Antiretroviral therapy does not reduce tuberculosis reactivation in a tuberculosis-HIV coinfection model

While the advent of combination antiretroviral therapy (ART) has significantly improved survival, tuberculosis (TB) remains the leading cause of death in the HIV-infected population. We used Mycobacterium tuberculosis/simian immunodeficiency virus-coinfected (M. tuberculosis/SIV-coinfected) macaques to model M. tuberculosis/HIV coinfection and study the impact of ART on TB reactivation due to HIV infection. Although ART significantly reduced viral loads and increased CD4+ T cell counts in blood and bronchoalveolar lavage (BAL) samples, it did not reduce the relative risk of SIV-induced TB reactivation in ART-treated macaques in the early phase of treatment. CD4+ T cells were poorly restored specifically in the lung interstitium, despite their significant restoration in the alveolar compartment of the lung as well as in the periphery. IDO1 induction in myeloid cells in the inducible bronchus-associated lymphoid tissue (iBALT) likely contributed to dysregulated T cell homing and impaired lung immunity. Thus, although ART was indispensable for controlling viral replication, restoring CD4+ T cells, and preventing opportunistic infection, it appeared inadequate in reversing the clinical signs of TB reactivation during the relatively short duration of ART administered in this study. This finding warrants the modeling of concurrent treatment of TB and HIV to potentially reduce the risk of reactivation of TB due to HIV to inform treatment strategies in patients with M. tuberculosis/HIV coinfection

Effect of case management on neonatal mortality due to sepsis and pneumonia.

BACKGROUND: Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST). METHODS: We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where appropriate. For interventions with biological plausibility but low quality evidence, a Delphi process was undertaken to estimate effectiveness. RESULTS: Searches of 2876 titles identified 7 studies. Among these, 4 evaluated oral antibiotics for neonatal pneumonia in non-randomised, concurrently controlled designs. Meta-analysis suggested reductions in all-cause neonatal mortality (RR 0.75 95% CI 0.64- 0.89; 4 studies) and neonatal pneumonia-specific mortality (RR 0.58 95% CI 0.41- 0.82; 3 studies). Two studies (1 RCT, 1 observational study), evaluated community-based neonatal care packages including injectable antibiotics and reported mortality reductions of 44% (RR = 0.56, 95% CI 0.41-0.77) and 34% (RR = 0.66, 95% CI 0.47-0.93), but the interpretation of these results is complicated by co-interventions. A third, clinic-based, study reported a case-fatality ratio of 3.3% among neonates treated with injectable antibiotics as outpatients. No studies were identified evaluating injectable antibiotics alone for neonatal pneumonia. Delphi consensus (median from 20 respondents) effects on sepsis-specific mortality were 30% reduction for oral antibiotics, 65% for injectable antibiotics and 75% for injectable antibiotics on pneumonia-specific mortality. No trials were identified assessing effect of hospital management for neonatal infections and Delphi consensus suggested 80%, and 90% reductions for sepsis and pneumonia-specific mortality respectively. CONCLUSION: Oral antibiotics administered in the community are effective for neonatal pneumonia mortality reduction based on a meta-analysis, but expert opinion suggests much higher impact from injectable antibiotics in the community or primary care level and even higher for facility-based care. Despite feasibility and low cost, these interventions are not widely available in many low income countries. FUNDING: This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US

COVID-19 in a mosaic trisomy 13 patient with polycystic kidney disease

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Presentation, management, and outcomes of COVID-19 infections among younger patients is an area of medicine with deficits in research, likely due to the lower incidence of severe COVID-19 disease among the younger population. Management can be challenging, and clinicians often guide their decision-making based on the ever-changing protocols that are tailored mostly to the elderly population. Even more underrepresented in COVID-19 research are patients with chromosomal abnormalities and trisomy syndromes, as they appear less frequently, but have risk of increased morbidity and mortality due to underlying medical conditions. We describe a case of severe COVID-19 infection in a young patient with mosaic trisomy 13 and pre-existing polycystic kidney disease, who developed severe acute hypoxic respiratory failure and acute chronic kidney injury. The patient was provided maximal pharmacological support and her clinical course helps to shape the understanding of COVID-19 infections in the setting of chromosomal abnormalities and complex medical history

Modifications in biphasic liquid-scintillation vial system for radiometry

Several modifications of the biphasic liquid-scintillation vial system for radiometry have been tried in order to improve the counting efficiency. The biphasic system consisted of an inner sterile vial containing medium and substrate, and an outer liquid-scintillation vial lined on the inside with filter paper impregnated with scintillation fluors and alkali. The system gave an overall counting efficiency of 14.6%. Substitution of methanolic NaOH for impregnation of the paper raised the counting efficiency to 29.1%. This could be further enhanced to 33.8% by lining only half of the outer vial with filter paper, thereby allowing improved optical transmission of scintillation light. Increasing the amount of fluor did not change the efficiency significantly. A complete interchange in the system, whereby half of the inner vial was lined with filter paper and was otherwise empty, while the outer vial contained the medium and substrate, gave the highest efficiency (36.9%). This also allowed the use of larger amounts of medium and the inoculum

Effect of case management on neonatal mortality due to sepsis and pneumonia

<p>Abstract</p> <p>Background</p> <p>Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST).</p> <p>Methods</p> <p>We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where appropriate. For interventions with biological plausibility but low quality evidence, a Delphi process was undertaken to estimate effectiveness.</p> <p>Results</p> <p>Searches of 2876 titles identified 7 studies. Among these, 4 evaluated oral antibiotics for neonatal pneumonia in non-randomised, concurrently controlled designs. Meta-analysis suggested reductions in all-cause neonatal mortality (RR 0.75 95% CI 0.64- 0.89; 4 studies) and neonatal pneumonia-specific mortality (RR 0.58 95% CI 0.41- 0.82; 3 studies). Two studies (1 RCT, 1 observational study), evaluated community-based neonatal care packages including injectable antibiotics and reported mortality reductions of 44% (RR= 0.56, 95% CI 0.41-0.77) and 34% (RR =0.66, 95% CI 0.47-0.93), but the interpretation of these results is complicated by co-interventions. A third, clinic-based, study reported a case-fatality ratio of 3.3% among neonates treated with injectable antibiotics as outpatients. No studies were identified evaluating injectable antibiotics alone for neonatal pneumonia. Delphi consensus (median from 20 respondents) effects on sepsis-specific mortality were 30% reduction for oral antibiotics, 65% for injectable antibiotics and 75% for injectable antibiotics on pneumonia-specific mortality. No trials were identified assessing effect of hospital management for neonatal infections and Delphi consensus suggested 80%, and 90% reductions for sepsis and pneumonia-specific mortality respectively.</p> <p>Conclusion</p> <p>Oral antibiotics administered in the community are effective for neonatal pneumonia mortality reduction based on a meta-analysis, but expert opinion suggests much higher impact from injectable antibiotics in the community or primary care level and even higher for facility-based care. Despite feasibility and low cost, these interventions are not widely available in many low income countries.</p> <p>Funding</p> <p>This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US.</p

Myeloid-derived suppressor cells mediate T cell dysfunction in nonhuman primate TB granulomas

Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell population comprised of immature myeloid cells and myeloid progenitors with very potent immunosuppressive potential. MDSCs are reported to be abundant in the lungs of active tuberculosis (TB) patients. We sought to perform an in-depth study of MDSCs during latent TB infection (LTBI) and active TB (ATB) using the nonhuman primate (NHP) model of pulmonary TB. We found a higher proportion of granulocytic, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the lungs of ATB animals compared to those with LTBI or naive control animals. Active disease in the lung, but not LTBI, was furthermore associated with higher proliferation, expansion, and immunosuppressive capabilities of PMN-MDSCs, as shown by enhanced expression of Ki67, indoleamine 2,3-dioxygenase (IDO1), interleukin-10 (IL-10), matrix metallopeptidase 9 (MMP-9), inducible nitric oxide synthase (iNOS), and programmed death-ligand 1 (PD-L1). These immunosuppressive PMN-MDSCs specifically localized to the lymphocytic cuff at the periphery of the granulomas in animals with ATB. Conversely, these cells were scarcely distributed in interstitial lung tissue and the inner core of granulomas. This spatial regulation suggests an important immunomodulatory role of PMN-MDSCs by restricting T cell access to the TB granuloma core and can potentially explain dysfunctional anti-TB responses in active granuloma. Our results raise the possibility that the presence of MDSCs can serve as a biomarker for ATB, while their disappearance can indicate successful therapy. Furthermore, MDSCs may serve as a potential target cell for adjunctive TB therapy

Body Dysmorphic Disorder: Gender differences and prevalence in a Pakistani medical student population

<p>Abstract</p> <p>Background</p> <p>Body dysmorphic disorder (BDD) is a psychiatric disorder characterized by a preoccupation with an imagined or slight defect which causes significant distress or impairment in functioning. Few studies have assessed gender differences in BDD in a non clinical population. Also no study assessed BDD in medical students. This study was designed to determine the point prevalence of BDD in Pakistani medical students and the gender differences in prevalence of BDD, body foci of concern and symptoms of BDD.</p> <p>Methods</p> <p>The medical students enrolled in a medical university in Karachi, Pakistan filled out a self-report questionnaire which assessed clinical features of BDD. BDD was diagnosed according to the DSM-IV criteria.</p> <p>Results</p> <p>Out of the 156 students, 57.1% were female. A total of 78.8% of the students reported dissatisfaction with some aspect of their appearance and 5.8% met the DSM-IV criteria for BDD. The male to female ratio for BDD was 1.7. Regarding gender differences in body foci of concern, the top three reported foci of concern in male students were head hair (34.3%), being fat (32.8%), skin (14.9%) and nose(14.9%), whereas in females they were being fat (40.4%), skin (24.7%) and teeth (18%). Females were significantly more concerned about being fat (p = 0.005). Male students were significantly more concerned about being thin (p = 0.01) and about head hair (p = 0.012).</p> <p>Conclusion</p> <p>BDD is fairly common in our medical student population, with a higher prevalence in males. Important gender differences in BDD symptomatology and reported body foci of concern were identified which reflected the influence of media on body image perception. The impact of cultural factors on the prevalence as well as gender differences in BDD symptomatology was also established.</p

Factors Influencing the Customer Dining Experience and Retention at Marrybrown in Malaysia

Marrybrown is a Malaysian brand that develops steadily in Halal fast-food chains, which deliver great value products and exceptional quality service. Marrybrown has utilized its competitive advantages and successfully sustained itself among the competitors in the same market. This study investigates the factors influencing the customer dining experience and retention at Marrybrown in Malaysia. The research method is an online survey and analyzed using V-ONE. The findings indicated that food quality, location preference, menu innovation, restaurant environment, and service quality are important variables that affect the customer dining experience and customer retention at Marrybrown located in Malaysia. The findings provide suggestions for future research and improvement of the services provided by Marrybrown located in Malaysia

Perceptions of anti-smoking messages amongst high school students in Pakistan

<p>Abstract</p> <p>Background</p> <p>Surveys have provided evidence that tobacco use is widely prevalent amongst the youth in Pakistan. Several reviews have evaluated the effectiveness of various tobacco control programs, however, few have taken into account the perceptions of students themselves regarding these measures. The aim of this study was to determine the most effective anti-smoking messages that can be delivered to high-school students in Pakistan, based on their self-rated perceptions. It also aimed to assess the impact of pictorial/multi-media messages compared with written health warnings and to discover differences in perceptions of smokers to those of non-smokers to health warning messages.</p> <p>Methods</p> <p>This study was carried out in five major cities of Pakistan in private English-medium schools. A presentation was delivered at each school that highlighted the well-established health consequences of smoking using both written health warnings and pictorial/multi-media health messages. Following the presentation, the participants filled out a graded questionnaire form, using which they rated the risk-factors and messages that they thought were most effective in stopping or preventing them from smoking. The Friedman test was used to rank responses to each of the questions in the form. The Wilcoxon Signed Rank test used to analyze the impact of pictorial/multi-media messages over written statements. The Mann Whitney U test was used to compare responses of smokers with those of non-smokers.</p> <p>Results</p> <p>Picture of an oral cavity cancer, videos of a cancer patient using an electronic voice box and a patient on a ventilator, were perceived to be the most effective anti-smoking messages by students. Addiction, harming others through passive smoking and impact of smoking on disposable incomes were perceived to be less effective messages. Pictorial/multi-media messages were perceived to be more effective than written health warnings. Health warnings were perceived as less effective amongst smokers compared to non-smokers.</p> <p>Conclusion</p> <p>Graphic pictorial/multi-media health warnings that depict cosmetic and functional distortions were perceived as effective anti-smoking messages by English-medium high school students in Pakistan. Smokers demonstrated greater resistance to health promotion messages compared with non-smokers. Targeted interventions for high school students may be beneficial.</p