The SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression.

Viruses use microRNAs (miRNAs) to impair the host antiviral response and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. miRNAs inhibit translation initiation of their target mRNAs by recruiting the GIGYF2-4EHP (or EIF4E2) translation repressor complex to the mRNA 5'-cap structure. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for blocking translation of the Ifnb1 mRNA that encodes the cytokine interferon ß, and thereby impairs the host antiviral response. However, it is not known whether NSP2 also affects miRNA-mediated silencing. Here, we demonstrate the pervasive augmentation of miRNA-mediated translational repression of cellular mRNAs by NSP2. We show that NSP2 interacts with argonaute 2 (AGO2), the core component of the miRNA-induced silencing complex (miRISC), via GIGYF2 and enhances the translational repression mediated by natural miRNA-binding sites in the 3' untranslated region of cellular mRNAs. Our data reveal an additional layer of the complex mechanism by which SARS-CoV-2 and likely other coronaviruses manipulate the host gene expression program by co-opting the host miRNA-mediated silencing machinery.

KARRIKIN UP-REGULATED F-BOX 1 (KUF1) imposes negative feedback regulation of karrikin and KAI2 ligand metabolism in Arabidopsis thaliana.

SignificanceKarrikins are chemicals in smoke that stimulate regrowth of many plants after fire. However, karrikin responses are not limited to species from fire-prone environments and can affect growth after germination. Putatively, this is because karrikins mimic an unknown signal in plants, KAI2 ligand (KL). Karrikins likely require modification in plants to become bioactive. We identify a gene, KUF1, that appears to negatively regulate biosynthesis of KL and metabolism of a specific karrikin. KUF1 expression increases in response to karrikin or KL signaling, thus forming a negative feedback loop that limits further activation of the signaling pathway. This discovery will advance understanding of how karrikins are perceived and how smoke-activated germination evolved. It will also aid identification of the elusive KL.

Karrikin signalling: impacts on plant development and abiotic stress tolerance.

Plants rely upon a diverse range of metabolites to control growth and development, and to overcome stress that results from suboptimal conditions. Karrikins (KARs) are a class of butenolide compounds found in smoke that stimulate seed germination and regulate various developmental processes in plants. KARs are perceived via a plant α/ß-hydrolase called KARRIKIN INSENSITIVE2 (KAI2), which also functions as a receptor for a postulated phytohormone, provisionally termed KAI2 ligand (KL). Considered natural analogues of KL, KARs have been extensively studied for their effects on plant growth and their crosstalk with plant hormones. The perception and response pathway for KAR-KL signalling is closely related to that of strigolactones, another class of butenolides with numerous functions in regulating plant growth. KAR-KL signalling influences seed germination, seedling photomorphogenesis, root system architecture, abiotic stress responses, and arbuscular mycorrhizal symbiosis. Here, we summarize current knowledge of KAR-KL signalling, focusing on its role in plant development, its effects on stress tolerance, and its interaction with other signalling mechanisms.

First Report of Wilt Caused by Fusarium nanum (FIESC 25) on Mungbean (Vigna radiata) in Pakistan.

Mungbean, Vigna radia (L.) R. Wilczek, is ranked 2nd next to chickpea (Cicer arietinum) in total cultivation and production in Pakistan. In August of 2022 and 2023, mungbean plants (cv. PRI Mung-2018) were found wilting in a field at the Ayub Agricultural Research Institute, Faisalabad, Pakistan. Wilted leaves turned yellow, died, but remained attached to the stem. Vascular tissue at the base of the stem showed light to dark brown discoloration. Roots were stunted with purplish brown to black discoloration. Symptomatic mungbean plants were collected from fields at five different locations (20 samples/location). Disease incidence was similar among the five fields, ranging from 5 to 10% at each location depending upon type of germplasm and date of sowing. For fungal isolation and morphological identification, symptomatic stem and root tissues were cut into ~5 mm2 pieces with a sterilized blade. Tissues were surface-sterilized for one min in a 0.5% sodium hypochlorite solution, rinsed twice in sterilized water, air dried on sterilized filter paper, and aseptically placed on potato dextrose agar (PDA) containing 0.5 g/L-1 streptomycin sulphate. Plates were incubated for 3-4 days at 25 ± 2°C with a 12-h photoperiod. Single-spore cultures were used for morphological and molecular analyses. Isolates on PDA grew rapidly and produced abundant white aerial mycelium that turned off-white to beige with age. Macroconidia were hyaline, falcate, typically 3-to-6 septate with a pointed apical cell and a foot-shaped basal cell, measuring 24.5-49.5 x 2.7-4.7 µm (n = 40). Globose to obovate chlamydospores measuring 5.8 ± 0.5 µm (n = 40) were produced singly or in chains and were intercalary or terminal and possessed roughened walls. The morphological data indicated the isolates were members of the genus Fusarium (Leslie and Summerell 2006). To obtain a species-level identification, a portion of translation elongation factor 1-α (TEF1), the largest subunit of RNA polymerase (RPB1), and the second largest subunit of RNA polymerase (RPB2) region were PCR amplified and sequenced using EF1/EF2 (O'Donnell et al. 1998), Fa/G2R (Hofstetter et al. 2007), and 5f2/7cr (Liu et al. 1999) primers, respectively. DNA sequences of these genes were deposited in GenBank under accession numbers MW059021, MW059017 and MW059019, respectively. The partial TEF1, RPB1 and RPB2 sequences were queried against the Fusarium MLST database (https://fusarium.mycobank.org/page/Fusarium_identification), using the polyphasic identification tool. The BLASTn search revealed 99.9% identity of the isolate to F. nanum (Xia et al. 2019), formerly FIESC 25 of the F. incarnatum-equiseti species complex (MRC 2610, NRRL 54143; O'Donnell et al. 2018). To confirm pathogenicity, roots of 3-5 leaf stage mungbean seedlings were soaked in a 106 spores ml-1 conidial suspension of the fungus for 15 min and then planted in 10 cm pots containing sterilized soil. Mock-inoculated plants with sterile water served as a negative control. Twenty pots that were used for each inoculated and control treatment were maintained at 25 ± 2°C, 14:8 h photoperiod, and 80% relative humidity in a growth chamber. After 15 days, leaf yellowing, internal browning from the base of stems and root discoloration was observed in all the inoculated plants. The uninoculated negative control plants remained asymptomatic. Fusarium nanum was re-isolated from artificially inoculated plants and identified by colony growth, conidial characteristics on PDA and molecular analyses (TEF1). To our knowledge, this is the first report of wilt caused by F.nanum on mungbean in Pakistan. In Pakistan, mungbean cultivation in irrigated areas has increased in recent years. It has been introduced frequently in citrus orchards, crop rotation of maize and sesame, intercropping with sugarcane and as green manure. However, citrus, maize, sesame and sugarcane are also hosts of Fusarium spp. Therefore, this information warrants sustainable crop protection and may have an impact on further interaction of F. nanum with other wilt pathogens.

Optimization of inclusion level of lipid in larval diet of Labeo rohita (Hamilton, 1822).

Formulation and preparation of larval feed according to the requirement of Indian major carp is a prerequisite for improving the survival (%) and growth during early developmental stages. A feeding trial of 50 days in a replicate of five was conducted to determine the optimal inclusion levels of fish oil (lipid) in the larval diet of Labeo rohita. Four isonitrogenous (50% CP) nanoparticulate diets with four lipid inclusion levels, L5 (5%), L7 (7%), L9 (9%), and L11 (11%) were prepared and fed to four groups of rohu (Labeo rohita) larvae. At the end of feeding trial, survival (%), growth performance, digestive enzyme activity, gut morphology, and expression of growth and feed intake genes were evaluated. All pairwise comparisons among groups indicated higher growth performance (weight gain, specific growth rate, and daily weight gain), survival (%), and IGF-1 gene expression of the L9 group followed by the L7 while the L11 showed poor performance even less than L5. All studied intestinal enzymes except amylase showed a similar trend. Amylase showed comparable results among L7, L9, and L5, while L11 showed the lowest value. The intestinal villi length also showed higher values in L9 followed by L7, and lowest in the L11 group. Feed intake regulating genes, leptin showed lipid inclusion level upregulation, while ghrelin showed the highest expression in the L9 group. Based on growth performance, gut morphology, intestinal enzyme activity, and gene expression analysis, 9% dietary lipid could be recommended to ensure the optimum growth and survival of L. rohita larvae.

KARRIKIN INSENSITIVE2 regulates leaf development, root system architecture and arbuscular-mycorrhizal symbiosis in Brachypodium distachyon.

KARRIKIN INSENSITIVE2 (KAI2) is an α/ß-hydrolase required for plant responses to karrikins, which are abiotic butenolides that can influence seed germination and seedling growth. Although represented by four angiosperm species, loss-of-function kai2 mutants are phenotypically inconsistent and incompletely characterised, resulting in uncertainties about the core functions of KAI2 in plant development. Here we characterised the developmental functions of KAI2 in the grass Brachypodium distachyon using molecular, physiological and biochemical approaches. Bdkai2 mutants exhibit increased internode elongation and reduced leaf chlorophyll levels, but only a modest increase in water loss from detached leaves. Bdkai2 shows increased numbers of lateral roots and reduced root hair growth, and fails to support normal root colonisation by arbuscular-mycorrhizal (AM) fungi. The karrikins KAR1 and KAR2 , and the strigolactone (SL) analogue rac-GR24, each elicit overlapping but distinct changes to the shoot transcriptome via BdKAI2. Finally, we show that BdKAI2 exhibits a clear ligand preference for desmethyl butenolides and weak responses to methyl-substituted SL analogues such as GR24. Our findings suggest that KAI2 has multiple roles in shoot development, root system development and transcriptional regulation in grasses. Although KAI2-dependent AM symbiosis is likely conserved within monocots, the magnitude of the effect of KAI2 on water relations may vary across angiosperms.

Long-Term Exposure of Graphene Oxide Suspension to Air Leading to Spontaneous Radical-Driven Degradation.

Understanding the environmental transformation and fate of graphene oxide (GO) is critical to estimate its engineering applications and ecological risks. While there have been numerous investigations on the physicochemical stability of GO in prolonged air-exposed solution, the potential generation of reactive radicals and their impact on the structure of GO remain unexplored. In this study, using liquid-PeakForce-mode atomic force microscopy and quadrupole time-of-flight mass spectroscopy, we report that prolonged exposure of GO to the solution leads to the generation of nanopores in the 2D network and may even cause the disintegration of its bulk structure into fragment molecules. These fragments can assemble themselves into films with the same height as the GO at the interface. Further mediated electrochemical analysis supports that the electron-donating active components of GO facilitate the conversion of O2 to •O2- radicals on the GO surface, which are subsequently converted to H2O2, ultimately leading to the formation of •OH. We experimentally confirmed that attacks from •OH radicals can break down the C-C bond network of GO, resulting in the degradation of GO into small fragment molecules. Our findings suggest that GO can exhibit chemical instability when released into aqueous solutions for prolonged periods of time, undergoing transformation into fragment molecules through self-generated •OH radicals. This finding not only sheds light on the distinctive fate of GO-based nanomaterials but also offers a guideline for their engineering applications as advanced materials.

Recent advances in the green synthesis of Betti bases and their applications: a review.

Well-known Betti bases are the products obtained by the one-pot multicomponent reaction of 1-naphthol/2-naphthol, aliphatic/aromatic aldehydes, and secondary amines, and this reaction is known as the Betti reaction. During recent years, due to the unveiling of the pharmacological and synthetic potential of Betti bases, a tremendous increase in the studies reporting novel synthetic methods for the efficient synthesis of Betti bases was observed. This review presents the recent key developments in the green synthesis of the Betti bases and accounts for the significant number of the literature reported during 2019-2022. Both catalyst free as well as the catalyst promoted synthesis (nanocatalyst, biocatalyst, transition metal catalyst, etc.) along with the synthetic applications (catalyst, ligands/chiral auxiliaries, and valuable synthons), optoelectronic applications (fluorescence sensors for phosgene gas, Hg2+, and Cr3+ detection, quasi-reversible redox potential) and biological properties (anticancer agents, antioxidant, anti-inflammatory agents, antitubercular agents, pesticidal agents, anti-Alzheimer agents, Topoisomerase I inhibitors, YAP-TEAD interaction inhibitors, and DNA binding and cleavage activity) are discussed. There is a surge of interest for the development of the green and efficient Betti reaction for the construction of C-C and C-N bond in a single-step reaction accessing Betti bases as products. Along with key methodological developments for the green synthesis of Betti bases, their applications in synthetic organic chemistry, optoelectronic sensors, advanced materials synthesis, agrochemicals and pharmaceutically active scaffolds, during the period of 2019-2022, have been considered.

Unstable fipronil resistance associated with fitness costs in fipronil-selected Aedes aegypti L.

Mosquitoes are very serious household and medically important pests transmitting many diseases of humans and animals. Among mosquitoes, Aedes aegypti L., is an active transmitter of dengue and lumpy skin disease virus, horrible and terrifying diseases, causing human and animal death throughout the world. Fipronil is a new chemistry insecticide used to control agriculture and medically important insect pests. It affects the GABA receptors in the nervous system and consequently causes the death of the pests. A laboratory experiment was conducted to investigate the onset of fipronil resistance and associated fitness costs in Ae. Aegypti. Moreover, the stability of fipronil resistance was evaluated after five generations of rearing without selection pressure. The population of Ae. Aegypti was exposed continuously for 12 generations to fipronil under controlled conditions. The fipronil selected population (Fipro-Sel Pop) had a 317 and 115.7-fold level of resistance compared to a susceptible and field population, respectively. Relative fitness for Fipro-Sel Pop was 0.57, with a significant disadvantage in larval duration, developmental time, percent hatchability, intrinsic rate of natural increase (rm), net reproductive rate (Ro), number of larvae in the next generation, and mean relative growth rate (MRGR) when compared to the Unselected population (Un-Sel Pop). However, the relative fitness value of Cross1 (Un-Sel Pop ♂ × Fipro-Sel Pop ♀) and Cross2 (Fipro-Sel Pop ♂ × Un-Sel Pop ♀) was 1.69 and 1.12, respectively. It is evident from the results that fipronil resistance comes with a fitness disadvantage, and it is unstable in the Fipro-Sel Pop of Ae. Aegypti. Therefore, the alternation of fipronil with other chemicals or suspension of fipronil usage for some time could improve its efficacy by delaying resistance development in Ae. Aegypti. Further research should be performed to investigate the field applicability of our findings.

Functional outcome of Hirschsprung's disease in children: A single center study at The Children's Hospital Lahore.

AIM: Hirschsprung's disease (HD) is a congenital bowel disorder resulting in functional dysmotility. Advancement in surgical techniques has improved outcomes, but recent studies have identified problems having significant impact on patient's quality of life. The aim of this study is to analyze postoperative functional outcome after definitive surgery for Hirschsprung's disease. METHOD: A retrospective study was conducted at the Department of Pediatric Surgery, The Children's Hospital Lahore. The record of 64 patients was reviewed from the year 2009 to 2019. Parents were interviewed on phone calls and a predesigned questionnaire was filled. Degree of constipation, incontinence and voluntary bowel movements was analyzed according to Krickenbeck classification. RESULTS: Median age at initial presentation was 11 days, with male to female ratio of 3.9:1. Most common presentation was delayed passage of meconium (38%). Diagnosis was made on biopsy in 70.3%, but contrast enema and biopsy in 29.7%. Aganglionosis was limited to short segment in 81.3% and long segment in 14.5%. Decompressing enterostomy was made in 63% at a mean age of 191 days. Definitive surgery included Duhamel pull-through in 89.1%. Mean age at follow-up was 10.6 ± 4.19 years and alive patients were 95.4%. Postoperative enterocolitis was reported by 27%, while 35.5% reported fecal incontinence and 16.1% complained of constipation. 80% could voluntarily hold bowel movement, among which 5% had a feeling of urge and 15% had the capacity to verbalize. In 25% of the patients, fecal incontinence was a constant social problem and in 25% of these patients constipation was resistant to diet and laxatives. CONCLUSION: On long-term follow-up, fecal incontinence was more worrisome, affecting quality of life and requiring help of the bowel management program. Such patients need close follow-up after definitive procedure, so that they have normal stooling habits in their adulthood and lead a normal life.

Does the sampling of date palm fruits help in early detection of date palm mite, Oligonychus afrasiaticus (Acari: Tetranychidae)?

Early pest detection in an agroecosystem is desired for efficient pest management. A proper sampling plan is thus required with adequate sampling units and a small sample size. The date palm mite, Oligonychus afrasiaticus, is a severe pest of date fruits and its early detection is most needed. The present research aimed to identify whether a certain bunch direction or strand position of date fruit bunches could help in the early detection of date palm mite. The research was conducted in two climatic regions of Saudi Arabia, on six date palm cultivars and during four fruiting seasons. The date palm mite population dynamics data were collected from four bunch directions and three strand positions. For early pest detection, the population estimation started from the first appearance of the mite on the fruit bunches in each season, continuing till the first 3 weeks. The results depicted a clumped distribution of date palm mite in all bunch directions and strand positions. There was no significant difference in the mean date palm mite population, neither among three-strand positions nor among the four bunch directions. The mean population over the weeks showed that date palm mite almost equally infested the fruit bunches from all four directions and increased with non-significant differences. It is suggested that the plant parts basally adjacent to fruit bunches should be focused on the early detection of date palm mite.

Clerodane Furanoditerpenoids from Tinospora bakis (A.Rich.) Miers (Menispermaceae).

Tinospora bakis (A.Rich.) Miers (Menispermaceae) has traditionally been used to alleviate headaches, rheumatism, mycetoma, and diabetes, among others. Despite its extensive use, the active components of the plant have never been investigated. In this work, a series of furanoditerpenoids (1-18) and five compounds from other classes (19-23) were isolated from T. bakis. Notably, two new compounds were discovered and named: tinobakisin (1) and tinobakiside (10). Their molecular structures were elucidated with NMR, MS, UV, IR, and ECD spectra. Additionally, known compounds (2-9 and 11-23) were corroboratively identified through spectral comparisons with previously reported data, while highlighting and addressing some inaccuracies in the prior literature. Remarkably, compounds 6, 7, 13, and 17 exhibited a superior anti-glycation effect, outperforming established agents like rutin and quercetin in a lab model of protein glycation with glucose. The overall findings suggest that furanoditerpenoids play a crucial role in the antidiabetic properties of T. bakis. This research marks the first comprehensive phytochemical investigation of T. bakis, opening the door for further investigation into furanoditerpenoids and their biological mechanisms.

Levofloxacin-Fatty Acid Systems: Dual Enhancement Through Deep Eutectic Formation and Solubilization for Pharmaceutical Potential and Antibacterial Activity.

Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their green properties, deep eutectic systems have been heralded as having the potential to be at the forefront of pharmaceutical applications. In this work, capric acid and geranic acid, two examples of medium-chain saturated and polyunsaturated fatty acids, were employed to enhance the pharmaceutical properties and the antibacterial activity of levofloxacin. To this end, levofloxacin formulations with either capric or geranic acid were prepared and characterized using appropriate techniques. Levofloxacin was utilized to create innovative deep eutectic systems in conjunction with capric acid at three different molar ratios: 1:9, 2:8 and 3:7. This was confirmed through a rigorous analysis involving nuclear magnetic resonance, infrared spectroscopy and differential scanning calorimetry. Furthermore, it is noteworthy that geranic acid demonstrated an impressive threefold improvement in levofloxacin's solubility compared to its solubility in aqueous solutions. The antibacterial activity of the novel combinations of levofloxacin with either fatty acid was evaluated using a checkerboard titration assay. Gratifyingly, both formulations exhibited synergistic effects against a panel of levofloxacin-sensitive and resistant Gram-negative bacteria. In conclusion, the observed superior antibacterial activity of levofloxacin illuminates the potential use of fatty acid-based formulations and deep eutectic systems as green and innovative strategies to combat the global antimicrobial resistance problem.

Controlling Factors and Predictive Models of Total Mercury and Methylmercury Accumulation in Rice (Oryza sativa L.) from Mercury-Contaminated Paddy Soils.

It is urgent to detect the major controlling factors and establish predictive models of mercury (Hg) accumulation in rice. A pot trial was conducted, exogenous Hg was added to 19 paddy soils at 4 concentration levels in this study. The major controlling factors of total Hg (THg) in brown rice were soil THg, pH and organic matter (OM) content, while those of methylmercury (MeHg) in brown rice were soil MeHg and OM. THg and MeHg in brown rice could be well predicted by soil THg, pH and clay content. The data from previous studies were collected to validate the predictive models of Hg in brown rice. The predicted values of Hg in brown rice were within the twofold prediction intervals of the observations, which demonstrated the predictive models in this study were reliable. The results could provide theoretical foundation for the risk assessment of Hg in paddy soils.

An assessment of knowledge, attitude, and practice regarding organ donation among students and physicians.

OBJECTIVE: To assess the knowledge, attitude and practice of students and physicians regarding tissue and organ donation at a teaching hospital. Methods: The cross-sectional study was conducted at the Dow University of Health Sciences, Karachi, in 2019, and comprised physicians and students of ether gender. Data was collected using a 43-item self-administered questionnaire. Dichotomous questions were scored as 1 or 0, while multiple-option questions were scored as 2, 1 or 0. Data was analysed using SPSS 25. RESULTS: Of the 859 subjects, 761(88.6%) were students with a mean age of 20.3±1.5 years and 98(11.4%) were physicians with a mean age of 30.6±9.4. Among the students, 630(82.8%) were medical students, while 131(17.2%) were dental. The largest group among the students was of those in the second year of their studies 271(35.6%). Besides, 531(69.8%) and 64(65.3%) physicians were females. Compared to males, female students reported better mean scores in terms of attitude, while higher practice scores were obtained by both male students and physicians (p=0.021). Muslim subjects scored comparatively lower in knowledge, attitude and practice terms than non-Muslims (p<0.05). CONCLUSIONS: There were high knowledge and attitude scores, while scores reflecting practice were low. Effective measures should be taken to encourage medical professionals to donate organs and promote organ donation.

Effect of Plant-Based Mouthwash (Morinda citrifolia and Ocimum sanctum) on TNF-α, IL-α, IL-ß, IL-2, and IL-6 in Gingival Crevicular Fluid and Plaque Scores of Patients Undergoing Fixed Orthodontic Treatment.

Background and Objectives: To investigate the antiplaque properties of two plant-based mouthwashes, Morinda citrifolia (MC) and Ocimum sanctum (OS), and their effect on TNF-α, IL-α, IL-ß, IL-2, and IL-6 in gingival crevicular fluid (GCF) of patients undergoing fixed orthodontic treatment. Materials and Methods: Seventy-five individuals were recruited according to defined inclusion and exclusion criteria. This study was structured into two distinct phases. Phase I was a combination of toothbrushing using toothpaste containing fluoride (Protocol A), while Phase II toothbrushing included fluoride toothpaste and use of a mouthwash (Protocol B). For Phase II, individuals participating in this study were allocated into different groups through a randomization process: Group 1-0.12% CHX, Group 2-5% MC, and Group 3-4% OS. Each individual's Phase I and Phase II scores were assessed. GCF was measured in three phases to determine the level of inflammatory biomarkers. The paired t-test evaluated the disparities between the pre- and post-plaque index. Categorical data were subjected to crosstab analysis to assess qualitative variables. The mean values of cytokine levels were presented. An unpaired t-test was employed to assess the levels of cytokines between individuals in Phase I and Phase II. Results: Toothbrushing, fluoride toothpaste, and the supplementary use of mouthwash (Phase II) resulted in mean plaque scores significantly lower than group A (p < 0.001). Cytokines TNF-α, IL-α, and IL-ß demonstrated a significant downward trend in herbal mouthwash users. Conclusions: In conjunction with fluoridated toothpaste and brushing, OS and MC can serve as a viable alternative to conventional synthetic mouthwash CHX. This combination demonstrates reducing mean plaque scores and diminishing the levels of cytokines TNF-α, IL-α, and IL-ß.

Levels of Inflammatory and Bone Metabolic Markers in the Gingival Crevicular Fluid of Individuals Undergoing Fixed Orthodontic Treatment in Comparison to Those Utilizing Invisalign.

Background and Objectives: Evaluation of the levels of cytokine and bone metabolic biomarkers (BMBs) in patients receiving fixed orthodontic therapy (FOT) and Invisalign. Materials and Methods: Sixty participants were enrolled after meeting the predefined inclusion criteria. Patients then underwent either FOT or Invisalign by allocating them randomly to each group (n = 30). The basic periodontal assessment was performed, including the plaque index (PI), gingival index (GI), and bleeding on probing (BoP), at baseline and again after 4 weeks. Gingival crevicular fluid (GCF) samples were taken from each individual at baseline and after 4 weeks. An enzyme-linked immunosorbent assay (ELISA) technique was used to determine the cytokine and BMB levels. An unpaired t-test compared the FOT and Invisalign group's means and SDs. Paired t-tests examined the difference between T0 baseline and T1. Results: Patients treated with either FOT or Invisalign presented no statistically significant difference in terms of periodontal parameters such as PI, GI, and BoP (p > 0.05). The levels of IL-6 were significantly higher in patients treated with FOT as compared to Invisalign at T1 (p < 0.05) The other tested cytokines, IL-10, 13, 17, and GM-CSF, were not significantly different in either the FOT or Invisalign group at baseline and 4 weeks follow-up (p > 0.05). Regarding BMBs, it was detected that NTx and OC levels in both of the investigated groups were not significantly different at baseline and after 4 weeks (p > 0.05). However, NTx levels rose significantly (p < 0.05) and OC levels fell from T0 to T1. Conclusions: FOT and Invisalign displayed comparable outcomes in terms of cytokine and BMB levels. However, only IL-6 and NTx were significantly different at week 4 from baseline.

Epidemiology of premalignant and malignant upper gastrointestinal lesions among patients presenting from a rural community in Karachi, Pakistan.

Objective: Understanding the epidemiology of upper gastrointestinal cancers in Pakistan may help in identifying important demographic risk factors for upper gastrointestinal malignancies in a particular rural population group. This will benefit in implementing tailored prevention approaches as well as effective management of health services. Method: A secondary data analysis of 1193 patients was conducted who went through diagnostic upper GI endoscopy between December 2016 to May 2019 at Fatima Hospital. The endoscopies were performed at Fatima Hospital which is the main health resource for the specifically targeted rural community. Data was analyzed using SPSS version 21. Results: The median age of patients included in the sample was 35 years (IQR=20 years). One third of all endoscopic findings were concluded as normal. The frequency of malignant upper gastrointestinal lesions was relatively higher among male and patients with age 65 years or more. The study didn't find any significant differences in the distribution of malignancies on the basis of ethnicity. Adenocarcinoma of esophagus was the most common malignant lesion. Conclusion: The average age of patients undergoing upper gastrointestinal endoscopy among rural community of Karachi was relatively low. The burden of upper GI malignancies was significantly higher among elderly. Male patients had significantly greater burden of premalignant and malignant lesions as compared to females. No differences in the distribution of diagnostic outcomes were observed on the basis of ethnicity.

A Serendipitous Outcome of COVID-19: Modifications to ICU Management.

Nosocomial infections are common in intensive care units (ICUs) and often cause increased morbidity and mortality rates in ICU patients. With the emergence of the highly infectious COVID-19, the high prevalence of hospital-acquired infections (HAIs) in ICU has caused much more concern because patients admitted to the ICU have a more severe and prolonged form of the disease. These patients are more likely to develop HAIs than non-ICU patients. Medical communities adopted several measures to make ICU management safer during the pandemic all over the world. In this study, we re-examined the challenges faced and the changes made in ICU management during the pandemic to speculate how these changes will be relevant post-pandemic and can be permanently incorporated into the ICU to improve safety, management, and critical care and make critical care better equipped for future disease breakouts.

Transcriptional changes in the peripheral blood leukocytes from Brangus cattle before and after tick challenge with Rhipicephalus australis.

BACKGROUND: Disease emergence and production loss caused by cattle tick infestations have focused attention on genetic selection strategies to breed beef cattle with increased tick resistance. However, the mechanisms behind host responses to tick infestation have not been fully characterised. Hence, this study examined gene expression profiles of peripheral blood leukocytes from tick-naive Brangus steers (Bos taurus x Bos indicus) at 0, 3, and 12 weeks following artificial tick challenge experiments with Rhipicephalus australis larvae. The aim of the study was to investigate the effect of tick infestation on host leukocyte response to explore genes associated with the expression of high and low host resistance to ticks. RESULTS: Animals with high (HR, n = 5) and low (LR, n = 5) host resistance were identified after repeated tick challenge. A total of 3644 unique differentially expressed genes (FDR < 0.05) were identified in the comparison of tick-exposed (both HR and LR) and tick-naive steers for the 3-week and 12-week infestation period. Enrichment analyses showed genes were involved in leukocyte chemotaxis, coagulation, and inflammatory response. The IL-17 signalling, and cytokine-cytokine interactions pathways appeared to be relevant in protection and immunopathology to tick challenge. Comparison of HR and LR phenotypes at timepoints of weeks 0, 3, and 12 showed there were 69, 8, and 4 differentially expressed genes, respectively. Most of these genes were related to immune, tissue remodelling, and angiogenesis functions, suggesting this is relevant in the development of resistance or susceptibility to tick challenge. CONCLUSIONS: This study showed the effect of tick infestation on Brangus cattle with variable phenotypes of host resistance to R. australis ticks. Steers responded to infestation by expressing leukocyte genes related to chemotaxis, cytokine secretion, and inflammatory response. The altered expression of genes from the bovine MHC complex in highly resistant animals at pre- and post- infestation stages also supports the relevance of this genomic region for disease resilience. Overall, this study offers a resource of leukocyte gene expression data on matched tick-naive and tick-infested steers relevant for the improvement of tick resistance in composite cattle.