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Purpose: Antibody-drug conjugates (ADCs) are a relatively recent advance in the delivery of chemotherapeutics that improve targeting of cytotoxic agents. However, despite their antitumor activity, severe ocular adverse effects, including vision loss, have been reported for several ADCs. The nonspecific uptake of ADCs into human corneal epithelial cells (HCECs) and their precursors via macropinocytosis has been proposed to be the primary mechanism of ocular toxicity. In this study, we evaluated the ability of a novel polymer, poly(l-lysine)–graft–poly(ethylene glycol) (PLL-g-PEG), to decrease the ADC rituximab-mc monomethylauristatin F (MMAF) (RIX) uptake into human corneal epithelial (HCE-T) cells. Methods: HCE-T cells were exposed to increasing concentrations of RIX to determine inhibition of cell proliferation. HCE-T cells were treated with PLL-g-PEG, the macropinocytosis inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA), or vehicle. After 30 min of incubation, RIX was added. ADC was detected by fluorescent anti-human immunoglobulin G and fluorescently conjugated dextran as viewed by microscopy. Results: RIX caused dose-dependent inhibition of HCE-T cell proliferation. EIPA significantly reduced RIX uptake and decreased macropinocytosis as assessed by direct quantification of RIX using a fluorescently conjugated anti-human antibody as well as quantification of macropinocytosis using fluorescently conjugated dextran. PLL-g-PEG resulted in a dose-dependent inhibition of RIX uptake with half-maximal inhibitory concentrations of 0.022%–0.023% PLL-g-PEG. Conclusion: The data show PLL-g-PEG to be a potent inhibitor of RIX uptake by corneal epithelial cells and support its use as a novel therapeutic approach for the prevention of ocular adverse events associated with ADC therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and tolerability of pooled human immune globulins, Flebogamma® 5% DIF and Flebogamma® 10% DIF, administered by topical ophthalmic instillation to New Zealand White (NZW) rabbits. Methods: Male NZW rabbits were used in this study. In the acute single dose tolerability study, rabbits (n = 12) received a single topical dose of Flebogamma® 5% DIF. In the two-week repeated-dose tolerability study, rabbits (n = 5 for each group) were administered either Flebogamma® 5% DIF or Flebogamma® 10% DIF by topical bilateral administration four times daily (q.i.d.) between 8 am and 6 pm for a period of two weeks. Full ophthalmic examinations were conducted to evaluate ocular tolerability at baseline, Day 7, and Day 14. Results: In the acute single dose study, mild hyperaemia was observed in 1 out of 4 eyes at each 4 h and 24 h post-instillation of Flebogamma® 5% DIF. In the repeated dose study, no ocular signs were detected after q.i.d. topical instillation of Flebogamma® 5% DIF, while Flebogamma® 10% DIF resulted in mild hyperaemia in 8 out of 10 eyes on Day 7, and 5 out of 10 eyes on Day 14. No positive corneal fluorescein staining was detected. Schirmer tear test results were unremarkable. No other ocular signs were observed. Administration of immune globulins had no effect on intraocular pressure. Conclusions: Flebogamma® 5% DIF and Flebogamma® 10% DIF were well-tolerated by NZW rabbits following single and repeat dose topical ophthalmic administration, supporting the future development of topical pooled human immune globulins for the treatment of ocular surface disease. [ABSTRACT FROM AUTHOR]

The immunotherapy has emerged as a treatment modality to treat recurrent and advanced tumors. Many immune markers are being evaluated in Oral squamous cell carcinoma (OSCC) including costimulatory molecules OX40 (Tumor necrosis factor receptor superfamily, member 4, TNFSRF4) and OX40L (tumor necrosis factor superfamily, member 4; TNFSF4). They function to potentiate T cells function to accentuate anti-tumor activity. The results of OX40 and OX40L in cancer immunotherapy are still limited and most of the studies have evaluated their expression in tumor biopsies. In this study we aimed to find out gene expression of costimulatory molecules in naïve oral squamous cell carcinoma patients in saliva and blood as noninvasive biological samples by qPCR. The results revealed significant difference between the cycle threshold (Ct) values in the saliva and blood of OX40 (p value=<0.001) and OX40L (p value=<0.001) in OSCC patients. The fold change overexpression in blood and saliva is also compared in relation to histological gradings and clinical staging. Based on our observations we suggest these particular markers can be evaluated in blood and saliva less invasively compared to tumor biopsies. [ABSTRACT FROM AUTHOR]

Brucellosis is a serious disease that affects both animals and humans. It is caused by consuming unpasteurized dairy products that are contaminated with the Brucella bacteria. To study the pathobiology of this disease and develop preventive strategies, researchers rely on in vivo and in vitro models. A systematic literature search was conducted in January 2024, which revealed 38 studies that used these models in the previous four years. Mice were the most commonly used model for studying the disease's virulence genes, immune responses, vaccination, and treatment testing. Out of the 38 articles discussing infection models in brucellae, 6 used only in vivo models, 9 used only in vitro models, and 24 used both models. In addition, there were 32 studies with in vitro experiments, most of which utilized macrophages to study intracellular survival mechanisms and host-pathogen interactions. The studies mainly focused on B. abortus, as it had a significant impact on public and livestock health. Both in vivo and in vitro models were used to understand comprehensive intracellular mechanisms, immune responses, and treatment evaluations. However, there were several challenges in using these models, such as ethical concerns and host pathogen-specific immune responses. While both models provided important insights, the final selection choice of the model mostly depended on the research objectives, pathogen type, and availability of resources. Nevertheless, validation and understanding of these models are important to predict responses in the natural hosts. [ABSTRACT FROM AUTHOR]

Photoactive interfaces derived from all organic double cable polymers (O-DCPs) consisting of covalently conjugated photoelectron donor (D) and electron acceptor (A) molecular components are being recognized as promising light energy harvesting systems. Compared to the limitations faced by the fullerene-based electron acceptors, organic non-fullerene acceptors (NFAs) offer superior properties. Expanding the toolbox of all organic DCP molecules, we have developed two distinct DCPs consisting of polythiophene (PTh) photoelectron D covalently conjugated to rhodanine and perylene diimide (PDI) based organic NFAs. Grignard Metathesis (GRIM) polymerization was used to synthesize the PTh copolymer bearing protected pendant hydroxyl groups. The deprotection of pendant hydroxyl groups followed by an esterification reaction with a boronic ester (BE) bearing acid chloride produced the PTh copolymer with pendant BE groups. The subsequent Suzuki coupling reaction with 7-bromo-2,1,3-benzothiadiazole-4-carboxaldehyde (BBTCA) followed by Knoevenagel condensation with 3-ethylrhodanine produced the polythiophene-rhodanine based covalent D–A hybrid (PTh-Rho-CH) DCP. BE functionalized polythiophene (PTh-BE) was separately functionalized with a PDI derivative to synthesize a polythiophene-PDI based covalent D–A hybrid (PTh-PDI-CH) DCP. Both the DCPs exhibited strong fluorescence quenching of the polythiophene component. The synthesized DCPs were employed as the photoactive layers in interdigitated gold electrode-based photodetector devices. The application of PTh-Rho-CH and PTh-PDI-CH as photoactive layers led to a strong enhancement (by a factor of ∼8 and 16, respectively) of photocurrent generation compared to when PTh lacking acceptor species was employed as the photoactive layer. This work systematically contributes to the development of NFA-based DCPs for application in light harvesting and conversion technologies. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is a widespread acceptance and shift towards sustainable, inclusive and smart mobility solutions around the world. However, in Karachi, poorly coordinated urban planning, lack of effective governance structure and investment in transport, has allowed the growth of an almost unregulated and ungovernable informal transport sector. Women are more severely affected by the poor service since men not only have more space allocated to them on public transport but also have the freedom to use alternative and cheaper private vehicles such as motorbikes and cycles. Poor representation of women in the transport sector further aggravates the situation. OBJECTIVE: The paper aims to highlight the gender-disaggregated effects of poor transport design, provision and lack of personal agency on mobility, for emphasising the social and cultural attitudes faced by female employees. It argues that not integrating the gender-based disadvantages faced by women into planning, reinforces their disadvantaged position and force them to take complex trips. METHODS: Scenario-based questions were designed for focus group discussion which covered not only the everyday mobility challenges but also their reactions to the potential solutions. For a gender-based comparative analysis, two separate focus group discussions were organised. RESULTS: Adopting a sector-based mapping approach of the issues discussed in the groups helped understand the complexity of female user experience at various levels, starting from planning or discussing the trips with families, to making modal choices. It also helped to tease out the impact of these issues on their employment opportunities as early-career women. CONCLUSION: The model proposed in this paper can help illustrate where changes can be made in the system considering the social aspects of transport. [ABSTRACT FROM AUTHOR]

Objective: The study aims to investigate the motivations driving female medical and dental students to pursue careers as doctors. It also seeks to understand the various factors shaping their decisions and compare the perspectives of first-year and final-year students in government and private medical and dental education programs in Karachi. Study type, settings & duration: This comparative cross-sectional study was conducted at government and private institutions in Karachi from July 2022 to February 2023. Methodology: The government and private medical and dental students of Karachi recruited by non-purposive convenience sampling. A pre-structured questionnaire with a sample size of 1550 students was used which included demographic details and factors and attitude related to the reasons behind to pursue the medical and dental education. Results: Total of 55.4% students of in public centers choose the profession because of their interest while 51.7% comply with parents' wishes. While 66% of students from private medical and dental colleges choose the profession in compliance with their parent's wishes followed by personal interest i.e. 61.8%. Among different reasons human care holds the major proportion. There is a significant change in attitude towards the reason to pursue the medical and dental education among students of first year and final year in both public and private medical and dental colleges. Conclusion: It has been concluded that female medical and dental students are primarily motivated to acquire medical and dental education due to their personal interest and a desire to fulfill their parents' wishes. Moreover, the research reveals that there was shift in their perspective on reasons for choosing the profession from first year to the final year in both government and private medical and dental colleges in Karachi. [ABSTRACT FROM AUTHOR]

Objective: To determine the correlation between hemoglobin and glycosylated hemoglobin level among patients with type 2 diabetes mellitus. Study Design: Cross Sectional Study. Place and Duration of Study: Department of Chemical, Combined Military Hospital, Multan Pakistan, from Jul to Dec 2019. Subject and method; After approval from ethical community and written informed consent from the patient, sample were obtained under strict aseptic technique and were immediately sent to hospital laboratory to detect glycosylated hemoglobin level. Result: One hundred and ninety-five (195) patients were studied out of which (161) were female gender and (34) were male gender. The correlation between hemoglobin and glycosylated hemoglobin level through Pearson correlation coefficient shows a very low negative correlation of -0.253 which is statistically significant with p-value <0.001. Conclusion; Correlation of hemoglobin and glycosylated hemoglobin level thus may prove to be useful and consistent predictive indicator in patients with type-2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Purpose: Clinical data suggest that alcohol use is associated with the development of signs and symptoms of dry eye disease. However, preclinical data investigating ocular toxicity after dietary alcohol consumption are lacking. In this study, we investigated the effects of alcohol on the ocular surface, in human corneal epithelial cells (HCE-T) in vitro and in C57BL/6JRj mice in vivo. Methods: HCE-T were exposed to clinically relevant doses of ethanol. To determine the effects of dietary alcohol consumption in vivo, wild-type mice were administered the Lieber–DeCarli liquid diet (5% vol/vol ethanol or isocaloric control) for 10 days ad libitum. Corneal fluorescein staining was performed to assess ocular surface damage. Histopathological and gene expression studies were performed on cornea and lacrimal gland tissue. Results: Sublethal doses of ethanol (0.01%–0.5%) resulted in a dose-dependent increase of cellular oxidative stress in corneal epithelial cells and a significant increase in NFE2L2 and downstream antioxidant gene expression, as well as an increase in NFκB signaling; short-term exposure (0.5%, 4 h) triggered significant corneal epithelial cell barrier breakdown. Exposure to the alcohol-containing diet caused a 3-fold increase in corneal fluorescein staining, with no effect on tear volumes. Corneal thickness was significantly reduced in the alcohol diet group, and corneal tissue revealed dysregulated antioxidant and NFκB signaling. Our data provide the first published evidence that alcohol exposure causes ocular toxicity in mice. Conclusions: Our results are consistent with clinical studies linking past alcohol consumption to signs of ocular surface disease. [ABSTRACT FROM AUTHOR]

Survey was conducted to analyze attitude of in-service teachers towards acquiring higher qualification. Teachers of schools, colleges and universities of 2-divisional headquarters of southern Punjab (Bahawalpur and Multan) constituted the population of the study. Sample consisted of 224 in-service teachers of schools, colleges and universities. To collect relevant information a questionnaire and observation sheet was used. The factor analysis with varimax rotation yielded seven major factors; departmental restrictions, the financial benefit, family responsibilities, departmental facilities,job security, teaching quality and quality of the educational institutions. The data was analyzed with independent t-test and one way ANOVA. It was concluded that 79.8% teachers faced departmental restriction, 77.5% faced financial constraints, 82% faced family responsibilities, only 42.05% were facilitated by department, 79.33% felt job security after higher education, 75.36% responded teaching quality was improved while 51.4% responded quality of educational institutions improved due to highly qualified teachers. Results provides significant information in decising about the relationships and reaching conclusion along with offering certain recommendations to policy makers for revisiting their polities and future researcher to conduct research from new dimensions. [ABSTRACT FROM AUTHOR]