Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India.

BACKGROUND: Excessive time between diagnosis and initiation of tuberculosis (TB) treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP) focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation. OBJECTIVES: To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB. METHODS: Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire. RESULTS: 2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35%) patients had >7 days between diagnosis and treatment and 262(13%) had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0-128 days). Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5-2.3) and 1.6 (95% CI 1.3-1.8) times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment delays

Direct grafting of tetraaniline via perfluorophenylazide photochemistry to create antifouling, low bio-adhesion surfaces.

Conjugated polyaniline has shown anticorrosive, hydrophilic, antibacterial, pH-responsive, and pseudocapacitive properties making it of interest in many fields. However, in situ grafting of polyaniline without harsh chemical treatments is challenging. In this study, we report a simple, fast, and non-destructive surface modification method for grafting tetraaniline (TANI), the smallest conjugated repeat unit of polyaniline, onto several materials via perfluorophenylazide photochemistry. The new materials are characterized by nuclear magnetic resonance (NMR) and electrospray ionization (ESI) mass spectroscopy. TANI is shown to be covalently bonded to important carbon materials including graphite, carbon nanotubes (CNTs), and reduced graphene oxide (rGO), as confirmed by transmission electron microscopy (TEM). Furthermore, large area modifications on polyethylene terephthalate (PET) films through dip-coating or spray-coating demonstrate the potential applicability in biomedical applications where high transparency, patternability, and low bio-adhesion are needed. Another important application is preventing biofouling in membranes for water purification. Here we report the first oligoaniline grafted water filtration membranes by modifying commercially available polyethersulfone (PES) ultrafiltration (UF) membranes. The modified membranes are hydrophilic as demonstrated by captive bubble experiments and exhibit extraordinarily low bovine serum albumin (BSA) and Escherichia coli adhesions. Superior membrane performance in terms of flux, BSA rejection and flux recovery after biofouling are demonstrated using a cross-flow system and dead-end cells, showing excellent fouling resistance produced by the in situ modification

Association between Medicaid expansion status and lung cancer screening exam growth: findings from the ACR lung cancer registry.

PURPOSE: To determine if Medicaid expansion is associated with increased volumes of lung cancer screenings. METHODS: A quasi-experimental study was performed to compare the annual growth rates in lung cancer screenings between states that expanded Medicaid (n = 31) versus those that did not (n = 17). Using the American College of Radiology Lung Cancer Screening Registry, we calculated the average annual growth rate between 2016 and 2019 for both groups. Secondary analyses between these two groups also included calculations of the percentages of studies considered appropriate by USPSTF criteria. RESULTS: No significant difference was identified in the average annual growth in lung cancer screenings between Medicaid expanding and non-expanding states (57.6%, 50.3%, P = 0.51). No difference was observed in the percentage of studies considered appropriate (Medicaid expanding = 89.6%, non-expanding = 90.2%, P = 0.72). At baseline, there were socioeconomic differences between both groups of states. Medicaid expanding states had a more urban population (76.5% versus 67.9%, P = 0.05) and higher average incomes ($56,947,$49,876, P \u3c 0.05). CONCLUSION: No association is found between Medicaid expansion and increasing volumes of lung cancer screening exams. Although no data is available in the registry for screening exams before the implementation of Medicaid expansion (2014), most nationwide estimates of lung screening rates report a low baseline (\u3c5%). Furthermore, despite being advantaged in other ways, such as with a more urban population or with higher incomes, the Medicaid expansion cohort does not demonstrate a higher growth rate. These findings suggest Medicaid expansion alone will not increase lung cancer screenings

Programmatic use of molecular xenomonitoring at the level of evaluation units to assess persistence of lymphatic filariasis in Sri Lanka

BACKGROUND:Sri Lanka's Anti Filariasis Campaign distributed 5 rounds of mass drug administration (MDA with DEC plus albendazole) to all endemic regions in the country from 2002-2006. Post-MDA surveillance results have generally been encouraging. However, recent studies have documented low level persistence of Wuchereria bancrofti in Galle district based on comprehensive surveys that include molecular xenomonitoring (MX, detection of filarial DNA in mosquitoes) results. The purposes of this study were to demonstrate the use of MX in large evaluation units (EUs) and to field test different mosquito sampling schemes. METHODOLOGY/PRINCIPAL FINDINGS:Galle district (population 1.1 million) was divided into two EUs. These included a coastal EU with known persistent LF and an inland EU with little persistent LF. Mosquitoes were systematically sampled from ~300 trap locations in 30 randomly selected clusters (health administrative units) per EU. Approximately 28,000 Culex quinquefasciatus were collected with gravid traps and tested for filarial DNA by qPCR. 92/625 pools (14.7%) from the coastal EU and 8/583 pools (1.4%) from the inland EU were positive for filarial DNA. Maximum likelihood estimates (MLE) for filarial DNA rates were essentially the same when the same number of mosquito pools were collected and tested from 75, 150, or 300 trap sites (range 0.61-0.78% for the coastal EU and 0.04-0.07% for the inland EU). The ability to use a smaller number of trap sites reduces the cost and time required for mosquito sampling. CONCLUSIONS/SIGNIFICANCE:These results suggest there is widespread persistence of W. bancrofti infection in the coastal Galle EU 8 years after the last round of MDA in 2006, and this is consistent with other data from the district. This study has shown that MX can be used by national programs to assess and map the persistence of W. bancrofti at the level of large EUs in areas with Culex transmission

Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting

We present an analytical method to quantify clustering in super-resolution localization images of static surfaces in two dimensions. The method also describes how over-counting of labeled molecules contributes to apparent self-clustering and how the effective lateral resolution of an image can be determined. This treatment applies to clustering of proteins and lipids in membranes, where there is significant interest in using super-resolution localization techniques to probe membrane heterogeneity. When images are quantified using pair correlation functions, the magnitude of apparent clustering due to over-counting will vary inversely with the surface density of labeled molecules and does not depend on the number of times an average molecule is counted. Over-counting does not yield apparent co-clustering in double label experiments when pair cross-correlation functions are measured. We apply our analytical method to quantify the distribution of the IgE receptor (Fc{\epsilon}RI) on the plasma membranes of chemically fixed RBL-2H3 mast cells from images acquired using stochastic optical reconstruction microscopy (STORM) and scanning electron microscopy (SEM). We find that apparent clustering of labeled IgE bound to Fc{\epsilon}RI detected with both methods arises from over-counting of individual complexes. Thus our results indicate that these receptors are randomly distributed within the resolution and sensitivity limits of these experiments.Comment: 22 pages, 5 figure

Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1) is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs) previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for therapy of bovine and canine neosporosis

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research