Neurotoxic stimulation alters prosaposin levels in the salivary systems of rats.

Prosaposin (PSAP), a potent neurotrophic factor, is found in neuronal and non-neuronal tissues and various biological fluids. Neuropathological conditions often alter PSAP production in neural tissues. However, little is known about its alterations in non-neural tissues, particularly in the salivary glands, which are natural reservoirs of various neurotrophic factors. In this study, we explored whether neurotoxic stimulation by kainic acid (KA), a glutamate analog, altered PSAP levels in the salivary system of rats. The results revealed that KA injection did not alter total saliva production. However, KA-induced neurotoxic stimulation significantly increased the PSAP level in the secreted saliva but decreased it in the serum. In addition, KA-induced elevated immunoreactivities of PSAP and its receptors have been observed in the granular convoluted tubule (GCT) cells of the submandibular gland (SMG), a major salivary secretory organ. Indeed, a large number of PSAP-expressing immunogold particles were observed in the secretory granules of the SMG. Furthermore, KA-induced overexpression of PSAP was co-localized with secretogranin in secretory acini (mostly in GCT cells) and the ductal system of the SMG, suggesting the release of excess PSAP from the salivary glands into the oral cavity. In conclusion, the salivary system produces more PSAP during neurotoxic conditions, which may play a protective role in maintaining the secretory function of the salivary glands and may work in distant organs.

Prenatal exposure to a natural disaster and early development of psychiatric disorders during the preschool years: stress in pregnancy study.

BACKGROUND: Growing evidence shows an association between in utero exposure to natural disasters and child behavioral problems, but we still know little about the development of specific psychopathology in preschool-aged children. METHODS: Preschool children (n = 163, mean age = 3.19, 85.5% racial and ethnic minorities) and their parents (n = 151) were evaluated annually at ages 2-5 to assess the emergence of psychopathology using the Preschool Age Psychopathological Assessment (PAPA), a parent-report structured diagnostic interview developed for preschool-age children. Sixty-six (40.5%) children were exposed to Sandy Storm (SS) in utero and 97 (59.5%) were not. Survival analysis evaluated patterns of onset and estimated cumulative risks of psychopathology among exposed and unexposed children, in total and by sex. Analyses were controlled for the severity of objective and subjective SS-related stress, concurrent family stress, and demographic and psychosocial confounders, such as maternal age, race, SES, maternal substance use, and normative prenatal stress. RESULTS: Exposure to SS in utero was associated with a substantial increase in depressive disorders (Hazard Ratio (HR) = 16.9, p = .030), anxiety disorders (HR = 5.1, p < .0001), and attention-deficit/disruptive behavioral disorders (HR = 3.4, p = .02). Diagnostic rates were elevated for generalized anxiety disorder (GAD; HR = 8.5, p = .004), attention-deficit/hyperactivity disorder (ADHD; HR = 5.5, p = .01), oppositional-defiant disorder (ODD; HR = 3.8, p = .05), and separation-anxiety disorder (SAD; HR = 3.5, p = .001). Males had distinctively elevated risks for attention-deficit/disruptive behavioral disorders (HR = 7.8, p = .02), including ADHD, CD, and ODD, whereas females had elevated risks for anxiety disorders (HR = 10.0, p < .0001), phobia (HR = 2.8, p = .02) and depressive disorders (HR = 30.0, p = .03), including SAD, GAD, and dysthymia. CONCLUSIONS: The findings demonstrate that in utero exposure to a major weather-related disaster (SS) was associated with increased risk for psychopathology in children and provided evidence of distinct psychopathological outcomes as a function of sex. More attention is needed to understand specific parent, child, and environmental factors which account for this increased risk, and to develop mitigation strategies.

Systematic review: emotion dysregulation and challenging behavior interventions for children and adolescents on the autism spectrum with graded key evidence-based strategy recommendations.

Challenging behavior, such as aggression, is highly prevalent in children and adolescents on the autism spectrum and can have a devastating impact. Previous reviews of challenging behavior interventions did not include interventions targeting emotion dysregulation, a common cause of challenging behavior. We reviewed emotion dysregulation and challenging behavior interventions for preschoolers to adolescents to determine which evidence-based strategies have the most empirical support for reducing/preventing emotion dysregulation/challenging behavior. We reviewed 95 studies, including 29 group and 66 single case designs. We excluded non-behavioral/psychosocial interventions and those targeting internalizing symptoms only. We applied a coding system to identify discrete strategies based on autism practice guidelines with the addition of strategies common in childhood mental health disorders, and an evidence grading system. Strategies with the highest quality evidence (multiple randomized controlled trials with low bias risk) were Parent-Implemented Intervention, Emotion Regulation Training, Reinforcement, Visual Supports, Cognitive Behavioral/Instructional Strategies and Antecedent-Based Interventions. Regarding outcomes, most studies included challenging behavior measures, while few included emotion dysregulation measures. This review highlights the importance of teaching emotion regulation skills explicitly, positively reinforcing replacement/alternative behaviors, using visuals and metacognition, addressing stressors proactively, and involving parents. It also calls for more rigorously designed studies and for including emotion dysregulation as an outcome/mediator in future trials.

Improvement of lipid profile and hepatic oxidative stress in high-fat-diet induced hyperlipidemic Swiss albino rats by Piper betle juice: evidences from in vivo and in silico studies.

Piper betle L. leaves are very popular and traditionally used to chew with betel nut in many Asian countries. In this study, P. betle leaves juice (PBJ) was subjected to evaluation for its antihyperlipidemic activity in the high-fat-diet-induced hyperlipidemic rats model. Swiss albino rats were allowed to high-fat- diet for one month, followed by concurrent administration of PBJ for another month. The rats were then sacrificed and collected blood, tissues and organs. Pharmacokinetic, toxicological studies and molecular docking studies were performed using SwissADME, admetSAR and schrodinger suit-2017. Our investigation showed a promising effect of PBJ on body weight, lipid profile, oxidative and antioxidative enzymes, and the principle enzyme responsible for the synthesis of cholesterol. PBJ at 0.5 - 3.0 mL/rat significantly reduced body weight of hyperlipidemic rats compared to control. PBJ at the doses of 1.0, 1.5, 2.0, and 3.0 mL/rat significantly (p<0.05, p<0.01, p<0.001) improved the levels of TC, LDL-c, TG, HDL-c and VLDL-c. Similarly, PBJ doses starting from 1.0 mL/rat to 3.0 mL/rat reduced the oxidative biomarkers AST, ALT, ALP, and creatinine. The level of HMG-CoA was significantly reduced by PBJ doses 1.5, 2, and 3 ml/rat. A number of compounds have been found to have good pharmacokinetic profile and safety and 4-coumaroylquinic acid exerted the best docking score among them. Thus our findings clearly demonstrated the potential lipid-lowering activities of PBJ both in vivo and in silico studies. PBJ can be a good candidate for the development of antihyperlipidemic medication or as an alternative medicine.

Glycoxidation of LDL Generates Cytotoxic Adducts and Elicits Humoral Response in Type 2 Diabetes Mellitus.

This study elucidates the immunological implications of methylglyoxal (MGO) modified LDL in diabetes type 2 patients (T2DM). Under in-vitro modifications, MGO altered the tertiary structure of LDL. TNBS and phenanthrenequinone assays confirmed lysine and arginine residues as main targets of MGO in LDL. HPLC and LCMS studies confirmed the generation of Nϵ-(carboxymethyl) lysine in the modified protein. Comet assay showing increased tail length of DNA in lymphocytes inferred the cytotoxicity of MGO-LDL. The easy penetration of MGO-LDL into the nucleus is possibly a consequence of its reduced size, post-modification, as observed from the studies on hydrodynamic radii studies in DLS experiments. MGO-LDL was found to be more immunogenic, as compared to native LDL, in immunological studies conducted on experimental rabbits. Our results reflect the presence of neo-antigenic determinants on modified LDL. Competitive inhibition ELISA suggested the presence of neo-epitopes with marked immunogenicity eliciting specific immune response. Binding studies on purified IgG confirmed the enhanced and specific immunogenicity of MGO-LDL. Studies on interaction of MGO-LDL with the circulating auto-antibodies from T2DM patients showed high affinity of serum-antibodies towards MGO-LDL. This study suggests a potent role of glycoxidatively modified LDL in the generation of auto-immune response in T2DM patients.

Illness-related suffering and need for palliative care in Rohingya refugees and caregivers in Bangladesh: A cross-sectional study.

BACKGROUND: Despite recognition that palliative care is an essential component of any humanitarian response, serious illness-related suffering continues to be pervasive in these settings. There is very limited evidence about the need for palliative care and symptom relief to guide the implementation of programs to alleviate the burden of serious illness-related suffering in these settings. A basic package of essential medications and supplies can provide pain relief and palliative care; however, the practical availability of these items has not been assessed. This study aimed to describe the illness-related suffering and need for palliative care in Rohingya refugees and caregivers in Bangladesh. METHODS AND FINDINGS: Between November 20 and 24, 2017, we conducted a cross-sectional study of individuals with serious health problems (n = 156, 53% male) and caregivers (n = 155, 69% female) living in Rohingya refugee camps in Bangladesh, using convenience sampling to recruit participants at the community level (i.e., going house to house to identify eligible individuals). The serious health problems, recent healthcare experiences, need for medications and medical supplies, and basic needs of participants were explored through interviews with trained Rohingya community members, using an interview guide that had been piloted with Rohingya individuals to ensure it reflected the specificities of their refugee experience and culture. The most common diagnoses were significant physical disabilities (n = 100, 64.1%), treatment-resistant tuberculosis (TB) (n = 32, 20.5%), cancer (n = 15, 9.6%), and HIV infection (n = 3, 1.9%). Many individuals with serious health problems were experiencing significant pain (62%, n = 96), and pain treatments were largely ineffective (70%, n = 58). The average age was 44.8 years (range 2-100 years) for those with serious health problems and 34.9 years (range 8-75 years) for caregivers. Caregivers reported providing an average of 13.8 hours of care per day. Sleep difficulties (87.1%, n = 108), lack of appetite (58.1%, n = 72), and lack of pleasure in life (53.2%, n = 66) were the most commonly reported problems related to the caregiving role. The main limitations of this study were the use of convenience sampling and closed-ended interview questioning. CONCLUSIONS: In this study we found that many individuals with serious health problems experienced significant physical, emotional, and social suffering due to a lack of access to pain and symptom relief and other essential components of palliative care. Humanitarian responses should develop and incorporate palliative care and symptom relief strategies that address the needs of all people with serious illness-related suffering and their caregivers.

The Psychosocial and Spiritual Experiences of Patients with Advanced Incurable Illness in Bangladesh: A Cross-Sectional Observational Study.

CONTEXT: The psychosocial and spiritual needs of individuals with life-limiting conditions in low- or middle-income countries have not been well described. Understanding these needs is important to providing holistic palliative care. AIM: This study aims to better understand the psychosocial and spiritual needs and supports of patients with advanced, incurable illness in Bangladesh. SUBJECTS AND METHODS: Individuals with advanced incurable illnesses (advanced cancer and HIV/AIDS) from a wide geographical distribution across Bangladesh were interviewed about their health status, emotional and spiritual experiences with their illness, coping and support systems, and greatest needs and fears. RESULTS: We interviewed 221 individuals with incurable cancer (82%) or HIV/AIDS (18%). Self-reported health status was poor or very poor for 48%, and 44% reported feeling unhappy all of the time. The majority (61%) rated their current level of unhappiness as 10/10. Spouses (50%), children (15%), and parents (13%) were the most common caregivers. Money and medical care were equally the most common needs (46%). Participants' greatest fears were for the future of their children (38%), being in pain (29%), and dying (28%). CONCLUSIONS: There is a significant burden of psychosocial and spiritual concerns among patients with advanced incurable illness in Bangladesh, with sadness being very frequent and of high intensity. Family and friends provide significant emotional and practical support to patients who are seriously ill, but very few patients access any professional support for these concerns.

Cluster Analysis of Symptoms of Bangladeshi Women with Breast Cancer.

BACKGROUND: Breast cancer (BC) patients may experience multiple symptoms due to the disease itself, cancer treatment or combination of both. AIM: The aim of the present study was to express multiple symptoms experienced by the patients with BC as clusters. METHODS: This was a retrospective study. We examined symptom profiles of 120 patients with BC who attended the Centre for Palliative Care, Bangabandhu Sheikh Mujib Medical University in Dhaka, Bangladesh, from January 2009 to December 2013. We included all case sheets of BC patients, which had documentation of needed information. Following symptoms were analyzed: pain, nausea, loss of appetite, constipation, weakness, cough, breathlessness, sleeplessness, lymphedema, sadness, anxiety, and depression. Hierarchical cluster analysis was used to identify the natural groupings within the set. RESULTS: We could identify three clusters, namely (1) "neuropsychiatric," (2) "gastro-respiratory," and (3) "miscellaneous" symptom clusters. The symptoms in cluster 2 comprised of cough, breathlessness, nausea, and constipation. Cluster 1 was characterized by pain, depression, anxiety, weakness, sleeplessness, and loss of appetite. Cluster 2 was comprised of cough, breathlessness, nausea, and constipation. Cluster 3 consisted of two symptoms lymphedema and sadness. The results revealed that the multiple symptoms of patients with BC experienced had been clustered together. Neuropsychiatric symptoms and weakness formed a significant strong relationship with each other. CONCLUSION: Knowledge obtained from this study could be beneficial for better understanding, assessment, and management of symptom clusters in women with BC. It may also help patients to plan ahead for them to seek management of concurrent symptoms to improve their quality of life.

Symptom Prevalence in Patients with Advanced, Incurable Illness in Bangladesh.

CONTEXT: There is a significant need for palliative care for patients living in low- and middle-income countries. The presence and intensity of physical symptoms is a major factor influencing the suffering of patients at the end of life. OBJECTIVES: The primary aim of this study was to determine the prevalence and characteristics of common physical symptoms experienced by patients with advanced, incurable illness in a developing country. METHOD: This study used semi-structured interviews in patients with advanced cancer or HIV/AIDS in Bangladesh. RESULTS: Pain was the most common symptom (70.6%) and was frequently reported to be severe (62.6%). Very few patients received strong opioids to treat their pain (13.7%). Other frequent symptoms included loss of appetite (23.5%) and fever (19.9%). The average number of physical symptoms reported was 3 (range: 0-23). The majority of patients rated their most recent symptom (excluding pain) as severe (64.3%), with 35.8% continuing to have severe symptom intensity despite treatment. CONCLUSIONS: This study reveals the significant burden of symptoms, and the associated suffering for patients living with incurable illness, in a developing country. Very few patients received strong opioids, despite frequently having severe pain. Frequently, the treatments that patients received did not alleviate their symptoms. Palliative care is vital for the relief of suffering for patients with advanced and incurable diseases, especially in low- and middle-income countries where access to curative treatments may be limited and patients often present to medical personnel when their illness is in an advanced stage or incurable.

Structural changes in histone H2A by methylglyoxal generate highly immunogenic amorphous aggregates with implications in auto-immune response in cancer.

The role of aberrant protein modifications in cancer and its diagnosis have emerged as a promising research field. Nonenzymatic glyco-oxidation of proteins under oxidative stress has been associated with carcinogenesis through advanced glycation end products (AGE)-receptors for advanced glycation end products (RAGE) axis. Modified proteins that are immunogenic and stimulate cellular and humoral immune responses are being studied to develop early detection markers of cancer. This study has probed the structural alternations; leading to the formation of adducts and aggregates, in histone H2A upon in vitro modification by methylglyoxal (MG). The immunogenicity of modified histone H2A and its binding with cancer autoantibodies was also assessed. MG induced lysine side chain modifications, blocking of free amino groups and the formation of condensed cross structures in histone H2A; and its effect was inhibited by carbonyl scavengers. It led to the adduct formation and generation of N-epsilon-(carboxyethyl)lysine (CEL) and its decomposition forms as revealed by Matrix-assisted laser desorption ionization-mass spectrometry, high-performance liquid chromatography and LC-MS. MG-H2A showed amorphous aggregate formation under electron microscopy and altered binding with DNA in circular dichroism studies. The modified histone elicited high titer immunogen-specific antibodies in rabbits when compared with the native, thus pointing toward the generation of neo-epitopes in MG-H2A. The autoantibodies derived from cancer patients exhibited enhanced binding with MG-H2A as compared with the native histone in enzyme-linked immunosorbent assay and gel retardation assay. This reflects sharing of epitopes on MG-H2A and histones in cancer patients. The neo-epitopes on H2A may be responsible for induction and elevated levels of antibodies in cancer patients. Thus, MG-H2A may be considered as potential antigenic candidate for auto-immune response in cancer.

Pretreatment and co-administration of oral anti-diabetic agent with clomiphene citrate or rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome.

AIM: The objective of this study was to explore the result of pretreatment and concomitant use of metformin with clomiphene citrate (CC) and rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: This randomized controlled trial was done in the Dhaka Medical College and Hospital and the Infertility Care and Research Centre, Dhaka, Bangladesh. A total of 165 infertile patients with CC-resistant PCOS who attended for treatment were the target population for this study. Patients were divided into three groups: groups A and B were given metformin and group C was the control. Along with metformin, group A received CC and group B received rFSH. Group C was treated with only rFSH. Metformin was given 1500 mg daily for 4 weeks. Afterwards CC or rFSH were added for induction of ovulation along with metformin. Six ovulatory cycles were assessed. Treatment was terminated when there was no response with maximum dose of CC and rFSH or after six ovulatory cycles without pregnancy or after achieving pregnancy. A P-value of <0.5 was considered as significant. RESULTS: Ovulation (89.09%) and pregnancy (54.55%) rates were higher in group B. Ovulation (74.55%) and pregnancy (29.09%) rates were also satisfactory in group C but a dose of rFSH requirement was significantly higher (P = 0.000). In group A, both ovulation and pregnancy rate were much lower than the other two groups (27.27% and 12.73%, respectively). CONCLUSIONS: Use of metformin increases the response of ovulation-inducing agents and can be used safely in PCOS.

Exploring the self-preparedness of frontline healthcare workers in a low- and middle-income country from a humanitarian context during the COVID-19 pandemic: A constructivist grounded theory study.

Background: While research has been conducted on the availability, accessibility, and affordability of personal protective equipment for healthcare workers during the COVID-19 pandemic, little information is available on the ways in which health workers, especially those in humanitarian settings see themselves, and engage in self-preparedness for social, physical, and mental health and practical care in the pandemic. We sought to address this gap. Methods: We followed a constructivist grounded theory approach to guide in-depth interviews with 30 frontline doctors, nurses, and community healthcare workers recruited from the Rohingya refugee camps in Bangladesh using the purposive and snowball sampling methods. Analyses were carried out through the identification of codes in three phases: an initial line-by-line open coding, then focused axial coding, and finally selective coding. Findings: An emergent-grounded theory of "Navigating Self-Preparedness through Pandemics" was developed as we built a five-phased theoretical framework examining health worker responses with the following pillars: (a) pandemic shock; (b) pandemic awareness; (c) pandemic learning; (d) pandemic resilience, and (e) pandemic resurgence. Interpretation: The theory emerged as a realistic, socially, and culturally sensitive COVID-19 strategy to support healthcare workers. Self-preparedness was characterized by two interwoven processes: (1) the experiences of the daily life span of healthcare workers attempting to improve their own protection using all their potential while providing care for patients in a vulnerable setting and time and (2) the inseparable role of physical, psychological, social, and spiritual factors in each stage of learning during the pandemic to achieve better outcomes.

A randomized control trial to support smoke-free policy compliance in public housing.

BACKGROUND: Smoke-free housing policies in multiunit housing are increasingly widespread interventions to reduce smoking and secondhand smoke exposure. Little research has identified factors that impede compliance with smoke-free housing policies in low-income multiunit housing and test corresponding solutions. METHODS: We are using an experimental design to test two compliance support interventions: (A) a "compliance through reduction (via relocation and reduction in personal smoking) and cessation" intervention targets households with smokers and involves support to shift smoking practices to areas beyond the apartment or building setting, reduce personal smoking, and deliver in-residence smoking cessation support services via trained peer educators and (B) a "compliance through resident endorsement" intervention involving voluntary adoption of smoke-free living environments through personal pledges, visible door markers, and/or via social media. We will compare randomly sampled participants in buildings that receive A or B or A plus B to the NYCHA standard approach. DISCUSSION: This RCT addresses key gaps in knowledge and capitalizes on key scientific opportunities by (1) leveraging the federal mandate to ban smoking in a public housing system of more than sufficient size to conduct an adequately powered RCT; (2) expanding our understanding of smoke-free policy compliance beyond policy implementation by testing two novel treatments: (a) in-residence smoking cessation and (b) resident endorsement, while (3) addressing population and location-specific tobacco-related disparities. At the conclusion of the study, this RCT will have leveraged a monumental policy shift affecting nearly half a million NYC public housing residents, many of whom disproportionately experience chronic illness and are more likely to smoke and be exposed to secondhand smoke than other city residents. This first-ever RCT will test the effects of much-needed compliance strategies on resident smoking behavior and secondhand smoke exposure in multiunit housing. TRIAL REGISTRATION: Clinical Trials Registered, NCT05016505. Registered on August 23, 2021.

A Randomized Control Trial to support smoke-free policy compliance in public housing.

• Background Smoke-free housing policies in multiunit housing are increasingly widespread interventions to reduce smoking and secondhand smoke exposure. Little research has identified factors that impede compliance with smoke-free housing policies in low-income multiunit housing and test corresponding solutions. • Methods We are using an experimental design to test two compliance support interventions: (A) a "compliance through reduction (via relocation and reduction in personal smoking) and cessation" intervention targets households with smokers and involves support to shift smoking practices to designated areas, reduce personal smoking, and deliver in-residence smoking cessation support services via trained peer educators and (B) a "compliance through resident endorsement" intervention involving voluntary adoption of smoke-free living environments through personal pledges, visible door markers and/or via social media. We will compare randomly sampled participants in buildings that receive A or B or A plus B to the NYCHA standard approach, • Discussion This RCT addresses key gaps in knowledge and capitalizes on key scientific opportunities by: 1) leveraging the federal mandate to ban smoking in a public housing system of more than sufficient size to conduct an adequately powered RCT; 2) expanding our understanding of smoke-free policy compliance beyond policy implementation by testing two novel treatments: a) in-residence smoking cessation and b) resident endorsement, while 3) addressing population and location-specific tobacco-related disparities. At the conclusion of the study, this RCT will have leveraged a monumental policy shift affecting nearly half a million NYC public housing residents, many of whom disproportionately experience chronic illness and are more likely to smoke and be exposed to secondhand smoke than other city residents. This first-ever RCT will test the effects of much-needed compliance strategies on resident smoking behavior and secondhand smoke exposure in multiunit housing. Trial registration: Clinical Trials Registered, NCT05016505 Registered: August 23, 2021 https://clinicaltrials.gov/ct2/show/NCT05016505.

Administration of prosaposin-derived neurotrophic factor to neural tube defects facilitates regeneration and restores neurological functions.

Neural tube defects (NTDs) cause fetal and pediatric deaths or lifelong neurological disabilities. No effective treatment is currently available for NTDs. We attempted to elucidate the pathogenesis of NTDs and propose a therapeutic strategy. Intra-amniotic treatment with prosaposin-derived 18-mer peptide (PS18) protected the spinal cord from secondary damage and rescued neurological function in an established chicken model of spina bifida aperta (SBA), the severe type of NTDs. PS18 promoted the formation of a neuroectodermal covering over the defective neural tube within 24-h after treatment, enhanced the regeneration/restoration process, and decreased apoptotic activity in the developing spinal cord. PS18 reduced the SBA wound and almost completely formed the spinal cord. SBA chicks that received PS18 exhibited relatively normal walking and sensorimotor responses, and reduced pain-associated behavior in postnatal life. In conclusion, PS18 is a promising therapeutic agent for NTDs and may be useful for treating other types of spinal cord injuries.

Tracking of Prosaposin, a Saposin Precursor, in Rat Testis.

We tracked prosaposin (PSAP), a trophic factor, using an antibody specific to its proteolytic portion and an antibody to sortilin that traffics PSAP only to the lysosome. Immunostaining revealed that PSAP was distributed mainly on the basal side of seminiferous tubules, where many Sertoli cells and pachytene spermatocytes contained PSAP and its distribution differed depending on the stage of the spermatogenic cycle. The PSAP-sortilin complex was sorted to large lysosomes in the basal cytoplasm of Sertoli cells, where it may be processed into saposins. In contrast, in the thinner apical cytoplasm of Sertoli cells, PSAP in small lysosomes was transported to the apical side around sperm heads or into the lumen for secretion. The results of in situ hybridization analyses suggested that immature tubular cells in young animals produce PSAP to self-stimulate proliferation. However, in adults, not only Sertoli cells but also pachytene spermatocytes produce and secrete PSAP around germ cells or into the tubular lumen to stimulate cell proliferation or differentiation in a paracrine or autocrine manner. In summary, PSAP is not only a precursor of lysosomal enzymes but also a pivotal trophic factor in organogenesis in the immature testis and spermatogenesis in the mature testis.

Systematic Review: Emotion Dysregulation and Challenging Behavior Interventions for Children andAdolescents with Autism with Graded Key Evidence-Based Strategy Recommendations.

Challenging behavior, such as aggression, is highly prevalent in children and adolescents with autism and can have a devastating impact. Previous reviews of challenging behavior interventions did not include interventions targeting emotion dysregulation, a common cause of challenging behavior. We reviewed emotion dysregulation and challenging behavior interventions for preschoolers to adolescents to determine which evidence-based strategies have the most empirical support for reducing/preventing emotion dysregulation/challenging behavior. We reviewed 95 studies, including 29 group and 66 single-case designs. We excluded non-behavioral/psychosocial interventions and those targeting internalizing symptoms only. We applied a coding system to identify discrete strategies based on autism practice guidelines with the addition of strategies common in childhood mental health disorders, and an evidence grading system. Strategies with the highest quality evidence (multiple randomized controlled trials with low bias risk) were Parent-Implemented Intervention, Emotion Regulation Training, Reinforcement, Visual Supports, Cognitive Behavioral/Instructional Strategies and Antecedent-Based Interventions. Regarding outcomes, most studies included challenging behaviors measures while few included emotion dysregulation measures. This review highlights the importance of teaching emotion-regulation skills explicitly, positively reinforcing replacement/alternative behaviors, using visuals and metacognition, addressing stressors proactively, and involving parents. It also calls for more rigorously-designed studies and for including emotion dysregulation as an outcome/mediator in future trials.

Acute ischemic strokes in patients with developmental disabilities: A cross-sectional analysis.

OBJECTIVE: Patients with developmental disabilities (DD) are frequently excluded from acute ischemic stroke (AIS) randomized control trials. We sought to evaluate the impact of having DD on this patient cohort. METHODS: The National Inpatient Sample was analyzed to explore the impact of AIS and treatment on discharge dispositions in patients with DD. Clinical characteristics, treatments, and outcomes were compared to fully-abled patients with AIS. RESULTS: 1,605,723 patients with AIS were identified from 2010-2019, of whom 4094 (0.30%) had a DD. AIS patients with DD were younger (60.31 vs 70.93 years, p < 0.01), less likely to be Caucasian (66.37%vs 68.09%, p = 0.01), and had higher AIS severity (0.63 vs 0.58, p < 0.01). Tissue plasminogen activator (tPA) was administered in 99,739 (6.2%) fully-abled patients and 196 (4.79%) of patients with DD (p < 0.01). Endovascular thrombectomy (EVT) was performed in 21,066 (1.31%) of fully-abled patients and 35 (0.85%) of patients with DD (p < 0.01). The presence of developmental disabilities were predictive of lower rates of tPA (OR:0.71,CI:0.56-0.87,p < 0.01) and EVT (OR:0.24,CI:0.16-0.36,p < 0.01). In a propensity score-matched cohort of all AIS patients who underwent EVT, there was no difference in functional outcome (p = 0.41), in-hospital mortality (0.10), and LOS (p = 0.79). CONCLUSION: AIS patients with DD were less likely to receive tPA and EVT compared to fully-abled patients. Individuals with DD had higher mortality and worse discharge disposition. There was no significant difference in post-EVT outcomes between fully-abled patients and patients with developmental disabilities. In the absence of prospective clinical trials, population based cross-sectional analyses such as the present study provide valuable clinical insight.

Aneurysmal Subarachnoid Hemorrhage and Cardiac Related Fatality: Who Dies and Why?

Medical complications are a notable source of in-hospital death following aneurysmal subarachnoid hemorrhage (aSAH). However, there is a paucity of literature examining medical complications on a national scale. This study uses a national dataset to analyze the incidence rates, case fatality rates, and risk factors for in-hospital complications and mortality following aSAH. We found that the most common complications in aSAH patients (N = 170, 869) were hydrocephalus (29.3%) and hyponatremia (17.3%). Cardiac arrest was the most common cardiac complication (3.2%) and was associated with the highest case fatality rate overall (82%). Patients with cardiac arrest also had the highest odds of in-hospital mortality [odds ratio (OR), 22.92; 95% confidence interval (CI), 19.24-27.30; P < 0.0001], followed by patients with cardiogenic shock (OR, 2.96; 95% CI, 2.146-4.07; P < 0.0001). Advanced age and National Inpatient Sample-SAH Severity Score were found to be associated with an increased risk of in-hospital mortality (OR, 1.03; 95% CI, 1.03-1.03; P < 0.0001 and OR, 1.70; 95% CI, 1.65-1.75; P < 0.0001, respectively). Renal and cardiac complications are significant factors to consider in aSAH management, with cardiac arrest being the strongest indicator of case fatality and in-hospital mortality. Further research is needed to characterize factors that have contributed to the decreasing trend in case fatality rates identified for certain complications.