Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART.

Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count >500 cells/µL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count >500 cells/µL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART.

Homeless Shelters: HIV Testing During the Atlanta Tuberculosis Outbreak (2008-2018).

People experiencing homelessness are at increased risk of tuberculosis (TB) and HIV. We examined the impact of integrating HIV testing and mandatory TB screening on HIV test uptake (HTU) during a multishelter TB outbreak in Atlanta, Georgia (2008-2018). Overall HTU was low; however, the intervention led to a reversal of declining HTU trend (rate ratio = 1.11; 95% confidence interval = 1.04, 1.19). Concerted efforts to increase HIV testing access and uptake alongside robust TB control efforts may increase progress toward the goals of End TB and Ending the HIV Epidemic. (Am J Public Health. 2022;112(6):881-885. https://doi.org/10.2105/AJPH.2022.306801).

Examining the extent and factors associated with interprofessional teamwork in primary care settings.

Despite growing emphasis on adopting team-based models of primary care to facilitate patient access to a diverse range of care providers, our understanding of team functioning within primary care teams remains limited. This study examined interprofessional teamwork within primary care practices (Family Health Teams [FHT] and Community Health Centers - [CHC]) in Ontario and explored team-level and organizational factors associated with interprofessional teamwork. Interprofessional teamwork was measured using the Collaborative Practice Assessment Tool (CPAT), which was completed by providers in each participating team. The CPAT responses of 988 providers representing on average 12 professions (sd = 2.1) across 66 teams (44 FHTs and 22 CHCs) were included in the analysis. The average CPAT score was 46.6 (sd = 2.5). CHCs had significantly higher CPAT scores than FHTs (mdiff = 1.7, p = .02). Using diverse communication mechanisms to share information, increasing quality improvement capacities, and age of practice, had a statistically significant positive association with CPAT scores. Increasing team size, using centralized administrative processes, a high level of information exchange, and having a mixed governance board were significantly negatively associated with CPAT score. Findings illustrate factors associated with interprofessional teamwork and offer insight into the comparative performance of two team-based primary care models in Ontario.

Septins and Generation of Asymmetries in Fungal Cells.

Polarized growth is critical for the development and maintenance of diverse organisms and tissues but particularly so in fungi, where nutrient uptake, communication, and reproduction all rely on cell asymmetries. To achieve polarized growth, fungi spatially organize both their cytosol and cortical membranes. Septins, a family of GTP-binding proteins, are key regulators of spatial compartmentalization in fungi and other eukaryotes. Septins form higher-order structures on fungal plasma membranes and are thought to contribute to the generation of cell asymmetries by acting as molecular scaffolds and forming diffusional barriers. Here we discuss the links between septins and polarized growth and consider molecular models for how septins contribute to cellular asymmetry in fungi.

Inappropriate disposal of 'flushable' consumer products - reasons for concern.

Inappropriate disposal of wipes and other products that are either explicitly labelled or assumed by the consumers to be flushable via toilets is increasingly being cited as the cause of a range of sewer systems issues. In the rapidly growing and diverse market for these consumer products, there are significant variations in consumer information provided by manufacturers, product composition and behaviour in different components of wastewater system. This paper summarizes the results of assessing the labelling, drainline clearance and disintegration testing of 101 consumer products, adopting the International Water Services Flushability Group flushability specifications. None of the products tested satisfy the product labelling Code of Practice, and all products other than bathroom tissue failed the disintegration test, including the 23 products that were labelled 'flushable'. The need for a global definition of a 'flushable' product exists and it is vital that it is brought into legislation in an effort to combat misconceptions around consumer products that may exist internationally.

Retrospective quality assurance audit of Lateral Cephalometric Radiographs at postgraduate teaching hospital.

OBJECTIVE: The objective of our audit was to assess the quality of lateral cephalometric radiographs by investigating the percentage of lateral cephalometric radiographic images that satisfied the good quality standards. METHODS: The standard-based retrospective audit was conducted at Riphah International University, Pakistan, from April to September 2018. The sample size was 50 radiographs that were randomly selected from the radiographs taken over one year. The radiographs were graded according to the standards set by the National Radiation Protection Board by two evaluators after the necessary calibration. Moreover, the percentages of images that met the criteria set by the Royal College of Surgeons of England were identified. The data analysis was carried out by the SPSS software version 23. RESULTS: Out of the 50 radiographs, thirty-one were Grade-I, sixteen were Grade-II and three radiographs were Grade-III. Furthermore, out of the criteria set by Royal College, one criterion met the 100% standard that was correct head positioning. Less frequent errors were comprised of poor visibility of soft tissue structures (16%), teeth not properly occluded (14%), Incorrect positioning of labels (12%), Sella and Nasion not visible (8%). According to the results of the quality assurance audit, the radiographs fell short of the required standards. CONCLUSION: Quality assurance by periodic auditing is important to yield radiographs with maximum diagnostic value, minimal errors, and avoid unnecessary radiation exposure by repeat radiographs. Recommendations were made for the formulation and implementation of comprehensive radiation protection regulations, at all the Dental institutes of Pakistan.

Preparation and characterization of resistant starch type III from enzymatically hydrolyzed maize flour.

Polysaccharides including resistant starch are categorized as dietary fiber and are used as an important prebiotic. Similar to soluble fibers, resistant starch also has a number of physiological effects that have been shown to be beneficial for health. Starch hydrolyzing enzymes, most importantly amylases, play essential roles in the production of resistant starch. This study aimed to develop α-amylase-treated maize flour with slow digestibility and unique physicochemical characteristics compared to native maize flour. In the current study, resistant starch type III from maize flour was prepared using α-amylase obtained from indigenously isolated Bacillus licheniformis. The α-amylase gene from B. licheniformis was amplified and cloned into the pET-24(a) vector, expressed in E. coli BL21 (DE3) cells and purified by metal ion affinity chromatography. The purified enzyme enhanced the yield of resistant starch 16-fold in maize flour. Scanning electron microscopy revealed that the granular structure of maize flour was disrupted into a dense network with irregular structure, and X-ray diffractograms confirmed the transformation from an amorphous to a crystalline structure upon α-amylase treatment. Thermogravimetric analysis revealed increased amylose content of α-amylase-treated maize flour. Moreover, α-amylase-treated maize flour resulted in a significant enhancement of the desired properties of maize flour, such as resistant starch content, amylose, milk absorption capacity, and iodine and fatty acid complexing ability, and a reduction in swelling power, water binding, oil absorption capacity, and in vitro digestibility compared to untreated maize flour. Resistant starch type III showed low digestibility and increased complexing ability with iodine and fatty acid and therefore could be a safe and beneficial alternative as a coating material for the delivery of active, sensitive ingredients to the colon.

Do family health clinics provide primary-level palliative care in Ontario and the eastern regions of Quebec?

OBJECTIVE: To explore the extent to which family health clinics in Ontario and the eastern regions of the province of Quebec provide palliative care. DESIGN: A cross-sectional survey. SETTING: Ontario and the eastern regions of Quebec. PARTICIPANTS: The clinic leads of a select group of family health clinics with patient enrolment models in Ontario and the eastern regions of Quebec. MAIN OUTCOME MEASURES: The types of palliative care services that the clinics provide, as well as the enablers of and barriers to providing palliative care within the 2 provinces. RESULTS: The overall response rate was 32%. Clinics in both provinces reported providing palliative care to ambulatory patients (83% of Ontario clinics and 74% of Quebec clinics). Only 29 of 102 (28%) Ontario clinics provided on-call services themselves, compared with 31 of 34 (91%) Quebec clinics, with the resulting effect being that more patients were directed to emergency departments in Ontario. Access to palliative care specialist teams for support was higher in Ontario than in Quebec (67% vs 41%, respectively). In Ontario, 56% of practices indicated that they had access to palliative care physicians who could take over the care of their patients with palliative care needs, but a lower number (44%) actually handed over care to these physicians. CONCLUSION: A group of clinics are providing full palliative care services to their own patients with palliative care needs, including "on-call" services and home visits, and these serve as role models. In Ontario in particular, substantial gaps still exist with respect to clinics providing their own after-hours coverage and home visits; many rely on other services to provide that care. In Quebec, lack of access to palliative care specialist teams appears to be a key challenge in the areas included in this survey. This survey could help policy makers and funders of health care services ensure that appropriate conditions are put in place for optimal palliative care provision in these clinics, such as coordinating access to on-call coverage and support from palliative care specialist teams, as well as providing education to all physicians and adequate remuneration.

Income inequalities in multimorbidity prevalence in Ontario, Canada: a decomposition analysis of linked survey and health administrative data.

BACKGROUND: The burden of multimorbidity is a growing clinical and health system problem that is known to be associated with socioeconomic status, yet our understanding of the underlying determinants of inequalities in multimorbidity and longitudinal trends in measured disparities remains limited. METHODS: We included all adult respondents from four cycles of the Canadian Community Health Survey (CCHS) (between 2005 to 2011/12), linked at the individual-level to health administrative data in Ontario, Canada (pooled n = 113,627). Multimorbidity was defined at each survey response as having ≥2 (of 17) high impact chronic conditions, based on claims data. Using a decomposition method of the Erreygers-corrected concentration index (CErreygers), we measured household income inequality and the contribution of the key determinants of multimorbidity (including socio-demographic, socio-economic, lifestyle and health system factors) to these disparities. Differences over time are described. We tested for statistically significant changes to measured inequality using the slope index (SII) and relative index of inequality (RII) with a 2-way interaction on pooled data. RESULTS: Multimorbidity prevalence in 2011/12 was 33.5% and the CErreygers was - 0.085 (CI: -0.108 to - 0.062), indicating a greater prevalence among lower income groups. In decomposition analyses, income itself accounted more than two-thirds (69%) of this inequality. Age (21.7%), marital status (15.2%) and physical inactivity (10.9%) followed, and the contribution of these factors increased from baseline (2005 CCHS survey) with the exception of age. Other lifestyle factors, including heavy smoking and obesity, had minimal contribution to measured inequality (1.8 and 0.4% respectively). Tests for trends (SII/RII) across pooled survey data were not statistically significant (p = 0.443 and 0.405, respectively), indicating no change in inequalities in multimorbidity prevalence over the study period. CONCLUSIONS: A pro-rich income gap in multimorbidity has persisted in Ontario from 2005 to 2011/12. These empirical findings suggest that to advance equality in multimorbidity prevalence, policymakers should target chronic disease prevention and control strategies focused on older adults, non-married persons and those that are physically inactive, in addition to addressing income disparities directly.

Antibiofilm potential of synthetic 2-amino-5-chlorobenzophenone Schiff bases and its confirmation through fluorescence microscopy.

Antibacterial/antibiofilm potential of microwave-assisted synthetic thirty-three 2-amino-5-chloro benzophenone Schiff bases have been carried out against four bacterial strains i.e. Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus and Streptococcus mutans. Among them compounds 5, 6, 8, 9, 14, 16, 22, 24, 26, and 30-32 showed antibiofilm activities against isolates at less than 100 µg/ml concentrations. These compounds showed enhanced antibiofilm activity against S. aureus as compared to cefixime used as control. However, remaining compounds were found to be active but at higher concentration. Fluorescence microscopy has been employed for confirmation of antibiofilm results. The structures of all synthetic molecules have been characterized on the basis of spectroscopic techniques including 1H NMR, 13C NMR, EI-MS, HREI-MS, and IR spectroscopy and their structure-activity relationship have been established.

Biofilm inhibitory effect of chlorhexidine conjugated gold nanoparticles against Klebsiella pneumoniae.

Klebsiella pneumoniae (K. pneumoniae) is one of the major pathogen associated with nosocomial infections, especially catheter associated urinary tract infections which involved biofilm formation. This study was designed to evaluate the antibiofilm efficacy of gold nanoparticle conjugated with chlorhexidine (Au-CHX) against K. pneumoniae isolates. Au-CHX was synthesized and analyzed for stability by using UV-Visible spectrophotometry, atomic force microscopy (AFM), fourier transform infrared spectroscopy (FT-IR) and electrospray ionization mass spectroscopy (ESI-MS). Biofilm inhibition and eradication was performed by crystal violet, 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and further confirmed by florescence and AFM microscopy. Au-CHX showed the maxima surface plasmon resonance (SPR) band at 535 nm, spherical morphology and polydispersity with size in the range of 20-100 nm. The micro molar concentrations (i.e. 25 and 100 µM) of Au-CHX completely inhibited the biofilm formation and metabolic activity within biofilms of K. pneumoniae reference and three tested clinical isolates, respectively. Time dependant biofilm inhibition assay showed that Au-CHX inhibited the early stage of biofilm formation. While at 75 and 100 µM concentrations, it also eradicated the established biofilms of K. pneumoniae isolates as compared to 2 mM chlorhexidine. Reduced florescence signals and surface roughness during microscopic analysis further confirms the antibiofilm activity of Au-CHX against K. pneumoniae ATCC13882 and clinical isolates. Thus it is concluded that chlorhexidine coated gold nanoparticle not only inhibits the biofilm formation of K. pneumoniae ATCC and clinical isolates but also eradicated the preformed biofilm.

Spatial phenotyping of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma with sparse tumor B-cells and a favorable prognosis. Variant growth patterns of NLPHL, however, often show advanced stage, progression to T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and a worse prognosis. We studied the tumor microenvironment (TME) of NLPHL and THRLBCL using highplex imaging and spatial profiling at the single cell level. Our findings show distinct differences in TME composition and spatial configuration that differ among typical and variant NLPHL and THRLBCL. Typical NLPHL show abundant helper T-cell subsets, while THRLBCL show abundant cytotoxic T-cells and macrophages. Tumor B-cell size and content is lowest in typical NLPHL, followed by variant NLPHL, and highest in THRLBCL, whereas an opposite trend characterized TME B-cells. CD4/CD8 double-positive T-cells are seen in all NLPHL but not in the majority of THRLBCL and are spatially distant from LP-cells and TFH-rosettes. The differences in macrophage/monocyte content in distinguishing NLPHL pattern E from THRLBCL is further corroborated in independent cohorts of cases. Our results validate the current approach to classification and in addition provide novel insights that could be leveraged to refine clinical management for patients with this spectrum of lymphomas.

Hematoxylin and Eosin Architecture Uncovers Clinically Divergent Niches in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the only cancers with an increasing incidence rate and is often associated with intra- and peri-tumoral scarring, referred to as desmoplasia. This scarring is highly heterogeneous in extracellular matrix (ECM) architecture and plays complex roles in both tumor biology and clinical outcomes that are not yet fully understood. Using hematoxylin and eosin (H&E), a routine histological stain utilized in existing clinical workflows, we quantified ECM architecture in 85 patient samples to assess relationships between desmoplastic architecture and clinical outcomes such as survival time and disease recurrence. By utilizing unsupervised machine learning to summarize a latent space across 147 local (e.g., fiber length, solidity) and global (e.g., fiber branching, porosity) H&E-based features, we identified a continuum of histological architectures that were associated with differences in both survival and recurrence. Furthermore, we mapped H&E architectures to a CO-Detection by indEXing (CODEX) reference atlas, revealing localized cell- and protein-based niches associated with outcome-positive versus outcome-negative scarring in the tumor microenvironment. Overall, our study utilizes standard H&E staining to uncover clinically relevant associations between desmoplastic organization and PDAC outcomes, offering a translatable pipeline to support prognostic decision-making and a blueprint of spatial-biological factors for modeling by tissue engineering methods.

Posterior reversible encephalopathy syndrome: A rare complication of rituximab therapy in rheumatoid arthritis.

Rituximab, a murine-human chimeric monoclonal antibody targeting CD20-positive B lymphocytes, has established itself as an effective and relatively safe biologic therapy for patients with refractory rheumatoid arthritis. Most common side effects associated with its use include infusion related reactions and cytopenia. Rare adverse effects such as progressive multifocal leukoencephalopathy and posterior reversible encephalopathy syndrome (PRES) have also been reported. Diagnosis of PRES following rituximab treatment requires a high index of suspicion correlated with clinical and radiological features in individuals at risk. Early diagnosis and prompt treatment is associated with a favorable prognosis. We present a case of a young man who developed PRES following rituximab administration on account of active rheumatoid arthritis. Timely diagnosis and prompt treatment ensured his uneventful recovery without residual neurological deficit.

Desmoplastic stromal signatures predict patient outcomes in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death. Hallmarks include desmoplasia with variable extracellular matrix (ECM) architecture and a complex microenvironment with spatially defined tumor, stromal, and immune populations. Nevertheless, the role of desmoplastic spatial organization in patient/tumor variability remains underexplored, which we elucidate using two technologies. First, we quantify ECM patterning in 437 patients, revealing architectures associated with disease-free and overall survival. Second, we spatially profile the cellular milieu of 78 specimens using codetection by indexing, identifying an axis of pro-inflammatory cell interactions predictive of poorer outcomes. We discover that clinical characteristics, including neoadjuvant chemotherapy status, tumor stage, and ECM architecture, correlate with differential stromal-immune organization, including fibroblast subtypes with distinct niches. Lastly, we define unified signatures that predict survival with areas under the receiver operating characteristic curve (AUCs) of 0.872-0.903, differentiating survivorship by 655 days. Overall, our findings establish matrix ultrastructural and cellular organizations of fibrosis linked to poorer outcomes.

Small Fiber Neuropathy Associated With the Moderna SARS-CoV-2 Vaccine.

Efforts of controlling viral transmission began soon after the first cases of coronavirus disease 2019 (COVID-19) infections were identified. Initial efforts were related to contact precautions, hand hygiene, and mask-wearing; however, it was soon evident that a robust global immunization drive was the most effective way to curb disease transmission. In the United States, the first doses of COVID-19 vaccines were rolled out soon after the FDA granted emergency use authorization for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. What this also meant was that many of the routine phases that any new drug or vaccine goes through before being released publicly were bypassed. Over the past two years, various side effects and reactions have been seen after COVID-19 vaccine administration, the most common being local injection site events (e.g., pain, redness, swelling) and systemic effects (e.g., fatigue, headaches, myalgias). We report the case of a 64-year-old female who developed bilateral lower extremity numbness and tingling within weeks of receiving the third dose of Moderna SARS-CoV-2 vaccine. The patient underwent extensive testing to ascertain the diagnosis. She had negative autonomic testing and normal nerve conduction study/electromyography (EMG), which did not reveal large fiber neuropathy. Eventually, the patient underwent a skin biopsy, which revealed small fiber neuropathy. This case report highlights the importance of keeping a broad differential for rare side effects, such as small fiber neuropathy, that are currently being seen and reported in the literature.

Tinnitus and biopsychosocial ramifications of COVID-19 associated with severe suicide attempt-a case report.

The COVID-19 disease has been linked to multiple physical and mental health consequences which may be partially attributed to multi-system modulation by inflammatory cytokines. Post-acute sequelae (PASC) of SARS-CoV-2 infection, colloquially known as "Long Covid", has become an established entity. However, screening guidelines and interventions for COVID-19 survivors remain elusive. The neuropsychiatric sequelae of COVID-19 seem to originate from a cumulation of biopsychosocial factors which may predispose individuals to acute psychiatric decompensation irrespective of a previously diagnosed mental illness. We present a case report which illustrates how cognitive issues and medical complaints may negatively interact resulting in significant depression and a severe suicide attempt.

Exploring Intra and Interorganizational Integration Efforts Involving the Primary Care Sector - A Case Study from Ontario.

Background: The primary care sector is uniquely positioned to lead the coordination of providers and organizations across health and social care sectors. This study explores whether intraorganizational (professional) integration within a primary care team might be related to interorganizational integration between primary care and other community partners involved in caring for complex patients. Methods: Two care coordination initiatives (Health Links) were selected - one led by a primary care team with a high level of intraorganizational integration as assessed by the Collaborative Practice Assessment Tool (CPAT), and the other led by a primary care team with a low level of intraorganizational integration. A case study design involving a social network approach was used to assess interorganizational integration across six types of relationships including regular contact, perceived level of integration, referrals, information sharing, joint care planning, and shared resources. Results: Compared to the high-CPAT led case, the low-CPAT led case had higher density (more ties among organizations) in terms of regular contact, integration, and sharing of resources, whereas the opposite was true for the referral, information sharing, and joint care planning networks. Network centralization (extent to which network activity is influenced by one or a group of organizations) was higher for the high-CPAT case compared to the low-CPAT case in the integration, referrals, and joint care planning networks, while the low-CPAT case had higher centralization with regard to regular contact, information sharing, and shared resources. Conclusion: The interplay between intra and interorganizational integration remains unclear. We found no consistent differences in the patterns of ties across the six types of networks examined between the two cases. Assessing changes in network metrics for different organizations in each case over time, and supplementing network findings through in-depth interviews with network members are key next steps to consider.

Enoxacin-based derivatives: antimicrobial and antibiofilm agent: a biology-oriented drug synthesis (BIODS) approach.

Background: To find alternative molecules against Klebsiella pneumonia, Proteus mirabilis and methicillin-resistant Staphylococcus aureus, new enoxacin derivatives were synthesized and screened. Methods: All derivatives exhibited promising antibacterial activities as compared to standard enoxacin (2 µg/ml) and standard cefixime (82 µg/ml). Compounds 2, 3 and 5 significantly downregulated the gene expression of biofilm-forming genes. Conclusion: Based on our results, these molecules may serve as potential drug candidates to cure several bacterial infections in the future.