained. Pretest assessment was done to know the knowledge of acne among students and an overall assessment was done by comparing the scores obtained during pretest and posttest to know the improvement in the knowledge of acne. The results were tabulated and analyzed using SPSS version 16. Descriptive statistics, namely, mean and standard deviation was applied to describe the data distribution. Qualitative data with respect to different grades of scoring was presented using frequency and percentages. Fischer's exact test was applied to test any association between the various scoring grades between pretest and posttest. Paired Of the 144 students of the batch, 95 (69.5%) completed both pretest and posttest questionnaires. In the pretest, 30% of students believed this condition to be hereditary, 54% did not know that male hormones are implicated in the pathogenesis, 82% of students did relate acne to diet, and 32% believed that excessive face wash can improve acne. The average pretest score was 14.1 (±2.3) and posttest score was 16.9 (±1.8) with a minimum score being 8 and a maximum score being 20. The percentage of improvement in mean score from pretest to posttest was 16.5 . In pretOf the 3 who were in Grade IV in pretest, 1 (33.3%) secured Grade I and 2 (66.7%) secured Grade II in posttest. Of the 50 who were in Grade III in pretest 14 (38%) moved to grade I, 29 (58%) to grade II and 7 (14%) remained in the same grade in posttest. Of the 34 who were in grade II in pretest, 14 (41.2%) secured grade I, 16 (47.1%) remained in the same grade, and 4 (11.8%) declined to grade III in posttest. All the 8 who were in grade I in pretest remained in the same grade in posttest with significant increase in their marks .P = 0.015 (P < 0.05). The paired t-test was applied to know improvement in mean scores between pretest and posttest which was significant at P < 0.001.Fischer's exact test was applied to analyze the improvement in scores between pretest and posttest which was significant at P < 0.001 on applying paired t-test, indicating that there has been a significant difference in mean scores between pretest and posttest. It was also observed that students who were in lower grades in pretest improved considerably by securing higher grades in the posttest and those who were in higher grades in pretest continued to be in higher grades with significant improvement in their posttest scores as analysed using Fischer's exact test (P = 0.015) indicating that there is significant increase in number of students securing higher grades of marks.Acne vulgaris is a disorder of sebaceous glands mainly affecting the adolescent population. It is estimated that up to 91% of males and 79% of females are affected among the general population. Its prevalence is about 56% to 62% amongst medical students with no significant gender predilection . It has What is new? The knowledge about acne among medical students is limited and improved significantly after clinical postings.This is one of the first assessment studies based on knowledge of acne among medical students. This study highlights the impact of clinical teaching which not only imparts knowledge but also eliminates misconceptions.


The use of standardized portlets and a generally modular approach allows for the simultaneous and independent implementation of frontends for different molecular simulation codes. To date, functional prototypes of portlets for applications from the quantum chemical and the molecular dynamics domain are available, being represented by Gaussian and Gromacs, respectively. The implementation of other quantum chemical codes, as requested by the community, and of codes for docking simulations is in preparation.MoSGrid will furthermore foster efficient and collaborative work by providing secure but shareable repositories for validated data, as well as for reusable recipes and workflows -3.


The diagnosis of gastrointestinal (GI) involvement in Kaposi's sarcoma (KS) is important to make because the need for treatment depends on the extent of the disease. Moreover, severe GI lesions can cause serious complications. Endoscopy with biopsy is an extremely useful method to diagnose GI-KS. However, determining the indications for endoscopy is difficult because KS can occur without GI symptoms or cutaneous KS. This study sought to clarify predictive clinical factors for GI-KS and its severity on endoscopy.A total of 1,027 HIV-infected patients who underwent endoscopy were analyzed. Sexual behavior, CD4 count, HIV RNA, history of highly active antiretroviral therapy (HAART), GI symptoms, and cutaneous KS were assessed. Endoscopic severity including bulky tumor, ulceration, and number of lesions were evaluated. Thirty-three patients had GI-KS and 46 patients cutaneous KS. Among the GI-KS patients, 78.8% (26/33) had no GI symptoms and 24.2% (8/33) had no cutaneous KS. Univariate analysis identified men who have sex with men (MSM), CD4 <100 cells/µL, HIV RNA ≥10,000 copies/mL, no history of HAART, and cutaneous KS were significantly associated with GI-KS. Among these factors, cutaneous KS was closely related to GI-KS on multivariable analysis. Among patients without cutaneous KS, MSM and CD4 count <100 cells/µL were the only independent clinical factors related to GI-KS. Bulky tumor was significantly associated with CD4 <100 cells/µL and large number of lesions was significantly associated with HIV-RNA ≥10,000 copies/mL.To diagnose GI-KS, clinical factors need to be considered before endoscopy. The presence of GI symptoms is not useful in predicting GI-KS. MSM and CD4 count <100 cells/µL are predictive factors among patients without cutaneous KS. Caution should be exercised especially in patients with low CD4 counts or high HIV viral loads as they are more likely to develop severe GI-KS lesions. Kaposi's sarcoma (KS) is a rare type of cancer of the lymphatic and blood vessels that most commonly involves the skin The diagnosis of visceral involvement of KS is important to make because the need for treatment and choice of treatment depend on the extent of the disease Endoscopically, GI-KS can vary from flat maculopapular or polypoid masses to severe lesions. The latter can cause serious complications such as hemorrhage, perforation, and obstruction and may require emergent treatment In Japan, screening endoscopy is frequently performed for the early detection of malignant or premalignant lesions, even as part of the examination for patients who are asymptomatic. In this study, we performed endoscopy in a large number of HIV-infected patients with or without GI symptoms and cutaneous involvement.We conducted a case-control study to identify predictive clinical factors for diagnosing GI-KS, especially among patients without GI symptoms and cutaneous disease. We also assessed macroscopic appearance in detail looking for predictors of severe GI-KS lesions on endoscopy.We recruited 1,064 HIV-infected patients who had undergone endoscopy between 2003 and 2009 at the National Center for Global Health and Medicine (NCGM), a 900-bed hospital located in the Tokyo metropolitan area and the largest referral center for HIV/AIDS in Japan. We excluded patients who had received endoscopy for follow-up evaluation shortly after treatment for GI disease.The institutional review board at NCGM approved this study. All patients from whom clinical samples were obtained during endoscopy or biopsy had provided written informed consent prior to endoscopy. No ethical problems exist with regard to the publication of this manuscript. We used anonymized data from patient medical records.Before endoscopy, we routinely enter “purposes of the inspection” into the electronic endoscopic database. Purposes include examination for symptoms, screening for malignant or premalignant lesions, and follow up for endoscopic procedure or surgery. GI symptoms were assessed by the physician who interviewed each patient in detail. Those without GI symptoms and negative screening endoscopy were considered to be symptom-free.CD4 cell counts were checked within 1 week of endoscopy. We categorized CD4 cell counts into four groups: ≥300 cells/µL; 200–299 cells/µL; 100–199 cells/µL; and <100 cells/µL. HIV-RNA viral load (VL) as determined by real-time quantitative polymerase chain reaction (PCR) was reviewed within 1 month of endoscopy. The minimum detection level was 40 copies/mL of plasma. A positive result for real-time HIV RNA was defined as ≥40 copies/mL. HIV-RNA VL was categorized into four groups: VL ≤40 copies/mL ; 40<VL≤10,000 copies/ml; 10,000<VL≤100,000 copies/mL; and VL>100,000 copies/mL.History of HAART was collected from medical records prior to endoscopy and was categorized into five groups according to duration of administration: without history of HAART; duration ≤6 months; 6 months<duration ≤1 year; 1 year<duration ≤5 years; duration >5 years.HIV infection route was determined by the medical staff who interviewed each patient on the first visit to our hospital and classified into five categories: MSM, heterosexual, hemophiliac, injection drug user, and unknown. We defined sexual behavior as MSM or heterosexual. Patients who were not homosexual or bisexual were regarded as heterosexual.We performed biopsy when abnormal findings were encountered on upper or lower endoscopy. If we performed both upper and lower endoscopy in the same individual, this was defined as one case. GI-KS was suspected based on endoscopic appearance, such as the presence of submucosal nodules, polypoid nodules, or deep-red mucosa , as prevGI-KS was defined as the presence of proliferating spindle cells in biopsy specimens as seen on hematoxylin and eosin (HE) staining . SpindleAfter summarizing the descriptive patient characteristics, to identify predictive clinical factors for diagnosing GI-KS, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). The relationship between GI-KS and categories of CD4 cell count, HIV-RNA VL, and HAART duration were evaluated using the chi-square test for linear trends. For multivariable analysis, we used a multiple logistic regression model that included all factors showing values of p<0.1 on univariate analysis. Exact logistic regression was also used if the number in a cell was 0. A final model was then developed by backward selection of factors showing values of p<0.10.The relationships between endoscopic severity of GI-KS and clinical factors were also evaluated using the chi-square test. Values of p<0.10 were considered significant. All statistical analysis was performed using Stata version 10 software .Of the 1,064 potential study subjects recruited who underwent endoscopy, we excluded 37 who underwent endoscopy for follow-up evaluation shortly after treatment for GI diseases. Ultimately, the remaining 1,027 patients were selected for data analysis.Characteristics of the 1,027 patients with HIV are shown in Routes of HIV infection included MSM (67.0%), heterosexual (17.0%), hemophilia (13.6%), drug usage (0.2%), and unknown (2.1%). Median CD4 count was 239 cells/µL . Median HIV-RNA VL was <40 copies/mL . A total of 739 patients (72.0%) had received HAART.GI symptoms were noted in 368 patients (35.8%) as follows: appetite loss (n = 6); throat pain (n = 8); dysphagia (n = 11); reflux or heartburn (n = 22); epigastric pain (n = 87); nausea or vomiting (n = 36); hematemesis (n = 25); tarry stool (n = 43); hematochezia (n = 54); diarrhea (n = 87); distended abdomen (n = 2); and lower abdominal pain (n = 17).Of the 1,027 patients, 33 (3.2%) were diagnosed with GI-KS . GI lesiFive of eight GI-KS patients without cutaneous involvement underwent HAART for a mean duration of 1.84 months.Univariate analysis identified MSM, CD4 count <100 cells/µL, HIV RNA VL ≥10,000 copies/mL, no history of HAART, and the presence of cutaneous KS as significant clinical factors for the development of GI-KS .As the CD4 count decreased , occurrence of GI-KS increased significantly , ulcerous lesions (n = 11), and multiple lesions (n = 9). Relationships between endoscopic severity of GI-KS and clinical factors are shown in Endoscopy is clearly a valuable diagnostic method for identifying GI-KS, but it is not recommended for all HIV-infected patients because of considerations of cost and invasiveness. The present study therefore sought to answer which HIV-infected patients need endoscopy to detect visceral KS.We found that MSM, low CD4 (<100 cells/µL), high HIV RNA VL , no history of HAART, and presence of cutaneous KS were predictive clinical factors for GI-KS on univariate analysis. Our findings are consistent with past studies on HIV-infected patients from Western countries that showed an association between clinical factors and cutaneous KS or visceral KS Endoscopy is usually considered to be indicated for GI-KS diagnosis in patients who have GI symptoms Previous studies have shown that KS occurs more commonly among MSM with AIDS than among heterosexual individuals with AIDS HAART is known to represent a highly effective treatment for GI-KS, and can improve the immune status of patients It has previously been shown that patients with KS typically have a low CD4 cell count (<150 cells/µL) and a high HIV RNA VL  KS manifests primarily as a cutaneous disorder, with visceral involvement considered to occur subsequently It has been reported that GI-KS can occur in the absence of cutaneous disease We investigated the possibility that HAART administration led to the disappearance of cutaneous KS prior to the diagnosis of GI-KS in patients without cutaneous involvement. In fact, five of eight GI-KS patients without cutaneous KS had a history of HAART. However, the mean duration of the administration was less than 2 months, and it is difficult to imagine that cutaneous KS disappeared from the whole body in such a short period of time. Therefore, it is unlikely that HAART administration had any involvement in the absence of cutaneous KS in these GI-KS patients.In this study, we assessed endoscopic severity such as tumor bulk, ulceration, and multiple lesions as these may cause obstruction, hemorrhage, and perforation A key limitation of this study was the single-center, retrospective nature of the investigation. When considering indications for endoscopy, a randomized controlled study is required to identify whether endoscopy can prevent the development of severe GI complications in HIV-infected patients, particularly among those with a low CD4 count. Second, the number of GI-KS patients was relatively small, especially those without cutaneous KS. The statistical power of the study might thus have been low due to the small number of cases.To diagnose GI-KS, clinical factors need to be considered before endoscopy is undertaken. Presence of GI symptoms is not useful in predicting GI-KS. The presence of cutaneous KS, MSM sexual behavior, low CD4 count (<100 cells/µL), high HIV RNA VL, and no history of HAART are predictive factors for GI-KS. Even if patients have no cutaneous KS, endoscopy may be suitable for patients with MSM and low CD4 count (<100 cells/µL). Caution should be exercised especially in patients with a low CD4 count (<100 cells/µL) or high HIV RNA VL  as they are more likely to develop severe GI-KS lesions. This diagnostic strategy could facilitate early diagnosis of GI-KS.


Background. Macroprolactin, the high-molecular prolactin isoform, is considered to be an inactive in vivo product with extrapituitary origin. Patients with macroprolactinemia are usually asymptomatic, with negative pituitary imaging. Based on these data, most authors do not recommend treatment and long-term followup in subjects with macroprolactinemia. However, there is evidence for overlapping clinical features among subjects with hyperprolactinemia due to monomeric or “big big” PRL isoform. Case Presentation. We present a 35-year-old female patient with secondary amenorrhea, mild obesity, hirsutism, headache and blurred vision. Hormonal evaluation revealed an extreme hyperprolactinemia (PRL = 10 610 mIU/L) almost exclusively due to macroprolactin isoform  and hypogonadotropic hypogonadism. An invasive pituitary macroadenoma was visualized on MRI, and cabergoline therapy was initiated. Disappearance of clinical signs and symptoms, normalization of gonadotropin levels, and restoration of regular ovulatory menstrual cycles after 1 year of treatment are arguments in favor of preserved-macroprolactin bioactivity in this case. The significant decrease in MPRL levels and tumor volume in response to dopamine agonist therapy is suggestive for the tumoral origin of this isoform. Conclusions. Although macroprolactinemia is considered to be a benign condition, pituitary imaging, dopamine agonist treatment, and prolonged followup should be recommended in some particular cases. Three different isoforms of circulating human prolactin (PRL) have been identified: a monomeric (“little” PRL with a molecular weight of 23 kDa), a 50 kDa “big” PRL, and a high-molecular form (>l00 kDa), termed “big big” or macroprolactin , 2. In pPhysical examination revealed mild hirsutism , visceral obesity (BMI  =  31.2%), and no galactorrhea. Hormonal analysis: Venous blood samples were taken in the morning, after 30 minutes of rest   Ultrasound Machine. Repeated exams demonstrated severely impaired folliculogenesis and anovulation. Contrast-enhanced high-resolution magnetic resonance imaging (MRI) revealed an invasive macroadenoma (21  ×  13 mm) with left cavernous sinus involvement  and no evidence of optic chiasm compression . Restoration of ovulation was objectified by transvaginal ultrasound folliculometry. Significant weight loss  and beneficial effect of dopamine agonist treatment on the headache and general condition were also reported by the patient  was started using a standard dosage regimen: 10 mg daily from the 16th to the 25th day of the menstrual cycle. A good therapeutic response was initially achieved, and the patient could maintain regular menstrual cycle for about one year. After that, recurrence of oligomenorrhea occurred in spite of the twofold increase of Didrogesterone dose. The treatment was discontinued which resulted in a permanent amenorrhea. The patient was referred to the University Hospital of Endocrinology where full clinical and hormonal evaluations were carried out. l cycle) . Serum P Figures . Ophthal patient . A marke patient .Issues regarding biological activity and the site of macroprolactin synthesis are still not completely resolved. According to the literature the majority of patients with macroprolactinemia are oligo- or asymptomatic which supports the hypothesis for a decreased biological activity of the high molecular prolactin isoform , 4, 16. Macroprolactin synthesis is thought to be an extrapituitary postsecretory phenomenon , 15, 24.Our female patient with invasive macroprolactinoma and proven macroprolactinemia with extremely high PRL levels and typical clinical presentation represents an example that in some although very rare cases the high-molecular PRL isoform may exert preserved biological activity. Restoration of regular ovulatory menstrual cycle under dopamine agonist treatment supports this hypothesis. The decrease of MPRL levels after dopamine agonist treatment could suggest a tumoral origin in this case. Marked reduction in the pituitary tumour volume well corresponding with the clinical and laboratory improvement is another strong argument in favour of this thesis.In the vast majority of cases, although long-lasting and relatively stable, macroprolactinemia is associated with mildly elevated prolactin levels, oligo- or asymptomatic presentation, and negative pituitary imaging and does not need further investigation and treatment. Macroprolactinemia associated with invasive pituitary prolactinoma presenting with hyperprolactinemia-related clinical manifestations is an extremely rare condition which requires long-term therapy and followup. Similar to monomeric hyperprolactinemia, conservative treatment with dopamine agonists seems to be safe and effective, thus preventing unnecessary transsphenoidal surgery and possible complications in these particular cases.


This Essay from Nicola Low and colleagues discusses the importance of the nucleic acid amplification tests for rapid detection of N. gonorrhoeae and its resistance determinants, as well as the importance of ensuring their rational use, as priorities for controlling both gonorrhoea and antimicrobial resistance.Please see later in the article for the Editors' Summary Antimicrobial resistance and overuse of antimicrobials are serious threats to the treatment of gonorrhoea.Neisseria gonorrhoeae susceptibility to extended spectrum cephalosporins is decreasing and treatment failures are spreading, but no new drug class is licensed to replace them for immediate treatment.Nucleic acid amplification tests are increasingly used to diagnose gonorrhoea but current commercially available tests do not detect antimicrobial resistance.Tests for gonorrhoea that allow individually tailored antimicrobial therapy at the first contact with health services will need to be point-of-care tests that can be integrated into the diagnostic process to give accurate results in around an hour.N. gonorrhoeae and its resistance determinants and ensuring the rational use of antimicrobials are priorities for controlling both gonorrhoea and antimicrobial resistance.Development of nucleic acid amplification tests that incorporate rapid detection of N. gonorrhoeae as becoming an untreatable superbug Antimicrobial resistance (AMR) is making the clinical management of infections such as gonorrhoea increasingly difficult worldwide Staphylococcus aureus (MRSA) and its main resistance gene The emergence of ESC resistance has coincided with the rapid expansion of molecular diagnostic testing for gonorrhoea . PCR is N. gonorrhoeae in the context of AMR and the implications of AMR for gonorrhoea treatment recommendations.The limitations of molecular diagnostic tests for sexually transmitted infections are less widely publicised and tend to focus on diagnostic test performance issues Prompt and appropriate treatment for patients with gonorrhoea and their sexual partners at the first contact with health services is the priority, endorsed by international guidelines N. gonorrhoeae infections and is completely specific if adequate confirmatory tests are done N. gonorrhoeae has fastidious growth requirements so highly nutritious selective culture media are needed  than culture-based testing (48 hours). But the actual turnaround time, from ordering the test to changing patient care, is not much faster if the molecular test is run on batched samples once a day or every other day N. gonorrhoeae genetic resistance determinants, minimum inhibitory concentrations of ESC, and treatment outcome currently makes it difficult to use genetic markers to guide therapy for gonorrhoea Molecular methods for AMR The first documented case of XDR-NG was diagnosed in a Japanese female sex worker who had a pharyngeal infection diagnosed initially by NAAT. A culture specimen was obtained two weeks later when she returned for treatment but there was no post-treatment culture specimen and she was lost to follow-up for three months, after receiving a second dose of ceftriaxone for presumed treatment failure diagnosed by NAAT N. gonorrhoeae on specimens taken for chlamydia screening in populations at low risk of gonorrhoea such as asymptomatic heterosexual adults tested in primary care N. gonorrhoeae show very high specificity Neisseria species Neisseria spp. develop resistance and that resistance determinants will be transferred horizontally to N. gonorrhoeaeSimplified specimen collection and multiplex testing have disadvantages. Over-testing is facilitated by simultaneous testing for N. gonorrhoeae and C. trachomatis even if the tests are done simultaneously in the same automated procedure The high cost of NAATs can result in over-testing or under-testing, depending on who has to pay for the test and who makes the profit. Over-testing with NAATs occurs if health care systems reimburse laboratories for the number of analytic targets. Laboratories can charge twice for a NAAT to detect Mycoplasma genitalium and experts have called for its use to treat all bacterial sexually transmitted infections to be limited Antimicrobial prescribing policies can also contribute to the emergence of AMR gonorrhoea Could the expansion of NAAT diagnosis for gonorrhoea exacerbate the continuing spread of AMR gonorrhoea? There is no definitive answer to this question yet but there are issues that should be investigated further, given the global increase in AMR, the lack of new first line antimicrobials for gonorrhoea treatment N. gonorrhoeae diagnosis than for C. trachomatisN. gonorrhoeae do not appear to mention the inability to give AMR data as a potential problem Another reasonable question is whether diagnostic test manufacturers, regulators, and researchers should have considered the implications that NAATs for gonorrhoea diagnosis might have on AMR before promoting and expanding their use so widely. The benefits of NAAT diagnosis for sexually transmitted infections often consider gonorrhoea and chlamydia together. The gains in sensitivity and technical complexity of NAATs compared to culture are smaller for N. gonorrhoeaeAcademic research groups have developed in-house molecular tests for one or more genetic determinants of AMR N. gonorrhoeae and AMR determinants reliably, particularly in resource poor settings. The true cost of ignoring gonococcal AMR will include the costs of treating the infection and its complications as experienced in the pre-antibiotic era Current knowledge and practice about the use of NAAT for gonorrhoea diagnosis could be improved in several ways. First, all national and international guidelines about the use of NAAT for gonorrhoea diagnosis should specify situations in which culture-based testing and tests of cure are needed; transport media that can be used for both NAAT and culture will facilitate this. The cost of additional testing should be borne by the health system because the information about AMR would be used for the public health good. Second, in the absence of empirical diagnostic trials, mathematical modelling will be needed to explore the impact of NAAT-based rapid tests for the detection of AMR gonorrhoea on the spread of resistance and on clinical outcomes. Dynamic transmission models can capture the net effects of competing factors such as increased detection and treatment of gonorrhoea, increased re-infection risk, and reduced or delayed detection of AMR on the transmission of gonorrhoea and of resistant strains. Third, clinicians should follow international guidelines for the early detection of ESC resistant gonorrhoea and clinical treatment failure, which take into account the role of NAAT diagnosis


Methods. A purposive sampling of 24 Somalis, including activists and practitioners, men and women, was conducted in Somalia. Unstructured interviews were employed to explore the participants' knowledge of FC, their attitudes toward the continuation/discontinuation of the practice, and the type they want to continue or not to continue.Result. The findings of this qualitative study indicate that there is a strong resistance towards the abandonment of the practice in Somalia. The support for the continuation of Sunna circumcision is widespread, while there is a quite large rejection of Pharaonic circumcision.Conclusion. Therefore, since the “zero tolerance policy” has failed to change people's support for the continuation of the practice in Somalia, programmes that promote the pinch of the clitoral skin and verbal alteration of status, with the goal of leading to total abandonment of FC, should be considered for the Somali context.Somalia has the highest global prevalence (98%) of female circumcision (FC), and, despite a long history of abandonment efforts, it is not clear as to whether or not these programmes have changed people's positive attitudes toward the practice. Against this background, this paper explores the attitudes of Somalis living in Hargeisa and Galkayo districts to the practice of FC.  The traditional practice involving the removal or injury of female external genitals, namely, female genital mutilation/cutting (FGM/C), or female circumcision (FC), which is the term we use in this paper and is a literal translation from the Somali language (gudniinka dumarka), has long survived in Africa in the name of tradition though in recent decades the practice has received worldwide attention, with its abolishment determined by a broad international consensus . AccordiFemale circumcision is most prevalent in 28 African countries, but is also found in Asia and Western countries that host immigrants from areas with FC traditions . ApproxiThe victims of this practice may suffer tissue damage that may negatively affect the health of the girls over the course of their lifetime . Local aThe efforts towards the abandonment of FC date back to the early 20th century when European missionaries and colonial powers in Africa attempted to stop the practice by introducing laws and church rules, the result of which was anger against the colonial powers . AccordiAccordingly, a number of professionals with extensive research experience on FC in Africa suggested the importance of reducing the harm when total abandonment is not feasible , 16. Othgudniinka sunniga ah), which is perceived as mild, but can encompass anything less than Pharaonic, and the Pharaonic form (gudniinka fircooniga ah), which is considered to be severe and involves suturing the side fleshes together, leaving a small opening for urine and menstrual blood to pass through  University in Egypt to come here, and they supported the total abandonment of FC. Somali religious leaders did not accept that by saying that the Sunna form should continue. One of the main obstacles toward the total abandonment of FC that emerged from the interviews was the fact that opinion shapers, such as religious leaders are sympathetic to Sunna circumcision, and therefore encourage its continuation: Yes I attended seminars. I was informed that the Pharaonic form should be abandoned because it is wrong. Girls should be subjected to the Sunna form, which is not harmful to girls.  I attended seminars…I have learned that Somalis should abandon the Pharaonic circumcision, as it causes a number of health problems. I attended seminars and I learned about the problems of Pharaonic circumcision. I did not attend a seminar, but I heard from the radio and the media that Pharoanic[sic] circumcision should be stopped. In response to a question about “whether the participants have attended awareness programmes and what they have learned from the programme,” almost all the participants who attended awareness programmes or heard about it on TV were told to abandon Pharaonic circumcision. Some participants stated that they were told to circumcise girls with Sunna circumcision and abandon Pharaonic: If the government accepts that girls are circumcised with Sunna circumcision, people will accept it, but surely people will not accept total abandonment. Rejecting the Sunna form that religion requires is like saying “abandon your religion”. This is a strong tradition that existed for a long time. If it is intervened through the legal system, it will grow even stronger. People may say that the government is against our culture, tradition and religion. This may put the government at risk. I would not support illegalization because if the government gets involved with this long tradition, while very few people shifted to Sunna and the majority still used Pharaonic, the government will have difficulties. I think they should wait until more people shift to Sunna. People should be encouraged to abandon the practice and be given knowledge about it. But the government and NGOs should leave the decision about its abandonment to the people. Participants were asked about their perspectives toward the criminalization of FC in their country. The vast majority of the study participants stated that the criminalization of the practice would not be a solution, but that it may instead create a confrontation between the government and the public. The illegalization of Sunna circumcision is perceived as a violation of religious rights and a serious issue that cannot be tolerated:  Sunna form in particular, while rejecting the Pharaonic form. This finding is consistent with prior quantitative findings in Somalia [Sunna circumcision. Given the fact that many Somalis may support one form of FC while rejecting others, the importance of the categorization of questions addressing FC by type is underlined; a failure to do that may cause a risk that researchers will draw the wrong conclusions. For instance, the Multiple Indicator Cluster Survey (MICS) by UNICEF in 2006 demonstrated that only 32% of people in the northwest region of Somalia support the continuation of FC [Sunna and Pharaonic, asking them which one should be continued or discontinued. The MICS also considered the categorization of the practice by type in their published questionnaire although they did not consider the answers to this question in their report [This qualitative study explored the attitudes toward FC among Somali men and women in the Hargeisa and Galka'ayo districts of Somalia. The findings show that almost all the participants supported the continuation of female circumcision, with the majority supporting the continuation of the Somalia , 44, in Sunna circumcision in Somalia, with the findings revealing that the most prevalent Sunna cut in Somalia involves either the partial or total removal of the clitoris, followed by two stitches. When the operation involves stitching, the WHO classifies it as Type III regardless of the number of stitches [The present study explored the extent of the cut involving the stitches , which istitches . Some ofstitches , 45. At Do not cut too severely, as that is better for a woman and more desirable for a husband.” However, many religious scholars regarded this passage as having little credibility or authenticity. Even so, the Koran clearly rejects an alteration of the human body from the way God has created it. Female circumcision is therefore a controversial topic within Muslim circles; still, the important point to note is that Islam safeguards women's rights to sexual enjoyment and health, and if female circumcision violated those rights it would automatically be considered as being forbidden. This study reports a pervasive resistance to the total abandonment of FC in Somalia. The majority of the participants in this study supported the continuation of Sunna circumcision, while few people supported the continuation of Pharaonic circumcision. The Sunna cut may involve anything different from the Pharaonic cut, and behind the support of the Sunna circumcision lies the belief that Sunna circumcision is a religious requirement. Generally speaking, supporters of Sunna circumcision use a single Hadith as a justification for their argument. The hadith says, “The participants who supported the continuation of Pharaonic circumcision used its importance for the virginity and marriageability of girls as a justification for the continuation of FC though it is unfortunate that the practice designed to make girls reproductive (marriageable) may ultimately cause them to become infertile . While bSunna circumcision is allowed by religion and it should be continued” [This study shows the number of obstacles toward the abandonment of the practice in a study setting, with the most important thing being the support and tolerance of the practice by opinion leaders. The importance of religious leaders/politicians' involvement in the abandonment of the practice has been documented . Howeverntinued” , as the This study also indicates that campaigners in Somalia reject the Pharaonic form only, and not the Sunna form. Hence, it is important to note that FC is a strongly believed in tradition, and that whoever dares to oppose it in Somalia does so against the tide of public sentiment. The campaigners themselves are part of society and cannot go against the will of the public or they may pay a heavy price. It is therefore very clear that the public rejection of the Pharaonic cut is widely prevalent in Somalia while the Sunna cut, which is anatomically undefined, entertains overwhelming support because of its association with religion and the perception that the Sunna cut does not have any health problems. Shell-Duncan states that “harm reduction strategies may be a sound and compassionate approach to improving women's health in settings where total abandonment of the practice is not immediately attainable” . The autIn 2011, the WHO published a policy brief entitled, Female Genital Mutilation programmes to date: what works and what does not . The repRecently, the Public Policy Advisory Network on Female Genital Surgeries in Africa published a policy report entitled, “Seven things to know about female genital surgeries in Africa” . This poThis study shows that both ordinary people and opinion leaders in Somalia are against the total abandonment of FC but supporting for the continuation of the Sunna form. Campaigners against the practice could not dare to also promote zero tolerance slogans since this goes against the will of the public majority. The Somali government adopted a zero tolerance strategy in 1988 after the pricking form strategy failed though it did not work well . As mentFor many ethnic groups in Africa, FC represents the central component of a traditional rite of passage ceremony in which girls are expected to pass through a transition from puberty to adulthood. In these communities, in making the decision to not circumcise their daughters, parents may face the dilemma of what to do about the traditional ritual that allows them and their daughters to publicly announce the transition to womanhood. To address this problem, the idea of an “alternative ritual,” which excluded genital cutting but maintained the ceremony and the public declaration for community recognition, has been adopted. A symbolic ceremony strategy without genital cutting has been reported to become successful in parts of Kenya . Thus, aThis study has some limitations. The results of the study reflect the perceptions of a limited number of participants in the study, and not necessarily those of the entire Somali population in Somalia. The failure to generalize the findings of this study to the Somali community in Somalia is a general limitation of the qualitative methods used. Most of the views and opinions were repeatedly expressed among different individuals, and the result is consistent with our earlier quantitative results in Hargeisa, thereby increasing our confidence in the validity of the findings.In conclusion, will the promotion of the pinch of the prepuce and verbal alteration of status may be a better strategy for the eventual abandonment of FC in Somalia? The idea is not to promote a shift to a milder form of FC, but to formulate a harmless situation that mimics a circumcision through a transition to untouched behaviour. The pinch of the prepuce will alleviate the suffering due to Type III, Type II, and even Type I, while it may be much less painful than widely tolerated practices such as genital piercing, ear piercing, and male circumcisions . The advThere are a number of assumptions for the potential of this strategy in abolishing FC in Somalia. First, the “the pinch of the clitoral hood” may break the religious argument surrounding the practice, which is the most important argument for the continuation of FC among Somalis, and it may neutralize the religious leaders' opposition to total abandonment. Nonetheless, it is important for programme leaders to avoid using the term “Sunna” when promoting this mild form, as detaching the practice from religion is crucial in any effort towards the total abandonment of FC in Somalia. Secondly, it will break the link between marriageability and FC, which is the second main reason for perpetuating FC in Somalia. In this case, the association between virginity (marriageability) and FC will eventually disappear as the Pharaonic, which has been perceived as guaranteeing virginity, will be eliminated through public consensus. Down the road, there is an expectation that people will gradually adopt uncut behaviour, as the pinch of the clitoral hood will no longer be seen as being necessary for virginity and marriageability; nor will people (peers or the groom) have a way to differentiate a girl with a pinched clitoral hood from an untouched girl. Thus, those who were already against the practice, but had it performed on their daughters because of the social pressure, may automatically abandon the practice at all.Thirdly, it may give a reasonable voice to activists to advance their advocacy against the practice, since they can easily convince politicians and religious leaders to be on board in their advocacy towards the abandonment of all other forms of FC. It is an idea that every person in Somalia can easily digest since the majority of Somalis are convinced that Pharaonic circumcision and all forms involving the cutting of tissues are neither religious nor a good part of the culture. The bottleneck for the past 30 years has been the notion that girls should be left untouched, which can be neutralized by adopting this circumcision mimicking form. The prerequisite here is that programme leaders should have a clear mind in terms of what is to be promoted , such that the pricking form should not serve as a cover-up for more severe forms of the practice.


Molecular Cytogenetics has received its first official Impact Factor of 2.36 in June 2013.We are pleased to announce that We sincerely thank our distinguished international editorial board for their efforts on behalf of the journal, and our publisher, BioMed Central, for their in-house contribution to the speed and efficiency with which manuscripts are processed. Most important of all, of course, are our authors and reviewers , and to Molecular Cytogenetics has considered 204 and published 179 articles, giving an acceptance rate of 86%. This exemplifies the journal’s inclusive editorial policy to publish manuscripts that are scientifically sound, and not just based on perceived impact. These articles cover a wide range of topics in molecular cytogenetics, including clinical and tumor cytogenetics, interphase architecture and karyotype evolution studies not only in human but also in other vertebrates. The journal is also open for molecular cytogenetic-based studies in any species, including invertebrates as well as plants. A rapid review process ensures that papers are published in a timely manner [Molecular Cytogenetics during the journal’s 5 years of publishing and Table Molecular Cytogenetics articles are mobile-device optimized to facilitate easy reading on phones and tablets.Since it was launched in 2008, Recently an obituary of a key person in our field, Prof. Dr. Lore Zech, inventor of banding cytogenetics was published and highly recognized in the community . To reflMolecular Cytogenetics will promote the popularity of the molecular cytogenetic approach during the post-genomic era.The field of molecular cytogenetics is now entering an exciting time. Following various large-scale sequencing projects that have revealed a high level of genetic heterogeneity, it is clear that single-cell resolution and cell population dynamics are essential to understanding the mechanisms of many common and complex diseases. Thus molecular cytogenetics has become increasingly important as it provides information on both individual cells and cell populations. We hope our journal Molecular Cytogenetics.With the help of its readers and authors we look forward to the continuing growth of


In complex feed structures, there exist main chemical functional groups which are associated with nutrient utilization and availability and functionality. Each functional group has unique molecular structure therefore produce unique molecular vibration spectral profile. Feed processing has been used to improve nutrient utilization for many years. However, to date, there was little study on processing-induced changes of feed intrinsic structure and functional groups on a molecular basis within intact tissue. This is because limited research technique is available to study inherent structure on a molecular basis. Recently bioanalytical techniques: such as Synchrotron Infrared Microspectroscopy as well as Diffuse Reflectance Infrared Fourier Transform molecular spectroscopy have been developed. These techniques enable to detect molecular structure change within intact tissues. These techniques can prevent destruction or alteration of the intrinsic protein structures during processing for analysis. However, these techniques have not been used in animal feed and nutrition research. The objective of this review was show that with the advanced technique, sensitivity and responses of functional groups to feed processing on a molecular basis could be detected in my research team. These functional groups are highly associated with nutrient utilization in animals. The unique structure results in unique molecular vibrational spectra. Functional groups are associated within unique feed intrinsic structure. These functional groups consist of macromolecular such as lipid, protein, structural and non-structural carbohydrates which are nutrient for animal and human. Under infrared vibrational molecular spectroscopy, these functional groups produced unique bands . From thobserved -4.-1) usually locate at several regions in mid-infrared regions. (a) It located at ca. 2800~3000 cm-1, asymmetric and symmetric stretching vibrations of CH3 (ca. 2956 and 2874 cm-1) and CH2 (ca. 2922 and 2852 cm-1) groups of acyl chains [-1, unsaturation (CH attached to C=C). (c) It locate at ca. 1800–1500 cm-1 at ca. 1740 cm-1 stretching vibration of the carbonyl ester C=O bond [-1. The amide I band arises predominantly from the C=O stretching vibration of the peptide bond and particularly sensitive to and can be used to predict protein secondary structure [-1 region of the infrared spectrum. There are some unique carbohydrate bands, such as band at 1420 cm-1 for β-glucan [-1 for structural carbohydrates [-1 for starch in endosperm of cereal grain [-1 for hemicellulose. These functional groups are highly related to nutrient availability [Several relatively unique absorption of lipid vibration spectra 4000–500 cm00 cm-1 ulability There are several molecular spectroscopy that could be used for molecular structure study for feeds. First one is cutting-edge bioanalytical technique: synchrotron-radiation based technique SR-IMS. This technique enables to detect molecular structure change within intact tissues within cellular and subcellular dimensions -14. ThisHowever, these molecular-based techniques have not been used in animal feed and nutrition research. The objective of this review was to show that with the advanced technique, sensitivity and responses of functional groups to feed processing on a molecular basis could be detected in my research team.Linum usitatissimum, cv. Vimy), that occurred on a molecular level during the treatment process using infrared molecular spectroscopy. We autoclaved flaxseed samples at 120°C for 20, 40 or 60 min for treatments 1, 2 and 3, respectively. The lipid CH3 asymmetric (ca. 2959 cm-1), CH2 asymmetric (ca. 2928 cm-1), CH3 symmetric (ca. 2871 cm-1) and CH2 symmetric (ca. 2954 cm-1) functional groups, lipid carbonyl C=O ester group (ca. 1745 cm-1), lipid unsaturation group (CH attached to C=C) (ca. 3010 cm-1) and their intensity ratios were determined. We also used hierarchical cluster analysis (CLA) and principal components analysis (PCA) to identify molecular structure difference. The results showed that there were linear and quadratic effects of the treatment time from 0, 20, 40 and 60 min on the ratios of the CH2 asymmetric to CH3 asymmetric stretching vibration intensity. But autoclaving had no significant effect on lipid carbonyl C=O ester group and lipid unsaturation group (CH attached to C=C). The results indicated that autoclaving had different impact on different functional groups which are related to lipid and molecular spectroscopy was able to pick up heat-induced changes in lipid conformation. A future study is needed to quantify the relationship between lipid molecular structure changes and functionality/availability [In one of our research , we studlability . In anotlability , we repoLc regulatory gene with non-transgenic alfalfa protein within cellular and subcellular dimensions and to quantify protein inherent structure profiles using Gaussian and Lorentzian methods of multi-component peak modeling [Lc alfalfa leaves contain similar proteins to non-transgenic alfalfa , but a subtle differences in protein molecular structure. Further study is needed to understand the relationship between these structural profiles and biological features such as protein nutrient availability, protein bypass and digestive behavior of livestock fed with this type of forage [The sensitivity and responses of protein-related functional group to various processing has been reviewed in details and published in Molecular Nutrition and Food . In thismodeling ,24. It wf forage . In the f forage , it was f forage . In the , reported the study on effect of bioethanol processing on carbohydrate functional groups by using DRIFT molecular spectroscopy. The following functional groups were studied, including: “A_Cell (peaks area region and baseline: ca. 1485–1188 cm-1) mainly associated with hemi- and cellulosic compounds, A_1240 (peak area centered at ca.1240 cm-1 with region and baseline: ca. 1292–1198 cm-1) mainly associated with cellulosic compounds, A_CHO (peaks region and baseline: ca. 1187–950 cm-1) associate with total CHO, A_928 (peak area centered at ca. 928 cm-1 with region and baseline: ca. 952–910 cm-1) and A_860 (peak area centered at ca. 860 cm-1 with region and baseline: ca. 880–827 cm-1) mainly associated with non-structural CHO, H_1415 (peak height centered at ca.1415 cm-1 with baseline: ca. 1485–1188 cm-1) and H_1370 (peak height at ca.1370 cm-1 with a baseline: ca. 1485–1188 cm-1) mainly associated with structural CHO”. The authors found that A_Cell, A_CHO, H_1415 and H_1370 had no correlation with CHO chemical and nutrient profiles in the bioethanol co-products. However, CHO molecular spectral intensity of the A_1240, A_928 and A_860 had strong correlation with rapidly degradable CHO fraction (CB1), lowly degradable CHO fraction (CB2) and an unavailable CHO fraction (CC) and could be a good indicator. In conclusion, the changes of the CHO molecular structures during the processing for bioethanol production were highly associated with carbohydrate degradable subfractions in ruminants.Feed processing has different impact on different functional groups in feeds which are related to carbohydrate. Yu , reporteThe review shows that molecular spectroscopy technique could be used to study the sensitivity and response of functional groups in complex feed systems to various feed processing on molecular basis. It has a potential to study processing impact directly on feed and nutrient utilization and availability. These functional groups are highly associated with nutrient utilization in animals.The authors declare that they have no competing interests.


Several molecular targeted agents have been approved for clinical use for metastatic renal cell carcinoma (mRCC). A case of a 32-year-old woman with mRCC is presented. These tumors could change vascularity by administration of molecular agents. We could select a drug timely based on findings of computed tomography. To our knowledge, this is the first report that tumor's character change induced by molecular targeted agents can be detected and the efficacy of molecular targeted agents can be predicted. Recently new molecular targeted agents were approved for metastatic renal cell carcinoma (mRCC) . These aWe report a case of mRCC, who received sequential therapy of sunitinib and temsirolimus as well as rechallenge of these drugs. We discuss the efficacy and the vascularity change of tumors. A 32-year-old woman presented with acute abdominal pain and fever. She had undergone a right radical nephrectomy for pT2N0M0, Fuhrman's grade 2, clear cell renal cell carcinoma 4 months ago. Enhanced abdominal computed tomography (CT) revealed multiple hypovascular tumors in the liver. Laboratory findings were increased white blood cells count, as well as elevations of serum C-reactive protein and lactic dehydrogenase (LDH), which was consisted of subtype 1 and 2 . BecauseTreatment of mRCC has changed dramatically over the past several years by using molecular targeted agents such as TKIs and mTOR inhibitors. However, cure is still rare. Sequential use of these targeted agents is standard because of dose limiting toxicities induced by combination therapy . In our The efficacy of rechallenge of molecular targeted drugs, which was failed in a previous line, has been reported , 5. SomeIn conclusion, our case showed two important points. The first point is that we should take into consideration the rechallenge of molecular target agents as a treatment option. Second, tumor might change character easily by administration of molecular target drugs. If we can detect these changes like this case, it will help greatly with the choice of agent and prolong survival.


Molecular typing of the pneumococcus has played a crucial role in understanding the epidemiology of the organism. However, most of what is known about molecular epidemiology of the pneumococcus pertains to the developed world. The brunt of pneumococcal infections is borne by sub-Saharan African countries, which makes epidemiological monitoring of the pneumococcus essential in this region of the world. This review paper focuses on molecular typing of the pneumococcus and what is known about epidemiology of the organism in sub-Saharan Africa based on the various typing methods. Several molecular typing methods are available for typing the pneumococcus and the major ones include multilocus sequence typing (MLST), multilocus enzyme electrophoresis (MLEE), serotyping and DNA fingerprinting methods such as pulsed field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP). Currently, MLST is the most suitable method for typing the pneumococcus. The pneumococcal population structure in sub-Saharan Africa appears to be quite different from that of the developed world, and pneumococcal serotype 1 related to the ST 618 clone and clones of the ST 217 clonal complex are responsible for outbreaks in sub-Saharan Africa. Streptococcus pneumoniae is part of the normal bacterial flora of the upper respiratory tract, but is also associated with severe invasive diseases, including meningitis, pneumonia, and septicaemia as well as non-invasive diseases such as otitis media . Generally, PCR-based serotyping has been shown to be reliable and accurate, and can often be used directly on clinical specimen. However, a key limitation of current PCR-based typing methods is the inability to distinguish between many serotypes of the same serogroup , Penicillin Binding Protein (PBP) Fingerprinting, BOX-PCR, Restriction Fragment Length Polymorphism (RFLP), and Amplified Fragment Length Polymorphism (AFLP). PFGE, a genotypic method for the evaluation of total chromosomal DNA, had been regarded as the “gold standard” for typing micro-organisms  explores the different electrophoretic mobilities of a large number of cellular enzymes encoded by house-keeping genes  of a strain. So far, over 8000 S. pneumoniae STs from a wide variety of geographical locations have been described in the S. pneumoniae MLST database http://speumoniae.mlst.net/. However, there is little MLST data on African isolates. The major advantage of MLST is that sequence data is unambiguous and the STs of isolates can be compared to those in a central database via the Internet, in contrast to other typing methods which involve comparing DNA fragment sizes on gels. Thus the portability of MLST means it is highly useful in monitoring the population structure of a given pathogen. Due to the sequence conservation in housekeeping genes, sometimes MLST has limited ability to differentiate bacterial strains, which limits its use in the epidemiological investigation of bacteria of a more clonal population structure. For a naturally transformable organism like S. pneumoniae, MLST is a valuable typing tool, as the high rates of recombination result in a high rate of genetic diversification of pneumococcal populations  shares the same principle with MLEE but assigns alleles to housekeeping genes directly by sequencing of those genes, and thus the level of resolution is much better than MLEE Spratt, . For eacOver the years, the various molecular typing schemes of pneumococcus have greatly facilitated our understanding of the molecular epidemiology of the organism. Serotyping data indicates that only a few of the discovered 94 serotypes are responsible for the vast majority of pneumococcal disease, and these serotypes may vary from one geographical region to another . On the other hand, serotypes such as 9V and 14 are associated with a wide variety of clonal types, which may also be seen with some other serotypes (http://spneumoniae.mlst.net/). The Pneumococcal Epidemiology Network (PMEN) provides surveillance on epidemiologically significant clones and currently, 43 such clones are known (http://www.sph.emory.edu/PMEN/index.html).Genotyping of pneumococci has provided further insights into the molecular epidemiology of pneumococcal serotypes. One of such insights is that isolates of certain serotypes such as 1 and 7F are associated with a limited number of clones, and these clones are hardly observed with other serotypes . Twenty-seven different serotypes and 72 different STs were identified, and there was no particular association of clones with specific presentation of invasive pneumococcal disease. For a given serotype, the genotype distribution varied considerably between vaccinated and un-vaccinated children. However, the population structure of serotype 1 obtained from vaccinated and non-vaccinated children were the same and comprised mainly ST 618. In The Gambia, an outbreak of pneumococcal pneumonia and septicaemia caused by serotype 1 occurred between 1997 and 2002  were found to be serotype 1. MLST was carried out on only three of these serotype 1 isolates, and two were found to be ST 618 with the other isolate being a novel ST, and a single locus variant of ST 618. An outbreak of pneumococcal meningitis similar to the outbreak in Burkina Faso also occurred in Ghana during the period of 2002–2003 , whereas in sub-Saharan Africa, the infections seem to be associated with STs 458 and 700 (Adetifa et al., Pneumococcal serotype 1 is also an important cause of invasive disease and epidemics in the developed world (Brueggemann and Spratt, Little is known about molecular epidemiology of the pneumococcus in sub-Saharan Africa though majority of pneumococcal infections occur in this setting. Lack of molecular typing data of the pneumococcus in sub-Saharan Africa is mainly due to lack of facilities as well as technical expertise required for the organism. Thus capacity building in the form of training personnel on the pneumococcus, and also providing adequate research funding constitute a major part of the solution to this problem. Currently, there is an urgent need for molecular epidemiology data on the pneumococcus in sub-Saharan Africa given the expected massive pneumococcal vaccination in the region (PneumoADIP, Few studies have employed molecular methods to investigate the pneumococcus in sub-Saharan Africa. Consequently, little is known about molecular epidemiology of the pneumococcus in sub-Saharan Africa, though majority of pneumococcal infections occur in this region. The pneumococcal population in sub-Saharan Africa appears to be quite divergent from what is known in the developed world, and pneumococcal serotype 1 related to the ST 618 clone and clones of the ST 217 clonal complex are responsible for outbreaks in sub-Saharan Africa. There is an urgent need for molecular epidemiology data on the pneumococcus in sub-Saharan Africa to help monitor evolutionary changes in the pneumococcal population following introduction of pneumococcal vaccines in the sub region.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Escherichia coli (E. coli) as model organisms. The nanofibers fabricated by this method showed obvious antibacterial activity. Electrochemical properties were characterized based on cyclic voltammetry measurements. The CV results showed redox peaks corresponding to the Fc+/Fc couple, which suggested that Fc molecules encapsulated inside PVP nanofibers retian their electrochemical activity. The properties and facile preparation method make the Fc/PVP nanofibers promising for antibacterial and sensing applications.Nanofibers containing ferrocene (Fc) have been prepared for the first time by electrospinning. In this paper, Fc was dispersed uniformly throughout the poly(vinypyrrolidone) (PVP) matrix for the purpose of combining the properties of PVP and Fc. The effects of solvents and Fc concentration on the morphologies and diameters of nanofibers were investigated. In the DMF/ethanol solvent, the morphologies of the obtained nanofibers significantly changed with the increase of Fc concentration. The results demonstrated that the morphologies of the nanofibers could be controlled through adjusting solvents and Fc concentration. Scanning electron microscopy (SEM) showed that the diameters of the obtained composite fibers were about 30–200 nm at different Fc concentrations. Thermogravimetric analysis (TGA) results confirmed the presence of ferrocene within the PVP nanofibers. X-ray diffraction (XRD) results showed that the crystalline structure of Fc in the fibers was amorphous after the electrospinning process. A biological evaluation of the antimicrobial activity of Fc/PVP nanofibers was carried out by using Gram-negative  Electrospinning is a simple and versatile technique for the production of polymers, composites and ceramic fibers –2. NanofFc is a kind of organometallic compound with a “sandwich” structure , and it The processing parameters such as polymer concentration, Fc concentration, type of solvent, electrospinning voltage, polymer-solution flow rate, etc., have an important effect on the morphologies and structures of the fibers. By tuning the electrospinning parameters, fibers having a diameter from a nanometer to a micrometer in scale can be obtained, and the fibers can be facilely electrospun into different surface morphologies –19. A prBlank PVP nanofibers and composite Fc/PVP nanofibers were prepared by the electrospinning method. A nonwoven product consisting of PVP or Fc/PVP nanofibers was obtained. The nanofibers were processed into a thin membrane with an increase of the electrospinning time. Then the thin membrane obtained could be cut into any shape by a pair of scissors. The optical photographs and scanning electron microscopy (SEM) images of the products are shown in As seen from the presented SEM micrographs , no Fc cThe degradation process of products was investigated using thermogravimetric analysis (TGA) from 20 to 600 °C in nitrogen gas. In order to find the optimum preparation conditions for Fc-loaded PVP nanofibers, the influences of solvents and Fc loading on the morphologies and diameters of the electrospun fibers were investigated. The selection of a desirable solvent or solvent system is fundamental for the optimization of electrospinning. Different solvent systems are pivotal in determining the morphologies and diameters of the final fibers –26. Vari2Cl2 solvents. It shows that their size strongly depends on the type of solvents used. Junctions of nanofibers from ethanol are observed in the sample. The phenomenon can be well understood: wet nanofibers are not dried during the solidification process before they reach the collector, resulting in the junction morphology as shown in 2Cl2 was added to the solution, the fiber diameter increased significantly compared to the fiber produced from pure ethanol [2Cl2 was replaced by DMF, the fiber diameter decreased sharply to 170 nm with a smooth surface  solution. When tryptophan was added, the peak current decreased with the increase of tryptophan concentration. The main reason was the coordination between Fc+ and tryptophan ion. Since the method demonstrated here is facile and a complex procedure is not involved in this work, the properties are not as good as reported for other materials. However, this work has provided us with a promising antibacterial and electrochemical sensing platform based on Fc/PVP composite nanofibers.In summary, composite Fc/PVP nanofibers have been successfully prepared by electrospinning. The effects of the type of co-solvent and Fc concentration on the diameter and morphology of the fibers were studied. In the DMF/ethanol solvent, the diameter of the nanofibers was smaller. Increasing the content of Fc, the morphologies of the obtained nanofibers significantly changed, which was attributed to the variation of solution conductivity and solvent volatility. The results demonstrated that the morphologies and diameters of nanofibers could be controlled by adjusting the type of solvents and Fc concentration. These electrospun Fc/PVP nanofibers had bactericidal activity against the Gram-negative bacteria Mw = 1,300,000) was purchased from Aldrich. Ferrocene was purchased from Shanghai Qingxi Chemistry and Technology Co., Ltd. . The solvents of N,N-dimethylformamide (DMF), dichloromethane (CH2Cl2) and ethanol (EtOH) were purchased from China Medicine (Group) Shanghai Chemical Reagent Corp . The above chemical reagents were analytical grade and used without further purification. Phosphate buffer solution (pH 7) was prepared by mixing Na2HPO4 and NaH2PO4 with distilled water. The strains used in this study were from our laboratory.Poly(vinylpyrrolidone)  over the 2-theta angle range of 10–70 °C with a scanning rate of 10 °C/min. The TGA data was obtained by a DSC-STA 449C Jupiter thermal analysis instrument. About 4 mg sample in an aluminium pan was heated from 20 to 600 °C at a heating rate of 10 °C/min. All electrochemical measurements were performed with a CHI660A electrochemical workstation . A conventional three-electrode cell setup was employed with Fc/PVP/GCE as the working electrode, a platinum electrode as the counter electrode, and a saturated calomel electrode (SCE) as the reference electrode.SEM images were obtained on a Philips XL-30E scanning electron microscope (SEM) after gold sputter-coating. The XRD patterns of samples were determined with an X-ray diffractometer with Cu Kα radiation (E. coli. Samples were prepared in the form of discs with a diameter of about 10 mm. Culture medium was prepared by mixing 3 g beef extract, 10 g peptone, 5 g NaCl, 16 g agar, and distilled water. After the activation, bacteria were inoculated and cultured in nutrient agar plate at 37 °C. For each bacterial suspension 100 µL was measured and evenly spread onto the solidified culture medium plate by the coating method. The Fc/PVP discs were placed onto the centre of substrates. The plates were then incubated at 37 °C for 24 h. Pictures of the plates were taken to illustrate the antibacterial performance of the samples.The sample containing 45 wt % Fc was tested for antibacterial activity against the Gram-negative


This is a case report of disseminated Kaposi's sarcoma in the context of immune reconstitution inflammatory syndrome in an HIV-infected patient on HAART regimen for 2 months. The patient rapidly progressed to death in 5 days after worsening pulmonary infiltrates and multiple organ failure. Kaposi's sarcoma (KS), a low-grade malignancy that is associated with human herpesvirus-8 (HHV-8), is a multifocal tumor that most commonly affects mucocutaneous sites. In its disseminated form, it can also involve lymph nodes and visceral organs, in particular the respiratory and gastrointestinal tract, but every organ can potentially be affected, including bone tissue.Four forms of the disease have been recognized: the classic form (occurring in Mediterranean elders), the endemic form (occurring in African children), the transplant-associated form (resulting from iatrogenic immunosuppression), and the epidemic form which is associated with HIV infection.Although antiretroviral therapy is a condition for AIDS associated KS improvement and resolution, in disseminated cases, HAART may rarely induce an immune reconstitution inflammatory syndrome (IRIS) of varying severity and even fatal cases. IRIS in the context of KS is rare and often not readily recognized, thus delaying the necessary immediate measures.A 29-year-old homosexual male patient was admitted at the emergency unit on February 22, 2012, complaining of shortness of breath and a dry cough for the past 3 days. He mentioned associated intermittent fever of 38°C, bloody sputum, and weight loss. 3. Highly active anti-retroviral therapy (HAART) consisting of lamivudine, zidovudine and efavirenz had been initiated. Two months prior to the emergency room admission, he had received a positive anti-HIV ELISA test and an initial CD4+ lymphocyte count of 136 cells/mmTwo weeks prior to hospital admission, he had been started on prophylactic sulfamethoxazole-trimethoprim (SMX-TMP), and on the same date, it had been noted that he presented purplish skin lesions on his anterior chest, right eyelid, right arm, and shoulder, as well as groin area, hard palate, and uvula, all suggestive of Kaposi's sarcoma (KS) in association with oral candidiasis.Due to worsening respiratory symptoms on the second day of hospital admission, he was referred to the intensive care unit of the Department of Infectious Diseases. On admission at the ICU, he was alert and oriented, with a stable blood pressure, but with a respiratory rate of 24 breaths per minute and hypoxemia with SPO2 = 82% at room air. Other notable examination findings were micropolyadenopathy and hepatosplenomegaly. His initial chest X-ray showed diffuse bilateral cotton-like infiltrates . His chePneumocystis pneumonia.Empirical antibiotic therapy for severe community acquired pneumonia (CAP) with ceftriaxone and clarithromycin was started immediately, as well as treatment for oral candidiasis with intravenous fluconazole. Antiretroviral therapy was modified to zidovudine, lamivudine, and lopinavir with booster ritonavir. SMX-TMP was increased to its therapeutic dose for The patient was submitted to endotracheal intubation due to severe hypoxemia. Bronchoscopy revealed purplish lesions in the respiratory tract with signs of alveolar hemorrhage. A digestive endoscopy also showed purplish lesions in the duodenum and stomach. Mucosal biopsy was hindered by the risk of severe uncontrolled hemorrhage. The skin biopsy confirmed cutaneous KS.On the fifth day of hospital, the patient presented hemodynamic instability unresponsive to vasoactive drugs , acute kidney failure with severe metabolic acidosis, and hyperkalemia requiring renal replacement therapy. The ordered chest X-ray at the ICU showed worsening diffuse bilateral nodular and patchy infiltrates . AntibacMycobacterium, except for a positive qualitative PCR for cytomegalovirus. The patient's CD4+ lymphocyte count at the time of expiry was 391 cells/mm3 with a viral load of 1,353 copies/mL (Log 3.13).All blood cultures were negative. The tracheal aspirate was negative for fungi, bacteria, and 3. The most common manifestations are purple skin lesions, prompting a thorough investigation of the pulmonary and gastrointestinal tracts for staging and therapeutics planning owing to the frequency of advanced KS at diagnosis. One case report showed that, in its disseminated form, KS can even affect the articulation [Kaposi's sarcoma (KS) is among the most common cancers in AIDS patients, especially in African countries, and occurs at all CD4 levels below 500 cells/mmculation . Regarding treatment options, targeted therapy for KS should be started based on disease severity on the initial patient evaluation. Localized or minimally disseminated cutaneous KS mostly responds to highly active anti-retroviral therapy (HAART) and either surgical resection of the lesion, cryotherapy, or radiotherapy can be associated. HAART does not have direct effects on HHV-8 but causes partial or complete resolution of KS lesions through a decrease in HIV viral load and immune reconstitution of memory CD4+ lymphocyte cells. Disseminated disease with visceral involvement would require an association of HAART regimen with chemotherapy agents, for example, paclitaxel and liposomal doxorubicin.Mycobacterium avium-intracellulare infection, and Pneumocystis jirovecii pneumonia. Although HAART is a condition for KS improvement and resolution, in disseminated cases, HAART may rarely induce an immune reconstitution inflammatory syndrome (IRIS) of varying severity and even fatal cases . In the In the presented clinical case, the patient's cutaneous lesions were evident approximately 6 weeks after initiating HAART, suggesting probable unmasking of occult HHV-8 infection and subclinical KS. According to a prospective study carried out in Mozambique, risk factors for KS-IRIS include pretreatment KS , detectable plasma HHV-8 DNA, hematocrit below 30%, and high plasma HIV viral load [In general, IRIS treatment depends on the clinical severity and disease agent. Treatment of KS-IRIS is a challenge because this entity is rarely recognized and its appropriate therapeutic management is still unclear. HAART discontinuation and corticosteroid use in moderate to severe IRIS cases is a widely known measure that diminishes inflammation to varying degrees. However, KS-IRIS is not routinely treated with corticosteroids due to the risk of further compromise of cellular immunity permitting HHV-8 replication and tumor growth . IdeallyIn one paper, it is suggested that starting or maintaining chemotherapy in association with continuing HAART may cause successful resolution on KS-IRIS. To highlight this, I exemplify Elizabeth Connick's brief report where the patient presented with facial KS and significant neck edema and lymphadenopathy while on HAART and this inflammation would resolve coincidentally with decreases in the CD4+ lymphocyte count during paclitaxel treatment. This patient KS finally cleared after prolonged HAART and chemotherapy. The authors thus concluded that clinicians should be aware of KS-IRIS and that they should realize that IRIS does not indicate failure of HAART or a need for changes in anti-retroviral regimen. Instead, chemotherapy in conjunction with HAART can effectively control the symptoms of IRIS and resolve KS .The patient in this case report presented with numerous skin lesions that already suggested a case of disseminated KS which was later confirmed. He was not promptly started on chemotherapy as indicated for disseminated visceral KS and this certainly may have contributed to his deteriorating clinical status and death due to KS-IRIS. Although pulmonary KS has a poor prognosis even when chemotherapy is started early, it can be concluded that chemotherapy is necessary and should be administered in pulmonary KS-IRIS due to its high mortality  rate.