Overexpression of a membrane transport system MSMEG_1381 and MSMEG_1382 confers multidrug resistance in Mycobacterium smegmatis.

Mycobacterium tuberculosis is a leading cause of human mortality worldwide, and the emergence of drug-resistant strains demands the discovery of new classes of antimycobacterial that can be employed in the therapeutic pipeline. Previously, a secondary metabolite, chrysomycin A, isolated from Streptomyces sp. OA161 displayed potent bactericidal activity against drug-resistant clinical isolates of M. tuberculosis and different species of mycobacteria. The antibiotic inhibits mycobacterial topoisomerase I and DNA gyrase, leading to bacterial death, but the mechanisms that could cause resistance to this antibiotic are currently unknown. To further understand the resistance mechanism, using M. smegmatis as a model, spontaneous resistance mutants were isolated and subjected to whole-genome sequencing. Mutation in a TetR family transcriptional regulator MSMEG_1380 was identified in the resistant isolates wherein the gene was adjacent to an operon encoding membrane proteins MSMEG_1381 and MSMEG_1382. Sequence analysis and modeling studies indicated that MSMEG_1381 and MSMEG_1382 are components of the Mmp family of efflux pumps and over-expression of either the operon or individual genes conferred resistance to chrysomycin A, isoniazid, and ethambutol. Our study highlights the role of membrane transporter proteins in conferring multiple drug resistance and the utility of recombinant strains overexpressing membrane transporters in the drug screening pipeline.

Risk factors of chronic kidney disease among type 2 diabetic patients with longer duration of diabetes.

Background: Chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM) is the major cause of end stage renal disease, characterized by proteinuria with a subsequent decline in glomerular filtration rate. Although hyperglycemia is the major risk factor for the development and progression of kidney disease among diabetic patients, many other risk factors also contribute to structural and functional changes in the kidneys. As recommended by Kidney Disease Improving Global Outcomes (KDIGO), CKD classification based on cause and severity, links to risk of adverse outcomes including mortality and kidney outcomes. Objective: The aim of this study is to investigate the involvement of risk factors associated with the severity of CKD among participants with longer duration of diabetes. This study also aims to find whether number of risk factors vary among risk of CKD progression categories based on KDIGO classification. Material and methods: This cross-sectional study retrospectively selected 424 participants from type 2 diabetic cohort and categorized them based on the classifications for the diagnosis of kidney diseases in patients with diabetes, according to the KDIGO guidelines. Odds ratios and 95% CI of each risk factors according to severity of renal disease were determined. Results: Based on KDIGO classification, participants with type 2 diabetes (T2D) were categorized in to low risk (n=174); moderately increased risk (n=98); and high/very high risk (n=152). Type 2 diabetic participants with risk factors such as, hyperlipidemia, hypertension, DM duration ≥15 years and diabetic retinopathy showed a high/very high risk of CKD progression when compared with low-risk category. While T2D participants with risk factors such as, lack of exercise, hypertension, and diabetic retinopathy showed a moderately increased risk of CKD progression. In addition, participants with highest number of risk factors were significantly distributed among high/very high risk of CKD progression category. Conclusion: This study findings conclude that patients with T2DM and duration of ≥15 years, hyperlipidemia, hypertension and diabetic retinopathy have an increased prevalence of advanced CKD. In addition to this, increased number of risk factors could be an indicator of the severity of CKD in T2D.

Evaluation of Risk Factors for Diabetic Peripheral Neuropathy Among Saudi Type 2 Diabetic Patients with Longer Duration of Diabetes.

Background: Neuropathy is the most common microvascular complications among diabetic patients. Diabetic peripheral neuropathy (DPN) is the predominant variety which may associate with increased in mortality and morbidity among type 2 diabetes mellitus (T2DM). Objective: To assess the prevalence of diabetic peripheral neuropathy and its correlation with risk factors among T2DM. Methods: This was a cross-sectional retrospective study, data was collected from a previous cohort study conducted at the University Diabetes Center, King Saud University Medical City (KSUMC), King Saud University, Riyadh, Saudi Arabia. The data of T2DM patients were collected from case report form, included demographic data, history of chronic diabetes neuropathy, and laboratory reports. Statistical analysis includes Student`s t test, chi square test, and Pearson correlation and logistic regression were performed. Results: A total of 430 patients with T2DM data was collected and analyzed, and of them 54% were females, with the mean age of 55.88 years. The prevalence of diabetic neuropathy among study participants were 40.2%, and 73.3% of them having the subtype polyneuropathy. The mean BMI; p = 0.006, FBS; p < 0.001, HbA1c; p < 0.001, cholesterol p = 0.001, LDL; p < 0.001, and triglyceride; p < 0.001 levels were a significantly higher among participants with diabetic neuropathy than without neuropathy. The male gender (Risk Ratio: 1.294, 95% CI:1.090, 1.536) p = 0.003, fasting blood glucose (Risk Ratio: 1.157, 95% CI:1.051, 1.273) p = 0.003 Cholesterol (Risk Ratio: 1.588, 95% CI:1.174, 2.147) p = 0.003, triglyceride (Risk Ratio: 1.290, 95% CI:1.086, 1.538), p = 0.004, and LDL (Risk Ratio: 1.299, 95% CI:1.073, 1.574), p = 0.007) were found to be significant risk factors for DPN. Conclusion: DPN is highly prevalent among T2DM patients in Saudi Arabia. Poor glycemic control and hyperlipidemia were associated with significantly higher risk for DPN patients among T2DM.

Two new species of Platensina Enderlein (Diptera, Tephritidae, Tephritinae, Dithrycini) from India.

Two new species of Platensina Enderlein, P.rabbanii David & Hancock, sp. nov., and P.flavistigma David & Hancock, sp. nov., are described from Meghalaya and southern India, respectively. Platensinarabbanii can be differentiated from P.alboapicalis Hering by the presence of a single hyaline indentation in cell r1 and the apical hyaline band in cell r2+3 restricted to the apex; P.flavistigma differs from P.quadrula Hardy by the presence of a yellow/fulvous pterostigma and shape of the epandrium. DNA barcode sequences of P.acrostacta (Wiedemann), P.flavistigma and P.platyptera Hendel were obtained and reported. Postabdominal descriptions and illustrations of P.acrostacta, P.platyptera and P.zodiacalis (Bezzi) are also provided along with keys to all 23 species and the 7 known from India.

The Error-Prone Polymerase DnaE2 Mediates the Evolution of Antibiotic Resistance in Persister Mycobacterial Cells.

Applying antibiotics to susceptible bacterial cultures generates a minor population of persisters that remain susceptible to antibiotics but can endure them for extended periods. Recent reports suggest that antibiotic persisters (APs) of mycobacteria experience oxidative stress and develop resistance upon treatment with lethal doses of ciprofloxacin or rifampicin. However, the mechanisms driving the de novo emergence of resistance remained unclear. Here, we show that mycobacterial APs activate the SOS response, resulting in the upregulation of the error-prone DNA polymerase DnaE2. The sustained expression of dnaE2 in APs led to mutagenesis across the genome and resulted in the rapid evolution of resistance to antibiotics. Inhibition of RecA by suramin, an anti-Trypanosoma drug, reduced the rate of conversion of persisters to resistors in a diverse group of bacteria. Our study highlights suramin's novel application as a broad-spectrum agent in combating the development of drug resistance.

Halyomorpha picus (Hemiptera: Heteroptera: Pentatomidae): first confirmed record from Pakistan and two new junior synonyms.

We provide the first confirmed record of Halyomorpha picus (Fabricius, 1794) (Hemiptera: Heteroptera: Pentatomoidea: Pentatomidae: Pentatominae: Cappaeini) from Pakistan: Islamabad Capital Territory, and provide habitus photographs and electron scanning micrographs of the male genitalia of the voucher specimens. Two species previously described from Pakistan are found to fit within the morphological variability of H. picus and the following two junior subjective synonyms are proposed: Halyomorpha picus (Fabricius, 1794) = Halyomorpha punjabensis Ahmad Kamaluddin, 1977, syn. nov., = Halyomorpha azhari Ahmad Zaidi, 1989, syn. nov. The record of Halyomorpha scutellata Distant, 1879, from Pakistan by Sharif et al. (2020) is based on misidentification of a species of Neohalys Ahmad Perveen, 1982 (Pentatominae: Halyini) and excluded from Pakistan fauna. Based on the analysis of female genitalia figures provided by Gadalla (2004), the record of H. picus from Egypt represents a misidentification of H. halys Stl, 1855, which extends the distribution of that invasive species to North Africa.

Review of the Oriental species of the genus Brachycerocoris Costa, 1863 (Hemiptera: Pentatomoidea: Pentatomidae: Podopinae s.l.) with description of two new species.

The Oriental species belonging to genus Brachycerocoris Costa, 1863 (Hemiptera: Pentatomoidea: Pentatomidae: Podopinae s.l.) are revised with description of two new species, B. petrii sp. nov. and B. davidii sp. nov. from India and Philippines respectively. Brachycerocoris camelus Costa, 1863 is diagnosed and illustrated for female genitalia and B. dromedarius (Vollenhoven, 1863) is diagnosed and illustrated for both male and female genitalia. Additionally, host record, bionomics of B. petrii sp. nov. and a key to the Oriental species are provided.

Taxonomic notes on emSarju/em Ghauri, 1977 (Hemiptera: Heteroptera: Pentatomidae) with description of a new species from India.

The genus Sarju Ghauri, 1977 (Hemiptera: Pentatomidae: Pentatominae: Halyini) is redescribed along with the description of a new species, Sarju brevirostrata sp. nov. S. farida Ghauri, 1977 and S. nigricollis (Westwood, 1837) are redescribed based on the availability of specimens and the species Cahara nodula Fan and Liu, 2013 was transferred from Cahara to Sarju and proposed Sarju nodula comb.nov. Therefore, at present Sarju comprises 11 species worldwide. A key to the eight species of Sarju occurring in India is also provided.

The genera emAgathocles/em and emSurenus/em (Hemiptera: Heteroptera: Pentatomidae): tribal reassessment, redescription, new synonyms, and description of two new species.

The genus Surenus Distant, 1901 (Hemiptera: Heteroptera: Pentatomoidea: Pentatomidae: Pentatominae: Halyini) is revisited and found to be a junior subjective synonym of the genus Agathocles Stål, 1876 (currently Pentatominae: Rolstoniellini). The genus Agathocles and its type species, Agathocles limbatus Stål, 1876, are redescribed. Lectotype of Surenus normalis Distant, 1901 (= Agathocles normalis (Distant, 1901) comb. nov.) is designated and the unknown male of the species is described. Agathocles yunnanensis Zhang Lin, 1984, syn. nov., is considered junior subjective synonym of A. limbatus. Two new species are described: Agathocles flavipes sp. nov. from India (Andhra Pradesh, Karnataka, Maharashtra, and Tamil Nadu) and A. joceliae sp. nov. from Malaysia (Kelantan, Perak). The new species differ from their congeners mainly by the morphology of mandibular plates, length of antennomeres I, IIa and IIb, body length, and structure of male genitalia. Agathocles dubius Distant, 1921 is transferred to the genus Caystrus Stål, 1861 (Pentatominae: Caystrini) based on examination of its holotype with the resulting new combination: Caystrus dubius (Distant, 1921), comb. nov. One new combination is proposed, Paramecocoris ruficornis (Fieber, 1851), comb. nov. (from preoccupied Paramecus Fieber, 1851), and its type locality is clarified as Tenasserim (south Myanmar). Gender agreement and authorship of the name Riazocoris niger Ahmad Afzal, 1977 in Ahmad et al. (1977: 161) are corrected and status of its name bearing type is clarified as lectotype. The following new distribution records are given: A. limbatus from Cambodia, China (Guangxi, Tibet), Laos and Thailand, A. normalis, Caystrus obscurus (Distant, 1901a) and Critheus lineatifrons Stål, 1869 from Laos, Amasenus corticalis Stål, 1863 from Cambodia, Indonesia (E Kalimantan), Laos, Myanmar and Thailand, and Rolstoniellus boutanicus (Dallas, 1849) from Vietnam. Based on characters of external morphology and genitalia, the genus Agathocles is compared with representatives of the genera Halys Fabricius, 1803 (Halyini), Caystrus (Caystrini), Laprius Stål, 1861 (Myrocheini), and Exithemus Distant, 1902 (currently in Rolstoniellini). As a result, the genus Agathocles is here transferred to the tribe Caystrini. The genus Kyrtalus Van Duzee, 1929 is tentatively placed in Myrocheini based on the presence of sulcate mesosternum and femora provided with teeth.

First record of the genus Lodosocoris Ahmad amp; Afzal (Hemiptera: Heteroptera: Pentatomidae: Halyini) from India with description of a new species.

The genus Lodosocoris Ahmad Afzal, 1986 (Hemiptera: Heteroptera: Pentatomidae: Pentatominae: Halyini) is recorded for the first time from India. Prior to this publication, the genus was monotypic so far, containing only Lodosocoris azhari Ahmad Afzal, 1986 from Pakistan. Herein, the genus Lodosocoris is redescribed along with the description of Lodosocoris santhae sp. nov., based on specimens from Arunachal Pradesh, a region in northeastern India. Lodosocoris santhae sp. nov is described and illustrated based on male and female genitalia. The diagnostic characters of the new species are compared with L. azhari.

Revision of the genus Halys (Hemiptera: Pentatomidae) with description of a new species from India.

The species of the genus Halys Fabricius, 1803 (Hemiptera: Heteroptera: Pentatomidae: Pentatominae: Halyini) from India are redescribed and revised. Examination of more than 300 specimens collected from all over the country revealed the presence of four species, including a new species: Halys mudigerensis sp. nov., H. serrigera Westwood, 1837, H. shaista Ghauri, 1988 and H. sulcata (Thunberg, 1783). The following synonymies are proposed: H. sulcata (Thunberg, 1783) = Halys sindillus Memon, Meier Manan, 2006, syn. nov. = Halys spinosus Shaikh, Memon Shah, 2011, syn. nov. = Halys mulberriensis Memon, Parveen, Ahmad Shaikh, 2016, syn. nov. = Halys noakoatensis Memon, Parveen, Ahmad Shah, 2017, syn. nov.; H. serrigera Westwood, 1837 = Halys fabricii Memon, Ahmad Perveen, 2002. Halys neelgiriensis, Halys rugosa and Halys persa are considered as incertae sedis. The diagnostic characters of species of Halys are compared and keys to males and females of Halys species occurring in India are provided. [Species Zoobank url: urn:lsid:zoobank.org:author:18A62E8C-4AFE-4180-AD5B-7F502BB819F2].

Functional outcome and multidimensional evaluation of patients with Mutars® reconstructions post lower limb tumor resection and rehabilitation: preliminary results.

Modular prostheses are commonly used to reconstruct defects of the distal femur and proximal tibia after bone tumor resection. Improving patient's autonomy and giving them a better quality of life are the main goals. Post-surgical rehabilitation is very relevant after surgery. The aim of this paper is to study the short and mean time functional outcomes in patients treated with Mutars® reconstructions after proximal and distal lower limb tumor resection with a multidimensional analysis and a standardized stabilometric examination. Twenty-one patients (7 male and 14 women, mean age and standard deviation: 61.76±14.68) affected by primitive bone tumor (28.6%) or metastatic bone tumor (71.4%), treated with MUTARS® reconstructions after proximal (71%) , distal(23.8%) and both (4.8%) lower limb tumor resections, accepted to take part to the study. They were evaluated after one week (T0), one month (T1), three months (T2), six months (T3) and one year (T4) after surgery with standardized clinic evaluation and with multidimensional validated scales. Visual Analogic Scale (VAS during active movement), Short Physical Performance Battery (SPPB), Eastern Cooperative Oncology Group (ECOG), Karnofsky Performance Status (KPS), MusculoSkeletal Tumor So¬ciety rating (MSTS), Toronto Extremity Salvage Score scale (TESS). Patients underwent to an instrumental standardized stabilometric test after one month from surgery and in following evaluations to measure stand¬ing balance. Patients underwent to a rehabilitation program during three months after surgery. There was a significant improvement of hip flexion range of movement (p level: 0.008), and gait modalities (without aids) after three months from surgery (p level 0.02). There was a significant reduction in VAS after one month of surgery (p level 0.00). It was observed an increase of the SPPB value at T3 (p level 0.01), of MSTS and TESS at T2. Balance stabilometric evaluation did not showed significant increase at each timing also if Romberg perimeter decrease progressively. These preliminary results showed that, oncological patients, affected by bone tumors or metastasis, surgical treated with MUTARS® implant and admitted to the rehabilitation programs, can improve their gait modalities and functional daily life outcomes, until three months from surgery. A large sample will allow, necessary to define standardized rehabilitation protocols after oncological orthopedic sur¬gery, in order to introduce guidelines that can be applied routinely.

Evaluation of quality of life and static balance in postmenopausal osteoporosis women after Tai Chi Chuan practice: an observational randomized case control study.

Post-menopausal osteoporosis women are at increased risk for skeletal fractures with higher mortality and lower quality of life. Some studies have reported fall risk reduction in the elderly after Tai chi practice. Tai chi is a weight bearing mind-body exercise that has been reported to positively influence bone mineral density and improve postural control in different pathologies. The aim of this observational randomized case control study is to evaluate the effect of Tai chi on balance and quality of life in postmenopausal women with osteoporosis. A total of 98 postmenopausal osteoporosis women, aged 70.6±8.2 years (mean and standard deviation), (mean T-score of the hip and spine were-2.9± 0.92 and -2.8±1.08), have been recruited in outpatients University Physical Medicine and Rehabilitation Hospital between June 2016 and September 2018. They have been randomized to a Tai group (56 patients, mean age 71.61±7.97 years) practiced 6-month Tai chi program, two times week, plus standard care or to a Control Group (42 patients, mean age 69.71±8.61 years) practiced usual care. Patients with oncological, neurological, cognitive, vestibular and visual diseases were excluded. Patients were evaluated at baseline (T0), prior Tai chi and after 6 month (T1) with 36-Item Short Form Health Survey (SF-36), and a stabilometric-standardized exam performed for the evaluation, respectively, of the quality of life and the static balance. The groups were homogenous at baseline. T1 evaluation showed better results in Tai chi group, in SF36 Physical functioning (p level: 0.021), Physical health pain (p level: 0.020), Physical composite score (p level: 0.003) scores, compared with control group. There were not significant differences between groups in stabilometric analysis. Tai chi group showed significant better stabilometric values at T1 compared with T0 in mean anterior-posterior (p level: 0.001) and medio-lateral (p level: 0.019) velocity, in perimeter (p level 0.001) , and in the area of the ellipse ( p level 0.006) in a within group analysis. Tai chi seemed to be effective in improving physical aspects of quality of life, in postmenopausal women with osteoporosis. Standing balance seems to increase after 6 months Tai chi program, in post-menopausal also if results were not significant. Further studies will be useful to measure effects of a Tai chi longer practice, as literature suggests, and a possible reduction of falling risk and fractures.

Revision of genus Acrozangis Breddin (Hemiptera: Pentatomidae: Pentatominae) with description of a new species from India.

The genus Acrozangis Breddin, 1900 is revised from India, with description of a new species, Acrozangis dakshinae sp. nov. from southern India. As the holotype female specimen of the type species of Acrozangis, Acrozangis semiprasina Breddin, 1900, is destroyed, the male specimen assigned to A. semiprasina by Breddin (1900) has been designated as the neotype. Though Acrozangis superficially resembles the genera Cuspicona or Glaucias, the very distinct morphological characters such as the resting of the apex of basal abdominal tubercle on a groove of the posterior apex of sternal carina or in other words the apex of basal abdominal tubercle concealed by the posterior apex of metasternal carina and well developed mesosternal carina, lamellate anteriorly and not surpassing forecoxae make this genus unique. A. semiprasina Breddin, 1900 and C. antica Vollenhoven, 1868 were found to be subjective synonyms. The species C. antica Vollenhoven, 1868 is not congeneric to species of Cuspicona Dallas and hence transferred from Cuspicona to Acrozangis and proposed A. antica comb. nov. A lectotype for Cuspicona antica Vollenhoven, 1868 is also designated. A. semiprasina is proposed as a new synonymy to A. antica. The morphological characters support the placement of A. antica in the tribe Nezarini rather than in the Rhynchocorini (where Cuspicona is placed) are discussed.

Urinary biomarkers reporting weakness and validation failure in Type 2 diabetic nephropathy: systematic review.

For better identification of novel diagnostic urinary biomarker in Type 2 diabetic nephropathy (T2DN), methodological and reporting quality is as important as validity of biomarkers. The aim of this systematic review is to find out the best-reported diagnostic urinary biomarkers study in T2DN based on STARD criteria. We also analyzed the validity of urinary markers in the selected articles those followed STARD criteria. The diagnostic accuracy of urinary biomarkers on T2DN is not conclusive because of the poor reporting quality and differences in adjustment for conventional risk factors. For a proper validation of urinary biomarkers on T2DN, in future large well-designed longitudinal studies, with specific prediction analysis and validation of the biomarkers by adjusting with possible conventional risk factors.

Animal-Derived Protein Consumption Is Associated with Muscle Mass and Strength in Community-Dwellers: Results from the Milan EXPO Survey.

OBJECTIVES: Behavioral factors, including protein intake, influence the quantity and quality of skeletal muscle. The aim of this study was to explore the relationship between animal-derived protein intake and muscle mass and function in a large sample of unselected community-dwellers. MATERIAL AND METHODS: The VIP (Very Important Protein) study, conducted during Expo 2015 in Milan, was a population survey aimed at assessing major health metrics in a population outside of the research setting, with a special focus on the relation between animal-derived protein intake and muscle mass and function. A brief questionnaire exploring lifestyle habits, dietary preferences and the consumption of selected foods was administered. Muscle mass was estimated by calf circumference (CC) and mid-arm muscle circumference (MAMC) of the dominant side. Muscle strength of upper and lower extremities was assessed through handgrip strength testing and repeated chair stand test, respectively. RESULTS: The mean age of the 1,853 participants was 50.3 years (standard deviation: 15.7; range: 18-98 years), of whom 959 (51.7%) were women. Participants in the highest tertile of protein consumption showed better performance at both the handgrip strength (p <0.001) and chair stand tests than those in the lowest tertile (p <0.01). The same results were found for CC (p <0.001) and MAMC (p <0.001). Participants with high protein intake and engaged in regular physical activity showed the higher scores in all the assessed domains. CONCLUSIONS: The results of the VIP survey suggest an association between animal-derived protein intake and muscle mass and strength across ages. Our findings also indicate a synergistic effect of animal-derived protein intake and physical activity on muscle-related parameters.