National Institutes Of Health Research Articles

Effect of Psychoeducation on Reducing Burden Among Primary Caregivers of People with Schizophrenia

Schizophrenia is a serious psychological illness that needs long-term treatment. Family members, especially those who care for a patient at home, experience the burden of providing long-term care. Psychoeducational intervention may enhance the caregiver’s outcomes. The major goal of the study was to explore the effect of psychoeducation on reducing the burden among primary carers of people with schizophrenia. In this study, thirty-two participants (32 caregivers) were purposefully selected based on the National Institute of Mental Health (NIMH). A personal information form and the Bangla version of the Zarit Burden Interview scale were administered. Total participants were divided by simple randomization into two groups (i.e., experimental and control groups). Following the baseline evaluation by questionnaire, the experimental group of 16 caregivers received two sessions of psychoeducation, but the control group of the same number of caregivers did not. The effectiveness of psychoeducation was evaluated using a pretest-posttest control group design. Findings suggested that psychoeducation decreased the level of burden, and after the intervention, the mean score of the experimental group was lower than that of the control group. These findings found that the psychoeducation intervention had a positive outcome in reducing the burden on caregivers of patients who deal with schizophrenia. Jagannath University Journal of Life and Earth Sciences, 9(1): 81–94, 2023 (June)

Objective response after immune checkpoint inhibitors in a chemotherapy-refractory pMMR/MSS metastatic rectal cancer patient primed with experimental AlloStim® immunotherapy

BackgroundImmune Checkpoint Inhibitor (ICI) immunotherapy is most effective in immune effector cell infiltrated ‘hot’ tumor lesions, such as occurs in deficient mismatch repair, microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). However, most all metastatic CRC tumors are mismatch repair proficient/microsatellite stable (pMMR/MSS) ‘cold’ lesions, without significant immune cell infiltration, and are unresponsive to ICI. AlloStim®, is an experimental, allogeneic immunomodulatory cell therapy designed to convert ‘cold’ metastatic tumor lesions to ‘hot’ inflamed lesions. After AlloStim® immunotherapy, this cold to hot inflammatory mechanism can make it difficult to distinguish between pseudoprogression and actual progression on restaging CT scans, as inflamed metastatic lesions can appear larger and occult disease can appear as new small lesions.MethodsTo explore whether radiological progression after AlloStim® immunotherapy is due to immune-flare or disease progression, we administered a short course of a combination ICI therapy to a pMMR/MSS chemotherapy-refractory metastatic colorectal cancer patient enrolled in the StimVax Phase IIb clinical study that presented with radiological progression after AlloStim® immunotherapy. Our rationale was that an accelerated response to ICI should occur if the lesions were inflamed, while if the enlarged lesions were due to disease progression there would not be a response.ResultsHere we report a rapid, significant reduction in tumor burden in response to ICI administration in an AlloStim® primed pMMR/MSS mCRC patient with retroperitoneal and lung metastases.ConclusionThis rare objective response to ICIs in a pMMR/MSS mCRC patient supports further evaluation of the combination of AlloStim® with ICI immunotherapy in MSS mCRC and other cold or ICI refractory tumors.Trial registrationNational Library of Medicine (NLM) at the National Institutes of Health (NIH). Registered 22 June 2020, https://clinicaltrials.gov/study/NCT04444622.

A model for supporting biomedical and public health researcher use of publicly available All of Us data at Historically Black Colleges and Universities.

The aim of this study was to describe opportunities and challenges associated with the development and implementation of a program for supporting researchers underrepresented in biomedical research. We describe a case study of the All of Us Researcher Academy supported by the National Institutes of Health (NIH), including feedback from participants, instructors, and coaches. Lessons include the importance of inviting role models into learning networks, establishing and maintaining trusted relationships, and making coaches available for technical questions from researcher participants. Although research has focused on learning outcomes in science, technology, engineering, and mathematics at Minority Serving Institutions in the United States, literature tends to lack models for initiatives to improve everyday research experiences of faculty and researchers at such institutions or to encourage researcher use of public-use data such as that available through NIH's All of Us Research Program. The All of Us Researcher Academy offers a model that addresses these needs.

An Epidemiological Study to Assess the Risk Factors and Symptoms of PCOS

The aim to present this study was to assess the most affected age group of girls from PCOD and to make them aware by our questionnaire in this descriptive study, 200 girls were selected randomly from hostels of MMDU, MULLANA. A questionnaire was formulated to obtain information regarding symptoms, changes, dietary patterns, etc. This data was differentiated, tabulated, and tested. The data collected shows that the majority of the respondents who participated in the survey were on the edge of PCOD. Stein and Leventhal are regarded to have been the first investigators of polycystic ovary syndrome however, in 1721 Vallisneri, an Italian scientist; he described a married, infertile woman with shiny ovaries with a white surface, and the size of pigeon eggs. It was not until early 1990 at a national institute of Health (NIH) sponsored conference on PCOD that formal diagnostic criteria were proposed and afterward largely utilized. Many scientists tried to explain the pathophysiology of PCOS and many studies were made. It is now accepted that it is multifactorial, partly genetic, however, a number of candidate genes have been postulated. Insulin resistance has been noted consistently among many women with PCOS, especially in those with Hyperandrogenism, but it is not included in any of the diagnostic criteria. Now there is strong evidence that cardiovascular diseases risk factors and disturbances in carbohydrate metabolism are all increased in patients with PCOS compared to healthy populations. The criteria was established by a group of experts during a conference in ROTTERDAM held in 2003 are obligatory. The subsequent ROTTERDAM CRITERIA incorporated the size and morphology as determined by an ultrasound of the ovary into the diagnostic criteria. The Center for Disease Control and Prevention, obesity among children in the U.S. has tripled since 1980 due to various factors like bad eating habits, and lack of physical exercise, and many more children are getting more and more obese. Many researchers have found that PCOD findings are increasing with time. Finding insulin resistance in obese adolescents gave a different diagnosis of PCOD. Upon further clinical testing, many other symptoms are found like Hirsutism, acne, and menstrual abnormalities. Emans (2005) described PCOS as a diagnosis related to the diagnosis of insulin resistance, not being overweight. For insulin resistance, females don't need to be overweight, they will have insulin resistance even a normal weight female adolescents also have insulin resistance.

Unlocking Health Literacy: The Ultimate Guide to Hypertension Education From ChatGPT Versus Google Gemini.

Background Google Gemini (Google, Mountain View, CA) represents the latest advances in the realm of artificial intelligence (AI) and has garnered attention due to its capabilities similar to the increasingly popular ChatGPT (OpenAI, San Francisco, CA). Accurate dissemination of information on common conditions such as hypertension is critical for patient comprehension and management. Despite the ubiquity of AI, comparisons between ChatGPT and Gemini remain unexplored. Methods ChatGPT and Gemini were asked 52 questions derived from the American College of Cardiology's (ACC) frequently asked questions on hypertension, following a specified prompt. Prompts included: no prompting (Form 1), patient-friendly prompting (Form 2), physician-level prompting (Form 3), and prompting for statistics/references (Form 4). Responses were scored as incorrect, partially correct, or correct. Flesch-Kincaid (FK) grade level and word count were recorded. Results Across all forms, scoring frequencies were as follows: 23 (5.5%) incorrect, 162 (38.9%) partially correct, and 231 (55.5%) correct. ChatGPT showed higher rates of partially correct answers than Gemini (p = 0.0346). Physician-level prompts resulted in a higher word count across both platforms (p < 0.001). ChatGPT showed a higher FK grade level (p = 0.033) in physician-friendly prompting. Gemini exhibited a significantly higher mean word count (p < 0.001); however, ChatGPT had a higher FK grade level across all forms (p > 0.001). Conclusion To our knowledge, this study is the first to compare cardiology-related responses from ChatGPT and Gemini, two of the most popular AI chatbots. The grade level for most responses was collegiate level, which was above average for the National Institutes of Health (NIH) recommendations, but on par with most online medical information. Both chatbots responded with a high degree of accuracy, with inaccuracies being rare. Therefore, it is reasonable that cardiologists suggest either chatbot as a source of supplementary education.

Effects of Alpha Lipoic Acid Supplementation on Slow Skeletal Muscle Mass and Contractile Functions in Type 2 Diabetic Male Sprague Dawley Rats

Objective: To see the Effects of Alpha-Lipoic Acid (ALA) supplementation on slow skeletal muscle mass andcontractile functions in type 2 diabetic male Sprague Dawley rats.Study Design: Quasi-experimental study.Place and Duration of Study: The study was carried out at the Physiology Research Lab, Army MedicalCollege, Rawalpindi, Pakistan from June 2019 to April 2021 in collaboration with the National Institute of Health(NIH) Islamabad, Pakistan.Methods: Sixty adult SD rats were divided into three equal groups. Rats were fed on a standard diet as per NIHprotocols. After 2 weeks type 2 Diabetes mellitus (T2DM) was induced in groups 2 and 3 by injecting low dose35mg of streptozotocin (STZ) in the abdomen intraperitoneally. T2DM was successfully developed andconfirmed by measuring glucose levels through a glucometer. Group 3 was injected with Alpha Lipoic acid30mg/kg/day at the lower abdomen for the next two weeks. After 04 weeks, soleus muscles were dissected.The animal data acquisition unit (iWorx) was used for assessing the contractile functions of soleus.Results: Alpha Lipoic acid group showed improvement in muscle mass, muscle tension strength, and recoveryfrom fatigue after applying fatigue protocol as compared to group 2.Conclusion: Alpha Lipoic acid supplementation improves contractile force and delays fatigue in the soleusmuscles of diabetic rats. How to cite this: Khan BU, Yousef I, Arshad S, Ikram F, Ali A, Ullah I. Effects of Alpha Lipoic Acid Supplementation on Slow Skeletal Muscle Mass and Contractile Functions in Type 2 Diabetic Male Sprague Dawley Rats. Life and Science. 2024; 5(2): 216-221. doi: http://doi.org/10.37185/LnS.1.1.408

Novel Role of Irbesartan in Elevating Serum High Density Lipoprotein in Hypercholesterolemic Animal Model

Objective: To explore the HDL cholesterol-raising capacity of Irbesartan (an antihypertensive drug) in rabbit'sserum.Study Design: Laboratory-based experimental study.Place and Duration of Study: The study was carried out at the Animal House of the National Institute of Health(NIH) Islamabad, Pakistan from January 2023 to November 2023.Methods: This study was conducted on 18 rabbits divided into three groups with six rabbits in each. Leaving one group as a normal control, two out of three groups were made hypercholesterolemic by a high-cholesterol diet. Irbesartan was given to one of the hypercholesteremic groups for 30 days. Blood samples were taken for serum analysis of HDL cholesterol.Results: Results of blood serum levels of all three groups were compared and analyzed on three differentoccasions i.e., on day zero, day 120, and day 150 for HDL cholesterol. Their means were calculated using SPSSVersion 20. The irbesartan-treated group showed obvious elevation in serum HDL cholesterol in comparisonwith the hypercholesteremic control group.Conclusion: It is concluded that Irbesartan, an antihypertensive drug has an additional role of elevating serumhigh-density lipoproteins and can provide the supplementary benefit of improving the lipid profile inhypertension and Hypercholesterolemia. How to cite this: Shakir S, Chaudhry ZR, Atif M, Sadaf R, Chaudhry ER, Chaudhry SR. Novel Role of Irbesartan in Elevating Serum High Density Lipoprotein in Hypercholesterolemic Animal Model. Life and Science. 2024; 5(2): 199-203. doi: http://doi.org/10.37185/LnS.1.1.536

Impact of Short-Term Arsenic Exposure on Hormonal Balance and Fibrosis in Sprague Dawley Rats

Objective: To evaluate the toxic effects of arsenic exposure on the female reproductive tract and endocrinesystem.Study Design: A laboratory-based experiment.Place and Duration of Study: The study was carried out at the Laboratory of the National Institute of Health(NIH) Islamabad, Pakistan from 1st January 2019 to 4th January 2020.Methods: non-probability convenient sampling technique was employed and 60 female healthy SpragueDawley rats were included in the study at the National Institute Islamabad. Animals were randomly allocatedinto control and experimental groups (n=30 each). In the first week, animals were acclimatized to the animalhouse of the College of Physicians and Surgeons Pakistan. In the second week, the control and experimentalgroups were given 10 ml of distilled water by oral gavage daily and 4μg of sodium arsenite dissolved in 10 ml ofdistilled water daily for two weeks respectively. After the experimental period, animals were taken to theanimal lab of the National Institute of Health Islamabad for blood sampling and tissue dissection. Rats wereeuthanized by chloroform inhalation and blood was drawn by single intracardiac puncture and stored in clotactivator vials at 4 0C for further workup. The female reproductive tract was dissected, and the tissue was stored in 10 % formalin for histological studies. Serum Gonadotropin-releasing hormone (GnRH) levels were assessed via the Enzyme-Linked Immunosorbent Assay (ELISA) method. Whereas histological effects of arsenic were observed under a microscope by tissue processing and staining with Masson trichrome stain. Mean ± SD of serum GnRH levels and percentage of fibrosis in uterine tissue of control and experimental groups wereevaluated by the software Statistical Package for Social Sciences version 22.0. Comparison of means evaluatedby Student T-test. The significant p-value was ≤ 0.05.Results: The experimental group showed significant elevation of serum GnRH levels and fibrotic changes withhigh collagen deposition (p ≤ 0.05).Conclusion: Exposure to arsenic via contaminated drinking water is disruptive for the female reproductive tractand endocrine system. How to cite this: Mir A, Mir UZ, Hussain W, Irfan A, Butt HA, Sarwar U. Impact of Short-Term Arsenic Exposure on Hormonal Balance and Fibrosis in Sprague Dawley Rats. Life and Science. 2024; 5(2): 187-192. doi: http://doi.org/10.37185/LnS.1.1.64

A Scholarly Dialog on Recent Trends in National Institutes of Health's Funding for the Thyroid Field.

Background: The National Institutes of Health (NIH) is the major funding agency for biomedical research in the United States. To initiate a scholarly dialog about research and career development in the thyroid field, here we reviewed recent trends in NIH funding for this area. We used the Research Portfolio Online Reporting Tool database to estimate the level of NIH extramural support during 2013-2022 (number of active grants/year and $amount/year weighed by the total number of active grants/year and $amount/year), provided by the NIH to the thyroid field. We determined that in 2013, the NIH supported ∼140 grants/year, totaling almost $50 million/year, the majority in the form of R01 grants. Within the thyroid field, support was evenly split between thyroid cancer and thyroid hormone metabolism and action subareas. In the subsequent years (2014-2022), the total number of active grants peaked at 150/year ($55 million) in 2014 but progressively decreased to about 100 active grants/year ($30 million) in 2022. This trend occurred while the NIH budget increased from $29 to $46 billion/year. Globally, the number of thyroid-related publications increased by ∼70% during the study period, and the fractional contribution of several countries remained relatively stable, except for China which increased by ∼600%. Remarkably, the fraction of thyroid-related publications in the United States sponsored by the NIH decreased from 5.5% to 3.1% of the global number. Conclusion: These results constitute a very concerning scenario for research and education in the thyroid field. We appeal to the NIH, the professional societies in endocrinology and thyroidology, and all other relevant stakeholders such as thyroid-related professionals and thyroid patients to engage in further discussions to identify the root causes of this trend and implement an action plan to stabilize and eventually reverse this situation.

Fear, defense, and emotion: A neuroethological understanding of the negative valence research domain criteria.

We describe the close correspondence between predatory imminence continuum theory (PICT) and the National Institute of Mental Health's Research Domain Criteria (RDoC) for negative valence. RDoC's negative valence constructs relate aversively motivated behavioral reactions to various levels of threat. PICT divides defensive responses into distinct modes that vary along a continuum of the psychological closeness of predatory threat. While there is a close correspondence between PICT modes and negative valence threat constructs, based on PICT, we describe some potential elaborations of RDoC constructs. Both have consonant views of fear and anxiety and provide explicit distinctions between these emotional states, relating them to specific defensive behaviors and functions. We describe recent data that causally implicate human subjective emotional states with amygdala activity, which is also critical for defensive behavior. We conclude that attention to neuroethological views of defense can advance our understanding of the etiology and treatment of anxiety and stress disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Safety and immunogenicity of a single dose of Tdap compared to Td in pregnant women in Mali and 3 its effect on infant immune responses: a single-centre, randomised, double-blind, active-controlled phase 2 study

While maternal pertussis vaccination is a strategy to reduce infant morbidity, safety and immunogenicity data are limited in sub-Saharan Africa. We aimed to evaluate the safety of a single dose of tetanus, diphtheria and acellular pertussis vaccine (Tdap) vaccine compared to tetanus and diphtheria vaccine (Td) vaccine in pregnant women in Bamako, Mali and to assess the pertussis toxin (PT) antibody response at birth. In this phase 2, single-centre, randomised, double-blind, active-controlled study, from 23 January 2019 to 10 July 2019, healthy 18-39 year old women in the second trimester of a singleton pregnancy were randomised 2:1 to receive Tdap or Td. Blood was tested for serum immunoglobulin G (IgG) against PT and other vaccine antigens using a qualified Meso Scale Discovery multiplex immunoassay. The co-primary objectives evaluated safety and birth anti-PT levels. Infant immune responses to whole-cell pertussis vaccine (DTwP) were assessed. Statistical analysis was descriptive. This trial is registered with clinicaltrials.gov, NCT03589768. 133 women received Tdap and 67 received Td, with 126 and 66 livebirths, respectively. In the Tdap group, 22 serious adverse events (SAEs) including one maternal death occurred in 20 participants (15·0%), with 10 SAEs in 10 participants (14·9%) in the Td group. Among infants, 18 events occurred among 13 participants (10.3%) and 8 SAEs in 6 participants (9.1%), including three and two infant deaths, occurred in Tdap and Td groups, respectively. None were related to study vaccines. Anti-PT geometric mean concentration (GMC) at birth in the Tdap group was higher than in the Td group (55.4 [46.2-66.6] IU/ml vs 7.9 [5.4-11.5] IU/ml). One month after the third dose of DTwP, the GMC in infants born to mothers in the Tdap group were lower compared to the Td group (20.2 [13.7-29.9] IU/ml vs 77.2 [32.2-184.8] IU/ml). By 6 months of age, the anti- PT GMCs were 17.3 [12.8-23.4] IU/ml and 67.1 [35.5-126.7] IU/ml in Tdap and Td groups, respectively. At birth, anti-tetanus toxin (TT) GMCs were higher in infants in the Td vs Tdap group (5.9 [5.0-7.0] IU/ml vs 4.1 [3.5-4.8] IU/ml). Anti-diphtheria toxin GMCs were similar in both groups. Tdap administered to pregnant women in Mali is safe and well-tolerated. Infants of mothers who received Tdap were born with high PT and protective anti-TT antibody levels. By six months of age, after primary vaccination, the PT levels were lower in the Tdap group compared to the Td group. The blunted immune responses to primary DTwP vaccination in the Tdap infant group warrant further study. This project was funded by National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under contract numbers 75N93021C00012 (The Emmes Company), and HHSN27220130000221 (University of Maryland, Baltimore). Dr. Susana Portillo was supported by NIH award no. T32AI007524. NIAID, NIH provided Tdap vaccine (BOOSTRIX).

Use of melatonin supplements and risk of type 2 diabetes and cardiovascular diseases in the USA: insights from three prospective cohort studies

Use of melatonin supplements has been increasing substantially in both children and adults in the USA; however, their long-term cardiometabolic effects remain unclear. We aimed to assess the associations between regular use of melatonin supplements and the risk of developing type 2 diabetes or cardiovascular disease in adults. In this study, we included individuals from three US cohorts: the Nurses' Health Study (women only), the Health Professionals Follow-up Study (men only), and the Nurses' Health Study II (women only). Women aged 25-55 years and men aged 45-75 years at baseline, who had no diagnosis of cancer at baseline, and who responded to the question about melatonin supplement use (yes or no) were included. We excluded baseline prevalent cardiovascular disease and baseline prevalent type 2 diabetes for the main analyses. The main outcomes were cardiovascular disease and type 2 diabetes incidence. In secondary analyses, we stratified by duration of rotating night shift work in the Nurses' Health Study and Nurses' Health Study II to examine whether the associations with melatonin supplement use differed by rotating night shift work. For the cardiovascular disease analysis, we included 67 202 women from the Nurses' Health Study (follow-up 1998-2019, mean age at baseline: 63·6 years [SD 7·1]), 26 629 men from the Health Professionals Follow-up Study (1998-2020, 62·9 years [8·8], and 65 241 women from the Nurses' Health Study II (2003-19, 48·2 years [4·7]). Follow-up for incident type 2 diabetes was from 1998 to June 30, 2021, for the Nurses' Health Study; 2003 to Jan 31, 2023, for the Nurses' Health Study II; and from 1998 to Jan 31, 2020, for the Health Professionals' Follow-up Study. Melatonin supplement use in the study cohorts doubled over recent decades from less than 2% in 1998-2007 to 4% or higher in 2014-15 (4·0% in men and 5·3% in women). We documented 16 917 incident cardiovascular disease events during 2 609 068 person-years of follow-up and 12 730 incident cases of type 2 diabetes during 2 701 830 person-years of follow-up. In a pooled analysis of the three cohorts, comparing users with non-users of melatonin supplements, the pooled multivariable-adjusted hazard ratios were 0·94 (95% CI 0·83-1·06, p=0·32) for cardiovascular disease and 0·98 (0·86-1·12, p=0·80) for type 2 diabetes. In secondary analyses, melatonin supplement use appeared to attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease (pinteraction=0·013) among the female nurses. With up to 23 years of follow-up of three large prospective cohorts of middle-aged and older men and women, self-reported melatonin supplement use was not associated with risk of type 2 diabetes or cardiovascular disease. Further research is warranted to assess if melatonin supplement use could mitigate the potential risks of type 2 diabetes and cardiovascular disease associated with rotating night shift work. US National Institutes of Health.

Ultra-processed food consumption and mortality among patients with stages I–III colorectal cancer: a prospective cohort study

Ultra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored. Data collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I-III CRC within the Nurses' Health Study and Health Professionals Follow-up Study during 1980-2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders. The mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths were documented, including 321 from CRC and 335 from CVD. Compared to those in the lowest quintile (median=3.6 servings/d), patients in the highest quintile (median=10 servings/d) of post-diagnostic UPF intake had higher CVD mortality (HR=1.65, 95% CI=1.13-2.40) but not CRC or all-cause mortality. Among UPF subgroups, higher consumption of fats/condiments/sauces was associated with a higher risk of CVD-specific mortality (highest vs. lowest quintile of intake, HR=1.96, 95% CI=1.41-2.73), and higher intake of ice cream/sherbet was associated with an increased risk of CRC-specific mortality (highest vs. lowest quintile, HR=1.86, 95% CI: 1.33-2.61). No statistically significant association was found between UPF subgroups and overall mortality. Higher post-diagnostic intake of total UPFs and fats/condiments/sauces in CRC survivors is associated with higher CVD mortality, and higher ice cream/sherbet intake is linked to higher CRC mortality. US National Institutes of Health and the American Cancer Society.

Safety and immunogenicity of a polyvalent DNA–protein HIV vaccine with matched Env immunogens delivered as a prime–boost regimen or coadministered in HIV-uninfected adults in the USA (HVTN 124): a phase 1, placebo-controlled, double-blind randomised controlled trial

An effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA-protein HIV vaccine with matching envelope (Env) immunogens. HVTN 124 was a randomised, phase 1, placebo-controlled, double-blind study, including participants who were HIV seronegative and aged 18-50 years at low risk for infection. The DNA vaccine comprised five plasmids: four copies expressing Env gp120 (clades A, B, C, and AE) and one gag p55 (clade C). The protein vaccine included four DNA vaccine-matched GLA-SE-adjuvanted recombinant gp120 proteins. Participants were enrolled across six clinical sites in the USA and were randomly assigned to placebo or one of two vaccine groups (ie, prime-boost or coadministration) in a 5:1 ratio in part A and a 7:1 ratio in part B. Vaccines were delivered via intramuscular needle injection. The primary outcomes were safety and tolerability, assessed via frequency, severity, and attributability of local and systemic reactogenicity and adverse events, laboratory safety measures, and early discontinuations. Part A evaluated safety. Part B evaluated safety and immunogenicity of two regimens: DNA prime (administered at months 0, 1, and 3) with protein boost (months 6 and 8), and DNA-protein coadministration (months 0, 1, 3, 6, and 8). All randomly assigned participants who received at least one dose were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT03409276) and is closed to new participants. Between April 19, 2018 and Feb 13, 2019, 60 participants (12 in part A [five men and seven women] and 48 in part B [21 men and 27 women]) were enrolled. All 60 participants received at least one dose, and 14 did not complete follow-up (six of 21 in the prime-boost group and eight of 21 in the coadminstration group). 11 clinical adverse events deemed by investigators as study-related occurred in seven of 48 participants in part B (eight of 21 in the prime-boost group and three of 21 in the coadministration group). Local reactogenicity in the vaccine groups was common, but the frequency and severity of reactogenicity signs or symptoms did not differ between the prime-boost and coadministration groups (eg, 20 [95%] of 21 in the prime-boost group vs 21 [100%] of 21 in the coadministration group had either local pain or tenderness of any severity [p=1·00], and seven [33%] vs nine [43%] had either erythema or induration [p=0·97]), nor did laboratory safety measures. There were no delayed-type hypersensitivity reactions or vasculitis or any severe clinical adverse events related to vaccination. The most frequently reported systemic reactogenicity symptoms in the active vaccine groups were malaise or fatigue (five [50%] of ten in part A and 17 [81%] of 21 in the prime-boost group vs 15 [71%] of 21 in the coadministration group in part B), headache (five [50%] and 18 [86%] vs 12 [57%]), and myalgia (four [40%] and 13 [62%] vs ten [48%]), mostly of mild or moderate severity. Both vaccine regimens were safe, warranting evaluation in larger trials. US National Institutes of Health and US National Institute of Allergy and Infectious Diseases.

Efficacy of assisted partner services for people who inject drugs in Kenya to identify partners living with HIV and hepatitis C virus infection: a prospective cohort study

People who inject drugs are at increased risk of both HIV and hepatitis C virus (HCV) infections but face barriers to testing and engagement in care. Assisted partner services are effective in locating people with HIV but are understudied among people who inject drugs. We assessed whether assisted partner services could be used to find, test for HIV and HCV infections, and link to care the partners of people who inject drugs in Kenya. In this prospective study at eight sites offering harm-reduction services in Kenya, we enrolled people aged 18 years or older who inject drugs and were living with HIV (index participants) between Feb 27, 2018, and Nov 1, 2021. Index participants provided information about their sexual and injecting partners (ie, anyone with whom they had had sexual intercourse or injected drugs in the previous 3 years), and then community-embedded peer educators located partners and referred them for enrolment in the study (partner participants). All participants underwent testing for HCV infection, and partner participants also underwent HIV testing. Index and partner participants with HIV but who were not on antiretroviral therapy (ART) were linked with treatment services, and those positive for HCV were linked to treatment with direct-acting antivirals. We calculated the number of index participants whom we needed to interview to identify partner participants with HIV and HCV infection. We enrolled 989 people living with HIV who inject drugs, who mentioned 4705 sexual or injecting partners. Of these 4705 partners, we enrolled 4597 participants, corresponding to 3323 unique individuals. 597 (18%) partner participants had HIV, of whom 506 (85%) already knew their status. 358 (71%) of those who knew they were HIV positive were virally suppressed. 393 (12%) partner participants were HCV antibody positive, 213 (54%) of whom had viraemia and 104 (26%) of whom knew their antibody status. 1·66 (95% CI 1·53-1·80) index participants had to be interviewed to identify a partner with HIV, and 4·24 (3·75-4·85) had to be interviewed to find a partner living with HIV who was unaware of their HIV status, not on ART, or not virally suppressed. To find a partner seropositive for HCV who did not know their antibody status, 3·47 (3·11-3·91) index participants needed to be interviewed. Among the 331 index and partner participants living with HIV who were not on ART at enrolment, 238 (72%) were taking ART at 6-month follow-up. No adverse events were attributed to study procedures. Use of assisted partner services among people with HIV who inject drugs was safe and identified partners with HIV and HCV infections. Assisted partner services was associated with increased uptake of ART for both index participants and partners. US National Institutes of Health.

Indications and Coverage of Metabolic and Bariatric Surgery: A Worldwide IFSO Survey Comparing Different National Guidelines.

Knowing how metabolic and bariatric surgery (MBS) is indicated in different countries is essential information for the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). To analyze the indications for MBS recommended by each of the national societies that comprise the IFSO and how MBS is financed in their countries. All IFSO societies were asked to fill out a survey asking whether they have, and which are their national guidelines, and if MBS is covered by their public health service. Sixty-three out of the 72 IFSO national societies answered the form (87.5%). Among them, 74.6% have some kind of guidelines regarding indications for MBS. Twenty-two percent are still based on the US National Institute of Health (NIH) 1991 recommendations, 43.5% possess guidelines midway the 1991s and ASMBS/IFSO 2022 ones, and 34% have already adopted the latest ASMBS/IFSO 2022 guidelines. MBS was financially covered in 65% of the countries. Most of the IFSO member societies have MBS guidelines. While more than a third of them have already shifted to the most updated ASMBS/IFSO 2022 ones, another significant number of countries are still following the NIH 1991 guidelines or even do not have any at all. Besides, there is a significant number of countries in which surgical treatment is not yet financially covered. More effort is needed to standardize indications worldwide and to influence insurers and health policymakers to increase the coverage of MBS.

MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Pick's disease is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. Pick's disease is pathologically defined by the presence in the frontal and temporal lobes of Pick bodies, composed of hyperphosphorylated, three-repeat tau protein, encoded by the MAPT gene. MAPT has two distinct haplotypes, H1 and H2; the MAPT H1 haplotype is the major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy and corticobasal degeneration), and the MAPT H2 haplotype is protective for these disorders. The primary aim of this study was to evaluate the association of MAPT H2 with Pick's disease risk, age at onset, and disease duration. In this genetic association study, we used data from the Pick's disease International Consortium, which we established to enable collection of data from individuals with pathologically confirmed Pick's disease worldwide. For this analysis, we collected brain samples from individuals with pathologically confirmed Pick's disease from 35 sites (brainbanks and hospitals) in North America, Europe, and Australia between Jan 1, 2020, and Jan 31, 2023. Neurologically healthy controls were recruited from the Mayo Clinic (FL, USA, or MN, USA between March 1, 1998, and Sept 1, 2019). For the primary analysis, individuals were directly genotyped for the MAPT H1-H2 haplotype-defining variant rs8070723. In a secondary analysis, we genotyped and constructed the six-variant-defined (rs1467967-rs242557-rs3785883-rs2471738-rs8070723-rs7521) MAPT H1 subhaplotypes. Associations of MAPT variants and MAPT haplotypes with Pick's disease risk, age at onset, and disease duration were examined using logistic and linear regression models; odds ratios (ORs) and β coefficients were estimated and correspond to each additional minor allele or each additional copy of the given haplotype. We obtained brain samples from 338 people with pathologically confirmed Pick's disease (205 [61%] male and 133 [39%] female; 338 [100%] White) and 1312 neurologically healthy controls (611 [47%] male and 701 [53%] female; 1312 [100%] White). The MAPT H2 haplotype was associated with increased risk of Pick's disease compared with the H1 haplotype (OR 1·35 [95% CI 1·12 to 1·64], p=0·0021). MAPT H2 was not associated with age at onset (β -0·54 [95% CI -1·94 to 0·87], p=0·45) or disease duration (β 0·05 [-0·06 to 0·16], p=0·35). Although not significant after correcting for multiple testing, associations were observed at p less than 0·05: with risk of Pick's disease for the H1f subhaplotype (OR 0·11 [0·01 to 0·99], p=0·049); with age at onset for H1b (β 2·66 [0·63 to 4·70], p=0·011), H1i (β -3·66 [-6·83 to -0·48], p=0·025), and H1u (β -5·25 [-10·42 to -0·07], p=0·048); and with disease duration for H1x (β -0·57 [-1·07 to -0·07], p=0·026). The Pick's disease International Consortium provides an opportunity to do large studies to enhance our understanding of the pathobiology of Pick's disease. This study shows that, in contrast to the decreased risk of four-repeat tauopathies, the MAPT H2 haplotype is associated with an increased risk of Pick's disease in people of European ancestry. This finding could inform development of isoform-related therapeutics for tauopathies. Wellcome Trust, Rotha Abraham Trust, Brain Research UK, the Dolby Fund, Dementia Research Institute (Medical Research Council), US National Institutes of Health, and the Mayo Clinic Foundation.

Evaluating GPT-V4 (GPT-4 with Vision) on Detection of Radiologic Findings on Chest Radiographs.

Background Generating radiologic findings from chest radiographs is pivotal in medical image analysis. The emergence of OpenAI's generative pretrained transformer, GPT-4 with vision (GPT-4V), has opened new perspectives on the potential for automated image-text pair generation. However, the application of GPT-4V to real-world chest radiography is yet to be thoroughly examined. Purpose To investigate the capability of GPT-4V to generate radiologic findings from real-world chest radiographs. Materials and Methods In this retrospective study, 100 chest radiographs with free-text radiology reports were annotated by a cohort of radiologists, two attending physicians and three residents, to establish a reference standard. Of 100 chest radiographs, 50 were randomly selected from the National Institutes of Health (NIH) chest radiographic data set, and 50 were randomly selected from the Medical Imaging and Data Resource Center (MIDRC). The performance of GPT-4V at detecting imaging findings from each chest radiograph was assessed in the zero-shot setting (where it operates without prior examples) and few-shot setting (where it operates with two examples). Its outcomes were compared with the reference standard with regards to clinical conditions and their corresponding codes in the International Statistical Classification of Diseases, Tenth Revision (ICD-10), including the anatomic location (hereafter, laterality). Results In the zero-shot setting, in the task of detecting ICD-10 codes alone, GPT-4V attained an average positive predictive value (PPV) of 12.3%, average true-positive rate (TPR) of 5.8%, and average F1 score of 7.3% on the NIH data set, and an average PPV of 25.0%, average TPR of 16.8%, and average F1 score of 18.2% on the MIDRC data set. When both the ICD-10 codes and their corresponding laterality were considered, GPT-4V produced an average PPV of 7.8%, average TPR of 3.5%, and average F1 score of 4.5% on the NIH data set, and an average PPV of 10.9%, average TPR of 4.9%, and average F1 score of 6.4% on the MIDRC data set. With few-shot learning, GPT-4V showed improved performance on both data sets. When contrasting zero-shot and few-shot learning, there were improved average TPRs and F1 scores in the few-shot setting, but there was not a substantial increase in the average PPV. Conclusion Although GPT-4V has shown promise in understanding natural images, it had limited effectiveness in interpreting real-world chest radiographs. © RSNA, 2024 Supplemental material is available for this article.

일상 속으로: 로버트 펠릭스(Robert H. Felix)와 정신보건법의 기원

This study traces the origins of the transition from an institution-based mental health structure to a community-based policy by examining the early career and contributions of Dr. Robert H. Felix, a major figure who helped pass the National Mental Health Act of 1946 and was the first director of the National Institute of Mental Health. Felix began his career in the U.S. Public Health (USPHS) in the 1930s and was stationed at various PHS-affiliated institutes in the early 1940s. Post-World War II (WWII), he leveraged his professional experiences with federal-level institutions, by laying the groundwork for overarching national mental health policy plans. Based on lessons learned from total war, his prospective plan mainly focused on the prevention of mental illness, whether chronic or acute. In this regard, this paper demonstrates how American mental health policies use centralized federal funds to help community-based prevention of early-stage illness.

Prediction of Chest X-Ray Abnormalities using Ensemble Learning

Abstract: Chest X-rays are a cornerstone of medical imaging, enabling rapid and cost-effective diagnosis of numerous chest pathologies. However, limitations in radiologist availability and long wait times can significantly delay diagnoses, potentially impacting patient outcomes. This study explores the potential of deep learning to address these challenges. Deep learning algorithms can analyse medical images and identify patterns associated with various diseases. In this study, Various deep learning models were trained and evaluated, including DenseNet121, EfficientNetB1, Xception, and an ensemble model combining EfficientNetB1 and Xception, using a random sample of 5,606 chest X-ray images from the National Institutes of Health (NIH) chest X-ray dataset. The ensemble model achieved the most promising results, demonstrating an accuracy of 72.66% and an AUC-ROC (Area Under the Receiver Operating Characteristic Curve) of 76.05%