NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic ß-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor ß1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1ß), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Pattern of Prescribing Analgesics and Their Response in Cancer Patients Attending Outpatient Department of Palliative Care Service in Two Teaching Hospitals of Bangladesh.

Palliative care is a valued aspect of clinical care which is an urgent humanitarian need for people worldwide with cancer and other chronic fatal diseases. Patients experience many different symptoms including severe pain in advanced cancer. Palliative care focuses on relief from symptoms, pain and stress by using different analgesics and adjuvant. The goal of palliative care is to improve the quality of life. So, this prospective observational study was carried out to assess pattern of drugs used and their response to pain in cancer patients attending out-patient department of palliative care service in two teaching hospitals of Bangladesh. One hundred forty (140) cancer patients were purposively selected who attended in out-patient department of palliative care unit in Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital (DMCH) from July 2018 to June 2019. Outcome variables were commonly presenting complaints, pain intensity, commonly prescribed drugs and analgesic prescription according to WHO three-step analgesic ladder, etc. The mean age ±SD of the respondents was 51.30±15.38 years, male-female ratio 1:1. Common sites of cancer were alimentary origin (20.0%), genitourinary system (17.86%), hepatobiliary system (11.43%), respiratory system (10.71%). The prescribed drugs were analgesics (96.4%), PPIs (74.3%), laxatives (62.1%), anti-emetics (38.6%), multivitamins (32.9%), H2 antagonists (17.1%), sedatives (17.1%), and corticosteroids (8.6%). Level 1 analgesics (Paracetamol or other NSAIDs) were prescribed to 42.65%, level 2 analgesics (Tramadol) were prescribed to 50.00% patients and level 3 analgesics (Morphine) were prescribed to 51.42% patients. The relation between and receiving three levels of analgesic prescriptions was statistically significant. The association between level of analgesic prescription was significant with site of cancer (p<0.001) and intensity of pain (p<0.001). This study showed that morphine was prescribed to more than half of the patients. Other level of analgesics were also used either single or in combination. Younger and male patients were treated more with level III analgesics. Prescribing analgesics were dependent on sites of cancer and intensity of pain.

Different Types of Management for Anastomotic Leak Post Esophagectomy.

Esophagectomy is a critical surgical procedure for managing various esophageal disorders, including malignancies, strictures, and reflux disease. Nonetheless, it is associated with significant postoperative complications, with anastomotic leak being a major concern. An anastomotic leak is defined as an unintended communication failure between the proximal esophageal segment and the conduit after surgery. This review explores evolving strategies for managing anastomotic leaks after esophagectomy, including factors contributing to leaks, such as patient-related, surgical, and perioperative factors. Diagnostic advancements, encompassing clinical evaluation, radiological imaging, and endoscopy, enable rapid and accurate detection, which is crucial for timely intervention. Management approaches have evolved beyond surgical revisions and now include conservative measures, antibiotics, and endoscopic therapies, particularly for high-risk surgical cases. Novel approaches, such as endoscopic stents, tissue sealants, and regenerative therapies, hold promise in revolutionizing treatment and outcomes. Prevention strategies, encompassing patient optimization, surgical techniques, and perioperative care, are key in minimizing leak occurrence. A multidisciplinary approach involving various specialists is essential for tailored treatments and optimized outcomes. In conclusion, anastomotic leaks post esophagectomy remain a significant challenge, and this review provides a comprehensive resource on evolving management strategies, from conservative measures to innovative techniques, assisting clinicians in decision-making for leak management.

Primary Thymic Hodgkin Lymphoma Coexisting with Thymoma and Myasthenia Gravis: A Case Report.

BACKGROUND Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the presence of myasthenia gravis with other tumors is uncommon, approximately 50% of patients with thymoma have myasthenia gravis. Thymic Hodgkin lymphoma should be considered due to the multiple reported cases of patients with myasthenia gravis and Hodgkin lymphoma. In this report, we present the case of 24-year-old woman with myasthenia gravis who was incidentally found to have coexisting thymoma with thymic Hodgkin lymphoma. CASE REPORT A 24-year-old woman with a known case of vitiligo presented with a 2-year history of diplopia and incidental anterior mediastinal mass. Following investigations, myasthenia gravis was diagnosed and managed by pyridostigmine, prednisolone, and azathioprine. Regarding the anterior mediastinal mass, thymoma was suspected based on the presence of myasthenia gravis and radiological findings. She underwent extended transsternal thymectomy. The final histopathological report of the dissected thymus disclosed Hodgkin lymphoma pathology coexisting with thymoma. After the diagnosis of Hodgkin lymphoma nodular sclerosis type IIA was confirmed, 6 cycles of chemotherapy were administered. Four years of follow-up revealed no evidence of Hodgkin lymphoma. However, her symptoms of myasthenia gravis persisted despite Hodgkin lymphoma remission. CONCLUSIONS There is an unclear association between myasthenia gravies and Hodgkin lymphoma. Prior reports revealed regression of myasthenia gravies following Hodgkin lymphoma management, which suggests that myasthenia could be a complication of Hodgkin lymphoma. However, in our case, myasthenia gravis persisted after Hodgkin lymphoma management; therefore, further studies are needed to explore this association.

Comparison of As removal efficiency and health risks from aqueous solution using as-synthesized Fe0 and Cu0: modelling, kinetics and reusability.

Batch scale removal of arsenic (As) from aqueous media was explored using nano-zero valent iron (Fe0) and copper (Cu0) particles. The synthesized particles were characterized using a Brunauer-Emmett-Teller (BET) surface area analyzer, a scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR). The BET result showed that the surface area (31.5 m2/g) and pore volume (0.0415 cm3/g) of synthesized Fe0 were higher than the surface area (17.56 m2/g) and pore volume (0.0287 cm3/g) of Cu0. The SEM results showed that the morphology of the Fe0 and Cu0 was flowery microspheres and highly agglomerated with thin flakes. The FTIR spectra for Fe0 showed broad and intense peaks as compared to Cu0. The effects of the adsorbent dose (1-4 g/L), initial concentration of As (2 mg/L to 10 mg/L) and solution pH (2-12) were evaluated on the removal of As. Results revealed that effective removal of As was obtained at pH 4 with Fe0 (94.95%) and Cu0 (74.86%). When the dosage increased from 1 to 4 g L-1, the As removal increased from 70.59 to 93.02% with Fe0 and from 67 to 70.59% with Cu0. However, increasing the initial As concentration decreased the As removal significantly. Health risk indices, including estimated daily intake (EDI), hazard quotient (HQ), and cancer risk (CR) were employed and a significant decline (up to 99%) in risk indices was observed in As-treated water using Fe0/Cu0. Among the adsorption isotherm models, the values of R2 showed that isothermal As adsorption by Fe0 and Cu0 was well explained by the Freundlich adsorption isotherm model (R2 > 0.98) while the kinetic experimental data was well-fitted with the Pseudo second order model. The Fe0 showed excellent stability and reusability over five sorption cycles, and it was concluded that, compared to the Cu0, the Fe0 could be a promising technology for remediating As-contaminated groundwater.

ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia.

INTRODUCTION: Acute myeloid leukaemia (AML) is a heterogeneous malignant disease with a high degree of treatment failure using chemotherapy. Leukaemia stem cells (LSCs) are CD34+CD38- early progenitors associated with poor prognosis in AML. A unique LSC phenotype that excludes rare normal haematopoietic stem cells (HSC) is still elusive. This study aimed to determine expression of selected potential LSC markers in normal and leukaemic myeloid cells and correlate prognosis in AML patients. MATERIALS AND METHODS: Flow cytometry and RT-qPCR measured expressions of ALDH, IL3RA/CD123, CLEC12A/CLL-1/CD371, HOXA3 and ENPP4. Normal cord blood (n=3) and blood monocytes (n=5) represented HSC and mature cells, respectively. Myeloid leukaemia cell lines (THP-1, KG-1a, K562 and HL-60) represented progenitor cells at various stages of maturation. AML samples included chemo-resistant (n=8), early relapse (n=2) and late relapse (n=18). RESULTS: Combining protein/gene expressions, CD34+CD38- was a feature of immature cells seen in cord blood, KG-1a, and K562 but not more mature cells (blood monocytes and HL-60). Normal cells expressed CD371 while mature cells (blood monocytes and HL-60) lacked CD123. ENPP4 was not expressed on normal cells while HOXA3 was expressed only on cord blood and THP-1. In AML, CD123, HOXA3, ENPP4 (but not CD371) were significantly increased in the CD34+CD38- fraction of chemo-resistant patients while ALDH was associated with chemo-resistance. CONCLUSION: CD34+CD38- presented an immature phenotype and with ALDH were associated with poor prognosis. CD123, HOXA3 and ENPP4 further enriched the LSC population. ENPP4 has not been reported and has the advantage of not being expressed on HSC and normal monocytes.

Toll-like receptor 10 is down-regulated in serum of patients with relapsing-remitting multiple sclerosis but not associated with Epstein-Barr virus.

In this study, toll-like receptor 10 (TLR10) and Epstein-Barr virus (EBV) were determined in the peripheral blood of 43 patients with relapsing-remitting multiple sclerosis and 41 age- and gender-matched controls. Serum TLR10 levels were assessed using an enzyme-linked immunosorbent assay kit. EBV DNA and viral load were detected using a real-time polymerase chain reaction assay kit. Results revealed that median TLR10 levels were significantly lower in patients than in controls (318 vs. 574 pg/mL; p < 0.001). Most patients were classified as low producers of TLR10 (≤ median of controls) compared to controls (84.0 vs. 51.0%; p < 0.001). Logistic regression analysis revealed that participants with low TLR10 production had an odds ratio of 4.52. Receiver operating characteristic curve analysis indicated that TLR10 is a good predictor of multiple sclerosis (area under the curve = 0.778; p < 0.001). Prevalence of EBV was less frequent in patients than in controls but the difference was not significant (23.3 vs. 41.5%; p = 0.102), while median EBV load was significantly higher in patients compared to controls (8.55 vs. 1.29 DNA copy/100 cells). When TLR10 levels were stratified according to age group, gender, EBV positivity, Expanded Disability Status Scale (EDSS), or therapy, no significant differences were found in each stratum. Further, no significant correlation was found between TLR10 levels and EDSS or EBV load. In conclusions, TLR10 was down-regulated in serum of multiple sclerosis patients, and this down-regulation was not affected by age, gender, EBV load, EDSS, or therapy.

Immunological Study of IFN-γ, ICAM-4, and Vitamin D3 Markers among Gastrointestinal Tumor Patients in Babylon Province, Iraq.

OBJECTIVE: The current study was conducted to investigate the roles of ICAM-4, IFN-γ, and vitamin D3 markers among benign and malignant gastrointestinal stromal tumors (GISTs). METHODOLOGY: Eighty-eight participants, admitted to the Babylon GIT Center, Merjan Medical City, Iraq from April to December 2020, were recruited for the study. Blood samples were collected from the participants, who were divided into four groups: malignant GIT tumor (N = 42), benign GIT tumor (N = 29), irritable bowel disease as a positive control (N = 10), and healthy individuals as a negative control (N = 7). Serum ICAM-4, IFN-γ, and vitamin D3 levels were determined using the blood samples. RESULTS: The younger males were more affected by malignant GIT tumors at a mean age of 53.39 years than benign GIT tumors, IBD, and healthy individuals. There is also an increase in ICAM-4, IFN-γ, and a decrease in vitamin D3 levels compared to healthy individuals. The vitamin D3 level decreased progressively with age and rose in ICAM-4 with a decrease in vitamin D3 level in patients, increasing the probability of infection with GIT tumor. ICAM-4 levels may grow and increase as interferon levels rise. CONCLUSION: The younger males are more prone to malignant GIT and the serum levels of ICAM-4, vitamin D3, and IFN-γ are high in malignant patients compared with benign GIT tumors and lower than the control.

Synchronous Malignant Peritoneal Mesothelioma and Sigmoid Adenocarcinoma: a Challenging Clinical Entity.

Background: Malignant peritoneal mesothelioma (MPM) represents a rare clinical entity. The synchronous existence of MPM with other malignancies as colonic adenocarcinoma have been rarely reported. Its diagnosis and management are challenging given its complexity and rarity. Objective: Herein, we report a case of epithelioid subtype of MPM occurring synchronously with sigmoid colonic adenocarcinoma, along with review of the literature. Case presentation: An elderly female patient was referred as case of rectosigmoid mass. She reported history of abdominal pain, per-rectal bleeding, anorexia, and significant weight loss. Her computed-tomography scan of the abdomen revealed a fistulizing sigmoid mass and multiple enlarged lymphnodes with omental nodulation. The colonoscopy revealed a large fungating mass and the endoscopic biopsies were reported as colonic adenocarcinoma. The patient was scheduled laparoscopic low anterior resection. However, the diagnostic laparoscopy revealed several nodules disseminated all over the peritoneum, suggestive of peritoneal mesothelioma. Therefore, the decision was changed to create transverse colostomy after examination obtaining multiple biopsies from the omental and peritoneal nodules. The histopathological revealed MPM and the final diagnosis was sigmoid adenocarcinoma with synchronous MPM. The patient was started on palliative chemotherapy (capecitabine) without active management of MPM because of her general condition. She was followed up with a good clinical course. Conclusion: MPM is an overlooked entity with vague clinical presentation. Synchronous MPM with colorectal cancer is rare with only few published case reports. Its diagnosis is challenging, and its management should be tailored according to the patient. This case is the first reported case in Saudi Arabia and the Middle East.

Toxic Metal -Mediated Neurodegradation: A Focus on Glutathione and GST Gene Variants.

Increasing pieces of evidence have supported those chemicals from industrial, agricultural wastes and organoleptic activities play important role in the development of neurological disorders. The frequency of neurological disorders is increased to a much extent in recent years with the advancements in science and technology. Google Scholar, PubMed, and Scopus databases were selected to search the relevant information by using keywords including "Heavy metals", "Neurotoxicity", "Glutathione", "Glutathione AND Neurodegenerative disorders" etc. Heavy metals are particularly recognized as a major resource of toxicities during the stage of early pregnancy where a fetus gets exposed to them from maternal activities and circulation. As infants have a weak immune system and cannot respond to the specific challenge as faced by the body during mercury, zinc, iron, and cadmium exposure. Daily diet and drinking habits in addition to industrial activities also form a major field of study under investigation. This study aims to investigate the role of these metals in the accumulation of pollutants in the brain, liver, and kidneys hence leading to serious consequences. Moreover, their prevalence in teenagers that are under the age of ten years is being observed that leads them to learn, writing, and intellectual abilities. Males are more affected due to their hormonal differences. The role of the GST gene in the development of cognitive conditions and its phenotypes has been discussed thoroughly in this review. The mutations of GST lead to the accumulation of peroxides and superoxides which exacerbate oxidative damage to cells. Binding of toxic metals to GSH genes and the role of glutathione transferase genes is was demonstrated in this review.

Extended-spectrum Beta-lactamases Encoding Genes among Salmonella Enterica serovar Typhi Isolates in Patients with Typhoid Fever from four Academic Medical Centers in Lagos, Nigeria

ABSTRACT Background: There is scarce information about the occurrence of extended-spectrum β-lactamases (ESBLs) in Salmonella enterica serovar Typhi (S. Typhi) from patients with typhoid fever. Objective: To study the antimicrobial resistance and ESBL encoding genes among S. Typhi isolates in aforesaid patients from Lagos, Nigeria. Methods: S. Typhi isolates were collected from blood samples of typhoid fever patients from 4 academic medical centers in Lagos, Nigeria. The identification of isolates and their antibiotic susceptibility testing were performed by standard bacteriological techniques and disc diffusion method, respectively. The production of ESBLs was investigated using combination disk test (CDT) and polymerase chain reaction (PCR). Results: A total of 27 S. Typhi isolates was collected. All isolates were susceptible to imipenem and nitrofurantoin. Fifteen (55.6%) isolates were multidrug-resistant (MDR). The CDT test showed 11 (40.7%) ESBL producer isolates. However, the PCR revealed a higher occurrence rate for ESBL producers (66.7%, n = 18/27). The ESBL genes were as follows: blaCTX-M (37.0%, n = 10/27), blaSHV (18.5%, n = 5/27), and blaTEM (44.4%, n = 12/27). All ESBL positive S. Typhi isolates were MDR. Conclusions: This study showed the emergence of ESBL-harboring S. Typhi in patients with typhoid fever from Nigeria.

Development of zerovalent iron and titania (Fe0/TiO2) composite for oxidative degradation of dichlorophene in aqueous solution: synergistic role of peroxymonosulfate (HSO5-).

Binary composite of zerovalent iron and titanium dioxide (Fe0/TiO2) was synthesized for the catalytic removal of dichlorophene (DCP) in the presence of peroxymonosulfate (PMS). The as-prepared composite (Fe0/TiO2) exhibits synergistic effect and enhanced properties like improved catalytic activity of catalyst and greater magnetic property for facile recycling of catalyst. The results showed that without addition of PMS at reaction time of 50 min, the percent degradation of DCP by TiO2, Fe0, and Fe0/TiO2 was just 5%, 11%, and 12%, respectively. However, with the addition of 0.8 mM PMS, at 10 min of reaction time, the catalytic degradation performance of Fe0, TiO2, and Fe0/TiO2 was significantly improved to 82%, 18%, and 88%, respectively. The as-prepared catalyst was fully characterized to evaluate its structure, chemical states, and morphology. Scanning electron microscopy results showed that in composite TiO2 causes dispersion of agglomerated iron particles which enhances porosity and surface area of the composites and X-ray diffraction (XRD), energy dispersive X-ray (EDX), and Fourier-transform infrared (FTIR) results revealed successful incorporation of Fe0, and oxides of Fe and TiO2 in the composite. The adsorption-desorption analysis verifies that the surface area of Fe0/TiO2 is significantly larger than bare Fe0 and TiO2. Moreover, the surface area, particle size, and crystal size of Fe0/TiO2 was surface area = 85 m2 g-1, particle size = 0.35 µm, and crystal size = 0.16 nm as compared to TiO2 alone (surface area = 22 m2 g-1, particle size = 4.25 µm, and crystal size = 25.4 nm) and Fe0 alone (surface area = 65 m2 g-1, particle size = 0.9 µm, and crystal size = 7.87 nm). The as-synthesized material showed excellent degradation performance in synthesized wastewater as well. The degradation products and their toxicities were evaluated and the resulted degradation mechanism was proposed accordingly. The toxicity values decreased in order of DP1 > DP5 > DP2 > DP3 > DP4 and the LC50 values toward fish for 96-h duration decreased from 0.531 to 67.2. This suggests that the proposed technology is an excellent option for the treatment of antibiotic containing wastewater.

Increasing Efficacy of Covid-19 Vaccines by Lifestyle Interventions.

COVID-19 caused a serious threat to the world population as it spread worldwide rapidly. Existing medicines and vaccines could not cure and control this deadly disease. In this regard, several vaccines have been proposed and designed to control this infection's spread effectively. Along with these vaccines, the general population should adopt specific lifestyle interventions to strengthen their immune system and combat deadly viruses. We used Google Scholar and PubMed databases to find the related information using key terms such as 'COVID-19', 'COVID-19 AND Vaccine efficacy', 'Lifestyle intervention AND COVID-19', and "Lifestyle intervention AND Vaccines," etc. Only articles that discussed the interactions between lifestyle intervention and the efficacy of COVID-19 vaccines were selected for this study. Several previous clinical trials and scientific observations with influenza, polio, and other viral vaccines have demonstrated that vaccine response varies across individuals for antibody titer, independent of vaccine antigenicity. This different vaccine response observed among individuals is attributed to several factors such as dietary and nutritional habits, physical activity, stress and sleep deprivation, deficiency of micronutrients (minerals, vitamins), gut microbiota composition, immunosenescence, smoking, and drinking habits. Although there is not much information about COVID-19 vaccine efficacy and lifestyle interventions, experience with other vaccines can undoubtedly be used to suggest lifestyle interventions to improve COVID-19 vaccine efficacy. These lifestyle interventions may boost antibody responses against COVID-19 vaccines, leading to higher protection from the disease, especially among elderly and immunocompromised people. In conclusion, the present review attempts to understand the role of various nutritional and psychological factors that lead to poor vaccine response and suggests specific nutritional and psychological interventions that can enhance vaccine efficacy and improve immune response against COVID-19 vaccines.

A Review on Metabolic Paradoxes and their Impact on Metabolism.

The current review paper portrays the important link of different nutrients like trace elements, proteins, fatty acids, vitamins, and amino acids with the immune system as well as information related to metabolic paradoxes. Optimum working of the metabolic system is essential because it gives various types of supplements to the human body and aid in chemical pathways. Here related data have been retrieved from two databases i.e., PubMed and Google scholar to grasp detailed knowledge about micronutrients and nutrients as well as their association in the metabolic system. Like protein play important role in the normal development of different immune components, amino acids including alanine, Arginine, and glutamic acid properly control the movement of neutrophils, macrophages, and cytokines. While fatty acids act as an anti-inflammatory agent because they possess the ability to inhibit the expression of the MHC class. Apart from these, many essential molecules like uric acid, proteins, calcium, lanolin are also obtained as end products after catabolic and anabolic reactions, and it was found that the uric acid paradox has a cancer inhibitory role. Additionally, TGF and IL-6 paradoxes have a role in the development of tumors, the onset of diabetes, and low-grade inflammatory disorders respectively. However, the entire functioning of metabolic processes depends upon daily diet because humans get the important nutrient from the diet which further vital role in the immune system. Moreover, it was also observed that calcium paradox is related to heart disorders because high calcium accumulation leads to cardiac disorders. Thus, the complete knowledge about these essential components as well as metabolic paradoxes is very important due to their antagonistic role to plan better and improved therapeutic strategies for various diseases.

IgE blockade with omalizumab reduces pruritus related to immune checkpoint inhibitors and anti-HER2 therapies.

BACKGROUND: Immunoglobulin E (IgE) blockade with omalizumab has demonstrated clinical benefit in pruritus-associated dermatoses (e.g. atopic dermatitis, bullous pemphigoid, urticaria). In oncology, pruritus-associated cutaneous adverse events (paCAEs) are frequent with immune checkpoint inhibitors (CPIs) and targeted anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we sought to evaluate the efficacy and safety of IgE blockade with omalizumab in cancer patients with refractory paCAEs related to CPIs and anti-HER2 agents. PATIENTS AND METHODS: Patients included in this multicenter retrospective analysis received monthly subcutaneous injections of omalizumab for CPI or anti-HER2 therapy-related grade 2/3 pruritus that was refractory to topical corticosteroids plus at least one additional systemic intervention. To assess clinical response to omalizumab, we used the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was defined as reduction in the severity of paCAEs to grade 1/0. RESULTS: A total of 34 patients (50% female, median age 67.5 years) received omalizumab for cancer therapy-related paCAEs (71% CPIs; 29% anti-HER2). All had solid tumors (29% breast, 29% genitourinary, 15% lung, 26% other), and most (n = 18, 64%) presented with an urticarial phenotype. In total 28 of 34 (82%) patients responded to omalizumab. The proportion of patients receiving oral corticosteroids as supportive treatment for management of paCAEs decreased with IgE blockade, from 50% to 9% (P < 0.001). Ten of 32 (31%) patients had interruption of oncologic therapy due to skin toxicity; four of six (67%) were successfully rechallenged following omalizumab. There were no reports of anaphylaxis or hypersensitivity reactions related to omalizumab. CONCLUSIONS: IgE blockade with omalizumab demonstrated clinical efficacy and was well tolerated in cancer patients with pruritus related to CPIs and anti-HER2 therapies.

A targeted review on fate, occurrence, risk and health implications of bisphenol analogues.

Due to its widespread applications and its ubiquitous occurrence in the environment, bisphenol A (BPA) and its alternatives have gained increasing attention, especially in terms of human safety. Like BPA, alternatives such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) have also been identified to be endocrine-disrupting chemicals (EDCs). Hence, in this study, we reviewed the literature of BPA and its alternatives mainly published between the period 2018-2020, including their occurrences in the environment, human exposure, and adverse health effects. The review shows that bisphenols are prevalent in the environment with BPA, BPS, and BPF being the most ubiquitous in the environment worldwide, though BPA remains the most abundant bisphenol. However, the levels of BPS and BPF in different environmental media have been constantly increasing and their fates and health risks are being evaluated. The studies show that humans and animals are exposed to bisphenols in many different ways through inhalation and ingestion and the exposure can have serious health effects. Urinary bisphenols (BPs) levels were frequently reported to be positively associated with different health problems such as cancer, infertility, cardiovascular diseases, diabetes and neurodegenerative diseases. Our literature study also shows that BPs generate reactive oxygen species and disrupt various signalling pathways, which could lead to the development of chronic diseases. Activated carbon-based and chitosan-based sorbents have been widely utilized in the removal of BPA in aqueous solutions. In addition, enzymes and microorganisms have also been getting much attention due to their high removal efficiencies.

Lifestyle Genetics-Based Reports in the Treatment of Obesity.

Obesity becomes a chronic disease due to the increasing number of mortality and morbidity cases around the world. In most regions, chronic illnesses, such as obesity, are important sources of morbidity and mortality. Due to a lack of effective strategies for prevention and management, the adverse effects of obesity and related diseases on health continue to be a serious problem. Relevant information was searched from Google Scholar, Scopus, and PubMed using such different terms as "Obesity", "Obesity Management", "Obesity AND Physical activity", "Obesity AND Genetics", "Obesity AND Diet", and "Obesity AND Nutrigenomics". Obesity is characterized by a complex interaction of hereditary and lifestyle factors, which includes food. Diet is an environmental element that plays an important and considerable role in the management of health and reduces the risk of obesity and its comorbidities. Changes in lifestyle patterns not only help burn extra calories but also prevent the development of obesity via its modulating effect on genetic factors. Different people respond differently to an obesogenic environment. The notion of nutrigenetics emerged as a result of various genetic variations that may explain this heterogeneity. Nutritional genomics, also known as nutrigenetics, is the study that investigates and analyses gene variations linked to varied responses to certain foods; moreover, it links this variation to diseases, such as obesity. As a result, tailored nutrition advice based on a person's genetic profile may improve the outcomes of a specific dietary strategy and offer a novel dietary strategy to improve life quality and preventing obesity. This study concluded that physical activity and dietary interventions play an effective role in the management of obesity. Moreover, understanding of the function of the most prominent obesity-related genes, as well as the interaction between nutrition and gene expression, will help researchers design personalized treatment strategies for humans.

Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment.

Oral aphthosis is a painful inflammatory process of the oral mucosa. Oral aphthous can appear alone or secondary to numerous distinct disease processes. If recurrence occurs frequently, it is called recurrent aphthous stomatitis. The pathophysiology of oral aphthous ulcers remains unclear but various bacteria are part of its microbiology. Three morphological types hold great importance in literature because these types help manage the illness properly. Google Scholar and PubMed databases were used to retrieve the relevant data and information. Different keywords including "Aphthous", "Aphthosis", "Canker sores", "Aphthous stomatitis", "Aphthous ulcer causes", "Aphthous ulcer AND Microbiota" and "Aphthous ulcer AND treatment". The causes for oral aphthous ulcerations are widespread and ranges from localized trauma to rare syndromes, underlying intestinal disease, or even malignant disease processes. A detailed history and thorough examination of systems can assist the physician or dermatologist in defining whether it is related to a systemic disease process or truly idiopathic. Management of oral aphthous ulcers is challenging. For oral aphthous or recurrent aphthous ulcers from an underlying disease, topical medications are preferred due to their minimum side effects. Systemic medications are necessary if the disease progresses. Within the limitation of research and literature provided, it is safe to say that topical corticosteroids are the first line of treatment. Herein, the author discusses the pathophysiology, types, causes, diagnosis, and appropriate treatment ladder of oral aphthous stomatitis as described in the literature.

Bismuth-Doped Nano Zerovalent Iron: A Novel Catalyst for Chloramphenicol Degradation and Hydrogen Production.

In this study, we showed that doping bismuth (Bi) at the surface of Fe0 (Bi/Fe0, bimetallic iron system)-synthesized by a simple borohydride reduction method-can considerably accelerate the reductive degradation of chloramphenicol (CHP). At a reaction time of 12 min, 62, 68, 74, 95, and 82% degradation of CHP was achieved with Fe0, Bi/Fe0-1 [1% (w/w) of Bi], Bi/Fe0-3 [3% (w/w) of Bi], Bi/Fe0-5 [5% (w/w) of Bi], and Bi/Fe0-8 [8% (w/w) of Bi], respectively. Further improvements in the degradation efficiency of CHP were observed by combining the peroxymonosulfate (HSO5 -) with Bi/Fe0-5 (i.e., 81% by Bi/Fe0-5 and 98% by the Bi/Fe0-5/HSO5 - system at 8 min of treatment). Interestingly, both Fe0 and Bi/Fe0-5 showed effective H2 production under dark conditions that reached 544 and 712 µM by Fe0 and Bi/Fe0-5, respectively, in 70 mL of aqueous solution containing 0.07 g (i.e., at 1 g L-1 concentration) of the catalyst at ambient temperature.

Hydrogeochemical investigation of arsenic in drinking water of schools and age dependent risk assessment in Vehari District, Punjab Pakistan: a multivariate analysis.

Globally, a large number of school-aged children is suffering from water-borne diseases, particularly in low-income countries. Arsenic (As) is a hazardous and potentially carcinogenic metal(loid) in drinking water. Nowadays, alarming levels of As have been reported in the groundwater of Vehari District, Punjab Pakistan. In this study, drinking water supplies for high and higher secondary schools were examined in Vehari District. A total of 164 water samples were collected from schools and subjected to heavy metal(loid) analysis (As) and basic water physicochemical parameters. The results were analyzed with respect to sampling area, school type, school education level, sources of sample collection, and the depth of the source. The results revealed that As concentration of water samples in boys' and girls' schools was 12.8 µg/L and 9.2 µg/L, respectively. However, when the As concentration in drinking water was evaluated at the school education level, a notable higher concentration of As was observed in the higher secondary schools than the high schools with an average of 19.5 and 9.7 µg/L, respectively. The risk assessment indices were calculated based on education level and different age groups of the children (primary, elementary, high, and higher secondary). High carcinogenic (cancer risk = 0.001) and non-carcinogenic (hazard quotient = 2.0) risks were noted for the children in higher secondary school. The current findings anticipated that the drinking water of schools in Vehari District did not meet the requirement of the World Health Organization (WHO) drinking water quality guidelines. Safe drinking water is crucial for the development and growth of children. Therefore, it is important for educational authorities to take steps for provision of As free safe drinking water to students and local inhabitants.