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Plain English summary Involving stakeholders in research about dementia care is recognized as an important approach to develop findings that are relevant to individuals living with dementia, family care partners, and health and social professionals in dementia care. Still, this approach is not often used and there is a need for more information about how researchers can engage stakeholders in the research process and the impact of engagement from the perspectives of stakeholders. In this paper, we describe how a mixed group of stakeholders was engaged for a project to identify priorities for dementia care research and their perspectives of the experience. A Stakeholder Advisory Council (SAC) worked together to develop their skills in research and connected with their communities to determine what is most important to be studied in the field of dementia care research. To understand the perspectives of the stakeholders involved in this project, we conducted individual interviews with members of the SAC. This study will help researchers understand how they can collaborate with stakeholders in dementia care and the benefits of including individuals living with dementia, family care partners, and professional stakeholders in the research process.

BackgroundOlder Latino individuals are disproportionally affected by various chronic conditions including impairments in physical and cognitive functions, which are essential for healthy aging and independent living. ObjectiveThis study aimed to evaluate the feasibility and acceptability of FITxOlder, a 12-week mind-body exercise program, in community-dwelling low-income, predominantly older Latino individuals, and assess its preliminary effects on health parameters relevant to healthy aging and independent living. MethodsThis 12-week, single-arm, stage 1B feasibility study had a pre- and poststudy design. A total of 13 older adults (mean age 76.4, SD 7.9 years; 11/13, 85% Latino) of a congregate meal program in a senior center were enrolled. FITxOlder was a tailored Chinese mind-body exercise program using Five Animal Frolics led by a bilingual community health worker (CHW) participating twice a week at the senior center and facilitated by mobile health technology for practice at home, with incrementally increasing goals moving from once a week to at least 3 times a week. The feasibility and acceptability of the study were examined using both quantitative and qualitative data. Healthy aging–related outcomes (eg, physical and cognitive function) were assessed using paired 2-tailed t tests. Qualitative interview data were analyzed using thematic analysis. ResultsThe attendance rate for the 24 exercise sessions was high (22.7/24, 95%), ranging from 93% (1.8/2) to 97% (1.9/2) over the 12 weeks. Participants were compliant with the incremental weekly exercise goals, with 69.2% (9/13) and 75.0% (9/12) meeting the home and program goals in the last 4 weeks, respectively. Approximately 83% (10/12) to 92% (11/12) of the participants provided favorable feedback on survey questions regarding the study and program implementation, such as program content and support, delivery by the CHW, enjoyment and appeal of the Five Animal Frolics, study burden and incentives, and safety concerns. The qualitative interview data revealed that FITxOlder was well accepted; participants reported enjoyment and health benefits and the desire to continue to practice and share it with others. The 5-time sit-to-stand test (mean change at posttest assessment=−1.62; P

To determine the contribution of injectable iron administered to hemodialysis (HD) patients in causing oxidative stress and the beneficial effect of N-acetylcysteine (NAC) in re-ducing it, we studied in a prospective, double blinded, randomized controlled, cross over trial 14 adult HD patients who were randomized into two groups; one group received NAC in a dose of 600 mgs twice daily for 10 days prior to intravenous iron therapy and the other group received placebo. Both the groups were subjected to intravenous iron therapy, 100 mg of iron sucrose in 100 mL of normal saline given over a period of one hour. Blood samples for the markers of oxidative stress were taken before and after iron therapy. After the allowance of a week of wash out period for the effect of N-acetylcysteine we crossed over the patients to the opposite regimen. We measured the lipid peroxidation marker, malondiaaldehyde (MDA), to evaluate the oxidative stress and total anti-oxidant capacity (TAC) for the antioxidant level in addition to the highly sensitive C-reactive protein (HsCRP). Non-invasive assessment of endothelial dysfunction was measured by digital plethysmography before and after intravenous iron therapy. There was an increase of MDA (21.97 + 3.65% vs 7.06 + 3.65%) and highly sensitive C-reactive protein (HsCRP) (11.19 + 24.63% vs 13.19 + 7.7%) after iron administration both in the placebo and the NAC groups. NAC reduced the baseline acute systemic generation of oxidative stress when com-pared to placebo, which was statistically significant with MDA (12.76 + 4.4% vs 9.37 + 4.40%: P = 0.032) but not with HsCRP though there was a declining trend (2.85 + 22.75 % vs 8.93 + 5.19%: P = 0.112). Pre-treatment with NAC reduced the endothelial dysfunction when compared to placebo, but it was not statistically significant, except for reflection index (RI). We conclude that in our HD patients NAC reduced the oxidative stress before and after the administration of intravenous iron therapy in addition to the endothelial dysfunction induced by this treatment.

In 2008, an outbreak of isoniazid-resistant tuberculosis was identified among residents of homeless shelters in Atlanta, Georgia, USA. When initial control efforts involving standard targeted testing failed, a comprehensive approach that involved all providers of services for the homeless successfully interrupted the outbreak.

Candida albicans overgrowth at various mucosal sites is an ongoing and complex clinical concern involving interactions with indigenous microbiota and therapeutic or preventive measures superimposed on the pathogen-microbiome interaction. In this paper we describe the use of quantitative flow cytometry (specific to the cytometer’s sample introduction mechanism) to explore the in vitro interaction between Candida albicans, probiotic lactobacilli and a topical vaginal therapeutic. Our central hypothesis was cytometric measurements of co-cultures of yeast and bacteria could provide a useful method for exploring the dynamics of different microbial species in culture, with and without inhibitors. Two commercial products were used as exemplars for this research, a vaginal antimicrobial gel and two species of probiotic lactobacillus intended or oral administration with crystalline bovine lactoferrin to augment the vaginal gel. The cytometer forward channel height parameter distinguished yeast from bacteria in co-culture experiments in the presence of a vaginal therapeutic gel or components of its formulation including EDTA, glycogen, polydextrose as well as the host defense factor, lactoferrin. Flow cytometry showed lactobacilli influenced yeast counts in co-culture, with the technique lending itself to wide-ranging test conditions including organisms, media composition and screening of various antimicrobials. Key findings: The proprietary vaginal gel augmented the effect of lactobacilli, as did EDTA and lactoferrin. Prebiotic compounds also enhanced Candida inhibition by lactobacilli. Propidium iodide (Fluorescence channel 3) discriminated between necrotic and non-necrotic yeast and bacteria in co-cultures under various culture conditions. This research demonstrates the value of flow cytometry to evaluate the population dynamics of yeast and bacteria in co-culture using a proprietary product and its components. We discuss both the limitations of the current study and describe how methods employed here would be transferrable to the investigation of organisms present in defined cultures or at body sites colonized by fungal species and the effects of therapeutics or probiotics on Candida.

Enterococcus, a Gram-positive facultative anaerobic cocci belonging to the lactic acid bacteria of the phylum Firmicutes, is known to be able to resist a wide range of hostile conditions such as different pH levels, high concentration of NaCl (6.5%), and the extended temperatures between 5°C and 65°C. Despite being the third most common nosocomial pathogen, our understanding on its virulence factors is still poorly understood. The current study was aimed to determine the prevalence of different virulence genes in Enterococcus faecalis and Enterococcus faecium. For this purpose, 79 clinical isolates of Malaysian enterococci were evaluated for the presence of virulence genes. pilB, fms8, efaAfm, and sgrA genes are prevalent in all clinical isolates. In conclusion, the pathogenicity of E. faecalis and E. faecium could be associated with different virulence factors and these genes are widely distributed among the enterococcal species.

Klebsiella pneumoniae is a common hospital-acquired pathogen, causing urinary tract infections, nosocomial pneumoniae, and intra-abdominal infections. K.pneumoniae is also a potential community acquired pathogen. The aims of this study are to determine epidemiology of ESBL-producing K.pneumoniae and Koxytoca in Iran during different seasons, to determine the prevalence of blaTEM, SHV and CTX-M responsible for ESBL production among ESBL-producing K.pneumoniae and Koxytoca in the different wards and hospitals in Iraa Klebsiella spp producing ESBLs were identified by phenotypic and genotyping methods. The findings in this study revealed that 36.5%, 51.7% and 45.6% of K.pneumoniae were producing ESBLs in Ham, Milad and Emam Reza hospitals, respectively. The results revealed blaSHV was responsible for ESBLs production. The analysis showed significant difference of ESBLs production by K.pneumoniae in winter (53%) in comparison to the other seasons P ≤ 0.01. The results also showed a significant difference in blaSHV that was the dominant gene responsible for ESBL production P ≤ 0.049 but no significant difference was observed between blaTEM and blaSHV. The results showed that the highest ESBL production was found in Koxytoca isolated from patients in Emam Reza Hospital and the lowest frequency of ESBL production was found among Koxytoca in Ham hospital. BlaSHV was found as dominant gene responsible for ESBLs production by K.pneumoniae and Koxytoca , followed by blaCTX-M.

Background: In women, breast cancer is currently among the most common cancers and the second major cause of cancer-related mortality. One therapeutic target for breast cancer is the progesterone receptor (PR), which can be inhibited by specific PR modulators. Methods: Current anti-cancer medications have notorious adverse effects. Consequently, an urgent need exists to identify less hazardous, more effective medicines with few to no adverse effects. One strategy uses ancient herbal remedies to create medications derived from nature. Herein, we used data from the Dr. Duke, IMPPAT, PubChem, Binding DB, UniProt, and DisGeNET databases to construct a network in Cytoscape 3.10.0. Through a polypharmacology approach, bioactives with similarity indices greater than 0.6 were screened and docked with the PR. The top ten ligands with good docking scores were further subjected to interaction analysis in AutoDock v.4.2 software. We additionally analyzed the ADMET properties of the phytochemicals. Results: Procurcumenol and alpha-turmerone exhibited superior interactions with PR, with binding affinities of −7.85 kcal/mol. All compounds met Lipinski’s rule of five and were effective ligands for the PR according to ADMET data analysis. Our findings suggest that procurcumenol and alpha-turmerone may serve as potential anti-breast cancer agents; specifically targeting the PR in breast cancer cells. Conclusion: Understanding of anti-breast cancer activity can be facilitated through experimental validation of network analysis and molecular docking findings.

Scrolling smartphones while sitting on the toilet is believed to be one of the reasons predisposing to haemorrhoidal disease. Not much is written about the problem of the use of smartphones and the development of haemorrhoidal disease in the literature, but the rising incidence of haemorrhoids globally does require guidelines to be set for toilet hygiene, especially in the young generation to prevent this issue from becoming an epidemic in future. It may be time to designate the washroom as a smartphone-free zone.

Giant subpectoral lipoma is an extremely rare case that can occasionally turn malignant. We highlight this case for the first time from India.

Little is known about co-occurring tuberculosis (TB) and COVID-19 in low TB incidence settings. We obtained a cross-section of 333 persons in the United States co-diagnosed with TB and COVID-19 within 180 days and compared them to 4,433 persons with TB only in 2020 and 18,898 persons with TB during 2017‒2019. Across both comparison groups, a higher proportion of persons with TB–COVID-19 were Hispanic, were long-term care facility residents, and had diabetes. When adjusted for age, underlying conditions, and TB severity, COVID-19 co-infection was not statistically associated with death compared with TB infection only in 2020 (adjusted prevalence ratio 1.0 [95% CI 0.8‒1.4]). Among TB–COVID-19 patients, death was associated with a shorter interval between TB and COVID-19 diagnoses, older age, and being immunocompromised (non-HIV). TB–COVID-19 deaths in the United States appear to be concentrated in subgroups sharing characteristics known to increase risk for death from either disease alone.

Cadavers have been used for dissection to learn the basics of anatomy since the 3rd century BC. Even today freshly admitted medical students are first taken to the Anatomy dissection hall to learn from cadavers and get an understanding of the enormity of the profession they chose. Most institutes have teachers explaining to the freshers what their reaction should be on seeing a cadaver and how it is to be treated. Some institutes make students take a cadaveric Oath. Today, the cadaver is not just an anatomy learning tool, but has far more uses in surgical basic and advanced training and enhancing our knowledge of medicine. And cadaver transplantation is a common practice now. With many places finding it difficult to access cadavers now, due to human rights issues, it is very important for the medical community to not only adopt but showcase to the world that they respect and acknowledge the role of a cadaver in both diagnostic and therapeutic modality. And frame a strong, uniform Cadaveric Oath to be taken by all medical students to emphasize that.

This cross-sectional study was carried out at the department of Pediatric Neurology, Institute of Pediatric Neurodisorder and Autism, Bangabandhu Sheikh Mujib Medical University, Dhaka with the aim to assess the relationship between gross motor function and MRI findings in children with cerebral palsy. The duration of the study was 12 months. All the cerebral palsy cases who met the selection criteria were enrolled. Detailed history taking and physical examination was done. The gross motor function of all cases was evaluated according to Gross Motor Function Classification System- Expanded and Revised (GMECS-E and R). Magnetic resonance imaging of brain was done in all enrolled patients and reports were evaluated. MRI findings were classified as maldevelopment, cortical and subcortical gray matter lesion, periventricular white matter injury, basal ganglia lesion, normal and other findings. A total of 45 children with cerebral palsy aged between 2 to 12 years were included in this study. Mean age of the children was 4.73 (+3.17) years. Male were 31 and female were 14 in number. Functionally majority patients were in GMFCS level IV (26.7%) and level V (20%). MRI findings were abnormal in 35 (77.78%) cases. Most common abnormal MRI finding was cortical and subcortical grey matter lesions 22 (48.9%). This study revealed that cortical and subcortical gray matter lesions were significantly associated with higher level of GMFCS (IV-V) (P=0.038) and maldevelopment of brain were also significantly associated with higher level of GMFCS (P=0.01). Normal MRI findings had significant association with mild to moderate GMFCS level (I-III) (P=0.012). From this study significant relationship was found between gross motor function and MRI of brain findings in children with cerebral palsy. Bangabandhu Sheikh Mujib Medical University Journal 2022;15(4):8-15

To determine the mechanisms that mediate resistance to Mycobacterium tuberculosis (M. tuberculosis) infection in household contacts (HHCs) of patients with tuberculosis (TB), we followed 452 latent TB infection–negative (LTBI–) HHCs for 2 years. Those who remained LTBI– throughout the study were identified as nonconverters. At baseline, nonconverters had a higher percentage of CD14+ and CD3–CD56+CD27+CCR7+ memory-like natural killer (NK) cells. Using a whole-transcriptome and metabolomic approach, we identified deoxycorticosterone acetate as a metabolite with elevated concentrations in the plasma of nonconverters, and further studies showed that this metabolite enhanced glycolytic ATP flux in macrophages and restricted M. tuberculosis growth by enhancing antimicrobial peptide production through the expression of the surface receptor sialic acid binding Ig-like lectin–14. Another metabolite, 4-hydroxypyridine, from the plasma of nonconverters significantly enhanced the expansion of memory-like NK cells. Our findings demonstrate that increased levels of specific metabolites can regulate innate resistance against M. tuberculosis infection in HHCs of patients with TB who never develop LTBI or active TB.

Background: Choledochal cysts are dilated portions of the biliary tract that account for 1% of all benign biliary diseases. It is prevalent among Asian and female populations and the incidence is 1:100,000–150,000. Among the different types, only 15–35% of all choledochal cysts are type IV cysts, with type I being the most common representing 50–80%. Clinical presentation and therapy of biliary cysts (BC) differ depending on the type. Case: We present a case of a 2-year-old male who presented with non-specific symptoms of multiple episodes of vomiting. Laboratory investigations revealed raised alkaline phosphatase and gamma-glutamyl transpeptidase. His symptoms of acute pancreatitis were resolved with conventional therapy. Ultrasonography of the abdomen showed intra and extra-hepatic cystic biliary tree dilatation suggestive of choledochal cyst Type IV A. Conclusions: Choledochal cysts present with clinical features varying with age and anatomical variants and can pose challenges in management that can be addressed by surgery to avoid further complications.

Background and Aim: Self-etching primers (SEPs) are used to reduce the chair side time. However, there are different SEPs that are used in orthodontics. This study is aimed to test the shear bond strength of brackets bonded using SEPs used in restorative dentistry in comparison to orthodontic SEPs. Settings and Design: Department of Orthodontics, Post-graduate dental college, Council of Scientific and Industrial Research (CSIR) laboratory, in vitro study. Methods and Material: Seventy-five freshly extracted human maxillary first premolar teeth were used in this study. Orthodontic maxillary first premolar McLaughlin Bennett Trevisi (MBT) metal brackets (3M Unitek) were used to bond the teeth. The study consisted of two groups. Group A: 25 teeth were etched with Orthodontic SEP Transbond Plus (3M Unitek). Group B: Experimental group which is divided into two subgroups, Experimental subgroup a and Experimental subgroup b. Subgroup a: 25 teeth were etched with Restorative purpose SEP Adper SE Plus (3M ESPE). Sub group-b: 25 teeth were etched with Restorative purpose SEP Adper Easy One (3M ESPE). In all the groups, the same adhesive material, Transbond XT (3M Unitek) was used for fixing the brackets. All the 75 teeth were subjected to shear force to test shear bond strength by using Instron machine. Statistical Analysis: ANOVA & Scheffe multiple comparison test were used. Results and Conclusion: Shear bond strength of brackets using orthodontic purpose SEP, Transbond Plus, is more than the SEPs used for restorative purpose, i.e., Adper SE Plus and Adper Easy One. Restorative purpose SEPs are not suitable for orthodontic bonding of brackets. Orthodontic bonding, self-etching primer (SEP), shear bond strength (SBS)

Background Leptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira that affects both humans and animals worldwide. Early detection of the pathogen in humans is crucial for early intervention and control of the progression of the disease to a severe state. It is also vitally important to be able to detect the presence of the pathogen in carrier animals to control the spread of the disease from the environment. Here we developed a simple and rapid loop-mediated isothermal amplification (LAMP) assay targeting the leptospiral secY gene. Results Several reaction conditions of the LAMP reaction were optimized to ensure efficient amplification of the target DNA. The sensitivity of the developed LAMP assay obtained using a pure Leptospira culture was 2 × 104 copies of genomic DNA per reaction (equivalent to 0.1 ng) for a 40-minute reaction time. No cross-reactions were observed in the LAMP reaction against a series of non-leptospiral bacteria, indicating a specific reaction. The applicability of the LAMP assay was demonstrated on human blood and urine specimens collected from suspected leptospirosis patients and rat kidney specimens collected from suspected leptospirosis outbreak areas and high-risk areas. The developed LAMP assay demonstrated a higher detection rate for leptospiral DNA compared with the polymerase chain reaction (PCR) assay, possibly due to the presence of inhibitory substances, especially in rat kidney specimens, to which the PCR method is more susceptible. The present findings also highlight the importance of urine sample collection from patients for routine monitoring of the disease. Conclusions In short, the developed LAMP assay can serve as a feasible alternative tool for the diagnosis of leptospirosis and be used for epidemiological and environmental surveillance of the disease, considering its robustness, rapidity, sensitivity, and specificity, as demonstrated in this study.

The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. We report on a patient who completed the regimen using a lower linezolid dose.

The coronavirus, which is causing the ongoing Covid-19 pandemic and has crippled the entire world, was discovered by June Dalziel Almeida - a school dropout from Scotland who had no formal medical education. She had to master the knowhow of immune electron microscopy to climb up the academic ladder and she finally discovered the coronavirus only to see her research paper getting rejected by reputed journals. A single mother is now associated with the coronavirus, as well as with a significant contribution to the classification of viruses, viral imaging and bringing Rubella virus, Hepatitis B virus and Human immunodeficiency virus into the limelight.

In the current study, we followed 839 household contacts (HHCs) of tuberculosis (TB) patients for 2 years and identified the factors that enhanced the development of TB. Fourteen of the 17 HHCs who progressed to TB were in the 15- to 30-year-old age group. At baseline (the “0“ time point, when all the individuals were healthy), the concentration of the thyroid hormone thyroxine (T4) was lower, and there were increased numbers of Tregs in PBMCs of TB progressors. At baseline, PBMCs from TB progressors stimulated with early secretory antigenic target 6 (ESAT-6) and 10 kDa culture filtrate antigen (CFP-10) produced less IL-1α. Thyroid hormones inhibited Mycobacterium tuberculosis (Mtb) growth in macrophages in an IL-1α–dependent manner. Mtb-infected Thra1PV/+ (mutant thyroid hormone receptor) mice had increased mortality and reduced IL-1α production. Our findings suggest that young HHCs who exhibit decreased production of thyroid hormones are at high risk of developing active TB disease.

Multiple matrix metalloproteinases have significant roles in tissue organization during lung development, and repair. Imbalance of proteinases may lead to chronic inflammation, changes in tissue structure, and are also highly associated to cancer development. The role of MMP20 is not well studied in lung organogenesis, however, it was previously shown to be present at high level in lung adenocarcinoma. The current study aimed to identify the functional properties of MMP20 on cell proliferation and motility in a lung adenocarcinoma in vitro cell model, and relate the interaction of MMP20 with other molecular signalling pathways in the lung cells after gaining tumoral properties. In this study, two different single guide RNA (sgRNAs) that specifically targeted on MMP20 sites were transfected into human lung adenocarcinoma A549 cells by using CRISPR-Cas method. Following that, the changes of PI3-K, survivin, and MAP-K mRNA gene expression were determined by Real-Time Polymerase Chain Reaction (RT-PCR). The occurrence of cell death was also examined by Acridine Orange/Propidium Iodide double staining. Meanwhile, the motility of the transfected cells was evaluated by wound healing assay. All the data were compared with non-transfected cells as a control group. Our results demonstrated that the transfection of the individual sgRNAs significantly disrupted the proliferation of the A549 cell line through suppression in the gene expression of PI3-K, survivin, and MAP-K. When compared to non-transfected cells, both experimental cell groups showed reduction in the migration rate, as reflected by the wider gaps in the wound healing assay. The current study provided preliminary evidence that MMP20 could have regulatory role on stemness and proliferative genes in the lung tissues and affect the cell motility. It also supports the notion that targeting MMP20 could be a potential treatment mode for halting cancer progression.

Objective Determine the impact of long-term non-surgical weight loss maintenance on clinical relevance for osteoarthritis, cancer, opioid use, and depression/anxiety and healthcare resource utilization. Methods A cohort of adults receiving primary care within Geisinger Health System between 2001–2017 was retrospectively studied. Patients with ≥3 weight measurements in the two-year index period and obesity at baseline (BMI ≥30 kg/m2) were categorized: Obesity Maintainers (reference group) maintained weight within +/-3%; Weight Loss Rebounders lost ≥5% body weight in year one, regaining ≥20% of weight loss in year two; Weight Loss Maintainers lost ≥5% body weight in year one, maintaining ≥80% of weight loss. Association with development of osteoarthritis, cancer, opioid use, and depression/anxiety, was assessed; healthcare resource utilization was quantified. Magnitude of weight loss among maintainers was evaluated for impact on health outcomes. Results In total, 63,567 patients were analyzed including 67% Obesity Maintainers, 19% Weight Loss Rebounders, and 14% Weight Loss Maintainers; median follow-up was 9.7 years. Time until osteoarthritis onset was delayed for Weight Loss Maintainers compared to Obesity Maintainers (Logrank test p 15% weight loss was associated with the greatest decrease in incident osteoarthritis. Healthcare resource utilization was significantly higher for Weight Loss Rebounders and Maintainers compared to Obesity Maintainers. Increased weight loss among Weight Loss Maintainers trended with lower overall healthcare resource utilization, except for hospitalizations. Conclusions In people with obesity, sustained weight loss was associated with greater clinical benefits than regained short-term weight loss and obesity maintenance. Higher weight loss magnitudes were associated with delayed onset of osteoarthritis and led to decreased healthcare utilization.

PurposeTuberculosis (TB) is the leading cause of infectious disease related mortality, and only 10% of the infected individuals develop active disease. The likelihood of progression of latent tuberculosis infection (LTBI) to active TB disease is high in HIV infected individuals. Identification of HIV+ individuals at risk would allow treating targeted population, facilitating completion of therapy for LTBI and prevention of TB development. NK cells have an important role in T cell independent immunity against TB, but the exact role of NK cell subsets in LTBI and HIV is not well characterized.MethodsIn this study, we compared the expansion and function of memory like NK cells from HIV-LTBI+ individuals and treatment naïve HIV+LTBI+ patients in response to Mtb antigens ESAT-6 and CFP-10.ResultsIn freshly isolated PBMCs, percentages of CD3-CD56+ NK cells were similar in HIV+LTBI+ patients and healthy HIV-LTBI+ individuals. However, percentages of CD3-CD56+CD16+ NK cells were higher in healthy HIV-LTBI+ individuals compared to HIV+LTBI+ patients. HIV infection also inhibited the expansion of memory like NK cells, production of IL-32α, IL-15 and IFN-γ in response to Mtb antigens in LTBI+ individuals.ConclusionWe studied phenotypic, functional subsets and activation of memory like-NK cells during HIV infection and LTBI. We observed that HIV+LTBI+ patients demonstrated suboptimal NK cell and monocyte interactions in response to Mtb, leading to reduced IL-15, IFN-γ and granzyme B and increased CCL5 production. Our study highlights the effect of HIV and LTBI on modulation of NK cell activity to understand their role in development of interventions to prevent progression to TB in high risk individuals.

The diagnosis of leptospirosis remains a challenge due to its non-specific symptoms and the biphasic nature of the illness. A comprehensive diagnosis that includes both molecular (polymerase chain reaction (PCR)) and serology is vital for early detection of leptospirosis and to avoid misdiagnosis. However, not all samples could be subjected to both tests (serology and molecular) due to budget limitation, infrastructure, and technical expertise at least in resource-limited countries. We evaluated the usefulness of testing the clinically suspected leptospirosis cases with both techniques on all samples collected from the patients on the day of admission. Among the 165 patient's blood/serum samples tested (from three hospitals in Central Malaysia), 43 (26%) showed positivity by microscopic agglutination test (MAT), 63 (38%) by PCR, while 14 (8%) were positive by both MAT and PCR. For PCR, we tested two molecular targets (lipL32 by qPCR and 16S rDNA or rrs by nested PCR) and detected lipL32 in 47 (29%) and rrs gene in 63 (38%) patients. The use of more than one target gene for PCR increased the detection rates. Hence, a highly sensitive multiplex PCR targeting more than one diagnostic marker is recommended for the early detection of Leptospira in suspected patients. When the frequencies for positivity detected either by MAT or PCR combined, leptospirosis was diagnosed in a total of 92 (56%) patients, a higher frequency compared to when samples were only tested by a single method (MAT or PCR). The results from this study suggest the inclusion of both serology and molecular methods for every first sample irrespective of the days post-onset of symptoms (DPO) collected from patients for early diagnosis of leptospirosis.

BackgroundPersons living with human immunodeficiency virus (HIV) are at a greater risk of developing tuberculosis (TB) compared to people without HIV and of developing complications due to the complexity of TB/HIV coinfection management.MethodsDuring 2013-2017, the Centers for Disease Control and Prevention (CDC) funded 5 TB Regional Training and Medical Consultation Centers (RTMCCs) (now known as TB Centers of Excellence or COEs) to provide medical consultation to providers for TB disease and latent TB infection (LTBI), with data entered into a Medical Consultation Database (MCD). Descriptive analyses of TB/HIV-related consultations were conducted using SAS® software, version [9.4] to determine the distribution of year of consultation, medical setting and provider type, frequency of consultations regarding a pediatric (ResultsOf 14,586 consultations captured by the MCD in 2013-2017, 544 (4%) were categorized as TB/HIV-related, with 100 (18%) received in 2013, 129 (24%) in 2014, 104 (19%) in 2015, 117 (22%) in 2016, and 94 (17%) in 2017. Most TB/HIV consultations came from nurses (54%) or physicians (43%) and from local (65%) or state health departments (10%). Only 17 (3%) of HIV-related consultations involved pediatric cases. Off the 544 TB/HIV consultations, 347 (64%) concerned the appropriate treatment regimen for TB/HIV or LTBI/HIV for a patient on or not on antiretroviral therapy (ART).ConclusionsThe data support a clear and ongoing gap in areas of specialized HIV knowledge by TB experts that could be supplemented with proactive educational outreach. The specific categories of TB/HIV inquiries captured by this analysis are strategically informing future targeted training and educational activities planned by the CDC TB Centers of Excellence, as well as guiding HIV educational efforts at regional and national TB meetings.

Mycobacterial infections resulting from cardiac implantable electronic devices are rare, but as more devices are implanted, these organisms are increasingly emerging as causes of early-onset infections. We report a patient with an implantable cardioverter-defibrillator pocket and associated bloodstream infection caused by an organism of the Mycobacterium fortuitum group, and we review the literature regarding mycobacterial infections resulting from cardiac device implantations. Thirty-two such infections have been previously described; most (70%) were caused by rapidly growing species, of which M. fortuitum group species were predominant. When managing such infections, clinicians should consider the potential need for extended incubation of routine cultures or dedicated mycobacterial cultures for accurate diagnosis; combination antimicrobial drug therapy, even for isolates that appear to be macrolide susceptible, because of the potential for inducible resistance to this drug class; and the arrhythmogenicity of the antimicrobial drugs traditionally recommended for infections caused by these organisms.

Quality of life (QOL) is a broader concept which represents experiences, states, appraisals, behaviors, capacities and emotional reactions to circumstances. The study aimed to evaluate the differences in various domains of QOL among the students of five schools (medicine, dentistry, veterinary medicine, pharmacy and nursing) and an optometry unit in the Faculty of Medical Sciences, Trinidad and Tobago. Further, the study evaluated the factors (sociodemographic variables and academic performance) predictive of physical, psychological, social and environment domains of quality of life. The research tool consisted of a validated questionnaire which had two sections; (1) sociodemographics inclusive of students’ cumulative grade point average and (2) the shorter version of WHO quality of life (WHOQOL-BREF). The data were transformed into a linear scale and exported into the IBM SPSS version 24 where t-tests, one-way ANOVA and stepwise regression were performed. Of the total 535 participants, most 383 (71.6%) were females. While comparing the differences in the domains of QOL that existed based on the schools (professions) they were enrolled, significant differences were recorded for physical (p < 0.05), psychological (p < 0.05) social (p < 0.05) and environmental domains (p < 0.05). Though the domains of physical health, psychological health and environment showed a significant association with the academic performance of students, the social domain had no such relationship. The overall quality of life has a positive connection with the academic performance of students in medical and health professions. Therefore, universities and all stakeholders involved in health professions need to play a critical role to ensure the students in health professions maintain a high QOL. At the same time, there is a great need for extra attention for students who showed poor academic performance in the previous semester to bring them on track.

Background: Friction plays a very crucial role in our daily life and orthodontics is no exception. Various materials possess friction of varying intensity, which ultimately affects tooth movement. Aim: The aim was to compare the frictional resistance (FR) between various bracket types and archwire materials when ligated with low-friction and conventional elastic ligatures so as to obtain best bracket-archwire combination possessing least FR for clinicians in achieving optimal mechanotherapy. Materials and Methods: Study consisted of three types of preadjusted edgewise brackets including ceramic, stainless steel (SS) and self-ligating brackets (0.022" slot, MBT prescription), two types of archwire materials, 0.019 × 0.025" SS and 0.019 × 0.025" Teflon coated (TC) and two types of ligatures including low-friction and conventional elastic ligature. A total of 10 combinations were formed with the above mentioned material. Each combination was tested 10 times on universal testing machine for FR. The data was statistically analyzed using one-way ANOVA and unpaired t-tests. Results: Self-ligating brackets exhibited least FR (2.35 ± 0.15N) followed by metal brackets. Ceramic brackets showed the highest FR (7.32 ± 0.10N). In general, the mean value for TC wire was less than that of SS wire indicating low FR possessed by TC wires. Results also showed that low-friction ligatures produce lower-friction when compared with conventional elastic module (P > 0.05). Conclusion: The study demonstrated that self-ligating brackets with TC wire showed the least FR and ceramic brackets with SS wire when ligated with conventional elastic ligature showed the highest FR.

Bile salt hydrolase (BSH) activity against the bile acid tauro-beta-muricholic acid (T-β-MCA) was recently reported to mediate host bile acid, glucose, and lipid homeostasis via the farnesoid X receptor (FXR) signaling pathway. An earlier study correlated decreased Lactobacillus abundance in the cecum with increased concentrations of intestinal T-β-MCA, an FXR antagonist. While several studies have characterized BSHs in lactobacilli, deconjugation of T-β-MCA remains poorly characterized among members of this genus, and therefore it was unclear what strain(s) were responsible for this activity. Here, a strain of L. johnsonii with robust BSH activity against T-β-MCA in vitro was isolated from the cecum of a C57BL/6J mouse. A screening assay performed on a collection of 14 Lactobacillus strains from nine different species identified BSH substrate specificity for T-β-MCA only in two of three L. johnsonii strains. Genomic analysis of the two strains with this BSH activity revealed the presence of three bsh genes that are homologous to bsh genes in the previously sequenced human-associated strain L. johnsonii NCC533. Heterologous expression of several bsh genes in E. coli followed by enzymatic assays revealed broad differences in substrate specificity even among closely related bsh homologs, and suggests that the phylogeny of these enzymes does not closely correlate with substrate specificity. Predictive modeling allowed us to propose a potential mechanism driving differences in BSH activity for T-β-MCA in these homologs. Our data suggests that L. johnsonii regulates T-β-MCA levels in the mouse intestinal environment, and that this species may play a central role in FXR signaling in the mouse.

Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%), human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans. Similarly, research has found only rare Nras mutations and no activating Braf mutations in canine oral melanomas, but they are still reliant on MAPK signaling. IQGAP1 is a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras- and Raf- driven cancers, including melanomas. To investigate whether IQGAP1 is a potential target in canine melanoma, we examined the expression and localization of IQGAP1 in primary canine melanomas and canine oral melanoma cell lines obtained from the University of California-Davis. Using CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream ERK1/2 pathway activity and assayed proliferation of cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2. We observed that canine IQGAP1 is expressed and localizes to a similar extent in both human and canine melanoma by qPCR, Western blot, and immunofluorescence. Deletion of IQGAP1 reduces MAPK pathway activation in cell lines, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with a blocking peptide in vitro.

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Lymphocyte- and leukocyte-mediated lymph node (LN) lymphatic sinus growth (lymphangiogenesis) is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC) surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10.1.1 Ab but not control hamster Abs identified rapid induction of LN LEC proliferation and extensive lymphangiogenesis within 23 h. BrdU pulse-chase analysis demonstrated incorporation of proliferating LYVE-1-positive LEC into the growing medullary lymphatic sinuses. The 10.1.1 Ab-induced LN remodeling involved coordinate increases in LECs and also blood endothelial cells, fibroblastic reticular cells, and double negative stroma, as is observed during the LN response to inflammation. 10.1.1 Ab-induced lymphangiogenesis was restricted to LNs, as mCLCA1-expressing lymphatic vessels of the jejunum and dermis were unaffected by 23 h 10.1.1 Ab treatment. These findings demonstrate that 10.1.1 Ab rapidly and specifically induces proliferation and growth of LN lymphatic sinuses and stroma, suggesting a key role of mCLCA1 in coordinating LN remodeling during immune responses.

To evaluate the efficacy and safety of the monthly pulse IV cyclophosphamide (IVC) therapy in patients with severe lupus nephritis, we studied 39 patients of lupus nephritis on IVC therapy between 1998 to 2002. Single monthly cyclophosphamide (0.75-1 g/m²) was infused intravenously with oral prednisolone (0.5 mg/kg per day) and appropriate hydration. Of the 39 pa-tients 25 (86.2%) patients were females and 4 (13.8%) were males. Six (2%) cases had irregular follow-up and 3 patients had expired during the initial cycles and were excluded from the study. The mean age was 25.6 + 6.72 years (range 10-40 years). The mean duration of the disease from the onset to renal biopsy was 24.2 + 18.5 months. The clinical presentations included nephrotic syndrome (34.5%), acute glomerulonephritis (31.0%), Pyrexia of unknown origin (PUO) (10.3%), and rapidly progressive renal failure (6.7%). Renal insufficiency was present in 47.2% cases. Twenty-two (75.9%) patients had diffuse proliferative glomerulonephritis (class IV), 6 (20.7%) focal proliferative glomerulonephritis (class III), and one (3.4%) class Vd. After a mean follow-up of 15.8 months, out of 29 patients, 13 (44.8%) had achieved complete remission, 7 (24.1%) partial remission and 9 (31.0%) cases did not respond to the therapy. Side effects of the therapy included vomiting and nausea (100%) and hair loss during the first few doses of IVC. In addition, one case had dysfunctional uterine bleeding and two patients had avascular necrosis of femoral head. We conclude that our data indicate that IVC in severe lupus nephritis is effective in Indian patients though longer follow-up is required.

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Objectives: To Evaluate and compare lipoprotein(a) [Lp(a)], lipid profile and novel lipid indices in chronic kidney disease(CKD) patients undergoing hemodialysis with healthy controls. To find the correlation between Lp(a) with novel lipid indices. Methodology:The study group included 30 patients with CKD andage and sex matched 30 healthy controls were selected for the study. Lp(a) was estimated by immunoturbidimetric method. Lipid profile by enzymatic method. Lipid indices were calculated using appropriate formula. Results: There was significant increase in Lp (a)(p

A revolution in thinking and redefinition of traditional scholarship by prioritising teaching skills and achievements has led to the birth of the Teaching Portfolio, designed to carry a comprehensive and dynamic record of the teaching activities of the faculty. A teaching portfolio documents the faculty’s teaching scholarship and effectiveness. It is a record of selected information on one’s teaching achievements, skills and strategies and dynamically represents the faculty’s growth, progress and teaching record. The author suggests a template for the Teaching Portfolio of a Medical Educator, which consists of four parts: (1) evaluation, (2) personal professional development, (3) learning processes and (4) an appendix.

Like in other medical fields, candidates seeking a career in Radiology requires special skills and aptitudes. Selecting candidates for radiology residency is made difficult by the fact that many of the essential qualities predictive of a good radiology consultant, such as interpersonal skills, recognition of limits, curiosity, conscientiousness, and confidence level, are “non-cognitive”, and thus difficult to assess. This paper describes the selection procedure developed by the Department of Radiology of Baylor College of Medicine to measure, as objectively as possible, both the cognitive and non-cognitive qualities of candidates, based on a combination of traditional screening and Objective Structured Interviews. This paper highlights efficacy of this selection procedure that includes both cognitive and non-cognitive factors, that is relevant also to other medical specialities.

DNA barcoding uses a short fragment of a DNA sequence to identify a taxon. After obtaining the target sequence it is compared to reference sequences stored in a database to assign an organism name to it. The quality of data in the reference database is the key to the success of the analysis. In the here presented study, multiple types of data have been combined and critically examined in order to create best practice guidelines for taxonomic reference libraries for environmental barcoding. 70 unialgal diatom strains from Berlin waters have been established and cultured to obtain morphological and molecular data. The strains were sequenced for 18S V4 rDNA (the pre-Barcode for protists) as well as rbcL data, and identified by microscopy. LM and for some strains also SEM pictures were taken and physical vouchers deposited at the BGBM. 37 freshwater taxa from 15 naviculoid diatom genera were identified. Four taxa from the genera Amphora, Mayamaea, Planothidium and Stauroneis are described here as new. Names, molecular, morphological and habitat data as well as additional images of living cells are also available electronically in the AlgaTerra Information System. All reference sequences (or reference barcodes) presented here are linked to voucher specimens in order to provide a complete chain of evidence back to the formal taxonomic literature.

Diatom cultures of the G. parvulum species complex were established from seven different sites in the Faroe Islands, Sweden, Germany, Mexico and Korea, and were studied in detail. Eight morphodemes were identified which corresponded to the descriptions of the cosmopolitan taxon G. parvulum (Kützing) Kützing sensu lato: its nominate variety (var. parvulum), G. parvulum var. exilissimum Grunow and G. parvulum f. saprophilum Lange-Bertalot & Reichardt, G. [parvulum var.] lagenula Kützing plus four unidentifiable morphodemes. The concatenated analysis of the sequences of the markers 18SV4, rbcL, and ITS as well as morphological data resulted in a separation of four taxa based on their biogeography in Mexico, Korea, central Continental Europe and Northern Atlantic Europe. Mantel tests showed a significant correlation between molecular and geographical distances. The diagnoses of two taxa, G. parvulum sensu stricto, and G. lagenula, were emended, G. saprophilum elevated to species rank and epitypes designated. One species was newly described.

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It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs) such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others have shown that amyloid-β (Aβ), the toxic trigger for Alzheimer's disease (AD), interacts with hippocampal α7 nicotinic acetylcholine receptors (nAChRs). Since α7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether Aβ could activate astrocytic α7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of Aβ1-42 elicited α7nAChR-dependent calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow inward currents (SICs) in CA1 neurons. In the Tg2576 AD mouse model for Aβ over-production and accumulation, we found that spontaneous astrocytic calcium elevations were of higher frequency compared to wildtype (WT). The frequency and kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly due to increased endogenous Aβ observed in this model. Activation of α7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while α7nAChRs on astrocytes of AD mice were abrogated. These findings suggest that, at an age that far precedes the emergence of cognitive deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits augmented astrocytic activity and glutamate GT release suggesting possible repercussions for preclinical AD hippocampal neural networks that contribute to subsequent cognitive decline.