Search

This study is intended to understand extent of help-seeking behavior of male college students. This study used descriptive quantitative research design. The participants were the male college students of the College Department of Kabankalan Catholic College, enrolled in the Academic Year 2022 - 2023. Moreover, this study used Attitude Toward Seeking Professional Psychological Help Test, a standardized instrument measuring the help-seeking behavior of the participants. The results revealed that male college students opt to seek psychological help when they are psychologically distressed. Moreover, it was also found out that the perception towards seeking help in matters pertaining to the time needed for the process hinders the participants to seek help. In addition, help-seeking inside the institution is free and readily accessible, yet the data gathered shown that participants still thought that to seek help may cost them a lot. Awareness for access to where the participants can seek help could be a great factor of this occurrence. Thus, the study suggests that further investigation discussing the factors of help-seeking behavior of certain population is significant to shed light on this phenomenon. Furthermore, this study highly recommends to all institutions to initiate programs and projects that will help combat the misconception of seeking help to the appropriate professionals in order to continuously promote accessible psychological help to all. [ABSTRACT FROM AUTHOR]

Over the past century, the demand for petroleum products has increased rapidly, leading to higher oil extraction, processing and transportation, which result in numerous oil spills in coastal-marine environments. As the spilled oil can negatively affect the coastal-marine ecosystems, its transport and fates captured a significant interest of the scientific community and regulatory agencies. Typically, the environment has natural mechanisms (e.g., photooxidation, biodegradation, evaporation) to weather/degrade and remove the spilled oil from the environment. Among various oil weathering mechanisms, biodegradation by naturally occurring bacterial populations removes a majority of spilled oil, thus the focus on bioremediation has increased significantly. Helping in the marginal recognition of this promising technique for oil-spill degradation, this paper reviews recently published articles that will help broaden the understanding of the factors affecting biodegradation of spilled oil in coastal-marine environments. The goal of this review is to examine the effects of various environmental variables that contribute to oil degradation in the coastal-marine environments, as well as the factors that influence these processes. Physico-chemical parameters such as temperature, oxygen level, pressure, shoreline energy, salinity, and pH are taken into account. In general, increase in temperature, exposure to sunlight (photooxidation), dissolved oxygen (DO), nutrients (nitrogen, phosphorous and potassium), shoreline energy (physical advection—waves) and diverse hydrocarbon-degrading microorganisms consortium were found to increase spilled oil degradation in marine environments. In contrast, higher initial oil concentration and seawater pressure can lower oil degradation rates. There is limited information on the influences of seawater pH and salinity on oil degradation, thus warranting additional research. This comprehensive review can be used as a guide for bioremediation modeling and mitigating future oil spill pollution in the marine environment by utilizing the bacteria adapted to certain conditions.

Introduction: Individuals with co-occurring mental and physical health issues have worse health outcomes in both domains. Integration improves outcomes and aligns with patient preference, but health services tend to be siloed. The Mental Health in Medicine Clinic (MHiM) supports patients receiving inpatient or outpatient medical or surgical care at a tertiary academic hospital in Toronto, Canada. The predominantly virtual clinic has an interdisciplinary team offering services via stepped care, matching patient need with service intensity. Measurement-based care (MBC), the systematic evaluation of patient reported outcomes, was not initially used routinely in the clinic, but its implementation may improve treatment decision-making and may be useful in allocating patients within a stepped care model. Objectives: 1) To describe the stepped care model, referral patterns, diagnoses, and level of care provided since implementation of stepped care. 2) To conduct a quality improvement initiative to implement MBC in the clinic, with a goal of 50% of patients completing at the time of first assessment and prior to discharge from the clinic. Methods: We reviewed the electronic medical record for referral source, diagnoses, and level of stepped care within the clinic. We conducted semi-structured interviews with stakeholders (clinicians, administrative staff, patients) to explore barriers to implementation of MBC. Interviews were analyzed for themes around barriers and facilitators to MBC. Plan, Do, Study, Act cycles were carried out around change concepts informed by stakeholder interviews and relevant literature. Results: The MHiM clinic began operations in August 2020. The clinic operated on a physician-only model until March 2022 and then shifted to a stepped care model with an interdisciplinary team. The most frequent referral sources were internal medicine, COVID19 clinics, consultation-liaison psychiatry, red blood cell disorders clinic and cardiology. Since the implementation of stepped care, 250 referrals were assessed. 58% of new referrals were assessed by the psychiatrist, 42% were managed by the NP, and 25% consulted with the social worker. Referrals consisted of trauma and stress-related disorders (32%), depression (21%) or anxiety disorders (20%). Personality, substance use, and psychotic disorders accounted for less than 10% of referrals combined. Some patients did not have any diagnosis (6%). Results from the quality improvement initiative to implement MBC will also be presented. Conclusions: The MHiM clinic provides an integrated care pathway addressing comorbid mental and physical health conditions. We describe a novel stepped care model and the implementation of MBC. Future directions include ongoing quality improvement of MBC and its integration within the clinic to assess and re-assess service intensity. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Background/purpose: Depressive symptoms are prevalent in student-athletes. Evidence for the factorial validity of measures assessing depressive symptoms in student-athletes is presently absent from the literature. This study examined the best fitting factorial structure and invariance across sexes of the PHQ-9., Methods: Data were collected from 1,524 student-athletes from institutions in the North-Eastern United States. Confirmatory factor analyses of 4 factorial structures of the Patient Health Questionnaire-9 (PHQ-9) were conducted, followed by invariance analyses across sexes., Results: All tested models showed an excellent fit for all tested models and a unidimensional model of the PHQ-9 was chosen for further analyses. Metric and scalar invariance for the identified model across sexes was supported. The participants in this study reported an unusually low (3.13%) prevalence of elevated depressive symptoms, which may indicate underreporting of symptoms., Conclusion: Using a unidimensional, composite score via the PHQ-9 is a valid assessment of depressive symptoms in male and female student-athletes.

BCL-xL and BCL-2 are validated therapeutic targets in small-cell lung cancer (SCLC). Targeting these proteins with navitoclax (formerly ABT263, a dual BCL-xL/2 inhibitor) induces dose-limiting thrombocytopenia through on-target BCL-xL inhibition in platelets. Therefore, platelet toxicity poses a barrier in advancing the clinical translation of navitoclax. We have developed a strategy to selectively target BCL-xL in tumors, while sparing platelets, by utilizing proteolysis-targeting chimeras (PROTACs) that hijack the cellular ubiquitin proteasome system for target ubiquitination and subsequent degradation. In our previous study, the first-in-class BCL-xL PROTAC, called DT2216, was shown to have synergistic antitumor activities when combined with venetoclax (formerly ABT199, BCL-2-selective inhibitor) in a BCL-xL/2 co-dependent SCLC cell line, NCI-H146 (hereafter referred to as H146), in vitro and in a xenograft model. Guided by these findings, we evaluated our newly developed BCL-xL/2 dual degrader, called 753b, in three BCL-xL/2 co-dependent SCLC cell lines and the H146 xenograft models. 753b was found to degrade both BCL-xL and BCL-2 in these cell lines. Importantly, it was considerably more potent than DT2216, navitoclax, or DT2216 + venetoclax in reducing the viability of BCL-xL/2 co-dependent SCLC cell lines in cell culture. In vivo, 5 mg/kg weekly dosing of 753b was found to lead to significant tumor growth delay, similar to the DT2216 + venetoclax combination in H146 xenografts, by degrading both BCL-xL and BCL-2. Additionally, 753b administration at 5 mg/kg every four days induced tumor regressions. At this dosage, 753b was well tolerated in mice, without observable induction of severe thrombocytopenia as seen with navitoclax, and no evidence of significant changes in mouse body weights. These results suggest that the BCL-xL/2 dual degrader could be an effective and safe therapeutic for a subset of SCLC patients, warranting clinical trials in future.

In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.

Abstract: Australia monitors its polio-free status by conducting surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years of age, as recommended by the World Health Organization (WHO). Cases of AFP in children are notified to the Australian Paediatric Surveillance Unit or the Paediatric Active Enhanced Disease Surveillance System, and faecal specimens are referred for virological investigation to the National Enterovirus Reference Laboratory. In 2022, no cases of poliomyelitis were reported from clinical surveillance and Australia reported 1.69 non-polio AFP cases per 100,000 children, thereby meeting the WHO's performance criterion for a sensitive surveillance system. The non-polio enteroviruses coxsackievirus A2, coxsackievirus A6, coxsackievirus A10, echovirus 18, enterovirus A71 and enterovirus C96 were identified from clinical specimens collected from AFP cases. Australia also performs enterovirus and environmental surveillance to complement the clinical system focussed on children. In 2022, thirty cases of wild poliovirus were reported from three countries (Afghanistan, Mozambique and Pakistan); 24 countries also reported cases of poliomyelitis due to circulating vaccine-derived poliovirus., (© Commonwealth of Australia CC BY-NC-ND.)

We previously showed that elevated TYMS exhibits oncogenic properties and promotes tumorigenesis after a long latency, suggesting cooperation with sequential somatic mutations. Here we report the cooperation of ectopic expression of human TYMS with loss of Ink4a/Arf, one of the most commonly mutated somatic events in human cancer. Using an hTS/Ink4a/Arf -/- genetically engineered mouse model we showed that deregulated TYMS expression in Ink4a/Arf null background accelerates tumorigenesis and metastasis. In addition, tumors from TYMS-expressing mice were associated with a phenotype of genomic instability including enhanced double strand DNA damage, aneuploidy and loss of G1/S checkpoint. Downregulation of TYMS in vitro decreased cell proliferation and sensitized tumor cells to antimetabolite chemotherapy. In addition, depletion of TYMS in vivo by TYMS shRNA reduced tumor incidence, delayed tumor progression and prolonged survival in hTS/Ink4a/Arf -/- mice. Our data shows that activation of TYMS in Ink4a/Arf null background enhances uncontrolled cell proliferation and tumor growth, supporting the development of new agents and strategies targeting TYMS to delay tumorigenesis and prolong survival., (© 2023. The Author(s).)

Although thymidylate synthase (TYMS) inhibitors have served as components of chemotherapy regimens, the currently available inhibitors induce TYMS overexpression or alter folate transport/metabolism feedback pathways that tumor cells exploit for drug resistance, limiting overall benefit. Here we report a small molecule TYMS inhibitor that i) exhibited enhanced antitumor activity as compared with current fluoropyrimidines and antifolates without inducing TYMS overexpression, ii) is structurally distinct from classical antifolates, iii) extended survival in both pancreatic xenograft tumor models and an hTS/Ink4a/Arf null genetically engineered mouse tumor model, and iv) is well tolerated with equal efficacy using either intraperitoneal or oral administration. Mechanistically, we verify the compound is a multifunctional nonclassical antifolate, and using a series of analogs, we identify structural features allowing direct TYMS inhibition while maintaining the ability to inhibit dihydrofolate reductase. Collectively, this work identifies nonclassical antifolate inhibitors that optimize inhibition of thymidylate biosynthesis with a favorable safety profile, highlighting the potential for enhanced cancer therapy.

Small-cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. The dismal prognosis in SCLC is in part associated with an upregulation of BCL-2 family anti-apoptotic proteins, including BCL-X L and MCL-1. Unfortunately, the currently available inhibitors of BCL-2 family anti-apoptotic proteins, except BCL-2 inhibitors, are not clinically relevant because of various on-target toxicities. We, therefore, aimed to develop an effective and safe strategy targeting these anti-apoptotic proteins with DT2216 (our platelet-sparing BCL-X L degrader) and AZD8055 (an mTOR inhibitor) to avoid associated on-target toxicities while synergistically optimizing tumor response. Through BH3 mimetic screening, we identified a subset of SCLC cell lines that is co-dependent on BCL-X L and MCL-1. After screening inhibitors of selected tumorigenic pathways, we found that AZD8055 selectively downregulates MCL-1 in SCLC cells and its combination with DT2216 synergistically killed BCL-X L /MCL-1 co-dependent SCLC cells, but not normal cells. Mechanistically, the combination caused BCL-X L degradation and suppression of MCL-1 expression, and thus disrupted MCL-1 interaction with BIM leading to an enhanced apoptotic induction. In vivo, the DT2216 + AZD8055 combination significantly inhibited the growth of cell line-derived and patient-derived xenografts and reduced tumor burden accompanied by increased survival in a genetically engineered mouse model of SCLC without causing appreciable thrombocytopenia or other normal tissue injuries. Thus, these preclinical findings lay a strong foundation for future clinical studies to test DT2216 + mTOR inhibitor combinations in a subset of SCLC patients whose tumors are co-driven by BCL-X L and MCL-1., (© 2023. The Author(s).)

Clinical studies of cancer patients have shown that overexpression or amplification of thymidylate synthase (TS) correlates with a worse clinical outcome. We previously showed that elevated TS exhibits properties of an oncogene and promotes pancreatic neuroendocrine tumors (PanNETs) with a long latency. To study the causal impact of elevated TS levels in PanNETs, we generated a mouse model with elevated human TS (hTS) and conditional inactivation of the Men1 gene in pancreatic islet cells (hTS/Men1-/-). We demonstrated that increased hTS expression was associated with earlier tumor onset and accelerated PanNET development in comparison with control Men1-/- and Men1+/ΔN3-8 mice. We also observed a decrease in overall survival of hTS/Men1+/- and hTS/Men1-/- mice as compared with control mice. We showed that elevated hTS in Men1-deleted tumor cells enhanced cell proliferation, deregulated cell cycle kinetics, and was associated with a higher frequency of somatic mutations, DNA damage, and genomic instability. In addition, we analyzed the survival of 88 patients with PanNETs and observed that high TS protein expression independently predicted worse clinical outcomes. In summary, elevated hTS directly participates in promoting PanNET tumorigenesis with reduced survival in Men1-mutant background. This work will refocus attention on new strategies to inhibit TS activity for PanNET treatment.

Background: Prostatic carcinomas are a leading cancer and leading cause of mortality in the developed world. The etiology is diverse with underlying patient genetics, environmental factors, and microbial associations. Sequencing DNA for microbes allows the detection of potential disease relationships., Objective: Targeted 16S (prokaryotic) and 18S (eukaryotic) rDNA sequencing was performed to map the tumor microbial flora., Design: Twelve patients undergoing elective laparoscopic prostatectomy for biopsy proven adenocarcinoma of the prostate were enrolled. PCR and amplicon based sequencing was conducted; a portion of the sequencing results were confirmed by special stains., Setting: Patients were recruited by the urologist were prospectively scheduled for radical prostatectomy by 'Da Vinci' robotically assisted procedure in an outpatient setting. Samples were portioned in the hospital surgical suite at the time of prostatectomy., Participants: Male patients were requested to enter the study on a first come basis., Outcome Measurement and Statistical Analysis: Average age of the 12 participants was 64.3 years., Results and Limitations: DNA reads were detected and by 'best match' were identified belonging to Perkinsus, Hydrurus, Diversispora and Funneliformis genera, few samples displayed bacteria. Out of the 12 total patients, 11 patients had detectable DNA sequences matching arbuscular mycorrhizal fungi in the Glomeromycetes Class; Funneliformis mosseae and Diversasporum versiformis. Specific PCR for arbuscular mycorrhizal fungi failed to confirm Glomeromycetes Class; in-depth taxonomic analysis suggests a newer fungal grouping, not falling within an accepted Phylum of fungi. Calcoflour white staining of histological sections confirmed potential fungal markers in all 12 cases. Ochratoxin A antigen was identified by immunofluorescence in all 12 patient samples. The study was limited by the low sample volume and disease free normal controls., Conclusions: Fungi may play a significant role in adenocarcinoma of the prostate., Competing Interests: Declaration of Competing Interest Stephen E. Fry – owner of Fry Laboratories, BioID Genomics, and founder of The Southwest Center for Chronic Disease. All other authors have no conflicts: We acknowledge the Southwest Center for Chronic Disease for their support., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: In vitro fertilization (IVF) has been a well-established method for treating infertility for over four decades. The mainstay method of culture of oocytes and embryos has been in gas incubators. More recently, the novel use of a gas-permeable closed vessel to culture oocytes and embryos in the vagina, intravaginal culture (IVC), has been introduced as a viable lower-cost option for infertility patients. Several studies have studied the efficacy of IVC; however, there is no data on the perinatal outcomes of the babies born using this newer technology., Methods: Our study is a retrospective case series (n = 66) from a single center, uniquely examining the perinatal outcomes of infants born after IVC., Results: There were 50 singleton and 16 twin gestations in this case series. For singleton infants conceived via IVC (n = 50), the mean gestational age at delivery was 38 weeks and 4 days, and the mean birth weight was 3159.1 + / - 501.5 g. Four infants were born with low birth weight, three were born preterm, and one was born macrosomic. The twin pregnancies had a mean gestational age at delivery of 33 weeks 4 days and a mean birth weight of 1992.9 + / - 620.7 g. Twenty-seven infants met the criteria for low birthweight, and twenty-four infants delivered preterm. No twin infants met the criteria for macrosomia., Conclusion: This case series provides an initial description of the perinatal outcomes of IVC conceived infants, which shows no concerning trends in adverse birth outcomes for singleton infants. As expected, IVC twin gestations had a high rate of low birth weight and preterm delivery. Continued larger studies are essential to provide more comprehensive data on perinatal outcomes of infants conceived by this new technology., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Using a case-control design, we determined risk factors associated with hypertension in a disadvantaged rural population in southern India. Three hundred adults with hypertension and 300 age- and sex-matched controls were extensively phenotyped. Underweight (29%, body mass index < 18.0 kg m -2 ), chronic kidney disease (25%, estimated glomerular filtration rate <60 ml min -1 1.73 m -2 ) and anemia (82%) were highly prevalent. The ratio of sodium to potassium excretion was high (8.2). In multivariable conditional logistic regression of continuous variables dichotomized by their median value, hypertension was independently associated with greater abdominal adiposity as assessed by waist-hip ratio [odds ratio (95% confidence interval), 1.89 (1.21-2.97)], lesser protein intake as assessed by 24 h urea excretion [0.39 (0.24-0.65)], and lesser plasma renin activity [0.54 (0.35-0.84)]. Hypertension tended to be independently associated with lesser serum potassium concentration [0.66 (0.44-1.01), P = 0.06]. Furthermore, those with hypertension reported less frequent intake of vegetables and urinary sodium-potassium ratio correlated positively with serum sodium-potassium ratio (r = 0.18). Hypertension was also independently associated with lesser blood hemoglobin concentration [0.48 (0.26-0.88)]. Blood hemoglobin concentration was positively associated with serum iron (r = 0.41) and ferritin (r = 0.25) concentration and negatively associated with total iron binding capacity (r = -0.17), reflecting iron-deficiency anemia. Our findings indicate potential roles for deficient intake of potassium and protein, and iron-deficiency anemia, in the pathophysiology of hypertension in a setting of disadvantage in rural India. Imbalanced intake of potassium and sodium may be driven partly by deficient intake of vegetables or fruit., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Abstract: Australia monitors its polio-free status by conducting surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years of age, as recommended by the World Health Organization (WHO). Cases of AFP in children are notified to the Australian Paediatric Surveillance Unit or the Paediatric Active Enhanced Disease Surveillance System and faecal specimens are referred for virological investigation to the National Enterovirus Reference Laboratory. In 2020, no cases of poliomyelitis were reported from clinical surveillance; Australia reported 1.09 non-polio AFP cases per 100,000 children, thereby meeting the WHO's performance criterion for a sensitive surveillance system. The non-polio enteroviruses coxsackievirus A10 and coxsackievirus A16 were identified from clinical specimens collected from AFP cases. Australia also performs enterovirus surveillance and environmental surveillance to complement the clinical system focussed on children. In 2020, there were 140 cases of wild poliovirus reported from the two remaining endemic countries: Afghanistan and Pakistan. Another 28 countries reported cases of circulating vaccine-derived poliovirus., (© Commonwealth of Australia CC BY-NC-ND.)