Comparison of two endoscope channel cleaning approaches to remove cyclic build-up biofilm.

Biofilm contributes significantly to bacterial persistence in endoscope channels. Enhanced cleaning methods capable of removing biofilm from all endoscope channels are required to decrease infection risk to patients. This head-to-head study compared cyclic build-up biofilm removal of an automated endoscope channel cleaner (AECC) to standard manual cleaning according to instructions for use (IFU) in polytetrafluorethylene channels. The automated cleaner significantly outperformed manual cleaning for all markers assessed (protein, total organic carbon, viable bacteria) in 1.4 mm and 3.7 mm channels representing air/water/auxiliary and suction/biopsy channels respectively. Manual cleaning failed to remove biofilm from the air/water and auxiliary channels. According to the IFU, these channels are not brushed, suggesting a potential root cause for a portion of the numerous endoscopy associated infections reported in the literature. AECC shows potential to deliver enhanced cleaning over current practice to all endoscope channels and may thereby address infection risk.

Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis.

BACKGROUND AND AIMS: The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency. APPROACH AND RESULTS: Data from all children with chronic cholestasis and either homozygous or compound heterozygous mutations in TJP2 were extracted and analyzed. The patients were categorized into 3 genotypes: TJP2-A (missense mutations on both alleles), TJP2-B (missense mutation on one allele and a predicted protein-truncating mutation [PPTM] on the other), and TJP2-C (PPTMs on both alleles). A total of 278 cases of genetic intrahepatic cholestasis were studied, with TJP2 deficiency accounting for 44 cases (15.8%). Of these, 29 were homozygous and 15 were compound heterozygous variants of TJP2 . TJP2-A genotype was identified in 21 (47.7%), TJP2-B in 7 cases (15.9%), and TJP2-C in 16 cases (36.4%), respectively. Patients with the TJP2-C genotype were more likely to experience early infantile cholestasis (87.5% vs. 53.5%, p =0.033), less likely to clear jaundice (12.5% vs. 52.2%, p =0.037), more likely to develop ascites, and had higher serum bile acids. Patients with the TJP2-C genotype were more likely to die or require liver transplantation (native liver survival: 12.5% vs. 78.6%, p <0.001), with a median age at death/liver transplantation of 2.5 years. Cox regression analysis revealed that TJP2-C mutations ( p =0.003) and failure to resolve jaundice ( p =0.049) were independent predictors of poor outcomes. CONCLUSIONS: Patients with the TJP2-C genotype carrying PPTMs in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.

Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure.

The HIV-1 capsid has emerged as a tractable target for antiretroviral therapy. Lenacapavir, developed by Gilead Sciences, is the first capsid-targeting drug approved for medical use. Here, we investigate the effect of lenacapavir on HIV capsid stability and uncoating. We employ a single particle approach that simultaneously measures capsid content release and lattice persistence. We demonstrate that lenacapavir's potent antiviral activity is predominantly due to lethal hyperstabilisation of the capsid lattice and resultant loss of compartmentalisation. This study highlights that disrupting capsid metastability is a powerful strategy for the development of novel antivirals.

Direct benefit transfer for nutritional support of patients with TB in India-analysis of national TB program data of 3.7 million patients, 2018-2022.

BACKGROUND: Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. METHODS: In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. RESULTS: Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. CONCLUSIONS: The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure.

Virtual and augmented reality in cardiovascular care in low and middle income country.

The global health sector has witnessed an escalating integration of Virtual Reality (VR) and Augmented Reality (AR) technologies, particularly in high-income countries. The application of these cutting-edge technologies is gradually extending to Low- and Middle-Income Countries (LMICs), notably in the domain of cardiovascular care. AR and VR technologies are revolutionizing cardiovascular care by offering solutions for diagnosis, medical training, and surgical planning. AR and VR provide detailed and immersive visualizations of cardiac structures, aiding in diagnosis and intervention planning. In cardiovascular care, VR reduces patient-reported pain, eases anxiety, and accelerates post-procedural recovery. AR and VR are also valuable for life support training, creating immersive and controlled learning environments. AR and VR have the potential to significantly impact healthcare in low- and middle-income countries with enhanced accessibility and affordability. This review outlines the existing spectrum of VR and AR adoption and its burgeoning utility in the cardiovascular domain within LMICs.

Cardiovascular Outcomes of Transcatheter Aortic Valve Implantation in Patients With Chronic Kidney Disease in Octogenarian Population.

Limited data are available regarding in-hospital outcomes of transcatheter aortic valve implantation (TAVI) in the octogenarian population with chronic kidney disease (CKD). We sought to study the cardiovascular outcomes of TAVI in CKD hospitalization with different stages at the national cohort registry. We used the National Inpatient Sample database to compare TAVI CKD low-grade (LG) (stage I to IIIa, b) versus TAVI CKD high-grade (HG) (stage IV to V) in octogenarians. Outcomes such as inpatient mortality, cardiogenic shock, new permanent pacemaker implantation, acute kidney injury), sudden cardiac arrest, mechanical circulatory support, major bleeding, transfusion, and resource utilization were compared between the 2 cohorts. A total of 74,766 octogenarian patients (TAVI CKD-HG n = 12,220; TAVI CKD-LG n = 62,545) were included in our study. On matched analysis, TAVI CKD-HG had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.18, 95% confidence interval [CI] 1.0-2.5, p <0.0001), cardiogenic shock (aOR 1.22, 95% CI 1.07 to 1.39, p = 0.0019), permanent pacemaker implantation (aOR 1.14, 95% CI 1.06 to 1.23, p = 0.0006), acute kidney injury (aOR 1.19, 95% CI 1.13 to 1.27, p <0.0001), sudden cardiac arrest (aOR 1.32, 95% CI 1.09 to 1.61, p = 0.004), major bleeding (aOR 1.1, 95% CI 1.006 to 1.22, p <0.0368) and higher rates of blood transfusion (aOR 1.62, 95% CI 1.5 to 1.75, p <0.0001) when compared with the TAVI CKD-LG cohort. However, there was no statistically significant difference in the odds of cerebrovascular accident and mechanical circulatory support use between the 2 groups.

Comparison of three modalities of teleophthalmology delivery in regional Western Australia during the COVID-19 lock-down.

CLINICAL RELEVANCE: In conjunction with local optometry services, telehealth may be used in to provide specialist care for patients living in rural areas underserved by ophthalmology. BACKGROUND: To combat travel restrictions for specialist outreach to regional areas during the 2020 COVID-19 lockdown, Lions Outback Vision introduced three different modalities of teleophthalmology consultations; home-based telephone, hospital-based video, and optometry-based video. This study evaluated the utility of these in providing specialist care to rural patients during the pandemic. METHODS: Data from patients referred during the COVID-19 lock-down period (23 March 2020 to 5 June 2020) were analysed. If sufficient clinical information and imaging were available then ophthalmologists conducted home-based telephone consultations. If further ocular imaging or examination was required, then optometry-based video or hospital-based video were used. Data were analysed using ANOVA and two-sided t tests for continuous data and Chi Square statistics for categorical data (p < 0.05). RESULTS: Majority of the 431 consultations were conducted via home telephone (38%) or optometry-based video (37%). Indigenous patients (p = 0.014) and patients in very remote communities (p < 0.01) were more likely to receive a home-based telephone consultation. Because sufficient clinical information had already been obtained for home-based consultations, these patients were more likely to be booked for surgery than optometry (p < 0.01).Cataracts were the predominant diagnosis in optometry consults compared to hospital (p < 0.01). CONCLUSION: Primary optometry and home telephone represent a new modality for providing specialist care for patients living in very remote regions and for Indigenous patients. When appropriate clinical testing has been completed, telephone-based ophthalmology may continue to be useful for certain conditions such as waitlisting patients for cataract surgery and should continue to be funded beyond the duration of the pandemic for rural patients.

Bone Marrow Quality Index: A Predictor of Acute Graft-versus-Host Disease in Hematopoietic Stem Cell Transplantation for Thalassemia.

Bone marrow (BM) continues to be the preferred source of stem cells in allogenic transplantation for nonmalignant disorders. Granulocyte colony-stimulating factor (G-CSF)-primed BM is associated with low rates of acute graft-versus-host disease (aGVHD) and allows reduced collection volumes while ensuring speedy engraftment. However, variability in BM harvest quality is a concern. This study evaluated the utility of a novel indicator, the Bone Marrow Quality Index (BMQI), to predict aGVHD. We analyzed 184 consecutive first matched related donor bone marrow transplants for thalassemia using G-CSF-primed bone marrow over 6 years from March 2017 to April 2023 across 2 centers in India. BMQI was defined as the ratio of the G-CSF-primed BM WBC count to the peripheral blood WBC count within 24 hours of harvest. European Society for Blood and Marrow Transplantation criteria were used to grade aGVHD. The log-rank test was used to assess the impact of BMQI on aGVHD. The chi-square test was used to compare categorical data, and the Wilcoxon rank-sum test was used to compare the numerical data. A Cox proportional hazards model was used to investigate the association of BMQI vis-à-vis other factors on aGVHD. Of the 184 patients studied, 19 had a BMQI <.9, 18 had a BMQI between .9 and 1, and the remaining 147 had a BMQI >1. The rate of aGVHD grade II-IV was 37% in patients with a BMQI <.9 , 22% in those with BMQI .9 to 1, and 12% in those with BMQI >1 (P = .018). Patients with BMQI <.9 had a 3.1-fold greater chance (95% confidence interval [CI], .9 to 10.6) and those with BMQI .9 to 1 had a 2-fold greater chance (95% CI, .5 to 6.6) of developing aGVHD grade II-IV. BMQI was the significant predictor associated with aGVHD hazard (P = .014). BMQI appears to be the most relevant and controllable predictor of aGVHD. It is a novel, informative, and very simple indicator that could influence aGVHD prophylaxis decision making. Our indicator is accurately measurable, inexpensive, precise, and timely; furthermore, it does not involve any sophisticated equipment and thus may be widely applicable. Prior knowledge of poor BM quality may help intensify prophylaxis and monitoring for aGVHD, as well as trigger a review of collection procedures.

Chronic skin ulcers in hemodialysis patient: A fatal case of calciphylaxis.

Calciphylaxis is a rare and deadly vascular disease with poorly understood pathophysiology and without definitive treatment. Early presentations include skin ulcers with risk factors including end stage renal disease on hemodialysis, hypertension, hyperlipidemia, and diabetes mellitus. In our case, we present an 80-year-old female with multiple risk factors including hemodialysis and clinical features of necrotic and gangrenous skin lesions diagnostic of calciphylaxis who became hemodynamically unstable and ultimately expired secondary to toxic sequelae. We illustrate this case to explore early clinical presentation, limitations of current disease management and treatments, and the role for further studies to improve diagnosis and reduce mortality.

Is it safe and efficacious to remove central lines in pediatric bone marrow transplant patients with platelets less than 20,000/µl?

Background: Patients with tunneled central venous lines (CVL) may develop bloodstream infections which at times are difficult to control without line removal. Concomitant severe thrombocytopenia with platelet transfusion refractoriness is often considered a major contraindication to any procedure involving a major blood vessel. There is very little literature on the clinical risks of tunneled central line removal in febrile pancytopenia patients. Procedure: We analyzed complications and outcomes in all our patients, a total of 52, who underwent CVL removal with platelets <20,000/µl. Results: CVL removal was done on a median day of 17.5 with 47 of the 52 patients never having achieved platelets engraftment prior to line removal. No bleeding episodes or unplanned transfusions could be associated with CVL removal. No other complications were also reported. All patients had time to hemostasis within 5 min of catheter removal. Removal of CVL under local anesthesia remained complication-free even at platelet counts less than 20,000/ul. A total of 31 patients were febrile at the time of CVL removal, of which 17 became afebrile within 2 days. We found no difference in defervescence when comparing those whose antibiotic therapy was changed/escalated versus those in whom it was not. Conclusion: Our findings suggest that central lines can be safely removed with platelet counts less than 20,000/ul and that this may result in enhanced bloodstream infection control. This might be particularly relevant to neutropenic patients in this day and age of multidrug-resistant organism emergence and paucity of new effective antibiotics.

Estimation of tuberculosis incidence at subnational level using three methods to monitor progress towards ending TB in India, 2015-2020.

OBJECTIVES: We verified subnational (state/union territory (UT)/district) claims of achievements in reducing tuberculosis (TB) incidence in 2020 compared with 2015, in India. DESIGN: A community-based survey, analysis of programme data and anti-TB drug sales and utilisation data. SETTING: National TB Elimination Program and private TB treatment settings in 73 districts that had filed a claim to the Central TB Division of India for progress towards TB-free status. PARTICIPANTS: Each district was divided into survey units (SU) and one village/ward was randomly selected from each SU. All household members in the selected village were interviewed. Sputum from participants with a history of anti-TB therapy (ATT), those currently experiencing chest symptoms or on ATT were tested using Xpert/Rif/TrueNat. The survey continued until 30 Mycobacterium tuberculosis cases were identified in a district. OUTCOME MEASURES: We calculated a direct estimate of TB incidence based on incident cases identified in the survey. We calculated an under-reporting factor by matching these cases within the TB notification system. The TB notification adjusted for this factor was the estimate by the indirect method. We also calculated TB incidence from drug sale data in the private sector and drug utilisation data in the public sector. We compared the three estimates of TB incidence in 2020 with TB incidence in 2015. RESULTS: The estimated direct incidence ranged from 19 (Purba Medinipur, West Bengal) to 1457 (Jaintia Hills, Meghalaya) per 100 000 population. Indirect estimates of incidence ranged between 19 (Diu, Dadra and Nagar Haveli) and 788 (Dumka, Jharkhand) per 100 000 population. The incidence using drug sale data ranged from 19 per 100 000 population in Diu, Dadra and Nagar Haveli to 651 per 100 000 population in Centenary, Maharashtra. CONCLUSION: TB incidence in 1 state, 2 UTs and 35 districts had declined by at least 20% since 2015. Two districts in India were declared TB free in 2020.

Generalizability of deep learning models for predicting outdoor irregular walking surfaces.

Observations from laboratory-based gait analysis are difficult to extrapolate to real-world environments where gait behavior is modulated in response to complex environmental conditions and surface profiles. Inertial measurement units (IMUs) permit real-world gait analysis; however, automatic detection of surfaces encountered remains largely unexplored. The aims of this study are to quantify for machine learning models the effect of (1) random and subject-wise data splitting and (2) sensor location and count on surface classification performance. Thirty participants walked on nine surface conditions (flat-even, slope-up, slope-down, stairs-up, stairs-down, cobblestone, grass, banked-left, banked-right) wearing IMUs (wrist, trunk, bilateral thighs, bilateral shanks). Data were separated into gait cycles, normalized to 101 samples, and spilt into train and test sets (85 and 15%, respectively). For random splitting, trials were randomly assigned to the train or test set. In subject-wise splitting, all trials from 4 random participants were selected for testing. Linear discriminant analysis extracted features from the IMUs. Features were delivered to a neural network. F1-score evaluated model performance. Models achieved F1 scores of 0.96 and 0.78 using random and subject-wise splitting, respectively. Random splitting performance was mainly invariant to sensor location/count; however, subject-wise splitting showed best performance using lower-limb sensors. In general, stairs and sloped surfaces were easily predicted (F1 > 0.85) while banked surfaces were challenging, especially for subject-wise models (F1 ≈ 0.6). Neural networks can detect surfaces based on subtle changes in walking behavior captured by IMUs. Data splitting approaches and sensor location/count (subject-wise) have a non-negligible effect on model performance.

Congenital Bile Acid Synthesis Defect Type 3 With Severe Neonatal Cholestasis.

Congenital bile acid synthesis defect type 3 is a rare metabolic liver disease with only eight patients reported in literature. We describe clinical, pathological and molecular features for a ninth patient. A 4-month-old infant presented to us with conjugated hyperbilirubinemia. His liver biopsy revealed giant cell change, steatosis, and activity with diffuse fibrosis. Immunostaining with bile salt export pump showed preserved canalicular pattern and γ-glutamyl transferase 1 staining showed unusual complete membranous pattern. Genetic workup revealed homozygous single base pair duplication in exon 3 of the CYP7B1 gene. He succumbed to liver disease at 7 months of age.

A rare case of delayed anaplasma phagocytophilum-induced pancytopenia: A diagnostic conundrum.

INTRODUCTION: Human granulocytic anaplasmosis (HGA) is a potentially fatal tick-borne disease caused by the obligate intracellular bacterium Anaplasma phagocytophilum. It is most commonly found in the Northeastern and Midwestern parts of the United States especially during spring and summer months. The clinical picture of anaplasmosis is varied ranging from common symptoms such as fever, headache and myalgia to rarer presentations such as pancytopenia. CASE PRESENTATION: We present a case of a 62 year old male who presented with watery diarrhea, fever, and pancytopenia. Although there is a broad differential for pancytopenia, a thorough history provides clues regarding the diagnosis. In our patient, a recent history of camping in Upstate New York was suggestive of an infectious etiology from a tick borne illness. CLINICAL DISCUSSION: A tick-borne panel guided us to identify the diagnosis of HGA. Although the exact underlying pathogenesis of tick-borne illnesses leading to pancytopenia is still unknown, the pancytopenia is postulated to be due to a multi-nodal mechanism involving immune and non immune platelet destruction, global bone marrow suppression, hemophagocytic lymphohistiocytosis and myelosuppressive chemokines release. CONCLUSION: We hope that this case report elucidates the importance of obtaining a meticulous history in guiding clinicians towards prompt diagnosis, even in instances where there may be an evolving clinical picture.

Compound Heterozygous Myosin 5B (Myo5b) Mutation with Early Onset Progressive Cholestasis and No Intestinal Failure.

Background: Exome sequencing studies have recently identified novel genes implicated in normal or low GGT pediatric cholestasis including myosin 5B (MYO5B). Case report: We identified novel compound heterozygote mutations in exon 14 and exon 19 of the MYO5B gene in an 18-month-old Indian child with history of fluctuating jaundice and severe pruritus. His liver biopsy showed portal and perivenular fibrosis with focal bridging septa and mild activity. He is currently on UDCA, cholestyramine and vitamin supplements. There is no history of diarrhea. His asymptomatic mother showed heterozygous mutation in exon 19 of the MYO5B gene and his asymptomatic father showed heterozygous mutation in exon 14 of the MYO5B gene. Conclusion: Our report confirms that patients with compound heterozygote mutations in MYO5B develop progressive cholestasis with no intestinal disease.

Do Weekly Surveillance Cultures Contribute to Antibiotic Stewardship and Correlate with Outcome of HSCT in Children? A Multicenter Real-World Experience of 5 Years from the Indian Subcontinent.

The utility of weekly rectal swab surveillance cultures (RSSCs) as a resource to identify gut colonization with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and guide empirical antibiotic therapy in hematopoietic stem cell transplantation (HSCT) recipients continues to be a subject of interest. There is an urgent need to assess and justify modifications to empirical antibiotics based on regional epidemiology and patient groups. This study aimed to study the utility of weekly rectal swab surveillance cultures (RSSCs) to guide empirical antibiotic therapy and to examine the impact of gut colonization on transplantation outcomes. This retrospective analysis of 317 successive first HSCTs performed mainly for hemoglobinopathies was conducted in 3 pediatric bone marrow transplantation centers in the Indian subcontinent between April 2016 and April 2021. Transplantation, infection control, and febrile neutropenia management protocols were identical in the 3 centers. First-line antibiotics were chosen based on RCCS reports, with meropenem used for ESBL and high-dose meropenem with colistin used for carbapenemase-resistant colonization for first half of the study, with no adjustment made in the second half. Clinical response to antibiotics, long-term outcomes, antibiotic-resistant bacteremia, and acute graft-versus-host disease (GVHD) were analyzed. The log-rank test, chi-square, and Wilcoxon rank-sum tests were used to compare data using R Statistical software. Of the 871 weekly RSSCs done, 162 were positive for ESBL- or KPC-resistant organism. RCCSs were ESBL-positive in 106 patients (33%) and KPC-positive in 10 patients (3%). Among the 97 ESBL-positive patients for whom a antimicrobial susceptibility testing report was available, only 22 (25%) demonstrated clinical resistance to piperacillin-tazobactam (Pip-Taz). Among the 10 KPC-positive patients, only 4 (40%) demonstrated clinical resistance to Pip-Taz and 3 (30%) had clinical resistance to meropenem. Two-thirds of patients with ESBL-positive RSSC in whom first-line empirical antibiotics were used responded clinically. Even among the 15 patients who were resistant to first-line empirical antibiotics (Pip-Taz) on RSSC reports, 67% responded clinically to Pip-Taz. Twenty-seven of these patients (56%) never needed carbapenem therapy. Empirical Pip-Taz therapy in ESBL-positive patients did not prolong meropenem use within 100 days of transplantation (P = .18). All patients with a KPC-positive RSSC who received first-line empirical antibiotics responded clinically, including 4 who were resistant to Pip-Taz and 3 who were meropenem-resistant on RCCS. Comparing patients who were ESBL-positive, KPC-positive, and not positive for either showed no statistically significant differences in overall survival (OS) (P = .95), disease-free survival (DFS) (P = .45), transplantation-related mortality (TRM) (P = .97), graft rejection (P = .68), or rate of acute GVHD grade II-IV (P = .78). No statistically significant differences were seen between the ESBL-positive patients who received and those who did not receive higher-level empirical antibiotics in OS (P = .32), DFS (P = .64), TRM (P = .65), graft rejection (P = .46), acute GVHD grade II-IV (P = .26), or antibiotic-resistant bacteremia (P = .3). In the context of HSCT for nonmalignant hematologic disorders, choosing empiric antibiotic therapy based on RSSCs is not justified, even in regions with a high prevalence of antimicrobial resistance. Antimicrobial susceptibility testing reports in surveillance cultures did not correlate with in vivo clinical response. Colonization reported on weekly RSSCs showed no correlation with clinical outcomes. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Rapid HIV-1 Capsid Interaction Screening Using Fluorescence Fluctuation Spectroscopy.

The HIV capsid is a multifunctional protein capsule that mediates the delivery of the viral genetic material into the nucleus of the target cell. Host cell proteins bind to a number of repeating binding sites on the capsid to regulate steps in the replication cycle. Here, we develop a fluorescence fluctuation spectroscopy method using self-assembled capsid particles as the bait to screen for fluorescence-labeled capsid-binding analytes ("prey" molecules) in solution. The assay capitalizes on the property of the HIV capsid as a multivalent interaction platform, facilitating high sensitivity detection of multiple prey molecules that have accumulated onto capsids as spikes in fluorescence intensity traces. By using a scanning stage, we reduced the measurement time to 10 s without compromising on sensitivity, providing a rapid binding assay for screening libraries of potential capsid interactors. The assay can also identify interfaces for host molecule binding by using capsids with defects in known interaction interfaces. Two-color coincidence detection using the fluorescent capsid as the bait further allows the quantification of binding levels and determination of binding affinities. Overall, the assay provides new tools for the discovery and characterization of molecules used by the HIV capsid to orchestrate infection. The measurement principle can be extended for the development of sensitive interaction assays, utilizing natural or synthetic multivalent scaffolds as analyte-binding platforms.

Paradigm shift in efforts to end TB by 2025.

TB is a deadly infectious disease, in existence since time immemorial. This article traces the journey of TB developments in the last few decades and the path breaking moments that have accelerated the efforts towards Ending TB from National Tuberculosis Control Program (NTCP 1962-1992) to Revised National Tuberculosis Control Program (RNTCP - 1992-2019) and to National Tuberculosis Elimination Program (NTEP) as per the vision of Honorable Prime Minister of India. From increased funding for TB, the discovery of newer drugs and diagnostics, increased access to health facilities, greater investment in research and expanded reach of public health education, seasoned with TB activism and media's proactive role, private sector participation to political advocacy and community engagement, coupled with vaccine trials has renewed the hope of finding the elusive and miraculous breakthrough to END TB and it seems the goal is within the realms of the possibility. The recent paradigm shift in the policy and the drive of several states & UTs to move towards TB free status through rigorous population-based vulnerability mapping and screening coupled with active case finding is expected to act as the driving force to lead the country towards Ending TB by 2025. Continued investments in research, innovations and availability of more effective drugs and the vaccines will add to existing armamentarium towards Ending TB.