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COVID-19 virus, since the detection of the first case in Wuhan in 2019, has caused a worldwide pandemic with significant human, economic and social costs. Fortunately, several vaccines and treatments, both IV and oral, are currently approved against the COVID-19 virus. Paxlovid is an oral treatment option for patients with mild-to-moderate disease, and it effectively reduces disease severity in high-risk patients. Paxlovid is an oral antiviral that consists of a combination of nirmatrelvir and ritonavi. As an oral medication suitable for outpatient treatment, it reduces the cost, hospitalization and mortality associated with COVID-19 infection. The pregnant population is a high-risk category for COVID-19 disease. Given their exclusion in clinical trials, there is limited data regarding Paxlovid use in pregnant and lactating women. Indirect evidence from ritonavir use as part of HAART therapy in the pregnant and lactating population with HIV has shown no significant teratogenicity. Moreover, animal studies on the use of nirmatrelvir do not suggest teratogenicity. This article summarizes the available data on ritonavir and nirmatrelvir use during pregnancy and in ongoing clinical trials. We also review the recommendations of major societies worldwide regarding Paxlovid use in pregnant and breastfeeding patients.

Obesity is characterized by the enlargement of adipose tissue due to an increased calorie intake exceeding the body's energy expenditure. Changes in the size of adipose tissue can lead to harmful consequences, with excessive fat accumulation resulting in adipocyte hypertrophy and promoting metabolic dysfunction. These adiposity-associated pathologies can be influenced by dietary components and their potential health benefits. Lupeol, a pharmacologically active pentacyclic triterpenoid found in medicinal plants, vegetables, and fruits, has been shown to exhibit antioxidant and anti-inflammatory properties. This study investigated the role of lupeol on adipocyte hypertrophy by evaluating key adipogenic regulators in vitro. First, 3T3-L1 MBX mouse embryonic cells were differentiated into adipocytes and hypertrophy was induced using 500 µM palmitic acid. The treated adipocytes showed a significantly increased lipid droplet size, confirming adipocyte hypertrophy. Both adipocytes and hypertrophied adipocytes were then treated with or without 60 µM lupeol, following a dose-dependent study. Lipid droplet size was assessed and validated by Oil Red O staining. Western blot analysis was performed to measure the expression of adipogenic and inflammatory markers. Differentiated adipocytes showed increased fatty acid-binding protein 4 (FABP4) expression and Oil Red O staining, indicating an increased lipid content. Western blot analysis revealed that lupeol treatment reduced the expression of FABP4, peroxisome proliferator-activated receptor-γ (PPARγ), and adipokines. In conclusion, the results suggest that lupeol reverts the inflammatory and adipogenic markers that are enhanced in adipocyte hypertrophy. Through its anti-inflammatory effects, lupeol offers protective effects against adipocyte hypertrophy and contributes to reducing hypertrophic adiposity.

Competing Interests: Conflict of Interest None declared.

Free flap procedure provides an overall success rate of 97%, which decreases to 85% in hypercoagulable states. COVID-19, as a pro-thrombotic disorder, therefore seems detrimental to free flap survival. We encountered a case of unique pattern of free flap partial failure in a young male who underwent extremity reconstruction. The patient was diagnosed as COVID-19 positive on the 3rd day post-reconstruction. The flap survived well for the first 7 days post-operatively, but gradually the skin got necrosed and the subcutaneous fat layer was preserved when debriding. To our knowledge, this is the only case in which the skin of the free flap of a COVID-19 positive patient was necrosed almost entirely subsequently, while the subcutaneous fat was relatively preserved., (Copyright © 2023 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Neurodegenerative diseases are a significant cause of mortality worldwide, and the blood-brain barrier (BBB) poses a significant challenge for drug delivery. An intranasal route is a prominent approach among the various methods to bypass the BBB. There are different pathways involved in intranasal drug delivery. The drawbacks of this method include mucociliary clearance, enzymatic degradation and poor drug permeation. Novel nanoformulations and intranasal drug-delivery devices offer promising solutions to overcome these challenges. Nanoformulations include polymeric nanoparticles, lipid-based nanoparticles, microspheres, liposomes and noisomes. Additionally, intranasal devices could be utilized to enhance drug-delivery efficacy. Therefore, intranasal drug-delivery systems show potential for treating neurodegenerative diseases through trigeminal or olfactory pathways, which can significantly improve patient outcomes.

Fipronil is a broad-spectrum phenyl pyrazole insecticide that has a high degree of environmental toxicity. Commonly available chilies in the market are treated with fipronil insecticides. Demand for insecticide-free chili has thus been increasing globally. This needs various sustainable and economical methods to remove insecticides from chilies. The present study examined the effectiveness of several cleaning methods to remove pesticide residues in chili fruits. A supervised field trial was conducted in randomized block design at Rajasthan Agricultural Research Institute, Durgapura, Jaipur, India. Chili samples were subjected to seven different household methods. The samples were extracted using the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. The residues were analyzed using a gas chromatograph-electron capture detector and confirmed by GC-MS. Of the seven methods, the acetic acid treatment removes the maximum residue effect of fipronil and its metabolites (desulfinyl [MB046513]), sulfide (MB045950), and sulfone (MB046136) on chili fruits. By contrast, the tap water treatment was the least effective. The Food Safety and Standards Authority of India (FSSAI) have set the maximum residue limit value of 0.001 mg kg -1 for fipronil on green chili., (© 2023 John Wiley & Sons Ltd.)

Polycystic ovarian syndrome (PCOS) develops due to hormonal imbalance and hyperandrogenism. Animal models are widely used to study PCOS because they mimic essential characteristics of human PCOS; however, the pathogenesis of PCOS remains unclear. Different sources of novel drugs are currently being screened as therapeutic strategies to alleviate PCOS and its symptoms. Simplified cell line in-vitro models could be preliminarily used to screen the bioactivity of various drugs. This review describes different cell line models focusing on the PCOS condition and its complications. Therefore, the bioactivity of the drugs could be preliminarily screened in a cell line model before moving to higher animal models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This paper presents a novel method that uses the cold metal transfer based wire arc additive manufacturing process to fabricate functionally graded Inconel 825-SS316L walls. The optical micrograph of Inconel 825 exhibits continuous and discontinuous dendritic structures. The SS316L region comprises 5% of δ-ferrite in primary austenitic (γ) dendrites which was confirmed by the Cr eq /Ni eq ratio of 1.305. The functionally graded interface reveals a partially mixed zone with a transition from the elongated dendrites to fine equiaxed dendrites. The tensile properties of the fabricated wall were determined at room temperature using specimens extracted from Inconel 825, SS316L, and the interface regions. The morphology of the tensile tested specimens revealed significant plastic deformation, indicating ductile failure. The fracture toughness of the wall was experimentally investigated by employing the crack tip opening displacement (CTOD) test. The fracture morphology exhibited a ductile mode of fracture with striations perpendicular to the direction of crack development. Elemental mapping revealed that there was no evidence of elemental segregation on the fractured surfaces, and the elements were uniformly dispersed. The CTOD measures 0.853 mm, 0.873 mm on the Inconel 825 side and the SS316L side respectively. The test results confirm that both the Inconel 825 and SS316L sides have good fracture toughness., (© 2023. The Author(s).)

BACKGROUNDThe free anterolateral thigh (ALTP) and free medial sural artery perforator (MSAP) flaps are time tested donor for head and neck, and extremities defect reconstruction. Proponents of either flap have concluded each as workhorse flap in their large cohort studies. However, we could not find any literature comparing the donor morbidities, or recipient site outcomes of these flaps, objectively.METHODSRetrospective data, such as demographic details, flap characteristics and post operative course, from patients who underwent free thinned ALTP (25 patients) and MSAP flap (20 patients) were included. At follow-up, donor site morbidity and recipient site outcomes were assessed, using previously defined protocols. These were compared in-between the two groups. RESULTSFree thinned ALTP (tALTP) flap had significantly more pedicle length and vessel diameter and harvest time than free MSAP flap (p value<.00). The differences in incidence of hyperpigmentation, itching, hypertrophic scar, numbness, sensory impairment and cold intolerance at the donor site in-between the two groups, were not significant statistically. Scar at free MSAP donor site was considered a significant social stigma (p value=.005). Recipient site cosmetic outcome was comparable (p value=.86), measured using aesthetic numeric analogue.CONCLUSIONSThe free tALTP flap is superior to free MSAP flap in terms of pedicle length, vessel diameter, donor site morbidity, while the latter takes lesser time for harvest.

The abrupt reduction in the human activities during the first lockdown of the COVID-19 pandemic created unprecedented changes in the background atmospheric conditions. Several studies reported the anthropogenic and air quality changes observed during the lockdown. However, no attempts are made to investigate the lockdown effects on the Atmospheric Boundary Layer (ABL) and background instability processes. In this study, we assess the lockdown impacts on the ABL altitude and instability parameters (Convective Available Potential Energy (CAPE) and Convective Inhibition Energy (CINE)) using WRF model simulations. Results showed a unique footprint of COVID-19 lockdown in all these parameters. Increase in the visibility, surface temperature and wind speed and decrease in relative humidity during the lockdown is noticed. However, these responses are not uniform throughout India and are significant in the inland compared to the coastal regions. The spatial variation of temperature (wind speed) and relative humidity shows an increase and decrease over the Indo Gangetic Plain (IGP) and central parts of India by 20% (100%) and 40%, respectively. Increase (80%) in the ABL altitude is larger over the IGP and central parts of India during lockdown of 2020 compared to similar time period in 2015-2019. This increase is attributed to the stronger insolation due to absence of anthropogenic activity and other background conditions. At the same time, CAPE decreased by 98% in the IGP and central parts of India, where it shows an increase in other parts of India. A prominent strengthening of CINE in the IGP and a weakening elsewhere is also noticed. These changes in CAPE and CINE are mainly attributed to the dearth of saturation in lower troposphere levels, which prevented the development of strong adiabatic ascent during the lockdown. These results provide a comprehensive observation and model-based insight for lockdown induced changes in the meteorological and thermo-dynamical parameters., Competing Interests: Declaration of competing interest The authors declare that they don't have any financial interests or personal relationships., (Copyright © 2022 Elsevier B.V. All rights reserved.)

East Asian dust episodes have a multitude of impacts, including on human health, environment, and climate over near-source and receptor regions. However, the mechanistic understanding of the synoptic conditions of these outbreaks at different altitude layers, and their eventual environmental impacts are less studied. The present study analyzed the synoptic transport patterns of East Asian dust during multiple dust generation episodes that occurred over only a few days apart in northern China, and which eventually delivered high PM 10 concentrations to surface level and high-altitude locations in Taiwan. Whether the dust plume was uplifted ahead of or behind the 700 hPa trough over East Asia determined its trajectory and eventual impact on the environment downwind. The total dust (iron) deposition over the ocean surface preceding arrival to Taiwan was 2.4 mg m -2 (0.95 μg m -2 ) for the episode impacting the surface level and 5.0 mg m -2 (4.6 μg m -2 ) for the episode impacting high-altitude Taiwan. Dust deposition in marine areas east of China was more intense for the higher altitude transport event that was uplifted behind the 700 hPa trough and resulted in twice higher marine Chl-a concentrations. Furthermore, we estimated a dust-induced direct radiative effect over a high mountainous region in Taiwan of -6.2 to -8.2 W m -2 at the surface, -1.9 to -2.9 W m -2 at the top of the atmosphere and +3.9 to +5.3 W m -2 in the atmosphere. This dust-induced atmospheric warming and surface cooling are non-negligible influences on the atmospheric thermal structure and biogeochemical cycle over the western North Pacific. Overall, this study highlights the significant impacts of dust particles on the marine ecosystem and atmospheric radiation budget over the downwind region, thus lays the foundation for linking these impacts to the initial synoptic conditions in the source area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In this study, the genetic diversity of local mango (Mangifera indica L.) germplasm including 14 genotypes were evaluated by using morphological, biochemical markers and DNA barcoding technique. Morphological characterization is the first step towards utilizing these germplasm in crop improvement studies. The advanced chloroplast based DNA barcode method can be utilized to assess the genetic diversity and phylogenetic structure in such populations., Methods: The study was carried out during 2018-2019 years to evaluate local mango germplasm including 14 diverse genotypes based on a number of morphological and biochemical traits and chloroplast DNA barcoding as well. The experiment was laid out in one way ANOVA design with fourteen germplasm indicated with indigenous collection number., Results: Among local mango germplasm, IC 589756 was found to be the most promising with respect to high magnitudes of fruit length, fruit width, fruit weight, pulp weight, soluble solid content (SSC)/Acidity ratio, pH and low acidity followed by IC 589746 exhibiting the highest pulp percentage and SSC accompanied with lowest stone weight and stone percent as compared to the other genotypes. Further, the dendrogram and cluster analyses based on sequencing of chloroplast marker i.e., trnH- psbA and trnCD depicted the relationship among mango genotypes and clearly clustered them into two main clusters at a similarity coefficient 0.035 and 0.150, respectively. The first cluster includes only one genotype and cluster-II contains 13 genotypes., Conclusions: Particularly results revealed that DNA barcoding of local mango germplasm can assist not only in molecular identification but also help in elucidation of their phylogenetic relationship and thus important in maintaining biodiversity inventories., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Next-Generation Sequencing allows for quick and precise sequencing of multiple genes concurrently. Recently, this technology has been employed for the identification of novel gene mutations responsible for disease manifestation among breast cancer (BC) patients, the most common type of cancer amongst Arabian women, and the major cause of disease-associated death in women worldwide. Genomic DNA was extracted from the peripheral blood of 32 Saudi Arabian BC patients with histologically confirmed invasive BC stages I-III and IV, as well from 32 healthy Saudi Arabian women using a QIAamp ® DNA Mini Kit. The isolated DNA was quantified using a Qubit™ dsDNA BR Assay Kit with a Qubit 2.0 Fluorometer. Ion semiconductor sequencing technology with an Ion S5 System and AmpliSeq™ Cancer Hotspot Panel v2 were utilized to analyze ~2,800 mutations described in the Catalogue of Somatic Mutations in Cancer from 50 oncogenes and tumor suppressor genes. Ion Reporter Software v.5.6 was used to evaluate the genomic alterations in all the samples after alignment to the hg19 human reference genome. The results showed that out of the 50 genes, 26 mutations, including 17 (65%) missense point mutations (single nucleotide variants), and 9 (35%) frameshift (insertion/deletion) mutations, were identified in 11 genes across the cohort in 61 samples (95%). Mutations were predominantly focused on two genes, PIK3CA and TP53, in the BC genomes of the sample set. PIK3CA mutation, c.1173A>G located in exon 9, was identified in 15 patients (46.9%). The TP53 mutations detected were a missense mutation (c.215C>G) in 26 patients (86.70%) and 1 frameshift mutation (c.215_216insG) in 1 patient (3.33%), located within exon 3 and 5, respectively. This study revealed specific mutation profiles for every BC patient, Thus, the results showed that Ion Torrent DNA Sequencing technology may be a possible diagnostic and prognostic method for developing personalized therapy based on the patient's individual BC genome., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Messaoudi et al.)

The diagnostic and prognostic utility of circulating cell-free DNA (cfDNA) in breast cancer (BC) patients was recently reported. Here, we investigated the use of cfDNA to examine microsatellite instability (MSI) and loss of heterozygosity (LOH) for early BC diagnosis. cfDNA and genomic DNA from 41 female BC patients and 40 healthy controls were quantified using NanoDrop spectrophotometry and real-time PCR. The stability of genomic and cfDNA was assessed using a high-resolution AmpFlSTR MiniFiler human identification kit. Significant increases in cfDNA plasma concentrations were observed in BC patients compared to controls. The genotype distribution of the eight autosomal short tandem repeat (STR) loci D7S820 , D13S317 , D21S11 , D2S1338 , D18S51 , D16S539 , FGA , and CSF1PO were in Hardy-Weinberg equilibrium. Significant differences in the allele frequencies of D7S820 allele-8, D21S11 allele-29, allele-30.2, allele-32.2, and CSF1PO allele-11 were seen between BC patients and controls. LOH and MSI were detected in 36.6% of the cfDNA of patients compared to genomic DNA. This study highlights the utility of plasma-derived cfDNA for earlier, less invasive, and cost-effective cancer diagnosis and molecular stratification. It also highlights the potential value of cfDNA in molecular profiling and biomarkers discovery in precision and forensic medicine.