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Background: Multiple host factors may influence immune reconstitution in HIV-infected people after the initiation of suppressive antiretroviral therapy (ART). Aberrant metabolic pathways have been reported in people with HIV (PWH) on ART. We hypothesized that alterations in plasma metabolites were associated with immune recovery following ART., Methods: In this cross-sectional study, the plasma metabolomic profiles of PWH on ART were evaluated. PWH of slow and fast immune recovery were classified by increase in CD4 T cells following 2 years of ART. Targeted plasma metabolite profiling by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to determine metabolite signatures for HIV recovery identified >200 metabolites., Results: Notably, indole-3-propionic acid was downregulated during HIV, possibly reflecting impaired gastrointestinal epithelium homeostasis. The most important metabolite discriminating between the PWH with fast and slow immune recovery was cysteine. Upregulated cysteine and cysteine pathways may contribute to redox-balance maintenance and T-cell function in PWH with fast immune recovery. Additionally, serine and glycine metabolism and bile acid biosynthesis were the most perturbed metabolic pathways in PWH., Conclusions: These results provide a starting point for developing biomarker candidates for immune recovery in PWH on ART and provide insight into the interplay of metabolism and immune response in HIV infection., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells., Competing Interests: PB, RE, MK, CS, MG, ÅK, JS, PM, ES, SN, ML No competing interests declared, (© 2020, Bhattacharya et al.)

Background: The 2019 coronavirus (COVID-19) pandemic has brought unprecedented challenges to the health sector nationwide and internationally. Across all disciplines, unique and novel modes of presentation with substantial morbidity and mortality are being encountered, and growing evidence suggests that psychiatric comorbidity is likely among COVID-19 patients., Objective: This article aims to broaden the current discussion on the psychiatric sequalae of COVID-19, which has largely focused on anxiety, and examine the recently documented psychiatric sequelae of COVID-19 infection, the secondary effects of the pandemic on public mental health, and future psychiatric conditions that may arise due to COVID-19., Methods: We conducted an in-depth review of the current global psychiatric literature and describe the wide range of psychopathological presentations reported among past COVID-19 patients worldwide and those that are expected to emerge., Results: Current discussions in the psychiatric literature on COVID-19 report anxiety and anxiety disorders as a predominant set of clinical presentations during the pandemic. The impacts of direct COVID-19 infection, associated psychopathological sequelae, and drastic lifestyle changes due to the COVID-19 pandemic in South Africa, are associated with a broad range of psychopathologies and other neuropsychiatric presentations. Pre-existing societal conditions and burdens on the health system in South Africa prompt healthcare providers and public health planners to accordingly prepare for the expected rise in new psychiatric presentations., Conclusion: Greater awareness of the various psychiatric conditions attributed to COVID-19 infection may allow for earlier screening, more effective treatment, and greater positive health outcomes and better prepare health systems to address the growing pandemic in South Africa.

The 11th Congress of the African Society of Human Genetics (AfSHG) was held from September 16, 2018 to September 21, 2018, in conjunction with the 12th Human Heredity and Health in Africa (H3Africa) Consortium meeting in Kigali, Rwanda. The event was organized by the AfSHG in partnership with the Rwanda Society of Human Genetics and the University of Rwanda. A 2-day workshop on the application of next-generation sequencing technologies for analyzing monogenic disease in African populations was organized as part of the conference (September 22, 2018-September 23, 2018, Kigali, Rwanda). The theme of the conference was "Building skills and resources for genomics, epigenetics and bioinformatics research for Africa." The conference served as a platform to bring together members from country-specific Societies of Human Genetics, including Rwanda, Cameroon, Democratic Republic of Congo, Egypt, Mali, Senegal, and South Africa, and included 435 delegates from 38 countries, including 29 African countries that attended the conference. A major topic of discussion was how to bridge the gap between the emerging knowledge on genomics and Omics in African populations. The importance of understanding the role of genetic variation in disease causation and susceptibility among Africans was a constant theme during the meeting, as was the need to develop research infrastructure and resources to enhance healthcare systems, so that they are not left behind in the genomic revolution. It was concluded that there is a need to inspire more African scientists to train and work as investigators, clinicians, and genetic counselors in the field of human genetics in Africa. Local investments, and South-South and South-North collaboration were identified as the key drivers for the successful implementation of research and development on the continent.

The multivariate challenges associated with successful ovarian cancer therapy severely compromises the outcome of therapy and patient quality of life. Coated cholesterol (CHO) and distearoylphosphatidylethanolamine (DSPE) nano-lipobubbles (NLBs) loaded with silibinin and camptothecin were synthesized and evaluated as a possible intravenous delivery system for the treatment of ovarian cancer. Cytotoxicity analysis in addition to in vitro release, zeta potential and drug entrapment studies were conducted on the NLBs. Results of the cytotoxicity evaluation on A2780 epithelial ovarian cancer cells corroborated the benefits of the altered drug release characteristics achieved following polymeric coating. Cumulative cytotoxicity demonstrated by the NLBs 72 h post-treatment ranged between 85%-95%. Cellular internalization of the NLBs was swiftly achieved, with the extent of internalization exhibiting time-dependent characteristics. A size-dependent cellular internalization correlation between the NLB systems was also achieved. Evaluation of the prepared NLBs displayed favorable characteristics for the achievement of passive targeting and satisfactory drug incorporation for application in ovarian cancer treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The skin microenvironment at the site of infection plays a role in the early events that determine protective T helper 1/type 1 immune responses during cutaneous leishmaniasis (CL) infection. During CL in nonhealing BALB/c mice, early interleukin-4 (IL-4) can instruct dendritic cells for protective Th1 immunity. Additionally, keratinocytes, which are the principal cell type in the skin epidermis, have been shown to secrete IL-4 early after Leishmania major infection. Here, we investigated whether IL-4/IL-13 signaling via the common IL-4 receptor alpha chain (IL-4Rα) on keratinocytes contributes to susceptibility during experimental CL. To address this, keratinocyte-specific IL-4Rα-deficient (KRT14 cre IL-4Rα -/lox ) mice on a BALB/c genetic background were generated by gene targeting and site-specific recombination (Cre/ loxP ) under the control of the keratinocyte-specific krt14 locus. Following high-dose infection with L. major IL-81 and LV39 promastigotes subcutaneously in the footpad, footpad swelling, parasite burden, IFN-γ/IL-4/IL-13 cytokine production, and type 1 and type 2 antibody responses were similar between KRT14 cre IL-4Rα -/lox and littermate control IL-4Rα -/lox BALB/c mice. An intradermal infection with low-dose L. major IL-81 and LV39 promastigotes in the ear showed results in infected KRT14 cre IL-4Rα -/lox BALB/c mice similar to those of littermate control IL-4Rα -/lox BALB/c mice, with the exception of a significant decrease observed in parasite burden only at the site of LV39 infection in the ear. Collectively, our results show that autocrine and paracrine signaling of IL-4/IL-13 through the IL-4Rα chain on keratinocytes does not influence the establishment of a nonhealing Th2 immune response in BALB/c mice during L. major infection., (Copyright © 2018 Govender et al.)

3D printed polycaprolactone (PCL)-blended scaffolds have been designed, prepared, and evaluated in vitro in this study prior to the incorporation of a polyvinyl alcohol⁻polyacrylic acid (PVA⁻PAA) hydrogel for the delivery of in situ-formed sodium indomethacin. The prepared PCL⁻PVA⁻PAA scaffold is proposed as a potential structural support system for load-bearing tissue damage where inflammation is prevalent. Uniaxial strain testing of the PCL-blended scaffolds were undertaken to determine the scaffold’s resistance to strain in addition to its thermal, structural, and porosimetric properties. The viscoelastic properties of the incorporated PVA⁻PAA hydrogel has also been determined, as well as the drug release profile of the PCL⁻PVA⁻PAA scaffold. Results of these analyses noted the structural strength, thermal stability, and porosimetric properties of the scaffold, as well as the ability of the PCL⁻PVA⁻PAA scaffold to deliver sodium indomethacin in simulated physiological conditions of pH and temperature. The results of this study therefore highlight the successful design, fabrication, and in vitro evaluation of a 3D printed polymeric strain-resistant supportive platform for the delivery of sodium indomethacin.

An orally administered site-specific Oral Ghost Drug Delivery (OGDD) device was developed and evaluated for the administration of salmon calcitonin. In vitro drug release studies have been undertaken using biorelevant media and aspirated gastrointestinal fluid from a large white pig in addition to characterization of a formulated trimethyl chitosan blend formulated and prepared into a loaded mini-pellet system. In vivo drug release analysis in a large white pig model has further been undertaken on the OGDD device and a commercial intramuscular injection to ascertain the release properties of the OGDD device in an animal model in comparison with the currently used treatment option for the administration of salmon calcitonin. Results of this study have detailed the success of the prepared system during both in vitro and in vivo analyses with the OGDD providing a greater control of release of salmon calcitonin when compared to the commercial product., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Chronic hepatitis B virus (HBV) infection poses a significant health challenge due to associated morbidity and mortality from cirrhosis and hepatocellular cancer that eventually results in the breakdown of liver functionality. Nanotechnology has the potential to play a pivotal role in reducing viral load levels and drug-resistant HBV through drug targeting, thus reducing the rate of evolution of the disease. Apart from tissue targeting, intracellular delivery of a wide range of drugs is necessary to exert a therapeutic action in the affected organelles. This review encompasses the strategies and techniques that have been utilized to target the HBV-infected nuclei in liver hepatocytes, with a significant look at the new insights and most recent advances in drug carriers and their role in anti-HBV therapy.

Purpose: This study aimed to develop and analyse poly(DL-lactic acid)-methacrylic acid nanospheres bound to the chelating ligand diethylenetriaminepentaacetic acid (DTPA)  for the targeted delivery of amantadine in Amyotrophic Lateral Sclerosis (ALS)., Methods: The nanospheres were prepared by a double emulsion solvent evaporation technique statistically optimized employing a 3-Factor Box-Behnken experimental design. Analysis of the particle size, zeta potential, polydispersity (Pdl), morphology, drug entrapment and drug release kinetics were carried out., Results: The prepared nanospheres were determined to have particle sizes ranging from 68.31 to 113.6 nm (Pdl ≤ 0.5). An initial burst release (50% of amantadine released in 24 hr) was also obtained, followed by a prolonged release phase of amantadine over 72 hr. Successful conjugation of the chelating ligand onto the surface of the optimised nanospheres was thereafter achieved and confirmed by TEM. The synthesized modified nanospheres were spherical in shape, 105.6 nm in size, with a PdI of 0.24 and zeta potential of -28.0 mV. Conjugation efficiency was determined to be 74%. In vitro and ex vivo cell study results confirmed the intracellular uptake of the modified nanospheres by the NSC-34 cell line and the non-cytotoxicity of the synthesized nanospheres., Conclusions: Biocompatible amantadine-loaded nanospheres were successfully designed, characterized and optimized employing the randomized Box-Behnken statistical design. Delivery of amantadine over 72 hrs was achieved, with the nanospheres being of a size capable of internalization by the NSC- 34 cells. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Experimental infection with the protozoan parasite Leishmania major has been extensively used to understand the mechanisms involved in T helper cell differentiation. Following infection, C57BL/6 mice develop a small self-healing cutaneous lesion and they are able to control parasite burden, a process linked to the development of T helper (Th) 1 cells. The local presence of IL-12 has been reported to be critical in driving Th1 cell differentiation. In addition, the early secretion of IL-4 was reported to potentially contribute to Th1 cell differentiation. Following infection with L. major , early keratinocyte-derived IL-4 was suggested to contribute to Th1 cell differentiation. To investigate a putative autocrine role of IL-4 signaling on keratinocytes at the site of infection, we generated C57BL/6 mice deficient for IL-4Rα expression selectively in keratinocytes. Upon infection with L. major , these mice could control their inflammatory lesion and parasite load correlating with the development of Th1 effector cells. These data demonstrate that IL-4 signaling on keratinocytes does not contribute to Th1 cell differentiation. To further investigate the source of IL-4 in the skin during the first days after L. major infection, we used C57BL/6 IL-4 reporter mice allowing the visualization of IL-4 mRNA expression and protein production. These mice were infected with L. major . During the first 3 days after infection, skin IL-4 mRNA expression was observed selectively in mast cells. However, no IL-4 protein production was detectable locally. In addition, early IL-4 blockade locally had no impact on subsequent Th1 cell differentiation and control of the disease. Taken together, the present data rule out a major role for skin IL-4 and keratinocyte IL-4Rα signaling in the development of a Th1 protective immune response following experimental infection with L. major .

Interleukin-4 (IL-4)-induced T helper (Th) 2 cells promote susceptibility to the protozoan parasite Leishmania major , while conferring immunity to the intestinal trematode Schistosoma mansoni Here, we report that abrogation of IL-4 receptor alpha (IL-4Rα) signaling on B cells in BALB/c mice ( mb1 cre IL-4Rα -/lox ) transformed nonhealer BALB/c to a healer phenotype with an early type 1 and dramatically reduced type 2 immune response and an absence of ulceration and necrosis during cutaneous leishmaniasis. From adoptive reconstitution and mixed bone-marrow chimera studies in B cell-deficient (µMT) mice, we reveal a central role for B cell-derived IL-4 and IL-4Rα in the optimal induction of the susceptible type 2 phenotype to L. major infection. We further demonstrate that the absence of IL-4Rα signaling on B cells exacerbated S. mansoni -induced mortality and pathology in BALB/c mice, due to a diminished type 2 immune response. In both disease models, IL-4Rα-responsive B cells displayed increased IL-4 production as early as day 1 after infection. Together, these results demonstrate that IL-4-producing and IL-4Rα-responsive B cells are critical in regulating and assisting early T helper dichotomy toward Th2 responses, which are detrimental in cutaneous leishmaniasis but beneficial in acute schistosomiasis., Competing Interests: The authors declare no conflict of interest.

Background: There is limited data on factors associated with loss to follow-up (LTFU) of health care workers (HCWs) following occupational exposure to HIV, and most studies were conducted in an era when poorly tolerated antiretrovirals like zidovudine were used., Methods: A retrospective cohort study was conducted of HCWs attending a referral hospital's Occupational Health Clinic in Cape Town, South Africa for post-exposure prophylaxis (PEP) during a period when tenofovir was available. Our primary outcome was LTFU at the 3-month visit. We selected seven variables a priori for our logistic regression model and ensured there were at least 10 outcome events per variable to minimize bias., Results: Two hundred and ninety-three folders were evaluated for descriptive analysis. LTFU worsened with successive visits: 36% at 6 weeks, 60% at 3 months, and 72% at 6 months. In multivariate analysis at the 3-month visit LTFU was associated with age (adjusted odds ratio (aOR), 0.6 per 10-year increase [95% CI, 0.5-0.9]), HCW category of doctor (aOR 2.7 [95% CI, 1.3-5.5]), and time from exposure to receiving PEP of more than 24 h (aOR 5.9 [95% CI, 1.3-26.9])., Conclusion: We identified factors associated with LTFU of HCWs after occupational HIV exposure, which could be used to target interventions to improve follow-up.

With a significant portion of the world suffering from chronic pain, the management and treatment of this condition still requires extensive research to successfully mobilize and functionalize its sufferers. This article details the in vitro and in vivo evaluation of a transdermal electro-modulated hydrogel-microneedle array (EMHM) device for the treatment of chronic pain. In vitro characterization of the electro-modulated hydrogel was undertaken before the determination of the in vivo release, histopathologic and pharmacokinetic profiles of the EMHM in a Sprague Dawley rat model. Pharmacokinetic modeling was conducted to establish a level A in vitro-in vivo correlation. Data analysis was carried out by segmenting the combined in vivo release profile into individualistic profiles before analysis., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Starch is a naturally occurring storage copolymer with unique physicochemical properties. There are, however, some key structural properties of starch that can be modified in order to functionalize the copolymer to meet specific requirements. Specifically, the chemical modification of starch provides a variety of physicochemical benefits, some of which have been used previously to functionalize preformed drug delivery systems. Of the three main chemical modification methods reviewed (namely: oxidation, esterification and etherification), surface chemical oxidation introduces more pertinent physicochemical properties that increase overall drug delivery system efficacy and applicability. Surface oxidation evidently is the more preferable chemical modification method of pre-formed starch particles and has the greatest potential for further development when compared to the other reviewed chemical modification methods. The use of modified starch in clinical trials as well as the potential future implications of these systems is also included in this review., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: A delayed release bio-polymeric Dual-Biotic system has been extensively evaluated in this study to overcome the therapeutic issue of probiotic killing due to incorrect administration with the antibiotic., Methods: In vitro and ex vivo release and characterization studies have been undertaken on the Dual-Biotic system. In vivo analyses utilizing a Large White pig model were also performed with commercial products used as a comparison. Intestinal fluid for probiotic quantification was aspirated using a surgically implanted intestinal cannula with Lactobacillus acidophilus cell counts determined through luminescence and inoculation onto Lactobacilli-specific agar. Plasma amoxicillin concentrations were determined through Ultra-Performance Liquid Chromatography. The reactional profile and crosslinking mechanism of ovalbumin and genipin was elucidated using molecular mechanic energy relationships in a vacuum system by exploring the spatial disposition of different concentrations of genipin with respect to ovalbumin with ovalbumin/genipin ratios of 1:1, 1:5 and 1:10., Results: In vivo evaluation of the Dual-Biotic system detailed maximum Lactobacillus viability (~455% baseline viability) 6 h after oral administration. Concurrent administration of the commercial products revealed a 75% decrease in bacterial viability when compared to the controls analyzed. A level A in vitro-in vivo correlation was also established with 96.9% predictability of amoxicillin release ascertained. The computational results achieved corroborated well with the experimental findings and physicochemical data., Conclusions: Evaluation and correlation of the Dual-Biotic system has detailed the success of the formulation for the concurrent delivery of an antibiotic and probiotic.

Oesophageal cancer is a disease with significant morbidity and mortality, and in South Africa most patients present with advanced disease.1 Self-expanding metal stents (SEMS) are now widely used in the palliation of oesophageal cancer, and in most institutions SEMS are deployed under fluoroscopic guidance. In our institution, we use an exclusive endoscopic deployment technique which is comparable to the traditional fluoroscopic technique in terms of safety and efficacy.2-4 We undertook a study to compare the two techniques with respect to their time- and cost-effectiveness., (Copyright© Authors.)

Aim: A delayed-release dual delivery system for amoxicillin and the probiotic Lactobacillus acidophilus was developed and evaluated., Materials & Methods: Statistical optimization of a cross-linked denatured ovalbumin protective matrix was first synthesized using a Box-Behnken experimental design prior to encapsulation with glyceryl monostereate. The encapsulated ovalbumin matrix was thereafter incorporated with amoxicillin in a gastro-resistant capsule. In vitro characterization and stability analysis of the ovalbumin and encapsulated components were also performed Results: Protection of L. acidophilus probiotic against the bactericidal effects of amoxicillin within the dual formulation was determined., Conclusion: The dual formulation in this study proved effective and provides insight into current microbiome research to identify, classify and use functional healthy bacteria to develop novel probiotic delivery technologies.

Pediatric oncology patients often experience fatigue and physical and mental deconditioning during and following chemotherapy treatments, contributing to diminished quality of life. Patient empowerment is a core principle of patient-centered care and reflects one's ability to positively affect his or her own health behavior and health status. Empowerment interventions may enhance patients' internal locus of control, resilience, coping skills, and self-management of symptoms related to disease and therapy. Clinical and technological advancements in therapeutic videogames and mobile medical applications (mobile health) can facilitate delivery of the empowerment interventions for medical purposes. This review summarizes clinical strategies for empowering pediatric cancer patients, as well as their relationship with developing a "fighting spirit" in physical and mental health. To better understand physiological aspects of empowerment and to elucidate videogame-based intervention strategies, brain neuronal circuits and neurotransmitters during stress, fear, and resilience are also discussed. Neuroimaging studies point to the role of the reward system pathways in resilience and empowerment in patients. Taken together, videogames and mobile health applications open translational research opportunities to develop and deliver empowerment interventions to pediatric cancer patients and also to those with other chronic diseases.

Background: Sex work has shifted from brothels to entertainment establishments (EEs) in Asia. Men who patronise EEs could act as a bridging population for human immunodeficiency virus (HIV) and sexually transmitted infection (STI) transmission through unprotected sex with the female EE workers to their spouses and regular partners. The aim of this study was to compare the prevalence and factors associated with risky sexual behaviours among the heterosexual men who patronised the EEs and brothels in Singapore., Methods: This was a cross-sectional survey involving 569 heterosexual men (297 recruited from brothels and 272 from EEs). A 2-stage sampling involving proportional stratified random sampling of the brothels and EEs, followed by time location sampling of the men, was conducted. For multivariable analysis, we used a mixed effects logistic model with backward elimination to account for clustering by venue and to obtain the adjusted odds ratio (aOR) for the association of various factors with consistent condom use in vaginal and oral sex respectively., Results: Men who patronised EEs were younger, more likely to be single, more highly-educated and comprised more professionals compared to the brothel group. On multivariable analysis, consistent condom use for vaginal sex decreased at the EE setting (aOR 0.64; 95 % CI: 0.42 -0.97) and with alcohol use before sex (aOR 0.67; 95 % CI: 0.46 - 0.98) and increased with perceived high risk of getting HIV/STIs from partner (aOR 2.08; 95 % CI: 1.30 - 3.32) and partner's request for condom use (aOR 5.48; 95 % CI: 1.20 - 25.11). For consistent condom use with oral sex, this decreased at the EE setting (aOR 0.64; 95 % CI: 0.39 - 0.98) and with alcohol use before sex (aOR 0.50; 95 % CI: 0.31 - 0.81) and increased with partner's request for condom use (aOR 5.19; 95 % CI: 1.38 - 19.57)., Conclusions: Men who patronised EEs practised risker sexual behaviours compared to the brothel group. Priority should be given for intervention programmes to target men who patronise EEs, which could involve the female EE workers, the EE owners as well as the managers for effective HIV/STI prevention.

Objectives: The viability of probiotic bacteria during formulation processes and delivery is vital to ensure health benefits. This study focuses on the use of gastro-resistant denatured ovalbumin for the targeted delivery of probiotic Lactobacillus acidophilus to simulated human intestinal and colon conditions through a bi-layered mini-tablet-in-tablet system (BMTTS)., Methods: The BMTTS consists of two gastro-resistant ovalbumin mini-tablets containing L. acidophilus suspended in lactose and eudragit S100 for targeted intestinal and colonic delivery respectively. Luminescence has been utilized to ensure probiotic viability during formulation processes in addition to determining all probiotic release profiles. The mechanism of probiotic release from the ovalbumin matrix was ascertained using mathematical modelling and molecular docking studies. Magnetic resonance imaging and differential scanning calorimetry are also included as part of the in-vitro characterization of the ovalbumin system., Key Findings: The BMTTS was effective in the delivery of L. acidophilus to simulated human intestinal and colon conditions. Formulation processes were furthermore determined to maintain probiotic viability. Statistical analysis of the release data noted a significant effect of pH denaturation on the release properties of ovalbumin. Magnetic resonance imaging results have indicated a decrease in ovalbumin matrix size upon exposure to simulated intestinal fluid. Molecular docking studies carried out depicted the interaction and binding positions inherent to the ovalbumin-pancreatic trypsin interaction complex indicating the possible enzymatic degradation of ovalbumin leading to the release of the probiotic from the protein matrix., Conclusions: The BMTTS has been determined to be effective in the protection and delivery of probiotic L. acidophilus to simulated human intestinal and colonic conditions. Molecular docking analysis has noted that pancreatin exerts a significant effect on probiotic release from the gastro-resistant ovalbumin matrix., (© 2015 Royal Pharmaceutical Society.)

Objective: To compare the prevalence of condom use and its associated factors within commercial and casual sex relationships between heterosexual men who seek sex online and those who frequent brothels in Singapore., Methods: A survey was conducted between 2011 and 2012 among Singaporean heterosexual men aged 21-70 years who reported engaging in sexual intercourse with commercial or casual partners in the past year. Men seeking sex online (n=304) were recruited from the two most frequented local internet sex forums. Men frequenting brothels (n=297, 97% response rate) were recruited from a stratified cluster random sample of licensed brothels., Results: Compared with men frequenting brothels, men seeking sex online reported significantly higher rates of oral and anal sex and sexually transmitted diseases but lower condom use for oral sex with commercial (16.5% vs 56.6%) and casual partners (21.2% vs 35.3%). In multivariate analyses, the online group showed that partner request for condom use was strongly associated with condom use for vaginal sex (adjusted ORs >3.0) but not with condom use for oral sex with both casual and commercial sex partners. The perceived risk of getting HIV from a partner was also associated with condom use for vaginal sex with commercial and casual partners; and for oral sex with casual partners. In contrast, condom use for oral and vaginal sex with both partners in the brothel group was only associated with partner request for condom use., Conclusions: Men seeking sex online should receive sexually transmitted infection (STI)/HIV prevention interventions that deal with the factors associated with condom use., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Mucoepidermoid carcinoma (MEC) is a rare primary esophageal malignancy. It is characterized by poor clinical recognition, pre-operative diagnostic challenges and a lack of standardized therapeutic guidelines. We report the clinicopathological features of a hitherto unreported variant of esophageal MEC, sclerosing MEC with "tissue eosinophilia", in a mid-esophageal location in a 51-year-old female. The diagnosis of the initial biopsy was challenging, because of the small size, poor orientation and inadequate representation of the MEC components. Recognition of the resectability of the tumor prompted surgical resection and enabled a demonstration of the low grade foci containing intermediate cells, mucin pools and the hitherto undescribed presence of stromal sclerosis and tissue eosinophils in esophageal MEC. Heightened clinicopathological awareness of esophageal MEC facilitated a definitive diagnosis and patient management. Increased recognition and global documentation of esophageal sclerosing MEC with "tissue eosinophilia" is necessary to improve the understanding and diagnosis of this malignancy in this location and to improve management guidelines.

Probiotic delivery systems are widely used nutraceutical products for the supplementation of natural intestinal flora. These delivery systems vary greatly in effectiveness to exert health benefits for a patient. Probiotic delivery systems can be categorized into conventional, pharmaceutical formulations, and non-conventional, mainly commercial food-based, products. The degree of health benefits provided by these probiotic formulations varies in their ability to deliver viable, functional bacteria in large enough numbers (effectiveness), to provide protection against the harsh effects of the gastric environment and intestinal bile (in vivo protection), and to survive formulation processes (viability). This review discusses the effectiveness of these probiotic delivery systems to deliver viable functional bacteria focusing on the ability to protect the encapsulated probiotics during formulation process as well as against harsh physiological conditions through formulation enhancements using coatings and polymer enhancements. A brief overview on the health benefits of probiotics, current formulation, patient and legal issues facing probiotic delivery, and possible recommendations for the enhanced delivery of probiotic bacteria are also provided. Newer advanced in vitro analyses that can accurately determine the effectiveness of a probiotic formulation are also discussed with an ideal probiotic delivery system hypothesized through a combination of the two probiotic delivery systems described.

We reviewed the current human immunodeficiency virus (HIV) prevention education programmes in Singapore, discussed the challenges faced and proposed prevention education interventions for the future. Education programmes on HIV prevention have shown some success as seen by reduced visits to sex workers among the general adult population and a marked increase in condom use among brothel-based sex workers. However, we still face many challenges such as low awareness of HIV preventive strategies and high prevalence of HIV stigma in the general population. Voluntary HIV testing and condom use remain low among the priority groups such as men who have sex with men (MSM) and heterosexual men who buy sex. Casual sex has increased markedly from 1.1% in 1989 to 17.4% in 2007 among heterosexuals in Singapore, with the majority (84%) practising unprotected sex. Sex workers have moved from brothels to entertainment venues where sex work is mostly hidden with lack of access to sexually transmitted infections (STIs)/ HIV prevention education and treatment programmes. Education programmes promoting early voluntary testing is hampered because of poor access, high cost and stigma towards people living with HIV. It remains a challenge to promote abstinence and consistent condom use in casual and steady sexual relationships among heterosexuals and MSM. New ways to promote condom use by using a positive appeal about its pleasure enhancing effects rather than the traditional disease-oriented approach should be explored. Education programmes promoting early voluntary testing and acceptance of HIV-infected persons should be scaled up and integrated into the general preventive health services.

In this letter, the production of multi-phase WO3 and WO3-x (where x could vary between 0.1 and 0.3) nanostructures synthesized by CO2-laser pyrolysis technique at varying laser wavelengths (9.22-10.82 mm) and power densities (17-110 W/cm2) is reported. The average spherical particle sizes for the wavelength variation samples ranged between 113 and 560 nm, and the average spherical particle sizes for power density variation samples ranged between 108 and 205 nm. Synthesis of W18O49 (= WO2.72) stars by this method is reported for the first time at a power density and wavelength of 2.2 kW/cm2 and 10.6 μm, respectively. It was found that more concentrated starting precursors result in the growth of hierarchical structures such as stars, whereas dilute starting precursors result in the growth of simpler structures such as wires.

Background: Colonic and intra-peritoneal rectal injuries may be managed by primary repair and extra-peritoneal rectal injuries by diverting colostomy. This study was undertaken to document our experience with this approach and to identify factors which might impact on outcome., Patients and Methods: Prospective study of all patients treated for colon and rectal injuries in one surgical ward at King Edward VIII hospital, Durban, over a 7-year period (1998-2004). Demographic data, clinical presentation, findings at laparotomy and outcome were documented., Results: Of 488 patients undergoing laparotomy, 177 (36%) had injuries to the colon and rectum with age 29.8+/-10.9 years. Injury mechanisms were firearms (118) stabs (54) and blunt trauma (5). Delay before laparotomy was 10+/-9.3 h. Complication and mortality rates were 36% and 17%, respectively. 68 patients (38%) required ICU management. Shock on admission and increased transfusion requirements were associated with a significantly increased mortality. Patients with delay < or = 12 h before laparotomy had a higher mortality rate than those with delay >12 h. The mortality rate increased with the number of associated injuries and it was higher the higher the Injury Severity Score (ISS); it was similar for stabs, firearms and blunt trauma. Hospital stay was 9.5+/-9.2 days., Conclusion: We reaffirm that primary repair is appropriate for colonic and intra-peritoneal rectal injuries and that extra-peritoneal rectal injuries require diverting colostomy. Shock on admission, increased blood transfusion requirements, associated organ injury and severity of the injury were associated with high mortality.

The syringyl to guaiacyl (S:G) ratio of hardwood lignin has long been identified as a significant parameter in delignification processes and more recent results have shown that it is also important in determining the amount of ethanol that can be obtained from fermentation of hydrolyzed wood. Acidolysis of Klason or acid insoluble lignin in dioxane/water/HCl was being investigated when syringyl and guaiacyl nuclei with a diketone-containing sidechain were observed as the major products. The area ratio of the two gas chromatogram peaks appeared to be indicative of the S:G ratio. After optimization of the method the relative standard deviation was found to be in the range of 0.3-3.76% for Klason lignin from a wide range of Eucalyptus grandis grown in South Africa. The method was then compared to nitrobenzene oxidation (NBO) using 13 poplars in a double-blind study. The respective S:G ratios were used to calculate percentages of S units and when these values were plotted against each other a linear correlation was obtained with a slope of approximately 1.0 (R(2)=0.86). The largest discrepancy for any poplar was 6.9% (62% vs. 58% S units). Both methods convincingly demonstrated a significant decrease in lignin content with an increase in the S:G ratio. Discussion is presented on a series of reaction that could lead to the formation of the two diketones.

Two oxidation techniques that afford high yields of monomers and dimers were used to more accurately estimate the syringyl to guaiacyl (S:G) ratio of hardwood lignins. Permanganate oxidation of the woodmeal after a CuO pre-hydrolysis step gave poor results and this was attributed to preferential oxidation and degradation of syringyl nuclei by CuO. However, this procedure did provide a good estimate of the percentages of both S and G phenylpropane (C(9)) units that were uncondensed. When the total S and G products from nitrobenzene oxidation (NBO) of the uncondensed fractions were corrected, credible S:G ratios were obtained. These ratios were in good agreement with results from KMnO4 oxidation of dissolved kraft lignin without CuO pre-hydrolysis. The corrected NBO method was used to determine the S:G ratio of 13 poplars, and the values ranged from 1.01 to 1.68. Unlike results from other investigations, an excellent linear correlation (R(2) =0.846) was obtained for a decreasing lignin content (28% to 16.5%) with an increase in the S:G ratio.

Legal instruments and litigation as a way to enforce the rights to life and to health is a relatively new strategy that is increasingly common. We show how legal measures have been used to attain health and human rights with case examples from India and South Africa that resulted in large public-health benefits.

A new Os/Cu-Al-hydrotalcite-like catalyst is described which, with N-methylmorpholine oxide as co-oxidant, heterogeneously catalyses the hydroxylation of olefins to give diols selectively and in high yield.

Background: Notification of occupational diseases to the Department of Labour (and in limited situations to other agencies) is an important aspect of surveillance and planning for interventions as well as compensation. A survey of general practitioners (GPs) was conducted to assess their knowledge and practice with regard to reporting of occupational diseases., Design: Descriptive telephonic survey., Setting: Independent general practices in the Western Cape., Participants: One hundred and forty GPs were randomly selected from a provincial sampling frame of 1,000 GPs., Main Outcome Measures: Knowledge of notification procedures for occupational diseases, and problems encountered with the reporting system., Results: Of a total of 109 GPs interviewed, 75% had diagnosed more than one case of occupational disease in the last 6 months. Twenty-four per cent of the total (95% confidence interval (CI) 16-32%) indicated that they were aware of the notification requirements, and 5% (95% CI 0.8-9%) knew the appropriate legislation. Only one GP notified the appropriate authority once the diagnosis was made. Factors influencing their reporting practice included lack of guidelines for diagnosis of common work-related conditions, lack of information regarding referral channels, problems with communicating with the patient and employer, and poor knowledge of the reporting process itself. Lack of motivation as a result of poor feedback on cases reported and the labour-intensive administration required, were also cited as factors., Conclusion: Although the majority of GPs diagnose occupational diseases, knowledge and practice regarding notification are poor. Recommendations to overcome obstacles to notification include a simplified, uniform notification system, adequate training and support of GPs, and timeous feedback to GPs.

Aim: To ascertain the prevalence and severity of phenytoin-induced gingival enlargement (PIGE) as well as the relationship between PIGE and risk factors., Method: An outpatient population of patients on phenytoin treatment and attending the epilepsy clinic at Prince Mshiyeni Memorial Hospital (PMMH) in Durban, South Africa, was requested to participate. A structured questionnaire was used to collect data on patients' demographics, social habits (e.g., drinking and smoking), dental and oral hygiene practices and medication history. Gingival enlargement, dental plaque and gingival bleeding was also measured to assess gingival health. Venous blood was collected for serum folate and phenytoin serum levels measurements. A regression analyses was then undertaken to ascertain the association between PIGE and the risk factors. Factors tested for correlation were serum phenytoin and folate levels, age, bacterial plaque, gingival inflammation, toothbrushing, smoking and alcohol consumption. The association between PIGE and the risk factors was assessed either individually, i.e., as a single entity or in combination--multifactorially., Results: Of the 134 patients studied, 62% had PIGE scores > or = 1, while 8% had a PIGE score of zero. With the exception of plaque, which showed a moderate association with PIGE (r=0.4), no other factor on its own was statistically significantly related to PIGE. In the multiple linear regression analysis, factors which on their own did not have a strong influence became more important. Bacterial plaque (p=0.0001), younger age (p=0.01) and higher free serum phenytoin levels (p= 0.03), were associated with PIGE. Although known to be associated with periodontal diseases, smoking and alcohol, (p=0.03 and p=0.04 respectively), appeared to give some protection against PIGE., Conclusion: Risk factors associated with PIGE may have a synergistic effect. Bacterial plaque, however, appears the most important determinant of PIGE severity. This latter finding emphasises the importance of instituting a preventive plaque-control programme, particularly in young patients on phenytoin therapy.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection and quantitation of antibodies (anti-HBs) to the surface antigen of the hepatitis B virus (HBsAg). The ELISA uses HBsAg as the solid phase, and, after conjugation to horseradish peroxidase, also as the conjugate. Conditions for this assay were optimized and a rapid (1.5 hours) ELISA has evolved which works very satisfactorily for the large-scale screening of donated blood. We have used this ELISA to examine donated blood in Natal and concluded that we cannot initiate a programme of anti-HBs supplementation of parenteral blood products without hyperimmunization and plasmapheresis of selected, voluntary donors.

A method is described for the production of mouse monoclonal antibodies to HBsAg. 4 clones produced antibodies directed at the a and one at the d determinant of HBsAg. These antibodies were conjugated to horse radish peroxidase and used in an Elisa for the detection of HBsAg in donated blood. Antibody C10 produced conjugate which rendered the Elisa as sensitive as a commercially obtainable immunoradiometric assay with which it was compared. Conditions for this assay were optimised and it may be used as a rapid (1 h) test for detecting HBsAg-positive blood. It is practicable to read this Elisa by eye instead of photometrically and it can be thus used under field conditions or in emergencies.