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Skin cancer is broadly classified into two categories i.e., non-melanoma skin cancer (NMSC) and malignant melanoma (MM), with MM having a greater fatality rate than NMSC. A large number of treatment strategies currently exist for these skin cancer types, ranging from monotherapies to complex multifaceted synergistic interventions including dual therapies, trimodality therapy, and multicomponent combinations therapy. These combinatorial cancer treatments have delivered more favorable results when compared with monotherapies, and although combination treatments increase the cost of treatment, these regimens have lower side effect profiles, decreased resistance, high efficacy and an improved long-term response. Synergistic combination treatments for skin cancer are often complex, wide-ranging and encompass diverse platforms with various mechanisms of action. An understanding of the physiological potential, as well the efficacy of such treatments, is therefore vital to ensure patients receive the best possible treatment. This review therefore focuses on the current advancements and existing non-surgical combinative drug delivery methods utilized for treating skin cancer. It encompasses the diverse pharmaceutical delivery systems, clinical outcomes, and oncology strategies employed and aims to highlight the role of non-surgical combination therapies in enhancing patient compliance, reducing treatment durations, and improving overall survival rates while addressing relapses and metastasis. The promising outlook of the research being conducted in this field has also been provided, as well as the barriers to the effective treatment of this complex condition., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Three-Dimensional (3D) microneedles have recently gained significant attention due to their versatility, biocompatibility, enhanced permeation, and predictable behavior. The incorporation of biological agents into these 3D constructs has advanced the traditional microneedle into an effective platform for wide-ranging applications., Areas Covered: This review discusses the current state of microneedle fabrication as well as the developed 3D printed microneedles incorporating labile pharmaceutical agents and biological materials for potential biomedical applications. The mechanical and processing considerations for the preparation of microneedles and the barriers to effective 3D printing of microneedle constructs have additionally been reviewed along with their therapeutic applications and potential for tissue engineering and regenerative applications. Additionally, the regulatory considerations for microneedle approval have been discussed as well as the current clinical trial and patent landscapes., Expert Opinion: The fields of tissue engineering and regenerative medicine are evolving at a significant pace with researchers constantly focused on incorporating advanced manufacturing techniques for the development of versatile, complex, and biologically specific platforms. 3D bioprinted microneedles, fabricated using conventional 3D printing techniques, have resultantly provided an alternative to 2D bioscaffolds through the incorporation of biological materials within 3D constructs while providing further mechanical stability, increased bioactive permeation and improved innervation into surrounding tissues. This advancement therefore potentially allows for a more effective biomimetic construct with improved tissue-specific cellular growth for the enhanced treatment of physiological conditions requiring tissue regeneration and replacement.

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas-Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications.

Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by low levels of antibodies. In addition to infections, many patients also suffer from T-helper 1-driven immune dysregulation, which is associated with increased mortality. The aim of this study was to perform in-depth characterization of the T and the B cell compartments in a well-defined cohort of patients affected by CVID and correlate the findings to the level of clinical immune dysregulation. We used mass cytometry, targeted proteomics, flow cytometry and functional assays to delineate the immunological phenotype of 15 CVID-affected patients with different levels of immune dysregulation. Unbiased clustering of T cell mass cytometry data correlated with CVID-related immune dysregulation and plasma protein profiles. Expanded CXCR3 + T-bet-expressing B cells correlated with effector memory CD4 + T cell clusters, and increased plasma levels of CXCR3-ligands. Our findings indicate an interplay between B cells and T cells in CVID-related immune dysregulation and provide a better understanding of the underlying pathological mechanisms., Competing Interests: Declaration of Competing Interest The authors have no financial or non-financial interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The differing roles of the pentameric (p) and monomeric (m) C-reactive protein (CRP) isoforms in viral diseases are not fully understood, which was apparent during the COVID-19 pandemic regarding the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we investigated the predictive value of the pCRP and mCRP isoforms for COVID-19 severity in hospitalized patients and evaluated how the levels of the protein isoforms changed over time during and after acute illness. This study utilized samples from a well-characterized cohort of Swedish patients with SARS-CoV-2 infection, the majority of whom had known risk factors for severe COVID-19 and required hospitalization. The levels of pCRP were significantly raised in patients with severe COVID-19 and in contrast to mCRP the levels were significantly associated with disease severity. Additionally, the pCRP levels remained elevated for at least six weeks post inclusion, which was longer compared to the two weeks for mCRP. Our data indicates a low level of inflammation lasting for at least six weeks following COVID-19, which might indicate that the disease has an adverse effect on the immune system even after the viral infection is resolved. It is also clear that the current standard method of testing pCRP levels upon hospitalization is a useful marker for predicting disease severity and mCRP testing would not add any clinical relevance for patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision, (Copyright © 2023 Hopkins, Nordgren, Fernandez-Botran, Enocsson, Govender, Svanberg, Svensson, Hagbom, Nilsdotter-Augustinsson, Nyström, Sjöwall, Sjöwall and Larsson.)

Background: There is a paucity of data around corrosive ingestion in South Africa over the last three decades. As such, we set out to review our experience with adult corrosive ingestion in our tertiary gastrointestinal surgical service., Methods: A retrospective, quantitative review was performed. The parameters analysed were demographics, substance ingestion, ingestion time to first presentation to a healthcare facility, clinical presentation, severity of injury based on endoscopic classification, computed tomography (CT) findings, management and outcomes. Patients presenting within 72 hours with alarm symptoms underwent flexible upper endoscopy and injury severity grading. In patients presenting after 72 hours, a water-soluble contrast study was obtained prior to upper endoscopy. Patients with signs of sepsis, surgical emphysema or physiological instability were referred for urgent CT to exclude oesophageal perforation and mediastinitis., Results: Between January 2012 and January 2019, a total of 64 patients presented with a history of corrosive ingestion - 40 (31%) were males and 24 (19%) females. The average time from ingestion to presentation was 72 hours. In 78% of patients, the agents were intentionally ingested, whilst 22% claimed accidental ingestion. A quarter of the patients (21%) presented to the unit clinically unstable, requiring emergent cardiorespiratory support. Eight (12%) patients required urgent surgical intervention due to the extent of injury. Nine (14%) patients demised during the acute admission. Of this group, three patients had undergone surgical intervention, and six were managed conservatively. Eighty-five per cent of all patients survived their initial admission., Conclusion: This paper has highlighted the problem of corrosive ingestion in our setting. It remains a complicated problem to manage associated with significant morbidity and mortality rates. The current trend in the assessment of these patients is increased use of CT scan to assess the extent of transmural necrosis. Our algorithms should change to reflect this contemporary approach., (Copyright© Authors.)

Estrogens locally delivered to the vagina by tablets, capsules, rings, pessaries, and creams are the most common and highly recommended platforms to treat the genitourinary syndrome of menopause (GSM). Estradiol, an essential estrogen, is routinely administered alone, or in combination with progestins, to effectively alleviate the symptoms associated with moderate to severe menopause when non-pharmacological interventions are not indicated. Since the risk and side effects of estradiol use depends on the administered amount and duration of use, the lowest effective dose of estradiol is recommended when long-term treatment is required. Although there is a wealth of data and literature comparing vaginally administered estrogen-containing products, there is a lack of information revealing the effect of the delivery system used and formulation constituent's attributes on the efficacy, safety, and patient acceptability of these dosage forms. This review therefore aims to classify and compare various designs of commercially available and non-commercial vaginal 17β-estradiol formulations and analyze their performance in terms of systemic absorption, efficacy, safety, and patient satisfaction and acceptance. The vaginal estrogenic platforms included in this review are the currently marketed and investigational 17β-estradiol tablets, softgel capsules, creams, and rings for the treatment of GSM, based on their different design specifications, estradiol loads, and materials used in their preparation. Additionally, the mechanisms of the effects of estradiol on GSM have been discussed, as well as their potential impact on treatment efficacy and patient compliance., Competing Interests: Conflicts of Interest The authors do not declare any conflicts of interest., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

A micro-in-macro gastroretentive and gastrofloatable drug delivery system (MGDDS), loaded with the model-drug ciprofloxacin, was developed in this study to address the limitations commonly experienced in narrow-absorption window (NAW) drug delivery. The MGDDS, which consists of microparticles loaded in a gastrofloatable macroparticle (gastrosphere) was designed to modify the release of ciprofloxacin, allowing for an increased drug absorption via the gastrointestinal tract. The prepared inner microparticles (1-4 µm) were formed by crosslinking chitosan (CHT) and Eudragit ® RL 30D (EUD), with the outer gastrospheres prepared from alginate (ALG), pectin (PEC), poly(acrylic acid) (PAA) and poly(lactic-co-glycolic) acid (PLGA). An experimental design was utilized to optimize the prepared microparticles prior to Fourier Transition Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM) and in vitro drug release studies. Additionally, the in vivo analysis of the MGDDS, employing a Large White Pig model and molecular modeling of the ciprofloxacin-polymer interactions, were performed. The FTIR results determined that the crosslinking of the respective polymers in the microparticle and gastrosphere was achieved, with the SEM analysis detailing the size of the microparticles formed and the porous nature of the MGDDS, which is essential for drug release. The in vivo drug release analysis results further displayed a more controlled ciprofloxacin release profile over 24 h and a greater bioavailability for the MGDDS when compared to the marketed immediate-release ciprofloxacin product. Overall, the developed system successfully delivered ciprofloxacin in a control-release manner and enhanced its absorption, thereby displaying the potential of the system to be used in the delivery of other NAW drugs.

Presence of autoantibodies targeting nuclear constituents, i.e., double-stranded DNA and small nuclear ribonucleoproteins (snRNPs), remain a cornerstone in systemic lupus erythematosus (SLE). Fcγ receptor IIa (FcγRIIa) dependent uptake of nucleic acid containing immune complexes (ICs) by plasmacytoid dendritic cells (PDCs) can activate toll-like receptors (TLRs) such as TLR7 and TLR9 resulting in type I interferon (IFN) production. Previously, the classical liver-derived acute-phase reactant C-reactive protein (CRP) has been suggested to reduce IC-induced type I IFN production, whereas monomeric (mCRP) vs. pentameric (pCRP) mediated effects have not yet been unraveled. Herein, peripheral blood mononuclear cells (PBMCs) or enriched blood DCs from healthy volunteers were stimulated with SLE sera, snRNP-IgG (ICs), or TLR ligands with or without pCRP, mCRP, or anti-FcγRIIa antibody. Type I IFNs and cytokine responses were investigated using quantitative PCR, ELISA, and flow cytometry. pCRP inhibited IFN gene expression in PBMCs and enriched DCs after incubation with ICs, compared to ICs alone, whereas mCRP had significantly less inhibitory effect. The effect was independent on the order in which IC or CRP was added to the cells. In addition, pCRP inhibited IFN induced by other TLR stimulators, implicating broader inhibitory effects induced by pCRP. We demonstrate pronounced immunoregulatory functions of CRP whereas the inhibitory properties were evidently dependent on CRP's intact conformational state. The inhibition of type I IFNs was not due to competition of FcγRs, or binding of CRP to the ICs. Our findings have implications for autoimmune IC-mediated conditions imprinted by type I IFN gene dysregulation., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19., Methods: Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection., Results: We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets., Conclusion: By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hopkins, Govender, Svanberg, Nordgren, Waller, Nilsdotter-Augustinsson, Henningsson, Hagbom, Sjöwall, Nyström and Larsson.)

Tyrosine kinase inhibitors (TKIs) are effective drug molecules for the treatment of various cancers. Nanomedicinal interventions and approaches may not only provide carrying capacities for TKIs but also potentially target tumor-specific environments and even cellular compartments. Nano-inspired drug delivery systems may hence enhance the efficacy of the drugs through enhanced tumour-availability resulting in greater efficacy and decreased side effects. A variety of nanosystems have been developed for the delivery of TKIs for the enhanced treatment of cancers, each with their own preparation methods and physicochemical properties. This review will therefore discuss the applicability of nano-interventions towards combination therapies, dose reduction, and greater potential treatment outcomes. The individual nanosystems have been highlighted with emphasis on the developed systems and their efficacy against various cancer cell lines and models., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

HIV-1 infection gives rise to a multi-layered immune impairment in most infected individuals. The chronic presence of HIV-1 during the priming and activation of T cells by dendritic cells (DCs) promotes the expansion of suppressive T cells in a contact-dependent manner. The mechanism behind the T cell side of this HIV-induced impairment is well studied, whereas little is known about the reverse effects exerted on the DCs. Herein we assessed the phenotype and transcriptome profile of mature DCs that have been in contact with suppressive T cells. The HIV exposed DCs from cocultures between DCs and T cells resulted in a more tolerogenic phenotype with increased expression of e.g., PDL1, Gal-9, HVEM, and B7H3, mediated by interaction with T cells. Transcriptomic analysis of the DCs separated from the DC-T cell coculture revealed a type I IFN response profile as well as an activation of pathways involved in T cell exhaustion. Taken together, our data indicate that the prolonged and strong type I IFN signaling in DCs, induced by the presence of HIV during DC-T cell cross talk, could play an important role in the induction of tolerogenic DCs and suppressed immune responses seen in HIV-1 infected individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Svanberg, Nyström, Govender, Bhattacharya, Che, Ellegård, Shankar and Larsson.)

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8 + TEMRA and exhausted CD57 + CD8 + T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69 + CD4 + T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Govender, Hopkins, Göransson, Svanberg, Shankar, Hjorth, Nilsdotter-Augustinsson, Sjöwall, Nyström and Larsson.)

Understanding social media networks and group interactions is crucial to the advancement of linguistic and cultural behavior. This includes how people accessed advice on health during COVID-19 lockdown. Some people turned to social media to access information on health when other routes were curtailed by isolation rules, particularly among older generations. Facebook public pages, groups and verified profiles using keywords "senior citizen health", "older generations", and "healthy living" were analyzed over a 12-month period to examine engagement with social media promoting good mental health. CrowdTangle was used to source status updates, photo and video sharing information in the English language, which resulted in an initial 116,321 posts and 6,462,065 interactions. Data analysis and visualization were used to explore large datasets, including natural language processing for "message" content discovery, word frequency and correlational analysis as well as co-word clustering. Preliminary results indicate strong links to healthy aging information shared on social media, which showed correlations to global daily confirmed cases and daily deaths. The results can identify public concerns early on and address mental health issues among senior citizens on Facebook.

Background: Efficient healthcare based on prognostic variables in hospitalised patients with COVID-19 could reduce the risk of complications and death. Recently, soluble urokinase Plasminogen Activator Receptor (suPAR) was shown to predict respiratory failure, kidney injury, and clinical outcome in patients with SARS-CoV-2 infection. The aim of this study was to investigate the value of suPAR as a prognostic tool, in comparison with other variables, regarding disease severity and length of hospital stay in patients with COVID-19. Patients and Methods: Individuals hospitalised with COVID-19 (40 males, 20 females; median age 57.5 years) with a median symptom duration of 10 days and matched, healthy controls ( n = 30) were included. Admission levels of suPAR were measured in serum by enzyme-linked immunosorbent assay. Blood cell counts, C-reactive protein (CRP) levels, lactate dehydrogenase (LDH), plasma creatinine and estimated glomerular filtration rates were analysed and oxygen demand, level of care and length of hospitalisation recorded. Results: Patients had significantly higher suPAR levels compared to controls ( P < 0.001). Levels were higher in severely/critically (median 6.6 ng/mL) compared with moderately ill patients (median 5.0 ng/mL; P = 0.002). In addition, suPAR levels correlated with length of hospitalisation (rho = 0.35; P = 0.006). Besides suPAR, LDH, CRP, neutrophil count, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratio, body mass index and chronic renal failure were discriminators of COVID-19 severity and/or predictors of length of hospitalisation. Conclusion: Admission levels of suPAR were higher in patients who developed severe/critical COVID-19 and associated with length of hospital stay. In addition, we showed that suPAR functioned as an independent predictor of COVID-19 disease severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Enocsson, Idoff, Gustafsson, Govender, Hopkins, Larsson, Nilsdotter-Augustinsson and Sjöwall.)

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.)

Summary: Cystic pancreatic lesions present a diagnostic challenge. Accurate characterisation of an isolated cystic pancreatic lesion is therefore vital as this dictates the management strategy which may vary from radical resection to simple observation. This report describes how a detailed preoperative assessment led to the correct diagnosis of an isolated pancreatic lesion and appropriate safe and curative surgical management., (Copyright© Authors.)

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&rsquo;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.)

Background: Diverticular disease was previously thought to be non-existent in the black African population. Studies over the past four decades, however, have shown a steady increase in the prevalence of the disease., Objective: To report on the profile and current prevalence of diverticular disease in the black South African (SA) population at Dr George Mukhari Academic Hospital, Pretoria, SA., Methods: A retrospective descriptive study was performed in black SA patients who were diagnosed with diverticular disease by colonoscopy between 1 January and 31 December 2015., Results: Of 348 patients who had undergone colonoscopies and who were eligible for inclusion in this study, 47 were diagnosed with diverticular disease - a prevalence of 13.50% (95% confidence interval 10.30 - 17.50). The greatest number of patients diagnosed were in their 7th and 8th decades, with an age range of 46 - 86 (mean 67) years. There was a female predominance of 57.45%. Lower gastrointestinal bleeding was the most common (65.96%) indication for colonoscopy. The left colon was most commonly involved (72.34%), followed by the right colon (55.31%). A substantial number of patients had pancolonic involvement (27.65%)., Conclusion: This retrospective study suggests that there has been a considerable increase in the prevalence of diverticular disease among black South Africans, possibly owing to changes in dietary habits and socioeconomic status.

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: Self-expanding metal stents (SEMS) are widely used to palliate patients with oesophageal cancer. Placement is usually done under endoscopic and fluoroscopic guidance. We have developed an exclusively endoscopic technique to deploy these stents. This article documents the technique and periprocedural experience., Patients and Methods: All patients who had SEMS placement for oesophageal cancer at Grey's Hospital, Pietermaritzburg, South Africa, over a 5-year period (2007-2011) were reviewed. Stenting was performed without radiological guidance using the technique documented in this article. At endoscopy, the oesophageal lesion was identified, dilated over a guidewire if necessary, and a partially covered stent was passed over the wire and positioned and deployed under direct vision. Data were captured from completed procedure forms and included demographics, tumour length, the presence of fistulas, stent size and immediate complications., Results: A total of 480 SEMS were inserted, involving 453 patients, of whom 43 required repeat stenting. There were 185 female patients (40.8%) and 268 male patients (59.2%). The mean age was 60 years (range 38 - 101). There were 432 black patients (95.4%), 15 white patients (3.3%) and 6 Indian patients (1.3%). The reasons for palliative stenting were distributed as follows: age>70 years n=95 patients, tumour>8 cm n=142, tracheo-oesophageal fistula (TOF) n=29, and unspecified n=170. One patient refused surgery, and one stent was placed for a post-oesophagectomy leak. Repeat stenting was for stent migration (n=15), tumour overgrowth (n=26) and a blocked stent and a stricture (n=1 each). Complications were recorded in six cases (1.3%): iatrogenic TOF (n=2), false tracts (n=3) and perforation (n=1). All six were nevertheless successfully stented. There was no periprocedural mortality., Conclusion: The endoscopic placement technique described is a viable and safe option with a low periprocedural complication rate. It is of particular use in situations of restricted access to fluoroscopic guidance.

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.)

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2(-) production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.

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.