How Do Mental Disorders and Combinations of Disorders Affect the Odds of Injuries and Poisoning?

ABSTRACT: Injuries and poisoning are associated with mental disorders. The association may be stronger if comorbid mental illness is involved. This study explores whether selected mental disorders (stress, anxiety, depression, attention deficit hyperactivity disorder [ADHD], bipolar, obsessive-compulsive disorder [OCD], schizophrenia) are associated with injuries and poisoning and if the presence and frequency of comorbid mental illness affect these associations. Analyses utilize medical claims data for adult employees of a large corporation during 2017-2021. Approximately half or more of the index mental disorders experience comorbid mental illness. Odds of injury and poisoning are significantly greater for each mental disorder and tend to be significantly greater when comorbid mental illness exists (vs. the mental disorder alone), especially for the associations involving poisoning. Schizophrenia alone and in combination with other mental illness has the strongest associations with injury and poisoning. OCD is only associated with injury and poisoning, and ADHD is only associated with poisoning, if accompanied by comorbid mental illness.

Comparison of lung aeration loss in open abdominal oncologic surgeries after ventilation with electrical impedance tomography-guided PEEP versus conventional PEEP: a pilot feasibility study.

Background: Existing literature lacks high-quality evidence regarding the ideal intraoperative positive end-expiratory pressure (PEEP) to minimize postoperative pulmonary complications (PPCs). We hypothesized that applying individualized PEEP derived from electrical impedance tomography (EIT) would reduce the severity of postoperative lung aeration loss, deterioration in oxygenation, and PPC incidence. Methods: A pilot feasibility study was conducted on 36 patients who underwent open abdominal oncologic surgery. The patients were randomized to receive individualized PEEP or conventional PEEP at 4 cm H2O. The primary outcome was the impact of individualized PEEP on changes in the modified lung ultrasound score (MLUS) derived from preoperative and postoperative lung ultrasonography. A higher MLUS indicated greater lung aeration loss. The secondary outcomes were the PaO2/FIO2 ratio and PPC incidence. Results: A significant increase in the postoperative MLUS (12 ± 3.6 vs 7.9 ± 2.1, P < 0.001) and a significant difference between the postoperative and preoperative MLUS values (7.0 ± 3.3 vs 3.0 ± 1.6, P < 0.001) were found in the conventional PEEP group, indicating increased lung aeration loss. In the conventional PEEP group, the intraoperative PaO2/FIO2 ratios were significantly lower but not the postoperative ratios. The PPC incidence was not significantly different between the groups. Post-hoc analysis showed the increase in lung aeration loss and deterioration of intraoperative oxygenation correlated with the deviation from the individualized PEEP. Conclusions: Individualized PEEP appears to protect against lung aeration loss and intraoperative oxygenation deterioration. The advantage was greater in patients whose individualized PEEP deviated more from the conventional PEEP.

Switchable Charge Storage Mechanism via in Situ Activation of MXene Enables High Capacitance and Stability in Aqueous Electrolytes.

The need for reliable renewable energy storage devices has become increasingly important. However, the performance of current electrochemical energy storage devices is limited by either low energy or power densities and short lifespans. Herein, we report the synthesis and characterization of multilayer Ti4N3Tx MXene in various aqueous electrolytes. We demonstrate that Ti4N3Tx can be electrochemically activated through continuous cation intercalation over a 10 day period using cyclic voltammetry. A wide operating window of 2 V is maintained throughout activation. After activation, capacitance at 2 mV s-1 increases by 300%, 140%, and 500% in 1 M H2SO4, 1 M MgSO4, and 1 M KOH, respectively, while maintaining ∼600 F g-1 at 2 mV s-1 after 50000 cycles in 1 M H2SO4. This activation process is possibly attributed to the unique morphology of the multilayered material, allowing cation intercalation to increase access to redox-active sites between layers. This work adds to the growing repository of electrochemically stable MXenes reported for aqueous energy storage applications. These findings offer a reliable option for reliable energy storage devices with potential applications in large-scale grid storage and electric vehicles.

Scoping review on the association between early childhood caries and responsible resource consumption and production: exploring Sustainable Development Goal 12.

BACKGROUND: The Sustainable Development Goal 12 (SDG12) promotes patterns that minimize waste and maximize resource utilization. It is therefore plausible that preventing Early Childhood Caries (ECC) and promoting oral health can contribute to sustainable consumption. In addition, sustainable consumption and production can contribute to the control of ECC. This scoping review aimed to explore the possible evidence on the link between ECC and the SDG12 targets. METHODS: This scoping review identified articles on the link between resource consumption and production and caries according to the PRISMA-ScR guidelines. Three electronic databases (PubMed, Web of Science, and Scopus) were systematically searched in August 2023, using specific search terms. Studies written in English, with full text available, addressing dental caries and linked with waste minimization and resource utilization maximisation, with results that could be extrapolated to ECC in children less than 6 years of age) were included. Descriptive statistics were planned to summarize the categories of retrieved papers. RESULTS: The initial search yielded 904 articles, with 863 screened for eligibility after the removal of duplicates. No studies were identified that reported data on an association between responsible consumption and production of resources factors and ECC. CONCLUSION: This scoping review did not identify any articles published in English on evidence of the direct associations between ECC and SDG12 targets. However, there is a plausibility of such a link using minimum intervention dentistry for ECC management as a waste prevention and resource utilisation maximization strategy.

Scoping review on the link between economic growth, decent work, and early childhood caries.

BACKGROUND: Early Childhood Caries (ECC) is a prevalent chronic non-communicable disease that affects millions of young children globally, with profound implications for their well-being and oral health. This paper explores the associations between ECC and the targets of the Sustainable Development Goal 8 (SDG 8). METHODS: The scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. In July 2023, a search was conducted in PubMed, Web of Science, and Scopus using tailored search terms related to economic growth, decent work sustained economic growth, higher levels of productivity and technological innovation, entrepreneurship, job creation, and efforts to eradicate forced labor, slavery, and human trafficking and ECC all of which are the targets of the SDG8. Only English language publications, and publications that were analytical in design were included. Studies that solely examined ECC prevalence without reference to SDG8 goals were excluded. RESULTS: The initial search yielded 761 articles. After removing duplicates and ineligible manuscripts, 84 were screened. However, none of the identified studies provided data on the association between decent work, economic growth-related factors, and ECC. CONCLUSIONS: This scoping review found no English publication on the associations between SDG8 and ECC despite the plausibility for this link. This data gap can hinder policymaking and resource allocation for oral health programs. Further research should explore the complex relationship between economic growth, decent work and ECC to provide additional evidence for better policy formulation and ECC control globally.

Comparing the Strength of Associations Between Male Genital Problems and Mental Illnesses and Sleep Disorders.

This study compares the rate of selected types of mental illnesses (stress, anxiety, depression) and sleep disorders (insomnia, sleep apnea) according to the status of eight male genital problems. Analyses utilize medical claims data for male employees aged 18 to 64 years of a large corporation, 2017 to 2021. Approximately 1,076 (7.3%) men per year have one or more genital problems. The most common being benign prostatic hyperplasia (BPH; 3.8%) and then erectile dysfunction (ED; 1.7%). For BPH patients, the rate experiencing stress, anxiety, depression, or a combination of these is 0.96%, 6.2%, 5.3%, and 5.1%, respectively. Corresponding rates for ED are 1.5%, 7.2%, 5.9%, and 7.5%. For BPH patients, the rate experiencing insomnia, sleep apnea, or both is 3.1%, 22.7%, and 2.0%, respectively. Corresponding rates for ED are 1.2%, 20.6%, and 2.2%. Male genital problems positively associate with having one or more mental illnesses (stress, anxiety, depression), except for hydrocele, with ED and penis disorder having the strongest associations. Male genital problems also positively associate with having insomnia and/or sleep apnea, except for infertility and orchitis, with BPH and ED having the strongest associations. The positive associations involving BPH and ED with mental illnesses are each more pronounced in the younger age group (18-49 vs. 50-64). Similar results are seen in the models involving sleep disorders. Thus, comorbid male genital problems, mental illnesses, and sleep disorders exist, with the strength of associations unique to the male genital problem and sometimes modified by age.

Dietary intake and associated risk factors among pregnant women in Mbeya, Tanzania.

Poor dietary intake among pregnant women has serious detrimental consequences for pregnancy and offspring both in developed and developing countries. This study aimed to assess dietary intake and associated risk factors among pregnant women. A cross-sectional study was conducted in Mbeya, Tanzania with a sample size of 420 pregnant women attending antenatal clinics to assess the factors associated with dietary intake. Dietary intake was assessed using a piloted questionnaire of the Prime Diet Quality Score. A tested standard questionnaire was also used to collect factors that are associated with dietary intake among pregnant women. The strengths of the associations between the dependent and independent variables were tested using the Pearson chi-square tests and the multivariate log-binomial regression method was performed to calculate the adjusted risk ratios (ARR) and 95% confidence interval (CI). The study revealed that out of 420 pregnant women who participated in this study only 12.6% and 29.3% consumed at least four servings of fruits and vegetables per week respectively. Poor dietary intakes were less likely among cohabiting pregnant women [Adjusted RR 0.22 (95% CI 0.09-0.50)] and; those who reported taking Fansidar tablets during the pregnancy [Adjusted RR 0.55 (95% CI 0.31-0.96)]. Further, we found that poor dietary intakes were more likely among pregnant women who were classified as overweight and obesity by the MUAC above 33cm [Adjusted RR 3.49 (95% CI 1.10-11.06)]. The study results affirm that cohabitation and obesity affect dietary intakes among pregnant women differently compared to married women in rural settings of Tanzania. Further research is needed to investigate the social aspects that link dietary intake outcomes for developing a tailored gestational intervention to improve maternal and birth outcomes in sub-Saharan African countries.

Healthcare-seeking behaviours among mother's having under-five children with severe wasting in Dodoma and Mbeya regions of Tanzania-A qualitative study.

Maternal healthcare-seeking behaviour affects the health and well-being of under-five children. Drawing from the concepts of the health belief model, this study seeks to understand the determinants of health-seeking behaviours among mothers or caregivers of under-five-year-old children having severe wasting in Tanzania. A qualitative study employing the ethnography method conducted 32 semi-structured and narrative interviews with healthcare workers, community health workers, traditional healers, religious and village leaders, and mothers or caregivers of children who had acute malnutrition. The analysis of transcripts was done by qualitative content analysis. Further, the thematic analysis was carried out by assigning data into relevant codes to generate categories based on study objectives. Severe wasting among under-five-year-old children was not observed as a serious disease by the majority of mothers or caregivers. The study established that the health systems parameters such as the availability of the community health workers or healthcare providers and the availability of medicines and supplies to the health facility impact on mothers' or caregivers' healthcare-seeking behaviours. The findings also show that long distances to the health facility, behavioural parameters such as lack of awareness, negative perception of the management of severe wasting at the health facility, superstitious beliefs, women's workload, household food insecurity, and gender issues have a significant role in seeking healthcare. The results reaffirm how a programme on integrated management of severe wasting in Tanzania should encompass sociocultural factors that negatively influence mothers or caregivers of children with acute malnutrition. The programme should focus on engaging community structures including traditional healers, religious and village leaders to address prevailing local beliefs and sociocultural factors.

Women's cardiovascular health - the cardio-oncologic jigsaw.

Improvements in cancer care have led to an exponential increase in cancer survival. This is particularly the case for breast cancer, where 5-year survival in Australia exceeds 90%. Cardiovascular disease (CVD) has emerged as one of the competing causes of morbidity and mortality among cancer survivors, both as a complication of cancer therapies and because the risk factors for cancer are shared with those for CVD. In this review we cover the key aspects of cardiovascular care for women throughout their cancer journey: the need for baseline cardiovascular risk assessment and management, a crucial component of the cardiovascular care; the importance of long-term surveillance for ongoing maintenance of cardiovascular health; and strong evidence for the beneficial effects of physical exercise to improve both cancer and cardiovascular outcomes. There is general disparity in cardiovascular outcomes for women, which is further exacerbated when both CVD and cancer co-exist. Collaboration between oncology and cardiac services, with an emergence of the whole field of cardio-oncology, allows for expedited investigation and treatment for these patients. This collaboration as well as a holistic approach to patient care and key role of patients' general practitioners are essential to ensure long-term health of people living with, during and beyond cancer.

Upper Airway-Related Symptoms According to Mental Illness and Sleep Disorders among Workers Employed by a Large Non-Profit Organization in the Mountain West Region of the United States.

The relationships between selected upper airway-related symptoms (speech disturbances, voice disorders, cough, and breathing abnormalities) and mental illness and sleep disorders have been previously demonstrated. However, these relationships have not been compared in a single study with consideration of potential confounding variables. The current research incorporates a descriptive study design of medical claims data for employees (~21,362 per year 2017-2021) with corporate insurance to evaluate the strength of these relationships, adjusting for demographic variables and other important confounders. The upper airway-related symptoms are each significantly and positively associated with several mental illnesses and sleep disorders, after adjusting for demographic and other potential confounders. The rate of any mental illness is 138% (95% CI 93-195%) higher for speech disturbances, 55% (95% CI 28-88%) higher for voice disorders, 28% (95% CI 22-34%) higher for cough, and 58% (95% CI 50-66%) higher for breathing abnormalities, after adjustment for the confounding variables. Confounding had significant effects on the rate ratios involving cough and breathing abnormalities. The rate of any sleep disorder is 78% (95% CI 34-136%) higher for speech disturbances, 52% (95% CI 21-89%) higher for voice disorders, 34% (95% CI 27-41%) higher for cough, and 172% (95% CI 161-184%) higher for breathing abnormalities, after adjustment for the confounding variables. Confounding had significant effects on each of the upper airway-related symptoms. Rates of mental illness and sleep disorders are positively associated with the number of claims filed for each of the upper airway-related symptoms. The comorbid nature of these conditions should guide clinicians in providing more effective treatment plans that ultimately yield the best outcome for patients.

Child dental neglect and legal protections: a compendium of briefs from policy reviews in 26 countries and a special administrative region of China.

Background: Child neglect is a public health, human rights, and social problem, with potentially devastating and costly consequences. The aim of this study was to: (1) summarize the oral health profile of children across the globe; (2) provide a brief overview of legal instruments that can offer children protection from dental neglect; and (3) discuss the effectiveness of these legal instruments. Methods: We summarized and highlighted the caries profile and status of implementation of legislation on child dental neglect for 26 countries representing the World Health Organization regions: five countries in Africa (Nigeria, South Africa, Sudan, Tanzania, Zimbabwe), eight in the Americas (Argentina, Brazil, Canada, Chile, Mexico, Peru, Unites States of America, Uruguay), six in the Eastern Mediterranean (Egypt, Iran, Libya, Jordan, Qatar, Saudi Arabia), four in Europe (Italy, Latvia, Serbia, United Kingdom), two in South-East Asia (India and Indonesia) and one country (China) with its special administrative region (Hong Kong) in the Western Pacific. Results: Twenty-five of the 26 countries have legal instruments to address child neglect. Only two (8.0%) of these 25 countries had specific legal instruments on child dental neglect. Although child neglect laws can be interpreted to establish a case of child dental neglect, the latter may be difficult to establish in countries where governments have not addressed barriers that limit children's access to oral healthcare. Where there are specific legal instruments to address child dental neglect, a supportive social ecosystem has also been built to facilitate children's access to oral healthcare. A supportive legal environment, however, does not seem to confer extra protection against risks for untreated dental caries. Conclusions: The institution of specific country-level legislation on child dental neglect may not significantly reduce the national prevalence of untreated caries in children. It, however, increases the prospect for building a social ecosystem that may reduce the risk of untreated caries at the individual level. Social ecosystems to mitigate child dental neglect can be built when there is specific legislation against child dental neglect. It may be more effective to combine public health and human rights-based approaches, inclusive of an efficient criminal justice system to deal with child dental neglect.

Geographical differences in the management of metastatic de novo renal cell carcinoma in the era of immune-combinations.

BACKGROUND: The upfront treatment of metastatic renal cell carcinoma (mRCC) has been revolutionized by the introduction of immune-based combinations. The role of cytoreductive nephrectomy (CN) in these patients is still debated. The ARON-1 study (NCT05287464) was designed to globally analyze real-world data of mRCC patients receiving first-line immuno-oncology combinations. This sub-analysis is focused on the role of upfront or delayed partial or radical CN in three geographical areas (Western Europe, Eastern Europe, America/Asia). METHODS: We conducted a multicenter retrospective observational study in mRCC patients treated with first-line immune combinations from 55 centers in 19 countries. From 1152 patients in the ARON-1 dataset, we selected 651 patients with de novo mRCC. 255 patients (39%) had undergone CN, partial in 14% and radical in 86% of cases; 396 patients (61%) received first-line immune-combinations without previous nephrectomy. RESULTS: Median overall survival (OS) from the diagnosis of de novo mRCC was 41.6 months and not reached (NR) in the CN subgroup and 24.0 months in the no CN subgroup, respectively (P<0.001). Median OS from the start of first-line therapy was NR in patients who underwent CN and 22.4 months in the no CN subgroup (P<0.001). Patients who underwent CN reported longer OS compared to no CN in all the three geographical areas. CONCLUSIONS: No significant differences in terms of patients' outcome seem to clearly emerge, even if the rate CN and the choice of the type of first-line immune-based combination varies across the different Cancer Centers participating in the ARON-1 project.

Biological implications of long-term anthelmintic treatment: what else besides resistance are we selecting for?

Long-term intensive use of anthelmintics for parasite control of livestock, companion animals, and humans has resulted in widespread anthelmintic resistance, a problem of great socioeconomic significance. But anthelmintic therapy may also select for other biological traits, which could have implications for anthelmintic performance. Here, we highlight recent examples of changing parasite dynamics following anthelmintic administration, which do not fit the definition of anthelmintic resistance. We also consider other possible examples in which anthelmintic resistance has clearly established, but where coselection for other biological traits may have also occurred. We offer suggestions for collecting more information and gaining a better understanding of these phenomena. Finally, we propose research questions that require further investigation and make suggestions to help address these knowledge gaps.

Does the Nightmare of Distressing Complications of Groin Dissection Over with "River Flow" Incision? - Experience of 240 Dissections from Tertiary Referral Oncology Centre, India.

OBJECTIVE: Groin dissection has been a nightmare for many surgeons due to its higher morbidity especially flap necrosis. Various modifications in incisions have been described in the literature to reduce the complications but with variable outcomes. By our novel "River Flow" incision technique, we have significantly reduced the procedure related complications without compromising onco surgical principles. METHODS: A prospective longitudinal clinical observational study was designed after Institutional Ethical Committee clearance, aiming to minimize the rate of complications, especially flap necrosis. All patients who underwent unilateral/bilateral ilio-inguinal block dissection (IIBD) from January 2014 to December 2021 were included in the study. The "River Flow" incision was made and standard ilio-inguinal block dissection was performed. Flap viability, seroma formation, lymphedema, infection, etc. were observed and noted during hospitalization and on followup. Clavien- Dindo classification was used to grade the postoperative complications. We have taken our historical data of 235 groin dissections as a control and compared them with the results of the present study. It is one of the largest studies on groin dissection so far. RESULTS: A total of 138 patients underwent 240 groin dissections. The most common diagnosis was carcinoma penis (44.9%) followed by carcinoma vulva (22.4%). Overall, the outcome of all groin dissections showed no postoperative mortality. None of the patients had complete flap necrosis. But in our historical data, the flap necrosis rate was 38%. The most common complication observed was seroma formation in 13.7% of cases followed by surgical site infection (6.52%). All the complications were managed conservatively. The postoperative stay of the patients was also significantly less. The median hospital stay was 3 days. CONCLUSION: "River Flow" incision technique is a simple but effective novel surgical technique for therapeutic ILND for any surgical setup without the learning curve. It can avoid flap necrosis, and decrease morbidity significantly without compromising the onco surgical principle of standard groin dissection. KEY WORDS: Groin dissection, skin necrosis, river flow incision.

Pattern of Care in Real-World Scenario on Advanced Epithelial Ovarian Cancer in a Tertiary Referral Oncology Centre in India - ISPSM Collaborative Study.

The treatment of advanced epithelial ovarian cancer (EOC) has evolved over time. With advent of platinum-based chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC), there is a paradigm shift in the patterns of care with improved survival. In this study, we analysed our advanced EOC patients aiming to gain insights into the pattern of care. An ambispective study of 250 patients of advanced EOC was done from our prospectively maintained computerised database in the Department of Surgical Oncology, tertiary care referral centre from 2013 to 2020. We analysed the demographic profile, treatment patterns, and perioperative outcomes. In this study, there were 83.6% stage III and 16.4% stage IVA. There were 62 (24.8%) upfront and 112 (44.8%) in interval settings. There was a higher number of patients receiving neo-adjuvant chemotherapy. One hundred twenty-six (50.4%) underwent cytoreductive surgery (CRS) only and 124 (49.6%) underwent CRS and HIPEC. CC-0 was achieved in 84.4% and CC-1 in 15.6% patients. HIPEC programme was started in 2013. With advent of RCTs in HIPEC, there was a substantial increase in the number of patients receiving HIPEC from 2015 (n = 10), 2017 (n = 20) to 2019 (n = 41). We offer secondary CRS in a limited subset of patients, n = 76 (30.4%). There was 24.8% early and 8.4% late postop complications. We have median follow-up of 50 months with attrition rate of 4%. With practice changing updates, the treatment of advanced EOC has been evolving over time. Though the primary CRS followed by systemic therapy is the standard to date, there is change in pattern of care with neo-adjuvant chemotherapy followed by interval CRS and HIPEC because of various RCTs. The addition of HIPEC has acceptable morbidity and mortality. There is a definite learning curve and the team has to evolve as a whole. In a tertiary care referral centre from LMIC, good patient selection, logistics, and implementing recent advances will definitely add to improved survival.

Can EPIC Be a Low-Cost Alternative to HIPEC in Advanced Epithelial Ovarian Cancer in Resource-Constraint Settings? Experience from Tertiary Care Oncology Center.

Management of advanced ovarian cancer underwent a paradigm shift with advent of cytoreductive surgery and intraperitoneal chemotherapy. Hyperthermic intraperitoneal chemotherapy requires complex machinery and costly disposables, and increased operative time. Early postoperative intraperitoneal chemotherapy is a relatively less resource-intensive alternative way of intraperitoneal drug delivery. We started our HIPEC programme in 2013. In select cases, we offer EPIC. This study is an audit of outcomes to look into the feasibility of EPIC as alternative to HIPEC. We performed analysis of prospectively maintained database in the Department of Surgical oncology from January 2019 to June 2022. We had 15 patients who underwent CRS + EPIC and 84 CRS+ HIPEC. We did a propensity-matched analysis for demographics, baseline data and PCI and compared 15 CRS + EPIC with 15 CRS + HIPEC patients. We compared the perioperative outcomes-morbidity, mortality, length of ICU and hospital stay. Procedure time was significantly higher in the HIPEC compared to EPIC as HIPEC is an intraoperative procedure. Patients were admitted to intensive care unit (ICU) after surgery for a longer mean duration in HIPEC arm (1.4 + 0.7 days) compared to EPIC arm (1.2 + 0.41 days). Patients in HIPEC arm had a significantly shorter hospital stay (mean 7.93 vs. 9.93 days. Four patients in EPIC arm had Clavien-Dindo grade 3 and 4 morbidity compared to 1 patient in HIPEC arm. Hematological toxicity was more common in EPIC group. CRS with EPIC can be explored as an alternative to HIPEC in centres lacking facilities and expertise for HIPEC.

Sleep disorders related to index and comorbid mental disorders and psychotropic drugs.

PURPOSE: Mental disorders positively associate with sleep disorders. This study will explore the moderating influence of comorbid mental disorders and whether selected psychotropic drugs correlate with sleep disorders after adjusting for mental disorders. METHODS: A retrospective cohort study design was employed using medical claim data from the Deseret Mutual Benefit Administrators (DMBA). Mental disorders, psychotropic drug use, and demographic data were extracted from claim files for ages 18-64, years 2016-2020. RESULTS: Approximately 11.7% filed one or more claims for a sleep disorder [insomnia (2.2%) and sleep apnea (9.7%)]. Rates for selected mental disorders ranged from 0.09% for schizophrenia to 8.4% for anxiety. The rate of insomnia is greater in those with bipolar disorder or schizophrenia than in other mental disorders. The rate of sleep apnea is greater in those with bipolar disorder and depression. There is a significantly positive association between mental disorders and insomnia and sleep apnea, more so for insomnia, especially if they had other comorbid mental disorders. Psychotropic drugs other than CNS stimulants, primarily sedatives (non-barbiturate) and psychostimulants, explain much of the positive association between anxiety, depression, and bipolar disorder with insomnia. Psychotropic drugs with the largest effect on sleep disorders are sedatives (non-barbiturate) and psychostimulants for insomnia and psychostimulants and anticonvulsants for sleep apnea. CONCLUSION: Mental disorders positively correlate with insomnia and sleep apnea. The positive association is greater when multiple mental illness exists. Bipolar disorder and schizophrenia are most strongly associated with insomnia, and bipolar disorder and depression are most strongly associated with sleep disorders. Psychotropic drugs other than CNS stimulants, primarily sedatives (non-barbiturate) and psychostimulants for treating anxiety, depression, or bipolar disorder are associated with higher levels of insomnia and sleep apnea.

Broad-Spectrum Inhibitors for Conserved Unique Phosphoethanolamine Methyltransferases in Parasitic Nematodes Possess Anthelmintic Efficacy.

In humans, nematode infections are prevalent in developing countries, causing long-term ill health, particularly in children. Worldwide, nematode infections are prevalent in livestock and pets, affecting productivity and health. Anthelmintic drugs are the primary means of controlling nematodes, but there is now high prevalence of anthelmintic resistance, requiring urgent identification of new molecular targets for anthelmintics with novel mechanisms of action. Here, we identified orthologous genes for phosphoethanolamine methyltransferases (PMTs) in nematodes within the families Trichostrongylidae, Dictyocaulidae, Chabertiidae, Ancylostomatoidea, and Ascarididae. We characterized these putative PMTs and found that they possess bona fide PMT catalytic activities. By complementing a mutant yeast strain lacking the ability to synthesize phosphatidylcholine, the PMTs were validated to catalyze the biosynthesis of phosphatidylcholine. Using an in vitro phosphoethanolamine methyltransferase assay with PMTs as enzymes, we identified compounds with cross-inhibitory effects against the PMTs. Corroboratively, treatment of PMT-complemented yeast with the PMT inhibitors blocked growth of the yeast, underscoring the essential role of the PMTs in phosphatidylcholine synthesis. Fifteen of the inhibitors with the highest activity against complemented yeast were tested against Haemonchus contortus using larval development and motility assays. Among them, four were found to possess potent anthelmintic activity against both multiple drug-resistant and susceptible isolates of H. contortus, with IC50 values (95% confidence interval) of 4.30 µM (2.15-8.28), 4.46 µM (3.22-6.16), 28.7 µM (17.3-49.5), and 0.65 µM (0.21-1.88). Taken together, we have validated a molecular target conserved in a broad range of nematodes and identified its inhibitors that possess potent in vitro anthelmintic activity.