Challenges of breastfeeding during COVID-19 and baby friendly protocols adopted at a maternity health center in the northern Emirates of UAE: a comprehensive review.

BACKGROUND: The outbreak of Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) has caused worldwide panic in the global population taking people's lives, creating fear, and affecting mother-child relationships. Many questions were raised on the dangers of being infected with COVID-19 for newborns and safety concerns during feeding by COVID-19-positive mothers. Moreover, questions and doubts about the safety of the administration of vaccinations for nursing mothers are still open. This review attempts to fill the existing literature gap by exploring concepts concerning COVID-19 and breastfeeding mothers, the safety of vaccinations, the beneficial effects of breastfeeding on both mother and child, important hygiene recommendations for SARS-CoV-2 infected mothers, and possible solutions to optimize breastfeeding and safety precautions amidst the fear of emergence of novel variants. METHODS: All relevant publications from Google Scholar, PubMed, Web of Science, and Scopus search engines from December 2019 to October 2022 related to SARS-CoV-2, breastfeeding, COVID-19, lactating guidelines, and vaccination were included using 'Breastfeeding AND vaccine AND SARS-CoV-2' as MESH TERMS. Apart from the literature review, existing maternity protocols followed in Northern UAE were gathered from lactation consultants practicing in the UAE. RESULTS: Out of 19,391 records generated, only 24 studies were analyzed and summarized in this exhaustive review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart. Previous studies suggest that breastmilk is predominantly the primary source of nutrition for neonates. Breast milk is a rich source of antibodies that help the baby to fight against infections including other benefits. Hygiene recommendations for suspected or confirmed COVID-19-infected mothers are required along with psychological and emotional support. CONCLUSIONS: The administration of vaccinations should be advised and encouraged to protect the mothers with antibodies and the neonates by the passive transmission of antibodies through breast milk. This is a significant reason for not stopping breastfeeding even in case of COVID-19 infection. With adherence to proper hygiene methods, breastfeeding is recommended to be continued as the benefits greatly outweigh the risks.

Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis.

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.

Eco-Friendly CuO/Fe3O4 Nanocomposite synthesis, characterization, and cytotoxicity study.

The current study report a convenient, simple, and low cost approach for the biogenic synthesis of CuO/Fe3O4 nanocomposites (NCs) from pumpkin seeds extract and their vitro cytotoxicity. The characterization of finally obtained CuO/Fe3O4 nanocomposites (NCs) performed using UV-Visible, FT-IR, XRD, XPS, GC-MS, SEM-EDX and TEM analysis. The formation and elemental analysis were determined using the energy-dispersive X-ray (EDX) microanalysis technique. The formation of rod-like monoclinic and spherical, having size range 5 nm-20 nm confirmed by scanning electron microscope (SEM) and transmission electron microscopy (TEM) respectively. Finally, the MTT assay of the synthesized composites was evaluated for toxicity against cancerous cell lines HCT-116 (Colon cancer cell) and A549 (human lung adenocarcinoma cell). The synthesized composite material showed moderate (IC50 = 199 µg/mL) to low (IC50 = 445 µg/mL) activity against HCT-116 and A549 cell lines, respectively.

CAR-T cell therapy: a game-changer in cancer treatment and beyond.

In recent years, cancer has become one of the primary causes of mortality, approximately 10 million deaths worldwide each year. The most advanced, chimeric antigen receptor (CAR) T cell immunotherapy has turned out as a promising treatment for cancer. CAR-T cell therapy involves the genetic modification of T cells obtained from the patient's blood, and infusion back to the patients. CAR-T cell immunotherapy has led to a significant improvement in the remission rates of hematological cancers. CAR-T cell therapy presently limited to hematological cancers, there are ongoing efforts to develop additional CAR constructs such as bispecific CAR, tandem CAR, inhibitory CAR, combined antigens, CRISPR gene-editing, and nanoparticle delivery. With these advancements, CAR-T cell therapy holds promise concerning potential to improve upon traditional cancer treatments such as chemotherapy and radiation while reducing associated toxicities. This review covers recent advances and advantages of CAR-T cell immunotherapy.

Evaluation of the cytotoxicity, antioxidant activity, and molecular docking of biogenic zinc oxide nanoparticles derived from pumpkin seeds.

This study aimed to investigate the characterization of zinc oxide nanoparticles (ZnONPs) produced from Cucurbita pepo L. (pumpkin seeds) and their selective cytotoxic effectiveness on human colon cancer cells (HCT 116) and African Green Monkey Kidney, Vero cells. The study also investigated the antioxidant activity of ZnONPs. The study also examined ZnONPs' antioxidant properties. This was motivated by the limited research on the comparative cytotoxic effects of ZnO NPs on normal and HCT116 cells. The ZnO NPs were characterized using Fourier-transform infrared spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Transmission Electron Microscope/Selected Area Electron Diffraction (TEM/SAED), and Scanning Electron Microscope-Energy Dispersive X-ray (SEM-EDX) for determination of chemical fingerprinting, heat stability, size, and morphology of the elements, respectively. Based on the results, ZnO NPs from pumpkins were found to be less than 5 µm and agglomerates in nature. Furthermore, the ZnO NPs fingerprinting and SEM-EDX element analysis were similar to previous literature, suggesting the sample was proven as ZnO NPs. The ZnO NPs also stable at a temperature of 380°C indicating that the green material is quite robust at 60-400°C. The cell viability of Vero cells and HCT 116 cell line were measured at two different time points (24 and 48 h) to assess the cytotoxicity effects of ZnO NP on these cells using AlamarBlue assay. Cytotoxic results have shown that ZnO NPs did not inhibit Vero cells but were slightly toxic to cancer cells, with a dose-response curve IC50 = ~409.7 µg/mL. This green synthesis of ZnO NPs was found to be non-toxic to normal cells but has a slight cytotoxicity effect on HCT 116 cells. A theoretical study used molecular docking to investigate nanoparticle interaction with cyclin-dependent kinase 2 (CDK2), exploring its mechanism in inhibiting CDK2's role in cancer. Further study should be carried out to determine suitable concentrations for cytotoxicity studies. Additionally, DPPH has a significant antioxidant capacity, with an IC50 of 142.857 µg/mL. RESEARCH HIGHLIGHTS: Pumpkin seed extracts facilitated a rapid, high-yielding, and environmentally friendly synthesis of ZnO nanoparticles. Spectrophotometric analysis was used to investigate the optical properties, scalability, size, shape, dispersity, and stability of ZnO NPs. The cytotoxicity of ZnO NPs on Vero and HCT 116 cells was assessed, showing no inhibition of Vero cells and cytotoxicity of cancer cells. The DPPH assay was also used to investigate the antioxidant potential of biogenic nanoparticles. A molecular docking study was performed to investigate the interaction of ZnO NPs with CDK2 and to explore the mechanism by which they inhibit CDK2's role in cancer.

Haematopoietic Stem Cell Transplant Trends in Pakistan: Activity Survey from Pakistan Bone Marrow Transplant Group.

Pakistan is the fifth most populous country with a population of 225 million and has health expenditure accounting for only 2.8 percent of gross domestic product (GDP). Accordingly, there are a limited number of haematology-oncology and transplant centers in the country. The Pakistan Blood and Marrow Transplant (PBMT) group was established in 2020, and this report is the first activity survey from January 2021 to December 2022 focusing on the trends of matched-related donor, haploidentical, and autologous transplants in a developing country. A total of 12 transplant centers contributed data on the modified PBMT survey form retrospectively and 806 haematopoietic stem cell transplants (HSCTs) were carried out during the study duration. Allogeneic HSCT constituted 595 (73.8%) of all the transplants; this is in stark contrast to Western data, where autologous HSCT accounts for the majority of transplants. ß-thalassemia major and aplastic anemia were the commonest indications for allogeneic HSCT, in contrast to Western data, where acute leukemia is the leading transplant indication. Autologous transplants were more frequently performed for Hodgkin's lymphoma as compared to non-Hodgkin's lymphoma and multiple myeloma. The use of peripheral and bone marrow stem cells was comparable. A myeloablative conditioning regimen was routinely used in patients with acute leukemia. This report provides an insight of HSCT trends in Pakistan which are different from those of Western centers contributing to transplant data from South Asia.

Screening of Cu4 O3 NPs efficacy and its anticancer potential against cervical cancer.

Cu4 O3 is the least explored copper oxide, and its nanoformulation is anticipated to have important therapeutic potential especially against cancer. The current study aimed to biosynthesize Cu4 O3 nanoparticles (NPs) using an aqueous extract of pumpkin seeds and evaluate its antiproliferative efficacy against cervical cells after screening on different cancer cell lines. The obtained NPs were characterized by different spectroscopic analyses, such as UV-vis, thermogravimetric, energy dispersive X-ray, and Fourier-transform infrared spectroscopy (FTIR). In addition, high-resolution transmission electron microscopes (HR-TEM) were used to observe the morphology of the biosynthesized NPs. The UV-vis spectra showed a peak at around 332 nm, confirming the formation of Cu4 O3 NPs. Moreover, FTIR and TAG analyses identified the presence of various bioactive phytoconstituents that might have worked as capping and stabilization agents and comparative stable NPs at very high temperatures, respectively. The HR-TEM data showed the spherical shape of Cu4 O3 NPs in the range of 100 nm. The Cu4 O3 NPs was screened on three different cancer cell lines viz., Hela, MDA-MB-231, and HCT-116 using cytotoxicity (MTT) reduction assay. In addition, Vero was taken as a normal epithelial (control) cell. The high responsive cell line in terms of least IC50 was further assessed for its anticancer potential using a battery of biological tests, including morphological alterations, induction of apoptosis/ROS generation, regulation of mitochondrial membrane potential (MMP), and suppression of cell adhesion/migration. Vero cells (control) showed a slight decline in % cell viability even at the highest tested Cu4 O3 NPs concentration. However, all the studied cancer cells viz., MDA-MB-231, HCT 116, and HeLa cells showed a dose-dependent decline in cell viability after the treatment with Cu4 O3 NPs with a calculated IC50 value of 10, 11, and 7.2 µg/mL, respectively. Based on the above data, Hela cells were chosen for further studies, that showed induction of apoptosis from 3.5 to 9-folds by three different staining techniques acridine orange/ethidium bromide (AO/EB), 4',6-diamidino-2-phenylindole (DAPI), and propidium iodide (PI). The enhanced production of reactive oxygen species (>3.5-fold), modulation in MMP, and suppression of cell adhesion/migration were observed in the cells treated with Cu4 O3 NPs. The current study obtained the significant antiproliferative potential of Cu4 O3 NPs against the cervical cancer cell line, which needs to be confirmed further in a suitable in vivo model. Based on our results, we also recommend the green-based, eco-friendly, and cost-effective alternative method for synthesizing novel nanoformulation.

Circulating and non-circulating proteins and nucleic acids as biomarkers and therapeutic molecules in ovarian cancer.

Ovarian cancer is the second most fatal gynecological cancer. For the last decade or so significant use of non-circulating and circulating biomarkers has been highlighted. However, the study of such biomarkers at nanovesicle technology such as exosomes, proteomic and genomics studies could further contribute to better identification of anomalous protein and networks which could act as potential targets for biomarker and immunotherapy development. This review provides an overview of the circulating and non-circulating biomarkers with the aim of addressing the current challenges and potential biomarkers that could lead to early ovarian cancer diagnosis and better management. By means of this review we also lay a hypothesis that characterization of exosomal protein, nucleic acid content from body fluids (serum, plasma, urine, etc.) can decode the secret of disease and potentially improve diagnostic sensitivity which could further lead to more effective screening and early detection of the disease.

In silico study to predict promiscuous peptides for immunodiagnosis of cystic echinococcosis.

Background: Cystic echinococcosis (CE), caused by Echinococcus granulosus, is a major zoonotic disease that causes significant human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat, and control. So far, crude extracts of hydatid cyst fluid containing antigen B or antigen 5 have been used as the primary antigenic source for its immunodiagnosis. The main issue is that it reacts with sera from people infected with other helminths. There is currently no standard, specific, or sensitive test for disease diagnosis, and no human vaccine has been reported. Aims and Objectives: Considering the need for efficient immunization and/or immunodiagnosis, six E. granulosus antigens, antigen 5, antigen B, heat shock proteins such as Hsp-8 and Hsp-90, phosphoenolpyruvate carboxykinase, and tetraspanin-1, were chosen. Materials and Methods: Using various in silico tools, T cell and B cell epitopes (promiscuous peptides) were predicted by targeting antigen 5, antigen B, heat shock proteins such as Hsp-8 and Hsp-90, phosphoenolpyruvate carboxykinase, and tetraspanin-1. Results: There are twelve promiscuous peptides with overlapping human leukocyte antigen (HLA) class-I, class-II, and conformational B cell epitopes. Such immunodominant peptides could be useful as subunit vaccines. Furthermore, six peptides specific for E. granulosus were also discovered, which may prove to be important markers in the diagnosis of CE, potentially preventing misdiagnosis and mismanagement. Conclusion: These epitopes may be the most important vaccine targets in E. granulosus because they have the most promiscuous peptides and B cell epitopes, as well as the highest affinity for different alleles, as determined by docking scores. However, additional research using in vitro and in vivo models is undertaken.

Increased health risk assessment in different vegetables grown under untreated sewerage irrigation regime due to higher heavy metals accumulation.

Heavy metals are environmental pollutants and carcinogenic for human health if ingested. In developing countries, including Pakistan, untreated sewerage water is one of the major sources of irrigation for vegetable production in the vicinities of urban areas which might be toxic to human health due to heavy metals contamination. The present study was conducted to investigate the uptake of heavy metals by sewage water application and its impact on human health. The experiment consisted of five vegetable crops (Raphanus sativus L, Daucus carota, Brassica rapa, Spinacia oleracea, and Trigonella foenum-graecum L.) and two irrigation sources (clean water irrigation and sewage water irrigation). Each treatment was three time replicated for all five vegetables, and standard agronomic practices were applied. The results demonstrated that shoot and root growth in radish, carrot, turnip, spinach, and fenugreek was enhanced significantly with sewerage water, probably due to enhanced organic matter. However, pithiness was observed in the root of radish under sewerage water treatment. Very high concentrations of Cd, up to 7.08 ppm in turnip roots while up to 5.10 ppm in fenugreek shoot, were observed, and other vegetables also contained higher concentrations of Cd. Zn concentrations in the edible parts of carrot (control (C) = 129.17 ppm, sewerage (S) = 164.10 ppm), radish (C = 173.73 ppm, S = 253.03), turnip (C = 109.77 ppm, S = 149.67 ppm), and fenugreek (C = 131.87 ppm, S = 186.36 ppm) were increased by sewerage water treatment but a decrease in Zn concentration in spinach (C = 262.17 ppm, S = 226.97 ppm) was observed. Fe concentration in edible parts of carrot (C = 888.00 ppm, S = 524.80 ppm), radish (C = 139.69 ppm, S = 123.60 ppm), turnip (C = 195.00 ppm, S = 121.37 ppm), and fenugreek (C = 1054.93 ppm, S = 461.77 ppm) were also decreased by sewerage water treatment while spinach leaves had accumulated higher Fe (C = 1560.33 ppm, S = 1682.67 ppm) in sewerage water treatment. The highest bioaccumulation factor value was 4.17 for Cd in carrots irrigated with sewerage water. The maximum value of bioconcentration factor was 3.11 for Cd in turnip under control, and the highest value of translocation factor was 4.82 in fenugreek irrigated with sewerage water. Daily intake of metals and health risk index (HRI) calculation indicated that HRI for Cd was more than 1, suggesting toxicity in these vegetables while HRI for Fe and Zn is still under safe limit. Correlation analysis among different traits of all vegetables under both treatments revealed valuable information for selecting traits in the next crop breeding programs. It is concluded that untreated sewerage-irrigated vegetables, highly contaminated with Cd, are potentially toxic for human consumption and should be banned in Pakistan. Furthermore, it is suggested that the sewerage water should be treated to eliminate toxic compounds, particularly Cd, before irrigation usage and non-edible/phytoremediation crops might be grown in contaminated soils.

Angiotensin-Converting Enzyme and Hypertension: A Systemic Analysis of Various ACE Inhibitors, Their Side Effects, and Bioactive Peptides as a Putative Therapy for Hypertension.

Hypertension is a major risk factor for heart attack, produce atherosclerosis (hardening of the arteries), congestive heart failure, stroke, kidney infection, blindness, end-stage renal infection, and cardiovascular diseases. Many mechanisms are involved in causing hypertension, i.e., via calcium channels, alpha and beta receptors, and the renin-angiotensin system (RAS). RAS has an important role in blood pressure control and is also involved in the metabolism of glucose, homeostasis, and balance of electrolytes in the body. The components of RAS that are involved in the regulation of blood pressure are angiotensinogen, Ang I (angiotensin I), Ang II (angiotensin II), ACE (angiotensin-converting enzyme), and ACE 2 (angiotensin-converting enzyme 2). These components provide for relevant therapeutic targets for the treatment of hypertension, and various drugs are commercially available that target individual components of RAS. Angiotensin receptor blockers (ARBs) and ACE inhibitors are the most popular among these drugs. ACE is chosen in this review as it makes an important target for blood pressure control because it converts Ang I into Ang II and also acts on the vasodilator, bradykinin, to degrade it into inactive peptides. This review highlights various aspects of blood pressure regulation in the body with a focus on ACE, drugs targeting the components involved in regulation, their associated side effects, and a need to shift to alternative therapy for putative hypertension treatment in the form of bioactive peptides from food.

Species composition, seasonal abundance and population dynamics of predatory spiders from cotton field plots of irrigated and semi-arid regions of Punjab, Pakistan.

The purpose of the current study was to document the variety of predatory spider species present in the cotton fields of two major cotton-producing districts in Punjab, Pakistan, as well as the population dynamics of those spiders. The research was carried out between May and October 2018 and 2019. Manual picking, visual counting, pitfall traps, and sweep netting were the procedures used to collect samples on a biweekly basis. A total of 10,684 spiders comprising 39 species, 28 genera, and 12 families were documented. Araneidae and Lycosidae families contributed a major share to the overall catch of spiders, accounting for 58.55 percent of the total. The Araneidae family's Neoscona theisi ) was the most dominating species, accounting for 12.80% of the total catch and being the dominant species. The estimated spider species diversity was 95%. Their densities were changed over time in the study, but they were highest in the second half of September and the first half of October of both years. The cluster analysis distinguished the two districts and the sites chosen. There was a relationship between humidity and rainfall and the active density of spiders; however, this association was not statistically significant. It is possible to increase the population of spiders in an area by reducing the number of activities detrimental to spiders and other useful arachnids. Spiders are considered effective agents of biological control throughout the world. The findings of the current study will help in the formulation of pest management techniques that can be implemented in cotton growing regions all over the world.

The learning curves of major laparoscopic and robotic procedures in urology: a systematic review.

BACKGROUND: Urology has been at the forefront of adopting laparoscopic and robot-assisted techniques to improve patient outcomes. This systematic review aimed to examine the literature relating to the learning curves of major urological robotic and laparoscopic procedures. METHODS: In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic literature search strategy was employed across PubMed, EMBASE, and the Cochrane Library from inception to December 2021, alongside a search of the grey literature. Two independent reviewers completed the article screening and data extraction stages using the Newcastle-Ottawa Scale as a quality assessment tool. The review was reported in accordance with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) guidelines. RESULTS: Of 3702 records identified, 97 eligible studies were included for narrative synthesis. Learning curves are mapped using an array of measurements including operative time (OT), estimated blood loss, complication rates as well as procedure-specific outcomes, with OT being the most commonly used metric by eligible studies. The learning curve for OT was identified as 10-250 cases for robot-assisted laparoscopic prostatectomy and 40-250 for laparoscopic radical prostatectomy. The robot-assisted partial nephrectomy learning curve for warm ischaemia time is 4-150 cases. No high-quality studies evaluating the learning curve for laparoscopic radical cystectomy and for robotic and laparoscopic retroperitoneal lymph node dissection were identified. CONCLUSION: There was considerable variation in the definitions of outcome measures and performance thresholds, with poor reporting of potential confounders. Future studies should use multiple surgeons and large sample sizes of cases to identify the currently undefined learning curves for robotic and laparoscopic urological procedures.

Biogenic Synthesis of Cu-Mn Bimetallic Nanoparticles Using Pumpkin Seeds Extract and Their Characterization and Anticancer Efficacy.

BACKGROUND: Cancer is a chronic, heterogeneous illness that progresses through a spectrum of devastating clinical manifestations and remains the 2nd leading contributor to global mortality. Current cancer therapeutics display various drawbacks that result in inefficient management. The present study is intended to evaluate the anticancer potential of Cu-Mn bimetallic NPs (CMBNPs) synthesized from pumpkin seed extract against colon adenocarcinoma cancer cell line (HT-29). METHODS: The CMBNPs were biosynthesized by continuously stirring an aqueous solution of pumpkin seed extract with CuSO4 and manganese (II) acetate tetrahydrate until a dark green solution was obtained. The characteristic features of biogenic CMBNPs were assessed by UV-visible spectrophotometry (UV-vis), X-ray powder diffraction (XRD), energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). A battery of biological assays, viz. neutral red uptake (NRU) assay, in vitro scratch assay, and comet assay, were performed for anticancer efficacy evaluation. RESULTS: The formation of spherical monodispersed bimetallic nanoparticles with an average size of 50 nm was recorded using TEM. We observed dose-dependent cytotoxicity of CMBNPs in the HT-29 cell line with an IC50 dose of 115.2 µg/mL. On the other hand, CMBNPs did not show significant cytotoxicity against normal cell lines (Vero cells). Furthermore, the treatment of CMBNPs inhibited the migration of cancer cells and caused DNA damage with a significant increase in comet tail length. CONCLUSIONS: The results showed substantial anticancer efficacy of CMBNPs against the studied cancer cell line. However, it is advocated that the current work be expanded to different in vitro cancer models so that an in vivo validation could be carried out in the most appropriate cancer model.

Potential of green-synthesized ZnO NPs against human ovarian teratocarcinoma: an in vitro study.

BACKGROUND: Ovarian cancer leads to devastating outcomes, and its treatment is highly challenging. At present, there is a lack of clinical symptoms, well-known sensitivity biomarkers, and patients are diagnosed at an advanced stage. Currently, available therapeutics against ovarian cancer are inefficient, costly, and associated with severe side effects. The present study evaluated the anticancer potential of zinc oxide nanoparticles (ZnO NPs) that were successfully biosynthesized in an ecofriendly mode using pumpkin seed extracts. METHODS AND RESULTS: The anticancer potential of the biosynthesized ZnO NPs was assessed using an in vitro human ovarian teratocarcinoma cell line (PA-1) by well-known assays such as MTT assay, morphological alterations, induction of apoptosis, measurement of reactive oxygen species (ROS) production, and inhibition of cell adhesion/migration. The biogenic ZnO NPs exerted a high level of cytotoxicity against PA-1 cells. Furthermore, the ZnO NPs inhibited cellular adhesion and migration but induced ROS production and cell death through programmed cell death. CONCLUSION: The aforementioned anticancer properties highlight the therapeutic utility of ZnO NPs in ovarian cancer treatment. However, further research is recommended to envisage their mechanism of action in different cancer models and validation in a suitable in vivo system.

Optimizing the Dosing Regimen of Cetuximab and Ramucirumab Using the Model-Informed Drug Development Paradigm.

Model-informed drug development (MIDD) is a process that integrates drug exposure-based, biological, and statistical models to enhance the benefit-risk balance in drug development. The US Food and Drug Administration (FDA) MIDD Paired Meeting Pilot Program provides a platform to apply MIDD approaches to drug development and to seek regulatory feedback in a collaborative and streamlined process prior to submission for approval. Eli Lilly and Company (Lilly) participated in the Pilot Program to seek agency alignment to enhance the initial approved dosing regimens of cetuximab (Erbitux; Eli Lilly and Company, Indianapolis, IN) and ramucirumab (Cyramza; Eli Lilly and Company) without conducting additional clinical trials. Here, we describe the overall MIDD strategy at Lilly, the process with the FDA, and the impact of implementing the approach.

Immune response of S. Typhi-derived Vi polysaccharide and outer membrane protein a conjugate in mice.

Typhoid fever is a serious concern precisely in developing nations. Still investigators are exploring a better conjugate partner for Vi-polysaccharide to develop a more effective vaccine for typhoid fever. Here, we cloned and expressed S. Typhi outer membrane protein A (OmpA). The conjugation of Vi-polysaccharide with OmpA was carried out by the carbodiimide (EDAC) method employing ADH as a linker. Total Ig and IgG generated against OmpA, and Vi polysaccharide was quantified by ELISA. Vi polysaccharide alone induced very low levels of Vi polysaccharide antibody. Vi-OmpA conjugate (Vi-conjugate) elicited a robust immune response compared to Vi polysaccharide alone and showed booster response. Further, IgG was only evoked by Vi-OmpA conjugate, not with Vi polysaccharide alone. OmpA antibody induction in both the Vi-OmpA conjugate and OmpA were similar level. Taken together, we show that OmpA as a carrier protein conjugated to Vi polysaccharide is immunogenic. We predict OmpA antibodies will contribute protection along with antibodies generated by Vi-polysaccharide. Past and current literature supports that OmpA is highly conserved protein not only among Salmonellae but entire Enterobacteriacea family with 96-100% identity.

Epidermolysis Bullosa Acquisita in a patient with End Stage Renal Disease: Case study.

The clinical presentation of COVID-19 varies from being asymptomatic to developing acute respiratory distress syndrome and multi-organ dysfunction. The diffuse microvascular thrombi in multiple organs seen in the autopsy of COVID-19 patients are similar to that of thrombotic microangiopathy (TMA). TMA is characterised by thrombus formation in the microvasculature with laboratory findings of microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. A 49-year-old male presented to the Aga Khan University Hospital, Karachi. with fever, diarrhoea, altered level of consciousness, and a positive nasopharyngeal swab for SARS-CoV-2. He developed severe thrombocytopenia, MAHA with 5.8% schistocytes, and worsening renal function on the sixth day of admission. Diagnosis of thrombotic thrombocytopenic purpura (TTP) was established based on PLASMIC score, and he was successfully treated with intravenous (IV) Methylprednisolone, therapeutic plasma exchange and IV Rituximab. The case emphasises the need to keep TTP in the differential diagnosis when a patient with COVID-19 develops severe thrombocytopenia, acute renal failure, or impaired level of consciousness, since prompt diagnosis and treatment is necessary to gain favourable outcome.

In vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity of Murraya koenigii leaf extract intercedes ZnO nanoparticles.

Nanotechnology is an emerging field with tremendous potential and usage of medicinal plants and green preparation of nanoparticles (NPs) is one of the widely explored areas. These have been shown to be effective against different biological activities such as diabetes mellitus, cancer, antioxidant, antimicrobial, etc. The current studies focus on the green synthesis of zinc NPs (ZnO NPs) from aqueous leaf extract of Murraya koenigii (MK). The synthesized Murraya koeingii zinc oxide NPs (MK ZnO NPs) were characterized using UV-visible spectroscopy, dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy-dispersive spectrum (EDS) and cyclic voltammetry (CV). The synthesized MK ZnO NPs were evaluated for their in vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity. They demonstrated significant antidiabetic and cytotoxic activity, as well as moderate free-radical scavenging and antibacterial activity.

Species composition and population dynamics of some arthropod pests in cotton fields of irrigated and semi-arid regions of Punjab, Pakistan.

The present study aimed to record seasonal dynamics and diversity of different insect pests in cotton agroecosystems. Two well-known cotton growing districts i.e. district Layyah and Vehari were selected for the study from the cotton belt of Punjab, Pakistan. Sampling was done bi-weekly for two consecutive years from July to October during 2018 and 2019. Sweep netting, visual counting, hand picking, wet finger method, beat sheets, aspirator and pitfall trapping methods were used for collection. Shannon-Wiener and Simpson indices were used to compute diversity while Menhinick and Margalef indices were used for the estimation of species richness. A total of 94,343 individuals representing 43 species, 40 genera, 28 families and 6 orders were recorded. Family Aleyrodidae dominated over other pest families. Bemisia tabaci (Gennadius, 1889) of family Aleyrodidae was the dominant species with 39.68% share among all pest species. Estimated species richness of all arthropod pest species belonging to both districts were about 94%. The densities of pests fluctuated with time. The peaks of sucking pest densities were observed in July and August while densities of chewing pests peaked in late September or early October each year. Population densities of jassids Amrasca biguttula (Ishida), armyworm Spodoptera litura (Fabricius), and pink bollworm Pectinophora gossypiella (Saunders), showed strong negative correlation with temperature, humidity and rainfall while thrips population density showed positive correlation with these parameters. Minor loss due to pests are acceptable everywhere, but it is only possible when their populations remain below their economic threshold levels. Present study will aid to design pest management strategies in cotton growing areas round the globe.