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FK506-binding protein 35, FKBP35, has been implicated as an essential malarial enzyme. Rapamycin and FK506 exhibit antiplasmodium activity in cultured parasites. However, due to the highly conserved nature of the binding pockets of FKBPs and the immunosuppressive properties of these drugs, there is a need for compounds that selectively inhibit FKBP35 and lack the undesired side effects. In contrast to human FKBPs, FKBP35 contains a cysteine, C106, adjacent to the rapamycin binding pocket, providing an opportunity to develop targeted covalent inhibitors of Plasmodium FKBP35. Here, we synthesize inhibitors of FKBP35, show that they directly bind FKBP35 in a model cellular setting, selectively covalently modify C106, and exhibit antiplasmodium activity in blood-stage cultured parasites.Measuring innovation in the pharmaceutical industry is challenging. Counts of new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) are commonly used, but this measure only gauges quantity not innovativeness. A new indicator of innovation for small molecule and peptide drugs based on structural novelty is proposed and used to analyze recent trends in pharmaceutical innovation. We show pharmaceutical innovation has significantly increased over the last several decades despite recent concerns over an innovation crisis and find Pioneers (a NME whose shape and scaffold were not used in any previously FDA-approved drugs) are significantly more likely to be the source of promising new therapies. Analysis of the underlying source of structural innovation indicates that scaffolds first reported in the CAS REGISTRY five or less years prior to their Investigational New Drug application (IND) or on scaffolds populated with 50 or less other compounds at the time of IND tend to be the main source of Pioneers. check details Our analysis also shows a widening structural innovation gap between large pharmaceutical companies (Big Pharma) and the rest of the ecosystem even though the number of Big Pharma originated Pioneers has increased.Decades of research efforts have conclusively provided overwhelming evidence that the cellular prion protein (PrPC) plays a central role in prion diseases, a set of fatal and incurable neurodegenerative disorders for which no therapy is yet available. In this Viewpoint, we provide an overview of the drug discovery strategies in the field, highlighting the current therapeutic hypotheses targeting, whether directly or indirectly, PrPC as well as the antiprion agents closest to clinical application.Potential consumer exposure to nanoparticles (NPs) from nanoenabled food contact materials (FCMs) has been a driving force for migration studies of NPs from FCMs. Although NP migration from fresh, unused FCMs was not previously observed, conditions that result in significant changes to the surface of FCMs have not been investigated for NP migration into food. Therefore, a quantitative assessment of nanoparticle release from commercially available nanosilver-enabled FCMs was performed using an abrasion protocol to simulate cleaning, cutting, scraping and other stressful use conditions. Laser scanning confocal microscopy (LSCM) analysis showed a general increase in root mean square (RMS) roughness after FCM abrasion, and particle count (for particle sizes from 80 nm to 960 nm) at the surface was 4 orders of magnitude higher for the abraded FCMs. Migration was evaluated using both water and 3% (v/v, volume fraction) acetic acid as food simulants. Low concentrations of total Ag were detected in water simulants with a small portion ( less then 10 ng dm-2) in the form of silver nanoparticles (AgNPs). Median particle diameter ranged from 39 nm to 50 nm with particle number concentrations on the order of 106 particles dm- 2. Total Ag migration into 3% (v/v) acetic acid was significantly higher than in water; however, 3% (v/v) acetic acid was not suitable for evaluation of NP release due to dissolution of AgNPs to Ag+ under acidic solution chemistries.

every year in Nigeria 12,695 babies are born with neural tube defects. Folic acid reduces the risk of neural tube defect by about 50% among peri-conceptional users. We conducted this study to determine the awareness and use of folic acid among women of childbearing age in Benue State, Nigeria.

we conducted a cross-sectional study among women attending selected among six secondary health facilities in Benue State using a multi-stage sampling technique. We interviewed 586 women aged 15-49 years using structured questionnaires to obtain information on awareness and use of folic acid. We performed univariate, bivariate and multivariate analysis at 5% significance.

interviewed 586 women with the mean age 27 ± 6.9 years; 281(48%) were aware of folic acid as a supplement, 178 (30.4%) knew the dietary source of folic acid while 152 (26%) knew the benefit of folic acid. The commonest source of information was health professionals [195 (51%)]. Only 221 (37.7%) used folic acid, 14 (1.7%) of them using it within the first trimester. The commonest reason why women did not take folic acid as supplement was unpleasant smell [124 (21%)]. Awareness of folic acid benefit (OR 6, 95%CI = 3.9-8.8), level of education (OR 2.0, 95%CI = 1.2-3.3) and employment status (OR 1.6, 95%CI= 1.1-22) were significantly associated with folic acid use. Awareness of folic acid use was an independent predictor of folic acid use (AOR 7.9 95%Cl 5.3-11.7).

awareness and use of folic acid among women of childbearing age was low. Awareness is a predictor of folic acid use. We recommend the promotion of awareness and use of folic acid in pregnant women.

awareness and use of folic acid among women of childbearing age was low. Awareness is a predictor of folic acid use. We recommend the promotion of awareness and use of folic acid in pregnant women.Chordoma is a rare malignant tumor of the spine. We report the case of a 26-year-old man who presented with facial paralysis and upper limbs paresthesia. Cerebral CT-scan and cerebro-spinal MRI revealed a 58mm locally advanced middle clival mass with deviation of median cerebral structures. Endoscopic biopsy concluded to a chondroid chordoma. Skeletal survey and thoraco-abdomino-pelvic CT-scan were normal. Treatment consisted in complete surgical removal of the tumor followed by adjuvant radiotherapy. The patient is alive free of disease with a follow up of 12 months.There has been an increased recognition of the importance of men in the global HIV response. Previous studies indicate that in different settings, men are generally less engaged in various HIV services besides having worse health outcomes in comparison to the women. Some of the main factors behind this, based on the previous studies include social factors, gender factors, economic factors, political factors, as well as institutional factors. Recently, various scholars have been reporting evidence concerning the strategies, which aims to improve the levels of engagement of men when it comes to HIV services. There are a number of highly promising approaches, which have been suggested, which includes community-based outreach programs, gender-transformative interventions aimed at shifting gender practices and norms, as well as the development of highly responsive and male-friendly health services. Despite the fact that a number of initiatives have been put in place, there are different kind of challenges, which still remain, more so with regards to costs, as well as sustainability, intersecting inequalities such as class and race, and the challenges, which are faced with regards to altering the community-level gender norms.

the role of surgery in managing massive midline abdominal wall defects has continued to rise, leading to higher demand for more effective techniques in order to limit recurrences. There is paucity of data on this subject in Southeast Nigeria. The aim of this study is to document the indications and challenges of treatment of complex, midline abdominal wall defects in our centre.

this was a cross-sectional study of adult patients with complex, midline abdominal wall defects managed with mesh implants over a five-year period.

a total of 182 adult patients, predominantly females 160(87.9%), received mesh implants for complex abdominal wall defects. The common indications were incisional hernia 128(70.3%), abdominal wound dehiscence 16(8.8%) and divarication of recti 16(8.8%). About one-third 62(34.1%) of the patients required additional abdominoplasty procedure. Delay towards prompt surgical repair was noted in 168(92.3%) patients, notably due to financial constraints 32(17.6%) followed by comorbidities requiring serial assessments 24(13.2%). Superficial wound infection rate was 5.5% while deep (mesh) infection was noted in two (1.1%) patients. Recurrence and perioperative mortality rates were 1.1% and 1.6% respectively. Diabetes mellitus in obese female patients was an independent predictor of perioperative death (p=0.000).

the most common indication for abdominal wall reconstruction in our environment is incisional hernia. The use of prosthetic meshes to repair complex abdominal wall defects is largely safe and effective in our practice, but timely reconstruction is commonly hampered by multi-faceted economic, clinical and pathological barriers.

the most common indication for abdominal wall reconstruction in our environment is incisional hernia. The use of prosthetic meshes to repair complex abdominal wall defects is largely safe and effective in our practice, but timely reconstruction is commonly hampered by multi-faceted economic, clinical and pathological barriers.

despite major strides in the prevention, diagnosis and management of tuberculosis, the disease continues to be one of the most pressing global health problems, particularly in developing countries. The purpose of the present study was to describe the epidemiological profile among tuberculosis patients in Laayoune, Morocco.

a retrospective study was conducted among tuberculosis patients (having extrapulmonary tuberculosis and pulmonary tuberculosis), registered in the diagnosis of tuberculosis and respiratory diseases reference center of Laayoune, between January 2017 and May 2018. Demographic characteristics, clinical presentation of TB and apparent risk factors of the disease were obtained from the medical case records of all patients.

during the study period, a total of 211 patients (125 males and 86 females) with tuberculosis were enrolled. The majority of cases (93.40%) were newly diagnosed and the segment with the pulmonary tuberculosis was 63.50%. The highest disease burden was found in the ≥15 year age group (92.40%; p=0.022). Men were more frequently affected by pulmonary tuberculosis (70.90%), while extrapulmonary tuberculosis was more commonly detected in women (61%) (p<0.0001). The most common sites of extrapulmonary disease were lymphatic (32.47%), pleural (16.88%) and spinal tuberculosis (15.58%). HIV infection and smoking seem to be the most important risk factors that affect host defense against TB infection.

the results obtained in tuberculosis patients in Laayoune, Morocco, showed that active tuberculosis was associated with risk factors such as sex, age and smoking.

the results obtained in tuberculosis patients in Laayoune, Morocco, showed that active tuberculosis was associated with risk factors such as sex, age and smoking.