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Bananas are among the world’s most important cash and staple crops but are threatened by various devastating pathogens. The phytohormone salicylic acid (SA) plays a key role in the regulation of plant immune response. Tracking the expression of SA-responsive marker genes under pathogen infection is important in pathogenesis elucidation. However, the common SA-responsive marker genes are not consistently induced in different banana cultivars or different organs. Here, we conducted transcriptome analysis for SA response of a banana cultivar, ‘Pei-Chiao’ (Cavendish, AAA genome), and identified three genes, MaWRKY40, MaWRKY70, and Downy Mildew Resistant 6 (DMR6)-Like Oxygenase 1 (MaDLO1) that are robustly induced upon SA treatment in both the leaves and roots. Consistent induction of these three genes by SA treatment was also detected in both the leaves and roots of bananas belonging to different genome types such as ‘Tai-Chiao No. 7’ (Cavendish, AAA genome), ‘Pisang Awak’ (ABB genome), and ‘Lady Finger’ (AA genome). Furthermore, the biotrophic pathogen cucumber mosaic virus elicited the expression of MaWRKY40 and MaDLO1 in infected leaves of susceptible cultivars. The hemibiotrophic fungal pathogen Fusarium oxysporum f. sp. cubense tropical race 4 (TR4) also consistently induced the expression of MaWRKY40 and MaDLO1 in the infected roots of the F. oxysporum f. sp. cubense TR4-resistant cultivar. These results indicate that MaWRKY40 and MaDLO1 can be used as reliable SA-responsive marker genes for the study of plant immunity in banana. Revealing SA-responsive marker genes provides a stepping stone for further studies in banana resistance to pathogens.

Breast cancer is among the lethal types of cancer with a high mortality rate, globally. Its high prevalence can be controlled through improved analysis and identification of disease‐specific biomarkers. Recently, long non‐coding RNAs (lncRNAs) have been reported as key contributors of carcinogenesis and regulate various cellular pathways through post‐transcriptional regulatory mechanisms. The specific aim of this study was to identify the novel interactions of aberrantly expressed genetic components in breast cancer by applying integrative analysis of publicly available expression profiles of both lncRNAs and mRNAs. Differential expression patterns were identified by comparing the breast cancer expression profiles of samples with controls. Significant co‐expression networks were identified through WGCNA analysis. WGCNA is a systems biology approach used to elucidate the pattern of correlation between genes across microarray samples. It is also used to identify the highly correlated modules. The results obtained from this study revealed significantly differentially expressed and co‐expressed lncRNAs and their cis‐ and trans‐regulating mRNA targets which include RP11‐108F13.2 targeting TAF5L, RPL23AP2 targeting CYP4F3, CYP4F8 and AL022324.2 targeting LRP5L, AL022324.3, and Z99916.3, respectively. Moreover, pathway analysis revealed the involvement of identified mRNAs and lncRNAs in major cell signalling pathways, and target mRNAs expression is also validated through cohort data. Thus, the identified lncRNAs and their target mRNAs represent novel biomarkers that could serve as potential therapeutics for breast cancer and their roles could also be further validated through wet labs to employ them as potential therapeutic targets in future.

Objective: Focused assessment with sonography for trauma (FAST) is a widely used imaging technique for the diagnosis of blunt abdominal trauma and has its limitations and advantages. A meta-analysis was completed to evaluate the reliability of FAST, in the diagnosis of blunt torso trauma. Materials and Methods: A search was completed with Google Scholar, PubMed, National Center for Biotechnology Information (NCBI), MEDLINE, and Medscape databases, from 1993 up to 2020. Eligible studies were included for information about FAST examination of abdominal trauma. The animal research was excluded from this review process. The eligible studies were first categorized and then data analysis was performed, according to specific pathologic conditions. This literature review retrieved studies’ sample size, application, sensitivity, and a specificity of diagnosis using FAST for abdominal trauma. Results: In total, 100 articles were identified through the database search. Besides, five articles were identified through other sources. Then, screening was performed, and as such, 46 published studies were included that had a qualitative synthesis. Conclusion: FAST has a high sensitivity and specificity in the diagnosis of blunt abdominal trauma. However, a large range of sensitivity and specificity of FAST in the evaluation of torso trauma reveal that sonography is operator, technique, and equipment dependent.

Recurrent selection is a cyclical breeding procedure in which selection is made generation after generation, with a reunion of selected plants to produce a new population for the next cycle of selection. Maize (Zea mays L.) base population 'PSEV3' was developed by using selfed progeny recurrent selection in spring and summer crop seasons during 2014 to 2016. During Summer 2017, two improved maize populations [PSEV3-(S1)-C1 and PSEV3-(S2)-C2], original genotype (PSEV3-C0) and three check varieties (two OPV - open-pollinated varieties - Azam and Jalal, and HV - hybrid variety - Kiramat) were assessed for silking and yield traits across four environments including two planting dates and two sites i.e., Cereal Crops Research Institute (CCRI), Pirsabak - Nowshera, and University of Agriculture (UAP), Peshawar, Pakistan. Genotypes and planting dates enunciated significant (p≤0.01) differences for majority of the traits. Maize improved populations (C1 and C2) enunciated comparable values with early flowering and least cob height compared to base population and check genotypes. On average, PSEV3-(S2)-C2 was foremost and exhibited maximum mean values for yield traits with enhanced grain yield with optimum planting at CCRI, followed by PSEV3-(S1)-C1. Base population - C0 and check genotypes were observed with delayed silking and least grain yield across the environments. Selfed progeny recurrent selection was established as an efficient breeding method in improving maize base populations.

Southern blight or collar rot of bell pepper (Capsicum annuum L.) caused by Sclerotium rolfsii Sacc., is a serious disease that results in significant yield losses annually. A pot experiment was carried out for the management of this disease using dry biomass of Datura metel, a medicinal plant of the family Solanaceae. The soil was amended with 0.5, 1.0, …, 3.0% dry biomass of D. metel with and without the inoculation of S. rolfsii. The highest disease incidence (100%) was recorded in the positive control where the soil was inoculated with S. rolfsii without any soil amendment. The disease was completely controlled by 2% soil amendment. This soil amendment treatment enhanced bell pepper yield by 30% over the negative control (without any inoculation or amendment) and 136% over the positive control. Activities of defense-related enzymes namely polyphenol oxidase (PPO), peroxidase (POX), and phenylalanine ammonia lyase (PAL) were significantly increased in the positive control. However, the activities of these enzymes were significantly dropped due to the soil amendment with D. metel. This study concluded that the application of 2% dry biomass of D. metel can control collar rot disease resulting in a significant increase in the yield of bell pepper.

Background The initial stages of human life including the fetal period, infancy and early childhood are the most critical periods of human growth and development. Due to immature immune system and rapid development phase, this is the most sensitive phase to health challenges. The exposure to xenobiotics of high toxicity, such as aflatoxins (AFs), can interfere with normal development of the body and potentially lead to severe health complications. Scope and approach This article provides a comprehensive review on the occurrence and health implications of AFs exposure in the early stages of life, including the impacts on child growth, development, immune and hepatic systems. The mechanisms involved in AFs’ toxicity and control measures in infant foods are also described, along with a discussion on recent intervention strategies to mitigate the early life exposure to dietary AFs. Key findings and conclusions Human AFs exposure via utero and through breast milk, infant formula milk and infant foods has been linked to a number of health implications including adverse birth outcomes, impaired growth and development, suppressed immune system, and hepatic dysfunction, especially in African and Asian countries. The occurrence of AFs in infant foods in developing countries, even when reasonably strict regulations are in place, indicate that much needs to be done to ensure the proper implementation of the regulations, in order to achieve significant reductions in exposure. This carries with it many economic and cultural challenges that need to be addressed, including implementation of good agricultural practices and intervention programs aiming to supplement nutrients to reduce child malnutrition and decrease the consumption of aflatoxin-contaminated foods.

Fast, accurate, and reliable diagnostic tests are critical for controlling the spread of the coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The current gold standard for testing is real-time PCR; however, during the current pandemic, supplies of testing kits and reagents have been limited. We report the validation of a rapid (30 minutes), user-friendly, and accurate microchip real-time PCR assay for detection of SARS-CoV-2 from nasopharyngeal swab RNA extracts. Microchips preloaded with COVID-19 primers and probes for the N gene accommodate 1.2-μL reaction volumes, lowering the required reagents by 10-fold compared with tube-based real-time PCR. We validated our assay using contrived reference samples and 21 clinical samples from patients in Canada, determining a limit of detection of 1 copy per reaction. The microchip real-time PCR provides a significantly lower resource alternative to the Centers for Disease Control and Prevention-approved real-time RT-PCR assays with comparable sensitivity, showing 100% positive and negative predictive agreement of clinical samples.

Summary Introduction: Medicinal plants are found throughout the world but most are considered weeds. They are – directly or indirectly – the major source of medicines in pharmaceutical and herbal industries. Formulations used to prepare medicines or the method of use for these plants are mainly based on folk or traditional knowledge. This folk knowledge is not documented in many areas and needs to be explored. Objectives: This study was aimed to enlist the seasonal weed species with traditional medicinal usage in Toba Tek Singh District, Punjab, Pakistan. Methods: Field surveys were arranged in winter and summer 2019–2020 to enlist the important medicinal weeds and traditional knowledge of the local community. Data collected were as follows: local name of weed, medicinal use, method and part used. Results: Numerous wild perennial, biennial and annual plants were identified, 30 of them were ethnomedicinally important in the local community. They were grouped in 16 families. It was found that whole weed is used in many prescriptions (37%). Achyranthes aspera L. (Amaranthaceae) was the most common weed used in treating fevers, respiratory problems and asthma. Cichorium intybus L. (Asteraceae) was used in summer drinks to reduce thirst, improve digestion and liver function. Chenopodium album L. (Amaranthaceae) was used with 0.71 UV and 0.147 RFC values. Medicago polymorpha L. (Fabaceae) was used to treat kidney, intestinal and bladder infections. Its UV was 0.65 and RFC was 0.121. Tribulus terrestris L. (Zygophyllaceae) was used in impotency treatment, and in the removal of kidney stones and urinary tract infections treatment. It has 0.63 UV and 0.21 RFC values. This weed also showed the highest Fidelity Level (FL) (77%), as compared to other weeds. Conclusion: It was concluded that there are many significant medicinal weeds in the Toba Tek Singh District, Punjab, Pakistan that are used in traditional medicines in treating various disorders. These plants also showed herbal or pharmacological importance that can be used to develop medicine at commercial scale.

Objective: Diabetes can lead to diabetic retinopathy, which damages the retina due to blood flow remodeling of occular vessels. Early stages of diabetic retinopathy may not present with patient symptoms. Doppler indices, of the ophthalmic arteries, could help in determining the effect of diabetic vascular remodeling. This research was designed to compare the Doppler indices, in the ophthalmic artery and central retinal artery, in both diabetic and nondiabetic patients. Materials and Methods: This was a cross-sectional observational study of 72 total patients. Sonography was performed on the ophthalmic arteries of 36 diabetics and 36 nondiabetics, to compare Doppler indices. All patients were voluntarily consented to this research that was approved by the university’s Institutional Review Board (IRB). Doppler parameters recorded were peak systolic velocity, end dystopic velocity, resistive index, and pulsatility index, which were taken in both patient groups and compared. Results: A significant difference was noted in the ophthalmic artery peak systolic velocity, end-diastolic velocity, pulsatility index, and resistive index for diabetic and nondiabetic individuals, with a statistically significant set at .01. Conclusions: There was a significant difference between diabetic and nondiabetic ophthalmic Doppler indices in this cohort of patients. This cohort demonstrated vascular remodeling of the ophthalmic arteries, caused by diabetes; therefore, blood flow resistance was increased due to diabetes.

Graphical abstract, An efficient protocol for in-vitro propagation of an important ornamental crop, Petunia hybrida Vilm. Cv. “Bravo” was developed. The explants that were used to carry out the experiment were Leaf segments, nodal segments and shoot tips. Nodal segments recorded highest per cent asepsis followed by shoot tips and leaf segments. Asepsis was found to be highest when the explants were sterilized with Fungicide (Carbendazim) 0.02% for the duration of 30 min followed by 0.1% HgCl2 for duration of 10 min and then ethanol 70% for 10 s. Longer duration of the sterilant treatment showed more necrotic effects on the explants, thus mercuric chloride treatment when given for 5 min proved to be more effective in terms of survival of the explants. Maximum establishment per cent was recorded in Murashige and Skoog (MS) media fortified with BAP (1.5 mg L−1) and IBA (0.5 mg L−1) in shoot tips and nodal segments, i.e. 97.90 and 95.74% respectively. Callus was efficiently induced and developed when PGR amalgamation of BAP (0.1 mg L−1) and 2,4-D (1.5mg L−1) was used. Kinetin at the concentration of 2.0 mg L−1 along with IBA at 0.5mg L−1 recorded highest callus regeneration in both leaf and internodal segment derived callus. Maximum proliferation percent of shoots (97.90%), highest number of shoots (20.50 explant−1) and maximum length of shoot (2.70 cm) was recorded in PGR combination of IBA and BAP both at 0.5 mg L−1 concentration level. Rhizogenesis was recorded to be highest in the MS media containing IBA 1.00 mg L−1. Best hardening media which recorded maximum survival per cent 92.50% was noticed on the media formulation comprised of equal ratio of perlite and vermiculite mix, under poly house conditions.

The major limitation with the oral administration of most of the phytochemicals is their low aqueous solubility and bioavailability. Thymoquinone (THQ) is one of the most widely used phytochemicals used to treat a variety of diseases. However, strong lipophilic characteristics limit its clinical application. Therefore, this study was aimed to design novel chitosan (C) modified polycaprolactone (PL) nanoparticles (NPs) for improved oral bioavailability of THQ. THQ-CPLNPs was optimized 33-Box–Behnken design. After that, the optimized THQ-CPLNPs was characterized by different parameters. THQ-CPLNPs showed the size, PDI, and ZP of 182.32 ± 6.46 nm, 0.179 ± 0.012, and +21.36 ± 1.22 mV, respectively. The entrapment and loading capacity were found to be 79.86 ± 4.36%, and 13.45 ± 1.38%, respectively. THQ-CPLNPs exhibited burst release in initial 2 h followed by prolonged release up to 24 h in simulated intestinal fluids. THQ-CPLNPs showed excellent mucoadhesion properties which were further confirmed with the intestinal permeation study as well as confocal microscopy. The study revealed higher permeation of THQ-CPLNPs compared to neat THQ suspension (THQ-S). Moreover, in vivo gastric irritation study revealed good compatibility of THQ-CPLNPs with the gastric mucosa. Furthermore, pharmacokinetic results depicted ∼3.53-fold improved oral bioavailability of THQ from THQ-CPLNPs than THQ-S. Therefore, from the findings, it was concluded that the prepared polymeric NPs could be an effective delivery system for improved oral bioavailability of THQ.

Staphylococcus aureus is a major causative agent of intra-mammary infections in dairy animals with potential virulence of surface components, toxins, and extracellular enzymes. About 74% quarter prevalence of S. aureus in bovine udder with overall prevalence exceeding 61% in dairy animals. About 17 different serotypes of dairy originated S. aureus have been reported with 24 virulence coding genes for leukocidins (lukED/lukM), pyrogenic toxin super antigen (PTSAg), haemolysins (hla-hlg), toxic-shock syndrome toxin (tst), enterotoxins (sea-seo, seu), exfoliative toxins (eta, etb), and genes for methicillin (mecA) and penicillin (blaZ) resistance. Attainment of refuge inside the macrophages and neutrophils is a major cause of S. aureus mastitis persistence. Mammary prebiotics and probiotics are recently being used as alternatives to antibiotic for the prevention of mastitis. Literature showed anti- staphylococcus vaccines with different results depending upon types of immunization, route of administration and adjuvant used. Studies has shown that herd specific as well as commercial S. aureus vaccines reduce new infections in dairy animals. Experiments are still in progress for the use of vaccines against S. aureus mastitis with optimal efficacy and reliability. Perhaps, there might be bright future because of highly satisfactory trial results of mastitis vaccines in the lab animals.

In this paper, we provide a family of bounds for the rate at which the functions of many inputs can be computed in-network on general topologies. Going beyond simple symmetric functions where the output is invariant to the permutation of the operands, e.g., average, parity, we describe an algorithm that is analyzed to provide throughput bounds (both lower and upper) for the general functions. In particular, we analyze our algorithm when the function to be computed is given as a binary tree schema. Our lower bounds depend on schema parameters like the number of operands and graph parameters like the second largest eigenvalue of the transition matrix of simple random walk on network graph, the maximum and minimum degree of any node in the network. The lower bounding technique that we have used is based on the network flows and can capture general multi-commodity flow settings. Our proposed algorithm uses the well-known simple random walk on a network as its basic primitive for routing. We show that the lower bound obtained on the rate of computation is tight for the complete network topology, the hypercube and the star topology. We also present an upper bound on the expected latency of any data operand in terms of the height of schema, well-studied random walk parameter like the hitting time, and the relative distance from the critical data rate. For the computation time of symmetric functions on the random geometric graph under the gossip model, our approach achieves an order-optimal $$\widetilde{O}(n)$$ time despite enforcing a binary tree schema for function computation. In general, Big-O notation represents an upper bound and $$\widetilde{O}$$ hides $$\text {poly}\log n$$ factors.

Selenium (Se) is an important microelement with numerous positive effects on human health and diseases. It is important to specify that the status and consumption of Se are for a specific community as the levels of Se are extremely unpredictable between different populations and regions. Our existing paper was based on the impacts of Se on human health and disease along with data on the Se levels in Middle Eastern countries. Overall, the findings of this comprehensive review show that the consumption and levels of Se are inadequate in Middle Eastern nations. Such findings, together with the growing awareness of the importance of Se to general health, require further work primarily on creating an acceptable range of blood Se concentration or other measures to determine optimal Se consumption and, consequently, to guarantee adequate Se supplementation in populations at high risk of low Se intake.

The success of chemical control depends on toxicity of insecticides against insect pests. Camponotus sericeus is an important urban pest with the ability to cause substantial damage to wooden structures, but there is a lack of information on toxicity of insecticides against C. sericeus. To determine the insecticide toxicity, workers of C. sericeus were exposed to 17 insecticides from different classes: carbamate (methomyl, bendiocarb), organophosphate (chlorpyrifos, profenofos, temephos), pyrethroid (bifenthrin, deltamethrin, permethrin), neonicotinoid (acetamiprid, imidacloprid, thiamethoxam), avermectin (abamectin, emamectin), pyrrole (chlorfenapyr), phenylpyrazole (fipronil), and spinosyn (spinosad and spinetoram), via residual bioassay method. The LC50 ranged from: 0.15 to 0.20 µg/vial for carbamates, 0.09 to 0.27 µg/vial for organophosphates, 0.09 to 0.44 µg/vial for pyrethroids, 0.02 to 0.67 µg/vial for neonicotinoids, 0.54 to 0.82 µg/vial for avermectins, 0.78 µg/vial for pyrrole, 0.62 µg/vial for phenylpyrazole, and 1.96 to 2.05 µg/vial for spinosyns. Overall, acetamiprid was the most toxic one among the tested insecticides followed by permethrin, temephos, profenofos, bendiocarb and methomyl, while spinosad and spinetoram were the least toxic insecticides. Considering the potential toxicity of different insecticides against C. sericeus, future studies could investigate the practical application of these insecticides in order to design an effective management plan.

Worm infestations are still quite common in the whole world and more so prevalent in tropical countries. Ascariasis is one of the most common form of parasitic infections in humans. It is found in any part of the gastrointestinal tract, including hepatobiliary system as well. It can present as a wide range of clinical spectrum ranging from asymptomatic carriers to anemia, bowel obstruction, cholangitis, and obstructive jaundice besides other manifestations. Various diagnostic modalities are used to establish diagnosis of this condition including clinical examination, ultrasonography, CT scan, and magnetic resonance cholangiopancreatography (MRCP). Most of the times, medical management is sufficient; however, many times due to complications associated with these worms, endoscopic or surgical intervention is required. In this review, we will discuss various clinical features, diagnostic modalities, and treatment options of this disease.

Background: This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe and effective passive immunization treatment option for COVID-19. Materials & methods: PCP was fractionated by modified caprylic acid precipitation followed by ultrafiltration/diafiltration to produce hyperimmune C-IVIG. Results: In C-IVIG, the mean SARS-CoV-2 antibody level was found to be threefold (104 ± 30 cut-off index) that of the PCP (36 ± 8.5 cut-off index) and mean protein concentration was found to be 46 ± 3.7 g/l, comprised of 89.5% immunoglobulins. Conclusion: The current method of producing C-IVIG is feasible as it uses locally available PCP and simpler technology and yields a high titer of SARS-CoV-2 antibody. The safety and efficacy of C-IVIG will be evaluated in a registered clinical trial (NCT 04521309).

The present study was designed to examine psychosocial predictors of quality of life (QoL) such as body image, self-esteem, impact of Vitiligo (psychologically and socially), and perceived stigmatization in patients with Vitiligo. The sample (N =120) comprised of individuals with Vitiligo recruited from dermatology units of different hospitals in Lahore. Body Image State Scale (Cash, Fleming, Alindogan, Steadman, & Whitehead 2002), Rosenberg Self-Esteem Scale (Rosenberg, 1965), Vitiligo Impact Scale (Rammam, Khaitan, Mehta, Sreenivas, & Gupta, 2014), Perceived Stigmatization Questionnaire (Lawrence, Fauerbach, Heinberg, & Thomas, 2006) and Dermatology Life Quality Index (Finlay & Khan, 1994) were used as assessment measures. Results revealed that most of the individuals with Vitiligo reported poorer perception of QoL; while, men with Vitiligo expressed better perceived QoL as compared to women. Individuals with both types of Vitiligo (lesions on exposed/unexposed regions) expressed poor body image, negative impact of Vitiligo on their psycho-social functioning, and higher levels of perceived stigmatization. Individuals with exposed Vitiligo affected regions exhibited lower self-esteem. In addition, body image, impact of Vitiligo (psychologically and socially), and perceived stigmatization (absence of friendly behavior) significantly predicted QoL. It was concluded that Vitiligo had a greater impact on individual’s psychological health and social functioning rather than physiological complications.

Human papillomavirus type-16 (HPV-16) is the major HPV type involved in causing cervical cancer among women. The disease burden is high in developing and underdeveloped countries. Previously, the constitutive expression of HPV-16 L1 protein led to male sterility in transplastomic tobacco plants. Here, the HPV-16 L1 gene was expressed in chloroplasts of Nicotiana tabacum under the control of an ethanol-inducible promoter, trans-activated by nucleus-derived signal peptide. Plants containing nuclear component were transformed with transformation vector pEXP-T7-L1 by biolistic gun. The transformation and homoplasmic status of transformed plants was verified by polymerase chain reaction and Southern blotting, respectively. Protein was induced by spraying 5% ethanol for 7 consecutive days. The correct folding of L1 protein was confirmed by antigen-capture ELISA using a conformation-specific antibody. The L1 protein accumulated up to 3 μg/g of fresh plant material. The L1 protein was further purified using affinity chromatography. All transplastomic plants developed normal flowers and produced viable seeds upon self-pollination. Pollens also showed completely normal structure under light microscope and scanning electron microscopy. These data confirm the use of the inducible expression as plant-safe approach for expressing transgenes in plants, especially those genes that cause detrimental effects on plant growth and morphology.

AIM We aimed to evaluate the genetic variation of tumor necrosis factor-α (TNF-α) 308 G>A (rs1800629) and transforming growth factor (TGF) β1G>C (rs1800471) to confer risk in patients with recurrent miscarriage in highly consanguineous population of Kashmir (North India). METHODS A total of 200 women who experienced two or more recurrent miscarriages (along with 100 spouses, 60 products of conception, and 240 healthy controls) with two or more full-term pregnancies were recruited from the same geographical region and evaluated by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS TNF-α 308 G>A variant genotype (AA) was significantly associated with recurrent miscarriage cases (2.5% vs. 0.4% controls, respectively; p C showed no association with recurrent miscarriage cases in our population. CONCLUSION The study found both TNF-α 308 G>A variants are significantly associated with an increased susceptibility for recurrent miscarriages to cause pregnancy losses but on the other hand TGF β1 does not seem to impact the outcome of pregnancy in our population.

Recent studies implicate the defects or altered expression of the orphan nuclear receptor Nurr1 gene in the substantia nigra in Parkinson's disease pathogenesis. In an attempt to corroborate the treatment-modifying disease that would replicate the effect of Nurr1, it has been found that amodiaquine and Nurr1 had the same chemical scaffolding, indicating a crucial structure-activity relationship. Interestingly, amodiaquine stimulate the transcriptional function of Nurr1 by physical interaction with its ligand-binding domain (LBD). However, the signaling route by which Nurr1 is activated by amodiaquine to cause the protective effect remains to be elucidated. We first demonstrated that amodiaquine treatment ameliorated behavioural deficits in 6-OHDA Parkinson's disease mouse model, and it promoted dopaminergic neurons protection signified by Tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA; Tyrosine hydroxylase (TH) protein expression level and the immunoreactivity in the substantia nigra compacta. Subsequently, we used inhibitors to ascertain the effect of amodiaquine on Akt and P38 Mapk as crucial signaling pathways for neuroprotection. Wortmannin (Akt Inhibitor) induced a significant reduction of Akt mRNA; however, there was no statistical difference between the amodiaquine-treated group and the control group suggesting that amodiaquine may not be the active stimulant of Akt. Western blot analysis confirmed that the phosphorylated Akt decreased significantly in the amodiaquine group compared to the control group. In the same vein, we found that amodiaquine substantially increased the level of phosphorylated P38 Mapk. When P38 Mapk inhibited by SB203580 (P38-Mapk Inhibitor), the total P38 Mapk but not the phosphorylated P38 Mapk decreased significantly, while tyrosine hydroxylase significantly increased. These results collectively suggest that amodiaquine can augment tyrosine hydroxylase expression via phosphorylated P38 Mapk while negatively regulating the phosphorylated Akt in protein expression.

Failed neuroprotection leads to the initiation of several diseases. SOX1 plays many roles in embryogenesis, oncogenesis, and male sex determination, and can promote glioma stem cell proliferation, invasion, and migration due to its high expression in glioblastoma cells. The functional versatility of the SOX1 gene in malignancy, epilepsy, and Parkinson's disease, as well as its adverse effects on dopaminergic neurons, makes it an interesting research focus. Hence, we collate the most important discoveries relating to the neuroprotective effects of SOX1 in brain cancer and propose hypothesis worthy of SOX1's role in the survival of senescent neuronal cells, its roles in fibroblast cell proliferation, and cell fat for neuroprotection, and the discharge of electrical impulses for homeostasis. Increase in electrical impulses transmitted by senescent cells affects the synthesis of neurotransmitters, which will modify the brain cell metabolism and microenvironment.

Cryptosporidium is regarded as one of the neglected, zoonotic, food and water-borne protozoal pathogens. Cryptosporidium species (C.) have been reported from more than 30 species of domestic, wild ...

Cyclodextrin-hydrolyzing enzymes are widespread in bacteria and archaea where they play their roles in carbohydrates metabolism. They were previously characterized as cyclodextrinases, neopullulanases and maltogenic amylases. In the Carbohydrate-Active enZyme (CAZy) database, most of these enzymes are grouped into the GH13_20 subfamily of the α-amylase family GH13. Here, we have summarized the information available on the substrate specificity, structural features, physiological roles and applications of cyclodextrin-preferring glycoside hydrolases. These enzymes form a distinct group in the α-amylase family. Members of this distinct group possess an extra extension at the N-terminus, which causes a modification of the active site geometry thus making these enzymes more specific for smaller molecules like cyclodextrins than for macromolecules such as starches or pullulan. Multi-substrate specificity, hydrolytic as well as transglycosylation activities make these enzymes attractive for applications in the food and pharmaceutical industries. We have tried here to collect information available on their biochemical properties, three-dimensional structures, physiological roles and potential applications.

Introduction: Acute coronary syndrome (ACS) comes under the ambit of cardiovascular disease.APOA-1 gene plays a vital role in lipid metabolism and has been observed to have plausible role in ACS. This cross sectional case-control study was conducted to evaluate association between APOA1-75G/A(rs1799837), +83C/T (rs5069) genotypes and risk for ACS. Methods: The current case-control study that included confirmed 90 ACS cases and 150 healthy controls were genotyped for APOA1-75 G/A and +83 C/T by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLF) method. Results: APOA1-75G/A distribution of genotypes/alleles among cases and controls was seen proportionally same with no association to ACS (P = 0.5). APOA1+83 C/T variants showed protective effect with ACS where variant TT genotype presented more in controls (12%) than cases (1.6%) (P = 0.004) and likewise variant ‘T’ allele was found more in controls than ACS cases (9.4% vs.28.5% respectively: P < 0.05). Further, significantly high difference of CT genotype was seen among cases and controls 15% vs. 33% respectively (P = 0.002). The overall distribution of different haplotypes showed a marked difference in GT when compared with GC between cases and controls (P = 0.0001). Conclusion: The study shows that TT genotype and variant T allele of APOA1 +83 C/T depicted a protective role with respect to ACS whereas APOA1-75G>A showed no relation. Haplotype GT was observed to significantly over-represent in controls with its protective effect in ACS as against wild type haplotype GC.

Plain English summary Researchers have explored different types of treatment to help people with a mental illness with other problems they might be experiencing, such as their health condition and quality of life. Care models that involve many different health care providers working together to provide complete physical and mental health care are becoming popular. There has been a push from the research community to understand the value of including people with lived experience in such programs. While research suggests that people with lived experience may help a patient’s treatment, there is little evidence on including them in a team based program. This paper describes how our research team included a person with lived experience of psychosis in both the research and care process. We list some guiding principles we used to work through some of the common challenges that are mentioned in research. Lastly, experiences from the research team, lessons learned, and a personal statement from the person with lived experience (AA) are provided to help future researchers and people with lived experience collaborate in research and healthcare. Abstract Background In our current healthcare system, people with a mental illness experience poorer physical health and early mortality in part due to the inconsistent collaboration between primary care and specialized mental health care. In efforts to bridge this gap, hospitals and primary care settings have begun to take an integrated approach to care by implementing collaborative care models to treat a variety of conditions in the past decade. The collaborative care model addresses common barriers to treatment, such as geographical distance and lack of individualized, evidence-based, measurement-based treatment. Person(s) with lived experience (PWLE) are regarded as ‘experts by experience’ in the scope of their first-hand experience with a diagnosis or health condition. Research suggests that including PWLE in a patient’s care and treatment has significant contributions to the patient’s treatment and overall outcome. However, there is minimal evidence of including PWLE in collaborative care models. This paper describes the inclusion of a PWLE in a research study and collaborative care team for youth with early psychosis. Aims To discuss the active involvement of a PWLE on the research and collaborative care team and to describe the research team’s experiences and perspectives to facilitate future collaborations. Method This paper describes the inclusion of a PWLE on our research team. We provide a selective review of the literature on several global initiatives of including PWLE in different facets of the healthcare system. Additionally, we outline multiple challenges of involving PWLE in research and service delivery. Examples are provided on how recruitment and involvement was facilitated, with the guidance of several principles. Lastly, we have included a narrative note from the PWLE included in our study, who is also a contributing author to this paper (AA), where she comments on her experience in the research study. Conclusion Including PWLE in active roles in research studies and collaborative care teams can enhance the experience of the researchers, collaborative care team members, and PWLE. We showcase our method to empower other researchers and service providers to continue to seek guidance from PWLE to provide more comprehensive, collaborative care with better health outcomes for the patient, and a more satisfying care experience for the provider.

Current studies were performed to evaluate the physico-chemical characteristics and therapeutic potential of Chutrun thermal springs located in the North-west of Shigar Valley, Gilgit-Baltistan (Pakistan). Thermal springs with different mineral contents have been used by people for bathing and health purposes since old timings. The mineral water of these springs contains elements like sodium, potassium, calcium, magnesium as chlorides, fluorides, sulphates, phosphates and bicarbonates which may be responsible for cure of various diseases. Chutrun hot springs have 7.21–7.8 pH, 40–42° C Temperature, 300–310 ppm TDS, 3.1–6.7 ppm DO, 278–285 ppm hardness, 1.62–2.42 ppm turbidity, 250–260 ppm alkalinity, 500–516 ppm conductivity, 12–18 ppm sodium, 3.8–4.1 ppm potassium, 80–82 ppm calcium, 20 ppm magnesium, 9.6–12 ppm chlorides, 3.4–3.9 fluorides, 260–282 bicarbonates and 80–85 ppm sulphates. Absence of E.Coli and faecal coliforms indicated that waters from thermal springs are free from organic wastes contaminations. Water from thermal springs of Chutrun was unsuitable for drinking purposes due to the presence of high fluoride content and also small amount of total coliforms which may be due to the presence of environmental bacteria and non-protective measures during sampling but it was found suitable for bathing and other body contact activities.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new oral drugs for the therapy of patients with type 2 diabetes mellitus (T2DM). Research in the past decade has shown that drugs of the SGLT2i class, such as empagliflozin, canagliflozin, and dapagliflozin, have pleiotropic effects in preventing cardiovascular diseases beyond their favorable impact on hyperglycemia. Of clinical relevance, recent landmark cardiovascular outcome trials have demonstrated that SGLT2i reduce major adverse cardiovascular events, hospitalization for heart failure, and cardiovascular death in T2DM patients with/without cardiovascular diseases (including atherosclerotic cardiovascular diseases and various types of heart failure). The major pharmacological action of SGLT2i is through inhibiting glucose re-absorption in the kidney and thus promoting glucose excretion. Studies in experimental models of atherosclerosis have shown that SGLT2i ameliorate the progression of atherosclerosis by mechanisms including inhibition of vascular inflammation, reduction in oxidative stress, reversing endothelial dysfunction, reducing foam cell formation and preventing platelet activation. Here, we summarize the anti-atherosclerotic actions and mechanisms of action of SGLT2i, with an aim to emphasize the clinical utility of this class of agents in preventing the insidious cardiovascular complications accompanying diabetes.

BackgroundSclerotium rolfsiiis a soil-borne fungal pathogen causing diseases in more than 500 plant species. It causes southern blight disease in chili. Chemical fungicides are used to control this disease, which also pollute the environment. The present study was designed to assess the potential of two species of plant-growth-promoting rhizobacteria (PGPR) viz.Bacillus megateriumandPseudomonas fluorescence, and an allelopathic weed,Anagallis arvensisL., for the control of southern blight disease of chili.ResultsInitially, three PGPR strains, viz.B. megateriumOSR3,B. megateriumZMR6, andP. fluorescencePF-097, were selected for their in vitro antagonistic assessment againstS. rolfsiiby dual culture technique on potato dextrose agar medium. OSR3 showed the highest antagonistic potential (68%), followed by PF-097 (54%) and ZMR6 (33%).In a pot experiment, the two best strains of PGPR, namely OSR3 and PF-097, and dried biomass ofA. arvensis(DBA) in different concentrations (1, 2 and 3%) were used to manage southern blight disease of chili.In positive control treatment (S. rolfsiionly), plant survival was low (73%) than the negative control (100%). OSR3, PF-097, OSR3 + 2% DBA, and PF-097 + 2% DBA significantly enhanced plant survival over positive control. The highest increase in chili growth over positive control was recorded due to OSR3, followed by PF-097 inoculations. Contents of carotenoid and chlorophyll were significantly decreased due to the fungal pathogen and improved due to PGPR strains. Application of the two PGPR strains and different concentrations ofA. arvensisdistinctly increased the catalase (CAT), peroxidase (POX), and polyphenol peroxidase (PPO) activities over positive control.ConclusionsThe present study concluded that PGPR strainsB. megateriumOSR3 andP. fluorescencePF-097 can control southern blight disease effectively and increase growth and yield of chili.

Background Forkhead box P3 (FOXP3) is a specific marker for immunosuppressive regulatory T (T-reg) cells. T-regs and an immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO), are associated with advanced disease in cancer. Aim To evaluate the co-expression of FOXP3 and IDO in triple negative breast cancer (TNBC) with respect to hormone-positive breast cancer patients from Pakistan. Methods Immunohistochemistry was performed to analyze the expression of FOXP3, IDO, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor on tissues of breast cancer patients (n = 100): Hormone-positive breast cancer (n = 51) and TNBC (n = 49). A total of 100 patients were characterized as FOXP3 negative vs positive and further categorized based on low, medium, and high IDO expression score. Univariate and multivariate logistic regression models were used. Results Out of 100 breast tumors, 25% expressed FOXP3 positive T-regs. A significant co-expression of FOXP3 and IDO was observed among patients with TNBC (P = 0.01) compared to those with hormone-positive breast cancer. Two variables were identified as significant independent risk factors for FOXP3 positive: IDO expression high (adjusted odds ratio (AOR) 5.90; 95% confidence interval (CI): 1.22-28.64; P = 0.03) and TNBC (AOR 2.80; 95%CI: 0.96-7.95; P = 0.05). Conclusion Our data showed that FOXP3 positive cells might be associated with high expression of IDO in TNBC patients. FOXP3 and IDO co-expression may also suggest its involvement in disease, and evaluation of FOXP3 and IDO expression in TNBC patients may offer a new therapeutic option.

Objective: The purpose of this literature search was to review the benefits of high-intensity focused ultrasound (HIFU) and its application for different pathologies. Methods: This review summarizes the implementation of HIFU for different pathologic conditions. An National Center for Biotechnology Information, PubMed, MEDLINE, Medscape, and Google Scholar database search (1992–2016) was done with the following keywords: high-intensity focused ultrasound; uses of HIFU; and applications of HIFU in the liver, bones, uterine fibroids, prostate, breast, thyroid, pancreas, kidneys, brain, urinary bladder, and so on. Tables and graphs were created for all the variables included in the study, and descriptive statistics were applied. Results: In total, 110 records were identified, through database search. In addition, 20 articles were identified through other sources. Screening of the articles was performed, and 20 were removed due to duplication; further screening was performed for 110 articles, and 30 records were further excluded. Full-text articles were assessed for eligibility and 30 were retained. Full-text articles were excluded (N = 36) on the basis that research was performed on animals, and this review article was performed solely for human application. There were 42 qualitative syntheses that researches added to the review. In addition, 42 quantitative synthesis (meta-analysis) were added to the review. Conclusion: The conclusion of this narrative review indicates that HIFU is noninvasive, nonharmful, and effective in treating diseases and tumors of the brain, breast, bone, hepatic, renal, pancreas, and prostate; uterine fibroids; and many other solid tumors. Recent technological development suggests that HIFU is likely to play a significant role in future surgical practices. Further research works should be conducted on a large sample size to obtain more accurate results in the application of HIFU.

Acacia species are very important tree species in tropical and subtropical countries of the World for their economic and medicinal benefits. Precise identification of Acacia is very important to distinguish the invasive species from rare species however, it is difficult to differentiate Acacia species based on morphological charcters. In addition, precise identification is also important for wood charcterization in the forest industry as these species are declining due to illegal logging and deforestation. To overcome thsese limitations of morphological identification, DNA barcoding is being used as an efficient and quick approach for precise identification of tree species. In this study, we selected two chloroplast and plastid base DNA markers (rbcL and matK) for the identification of five selected tree species of Acacia (A. albida, A. ampliceps, A. catechu, A. coriacea and A. tortilis). The genomic DNA of the selected Acacia species was extracted, amplified through PCR using specific primers and subsequently sequenced through Sanger sequencing. In matK DNA marker the average AT nucleotide contents were higher (59.46%) and GC contents were lower (40.44%) as compared to the AT (55.40%) and GC content (44.54%) in rbcL marker. The means genetic distance K2P between the Acacia species was higher in matK (0.704%) as compared to rbcL (0.230%). All Acacia species could be identified based on unique SNPs profile. Based on SNP data profiles, DNA sequence based scannable QR codes were developed for accurate identification of Acacia species. The phylogenetic analysis based on both markers (rbcL and matK) showed that both A. coriacea and A. tortilis were closely related with each other and clustered in the same group while other two species A. albida and A. catechu were grouped together. The specie A. ampliceps remained ungrouped distantly, compared with other four species. These finding highlights the potential of DNA barcoding for efficient and reproducible identification of Acacia species.

Objective The main objective was to describe and review a unique case that presented with diabetic ketoacidosis, positive insulin autoantibodies (IAAbs, which are found in Hirata disease and are usually present with hypoglycemia), and laboratory findings characteristic of type B insulin resistance syndrome (TBIRS) and systemic lupus erythematosus. Confirmation of TBIRS was obtained in Germany as immunoassay for insulin receptor antibodies (IRAbs) is not available in the United States. Methods A literature review on TBIRS and cases that present with IAAbs and IRAbs simultaneously was conducted. Results We found 6 cases presenting with hypoglycemia, both antibodies, and treatment attempts with various management approaches that were different from the proposed National Institutes of Health (NIH) protocol for TBIRS. Our case is distinct because of the demographic background, presentation with diabetic ketoacidosis, comparatively lower insulin requirement, and no significant hypoglycemic episodes in the third phase. Conclusion We propose that access to IRAb immunoassays may be important for diagnosing milder cases of TBIRS, while IAAbs may provide prognostic and therapeutic insights. Despite completely different presentation from other TBIRS patients reviewed, we observed that the proposed NIH protocol consisting of dexamethasone, rituximab, and cyclophosphamide was successfully employed in our patient. Thus, we propose that our case and the findings regarding antibody testing and the NIH treatment regimen may assist clinicians with earlier recognition and effective management of milder cases of TBIRS.

Objective: To determine the use of sonography and test-feeding in the diagnosis of infantile hypertrophic pyloric stenosis (IHPS). Methodology: A total of 79 infants from 2 weeks up to 12 weeks presenting with clinical signs (projectile vomiting) of IHPS were included in the study while sent to sonography. The study duration was February 2014 to December 2019. Results: The mean age of patients was 5.18 ± 2.69 weeks ranging from 1 to 12 weeks. Male gender was predominant with 62 (78.5%) cases. Of the total 79 cases, 36 (54.6%) were suggested as positive cases of IHPS and 43 (54.4%) were as normal with sonography. Most of the cases of IHPS (23; 29.1%) were observed in firstborn babies. Mean pyloric length in normal and IHPS was 12.69 ± 0.87 and 20.78 ± 2.28 mm, respectively, and mean pyloric muscle thickness in the normal and IHPS was 2.24 ± 0.36 and 5.27 ± 0.82 mm, respectively, while mean pyloric diameter in normal and IHPS was 12.69 ±0.87 and 15.01± 2.52 mm, respectively. Conclusion: The reliability of sonographic findings was better than test-feeding in the diagnosis of IHPS. Male infants, in this cohort, were five times more susceptible to develop IHPS, compared with females.

ETMRs are highly lethal, pediatric embryonal brain tumors, previously classified as various histologic diagnoses including supratentorial primitive neuroectodermal tumors (sPNET) and CNS PNET. With recognition that these tumors harbor recurrent amplification of a novel oncogenic miRNA cluster on chr19, C19MC, ETMRs were designated as a distinct biological and molecular entity with a spectrum of histologic and clinical manifestations. We reviewed published literature describing clinical presentation, the genetic and epigenetic drivers of oncogenesis, and recent therapeutic strategies adopted to combat these aggressive tumors. As a consequence of C19MC amplification, ETMRs upregulate several oncogenic and pluripotency proteins, including LIN28A, DNMT3B and MYCN, that confer a unique epigenetic signature reminiscent of nascent embryonic stem cells. In this review, we focus on the dysregulation of miRNAs in ETMR, the major pathogenic mechanism identified in this disease. Despite the use of multi-modal therapeutic regimens, ETMR patients have dismal survival. Understanding the unique biology of these tumors has provided new insights towards novel therapeutic targets.

Prune belly syndrome is a rare disorder characterized by the absence of anterior abdominal wall muscles, bilateral cryptorchidism, and urinary tract malformations. The aim of this case study was to illustrate the developmental sequelae of prune belly syndrome, acquired through a series of antenatal sonography. A 20-year-old woman visited a diagnostic medical sonography center for an obstetrical sonogram. Her fetus was diagnosed with megacystis at 15 weeks’ gestation. The mother returned for repeated appointment and to observe fetal changes during the development of prune belly syndrome. First, the megacystis, hydroureter, and hydronephrosis were noted followed by hazy ascitic and amniotic fluid. The hemodynamics were altered in the umbilical artery, middle cerebral artery, and ductus venosus. Subsequently, the pressure was neutralized, but it was observed after birth that the newborn had cryptorchidism, a distended abdomen with wrinkled wall, and absent right kidney. In conclusion, prune belly syndrome could be caused by megacystis due to bladder outlet obstruction in otherwise normal karyotype fetuses. Megacystis leads to hydroureter, hydronephrosis, and abdominal distention. The persistent abdominal distention gives rise to the underdevelopment of anterior abdominal wall muscles and cryptorchidism.

Background and Aims: The aim of this study was to identify the delay and the factors associated with delay in initiating post exposure prophylaxis. Methods: A consecutive sampling method was proceeded, and 199 patients attending the anti-rabies clinic with a history of animal bite reported at SMHS Hospital were the subjects of the study. Results: Majority of the patients (72.36%) reported a delay within 6 h after exposure, 18.59% within (6-48) h and 9.04% after 48 h of exposure. Conclusion: Increasing the number of accessible anti-rabies clinics as well as increasing the awareness among general public about timely post exposure prophylaxis in the community are some of the factors that need to be implemented.

The gene sequence encoding the mannose-binding homodimeric protein Allium sativum leaf agglutinin (ASAL) was introduced into maize inbred lines to achieve resistance against sap-sucking corn leaf aphids in transgenic lines. Maize transformants were generated after the co-cultivation of immature maize embryos with the Agrobacterium strain LB4404 harbouring a recombinant Ti-binary ASAL construct driven by the polyubiquitin promoter. The preliminary screening of maize transformants was performed via GUS histochemical analysis, and PCR and Southern blotting confirmed the insertion of the transgene and its stable integration in five transgenic maize lines. Transcript abundance was quantified by a quantitative real-time PCR assay, which revealed variable expression of the ASAL transgene among five transgenic maize lines. The highest mRNA expression of the ASAL gene was found in the A23 transgenic maize line, while the lowest expression was found in the AU1 transgenic maize line. In planta bioassays in the T1 progeny of the transgenic maize lines revealed high resistance against corn leaf aphids compared to the control non-transgenic line. The mortality of the infesting aphids (Rhopalosiphum maidi) was found to vary from 40 to 71% compared to that of the non-transgenic control maize line.

Objective: To determine the association between spectral Doppler cardiac activity in the lower limb veins and echocardiographic findings in patients with tricuspid regurgitation. Material and methods: A cross-sectional analysis was performed in the Gilani Ultrasound Center over a period of 13 months. The total study sample comprised 400 subjects. All individuals referred for abdominal ultrasound having cardiac activities in external iliac vein, popliteal and posterior tibial vein, individuals having normal venous Doppler ultrasound, both genders and all ages, were included, and unwilling and non-cooperative patients were excluded from the study. Results: Out of 400 individuals, 200 showed cardiac activity in the lower limb veins on Doppler vascular ultrasound, while 200 did not show cardiac activity. On echocardiography, 204 individuals were diagnosed with tricuspid regurgitation, and 196 individuals had a competent tricuspid valve. According to the independent sample t-test the mean difference in the posterior tibial vein was 25.54 (95% CI: 24.09; 26.98), while the mean difference in the iliac vein was 2.34 (95% CI: 0.64; 4.03) among normal and tricuspid regurgitation. Conclusion: A correlation was found between the cardiac activities in the lower limb veins and tricuspid regurgitation. Objective: To determine the association between spectral Doppler cardiac activity in the lower limb veins and echocardiographic findings in patients with tricuspid regurgitation. Material and methods: A cross-sectional analysis was performed in the Gilani Ultrasound Center over a period of 13 months. The total study sample comprised 400 subjects. All individuals referred for abdominal ultrasound having cardiac activities in external iliac vein, popliteal and posterior tibial vein, individuals having normal venous Doppler ultrasound, both genders and all ages, were included, and unwilling and non-cooperative patients were excluded from the study. Results: Out of 400 individuals, 200 showed cardiac activity in the lower limb veins on Doppler vascular ultrasound, while 200 did not show cardiac activity. On echocardiography, 204 individuals were diagnosed with tricuspid regurgitation, and 196 individuals had a competent tricuspid valve. According to the independent sample t-test the mean difference in the posterior tibial vein was 25.54 (95% CI: 24.09; 26.98), while the mean difference in the iliac vein was 2.34 (95% CI: 0.64; 4.03) among normal and tricuspid regurgitation. Conclusion: A correlation was found between the cardiac activities in the lower limb veins and tricuspid regurgitation.

The present study aimed to investigate the impact of self-generated thoughts (daydreaming) on symptoms of anxiety among university students. Furthermore, mediating role of rumination was also studied. A sample of 300 university students aged 18-28 years and with minimum education of 14 years was collected through purposive sampling technique from different universities of Rawalpindi and Islamabad. Self-report measures including Day-Dreaming Frequency Subscale of Imaginal Process Inventory (Singer & Antrobus, 1970) Ruminative Response Scale (Treynor, Gonzalez, & Nolen-Hoeksema, 2003), and Beck Anxiety Inventory (Beck, Epstein, Brown, & Steer, 1988) were administered to measure study variables. Results yielded self-generated thoughts as a significant positive predictor of anxiety symptoms, whereas rumination was found to significantly predict anxiety in positive direction. Moreover, rumination mediated the relationship between self-generated thoughts and symptoms of anxiety. Female students scored significantly higher on daydreaming, rumination, and anxiety symptoms as compared to male university students. This study will be helpful for mental health professionals to gain a better understanding that how daydreaming can have an impact on individual’s cognition and thus can raise more awareness about dangers associated with excessive daydreaming.

Acinetobacter baumannii is a biofilm forming multidrug resistant (MDR) pathogen responsible for respiratory tract infections. In this study, aluminium oxide nanoparticles (Al2O3 NPs) were synthesiz...

Purpose: To evaluate the antidiabetic, hypolipidemic and antioxidant potential of seed oil of Nigella sativa L (NSO). Methods: Nigella sativa seed oil (NSO) was extracted with Soxhlet apparatus using petroleum ether, and was given orally at a dose of 2.5 ml/kg body weight to alloxan-induced diabetic rabbits daily for 24 days. Biochemical parameters including total cholesterol (TC), triglycerides (TGs), low density lipoprotein cholesterol (LDL), very low lipoprotein cholesterol (VLDL), high density lipoprotein (HDL) and plasma glucose were determined in the treatment and control groups. Furthermore, bilirubin, vitamin C, catalase and mean body weight were assessed. Results: NSO treatment significantly lowered serum blood glucose levels and lipid contents, but increased the mean body weight, HDL-C and vitamin C levels of diabetic rabbits (p < 0.001). Moreover, NSO significantly decreased catalase activity, TC, TGs, LDL-C and VLDL-C levels, but normalized bilirubin levels in diabetic rabbits. Conclusion: These results indicate that NSO possesses significant antidiabetic potential. Thus, it may be useful as an adjunct with antidiabetic medication but further studies are required to ascertain this. Keywords: Black cumin, Diabetes, Hypoglycemic, Hypolipidemic, Antioxidants

Background and purpose Drug-eluting balloons (DEBs) have been proposed as an option for the treatment of in-stent restenosis (ISR) following carotid artery stent placement. We report our experience and review of literature to provide additional data. Methods For literature review, PubMed search was conducted to identify studies published between 2005 and 2019, reporting data on management of carotid ISR with DEBs. Two cases with carotid ISR, which were successfully treated with DEB at our facility, were also included in the final compilation of results RESULTS: A total of seven studies demonstrating the use of the DEBs for treatment of carotid ISR were identified. They encompassed 31 patients, 11 (35.5%) of whom presented with symptomatic ISR, with the remaining 20 patients (64.5%) asymptomatic. DEB angioplasty followed by stent placement was performed in 3 patients, whereas DEB alone was utilized in 28 patients. Periprocedural complications included asymptomatic dissection from DEB inflation in 1 patient and transient neurological deficits in another patient. Follow-up period was variable and ranged from 1 month to 5 years. Three patients were noted to develop recurrent asymptomatic stenosis, whereas 1 patient developed an episode of symptomatic restenosis post procedural on follow-up. In our two cases, both patients were noted to have protracted period of hypotension postprocedure without any new or recurrent neurological symptoms. Conclusion The use of DEBs is a promising development and a viable alternative for management of severe and recurrent carotid ISR.

Sustainable agriculture requires management of insect pests through resistance development. The biological potential of Cry toxins and Vip protein, derived from Bacillus species, is widely recognized in this context. The identification, evaluation of new insecticidal protein genes with different mode of action and entomotoxicity against sugarcane stem borer (Chilo infuscatellus) is important to overcome evolved insect resistance. In this study, we reported the generation of transgenic sugarcane lines expressing Vip3A toxin driven by polyubiquitin promoter for resistance against sugarcane stem borer. The V0 transgenic sugarcane plants were initially characterized by GUS histochemical staining, PCR and Southern blot assays that confirmed genetic transformation of twelve independent sugarcane lines. Variable transgene expression was found among transgenic sugarcane lines when revealed through Realtime quantitative PCR (RT-qPCR) with highest in S10 line while minimum was observed in V5 line. A similar expression pattern was observed in transgenic sugarcane lines for Vip3A protein concentration which ranged from 5.35 to 8.89 µg/mL. A direct correlation was observed between the Vip3A protein and Vip3A transgene expression in the transgenic sugarcane lines. In in-vitro insect bioassay on V1, Vip3A transgenic sugarcane lines exhibited high resistance to C. infuscatellus with upto 100% mortality compared to the control sugarcane line. Our findings suggest that a single copy insertion of Vip3A gene in transgenic sugarcane lines render them resistant to borer and these lines can be potentially used for generation of insect resistant transgenic sugarcane and could also be employed in gene pyramiding with Bt toxin to prolong resistance.

Stripe rust (yellow rust), caused by Puccinia striiformis f. sp. tritici (Pst), is considered as a major threat to the wheat production worldwide, including Pakistan. In the current study, 80 wheat landraces collected from different agroecological zones of Pakistan were screened for their stripe rust resistance. Molecular markers were used to identify/postulate the stripe rust genes in these landraces. The results indicated that 46 (57.5%) landraces had all-stage resistance, and only 4 (5%) landraces showed adult-plant resistance. The possible stripe rust resistance genes in these entries were postulated by the using already reported linked molecular markers of all-stage resistance and adult plant stage resistance genes (Yr4 Yr5, Yr10, Yr15 and Yr24/26 and adult-plant resistance genes Yr18, Yr29 and Yr32). Molecular analysis indicated that resistant genes Yr4, Yr5, Yr10, Yr15, Yr17, Yr18, Yr26/24, Yr29 and Yr32 were found in 16(20%), 12(15%), 4(5%), 15(18.75%), 16(20%), 13(16.25%), 39(48.75%), 20(25%) and 7(7.5%) of landraces, respectively. Majority of the landraces showed the presence of more than one gene. These lines could be used effectively in the wheat breeding programs.

Background People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. Hypothesis Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. Design Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. Entry criteria South Asian, men or women, age 40–70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0–6.4% inclusive). Exclusion criteria: known type 1 or 2 diabetes, normal or underweight (body mass index 2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. Endpoints The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. Intervention Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. Results We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). Conclusion The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB approval 16/WM/0171 Trial registration EudraCT 2016-001350-18. Registered on 14 April 2016. ClinicalTrials.govNCT02949739. Registered on 31 October 2016, First posted on 31/10/2016.

Graves’ disease is an autoimmune disorder in which hyperthyroidism (over active thyroid) is caused by the autoantibodies against the TSH receptor. It is mainly characterized by the appearance of goiter. The symptoms are wide ranging as thyroid hormone affects many body systems. It is common in women and in people with age below than 40. Graves’ disease is caused by a combination of genetic and environmental factors while genetics being the main cause. Graves’ disease is not a single gene defect but has a complex pattern of inheritance. Today it is clear that genetic predisposition to Graves’ disease is caused by multiple genes. HLA gene is one the most studied gene predisposing to Graves’ disease. Lot of polymorphisms in this gene has been to be associated with the disease. Lymphoid tyrosine phosphatase encoded by the gene PTPN22 has been found to increase the risk of many autoimmune diseases including Graves’ disease. The best documented association of PTPN22 variants to autoimmune disorders including GD is rs2476601 (C1858T). Other genes associated with the risk of GD are thyrotropin receptor (TSHR), thyroglobulin gene, FCRL3, SCGB3A2, and CTLA4. This chapter will discuss in detail the genetics, pathophysiology, diagnosis and treatment of Graves’ hyperthyroidism.

The demographic patterns of COVID-19 spread can provide clues to develop roadmaps for devising better prevention and control. It is high time to analyze and re-evaluate the zoonotic/reverse zoonotic spread of SARS-CoV-2 globally. To this end, lessons from epidemiology and associated determinants from previous outbreaks of SARS-CoV-1 and MERS need to be cultured and re-visited. Ways to minimize the rates of infection and promote the well-being of the masses need urgent attention owing to the subsequent waves of the global pandemic in most countries. Efforts are being directed for the provision of efficient and cost-effective diagnostics, prophylaxis and therapeutic options for COVID-19. The chapter provides insights, suggesting a potential roadmap for efficiently preventing the future outbreaks of COVID-19, based on the tools of epidemiology, transmission probabilities and public health safety concerns.

IntroductionSouth Asians are at high risk of type 2 diabetes (T2D). We assessed whether intensive family-based lifestyle intervention leads to significant weight loss, improved glycaemia and blood pressure in adults at elevated risk for T2D.MethodsThis cluster randomised controlled trial (iHealth-T2D) was conducted at 120 locations across India, Pakistan, Sri Lanka and the UK. We included 3684 South Asian men and women, aged 40–70 years, without T2D but with raised haemoglobin A1c (HbA1c) and/or waist circumference. Participants were randomly allocated either to the family-based lifestyle intervention or control group by location clusters. Participants in the intervention received 9 visits and 13 telephone contacts by community health workers over 1-year period, and the control group received usual care. Reductions in weight (aim >7% reduction), waist circumference (aim ≥5 cm reduction), blood pressure and HbA1C at 12 months of follow-up were assessed. Our linear mixed-effects regression analysis was based on intention-to-treat principle and adjusted for age, sex and baseline values.ResultsThere were 1846 participants in the control and 1838 in the intervention group. Between baseline and 12 months, mean weight of participants in the intervention group reduced by 1.8 kg compared with 0.4 kg in the control group (adjusted mean difference −1.10 kg (95% CI −1.70 to −1.06), pConclusionAn intensive family-based lifestyle intervention adopting low-resource strategies led to effective reduction in weight and waist circumference at 12 months, which has potential long-term benefits for preventing T2D. A higher number of attended sessions increased the effect on waist circumference, blood pressure and HbA1c.Trial registration numberEudraCT: 2016-001350-18; ClinicalTrials.gov: NCT02949739.

Candida albicans is the most common cause of death from fungal infections. The emergence of resistant strains reducing the efficacy of first-line therapy with echinocandins, such as caspofungin calls for the identification of alternative therapeutic strategies. Tra1 is an essential component of the SAGA and NuA4 transcriptional co-activator complexes. As a PIKK family member, Tra1 is characterized by a C-terminal phosphoinositide 3-kinase domain. In Saccharomyces cerevisiae, the assembly and function of SAGA and NuA4 are compromised by a Tra1 variant (Tra1Q3) with three arginine residues in the putative ATP-binding cleft changed to glutamine. Whole transcriptome analysis of the S. cerevisiae tra1Q3 strain highlights Tra1’s role in global transcription, stress response, and cell wall integrity. As a result, tra1Q3 increases susceptibility to multiple stressors, including caspofungin. Moreover, the same tra1Q3 allele in the pathogenic yeast C. albicans causes similar phenotypes, suggesting that Tra1 broadly mediates the antifungal response across yeast species. Transcriptional profiling in C. albicans identified 68 genes that were differentially expressed when the tra1Q3 strain was treated with caspofungin, as compared to gene expression changes induced by either tra1Q3 or caspofungin alone. Included in this set were genes involved in cell wall maintenance, adhesion, and filamentous growth. Indeed, the tra1Q3 allele reduces filamentation and other pathogenesis traits in C. albicans. Thus, Tra1 emerges as a promising therapeutic target for fungal infections.