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INTRODUCTION In July 2018, twenty-year-old Sarita approached the Supreme Court of India seeking permission to terminate her twenty-five-week pregnancy. (1) Sarita was a domestic violence survivor and suffered from other [...]

BackgroundA potential benefit of electronic health records (EHRs) is that they could potentially save clinician time and improve documentation by auto-generating the history of present illness (HPI) in partnership with patients prior to the clinic visit. We developed an online patient portal called AEGIS (Automated Evaluation of Gastrointestinal [GI] Symptoms) that systematically collects patient GI symptom information and then transforms the data into a narrative HPI that is available for physicians to review in the EHR prior to seeing the patient. ObjectiveThis study aimed to compare whether use of an online GI symptom history taker called AEGIS improves physician-centric outcomes vs usual care. MethodsWe conducted a pragmatic controlled trial among adults aged ≥18 years scheduled for a new patient visit at 4 GI clinics at an academic medical center. Patients who completed AEGIS were matched with controls in the intervention period who did not complete AEGIS as well as controls who underwent usual care in the pre-intervention period. Of note, the pre-intervention control group was formed as it was not subject to contamination bias, unlike for post-intervention controls. We then compared the following outcomes among groups: (1) documentation of alarm symptoms, (2) documentation of family history of GI malignancy, (3) number of follow-up visits in a 6-month period, (4) number of tests ordered in a 6-month period, and (5) charting time (difference between appointment time and time the encounter was closed). Multivariable regression models were used to adjust for potential confounding. ResultsOf the 774 patients who were invited to complete AEGIS, 116 (15.0%) finished it prior to their visit. The 116 AEGIS patients were then matched with 343 and 102 controls in the pre- and post-intervention periods, respectively. There were no statistically significant differences among the groups for documentation of alarm symptoms and GI cancer family history, number of follow-up visits and ordered tests, or charting time (all P>.05). ConclusionsUse of a validated online HPI-generation portal did not improve physician documentation or reduce workload. Given universal adoption of EHRs, further research examining how to optimally leverage patient portals for improving outcomes are needed.

BackgroundDuring 2013, a mobile health (mHealth) program, Innovative Mobile Technology for Community Health Operation (ImTeCHO), was launched in predominantly tribal and rural communities of Gujarat, India. ImTeCHO was developed as a job aid for Accredited Social Health Activists (ASHAs) and staff of primary health centers to increase coverage of maternal, neonatal, and child health care. ObjectiveIn this study, we assessed the incremental cost per life-years saved as a result of the ImTeCHO intervention as compared to routine maternal, neonatal, and child health care programs. MethodsA two-arm, parallel, stratified cluster randomized trial with 11 clusters (primary health centers) randomly allocated to the intervention (280 ASHAs, n=2,34,134) and control (281 ASHAs, n=2,42,809) arms was initiated in 2015 in a predominantly tribal and rural community of Gujarat. A system of surveillance assessed all live births and infant deaths in the intervention and control areas. All costs, including those required during the start-up and implementation phases, were estimated from a program perspective. Incremental cost-effectiveness ratios were estimated by dividing the incremental cost of the intervention with the number of deaths averted to estimate the cost per infant death averted. This was further analyzed to estimate the cost per life-years saved for the purpose of comparability. Sensitivity analysis was undertaken to account for parameter uncertainties. ResultsOut of a total of 5754 live births (3014 in the intervention arm, 2740 in the control arm) reported in the study area, per protocol analysis showed that the implementation of ImTeCHO resulted in saving 11 infant deaths per 1000 live births in the study area at an annual incremental cost of US $163,841, which is equivalent to US $54,360 per 1000 live births. Overall, ImTeCHO is a cost-effective intervention from a program perspective at an incremental cost of US $74 per life-years saved or US $5057 per death averted. In a realistic environment with district scale-up, the program is expected to become even more cost-effective. ConclusionsOverall, the findings of our study strongly suggest that the mHealth intervention as part of the ImTeCHO program is cost-effective and should be considered for replication elsewhere in India. Trial RegistrationClinical Trials Registry of India CTRI/2015/06/005847; http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=11820&EncHid=&modid=&compid=%27,%2711820det%27

Objectives/hypothesis: The avian cochlea regenerates hair cells following aminoglycoside treatment through supporting cell proliferation. Immunocytochemical labeling of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, is a popular nonradioactive marker for identifying cells in the DNA synthesis (S phase) of the cell cycle. However, it requires harsh treatments to denature double-stranded DNA for the antibody to bind BrdU. We explored a new method using 5-ethynyl-2'-deoxyuridine (EdU) as a thymidine analog and a nonantibody azide/alkyne reaction between EdU and the fluorescent probe. We propose that EdU is as effective as BrdU, but without the requirement for harsh denaturation or the use of antibodies for detection.Study Design: Two-week-old chicks received a single gentamicin injection followed by a single EdU injection 72 hours later. Cochleae were extracted 4-8 hours later, fixed, and processed for fluorescent detection of EdU.Methods: Cochleae were processed for detection of incorporated EdU using the Click-iT Imaging Kit (Invitrogen/Molecular Probes, Carlsbad, CA) and colabeled with Sox2, myosin VI, or myosin VIIa antibodies. Whole-mount cochlear preparations were examined with confocal microscopy.Results: Supporting cells incorporated EdU into their newly synthesized DNA during the 4-8 hours following the EdU injection and were readily detected with little background signal. The intensity and quantity of cells labeled were similar to or better than that seen for BrdU.Conclusions: The EdU method is as effective as BrdU, without requiring harsh denaturation or secondary antibodies to identify proliferating cells. Thus, the nonantibody EdU system allows more flexibility by enabling colabeling with multiple antibodies to other cellular proteins involved in regeneration. [ABSTRACT FROM AUTHOR]

Aim: Presumed congenital simple retinal pigment epithelium hamartoma is a rare benign lesion of the macula that mimics congenital hypertrophy of the retinal pigment epithelium (RPE) and combined hamartoma of the retina and the RPE; newer imaging modalities can help in diagnosis. We report three patients with presumed congenital simple RPE hamartoma, and describe the enhanced-depth imaging optical coherence tomography (EDI-OCT) and fundus autofluorescence (FAF) findings. Methods: Two patients were asymptomatic; one had an intraocular foreign body in addition to the hamartoma. All had a similar jet black, elevated lesion in the macula, sparing the fovea. EDI-OCT showed a characteristic hyperreflective layer with complete optical shadowing of the deeper layers; FAF showed pronounced hypoautofluorescence of the lesion. Conclusion: Multimodal imaging with FAF and EDI-OCT can help to differentiate simple RPE hamartoma from similar RPE lesions, and may serve as a useful adjunct to clinical diagnosis of this rare tumor. We present the second largest series of presumed congenital simple RPE hamartoma, and – to the best of our knowledge – the first report of FAF findings of this tumor.

Objective: Ocular ischemic syndrome is a rare blinding condition generally caused by disease of the carotid artery. We describe a 69-year-old female with a 50 pack-year smoking history with aortic arch syndrome causing bilateral ocular ischemic syndrome. Methods: The patient presented with progressive visual loss and temple pain. Slit lamp biomicroscopy revealed bilateral iris neovascularization. This finding prompted a cardiovascular work up. Panretinal photocoagulation with retrobulbar block was performed in the right eye. Results: A temporal artery biopsy was negative. The carotid duplex sound showed only a 1–39% stenosis. MRA revealed a more proximal occlusion of the aortic branch for which she underwent subclavian carotid bypass surgery. At the one month follow up, the right eye suffered profound vision loss secondary to a central retinal artery occlusion. Conclusion: Ocular neovascularization may be one of the clinical manifestations of aortic arch syndrome. This case also illustrates the limitations of relying solely on carotid duplex ultrasound testing. We caution against overly aggressive panretinal photocoagulation utilizing retrobulbar anesthesia.

Galactosemia, an inborn neurometabolic disorder, results from an aberrant galactose metabolism due to the deficiency of serum galactose-1-phosphate uridyltransferase activity. It manifests in the central nervous system in the form of hypotonia, seizures, mental retardation, tremor, ataxia, and progressive cerebellar as well as extrapyramidal features. To the best of our knowledge, chorea due to galactosemia has not been reported in infancy. [ABSTRACT FROM AUTHOR]

Background: Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer., Methods: Isogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were evaluated in these isogenic tumor lines and T cells in vitro and in vivo . Transcriptomic and proteomic changes in tumors and T cells were characterized in response to PRMT5i treatment. Furthermore, the efficacy of MRTX1719 in combination with immune checkpoint blockade was assessed in two syngeneic murine models with MTAP-loss tumor., Results: GSK3326595 significantly suppresses PRMT5 activity in tumors and T cells regardless of the MTAP status. However, MRTX1719, a methylthioadenosine-cooperative PRMT5 inhibitor, exhibits tumor-specific PRMT5 inhibition in MTAP-loss tumors with limited immunosuppressive effects. Mechanistically, transcriptomic and proteomic profiling analysis reveals that MRTX1719 successfully reduces the activation of the PI3K pathway, a well-documented immune-resistant pathway. It highlights the potential of MRTX1719 to overcome immune resistance in MTAP-loss tumors. In addition, MRTX1719 sensitizes MTAP-loss tumor cells to the killing of tumor-reactive T cells. Combining MRTX1719 and anti-PD-1 leads to superior antitumor activity in mice bearing MTAP-loss tumors., Conclusion: Collectively, our results provide a strong rationale and mechanistic insights for the clinical development of MRTX1719-based IO combinations in MTAP-loss tumors., Competing Interests: Competing interests: JRA reports non-financial support and reasonable reimbursement for travel from European Society for Medical Oncology and Loxo Oncology; receiving consulting and travel fees from Ellipses Pharma, Molecular Partners, IONCTURA, Sardona, Mekanistic, Amgen, Merus, MonteRosa, Aadi and Bridgebio (including serving on the scientific advisory board); consulting fees from Vall d’Hebron Institute of Oncology/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, Boxer Capital, LLC, Tang Advisors, LLC and Guidepoint, receiving research funding from Blueprint Medicines, Merck Sharp and serving as investigator in clinical trials with Cancer Core Europe, Symphogen, BioAlta, Pfizer, Kelun-Biotech, GlaxoSmithKline, Taiho, Roche Pharmaceuticals, Hummingbird, Yingli, Bicycle Therapeutics, Merus, Aadi Bioscience, ForeBio, Loxo Oncology, Hutchison MediPharma, Ideaya, Amgen, Tango Therapeutics, Mirati Therapeutics, Linnaeus Therapeutics, MonteRosa, Kinnate, Yingli, Debio, BioTheryX, Storm Therapeutics, Beigene, MapKure, Relay, Novartis, FusionPharma, C4 Therapeutics, Scorpion Therapeutics, Incyte, Fog Pharmaceuticals, Tyra, Nuvectis Pharma. MTB is a co-founder of EpiCypher. No potential conflicts of interest were disclosed by other authors., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the association between thyroid dysfunction and mortality among patients hospitalized with COVID-19. Design: This is a retrospective multi-center study, which examined all patients admitted with Covid-19 diagnoses, and thyroid function results in absence of known thyroid disease., Results: 10,933 hospitalized COVID-19 positive patients were included in the study. These patients were without prior diagnosis or treatment of thyroid disease. Outcomes assessed were mortality, ICU admission, Ventilator use, length of stay, readmission and complications during hospital stay. Patients with low TSH and Low free T4 had odds of mortality of 10.07(95% CI [7.44-13.6]) compared to patients with Normal TSH and any free T4 levels. Patients with Low TSH and High free T4 also had odds of mortality of 1.38 (95% CI [1.19-1.59]) compared to patients with Normal TSH and Any free T4 level. Patients with Low TSH and Normal free T4 levels also had an Odds of mortality of 1.46 (95% CI [1.31-1.62]) compared to patients with Normal TSH and any free T4 level. Patients with Low TSH also had higher odds of ICU admission and Ventilator use when compared to patients with normal TSH., Conclusions: This study shows that patients with low TSH, regardless of free T4 level, indicates poor prognosis for hospitalized patients with SARS-CoV-2 infection and offers further insights into possible prognostic value of TSH levels for severe COVID-19 outcomes., Competing Interests: Conflicts of interest: All authors have no financial disclosures or conflicts of interest to report., (© 2024 Greater Baltimore Medical Center.)

Psoriasis is a chronic inflammatory disease that is becoming widespread and is associated with many kinds of additional severe diseases. The present study aimed to develop a methotrexate-loaded almond oil-based nanoemulsion formulation (MTX NE) for topical administration. The drug-loaded nanoemulsion formulation was prepared by high shear homogenization technique. The formulation's stability, as well as other physical and chemical characteristics, including entrapment effectiveness, drug release kinetics, skin permeability, skin irritation, and in vivo evaluation of the optimized formulation, was assessed. Additionally, imiquimod-induced psoriasis in rats was employed to investigate the efficacy of MTX NE against skin disorders. The MTX NE formulation was developed with a particle size of 18.74 ± 9.748 nm, a polydispersity index (PDI) of 0.198 ± 0.01, and an average entrapment efficiency of 79.65 ± 3.84%. The release kinetics model estimates 81.08% drug release at pH 5.5 after 24 h. The major layers of the skin, the epidermis, and dermis were successfully fluidized by the optimized MTX NE formulation, as shown by FTIR results, most likely enhancing drug retention and permeability. However, since Tween 80 and PEG 400 are well-known penetration enhancers, their application greatly accelerates these effects. Permeation data indicate that after 24 h, methotrexate was released from the nano-emulsion at 76.83 ± 4.98 g/cm 2 with a flux rate of 2.385 ± 0.61 µg/cm 2 /h. The in vivo study conducted on rabbit skin showed that the enhanced skin penetration of the prepared MTX-loaded nanoemulsion formulation does not cause any structural modifications in the inter-cellular lipid layers of the stratum corneum. Rabbits used in the in vivo anti-psoriatic investigation demonstrated that MTX NE produced a 95% reduction in PASI. The pharmacokinetic profile revealed that the C max , T max , and t 1/2 values were 8.63 µg/mL, 12.5 h, and 17.77 ± 2.21 h, respectively. These findings suggest that the formulation MTX NE is effective in treating psoriasis and may reduce psoriasis symptoms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 1 in 3-4 adult individuals and can progress to metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Insulin resistance plays a central role in MASLD/MASH pathophysiology with higher rates of MASLD (2 in 3) and MASH with fibrosis (1 in 5) in adults with obesity and diabetes. This review summarizes the role of glucagon-like peptide-1 receptor agonists in treating MASLD/MASH. Although not approved by the Food and Drug Administration for the treatment of MASLD, this class of medication is available to treat obesity and type 2 diabetes and has been shown to reverse steatohepatitis, reduce cardiovascular risk, and is safe to use across the spectrum of MASLD with or without fibrosis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Head and neck cancers are fairly common in India due to the widespread consumption of tobacco and neck dissection is a major component in the surgical management. The objective of this study is to analyze the effect of MRND and SND on shoulder function and quality of life in patients of head and neck cancer. Our study is a prospective comparative study on 65 head and neck cancer patients divided into 2 groups-33 in group A (MRND group) and 32 in group B (SND group). Clinical evaluation of shoulder function was done pre-operatively, 1 week, 1 month, 3 month and 6 month post-operatively using arm abduction scores (AAS) and shoulder pain and disability index (SPADI). Nerve-conduction study (NCS) was done pre-operatively and 3 months post-operatively for assessment of SAN. Neck dissection quality of life questionnaire (NDQOL) was used as a quality-of-life measure. A total of 65 neck dissections were included in the analysis (33 in group A and 32 in group B) out of which 53 were males and 12 were females. The mean AAS on the 6th post-operative month in group A was significantly lower than that of group B ( p  = 0.01). The mean SPADI scores on the 6th post-operative month was significantly worse in group A than group B ( p value 0.01). On NCS, a significant decrease in amplitude was seen in group A ( p  = 0.02) and a significant increase in latency was noted in group B ( p  = 0.005). Quality of life score on 6th post-operative month showed no significant difference between both the groups ( p  > 0.05). Level V dissection in MRND is associated with higher incidence and greater severity of shoulder dysfunction. AAS and SPADI score are useful tools in post operative follow up of shoulder dysfunction. NCS helps in the detection of neuropathy and to determine its severity. Early rehabilitation promotes long term recovery., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Amorphous solid dispersion (ASD) has emerged to be an outstanding strategy among multiple options available for improving solubility and consequently biological activity. Interestingly several binary SD systems continue to exhibit insufficient solubility over time. Therefore, the goal of current research was to design ternary amorphous solid dispersions (ASDs) of hydrophobic model drug curcumin (CUR) to enhance the solubility and dissolution rate in turn, presenting enhanced anti-bacterial, antioxidant and anti-inflammatory activity. For this purpose several ternary solid dispersions (TSDs) consisting of Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 in combination with HPMC E5 (binary carrier) were prepared using solvent evaporation method. Both solubility and dissolution testing of prepared solid dispersion were performed to determine the increase in solubility and dissolution. Solid state investigation was carried out utilizing infrared spectroscopy, also known as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),Differential scanning calorimetry (DSC) and X-ray diffraction (XRD).Optimized formulations were also tested for their biological effectiveness including anti-bacterial, anti-oxidant and anti-inflammatory activity. Amid all Ternary formulations F3 entailing 20 % soluplus® remarkably improved the solubility (186 μg/ml ± 3.95) and consequently dissolution (91 % ± 3.89 %) of curcumin by 3100 and 9 fold respectively. These finding were also supported by FTIR, SEM, XRD and DSC. In-vitro antibacterial investigation of F3 also demonstrated significant improvement in antibacterial activity against both gram positive ( Staphylococcus aureus, Bacillus cereus) and gram negative ( Pseudomonas aeruginosa , Escherichia coli) bacteria. Among all the tested strains Staphylococcus aureus was found to be most susceptible with a zone of inhibition of 24 mm ± 2.87. Antioxidant activity of F3 was also notably enhanced (93 % ± 5.30) in contrast to CUR (69 % ± 4.79). In vitro anti-inflammatory assessment also exhibited that F3 markedly protected BSA (bovine serum albumin) from denaturation with percent BSA inhibition of 80 % ± 3.16 in comparison to CUR (49 % ± 2.91). Hence, F3 could be an effective solid dispersion system for the delivery of model hydrophobic drug curcumin., Competing Interests: 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., (© 2024 The Authors.)

Background: Disabled 2 (DAB2) is a multifunctional protein that has emerged as a critical component in the regulation of tumor growth. Its dysregulation is implicated in various types of cancer, underscoring its importance in understanding the molecular mechanisms underlying tumor development and progression. This review aims to unravel the intricate molecular mechanisms by which DAB2 exerts its tumor-suppressive functions within cancer signaling pathways., Methods and Results: We conducted a comprehensive review of the literature focusing on the structure, expression, physiological functions, and tumor-suppressive roles of DAB2. We provide an overview of the structure, expression, and physiological functions of DAB2. Evidence supporting DAB2's role as a tumor suppressor is explored, highlighting its ability to inhibit cell proliferation, induce apoptosis, and modulate key signaling pathways involved in tumor suppression. The interaction between DAB2 and key oncogenes is examined, elucidating the interplay between DAB2 and oncogenic signaling pathways. We discuss the molecular mechanisms underlying DAB2-mediated tumor suppression, including its involvement in DNA damage response and repair, regulation of cell cycle progression and senescence, and modulation of epithelial-mesenchymal transition (EMT). The review explores the regulatory networks involving DAB2, covering post-translational modifications, interactions with other tumor suppressors, and integration within complex signaling networks. We also highlight the prognostic significance of DAB2 and its role in pre-clinical studies of tumor suppression., Conclusion: This review provides a comprehensive understanding of the molecular mechanisms by which DAB2 exerts its tumor-suppressive functions. It emphasizes the significance of DAB2 in cancer signaling pathways and its potential as a target for future therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The concurrent seropositivity of HBsAg and anti-HBs has been described among patients with chronic hepatitis B (CHB), but its prevalence is variable. HBV S-gene mutations can affect the antigenicity of HBsAg. Patients with mutations in the 'α' determinant region of the S gene can develop severe HBV reactivation under immunosuppression. In this study at a tertiary liver center in the United States, we evaluated the frequency and virological characteristics of the HBsAg mutations among CHB patients with the presence of both HBsAg and anti-HBs. In this cohort, 45 (2.1%) of 2178 patients were identified to have a coexistence of HBsAg and anti-HBs, and 24 had available sera for the genome analysis of the Pre-S1, Pre-S2, and S regions. The frequency of mutations in the S gene was significantly higher among those older than 50 years (mean 8.5 vs. 5.4 mutations per subject, p = 0.03). Twelve patients (50%) had mutations in the 'α' determinant region of the S gene. Mutations at amino acid position 126 were most common in eight subjects. Three had a mutation at position 133. Only one patient had a mutation at position 145-the classic vaccine-escape mutation. Despite the universal HBV vaccination program, the vaccine-escape mutant is rare in our cohort of predominantly Asian patients.

Objectives: To test whether Kangaroo mother care (KMC) aids in transfer of favourable skin microbiome from mother to infant by comparing the microbiome composition before and after KMC., Methods: A prospective cohort pilot study was conducted in a Level III neonatal intensive care unit (NICU) in South India, recruiting 30 preterm infants with gestation <32 wk from October 2020 through December 2020. Neonatal skin involving the area in contact with the mother during KMC i.e., axilla, chest and abdomen was swabbed at the end of first week of life, prior to initiation of KMC. The 2nd swab involving the same areas was taken following KMC for 7 d for at least 6 h a day. The swabs were analysed using Next Generation Sequencing (NGS) - 16sRNA and abundance of organisms isolated were mapped. Statistical analyses using t-test and PERMANOVA were performed to compare phyla and genera of bacterial abundance pre-KMC and post-KMC., Results: KMC at phyla level increased the relative abundance of Firmicutes (p=0.52) and significantly decreased Proteobacteria (p=0.02). At species level, KMC decreased pathogenic bacterial count of Escherichia (p=0.05), while counts of S. hemolyticus (p=0.01) and S. hominis (p=.002) significantly increased post KMC., Conclusions: KMC has a potential role in altering the neonatal skin microbiota towards a more favourable microenvironment. The clinical significance of these novel findings needs to be validated with larger studies., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Introduction: The COVID-19 pandemic has offset some of the gains achieved in global health, particularly in relation to maternal, child health and nutrition. As pregnancy is a period of plasticity where insults acting on maternal environment have far-reaching consequences, the pandemic has had a significant impact on prenatal outcomes, intrauterine and postnatal development of infants. This research will investigate both the direct and indirect impacts of the COVID-19 pandemic during pregnancy on prenatal outcomes, growth and development in early childhood., Methods and Analysis: Community and hospital data in Hyderabad and Gujarat, India will be used to recruit women who were pregnant during the COVID-19 pandemic and contracted SARS-CoV-2 infection. In comparison with women who were pregnant around the same time and did not contract the virus, the study will investigate the impact of the pandemic on access to healthcare, diet, nutrition, mental health and prenatal outcomes in 712 women (356 per study arm). Children born to the women will be followed prospectively for an 18-month period to investigate the impact of the pandemic on nutrition, health, growth and neurocognition in early childhood., Ethics and Dissemination: Ethics approval was granted from the institutional ethics committees of the Indian Institute of Public Health Gandhinagar (SHSRC/2021/2185), Indian Council of Medical Research-National Institute of Nutrition (EC/NEW/INST/2021/1206), and London School of Hygiene and Tropical Medicine (72848). The findings of the study will be disseminated to policy and research communities through engagements, scientific conferences, seminars, and open-access, peer-reviewed publication., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Neurocutaneous syndromes comprise a heterogeneous group of congenital or hereditary conditions that are known to be associated with the risk of different disorders and complications. Two of the most common neurocutaneous syndromes are Neurofibromatosis type 1 (NF1) and Tuberous Sclerosis Complex (TSC). Although there appears to be a general consensus on the importance of a multidisciplinary approach in managing these cases, there is still very little emphasis in discussions addressed in the literature on the role of dentistry in accordance with the perspective of comprehensive care. Evidence-based propositions, together with a broad discussion of new insights in this regard, should have the ability to strongly impact related future perspectives, aiming for greater advances and better outcomes for these patients. In this review article, the authors discuss updated general aspects of NF1 and TSC, and the potential additional roles of dentistry, in addition to addressing suggestions for actions in dentistry at related levels of care, as well as priorities for future research., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Every year Invasive Fungal Infections (IFI) are globally affecting millions of people. Candida albicans and Aspergillus niger have been reported as the most infectious and mortality-inducing fungal strains among all pathogenic fungi., Aims & Objectives: To tackle this problem in the current study Pyranopyrazoles and Pyrazolopyrano- pyrimidine derivatives were developed using molecular hybridization, green chemistry and one-pot multicomponent reaction., Materials and Methods: In the present work, New Chemical entities (NCE's) were developed on the basis of Structure activity relationship. All designed NCE's were screened for ADMET studies using the QikProp module of Schrodinger software. NCE's with zero violations were further docked on the crystal structure of 14α demethylase, cytochrome P450 and thymidine synthase (PDB ID: 5V5Z, 7SHI, 1BID). Selected molecules were synthesized using green chemistry techniques and evaluated for in vitro antifungal activity against Candida albicans and Aspergillus niger ., Results and Discussion: Designed NCE's (B1-12 and C1-11) showed favorable results in ADMET studies. In the docking study six compounds from series-B and five molecules from series- C showed good dock score and binding interaction when compared with the standard drugs. Compounds B-3 and C-4 showed the highest zone of inhibition activity against Candida albicans, where as B-1 and C-3 had shown highest zone of inhibition activity against Aspergillus niger., Conclusion: Bicyclic ring (series B) showed better activity as compare to fused tricyclic ring (series C)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Competing Interests: Competing interests: None declared.

Given the ubiquity of these plant-based oils, your patients might ask about using them. Here's the evidence on safety and efficacy to guide your response.

The paper describes biogenic synthesis of silver nanoparticles (AgNPs) using Adhatoda vasica leaf extracts at room temperature. The prepared AgNPs were characterized by UV-visible spectroscopy, Fourier-transform infrared spectroscopy, powder X-ray diffraction, Energy dispersive X-ray (EDX), High Resolution Transmission Electron Microscope, Scanning Electron Microscopy and Thermogravimetric analyser. The bio reduction method is devoid of any toxic chemicals, organic solvents, and external reducing, capping and stabilizing agent. The synthesized AgNPs had spherical shape with particle size ranging between 3.88 and 23.97 nm and had face centered cubic structure. UV-visible spectral analysis confirmed the formation of AgNPs with a characteristic surface plasmon resonance band at 419 nm. The EDX pattern revealed the presence of elemental Ag in AgNPs. The prepared AgNPs were used for degradation of Amaranth, Allura red and Fast green in aqueous medium, with ≥ 92.6% efficiency within 15 min using 5 mg of AgNPs. The optical bandgap, Eg value of 2.26 eV for AgNPs was found to be effective for rapid photocatalytic degradation of all the three dyes. The degradation process was observed to follow pseudo first order kinetics., (© 2023. The Author(s).)

Curcumin's applications in the treatment of conditions including osteoarthritis, dementia, malignancies of the pancreas, and malignancies of the intestines have drawn increasing attention. It has several wonderful qualities, including being an anti-inflammatory agent, an anti-mutagenic agent, and an antioxidant, and has substantially reduced inherent cytotoxicity outcomes. Although curcumin possesses multiple known curative properties, due to its limited bioavailability, it is necessary to develop efficient strategies to overcome these hurdles. To establish an effective administration method, various niosomal formulations were optimized using the Box-Behnken design and assessed in the current investigation. To examine the curcumin niosomes, zeta sizer, zeta potential, entrapment efficiency, SEM, antioxidant potential, cytotoxicity, and release studies were performed. The optimized curcumin niosomes exhibited an average particle size of 169.4 nm, a low PDI of 0.189, and high entrapment efficiency of 85.4%. The release profile showed 79.39% curcumin after 24 h and had significantly higher antioxidant potential as compared with that of free curcumin. The cytotoxicity results of curcumin niosomes presented increased mortality in human ovarian cancer A2780.

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of β-cyclodextrin (βCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with βCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with βCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: βCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:βCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: βCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban., Competing Interests: 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., (© 2023 The Authors.)

Depression is the major mental illness which causes along with loss of interest in daily life, a feeling of hopelessness, appetite or weight changes, anger and irritability. Due to the hepatic first-pass metabolism, the absolute bioavailability of fluvoxamine (FVM) after oral administration is about 50%. By avoiding the pre-systemic metabolism, nasal delivery would boost bioavailability of FVM. Additionally, the absorption is anticipated to occur more quickly than it would via the oral route because of the existence of microvilli and high vasculature. A nonionic surfactant, cholesterol and an arachidonic acid-carboxymethyl chitosan (AA-CMCS) conjugate were used to develop FVM-loaded novasomes. To investigate the effects of surfactant concentration, AA-CMCS conjugate concentration and stirring speed on the novasomes' characteristics, a Box-Behnken design was used. The dependent variables chosen were zeta potential, polydispersity index and particle size. The AA-CMCS conjugate was confirmed by 1 H-NMR and FTIR. Using Design Expert software (version 7; Stat-Ease Inc., Minneapolis, MN, USA), novasomes were further optimized. The chosen optimal formulation (NAC8) was made up of AA-CMCS conjugate, Span 60 and cholesterol. Particle size, zeta potential and PDI values for NAC8 formulation were 101 nm, -35 mV and 0.263, respectively. The NAC8 formulation's DSC and TGA analysis demonstrated that the medication had been uniformly and amorphously distributed throughout the novasomes. The NAC8 formulation showed 99% and 90% FVM release and permeation, respectively, and the novasome adherence time was 24 h. An improved antidepressant effect along with five-fold increase in bioavailability of FVM was observed after trans-nasal administration of NAC8 formulation compared to the reference commercially available Flumin ® tablets. FVM-loaded novasomes administered via the nasal route may therefore constitute an advancement in the management of depression.

Asthma is a common chronic inflammatory condition of the airways that affects about 350 million people globally. In 5%-10% of individuals, it is severe, with considerable morbidity and high health care utilization. The goal of asthma management is disease control by reducing symptoms and exacerbations and reducing corticosteroid-related morbidity. The era of biologics has revolutionized the management of severe asthma. Biologics have changed our expectations for severe asthma, especially in those people with type-2 mediated immunity. We can now explore the potential for changing disease trajectory and inducing remission. However, biologics are not a panacea for all severe asthma sufferers and despite their success there remains substantial unmet clinical need. We review the pathogenesis of asthma, phenotyping the heterogeneity of asthma, currently licensed and future biologic agents, how to choose the initial biologic, assessing the response, remission and switching of biologic therapies., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

The recently explained cytokine, which is produced after the stimulation of interferon (IFN)-c, interleukin (IL)-2, and IL-18 is IL-32, has pro-inflammatory IFN-c, IL-2 and IL-18 are IL-32 mediator's properties that are generally entailed in many diseases, including infections, cancer, and chronic inflammation. After the initial statement in 2005, it promoted the osteoclast precursor's differentiation into TRAcP plus VNR plus multinucleated cells that express explicit osteoclast indicators. Furthermore, the loss of bone resorption might be accredited because of the collapse of the multinucleated cells, which are produced of the reaction to IL-32 to direct factoring that is ultimately essential for attaching the cells for bone resorption. Thus, in conclusion, IL-32, the pro-inflammatory mediator, has an important and indirect role in regulating osteoclast differentiation. In bone disorder's pathophysiology, critical role of IL-32 needs more scientific evidence to develop a rational treatment protocol. IL-32 can become a potent mediator of active osteoclast generation in the presence of receptor activator of NF-κB ligand (RANKL). This novel cytokine can introduce more favorable conditions for osteoclastogenesis in the rheumatic arthritis by increasing the RANKL and osteoprotegerin ratio in fibroblast-like synoviocytes., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by Turkish Pharmacists' Association / Turkish Journal of Pharmaceutical Sciences published by Galenos Publishing House.)

Background: The loss of HBV HBsAg or functional cure is a desirable goal of hepatitis B management. The relative abundances of HBsAg isoforms may offer additional diagnostic and predicting values. To evaluate the clinical utility of HBsAg isoforms, we developed novel prototype assays on the ARCHITECT automated serology platform that specifically detects total-HBsAg (T-HBsAg), large (L-HBsAg), and middle (M-HBsAg) products of the S gene to determine the isoform composition of human specimens from acute and chronic HBV infection and during long-term nucleos(t)ide analog therapy., Results: In the early phase of acute HBV infection, L-HBsAg and M-HBsAg emerged within days and were in parallel to T-HBsAg during the entire course of infection. M-HBsAg levels were consistently higher than L-HBsAg levels. Patients with HBeAg(+) chronic hepatitis B had higher T-HBsAg, M-HBsAg, and L-HBsAg levels compared with HBeAg(-) patients. Correlations of M-HBsAg and L-HBsAg to T-HBsAg were similar in both. In contrast, there was no strong correlation between L-HBsAg or M-HBsAg with HBV DNA levels. During long-term nucleos(t)ide analog treatment, changes in HBsAg isoform abundance were proportional to T-HBsAg regardless of treatment responses for both HBeAg(+) and HBeAg(-) chronic hepatitis B. A larger sample size may be necessary to detect a significant difference., Conclusion: HBsAg isoform compositions parallel T-HBsAg levels in both acute and chronic hepatitis B infection. L-HBsAg and M-HBsAg individual biomarkers do not appear to provide an additional diagnostic benefit for staging chronic disease or monitoring response to treatment with current therapies., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Multiple Sclerosis, Hereditary Spastic Paraplegia, and Amyotrophic Lateral Sclerosis have emerged as the most dreaded diseases due to a lack of precise diagnostic tools and efficient therapies. Despite the fact that the contributing factors of NDs are still unidentified, mounting evidence indicates the possibility that genetic and cellular changes may lead to the significant production of abnormally misfolded proteins. These misfolded proteins lead to damaging effects thereby causing neurodegeneration. The association between Neurite outgrowth factor (Nogo) with neurological diseases and other peripheral diseases is coming into play. Three isoforms of Nogo have been identified Nogo-A, Nogo-B and Nogo-C. Among these, Nogo-A is mainly responsible for neurological diseases as it is localized in the CNS (Central Nervous System), whereas Nogo-B and Nogo-C are responsible for other diseases such as colitis, lung, intestinal injury, etc. Nogo-A, a membrane protein, had first been described as a CNS-specific inhibitor of axonal regeneration. Several recent studies have revealed the role of Nogo-A proteins and their receptors in modulating neurite outgrowth, branching, and precursor migration during nervous system development. It may also modulate or affect the inhibition of growth during the developmental processes of the CNS. Information about the effects of other ligands of Nogo protein on the CNS are yet to be discovered however several pieces of evidence have suggested that it may also influence the neuronal maturation of CNS and targeting Nogo-A could prove to be beneficial in several neurodegenerative diseases., 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.)

The coronavirus disease 2019 (COVID-19) pandemic has imposed a radical change in daily life and work routine. In this context, health systems have suffered important and serious repercussions in all fields. Among the changes brought about by the state of global health emergency, adjustments to guidelines, priorities, structures, professional teams, and epidemiological data stand out. In light of this, the oncological field has witnessed several changes in the approach to cancer, whether due to delay in diagnosis, screening deficit, personnel shortage or the psychological impact that the pandemic has had on cancer patients. This article focuses on the management of oral carcinoma and the surgical approaches that oral and maxillofacial specialists have had at their disposal during the health emergency. In this period, the oral and maxillofacial surgeons have faced many obstacles. The proximity of maxillofacial structures to the airways, the need of elective and punctual procedures in cancerous lesions, the aggressiveness of head and neck tumors, and the need for important healthcare costs to support such delicate surgeries are examples of some of the challenges imposed for this field. One of the possible surgical 'solutions' to the difficulties in managing surgical cases of oral carcinoma during the pandemic is locoregional flaps, which in the pre-COVID-19 era were less used than free flaps. However, during the health emergency, its use has been widely reassessed. This setback may represent a precedent for opening up new reflections. In the course of a long-term pandemic, a reassessment of the validity of different medical and surgical therapeutic approaches should be considered. Finally, given that the pandemic has high-lighted vulnerabilities and shortcomings in a number of ways, including the issues of essential resource shortages, underinvestment in public health services, lack of coordination and versatility among politicians, policymakers and health leaders, resulting in overloaded health systems, rapid case development, and high mortality, a more careful analysis of the changes needed in different health systems to satisfactorily face future emergencies is essential to be carried out. This should be directed especially towards improving the management of health systems, their coordination as well as reviewing related practices, even in the surgical field., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

A cancerous tumour termed hepatocellular carcinoma (HCC) is characterized by inflammation and subsequently followed by end-stage liver disease and necrosis of the liver. The liver's continuous exposure to microorganisms and toxic molecules affects the immune response because normal tissue requires some immune tolerance to be safeguarded from damage. Several innate immune cells are involved in this process of immune system activation which includes dendritic cells, macrophages, and natural killer cells. The liver is an immunologic organ with vast quantities of innate and innate-like immune cells subjected to several antigens (bacteria, fungal or viral) through the gut-liver axis. Tumour-induced immune system engagement may be encouraged or suppressed through innate immunological systems, which are recognized promoters of liver disease development in pre-HCC conditions such as fibrosis or cirrhosis, ultimately resulting in HCC. Immune-based treatments containing several classes of drugs have transformed the treatment of several types of cancers in recent times. The effectiveness of such immunotherapies relies on intricate interactions between lymphocytes, tumour cells, and neighbouring cells. Even though immunotherapy therapy has already reported to possess potential effect to treat HCC, a clear understanding of the crosstalk between innate and adaptive immune cell pathways still need to be clearly understood for better exploitation of the same. The identification of predictive biomarkers, understanding the progression of the disease, and the invention of more efficient combinational treatments are the major challenges in HCC immunotherapy. The functions and therapeutic significance of innate immune cells, which have been widely implicated in HCC, in addition to the interplay between innate and adaptive immune responses during the pathogenesis, have been explored in the current review., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity worldwide. With the obesity pandemic, NAFLD-related HCC is contributing to the burden of disease exponentially. Genetic predisposition and clinical risk factors for NAFLD-related HCC have been identified. Cirrhosis is a well-known and major risk factor for NAFLD-related HCC. However, the occurrence of NAFLD-related HCC in patients without cirrhosis is increasingly recognized and poses a significant challenge regarding cancer surveillance. It is of paramount importance to develop optimal risk stratification scores and models to identify subsets of the population at high risk so they can be enrolled in surveillance programs. In this review, we will discuss the risks and prediction models for NAFLD-related HCC., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study evaluated newborn gentamicin serum concentrations after birth and the effects on the newborn after extended interval gentamicin dosing in peripartum mothers., Methods: This was a single-center, retrospective chart review of neonates born to mothers that received peripartum once-daily gentamicin dosing of approximately 5 mg/kg within 12 hours of delivery. A gentamicin serum concentration was obtained immediately after birth in the newborn. The primary outcome was initial neonatal gentamicin serum concentration after birth. Several secondary outcomes were evaluated including nephrotoxicity and ototoxicity. A subgroup analysis comparing baseline demographics of mother-newborn dyads with birth neonatal serum concentrations of less than 2 mcg/mL versus 2 mcg/mL or greater was performed., Results: A total of 32 mother-newborn dyads were included. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.4 kg. The mean initial gentamicin serum concentration was elevated at 3.1 ± 1.9 mcg/mL among all newborns. The median maternal dose based on actual body weight in newborns with gentamicin serum concentrations less than 2 mcg/mL was 3.5 (IQR, 3.3-4.8) mg/kg versus 4.8 (IQR, 4.3-5.2) mg/kg in those that had serum concentrations of 2 mcg/mL or greater (p = 0.025). All newborn gentamicin serum concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n = 8). There were no significant differences in nephrotoxicity or ototoxicity., Conclusions: Peripartum once daily dosing of gentamicin administered between 1 to 12 hours of birth may lead to clinically significant serum concentrations in newborns., Competing Interests: Disclosures. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org.)

Background: PI3K/mTOR inhibition leads to apoptosis of NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC) cells. We tested the efficacy of the PI3K/mTOR inhibitor bimiralisib in patients with NOTCH1-mutant HNSCC., Methods: Patients with recurrent/metastatic NOTCH1-mutant HNSCC who had progressed during chemotherapy and immunotherapy received bimiralisib until unacceptable toxicity or progression. To assess whether NOTCH1 mutations can be detected in blood, we measured circulating tumor DNA (ctDNA). To assess activated NOTCH1 protein levels, we quantitated cleaved NOTCH1 (cl-NOTCH) by immunohistochemistry., Results: Eight patients were treated, and 6 were evaluable for response. The objective response rate was 17%. For all 8 patients, median progression-free and overall survival was 5 and 7 months, respectively. Bimiralisib was well tolerated, with expected hyperglycemia. Pharmacokinetic values were consistent with published studies. NOTCH1 mutations were detected in 83.3% of ctDNA. Staining for tumor cl-NOTCH1 was negative. The trial closed early due to sponsor insolvency., Conclusion: Although the trial was small, outcomes with bimiralisib were better than the historical standard of care; Results will need to be confirmed in a larger trial. The lack of cl-NOTCH1 was consistent with loss-of-function mutations and validated our mutation function algorithm. The ability to detect NOTCH1 mutations in blood will help future studies. (ClinicalTrials.gov Identifier: NCT03740100)., (© The Author(s) 2022. Published by Oxford University Press.)

Liquid crystals are considered to be the fourth state of matter with an intermediate order and fluidity in comparison to solids and liquids. Calixarenes are among one of the most versatile families of building blocks for supramolecular chemistry due to their unique vaselike structure that can be chemically engineered to have different shapes and sizes. During the last few decades, calixarenes have drawn much attention in the field of supramolecular chemistry due to their diverse applications in the fields of ion and molecular recognition, ion-selective electrodes for catalysis, drug delivery, gelation, organic electronics and sensors, etc. Imbuing liquid crystallinity to the calixarene framework leads to functionalized calixarene derivatives with fluidity and order. Columnar self-assembly of such derivatives in particular enhance the charge migration along the column due to the 1D stacking due to the enhanced π-π overlap. Considering limited reports and reviews on this new class of calixarene based liquid crystals, a comprehensive account of the synthesis of calixarene liquid crystals along with their mesomorphic behavior and potential applications are presented in this review., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Tumor suppressor mutations in head and neck squamous cell carcinoma (HNSCC) dominate the genomic landscape, hindering the development of effective targeted therapies. Truncating and missense mutations in NOTCH1 are frequent in HNSCC, and inhibition of PI3K can selectively target NOTCH1 mutant (NOTCH1MUT) HNSCC cells. In this study, we identify several proteins that are differentially regulated in HNSCC cells after PI3K inhibition based on NOTCH1MUT status. Expression of Aurora kinase B (Aurora B), AKT, and PDK1 following PI3K inhibition was significantly lower in NOTCH1MUT cell lines than in wild-type NOTCH1 (NOTCH1WT) cells or NOTCH1MUT cells with acquired resistance to PI3K inhibition. Combined inhibition of PI3K and Aurora B was synergistic, enhancing apoptosis in vitro and leading to durable tumor regression in vivo. Overexpression of Aurora B in NOTCH1MUT HNSCC cells led to resistance to PI3K inhibition, while Aurora B knockdown increased sensitivity of NOTCH1WT cells. In addition, overexpression of Aurora B in NOTCH1MUT HNSCC cells increased total protein levels of AKT and PDK1. AKT depletion in NOTCH1WT cells and overexpression in NOTCH1MUT cells similarly altered sensitivity to PI3K inhibition, and manipulation of AKT levels affected PDK1 but not Aurora B levels. These data define a novel pathway in which Aurora B upregulates AKT that subsequently increases PDK1 selectively in NOTCH1MUT cells to mediate HNSCC survival in response to PI3K inhibition. These findings may lead to an effective therapeutic approach for HNSCC with NOTCH1MUT while sparing normal cells., Significance: Aurora B signaling facilitates resistance to PI3K inhibition in head and neck squamous cell carcinoma, suggesting that combined inhibition of PI3K and Aurora kinase is a rational therapeutic strategy to overcome resistance., (©2022 American Association for Cancer Research.)

The coronavirus disease 2019 (COVID-19) pandemic has caused a paradigm shift in the cancer care landscape, shifting from a palliative care approach to a need-based approach. In these current and upcoming future times, patient- and community-centred research becomes the cornerstone of collaborative assessment efforts for understanding and assessing Targeted Palliative Care (TPC) Accessibility Models for patients with oncological malignancies in resource-limited settings. This short communication focuses on the models available for TPC for the continuation of care in oncological settings in resource-limited geographic areas. Some programmes have used a Mixed Method Approach, highlighting their importance based on engagement volunteers and building trust and relationships in the community. Other studies have addressed the care system using a Rural Palliative Supportive Service Model for older adults living with life-limiting chronic illness, showing that home-based treatment for this population is feasible. Moreover, the Home Palliative Care Units (HPCU) model showed promising results in that patients cared for by HPCU had a fewer emergency visits and hospital admissions, in addition to being more likely to die at home with adequate palliation. During the ongoing pandemic, patients have experienced rapid clinical decline, requiring urgent conversations about their care wishes. They have been forced to make decisions on so-called 'Life and death' issues. In this article we discuss the advantages, disadvantages, and possible changes implemented in the context of cancer surgical care in resource-limited settings, in order to create a better assessment of geographic or demographic-based, patient- and community-centred TPC accessibility models for a more holistic development of cancer care programs., (© 2022 John Wiley & Sons Ltd.)

Background: Ongoing need of alternative strategies for SARS-CoV-2 detection is undeniable. Self-collected samples without viral transport media (VTM), coupled with simple nucleic acid extraction methods for SARS-CoV-2 PCR are beneficial., Objectives: To evaluate results of SARS-CoV-2 PCR using simple nucleic acid extraction methods from self -collected saliva and oral swabs without VTM., Methods: A cross-sectional single-centre study was conducted on 125 participants (101 SARS-CoV-2 positive cases and 24 controls). PCR was performed following five simple nucleic acid extraction methods on self -collect saliva and oral swabs without VTM and results were compared with gold standard PCR. For saliva, kit-based extraction (SKE), Proteinase K and Heat extraction (SPHE), only Heat extraction (SHE) methods and for dry oral swabs, Proteinase K and Heat extraction (DPHE) and only Heat extraction (DHE) was performed., Results: SARS-CoV-2 was detected in self-collected saliva and oral swabs. 93.07% were correctly classified as positive by SKE, 69.31% by SHE, 67.33% by SPHE, 67.33% by DPHE and 55.45% by DHE. Discriminant power of SKE was significantly higher than other methods (p-value < 0.001) with good- fair agreement of alternate extraction methods against gold standard., Conclusion: Combination of self-collected saliva/ oral-swab without VTM and alternative RNA extraction methods offer a simplified, economical substitute strategy for SARS-CoV-2 detection., Competing Interests: 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., (© 2022 The Author(s).)

Purpose: Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers., Experimental Design: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression., Results: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein expression correlates with Aurora inhibition-induced apoptosis. Manipulating Rb directly, or by inducing E7 expression, altered cells' sensitivity to Aurora kinase inhibitors. Rb affects expression of the mitotic checkpoint genes MAD2L1 and BUB1B, which we found to be highly expressed in HPV-positive patient tumors. Knockdown of MAD2L1 or BUB1B reduced Aurora kinase inhibition-induced apoptosis, whereas depletion of the MAD2L1 regulator TRIP13 enhanced it. TRIP13 is a potentially druggable AAA-ATPase. Combining Aurora kinase inhibition with TRIP13 depletion led to extensive apoptosis in HPV-positive cancer cells but not in HPV-negative cancer cells., Conclusions: Our data support a model in which HPV-positive cancer cells maintain a balance of MAD2L1 and TRIP13 to allow mitotic exit and survival in the absence of Rb. Because it does not affect cells with intact Rb function, this novel combination may have a wide therapeutic window, enabling the effective treatment of Rb-deficient cancers., (©2022 American Association for Cancer Research.)

Intrahepatic cholestasis of pregnancy is one of the most common liver diseases during the second and third trimesters of pregnancy, but its pathogenesis remains unclear. Intrahepatic cholestasis of pregnancy is associated with elevations of maternal bile acids, serum aminotransferases, and adverse fetal outcomes. Besides direct cytotoxic liver injury by bile acids, it has been suggested that bile acid-induced oxidative stress and mitochondrial injury lead to a cascade of inflammatory responses. Here, we demonstrate that the extended elevation of serum aminotransferases after normalization of bile acid levels coincides with an extended increase of the chemokine CXCL10 and inflammatory cytokines., (© 2022 Published by Elsevier Inc. on behalf of the AGA Institute.)

A reliable and robust bioanalytical method was developed to quantify neratinib, a tyrosine kinase inhibitor in human plasma, using UPLC-MS/MS. The extraction of neratinib and its deuterated internal standard, neratinib-d6, was successfully performed on hybrid solid-phase extraction ultra-cartridges to remove the interference of phospholipids and proteins. Chromatographic analysis was performed on a UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column using 0.1% formic acid and acetonitrile under gradient conditions. The total analysis time was 1.5 min. Neratinib was quantified using electrospray ionization source operated in the positive-ion multiple reaction monitoring mode. The mass transitions of neratinib and neratinib-d6 were m/z 557.3/112.1 and m/z 563.1/118.2, respectively. The linear concentration range for neratinib was 0.5-500 ng/mL, which adequately covers concentration levels expected in real subject samples. The assay was extensively validated for various validation parameters following standard guidelines for a bioanalytical assay. The intra- and inter-batch precision was ≤4.6%, and neratinib was found to be stable under various stability conditions. The mean internal standard-normalized matrix factor and recovery were 0.997 and 95.4%, respectively. The validated method was successfully applied to a pharmacokinetic study in healthy subjects with different doses., (© 2022 John Wiley & Sons Ltd.)

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancers worldwide. More than half of patients with HNSCC eventually experience disease recurrence and/or metastasis, which can threaten their long-term survival. HNSCCs located in the oral cavity and larynx are usually associated with tobacco and/or alcohol use, whereas human papillomavirus (HPV) infection, particularly HPV16 infection, is increasingly recognized as a cause of oropharyngeal HNSCC. Despite clinical, histologic, and molecular differences between HPV-positive and HPV-negative HNSCCs, current treatment approaches are the same. For recurrent disease, these strategies include chemotherapy, immunotherapy with PD-1-inhibitors, or a monoclonal antibody, cetuximab, that targets epidermal growth factor; these therapies can be administered either as single agents or in combination. However, these treatment strategies carry a high risk of toxic side effects; therefore, more effective and less toxic treatments are needed. The landscape of HNSCC therapy is changing significantly; numerous clinical trials are underway to test novel therapeutic options like adaptive cellular therapy, antibody-drug conjugates, new targeted therapy agents, novel immunotherapy combinations, and therapeutic vaccines. This review helps in understanding the various developments in HNSCC therapy and sheds light on the path ahead in terms of further research in this field.

Recently, the World Health Organization (WHO) approved RTS, S/AS01 (RTS, S) as the world's first malaria vaccine for partial malaria protection in young children at risk. While this immunization drive begins during the unprecedented pandemic of the SARS-CoV-2 Virus, the WHO has also approved 7 Vaccines in 2021 for the vaccination of children at risk. This article explores the quandary that would occur to the officials in charge of carrying out large vaccination campaigns against these two deadly infectious illnesses in several regions including the continent of Africa. The article also outlines the priorities for resolving this dilemma, offers evidence-based solutions, and provides a summary of recent significant events and their consequences. While providing the latest data, a discussion on the causation of the dilemma with clear recommendations for possible solutions has been explored as well., Competing Interests: NA., (© 2022 The Authors.)

Hertia intermedia is a traditional medicinal plant of Balochistan, used for pain management and stomach problems. Current research work was intended to evaluate the anti-inflammatory and analgesic activities of crude ethanolic extract of H. intermedia. Anti-inflammatory activity was determined by the carrageenan-induced and histamine-induce Rat paw edema in rats, analgesic activity was determined by acetic acid-Induced writhing test, formalin-induced hind paw licking in mice and Tail immersion test. H. intermedia crude ethanolic extract showed significant (p<0.05) effect in both carrageenan and histamine-induced rat paw edema at both 250 and 500 mg/kg oral doses. There were significant analgesic activities in comparison with standard drug and control (p<0.05). It is concluded that H. intermedia crude ethanolic extract possesses significant anti-inflammatory and analgesic effects. However further studies may be carried out to isolate the phytochemicals responsible for anti-inflammatory and analgesic activities.

Meloxicam (MEL) is an oxicam derivative with low water solubility that is useful in the treatment of colorectal cancer (CRC) as a COX-2 inhibitor. MEL-loaded HPMC micro particles were fabricated using an oil-in-oil (o/o) emulsion solvent evaporation (ESE) method. FTIR, XRD, particle size analysis, DSC, SEM and in vitro dissolution investigation were utilized to evaluate the produced micro particles physiochemically. Finally, rabbits were used as animal models in an in vivo pharmacokinetic study to assess the MEL concentration in the plasma of rabbits. Pure MEL, F1 and F2 were given to rabbits by a single dose for in vivo pharmacokinetic investigations. The XRD and DSC results confirmed the transformation of MEL from its crystalline nature to the amorphous state in micro particles. The formulations F1 and F2 particle sizes were determined 92.43μm and 163.26μm, respectively. The prepared micro particles had a smooth, non-porous and spherical surface. In comparison to the pure drug (22.4%), the F1 and F2 cumulative drug release (%) was 86.19% and 79.57%, respectively. Pure MEL, F1 and F2 have estimated C max values of 7.21, 25.41 and 22.38μg/mL, respectively. MEL had a half-life of 19.98 hours, which rose to 22.19 hours and 24.75 hours for F1 and F2, respectively. MEL, F1 and F2 had AUC0-α values of 116.034, 445.95 and 462.72μg/mL*h, respectively. Considering these aspects, MEL-loaded HPMC micro particles may have the potential to better the delivery and control the release of drug that is not easily dissolved in water which could lead to improved therapeutic efficacy and limited side effects.