Subset Of Individuals Research Articles

Acceptability of multi-level sexual health interventions and sexually transmitted infection screening and testing among persons with HIV across three clinical sites in Florida.

The US state of Florida has the third highest rate of HIV as well as high rates of sexually transmitted infections (STIs) indicating critical HIV and STI prevention needs remain unmet. To address gaps in the STI care continuum in people with HIV (PWH), evidence-based interventions were implemented across three Ryan White HIV/AIDS Program (RWHAP) funded clinics in Florida between August 2020-August 2021. Interventions included comprehensive sexual health history (SHH) taking using audio computer-assisted self-interview (ACASI) software, self-collected extragenital gonorrhea and chlamydia testing, and the introduction of a lesbian, gay, bisexual, transgender, and queer (LGBTQ+) welcoming environment. We 1) assessed the acceptability of these interventions and examined if acceptability differed among youth and sexual, racial and ethnic minorities, 2) determined the proportion of appropriate STI testing completed based on the SHH assessment, 3) examined whether STI at-risk individuals underwent STI screening 3-6 months after initial evaluation, and 4) determined the proportion of positive STI test results among priority intervention groups in Florida. Acceptability of all interventions was high. Youth, lesbian, gay, and bisexual, and Hispanic individuals were significantly more likely to notice and like LGTBQ+ welcoming measures. The proportion of recommended tests completed was high, although only a subset of at-risk individuals completed re-screening. 11.9% of rectal samples were positive for chlamydia and 6.5% of pharyngeal samples were positive for gonorrhea. Our study highlights the importance of incorporating comprehensive sexual health care protocols, including extragenital STI testing, into the overall care of PWH.

Traumatic Brain Injury and Risk of Incident Dementia: Forensic Applications of Current Research.

Traumatic Brain Injury (TBI) has been identified as a risk factor for later developing neurodegenerative disorders, and there has been significant attention on this association in forensic settings. As a result, forensic neuropsychologists are frequently asked to comment on risk for dementia after an alleged TBI in litigation and criminal cases. This article provides an evidence-based foundation to aid forensic practice by synthesizing comprehensive information pertaining to: (i) the role of the neuropsychologist in TBI-related litigation, (ii) the complexities associated with identifying TBIs in forensic cases, (iii) the science of TBI in relation to incident dementia, and (iv) current scientific evidence for chronic traumatic encephalopathy. Developing a neurodegenerative disorder after TBI is the exception rather than the rule. Prevalence rates suggest that only a small subset (< 5%) of individuals with moderate-to-severe TBI, and even fewer (< 1%) with mild TBI (mTBI), appear to develop certain neurodegenerative diseases, and the characteristics that place some at risk remain unclear. The literature is mixed in terms of identifying a relationship between mTBI and later-in-life dementia risk. Also, the quality of positive evidence for risk of dementia after mTBI is weak and mostly consists of observational studies characterized by methodological limitations. Methods used to establish the likely occurrence of a TBI in a forensic context are typically more extensive than those used in a routine clinical evaluation. Research methodology to define TBI is often even more rudimentary and inconsistent. Applying clinical research results of TBI and dementia outcomes to forensic cases at an individual level carries significant limitations. Estimating the contribution of remote head hits or concussion in a causal manner to dementia is a challenge forensic experts sometimes face, yet at present, the task is impossible beyond correlations and speculation.

COVID-19 vaccination survey and anti-SARS-CoV-2 IgG responses in a human cohort from Schistosoma mansoni-endemic villages in Mayuge District, Uganda: a cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in devastating health and economic consequences worldwide. Vaccination has been a central pillar for COVID-19 prevention and control. Understanding the immunomodulatory effects of helminth infections on COVID-19 vaccine-induced immune responses and vaccine efficacy is crucial to the development and deployment of effective vaccination strategies in low- and middle-income countries with a high prevalence of worms. In September 2022, we conducted a cross-sectional, population-based survey in five Schistosoma mansoni endemic villages in Mayuge District, Uganda (n = 450). The prevalence of schistosomiasis and soil-transmitted helminths was determined by the Kato-Katz (KK) technique on two stool samples collected from each participant. A subset of individuals (n = 204) were interviewed in a COVID-19 vaccination survey. IgG levels against the SARS-CoV-2 spike S1 subunit (anti-S1 IgG) were measured by enzyme-linked immunosorbent assay (ELISA) in collected serum samples. The overall schistosomiasis and hookworm prevalence rates in the five villages were 36.4% (166/450) and 36.9% (168/450), respectively. Within the cohort, 69.78% (314/450) of the subjects had a positive anti-S1 IgG response. COVID-19 vaccination coverage among the interviewed participants was 93.14% (190/204; 95% CI, 88.8% - 95.9%). However, 81% (154/190) of COVID-19 vaccinees had an anti-S1 IgG titre ≤200. In an adolescent group receiving a single dose of the BNT162b2 mRNA vaccine (n = 23), an inverse correlation was observed between anti-S1 IgG antibody level/titre and faecal egg count. Within the above group, anti-S1 IgG levels/titres were significantly lower in subjects with moderate or heavy S. mansoni infection (n = 5) than those in KK-negative individuals (n = 9). Although the acceptance rate of COVID-19 vaccination was high, the majority of participants received only a single vaccine dose and the overall anti-S1 IgG titres in confirmed vaccinees were low. Moderate-to-heavy schistosome infections blunted the antibody responses following vaccination with a single dose of BNT162b2. These observations confirm the necessity for a second COVID-19 vaccine dose for two-dose primary immunization series and call for implementation research that may inform the development of a 'treat and vaccinate' policy during vaccination roll-out in regions with heavy worm burdens.

Morphological and molecular data demonstrate the existence of Betula fruticosa and B. middendorffii and the absence of B. ovalifolia in northeastern China

Abstract Shrub birches are important components of massive wetlands in Northeast China, although much of these habitats have been lost over the past two decades. However, the taxonomy of shrub birches has been ambiguous owing to their morphological variation. In this study, we incorporated morphological and molecular data to address the taxonomic challenges associated with shrub birches. We characterized the morphological variation in the leaves, seeds, and bracts of 11 shrub birch populations in Northeast China and a population of Betula ovalifolia in northern Japan. We genotyped birch individuals from Northeast China at 15 microsatellite loci as well as a subset of individuals, using restriction site-associated DNA sequencing (RAD-seq). The populations in Northeast China consisted of B. fruticosa and B. middendorffii. These two species and B. ovalifolia differ in the width of their seed wings and the angle between the side lobes of their bracts, despite substantial intraspecific variation. Our genetic data revealed two distinct clusters, corresponding to B. fruticosa and B. middendorffii. Ploidy level assessment via RAD-seq revealed that B. fruticosa is diploid and B. middendorffii is tetraploid. Phylogenetic analysis revealed that B. fruticosa formed a sister clade to diploid B. humilis, and B. middendorffii formed a clade with diploid B. nana. Our results indicate the existence of B. fruticosa and B. middendorffii and the probable absence of B. ovalifolia in the northern Daxing’an Range, as all the tetraploid individuals sampled there represented B. middendorffii. In addition, our results suggest that B. humilis and B. nana may have served as diploid parents of the tetraploid species B. ovalifolia and B. middendorffii, respectively.

Investigating frank autism: clinician initial impressions and autism characteristics

Background“Frank autism,” recognizable through the first minutes of an interaction, describes a behavioral presentation of a subset of autistic individuals that is closely tied to social communication challenges, and may be linked to so-called “prototypical autism.” To date, there is no research on frank autism presentations of autistic adolescents and young adults, nor individuals diagnosed with autism spectrum disorder (ASD) in childhood who do not meet diagnostic criteria during or after adolescence (loss of autism diagnosis, LAD). In addition, there are currently no data on the factors that drive frank autism impressions in these adolescent groups.MethodsThis study quantifies initial impressions of autistic characteristics in 24 autistic, 24 LAD and 26 neurotypical (NT) individuals ages 12 to 39 years. Graduate student and expert clinicians completed five-minute impressions, rated confidence in their own impressions, and scored the atypicality of behaviors associated with impressions; impressions were compared with current gold-standard diagnostic outcomes.ResultsOverall, clinicians’ impressions within the first five minutes generally matched current gold-standard diagnostic status (clinical best estimate), were highly correlated with ADOS-2 CSS, and were driven primarily by prosodic and facial cues. However, this brief observation did not detect autism in all cases. While clinicians noted some subclinical atypicalities in the LAD group, impressions of the LAD and NT groups were similar.LimitationsThe brief observations in this study were conducted during clinical research, including some semi-structured assessments. While results suggest overall concordance between initial impressions and diagnoses following more thorough evaluation, findings may not generalize to less structured, informal contexts. In addition, our sample was demographically homogeneous and comprised only speaking autistic participants. They were also unmatched for sex, with more females in the non-autistic group. Future studies should recruit samples that are diverse in demographic variables and ability level to replicate these findings and explore their implications.ConclusionsResults provide insights into the behavioral characteristics that contribute to the diagnosis of adolescents and young adults and may help inform diagnostic decision making in the wake of an increase in the demand for autism evaluations later than childhood. They also substantiate claims of an absence of apparent autistic characteristics in individuals who have lost the diagnosis.

Efficient Search Algorithms for Identifying Synergistic Associations in High-Dimensional Datasets.

In recent years, there has been a notably increased interest in the study of multivariate interactions and emergent higher-order dependencies. This is particularly evident in the context of identifying synergistic sets, which are defined as combinations of elements whose joint interactions result in the emergence of information that is not present in any individual subset of those elements. The scalability of frameworks such as partial information decomposition (PID) and those based on multivariate extensions of mutual information, such as O-information, is limited by combinational explosion in the number of sets that must be assessed. In order to address these challenges, we propose a novel approach that utilises stochastic search strategies in order to identify synergistic triplets within datasets. Furthermore, the methodology is extensible to larger sets and various synergy measures. By employing stochastic search, our approach circumvents the constraints of exhaustive enumeration, offering a scalable and efficient means to uncover intricate dependencies. The flexibility of our method is illustrated through its application to two epidemiological datasets: The Young Finns Study and the UK Biobank Nuclear Magnetic Resonance (NMR) data. Additionally, we present a heuristic for reducing the number of synergistic sets to analyse in large datasets by excluding sets with overlapping information. We also illustrate the risks of performing a feature selection before assessing synergistic information in the system.

Gestational SARS-CoV-2 Infection in a Ugandan Birth Cohort: High Incidence, Mild Maternal Disease, and Evidence of Association with Transient Infant Stunting.

Many questions remain about the prevalence and effects of SARS-CoV-2 infection in malaria-endemic African countries like Uganda, particularly in vulnerable groups such as pregnant women. We describe SARS-CoV-2 immunoglobulin (Ig)G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. From December 2020-February 2022, among 400 unvaccinated pregnant women enrolled at 12-20 weeks gestation and followed through delivery, 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time, consistent with affinity maturation of the antibody response in the cohort. No women experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infect (-1.54 versus -0.37 and -0.51, P = 0.009). These findings suggest that pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with transient shorter stature in early infancy. Further research should explore the significance of this finding and define targeted measures to prevent infection in pregnancy.

Androgen Receptor Mediates Dopamine Agonist Resistance by Regulating Intracellular Reactive Oxygen Species in Prolactin-Secreting Pituitary Adenoma.

Aims: Dopamine agonists (DAs) are the first-line treatment for patients with prolactin-secreting pituitary adenoma (PRL adenoma). However, a subset of individuals exhibits poor responses, known as DA resistance. Previous studies have reported that DA resistance is more prevalent in male patients. This study aims to investigate the relationship between androgen receptor (AR) expression and DA resistance, as well as to explore underlying mechanisms of AR-mediated DA resistance. Results: Our results demonstrated that patients with higher AR expression exhibit greater resistance to DA in our cohort of DA-resistant PRL adenoma. Furthermore, AR was found to be involved in cell proliferation, PRL secretion, and resistance to bromocriptine (BRC) both in vitro and invivo. Mechanistically, we demonstrated that intracellular reactive oxygen species (ROS) function as upstream mediators of apoptosis and ferroptosis following BRC treatment. As a ligand-dependent transcription factor, AR could translocate to the nucleus and transcriptionally promote NFE2-like bZIP transcription factor 2 (NRF2) expression, which regulates intracellular ROS levels, thereby enhancing cell viability and conferring DA resistance to pituitary adenoma (PA) cells. Finally, AR targeting agents were used to inhibit AR signaling, downregulate NRF2 transcription, and sensitize PA cells to BRC treatment. Conclusion and Innovation: We demonstrated that AR plays a crucial role in mediating DA resistance in PRL adenoma. Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas. Antioxid. Redox Signal. 00, 000-000.

Peripheral Endothelial Dysfunction Is Associated With Incident Major Depressive Disorder.

A subset of individuals with major depressive disorder (MDD) have a high burden of cardiovascular risk factors and cerebral small-vessel disease, implicating vascular disease in the development of depression. Cross-sectional studies demonstrate a link between endothelial dysfunction and MDD, but the prospective association between peripheral endothelial dysfunction (PED) and an incident diagnosis of MDD is unknown. Patients undergoing a baseline assessment of cardiovascular risk were evaluated for PED using reactive hyperemia-peripheral arterial tonometry (≤1.8 consistent with PED). Patient medical records were reviewed to identify those who underwent a formal clinical evaluation of MDD after the index PED evaluation. The frequency of PED was compared in those with and without MDD. Logistic regression analyses were performed to assess the association between baseline PED and incident MDD. Between January 2006 and December 2020, 1614 patients underwent testing for PED. Four hundred eighty-four (30.1%) patients underwent a formal evaluation for MDD after (0-15 years) the index procedure (mean±SD age, 52.8±13.8 years; 65.2% women). Of these, 157 (32.4%) had PED and 108 (31.0%) were diagnosed with MDD. Individuals with MDD had a higher frequency of PED (40.2% versus 30.2%; P=0.034) compared with those without MDD. In multivariable analyses, PED was significantly associated with MDD (odds ratio, 2.3 [95% CI, 1.4-3.8]; P<0.001). PED is significantly associated with incident MDD. Thus, PED may be a useful marker to identify individuals at increased risk of depression who may benefit from more frequent and earlier management strategies.

ACT with CF: A randomized trial of acceptance and commitment therapy vs supportive psychotherapy for adults with cystic fibrosis

PurposePsychological distress, including anxiety and depression, is common among adults with CF, associating with poor quality of life, lung function, and healthcare utilization. This 3-year, multi-site, telehealth-delivered randomized trial sought to determine whether Acceptance and Commitment Therapy (ACT with CF) is superior to supportive psychotherapy (SP), in improving psychological functioning for adults with CF. MethodsOne hundred twenty-four adults with CF and elevated anxiety and/or depressive symptoms were recruited coincident with the first COVID lockdown, from Thomas Jefferson University Hospitals, University of Virginia, Augusta University, Duke University Medical Center, and social media. Participants were randomized to 6 weeks of either ACT with CF or SP, delivered via Zoom. They completed measures of psychological functioning: depression (BDI-II), anxiety (BAI), cognitive fusion (CFQ-13), acceptance and committed action (AAQ-II); and barriers to adherence at baseline, post-treatment, and at 3-months follow-up. Biobehavioral outcomes, including CF severity and treatment burden, were gathered using EMR data. ResultsParticipants were young adults (mean age 25 years [SD = 12]), female (75 %), on CFTR modulators (67 %), psychotropic medication(s) (60 %), with previous psychotherapy engagement (72 %). Treatment effects were evaluated using analysis of covariance, controlling for baseline levels of respective outcomes, age, biological sex, and FEV1. ACT demonstrated greater improvements in psychological functioning at 6-weeks (mean score = 57.3 [51.6, 63.0]) relative to SP (mean score = 67.8 [62.2, 73.5], Cohen's d = 0.59, P = .017), with largest improvements in cognitive fusion (CFQ-13) and acceptance and committed action (AAQ-II). Treatment improvements in psychological functioning persisted at 3-months (ACT: 59.7 (53.5, 65.9) vs. SP: 69.0 [62.6, 75.4], Cohen's d = 0.40, P = .041), with ACT demonstrating continued improvements in the CFQ-13 and AAQ-II. Negative affect scores were not consistently improved on our mean-rank composite outcome variable (Cohen's d = 0.22, P = .170), despite post hoc reductions in BDI-II scores (ACT: −7.4 [−9.4, −5.4] vs. SP: −4.5 [−6.4, −2.6], P = .040). Improvements in psychological flexibility (CFQ-13 and AAQ-II) were also robustly associated with reductions in negative affect (B = −0.45, P < .001). Individuals in ACT with greater baseline barriers to medication adherence reported greater reductions in barriers after treatment (P = .026). Individuals with lower baseline FEV1/FVC ratios (e.g. ≤ 65 %) demonstrating greater improvements in ACT compared with SP (ACT: 7.3 [1.7, 12.8] vs. SP: 1.3 [−3.2, 5.8], P = .036 for interaction). ConclusionsACT with CF was superior to SP in improving psychological functioning among adults with CF and elevated psychological distress, with additional benefits in secondary biobehavioral outcomes in a subset of individuals with greater medical burden. Improvements in psychological flexibility strongly associated with reductions in negative affect.Clinicaltrials.gov ID #NCT04114227Supported by the Boomer Esiason Foundation.

Process and Validity of Linking Cystic Fibrosis Patient Registry with National Medicaid Databases

BackgroundThe Cystic Fibrosis Foundation Patient Registry (CFFPR) provides valuable clinical and demographic data but includes limited information on health services and medications provided outside of CF Care Centers. Linking CFFPR to claims databases such as national Medicaid data could address these data gaps. MethodsLinkage algorithms based on state of residence, gender, and date of birth were utilized to match individuals with CF diagnostic codes in national Medicaid databases (2016) to individuals in the CFFPR (2015-2016). Subsets of individuals with partial social security numbers or residing in the state of North Carolina were utilized to validate the accuracy of linkages and perform exploratory analyses on care utilization and costs. ResultsOf the 32,152 individuals in CFFPR, 10,616 were uniquely linked to national Medicaid databases. The 372 linked individuals within the NC extract had 8.0±7.6 visits to outpatient providers, substantially higher than the 4.2±2.4 CF Care Center outpatient visits documented within CFFPR. Similarly, linked individuals had 2.1±1.7 oral antibiotic prescriptions within CMS pharmacy databases versus 0.5±1.9 oral antibiotic prescriptions in CFFPR. Total pharmacy costs for the linked individuals in NC were $16.4 million, with pancrealipase (19%), dornase alfa (24%), and CFTR modulators (29%) the largest expenditures. Total non-pharmacy costs were $7.5 million, with inpatient hospitalization representing 53% of costs. ConclusionLinkage of data from Medicaid and CFFPR can produce valid comprehensive data on low-income people with CF and provide opportunities to examine utilization/adherence or comparative effectiveness and safety of medications as well as conduct economic analyses in the low-income CF population.

Distinct populations suppress or escalate intake of cocaine paired with aversive quinine

BackgroundOnly a subset of individuals who encounter illicit drugs become persons with a substance use disorder. Individual differences in aversive reactions to drug-associated phenomena like smoke inhalation and unpleasant taste are predictors for continued use. While several preclinical studies have explored self-administration involving aversive cues, none have simultaneously introduced aversion with the initial drug self-administration. We aimed to develop such a model by pairing intravenous cocaine with intraoral quinine self-administration from the outset and investigate whether repeated exposure to an aversive stimulus would alter its hedonic value under laboratory conditions. MethodsTwenty-seven male and female Sprague Dawley rats self-administered intravenous/intraoral (cocaine/quinine) for 2h/day over 14 days. This was followed by a 1-day quinine-only extinction session, a 3-day return to self-administration, and an intraoral infusion session to assess quinine taste reactivity (TR). ResultsWe identified three distinct groups. The first self-administered very little cocaine, while the second sharply escalated cocaine intake. Both groups had similar aversive TR to quinine, suggesting that the escalating group did not habituate to the aversive cue but pursued drug despite it. We also identified a third group with high initial intake that decreased over time. This decrease predicted high aversive TR, and we argue this group may represent individuals who engage in excessive use on their first encounter and subsequently find self-administration to be aversive. ConclusionsOur novel model yields three distinct groups that differ in self-administration patterns and aversive cue valuation.

Arterial blood gases in SCUBA divers at depth

BackgroundCurrent diving physiology postulates that SCUBA divers’ arterial blood gas (ABG) levels vary proportionally to environmental pressure, but, to date, ABGs have only been obtained during simulated dives. Also, recent evidence supports the use of the arterial/alveolar (a:A) partial pressures of oxygen (PO2) ratio to predict the arterial PO2 (PaO2) under hyperbaric conditions from measurements obtained at 1 atmosphere absolute (ATA). This work summarizes ABGs obtained in SCUBA divers in real underwater conditions and aims to validate the a:A ratio in predicting PaO2 in this subset of individuals at depth.MethodsThe study was approved by the local ethics committee. After cannulating the radial artery of the non-dominant limb, ABGs were sampled at the surface before the dive (A), at depth (15 meters of freshwater (mfw) or 42 mfw) before (B) and after (C) pedaling on a submersed bicycle for 10 minutes, and back at surface (D). After calculating the surface alveolar PO2 for each subject, the a:A ratio was obtained and used to predict PaO2 at depth. A linear regression between measured and predicted PaO2 was reported, along with the goodness-of-fit F test.ResultsSix subjects performed the dive at 15 mfw, and four others at 42 mfw. The PaO2 proportionally increased at both depths, remaining stable before and after pedaling. The a:A calculated from the baseline ABG obtained at rest, out of the water, adequately predicted the PaO2 at depth (R2 = 0.97, p&amp;lt;0.001), better at 15 mfw but losing accuracy at 42 mfw.ConclusionsThe ABGs confirmed the proportional rise of PaO2 in SCUBA divers underwater. The a:A ratio could be used to predict the magnitude of PaO2 rise at depth to limit exposure to hyperoxia, especially in repetitive recreational dives and professional divers.

Blood pressure polygenic risk scores associate with resistant hypertension in individuals with type 1 diabetes

Abstract Background Hypertension is a major risk factor of global disease burden, but treatment goals are often not met. A subset of individuals with hypertension is affected by treatment-resistant hypertension (RHTN), and they suffer from increased cardiovascular morbidity and mortality. Early identification of individuals at risk of RHTN could lead to more efficient antihypertensive drug treatment. Purpose The aim of this study was to investigate whether polygenic risk scores (PRS) for systolic (SBP) and diastolic blood pressure (DBP) predict RHTN in individuals with or without type 1 diabetes (T1D). Methods We performed association analyses between PRSs and RHTN in two Finnish cohorts: The Finnish Diabetic Nephropathy Study (FinnDiane) and the Finnish individuals of the LIFE Study (LIFE-Fin). FinnDiane is an ongoing, observational nationwide study aiming to identify genetic and clinical risk factors for complications of T1D. We included data from 778 adults (476 with RHTN and 302 with controlled hypertension). LIFE is a randomized, double-blind study evaluating long-term effects of losartan compared with atenolol in patients with signs of left ventricular hypertrophy. We used SBP and DBP data from 378 Finnish individuals (173 with RHTN and 205 with controlled hypertension) at the four-year visit of the study. In FinnDiane, RHTN was defined as SBP ≥130 or DBP ≥85 mmHg and the use of three or more antihypertensive drugs, or SBP &amp;lt;130 and DBP &amp;lt;85 mmHg and the use of four or more antihypertensive drugs. In LIFE-Fin, RHTN was defined as SBP ≥140 or DBP ≥90 mmHg and the use of three or more antihypertensive drugs. Controlled hypertension was defined as the use of three or fewer antihypertensive drugs and SBP &amp;lt;130 and DBP &amp;lt;85 mmHg in FinnDiane, and as SBP &amp;lt;140 and DBP &amp;lt;90 mmHg in LIFE-Fin. We calculated a PRS for each participant using genome-wide association study data for 1,098,015 genetic variants; the variant-specific data were derived from UK Biobank based PRS-CS-method computed PRSs (1). Results We observed significant associations of SBP and DBP PRSs with RHTN in FinnDiane (OR 1.56 [1.30; 1.87], P = 1.8e-6, and OR 1.25 [1.04; 1.50], P = 0.02, per one-SD increase of the PRS value) when adjusted for age, sex, estimated glomerular filtration rate and body mass index. The association between SBP PRS and RHTN remained significant when T1D individuals with or without albuminuria were analysed separately. Neither SBP nor DBP PRSs were significantly associated with RHTN in LIFE-Fin. Conclusion Higher SBP PRSs associate with higher risk of RHTN in individuals with T1D, with or without albuminuria, but not in nondiabetic individuals with hypertension. It remains to be investigated whether general blood pressure genetics contribute to RHTN in the general population.

Cell type-specific driver lines targeting the Drosophila central complex and their use to investigate neuropeptide expression and sleep regulation.

The central complex (CX) plays a key role in many higher-order functions of the insect brain including navigation and activity regulation. Genetic tools for manipulating individual cell types, and knowledge of what neurotransmitters and neuromodulators they express, will be required to gain mechanistic understanding of how these functions are implemented. We generated and characterized split-GAL4 driver lines that express in individual or small subsets of about half of CX cell types. We surveyed neuropeptide and neuropeptide receptor expression in the central brain using fluorescent in situ hybridization. About half of the neuropeptides we examined were expressed in only a few cells, while the rest were expressed in dozens to hundreds of cells. Neuropeptide receptors were expressed more broadly and at lower levels. Using our GAL4 drivers to mark individual cell types, we found that 51 of the 85 CX cell types we examined expressed at least one neuropeptide and 21 expressed multiple neuropeptides. Surprisingly, all co-expressed a small neurotransmitter. Finally, we used our driver lines to identify CX cell types whose activation affects sleep, and identified other central brain cell types that link the circadian clock to the CX. The well-characterized genetic tools and information on neuropeptide and neurotransmitter expression we provide should enhance studies of the CX.

Generalized tetanus complicated with Takotsubo-cardiomyopathy in a septuagenarian following a laceration injury with soil contamination – a case report

BackgroundTetanus is a clinical rarity due to the successful globally adopted childhood vaccination programme. The rising elderly population in the United Kingdom creates a subset of individuals whom are prone to develop Tetanus as they preceded this vaccination drive.Case summaryA 76 year old Caucasian lady presented with a soil contaminated laceration injury on her knee following a fall. Though she received urgent assessment and wound care, the relevance of the injury in the backdrop of her age was not appreciated and her tetanus post exposure prophylaxis was overlooked. She readmitted seeking further management 1 week later with an infected wound with Trismus and clinical features favoring Generalized tetanus. During her stay she developed Takotsubo-cardiomyopathy with congestive cardiac failure and required prolonged care in the intensive unit with mechanical ventilation and rehabilitation before being discharged home.ConclusionFirst contact physicians should have a greater appreciation of the types of injuries and at-risk individuals who are more prone to develop tetanus upon exposure to ensure early and appropriate identification. There should be greater situational awareness with regard to the elderly in view of their heightened risk of development of tetanus specially those born before the vaccination drive. Knowledge regarding post exposure prophylaxis measures for tetanus should be regularly updated using local guidance to ensure awareness, so as to despite its rarity Tetanus remains an adequately appreciated disease.

Outcomes of Single Corticosteroid Injection in De Quervain's Tenosynovitis.

The aim is to demonstrate the effectiveness of steroid injection in treating De Quervain disease. This study took place in the Orthopedic and Spine unit of Hayatabad Medical Complex. This study started in June 2022 and ended in February 2023. Seventy-five patients and 76 hands with De Quervain's Tenosynovitis were recruited for the study. Of these 75 patients, 54 (72%) were female and 21 (28%) were male. The diagnosis of De Quervain's Tenosynovitis was established from the patients' histories, physical examinations, and special tests. One ml of local anesthetic (2% of xylocaine) mixed with 1 ml of Corticosteroid (Depo-Medrol®, containing methylprednisolone acetate 40 mg/ml) were injected between abductor pollicis longus (APL) and extensor pollicis brevis (EPB), 3-4 cm proximal to radial styloid on the effected side. Patients were reviewed at two- and three-weeks period after injection. Results: Sixty-three (84%) patients were completely pain-free, 9 (12%) patients had mild pain, while 2 (2.2%) patients had no improvement in pain status at all. 1 (1.3%) patient didn't show up on the second follow-up. Injecting corticosteroids into the first compartment of the dorsal extensor tendon is a good treatment for De Quervain's tenosynovitis. The incidence of De Quervain's disease is higher in females and in the right hand. Only a limited subset of individuals who have not responded to non-invasive and minimally invasive treatments can be considered for surgical intervention. The study's limitations include a small sample size and fewer follow-ups. Further studies, especially randomized controlled trials with large sample sizes and long follow-ups, are needed to determine the long-term efficacy of steroid injection in De Quervain's tenosynovitis and whether the documented effect is likely to have occurred due to the treatment.

Association between dietary fiber intake and chronic kidney disease in adults with and without hypertension in the United States: a cross-sectional study of NHANES 2009–2020

While previous research has highlighted the potential advantages of increasing dietary fiber intake (DFI) for managing hypertension and chronic kidney disease (CKD), there is a gap in large-scale empirical studies examining the relationship between DFI and CKD among hypertensive and nonhypertensive cohorts independently. This study involved 22,871 participants sourced from the NHANES database spanning 2009 to 2020, who were divided into hypertensive (n = 9,861) and nonhypertensive (n = 13,010) groups. The analysis revealed a significant inverse correlation between DFI and CKD prevalence across the sample after adjusting for various covariates (OR = 0.98, 95% CI: 0.97–0.99, p = 0.001). Within the subset of hypertensive individuals, this inverse association mirrors the findings of the overall sample, indicating that a higher DFI was associated with a reduced occurrence of CKD (OR = 0.97, 95% CI: 0.96–0.99, p < 0.001). However, this correlation was not detected in the nonhypertensive group (OR = 0.99, 95% CI: 0.98–1.01, p = 0.285). The RCS analysis further confirmed a pronounced nonlinear inverse relationship between DFI and CKD prevalence in both the entire cohort and the hypertensive group but not in the nonhypertensive group. Further scrutiny of the hypertensive group revealed that individuals with a higher DFI had 33% lower odds of CKD progression for the moderate risk level and 36% lower odds for the high to very high risk level. Subgroup analyses confirmed the consistency of these relationships across various demographics. In summary, this investigation revealed a significant inverse relationship between DFI and CKD prevalence in US adults with hypertension, a relationship not observed in nonhypertensive individuals.

Pulmonary sarcoidosis: differences in lung function change over time

IntroductionGiven the heterogeneity of sarcoidosis, predicting disease course of patients remains a challenge. Our aim was to determine whether the 3-year change in pulmonary function differed between pulmonary function phenotypes...

Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD)study: a pilot, double-blind placebo-controlled crossover trial.

To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure. We performed a randomized, double-blind, placebo-controlled crossover pilot study in individuals with mild-to-moderate Alzheimer's disease. Electroencephalography was performed at baseline and those with active epileptiform discharges were excluded. Eligible participants were randomized to placebo for 12 weeks or an active arm of oral levetiracetam (4 weeks up-titration to levetiracetam 500 mg twice daily, 4 weeks maintained on this dose followed by 4 weeks down-titration to nil). Participants then crossed over to the other arm. The primary outcome was change in cognitive function assessed by the Oxford Memory Task, a task sensitive to hippocampal memory binding. Secondary outcomes included tolerability, other neuropsychological scales, and general questionnaires. Recruitment numbers were severely limited owing to restrictions from the COVID-19 pandemic at the time of the study. Eight participants completed both arms of the study (mean age 68.4 years [SD = 9.2]; 5 females [62.5%]). No participants withdrew from the study and there was no significant difference between reported side effects in the active levetiracetam or placebo arm. Measures of mood and quality of life were also not significantly different between the two arms based on participant or carer reports. In limited data analysis, there was no statistically significant difference between participants in the active levetiracetam and placebo arm on the memory task. This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease who do not have a history of seizures and has no detrimental effect on mood or quality of life. Larger studies are needed to assess whether levetiracetam may have a positive effect on cognitive function in subsets of individuals with Alzheimer's disease. Abnormal electrical activity within the brain, such as is seen in seizures, might contribute to memory problems in people with dementia. We completed a clinical trial to see if an antiseizure medication, levetiracetam, could help with memory difficulties in people with Alzheimer's disease (the most common cause of dementia). In this pilot study, we could not prove whether levetiracetam helped memory function. We did show that the drug is safe and well tolerated in people with dementia who have not had a seizure. This work, therefore, offers a platform for future research exploring antiseizure medications in people with dementia.