Candida pneumonia in young and immunocompetent lady: A case report and literature review.

Background: Candida is a frequent respiratory tract colonizer. True candida pneumonia is rare and seen with predominance in immunosuppressed patients. Our aim is to document a previously unreported case of Candida pneumonia in a young and immunocompetent patient, highlighting, an unusual pathological manifestation of this infection in immunocompetent individuals. Case summary: We report a previously healthy young lady who remained symptomatic with fever, cough and shortness of breath for three weeks duration despite treatment with extensive antibiotics regimen for community acquired pneumonia. She was eventually treated as a probable, rare case of candida pneumonia. The patient demonstrated a dramatic response to single antifungal treatment both clinically and biochemically within the first 24hrs of treatment. Candida albican was isolated on repetitive cultures form the sputum and bronchoalevolar lavage samples. The patient had negative blood cultures. Her HRCT scan revealed bilateral basal air space opacities with peri bronchovascular distribution and centrilobular nodules with branching pattern suggestive of tree in bud predominantly in lower lobes. Her endobronchial biopsies was mostly unremarkable apart from rare non-necrotizing granuloma. Conclusion: Candida can rarely cause clinically significant pneumonia in immunocompetent patients and should be considered in the differential diagnosis of granulomatous lung disease.

Halogens engineering-based design of agonists for boosting expression of frataxin protein in Friedreich's ataxia.

OBJECTIVE: Decreased expression of the mitochondrial protein frataxin is the cause of the neurodegenerative disorder Friedreich's ataxia. In patients with cardiac disorders, the death rate of this disease is very high, up to 66%. In order to combat Friedreich ataxia, which is a potentially toxic disorder, de novo drug discovery and design have been created utilizing the approach of compound engineering with halogens. This study aimed to investigate the potential for effective treatment of Friedreich ataxia. MATERIALS AND METHODS: The screening of twenty different agonist compounds was carried out in order to find the most promising agonist compound that may be used for molecular docking prediction against the Frataxin Protein. The compound with the lowest binding energies is then optimized by halogens. The final candidate's drug-like properties are identified through Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling. Lipinski's rule of five was checked. Molecular dynamic stimulations were evaluated. RESULTS: The most potent agonist compound was identified out of twenty different compounds utilizing a docking approach against the Frataxin Protein. The compound with the lowest binding energies was next subjected to optimization by halogens. The optimized agonist 9-[1-[(1S, 5R)-8, 8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl]triazol-4-yl]fluoren-9-ol  has higher binding energy of -10.4Kcal/mol with molecular weight of 705.63 g/mol. Drug-like properties are identified through ADMET profiling, having water solubility of about -7.59, skin permeation -7.08 cm/s, bioavailability score 0.17, and high GI absorption. The candidate fulfills the Lipinski rule of five and portrays efficient molecular dynamic stimulations. CONCLUSIONS: The selected agonist is one of the most potent compounds in increasing Frataxin protein expression. Furthermore, optimization with halogens can be a productive approach to improve the candidate's drug efficacy. The development of effective medications for the treatment of Friedreich ataxia would be aided by the results of these computational investigations.

A one-health approach to design an mRNA-based vaccine candidate against the lumpy skin disease virus as an alternative to live-attenuated vaccines.

OBJECTIVE: Recently, lumpy skin disease (LSD) has been spread over the Asian, European, and Middle Eastern regions making it a significant hazard to the chain of cattle production, milk production, and human milk consumption, requiring prompt attention. Lumpy skin disease virus has high morbidity and low fatality rates, but its infections have led to terrible economic and agricultural consequences. Although live-attenuated vaccines have been commercialized, farmers in different regions have not taken them well because of the allergic responses against the vaccines. The study aims to develop an mRNA-based vaccine candidate for LSDV, using immunoinformatic approaches to minimize allergenicity and homology while maximizing immunogenic potential. MATERIALS AND METHODS: The study used extensive immunoinformatic approaches to shortlist five proteins from the LSDV genome that belong to the transmembrane region and are crucial in early viral interaction with host cells. The B-cell and T-cell-specific epitopes were chosen based on non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. The construct's stability, hydrophilicity, and antigenic potential were analyzed using the instability index, Grand Average of Hydropathicity (GRAVY) index, and antigenicity, respectively. RESULTS: We selected a total of 34 epitopes, consisting of 12 B-cell-specific epitopes and 22 T-cell-specific epitopes. These epitopes were chosen based on their characteristics such as non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. Specifically, 11 epitopes were selected for Major Histocompatibility Complex-I, and another 11 epitopes were chosen for Major Histocompatibility Complex-II. The inclusion of the RS09 adjuvant enhanced the immunogenic potential of the vaccine. The instability index was found to be 38.60. Additionally, the GRAVY index, indicating hydrophilicity, was calculated as -0.151. Furthermore, the antigenicity value of 0.6073 confirmed its potential to elicit an immune response. Further supporting its immunogenic potential, strong immune stimulation was observed, with IgM+IgG titers reaching 6,000 (arbitrary units) and IFNg titers measuring 400,000 ng/mL. These results provide additional evidence of the vaccine's ability to stimulate a robust immune response. CONCLUSIONS: The study results indicate that the developed mRNA-based vaccine candidate for LSDV has high immunogenic potential and could serve as an effective alternative to live-attenuated vaccines. Further experimental validations are required to test its efficacy. The study also highlights the potential of the One-Health approach to tackle non-zoonotic diseases that have significant consequences for the environment and humanity.

Side chain inset of neurogenerative amino acids to metalloproteins: a therapeutic signature for huntingtin protein in Huntington's disease.

OBJECTIVE: Huntington's disease is a dominant autosomal inherited neurodegenerative disease that results in progressive impairment, characterized by dementia, chorea, and behavioral and cognitive decline. The objective of this study was to investigate the potential activity of metalloproteins against the huntingtin protein using various insertion-based engineering computational methods. Metalloproteins, metal protein complexes involved in important biochemical and physiological processes, were explored as potential drug candidates for Huntington's disease. MATERIALS AND METHODS: A total of 18 metalloproteins were selected as drug candidates and studied to assess their potential inhibitory effects on the huntingtin protein. The screening process was based on the lowest binding energy. The metalloprotein with the lowest docking score was chosen for side chain insertion of neurogenerative amino acids. The engineered metalloprotein was then evaluated based on physiochemical properties, allergenicity, toxicity, and surface accessibility. Cloning and expression analysis was performed to further investigate its potential as a therapeutic agent. RESULTS: The metalloprotein chosen for side chain insertion, cytochrome C oxidase, showed promising results. It was computed as a probable non-allergen and exhibited no toxic domains, indicating its non-toxic nature. Additionally, it demonstrated a strong binding affinity with the huntingtin protein, with a binding energy of -1,253.3 Kcal/mol. CONCLUSIONS: Metal-based proteins, when engineered with additional neurogenerative amino acids, hold potential as drug candidates for treating neurodegenerative diseases such as Huntington's disease. The successful development of these engineered metalloproteins could offer therapeutic advantages. Further testing, both in vitro and in vivo, is necessary to evaluate their efficacy and validate their potential activity as novel drugs for the treatment of neurodegenerative diseases.

A pharmacophore screening approach of homeopathic phenols for a renovated design of fragment-optimized Bauhiniastatin-1 as a drug against acromegaly.

OBJECTIVE: Acromegaly is a fatal and chronic disease that is caused by the abnormal secretion of growth hormone (GH) by the pituitary adenoma or pituitary tumor, resulting in an increased circulated concentration of insulin-like growth factors 1 (IGF-1), where in most of the cases it is secreted by a pituitary tumor. Higher levels of GH cause an increase in IGF-1 in the liver leading to multiple conditions such as cardiovascular diseases, glucose imbalance, cancer, and sleep apnea. Medical treatments such as surgery and radiotherapy can be used as the first choice of patients; however, specified human growth hormone control should be an essential treatment strategy due to an incidence rate of 0.2-1.1 yearly. Therefore, the main focus of this study is to develop a novel drug for treating acromegaly by exploiting medicinal plants that have been screened using phenol as a pharmacophore model to identify target therapeutic medicinal plant phenols. MATERIALS AND METHODS: The screening identified thirty-four pharmacophore matches of medicinal plant phenols. These were selected as suitable ligands and were docked against the growth hormone receptor to calculate their binding affinity. The candidate with the highest screened score was fragment-optimized and subjected to absorption, distribution, metabolism, and excretion (ADME) analysis, in-depth toxicity predictions, interpretation of Lipinski's rule, and molecular dynamic simulations to check the behavior of the growth hormone with the fragment-optimized candidate. RESULTS: The highest docking energy was calculated as -6.5 K/mol for Bauhiniastatin-1. Enhancing the performance of Bauhiniastatin-1 against the growth hormone receptor with fragment optimization portrayed that human growth hormone inhibition can be executed in a more efficient and better way. Fragment-optimized Bauhiniastatin-1 (FOB) was predicted with high gastrointestinal absorption, a water solubility of -2.61 as soluble, and synthetic accessibility of 4.50, achieving Lipinski's rule of 5, with low organ toxicity prediction and interpreting a positive behavior against the targeted protein. The discovery of a de novo drug candidate was confirmed by the docking of fragment-optimized Bauhiniastatin-1 (FOB), which had an energy of -4,070 Kcal/mol. CONCLUSIONS: Although successful and completely harmless, present healthcare treatment does not always eradicate the disease in some individuals. Therefore, novel formulas or combinations of currently marketed medications and emergent phytochemicals will provide new possibilities for these instances.

Revolutionizing treatment for toxic shock syndrome with engineered super chromones to combat antibiotic-resistant Staphylococcus aureus.

OBJECTIVE: Staphylococcus aureus-induced toxic shock syndrome (TSS) is a rare, but potentially fatal disease with limited treatment options. The emergence of antibiotic-resistant strains has led to a pressing need for the development of effective therapies. This study aimed to identify and optimize potential drug candidates against toxic shock syndrome by targeting the pathogenic toxin protein using chromones as lead compounds. MATERIALS AND METHODS: In this study, 20 chromones were screened for their ability to bind to the target protein. The top compounds were further optimized through the addition of cycloheptane and amide groups, and the resulting compounds were evaluated for their drug-like properties using chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. RESULTS: Among the compounds screened, 7-Glucosyloxy-5-hydroxy-2-[2-(4-hydroxyphenyl) ethyl] chromone exhibited the highest binding affinity with a molecular weight of 341.40 g/mol and a binding energy of -10.0 kcal/mol. The optimized compound exhibited favorable drug-like properties, including high water solubility, synthetic accessibility, skin permeation, bioavailability, and gastrointestinal absorption. CONCLUSIONS: This study suggests that chromones can be engineered to develop effective drugs against TSS caused by S. aureus. The optimized compound has the potential to be a promising therapeutic agent for the treatment of TSS, providing new hope for patients suffering from this life-threatening disease of toxic shock syndrome.

A novel approach to infectious disease control and radiotherapy risk management.

BACKGROUND: Infectious disease outbreaks have always presented challenges to the operation of healthcare systems. In particular, the treatment of cancer patients within Radiation Oncology often cannot be delayed or compromised due to infection control measures. Therefore, there is a need for a strategic approach to simultaneously managing infection control and radiotherapy risks. PURPOSE: To develop a systematic risk management method that uses mathematical models to design mitigation efforts for control of an infectious disease outbreak, while ensuring safe delivery of radiotherapy. METHODS: A two-stage failure mode and effect analysis (FMEA) approach is proposed to modify radiotherapy workflow during an infectious disease outbreak. In stage 1, an Infection Control FMEA (IC-FMEA) is conducted, where risks are evaluated based on environmental parameters, clinical interactions, and modeling of infection risk. occupancy risk index (ORI) is defined as a metric for infection transmission risk level in each room, based on the degree of occupancy. ORI, in combination with ventilation rate per person (Rp ), is used to provide a broad infection risk assessment of workspaces. For detailed IC-FMEA of clinical processes, infection control failure mode (ICFM) is defined to be any instance of disease transmission within the clinic. Infection risk priority number (IRPN) has been formulated as a function of time, distance, and degree of protective measures. Infection control measures are then systematically integrated into the workflow. Since the workflow is perturbed by infection control measures, there is a possibility of introducing new radiotherapy failure modes or increased likelihood of existing failure modes. Therefore, in stage 2, a conventional radiotherapy FMEA (RT-FMEA) should be performed on the adjusted workflow. RESULTS: The COVID-19 pandemic was used to illustrate stage 1 IC-FMEA. ORI and Rp values were calculated for various workspaces within a clinic. A deep inspiration breath hold (DIBH) CT simulation was used as an example to demonstrate detailed IC-FMEA with ICFM identification and IRPN evaluation. A total of 90 ICFMs were identified in the DIBH simulation process. The calculated IRPN values were found to be progressively decreasing for workflows with minimal, moderate, and enhanced levels of protective measures. CONCLUSION: The framework developed in this work provides tools for radiotherapy clinics to systematically assess risk and adjust workflows during the evolving circumstances of any infectious disease outbreak.

The schedule of ATR inhibitor AZD6738 can potentiate or abolish antitumor immune responses to radiotherapy.

Inhibitors of the DNA damage signaling kinase ATR increase tumor cell killing by chemotherapies that target DNA replication forks but also kill rapidly proliferating immune cells including activated T cells. Nevertheless, ATR inhibitor (ATRi) and radiotherapy (RT) can be combined to generate CD8+ T cell-dependent antitumor responses in mouse models. To determine the optimal schedule of ATRi and RT, we determined the impact of short-course versus prolonged daily treatment with AZD6738 (ATRi) on responses to RT (days 1-2). Short-course ATRi (days 1-3) plus RT caused expansion of tumor antigen-specific, effector CD8+ T cells in the tumor-draining lymph node (DLN) at 1 week after RT. This was preceded by acute decreases in proliferating tumor-infiltrating and peripheral T cells and a rapid proliferative rebound after ATRi cessation, increased inflammatory signaling (IFN-ß, chemokines, particularly CXCL10) in tumors, and an accumulation of inflammatory cells in the DLN. In contrast, prolonged ATRi (days 1-9) prevented the expansion of tumor antigen-specific, effector CD8+ T cells in the DLN, and entirely abolished the therapeutic benefit of short-course ATRi with RT and anti-PD-L1. Our data argue that ATRi cessation is essential to allow CD8+ T cell responses to both RT and immune checkpoint inhibitors.

Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Impact of root hairs on microscale soil physical properties in the field.

Aims: Recent laboratory studies revealed that root hairs may alter soil physical behaviour, influencing soil porosity and water retention on the small scale. However, the results are not consistent, and it is not known if structural changes at the small-scale have impacts at larger scales. Therefore, we evaluated the potential effects of root hairs on soil hydro-mechanical properties in the field using rhizosphere-scale physical measurements. Methods: Changes in soil water retention properties as well as mechanical and hydraulic characteristics were monitored in both silt loam and sandy loam soils. Measurements were taken from plant establishment to harvesting in field trials, comparing three barley genotypes representing distinct phenotypic categories in relation to root hair length. Soil hardness and elasticity were measured using a 3-mm-diameter spherical indenter, while water sorptivity and repellency were measured using a miniaturized infiltrometer with a 0.4-mm tip radius. Results: Over the growing season, plants induced changes in the soil water retention properties, with the plant available water increasing by 21%. Both soil hardness (P = 0.031) and elasticity (P = 0.048) decreased significantly in the presence of root hairs in silt loam soil, by 50% and 36%, respectively. Root hairs also led to significantly smaller water repellency (P = 0.007) in sandy loam soil vegetated with the hairy genotype (-49%) compared to the hairless mutant. Conclusions: Breeding of cash crops for improved soil conditions could be achieved by selecting root phenotypes that ameliorate soil physical properties and therefore contribute to increased soil health. Supplementary Information: The online version contains supplementary material available at 10.1007/s11104-022-05530-1.

Molecular evidence, risk factors analysis, and hematological alterations associated with Theileria spp. spillover in captive wild mouflon sheep in Punjab, Pakistan.

Background: Landscape anthropization and interaction between domestic and wild animals are the major contributing factors involved in the emergence of new pathogens in wild animals. Theileriosis is an emerging issue of wild ungulates, especially in the tropical and subtropical areas of the globe. Aims: The current study investigated the mouflon sheep for Theileria infection using molecular methods and hematological analysis. Methods: This study was conducted on a total of 103 captive wild mouflon sheep present in eight different recreational zoos, and wildlife parks in Punjab, Pakistan to investigate the genotypic prevalence of Theileria spp. by targeting 18S rRNA and molecular evidence for Theileria spillover between domestic and wild mouflon sheep by phylogenetic analysis. The association of assumed risk factors and the effect of Theileria spp. on various hematological parameters were also assessed. Results: The results depicted that Theileria spp. was prevalent in 8 (7.77%, CI 95%: 3.99-14.59%), and 11 (10.68%, CI 95%: 06.07-18.12%) animals based on microscopy, and PCR, respectively. The phylogenetic analysis of the 18S rRNA gene of Theileria spp. from mouflon revealed a close resemblance with T. annulata from domestic animals. The risk factor analysis revealed that tick infestation, enclosure hygiene, previous tick infestation history, and the presence of wooden logs in the enclosure were significantly (P<0.05) associated with the occurrence of Theileria spp. infection in the captive mouflon sheep of Pakistan. Furthermore, a significant reduction in blood parameters like PCV, RBCs count, Hb, and platelets was observed in Theileria-positive animals. Conclusion: This study is the first evidence at the molecular level to characterize the spillover of Theileria spp. between the captive wild mouflon sheep and domestic animals of Pakistan, and it will be useful in developing control strategies for emerging theileriosis in captive wild animals.

Effectiveness of typhoid conjugate vaccine against culture-confirmed Salmonella enterica serotype Typhi in an extensively drug-resistant outbreak setting of Hyderabad, Pakistan: a cohort study.

BACKGROUND: Salmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middle-income countries. We aimed to investigate the effectiveness and impact of the typhoid conjugate vaccine Typbar-TCV against S Typhi among children in an outbreak setting of extensively drug-resistant (XDR) S Typhi in Pakistan. METHODS: This cohort study was done from Feb 21, 2018, to Dec 31, 2019. A census survey of all households located in the Qasimabad and Latifabad subdistricts of Hyderabad, Pakistan, was done at baseline, and 174 005 households were registered in the census. The Typbar-TCV immunisation campaign was initiated at temporary vaccination centres and 207 000 children aged 6 months to 10 years were vaccinated from Feb 21, 2018, to Dec 31, 2018. Social mobilisers informed parents about the vaccination process. Vaccination records were maintained electronically and linked with the household census surveys. Active surveillance for suspected and blood-culture-confirmed S Typhi was established in hospitals, clinics, and laboratories to assess the following outcomes: cases of suspected typhoid fever, culture-confirmed S Typhi, and antimicrobial resistance. An age-stratified cohort of 1100 vaccinated children was randomly selected from the vaccination registry, tested for Vi-IgG antibodies (data not reported), and followed up fortnightly (via telephone calls or household visits) until Dec 31, 2019, for ascertainment of outcomes during the study period. 20 847 vaccinated and unvaccinated children were randomly selected from the census registry as a quality control cohort and followed up from Oct 1 to Dec 31, 2019, for ascertainment of outcomes. Vaccine effectiveness against suspected, culture-confirmed, and XDR S Typhi was calculated. FINDINGS: 23 407 children from the census registry and surveillance system were included in the vaccine effectiveness analysis. 13 436 (57·4%) children were vaccinated, 12 214 (52·2%) were male, and 10 168 (43·4%) were aged 6-59 months. 5378 (23·0%) of 23 407 children had suspected S Typhi, among whom 775 (14·4%) had culture-confirmed S Typhi and 361 (68·6%) of 526 had XDR S Typhi. Vaccine effectiveness was 55% (95% CI 52-57) against suspected S Typhi (regardless of culture confirmation), 95% (93-96) against culture-confirmed S Typhi, and 97% (95-98) against XDR S Typhi. INTERPRETATION: Typbar-TCV is effective in protecting children against S Typhi infection in an outbreak setting, and was able, with moderate deployment, to curtail a major XDR S Typhi outbreak in a densely populated setting. The vaccine shows efficacy against S Typhi irrespective of antimicrobial resistance. FUNDING: Bill & Melinda Gates Foundation.

Review of potential risk groups for coronavirus disease 2019 (COVID-19).

The current pandemic of coronavirus disease 19 (COVID-19) is a global issue caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Studies have revealed that this virus results in poorer consequences and a higher rate of mortality in older adults and those with comorbidities such as cardiovascular disease, hypertension, diabetes and prolonged respiratory illness. In this review, we discuss in detail the potential groups at risk of COVID-19 and outline future recommendations to mitigate community transmission of COVID-19. The rate of COVID-19 was high in healthcare workers, smokers, older adults, travellers and pregnant women. Furthermore, patients with severe medical complications such as heart disease, hypertension, respiratory illness, diabetes mellitus and cancer are at higher risk of disease severity and mortality. Therefore, special effort and devotion are needed to diminish the threat of SARS-CoV-2 infection. Proper vaccination, use of sanitizers for handwashing and complete lockdown are recommended to mitigate the chain of COVID-19 transmission.

ASGE guideline on the role of endoscopy in the management of benign and malignant gastroduodenal obstruction

This American Society for Gastrointestinal Endoscopy guideline provides evidence-based recommendations for the endoscopic management of gastric outlet obstruction (GOO). We applied the Grading of Recommendations, Assessment, Development and Evaluation methodology to address key clinical questions. These include the comparison of (1) surgical gastrojejunostomy to the placement of self-expandable metallic stents (SEMS) for malignant GOO, (2) covered versus uncovered SEMS for malignant GOO, and (3) endoscopic and surgical interventions for the management of benign GOO. Recommendations provided in this document were founded on the certainty of the evidence, balance of benefits and harms, considerations of patient and caregiver preferences, resource utilization, and cost-effectiveness.

Significance of root hairs for plant performance under contrasting field conditions and water deficit.

BACKGROUND AND AIMS: Previous laboratory studies have suggested selection for root hair traits in future crop breeding to improve resource use efficiency and stress tolerance. However, data on the interplay between root hairs and open-field systems, under contrasting soils and climate conditions, are limited. As such, this study aims to experimentally elucidate some of the impacts that root hairs have on plant performance on a field scale. METHODS: A field experiment was set up in Scotland for two consecutive years, under contrasting climate conditions and different soil textures (i.e. clay loam vs. sandy loam). Five barley (Hordeum vulgare) genotypes exhibiting variation in root hair length and density were used in the study. Root hair length, density and rhizosheath weight were measured at several growth stages, as well as shoot biomass, plant water status, shoot phosphorus (P) accumulation and grain yield. KEY RESULTS: Measurements of root hair density, length and its correlation with rhizosheath weight highlighted trait robustness in the field under variable environmental conditions, although significant variations were found between soil textures as the growing season progressed. Root hairs did not confer a notable advantage to barley under optimal conditions, but under soil water deficit root hairs enhanced plant water status and stress tolerance resulting in a less negative leaf water potential and lower leaf abscisic acid concentration, while promoting shoot P accumulation. Furthermore, the presence of root hairs did not decrease yield under optimal conditions, while root hairs enhanced yield stability under drought. CONCLUSIONS: Selecting for beneficial root hair traits can enhance yield stability without diminishing yield potential, overcoming the breeder's dilemma of trying to simultaneously enhance both productivity and resilience. Therefore, the maintenance or enhancement of root hairs can represent a key trait for breeding the next generation of crops for improved drought tolerance in relation to climate change.

Selection and screening of drought tolerant high yielding chickpea genotypes based on physio-biochemical indices and multi-environmental yield trials.

BACKGROUND: Chickpea is one of the major legume crops being cultivated in the arid and semi-arid regions of Pakistan. It is mainly grown on the marginal areas where, terminal drought stress is one of the serious threats to its productivity. For defining the appropriate selection criteria for screening drought tolerant chickpea genotypes, present study was conducted. Distinct chickpea germplasm was collected from different pulses breeding institutes of Pakistan and evaluated for drought tolerance at germination and early seedling stages, furthermore, at late vegetative growth stages physiochemical traits and multi-environment yield performance were also tested. RESULTS: Chickpea genotypes under different environments, were significantly varied for different seedling traits, physio-chemical attributes and seed yield. Genotypes showing drought tolerance by performing better at an early seedling stages were not correspondingly high yielding. Screening for drought tolerance on seed yield basis is the most appropriate trait to develop the drought tolerant as well as high yielding chickpea genotypes. Results confirmed that traits of early growth stages were not reflecting the drought tolerance at terminal growth stages and also did not confer high yielding. NIAB-rain fed environment proved ideal in nature to screen the chickpea genotypes whereas, NIAB-lysimeter and Kalur Kot was least effective for selecting genotypes with high seed yield. Genotypes D0091-10, K010-10, D0085-10, K005-10, D0078-10, 08AG016, 08AG004, D0080-10, 09AG002, K002-10 and D0099-10 were high yielding and drought tolerant based on their performance across multiple hotspot environments. CONCLUSIONS: The selected genotypes are intended for further evaluation for varietal approval to recommend for general cultivation on farmer fields in drought hit areas of Pakistan. Among physio-biochemical traits, higher proline, glycine betain, RWC and CMS were reflecting the higher capability to tolerate the drought stress in chickpea. Drought sensitive genotypes (K0037-10, 2204, K0052-10, 09AG015, K0042-10, CM709/06, K0068-10, K004-10, K0026-10 and K0063-10) were also identified in present study which were resourceful asset for using as contrasting parents in hybridization programs. To our knowledge, this is first report using an integrated approach involving, physio-biochemical indices, and multi-environmental yield trials, for comparison, screening and selection of chickpea genotypes for drought tolerance.

Bronchiectasis in India: results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry.

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0·0001]) and more likely to be men (1249 [56·9%] of 2195). Previous tuberculosis (780 [35·5%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13·7%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1·17, 95% CI 1·03-1·32; p=0·015), P aeruginosa infection (1·29, 1·10-1·50; p=0·001), a history of pulmonary tuberculosis (1·20, 1·07-1·34; p=0·002), modified Medical Research Council Dyspnoea score (1·32, 1·25-1·39; p<0·0001), daily sputum production (1·16, 1·03-1·30; p=0·013), and radiological severity of disease (1·03, 1·01-1·04; p<0·0001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation.

Surface tension, rheology and hydrophobicity of rhizodeposits and seed mucilage influence soil water retention and hysteresis.

AIMS: Rhizodeposits collected from hydroponic solutions with roots of maize and barley, and seed mucilage washed from chia, were added to soil to measure their impact on water retention and hysteresis in a sandy loam soil at a range of concentrations. We test the hypothesis that the effect of plant exudates and mucilages on hydraulic properties of soils depends on their physicochemical characteristics and origin. METHODS: Surface tension and viscosity of the exudate solutions were measured using the Du Noüy ring method and a cone-plate rheometer, respectively. The contact angle of water on exudate treated soil was measured with the sessile drop method. Water retention and hysteresis were measured by equilibrating soil samples, treated with exudates and mucilages at 0.46 and 4.6 mg g-1 concentration, on dialysis tubing filled with polyethylene glycol (PEG) solution of known osmotic potential. RESULTS: Surface tension decreased and viscosity increased with increasing concentration of the exudates and mucilage in solutions. Change in surface tension and viscosity was greatest for chia seed exudate and least for barley root exudate. Contact angle increased with increasing maize root and chia seed exudate concentration in soil, but not barley root. Chia seed mucilage and maize root rhizodeposits enhanced soil water retention and increased hysteresis index, whereas barley root rhizodeposits decreased soil water retention and the hysteresis effect. The impact of exudates and mucilages on soil water retention almost ceased when approaching wilting point at -1500 kPa matric potential. CONCLUSIONS: Barley rhizodeposits behaved as surfactants, drying the rhizosphere at smaller suctions. Chia seed mucilage and maize root rhizodeposits behaved as hydrogels that hold more water in the rhizosphere, but with slower rewetting and greater hysteresis.

Antibiotic resistance profile in relation to virulence genes fimH, hlyA and usp of uropathogenic E. coli isolates in Lahore, Pakistan.

Uropathogenic E. coli (UPEC) is the major etiological agent of urinary tract infections. The objectives of this study were to evaluate E. coli isolates from these patients for the phenotypic pattern of antibiotic resistance and to detect the genes responsible for virulence namely fimH, hlyA and usp. A total of 110 E. coli isolates were studied and 30 antibiotics were applied for susceptibility testing. PCR detection of the genes fimH, hlyA and usp was done followed by sequencing and phylogenetic analysis. The results showed that the isolates were highly resistant to cephalaxin (100%) and cephradine (100%) but displayed high sensitivity to amikacin (96.27%), Imipenem (92.63%) and Meropenem (92.63%). The prevalence of fimH, hlyA and usp was 86%, 83% and 16%, respectively. The sequencing showed 99% similarity with previously reported sequences in NCBI GenBank database. The co-existence of multiple drug-resistant bodies and virulent genes has important implications for the treatment of patients with urinary tract infection. This study provides information about treating drug-resistant E. coli and the relationship of virulent genes with phenotypic resistance patterns.

Antibiotic resistance profile in relation to virulence genes fimH, hlyA and usp of uropathogenic E. coli isolates in Lahore, Pakistan

@#Uropathogenic E. coli (UPEC) is the major etiological agent of urinary tract infections. The objectives of this study were to evaluate E. coli isolates from these patients for the phenotypic pattern of antibiotic resistance and to detect the genes responsible for virulence namely fimH, hlyA and usp. A total of 110 E. coli isolates were studied and 30 antibiotics were applied for susceptibility testing. PCR detection of the genes fimH, hlyA and usp was done followed by sequencing and phylogenetic analysis. The results showed that the isolates were highly resistant to cephalaxin (100%) and cephradine (100%) but displayed high sensitivity to amikacin (96.27%), Imipenem (92.63%) and Meropenem (92.63%). The prevalence of fimH, hlyA and usp was 86%, 83% and 16%, respectively. The sequencing showed 99% similarity with previously reported sequences in NCBI GenBank database. The co-existence of multiple drug-resistant bodies and virulent genes has important implications for the treatment of patients with urinary tract infection. This study provides information about treating drug-resistant E. coli and the relationship of virulent genes with phenotypic resistance patterns.