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In this present study physicochemical composition of 6 mango varieties (Tommy, Kent, Keitt, Dodo, Local and Apple mango) were characterized on the bases of their suitability for jam preparation. According to the results of fruit physicochemical analysis, apple mango varieties was observed for best Total Soluble Solids (17.06%), Total Solids (15.57%), and Moisture Content (71.30%), Ash Content (0.36%), Reducing Sugars (2.63%), pH (3.33) and Titratable Acidity (0.27 mg/100 g). In the later study, investigated the effect of pH in two levels (3 and 3.3) pectin in three levels (0, 1 and 1.5%) and sugar amount in two levels (50 and 60%) on quality of apple mango jam. Analysis of variance was carried out using Minitab 18.1 software. Jam sample formulated with pectin (1.5%), sugar (60%) and pH (3.3) reported high vitamin C content and TS and also more acceptable in appearance, flavor, consistency, color and overall acceptability by the sensory panelists. Finally, the quality of the jam is highly dependent on the concentrations of each ingredient. Keywords: Acidity, Jam, Mango cultivars, Pectin, Sugar

The current work envisages synthesis of an ester prodrug of flurbiprofen whereby its carboxylic group was condensed with a skeletal muscle relaxant methocarbamol, with the aim of synergistic activity of two drugs, avoid flurbiprofen mediated gastro-intestinal damage and minimize the ulceration tendency of flurbiprofen. The synthesized prodrug was characterized and confirmed by physicochemical and spectroscopic studies. Solubility and partition coefficient studies indicated an increased lipophilicity and thus better suitability for oral administration than the parent drugs and the protein binding studies revealed a low protein binding capacity of the mutual prodrug. Subsequently, in-vitro hydrolysis was studied in different pH, simulated gastric fluid, simulated intestinal fluid and plasma and quantitative evaluation was performed by high performance liquid chromatography. It was found that the prodrug remained unhydrolyzed in the stomach after absorption however, underwent rapid cleavage by the esterases in blood to give the parent drug. Furthermore, the mutual ester prodrug was evaluated for its anti-inflammatory, analgesic, skeletal muscle relaxation, ulcerogenic and total acid content activity and was found to possess comparable activity with that of the parent drugs. Microscopic structures of the stomach tissues revealed significant reduction in gastric ulcer formation of mice gastric mucosa as compared to parent carboxylic acid drug.

A hybrid Mg composite filled with micro Al2O3 and nano TiO2 is manufactured through a blend press sinter powder metallurgy route. To appraise the significance of filler incorporation on the mechanical and corrosion strength, the composite is undergoing a series of characterizations. Initially the filler distribution was analyzed through electron microscopes. Static mechanical tests as per ASTM are conducted to measure the influence of fillers on the tensile and compression properties. The corrosion characteristics were studied by immersing the composites into the laboratory synthesized stimulated body fluid (SBF). Through the Tafel Polarization, the corroded surfaces are examined. The corrosion resistance of the composites exhibited a change that closely resembled that of pure magnesium. Based on the experimental findings, it appears that the composite being examined is well-suited for various biomedical applications, particularly in the field of dental implants.

Childhood malnutrition is a major problem in developing countries, particularly in Ethiopia. This study aimed to create nutritious emmer wheat and cowpea extruded porridge with optimal macronutrient levels and sensory quality. Utilizing Design-Expert software, the effects of cowpea blending ratios (10–25 %), barrel temperatures (80–120 °C), and feed moisture content (22–26 %) were analyzed using a three-factor, three-level Box-Behnken design. Significant impacts on nutritional characteristics were observed, leading to the identification of optimal extrusion conditions (cowpea blend: 20.17 %, moisture content: 25.91 %, barrel temperature: 117.20 °C). Blending emmer wheat with cowpea flour significantly enhanced the porridge's color, taste, and aroma. The highest color intensity (4.36 %) was at 10 % cowpea and 22 % moisture processed at 100 °C. The best taste (4.41 %) was with 25 % cowpea and 22 % moisture at 100 °C, while the highest aroma was in blends with 10 % and 25 % cowpea at 100 °C. The control had the best mouthfeel (4.36 %), but a blend with 25 % cowpea, 24 % moisture, and 80 °C barrel temperature had the highest overall acceptability (4.31 %). The study highlighted the potential of these protein-rich porridge products to address protein-energy malnutrition, particularly in Ethiopia, by introducing awareness about the unique nutritional composition of Ethiopian emmer wheat and underutilized cowpea, thus creating a new market for nutritious food options.

Injera, bread, and other baked Ethiopian foods are typically made from a single cereal grain, which is insufficient to meet the nutritional requirements of all age groups. Enrichment of cereal with easily affordable cereals and pseudocereals that have superior nutritional value is an important approach to producing nutrient-dense food products. Therefore, this study aimed to evaluate the nutritional composition, phytochemical content, functional and pasting properties of teff, pearl millet, and buckwheat composite flour. The design used during the conducting of the experiment was a completely randomized design (CRD). The nutritional composition, functional and pasting properties of composite flour were determined using standard procedures. The resulting composite flour from the study contained protein of 8.59–9.94 %, crude fat of 3.70–5.40 %, crude fiber of 2.28–2.62 %, total ash of 1.86–2.28 %, carbohydrate of 71.80–74.90 % and energy of 367.24–375.88 kcal/100 g. The mineral content (mg/100 g) ranged from 8.64 to 11.12, 72.82–93.14, and 1.32–1.74 iron, calcium, and zinc, respectively. Functional properties of composite flours such as bulk density (BD), water absorption index (WAI), and water solubility index (WSI) ranged from 555.08 to 596.23 kg/m, 2.12–2.18 g/g and 6.63–7.00 % respectively. The highest and lowest total phenolic content values were observed in composite flour of 10 % pear millet,70 % teff, and 20 % buckwheat (110.42 mg GAE/100 g) and composite flour of 40 % pear millet,55 % teff, and 5 % buckwheat (101.42 mg GAE/100 g), respectively. The addition of pearl millet and buckwheat flours to teff flour significantly (p ˂ 0.05) increases the functional and pasting properties of composite flour. Pasting properties of composite flours contained peak viscosity ranging from 1454 to 2071cP, trough viscosity 619–883cP, breakdown viscosity 835–1188cP, setback viscosity 1127–1483cP, pasting temperature 73.77–75.10 °C, and peak time 5.22–5.27 min. Pearl millet, buckwheat, and teff are three gluten-free grains that are increasingly being used in industrial applications. Teff, pearl millet, and buckwheat composite flour are all high in nutrients, and they offer a variety of health benefits. Blending these three grains can create a nutritious and delicious product that is also gluten-free. This study found that composite flour made from 70 % teff, 20 % buckwheat, and 10 % pearl millet has improved nutritional properties and could be used to make healthier food products in the food industry.

(a) Background: Technological advancement in the recent years has enabled the application of single photon emission tomography (SPECT) to evaluate myocardial blood flow (MBF). This method offers increased sensitivity in the assessment of coronary health, quantifiable through non-invasive imaging beyond the more conventional methods such as with myocardial perfusion imaging (MPI). (b) Aims: To correlate MBF, derived by dynamic SPECT, both global and by coronary territories to the summed stress scores (SSS) on conventional MPI. (c) Methods: Images obtained from dipyridamole-gated SPECT MPI stress and rest studies performed on recruited subjects were examined. We calculated the global and regional coronary flow reserve (CFR) via a standard software package, taken as the ratio of stress MBF to rest MBF, using CFR 50%). We observed a progressive reduction in global and regional CFR across the normal SSS category to that of severely abnormal (SSS >13). Reduced global CFR with correspondent lower CFR across the regional arteries were detected in scans within normal limits of MPI scans in subjects who were older (69 ± 7 vs. 62 ± 9 years, p = 0.034). Decreasing CFR was significantly associated with increasing age across the regional arteries. (e) Conclusion: In our study we depict the global and regional MBF values obtained via SPECT MPI in correlation to the respective SSS categories. Our data proposes that dynamic SPECT has a part in refining cardiac risk stratification, particularly in the older adult population, who are at greater risk.

Cereal crops dominate crop production and human diet in Ethiopia. In the present study major cereal crops production data for Ethiopia was analyzed using time-series analysis. Major cereal crops production of years 2000/01 to 2020/21 at national level of private peasant holdings during “Meher” season in Ethiopia was used as input to forecast the cereal crops production up to the year 2020 to 2030. The non-parametric Mann Kendall trend test was used with PAST (Paleontological Statistics Software Package for Education and Data Analysis) software to conduct the trend test. The Box-Jenkins Aautoregressive Integrated Moving Average (or ARIMA) method was put into use to forecast the production. The result shows that grain production had a significant increasing trend. Despite the differences in magnitude, all crops showed an increasing trend in production over the years. Mann-Kendall trend test showed significant trend for all crops. ARIMA and any of the smoothing models were found good in terms of R2 and AIC. Predictions of cereal crops production using ARIMA between 2020 and 2030 years showed increasing trends in all crops. Teff was forecasted from 5.8 tons at the beginning (2020/1) to 7.8 tons at the end of the forecast period (2030). Similarly, maize was forecasted from about 11 to 14, wheat from 6 to 7.5, sorghum from 5 to 7, and barley from 2.3 to 2.7. Increments ranged in between about 20% to 40%.

The papain-like protease (PLpro) of SARS-CoV-2 (COVID-19) is a high-profile drug target for treating COVID-19 due to its critical role in making essential proteins crucial in viral replication and host immune sensing. The development of small molecule inhibitors of PLpro is an area of ongoing research and interest. To investigate the development of PLpro inhibitors, a series of novel flavanone derivatives were designed using in silico docking against the papain-like protease of COVID-19. The most promising targets were synthesized and structurally characterized by NMR and mass spectrometry. Using isothermal calorimetry studies, two synthesized derivatives were found to bind PLpro in the low micromolar to nanomolar range.

Reducing post-harvest loss conserves resources such as natural, human, and financial inputs that help reduce poverty, raise household incomes, and improve rural livelihoods. The plant-based protein, higher unsaturated fat content, and higher fiber value of groundnuts make them preferable for nutrition enhancement. Groundnut is also well known for its environmental significance, as it reduces the use of chemical fertilizer by fixing nitrogen from the air and enriching soil fertility. However, there are few published scientific reports on groundnut post-harvest loss assessment in African countries. Moreover, published studies of groundnut post-harvest loss focused primarily on biodeterioration during storage. Hence, this review aimed to assess the underlying causes, extent of post-harvest quality and quantity loss of groundnut in the supply chain, and post-harvest loss mitigating technologies in Africa and their implications for food and nutrition security. This review found that the higher drudgery required in the groundnut supply chain is a limiting factor for smallholder farmers in sub-Saharan African countries. Groundnut qualitative and quantitative post-harvest loss is higher during groundnut pod stripping and shelling and also during on-farm and warehouse storage of groundnut in the supply chain. Post-harvest losses of groundnut in African countries extend from 8.9% (Ghana) to 31% (Uganda). Higher-quality groundnut producers do not receive a higher market price as traders and processing factories do not test for aflatoxin content during purchase, which lets producers not follow labor- and cost-demanding good agricultural practices. In conclusion, adopting and providing improved groundnut varieties, aflatoxin control mechanisms, and post-harvest technologies of higher efficiency, lower cost, and local availability should be carried out. In addition, public awareness of aflatoxin toxicity and mitigation measures should be widely disseminated.

IgG4-related disease (IgG4-RD) is an immune-mediated inflammatory condition of unknown etiology characterized by invasion of tissue by IgG4-producing plasma cells. It can affect almost any organ system, but central nervous system involvement is a rare occurrence. A careful clinicopathological correlation is required to establish the diagnosis. The condition is highly treatable with glucocorticoids, but it is likely that it is underdiagnosed. Although IgG4-related disease responds quickly to glucocorticoids, if left untreated, can lead to end-stage organ failure and even death. We present a case of a 46-year-old female patient who presented with headache, tingling, numbness, flickering movement in her left lower limb gradually extending to torso and head, and loss of consciousness. After radiological and immunohistochemical studies, the diagnosis of IgG4-related hypertrophic pachymeningtis was confirmed. Corticosteroid therapy was administered, and the patient symptomatically improved. Clinicians should be aware of this rare condition, and the importance of early diagnosis and appropriate corticosteroid therapy should be emphasized.

Latent tuberculosis infection (LTBI) constitutes an important public health problem because of risk of progression to TB disease. Effective treatment of multi-drug resistant (MDR) LTBI would prevent progression to MDR TB disease, which would improve patient and public health outcomes. The majority of MDR LTBI treatment studies have focused on the use of fluoroquinolone-based antibiotic regimens. Options for and experience in the treatment of fluoroquinolone-resistant MDR LTBI are limited in the published literature and not comprehensively addressed in current guidelines. In this review, we share our experience with the treatment of fluoroquinolone-resistant MDR LTBI with linezolid. We discuss treatment options for MDR TB that provide context for predicting effective MDR LTBI treatment, with a focus on the microbiologic and pharmacokinetic properties of linezolid that support its use. We then summarize the evidence for treatment of MDR LTBI. Finally, we present our experiences treating fluoroquinolone-resistant MDR LTBI with linezolid with an emphasis on dosing considerations to optimize efficacy and minimize potential toxicities.

Intro: Leptospirosis is an emerging zoonotic tropical disease caused by bacteria of the genus Leptospira. The condition is an increasingly global public health challenge facilitated by environmental and socioeconomic factors. Hence, we conducted this systematic review to determine the significant predisposing factors of the disease transmission. Methods: We prepared an a priori protocol for this systematic review and conducted a literature search from Ovid, PubMed, and Scopus databases. The searched articles were identified, screened, and evaluated for quality through the risk of bias assessment, which led to the extraction of relevant data in the study. As a result, we retrieved 927 articles from the databases; however, only 23 have passed the screening processes and were involved in this article. Findings: We found various studies recorded within the study period with a wide range of sporadic incidence. Association with rodents had the highest mean incidence (40.53%), the least being proximity to sewers (2.18%) among the environmental variables. Low income (9.32%) and occupational exposure (9.06) are the socioeconomic factors of leptospirosis transmission, with a high percentage of incidences. Discussion: Leptospirosis, an emerging tropical and subtropical bacterial zoonosis has been on the rise worldwide. The spread of the bacteria to humans is partly due to associated transmission factors such as rodents and other animals, recreational activities, and proximity to water bodies Conclusion: Environmental and socioeconomic risk factors contribute to the transmission of leptospirosis; their management could help to minimize the disease transmission.

Pectin-based edible film plasticized with glycerol has been developed, and the effect of pectin and glycerol concentration was optimized using response surface methodology for better mechanical properties and transparency. The upper and lower concentration of pectin (3–5 g) and glycerol (15%–25%) concentration ranges were considered in this study based on the preliminary experiment. The responses of the edible film determined were tensile strength, elongation at break and elastic modulus and opacity. The interaction effects of glycerol and pectin concentrations on edible film properties significantly affected the film properties. Tensile strength and opacity were positively affected by pectin concentrations; however, elastic modulus and elongation at break were negatively affected. Glycerol concentration negatively affected the edible film's tensile strength and elastic modulus. The decrease in the opacity of the biofilm was observed as the pectin concentration increased; however, glycerol had not shown a significant influence on opacity. The numerical optimization provided 4 g of pectin, and 20% of glycerol showed a strong and transparent edible film. The TGA curve showed that the maximum weight loss occurred between the temperatures 250–400 °C due to the loss of polysaccharides. From FTIR analysis, observed peaks around 1037 cm−1 represented the C–O–C stretching vibrations of the saccharide found in pectin and glycerol.

The non-biodegradable synthetic plastic is one of the greatest challenges facing the food packaging business since it seriously harms the environment. To solve this problem, non-biodegradable plastic may be disposed of more affordably and with less harm on the environment by using edible starch-based biodegradable film. Therefore, the present study was focused on the development and optimization of tef starch based edible films based on mechanical properties. In this study response surface methodology was employed by considering 3–5g of tef starch, 0.3–0.5% of agar and 0.3–0.5% of glycerol. The prepared film showed the tensile strength of 17.97–24.25 Mpa, elongation break of 1.21–2.03%, elastic modulus of 17.58–108.69 MPa, puncture force of 2.55–15.02 N, puncture formation of 9.59–14.95 mm. The findings showed that as glycerol concentrations in the film-forming solution increased, the prepared tef starch edible films' tensile strength, elastic modulus, and puncture force declined while their elongation at break and puncture deformation increased. Tef starch edible films' mechanical characteristics, including as tensile strength, elastic modulus, and puncture force, were increased by the increase of agar concentration. The optimized (from 5 gm tef starch, 0.4 g agar and 0.3% glycerol) tef starch edible film exhibited higher tensile strength, elastic modulus, and puncture force while lower elongation at break and puncture deformation. The composite edible film based tef starch with agar exhibited good mechanical properties and can be suggested for application in food industry as food packaging.

The burdens associated with acute gastroenteritis involve billions of dollars in expenses, coupled with significant morbidity and mortality globally. To reduce these burdens, health officials and policymakers require up-to-date data (health and economic) to request and allocate resources in guiding the development and implementation of preventative strategies. In 2021, the estimate for one case of acute gastroenteritis was calculated using multiple sources of data: the 2009 national health burden survey on acute gastroenteritis; a 2021 telephone survey of five major private hospitals; a 2021 telephone survey of 30 private pharmacies; and the 2021 Minimum Wages Act of Trinidad and Tobago. For each case of illness, an average cost of $1614 TTD ($238 USD) was estimated. For residents who sought private health care, the average GP visit cost was $500–$700 TTD ($73–$103 USD), while costs for medication prescribed ranged between $327 and $1166 TTD ($48–$172 USD). Productivity losses amounted to almost $21.7 million TTD ($3.2 million USD) for residents who took time off from work or required caregiving services. The overall annual cost was estimated to be $204 million TTD ($30.1 million USD) and, therefore, warrants measures by health officials to reduce the economic and social burdens of acute gastroenteritis in Trinidad and Tobago.

Orange Fleshed Sweet Potato (OFSP) tuber is a rich source of β-carotene with potential antioxidants and phenolic compounds, nevertheless it is highly perishable root crop. Hence, we considered the optimization of parameters for the preparation of OFSP powder in spray drying technique. This study was designed by the Response Surface Methodology (RSM) with three factors in three levels considered in Central Composite Design (CCD). In case of spray drying process specification, inlet air temperature (IAT) (150 °C–190 °C), flow rate (FR) (10–20 ml/min), and carrier (Maltodextrin) concentration (MDC) (5–15%) were considered and optimized for better quality OFSP powder. As concentration of maltodextrin increased the powder yield, solubility, β-carotene content of OFSP powder increased, while hygroscopicity is decreased. The optimized conditions comprised of an inlet temperature of 172.71 °C, feed flow rate of 20 ml/min, and maltodextrin of 1% concentration. Under this optimized conditions, OFSP powder yield of 48.460%, with the solubility of 26.839%, β-carotene of 25.823 mg/100 g and minimum hygroscopicity of 13.862% was attained. The SEM images of spray-dried OFSP powder produced from the optimized conditions showed hexagonal in shapes, irregular in arrangement and compact. The OFSP powder had lower relative crystallinity (34.7%). In conclusion, the optimized OFSP powder with highest β-carotene and desirable physiochemical properties was produced and it can effectively utilize in the food formulation products.

This study was conducted to evaluate the effect of storage materials (Storage bags) and durations on seed quality and proximate composition of emmer wheat in farmer storage practices. The emmer wheat samples were stored for nine consecutive months in PICS (Purdue Improved Crop Storage) bag (PB), Grainpro® Bag (GPB), Polypropylene Bag (PPB), emmer wheat treated with Filter Cake (a byproduct of Aluminum Sulphate factory) (FC), stored in Polypropylene bag (PPBFC) and Emmer wheat treated with triplex (a by-product of soap factory) (TX) stored in Polypropylene bag (PPBTX). Data on seed quality and proximate composition were evaluated every three months’ interval for 9 months. As storage period increased from three to nine months; Germination Percentage, Speed of Germination, Vigour, Thousand Seed Weight (TSW), Bulk Density (BD), Seed Damage%, Seed Weight Loss, Protein and Carbohydrate contents were significantly influenced by the interaction effect of storage period and storage bag used. The highest germination (98%) was recorded from seeds stored in GPB for three months. The protein content of grains stored in GPB for three months showed the highest (8.3%) whereas, the lowest (6.5%) was for PPB at nine months of storage. Minimal insect incidence and lower seed weight loss were observed in emmer wheat stored in bags such as BP, GPB, PPBFC, and PPBTX. The use of PB and GPB, as well as the application of FC and TX maintained the proximate and seed quality of emmer wheat.

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are the producers of the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). Welding fumes have been classified as carcinogenic to humans (Group 1) by the WHO International Agency for Research on Cancer (IARC) in IARC Monograph 118; this assessment found sufficient evidence from studies in humans that welding fumes are a cause of lung cancer. In this article, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from trachea, bronchus, and lung cancer attributable to occupational exposure to welding fumes, to inform the development of WHO/ILO Joint Estimates on this burden of disease (if considered feasible). Objectives: We aimed to systematically review and meta-analyse estimates of the effect of any (or high) occupational exposure to welding fumes, compared with no (or low) occupational exposure to welding fumes, on trachea, bronchus, and lung cancer (three outcomes: prevalence, incidence, and mortality). Data sources: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CENTRAL and CISDOC. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. Study eligibility and criteria: We included working-age (≥15 years) workers in the formal and informal economy in any Member State of WHO and/or ILO but excluded children (

Abstract Background Low cardiorespiratory fitness (CRF), high body mass index, and excess visceral adiposity are each associated with impairment in left ventricular (LV) peak circumferential strain (Ecc), an intermediate phenotype that precedes the development of clinical heart failure (HF). However, the association of regional fat distribution and CRF with Ecc independent of each other and other potential confounders is not known. Methods Participants from the Dallas Heart Study Phase 2 who underwent dual energy X-ray absorptiometry assessment of regional fat distribution, CRF assessment by submaximal treadmill test, and Ecc quantification by tissue-tagged cardiovascular magnetic resonance were included in the analysis. The cross-sectional associations of measures of regional adiposity, namely visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and lower-body fat (LBF) with Ecc after adjustment for CRF and other potential confounders (independent variables) were assessed using multivariable linear regression analysis. Results The study included 1089 participants (55% female, 39% black). In the unadjusted analysis, higher VAT was associated with greater impairment in Ecc. After adjustment for baseline risk factors, CRF, parameters of LV structure and function, and other fat depots such as SAT and LBF, higher VAT remained associated with greater impairment in Ecc (β: 0.19, P = 0.002). SAT and LBF were not significantly associated with Ecc, however, CRF remained associated with Ecc in the fully adjusted model including all fat depots (β: − 0.15, P

Summary: Biomedical health interventions now have global reach and interact in complex and often poorly understood ways with traditional medical rituals that precede biomedicine. People often experience biomedical practices and treatments as rituals because they are very similar from an experiential perspective.1 Yet the global public health community often views ritual practices of communities as obstacles to adopting new health-promoting behaviors. The lack of engagement with the biomedical and traditional medical rituals of local populations has obscured understanding the critical functions of these behaviors, limited the potential to leverage ritualization to increase behavioral uptake, and stymied social and behavioral change efforts. Our large-scale, mixed methods research with Community Health Workers (CHW) in Bihar, India, has shown that understanding the rituals of a community provides critical insight into their identities, norms, values, and goals. We propose that health interventions should be informed by, and build upon, knowledge of health rituals. A deep understanding of existing beliefs and behaviors will allow local health ''influencers'' such as CHW to encourage new and modified rituals that integrate the best of biomedical and traditional health practices in ways that preserve their meaning and shared purpose. Funding: Grants INV-008582 and INV-016014 to C.L. from The Bill & Melinda Gates Foundation funded this manuscript.

The data provided in this article is the genomic sequence of new Leptospira isolate, Leptospira interrogans strain HP358 (L. interrogans HP358) isolated from rodent, Sundamys muelleri (S. muelleri), captured from the human leptospirosis suspected area, in forest environment, Hulu Perdik, Selangor. The kidney of the rodent was cultured, and the genomic DNA of pure Leptospira isolate was extracted and sequenced. The de novo assembly of genome generated 118 contigs with N50 of 133,176bp. The genome size of the L. interrogans HP358 was determined with a length of 4,808,724 and 35.01% G+C content with 229 subsystems, 5236 coding sequences and 39 RNAs. The whole genome shotgun project has been deposited in NCBI GenBank under the accession number JAFCYY000000000.1.

Purpose and objectives: Detection of drug resistance plays a crucial role in tuberculosis (TB) treatment and prevention of Mycobacterium tuberculosis (MTB) transmission. The aim of this study was to determine the levels and patterns of resistance of MTB isolates to two key anti-TB drugs (rifampicin, RIF and isoniazid, INH) and the type of mutations in drug resistance genes (rpoB, katG and inhA) of the isolates at the southern coastal region of Andhra Pradesh, India, using commercially available GenoType MTBDRplus assay under the Revised National TB Control Program. Methods: GenoType MTBDRplus assay was performed on 2859 sputum smear-positive samples and the mutations in the genes responsible for resistance (rpoB, katG and inhA) were analyzed. Results: Among the line probe assay (LPA) valid isolates (2894), 1990 (68.76%) were drug susceptible, 437 (15.13%) were INH monoresistant, 104 (3.59%) were RIF monoresistant, and 363 (12.54%) were multidrug resistant. Codon 531 of rpoB gene and codon 315 of katG gene were found to have the highest mutation frequency for RIF resistance (270/467; 57.81%) and INH resistance (501/800; 62.62%), respectively. The RIF resistant rpoB mutations observed in the samples were S531 L (57.81%), H526Y (8.56%), D516 V (6.42%), and H526D (6.20%). Mutations in inhA promoter were found in 24.75% INH resistant isolates with C15 T being the most common (85.85%). The turnaround times of the LPA test were from 48 to72 h. Conclusion: The frequency of mutations in MTB in the coastal region of Andhra Pradesh, India, is similar to that in retreatment cases from most settings, with close to 80% in rpoB codon 516, 526, and 531, and over 80% in codons katG 315 and/or inhA promoter. The increase in INH monoresistance underlines the need for greater enforcement of national TB control programs. Keywords: Multidrug resistance, Mycobacterium tuberculosis, MTBDRplus assay, Mutations, Molecular detection

Background: Leptospirosis is often misdiagnosed with several other tropical febrile illnesses in Malaysia due to similarities in clinical manifestations. Although treatment regimens could be started based on clinical judgments, early diagnosis has become paramount as a guide to chemotherapeutic interventions. Confirmed laboratory diagnosis through MAT or PCR is time consuming and usually available only in reference laboratories and not practical in healthcare settings. Rapid and easy to perform diagnostic tests are widely used in these settings as the point of care diagnosis. The present study was undertaken to compare the diagnostic performance of two IgM based immunodiagnostic assay kits for acute leptospirosis. Methods: A total of 50 serum samples were collected from patients clinically suspected for acute leptospirosis on admission in the Hospital Serdang, from June 2016 to June 2017. All the samples were subjected to MAT, lipL32 PCR and the two rapid tests (Leptocheck-WB and ImmuneMed Leptospira IgM Duo Rapid test). Results: Out of the 50 clinically suspected patients sampled, 19 were confirmed positive for leptospirosis. Six (12%) were confirmed by MAT and 13 (26%) by PCR. Similarly, of the 50 clinically suspected cases, 17 (34%) showed positivity for Leptocheck-WB and 7 (14%) for ImmuneMed Leptospira IgM Duo Rapid test. The overall sensitivity and specificity was 47.37% and 80.65% for Leptocheck-WB, and 21.05% and 90.32% for ImmuneMed Leptospira IgM Duo Rapid test. In another set of previously confirmed MAT positive samples (1:400–1:3600) obtained from a reference laboratory, Leptocheck-WB showed higher sensitivity (90.72%) than ImmuneMed Leptospira IgM Duo Rapid test (40.21%), and comparable specificity for ImmuneMed Leptospira IgM Duo Rapid test (88.89%) and Leptocheck-WB (82.86%). Conclusion: The sensitivity was higher for Leptocheck-WB and had a comparable specificity with ImmuneMed Leptospira IgM Duo Rapid test. Therefore, based on the present study, Leptocheck-WB is found to be a more sensitive rapid immunodiagnostic test for acute leptospirosis screening in hospital settings. Keywords: Leptospirosis, Rapid diagnostic test, ImmuneMed Leptospira IgM Duo Rapid test kit, Leptocheck-WB rapid diagnostic kit, Malaysia

Background: In 2019, the World Health Organization released guidelines reflecting major changes in multidrug-resistant tuberculosis (MDR-TB) management—prioritizing fluoroquinolones, bedaquiline, and linezolid (LZD) while de-emphasizing previously favored injectable agents. In some cases, linezolid use is associated with gastrointestinal intolerance, mitochondrial toxicity, and significant drug interactions. CDC’s Division of Tuberculosis Elimination supports a network of regional TB Centers of Excellence, which provide medical consultation to healthcare providers. Consultations are documented in a medical consultation database (MCD) enabling evaluation of management questions and recommendations. We describe the scope of clinical inquiries and responses specific to linezolid use for MDR-TB in the US. Research Question: What are the major themes of provider and patient challenges regarding the use of linezolid for the treatment of MDR-TB in the US? Methods: We queried MCD consults categorized as “MDR/XDR-TB” from 1/1/2013 to 12/31/2018. Only linezolid-specific consultations were included; incomplete and duplicate entries were excluded as were those citing linezolid historically or theoretically. Subgroup characteristics were assessed (e.g., Center, year, provider type). A descriptive coding scheme was developed through inductive thematic analysis. Results: In 2013–2018 of the 1889 consults regarding MDR/XDR-TB, 934 MDR-TB consults referenced linezolid; 137 met inclusion criteria, representing between 4 and 10% of MDR-TB consults annually. Four main themes emerged: adverse effects (71.5%); concerns about linezolid use due to co-morbidities or concurrent medication use (15.3%); dosing adjustments (8.8%); and monitoring and maintenance logistics (4.4%). Interpretations: Linezolid consults consistently exceeded 4% of all consults annually over the 6-year period, suggesting a need for access to expert opinion for providers using linezolid to manage MDR-TB. While only a snapshot of MDR-TB in the US, this evaluation summarizes major provider concerns regarding particular adverse effects, and highlights a need for evidence-based guidance regarding linezolid dosing and toxicity management.

Leptospirosis is an important zoonotic bacterial disease caused by Leptospira spp. Earlier studies from North Khorasan province (Iran) reported the presence of Leptospira in wild canines and rodents. To date, there is no data on the seroprevalence of leptospirosis among humans in this province. This study was performed to determine the prevalence of human leptospiral infection among people with different occupations. The study was conducted in urban and rural areas of the province. Among the serum samples collected from 278 subjects, 3 (1.1%) showed positive reaction with titer of 1:100 by the microscopic agglutination test (MAT). Positive reactions were detected against Leptospira interrogans Canicola and L. interrogans icterohemorrhagic and all these samples were from livestock farmers (n = 3/106, 2.7%). The current study revealed that, though Leptospira infection is low in North Khorasan province, regular monitoring of the livestock and the farmers are important.

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Welding fumes have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer (IARC); this assessment found sufficient evidence from studies in humans that welding fumes are a cause of lung cancer. In this article, we present the protocol for a systematic review of parameters for estimating the number of deaths and disability-adjusted life years from trachea, bronchus and lung cancer attributable to occupational exposure to welding fumes, to inform the development of the WHO/ILO Joint Estimates. Objectives: We aim to systematically review and meta-analyse estimates of the effect of occupational exposure to welding fumes on trachea, bronchus and lung cancer, applying the Navigation Guide systematic review methodology as an organizing framework. Data sources: We will search electronic bibliographic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, and CISDOC. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand search reference list of previous systematic reviews and included study records; and consult additional experts. Study eligibility and criteria: We will include working-age (≥15 years) workers in the formal and informal economy in any Member State of WHO and/or ILO but exclude children (

We provide notes on how to use a graphical user interface (GUI), implemented with MATLAB, for aligning imaging datasets of biological tissue. The original use was for matching two imaging data sets, where one set was taken of the living preparation and another was taken post-fixation and following immunohistochemical processing. This technique is described in detail in an accompanying paper (Parrish et al., [1], where we also include information about the experimental procedures, and examples of the usage of the GUI. Keywords: Pyramidal neurons, Interneurons, Glia, Astrocytes, MATLAB, Immunohistochemistry, Ca2+ imaging

Summary: Background/purpose: The purpose of this study is to characterize GBS isolates that were collected from three major hospitals in a densely populated area of Klang Valley for their demographics, serotypes, antibiotic susceptibility patterns and genetic background. Methods: Sixty GBS isolates from sterile and non-sterile samples in three major hospitals in the Klang Valley area of Malaysia were collected by convenience sampling from 2012 until March 2014. These isolates were studied for their antimicrobial susceptibilities, serotypes and genotypes. Patients’ demographic data and clinical information were collected from lab request forms. Results: Diabetes mellitus was the only underlying condition (7 patients, 23.3%); the remaining samples were from patients who were immunocompromised due to medications. Fifty-nine (98%) isolates were sensitive to penicillin, while 78.3% and 88.3% of the isolates were sensitive to erythromycin and clindamycin, respectively. Serotype Ia was the most common serotype (n = 27, 45%), followed by serotype III (n = 10, 16.7%), V (n = 9, 15%), VI (n = 8, 13.3%), VIII (n = 2, 3.3%) and VII (n = 1, 1.7%). Random Amplified Polymorphic DNA (RAPD) typing showed a diverse genetic pedigree for all isolates, including four major groups that clustered according to geographical location. Conclusion: This preliminary study determines the prevalence of limited common serotypes and antimicrobial resistance in distinct GBS isolates. Nonetheless, the RAPD clustering pattern suggests a close genetic lineage of the GBS isolates based on their isolation sites and location of hospitals. Keywords: Group B Streptococcus, Resistant, Serotype

The current tuberculosis (TB) case reporting system for the United States, the Report of Verified Case of TB (RVCT), has minimal capture of multidrug-resistant (MDR) TB treatment and adverse events. Data were abstracted in five states using the form for 13 MDR TB patients during 2012–2015. The Centers for Disease Control and Prevention Guidelines for Evaluating Public Health Surveillance Systems were used to evaluate attributes of the form. Unstructured interviews with pilot sites and stakeholders provided qualitative feedback. The form was acceptable, simple, stable, representative, and provided high-quality data but was not flexible or timely. For the 13 patients on whom data were collected, the median duration of treatment with an injectable medication was 216 days (IQR 203–252). Six (46%) patients reported a side effect requiring a medication change and eight (62%) had a side effect present at treatment completion. A standardized MDR TB supplemental surveillance form was well received by stakeholders whose feedback was critical to making modifications. The finalized form will be implemented nationally in 2020 and will provide MDR TB treatment and morbidity data in the United States to help ensure patients with MDR TB receive the most effective treatment regimens with the least toxic drugs. Keywords: Drug resistance, Surveillance, Tuberculosis

Design and discovery of novel antifungal compounds is the need of time, more than ever before due to the unavailability of effective antifungal therapy to treat resistant fungal infections. Due to morphological and functional similarities of fungi both with plant cell and human cell, the search for effective targets leading to specificity of antifungal drug action becomes all that more difficult. For the design of novel antifungal agents, it is necessary to comprehend the life cycle, morphology, metabolic pathways, etc. of fungi scientifically and systematically to identify critical targets for antifungal drug design. Fungi specific riboflavin metabolism involves lumazine synthase catalyzed synthesis of 6,7-dimethyl-8-D-ribityl lumazine which is converted to riboflavin by a riboflavin synthase. Therefore lumazine synthase has been targeted for the design of newer antifungal agents. The pharmacophore modeling and 3D QSAR studies were carried out on 32 N-substituted aryl amine derivatives as fungal lumazine synthase inhibitors. The selected model of 3D QSAR showed positive correlation of electronic descriptors with antifungal activity while steric and hydrophobic descriptors showed negative correlation with antifungal activity. The resulting model exhibited good q2 and r2 values up to 0.9109 and 0.845 respectively.

Preventing neuronal death is a priority for treating neurological diseases. However, therapies that inhibit pathological neuron loss could promote tumorigenesis by preventing the physiological death of cancerous cells. To avert this, we targeted the transcriptional upregulation of p21waf1/cip1 (p21), an endogenous tumor suppressor with neuroprotective and pro-regenerative activity. We identified potential p21 indcuers by screening a FDA-approved drug and natural product small molecule library against hippocampal HT22 cells stably expressing a luciferase reporter driven by the proximal 60 bp of the p21 promoter, and tested them for neuroprotection from glutathione depletion mediated oxidative stress, and cytotoxicity to cancer cell lines (DLD-1, Neuro-2A, SH-SY5Y, NGP, CHLA15, CHP212, and SK-N-SH) in vitro. Of the p21 inducers identified, only ciclopirox, a hypoxia-inducible factor prolyl-4-hydroxylase (HIF–PHD) inhibitor, simultaneously protected neurons from glutathione depletion and decreased cancer cell proliferation at concentrations that were not basally toxic to neurons. We found that other structurally distinct HIF–PHD inhibitors (desferrioxamine, 3,4-dihydroxybenzoate, and dimethyloxalyl glycine) also protected neurons at concentrations that killed cancer cells. HIF–PHD inhibitors stabilize HIF transcription factors, mediating genetic adaptation to hypoxia. While augmenting HIF stability is believed to promote tumorigenesis, we found that chronic HIF–PHD inhibition killed cancer cells, suggesting a protumorigenic role for these enzymes. Moreover, our findings suggest that PHD inhibitors can be used to treat neurological disease without significant concern for cell-autonomous tumor promotion.

2-Methoxyestradiol (2-ME2) was reported to elicit both stimulation and inhibition of tumor angiogenesis and growth depending on the dosage used. However, the mechanism(s) of the biphasic action of 2-ME2 has been elusive. Here we describe a regulatory role of vascular endothelial growth factor-A (VEGF-A) in the biphasic effects on estrogen receptor (ER)+ GH3 rat pituitary tumor cells and MCF-7 human breast tumor cells depending on the dosage of 2-ME2 used. We observed that acute exposure to 2-ME2, irrespective of dosage, did not alter cellular proliferation, but enhanced the VEGF-A mRNA level. As the treatment duration increased, biphasic effect was elicited. A concentration of 1 μM 2-ME2 increased both cell proliferation and VEGF-A levels in these cells, whereas higher doses exhibited reversed impact. A low dose of 2-ME2 also increased the VEGF-A mRNA expression in ER-α-transfected human mammary epithelial cells (HMECs). The effect was reversed in ER- cells. The enhanced expression of VEGF-A mRNA could be blocked by the pure estrogen antagonist, ICI 182,780, reveal that the upregulation of VEGF-A expression by 2-ME2 is mediated through ER-α. Furthermore, the biphasic effect of 2-ME2 on cell proliferation can be modulated by administrating VEGF-A antibodies or VEGF-A proteins. Studies also demonstrate that the VEGF-A protein, induced by 2-ME2, is functionally active and upregulates the proliferation of adjacent endothelial cells.

WISP-2 mRNA and protein was overexpressed in preneoplastic and cancerous cells of human breast. Statistical analyses show a significant association between WISP-2 expression and estrogen receptor (ER) positivity. In normal breast, the expression was virtually undetected. The studies showed that WISP-2 is an estrogen-induced early response gene in MCF-7 cells and the expression was continuously increased to reach a maximum level at 24 h. The estrogen effect was inhibited by a pure antiestrogen (ICI 182,780). Human mammary epithelial cells, in which WISP-2 expression was undetected or minimally detected, responded to 17β-estradiol by upregulating the WISP-2 gene after transfection with ER-α, providing further evidences that WISP-2 expression is mediated through ER-α. Overexpression of WISP-2 mRNA by estrogen may be accomplished by both transcriptional activation and stabilization. MCF-7 cells exposed to progesterone had a rapid but transient increase in WISP-2 expression, and PR antagonist RU38486 blocked this mRNA induction. In combination with estradiol, progesterone acted as an antagonist inhibiting the expression of WISP-2 mRNA. Moreover, disruption of WISP-2 signaling in MCF-7 cells by use of antisense oligomers caused a significant reduction in tumor cell proliferation. The results are consistent with the conclusion that WISP-2 expression is a requirement for breast tumor cells proliferation.