UNASSIGNED: How often hypertensive patients could achieve remission to normal blood pressure (BP) (i.e., <140/90 mmHg) in the absence of antihypertensive drugs, which is important for the management of hypertension, remains largely unknown. This observational study aimed to investigate the change of BP in older adults with hypertension who did not take antihypertensive drugs and preliminarily examine whether the remission from hypertension to normal BP observed in this setting was associated with lower risk of cardiovascular disease (CVD).
UNASSIGNED: 2760 participants aged 33-99 years (median 60 years, interquartile 54-68 years) from the Health and Retirement Study (wave 2006 to wave 2018) and the English Longitudinal Study of Ageing (wave 1998 to wave 2016), who had no major CVD, were hypertensive, and were not on antihypertensive drugs at the time of baseline BP measurement, and had at least one follow-up BP measurement before which no antihypertensive drugs were taken, were included for analysis. The main outcome was the proportion of patients who achieved remission of hypertension at the last wave of measurement.
UNASSIGNED: During a median follow-up of six years, 52% of the participants showed a reduction of ≥6 mmHg in systolic BP and 60% a reduction of ≥3 mmHg in diastolic BP. 1171 participants (42%, 95% CI: 41-44%) achieved remission at the last measurement, and by that time 67%, 43%, and 29% of them had maintained the normotensive state for around 4, 8, and 12 years, respectively. Various supplementary analyses that aimed to examine the impact of chance and bias yielded similar results. Preliminary analyses showed that being non-smokers at baseline, achieving a normal body mass index during follow-up, and quitting alcohol drinking during follow-up, among others, were associated with the remission of hypertension. Compared with the participants who remained hypertensive, those who achieved remission had a lower CVD risk (adjusted hazard ratio 0.66, 95% CI: 0.47-0.92).
UNASSIGNED: In many of this study population, hypertension could be reversed without the intervention of drug treatment in the first few years after diagnosis. This finding may have implications for more individualized management of hypertension. Further studies to identify the factors or algorithms predictive of such hypertension remission are warranted.
UNASSIGNED: The Chinese University of Hong Kong (7106452; 7105959),Shenzhen Science and Technology Program (KQTD20190929172835662), Strategic Priority Research Program of Chinese Academy of Sciences (XDB 38040200), National Institute on Aging (R01AG017644; NIA U01AG009740).

Our objectives were to ascertain the following: (1) the prevalence and socioeconomic distribution of hypertension (HTN), undiagnosed for HTN, and untreated cases of HTN-diagnosed individuals; (2) the relationship between SES and the prevalence of HTN, undiagnosed for HTN, and untreated for HTN; and (3) whether sex moderate this association. Data from the 2017-18 Bangladesh Demographic Health Survey were used. 11,776 participants who were 18 years of age or older responded to our analysis. The age-adjusted prevalence of HTN, undiagnosed for HTN, and untreated cases was 25.1%, 57.2%, and 12.3%. Compared to females, males were less likely to have HTN but more likely to have undiagnosed HTN. People in the rich SES groups had a higher odd of (adjusted odds ratio [aoR] 1.25; 95% confidence interval [CI] 1.08-3.45) of having HTN compared to those in the poor SES group. When compared to individuals in the poor SES group, those in the rich SES group had lower odds of undiagnosed (aoR 0.57; 95% CI 0.44-0.74) and untreated (aoR 0.56; 95% CI 0.31-0.98) for HTN. Sex moderated the association between SES and HTN prevalence, which showed that men from rich SES were more likely to suffer from HTN than men from poor SES. According to this study, the government and other pertinent stakeholders should concentrate more on developing suitable policy measures to reduce the risk of HTN, particularly for men in rich socioeconomic groups. They should also concentrate on screening and diagnosing HTN in socioeconomically disadvantaged populations, regardless of sex.

UNASSIGNED: This study aimed to clarify the association between treatment status (untreated or treated) at the start of community mental health outreach services and service intensity.
UNASSIGNED: This retrospective cohort study was conducted using the Tokorozawa City mental health outreach service users\' data. Treatment status at the start of service (exposure variable) and the service intensity (outcome variables) were taken from clinical records. Poisson regression and linear regression analyses were conducted. The frequency of medical or social service use 12 months after service initiation was also calculated. This study was approved by the Research Ethics Committee at the National Center of Neurology and Psychiatry (No. A2020-081).
UNASSIGNED: Of 89 people, 37 (42%) were untreated. Family members in the untreated group were more likely to be targets or recipients of services than in the treated group (b = 0.707, p < 0.001, Bonferroni-adjusted p < 0.001). Compared to the treated group, the untreated group received fewer services themselves (b = -0.290, p = 0.005), and also fewer services by telephone (b = -0.252, p = 0.012); by contrast, they received more services at the health center (b = 0.478, p = 0.031) and for family support (b = 0.720, p = 0.024), but these significant differences disappeared after Bonferroni adjustment. At least 11% of people in the untreated group were hospitalized and 35% were outpatients 12 months after service initiation.
UNASSIGNED: Family involvement may be a key service component for untreated people. The service intensity with and without treatment may vary by service location.

UNASSIGNED: Schizophrenia is considered to be a disorder of dysconnectivity characterized by abnormal functional integration between distinct brain regions. Different brain connection abnormalities were found to be correlated with various clinical manifestations, but whether a common deficit in functional connectivity (FC) in relation to both clinical symptoms and cognitive impairments could present in first-episode patients who have never received any medication remains elusive.
UNASSIGNED: To find a core deficit in the brain connectome that is related to both psychopathological and cognitive manifestations.
UNASSIGNED: A total of 75 patients with first-episode schizophrenia and 51 healthy control participants underwent scanning of the brain and clinical ratings of behaviors. A principal component analysis was performed on the clinical ratings of symptom and cognition. Partial correlation analyses were conducted between the main psychopathological components and resting-state FC that were found abnormal in schizophrenia patients.
UNASSIGNED: Using the principal component analysis, the first principal component (PC1) explained 37% of the total variance of seven clinical features. The ratings of GAF and BACS contributed negatively to PC1, while those of PANSS, HAMD, and HAMA contributed positively. The FCs positively correlated with PC1 mainly included connections related to the insula, precuneus gyrus, and some frontal brain regions. FCs negatively correlated with PC1 mainly included connections between the left middle cingulate cortex and superior and middle occipital regions.
UNASSIGNED: In conclusion, we found a linked pattern of FC associated with both psychopathological and cognitive manifestations in drug-naïve first-episode schizophrenia characterized as the dysconnection related to the frontal and visual cortex, which may represent a core deficit of brain FC in patients with schizophrenia.

暂无摘要。

Gambling disorder is common, affects 0.5-2% of the population, and is under-treated. Duration of untreated illness (DUI) has emerged as a clinically important concept in the context of other mental disorders, but DUI in gambling disorder, has received little research scrutiny.
Data were aggregated from previous clinical trials in gambling disorder with people who had never previously received any treatment. DUI was quantified, and clinical characteristics were compared as a function of DUI status.
A total of 298 individuals were included, and the mean DUI (standard deviation) was 8.9 (8.4) years, and the median DUI was 6 years. Longer DUI was significantly associated with male gender, older age, earlier age when the person first started to gamble, and family history of alcohol use disorder. Longer DUI was not significantly associated with racial-ethnic status, gambling symptom severity, current depressive or anxiety severity, comorbidities, or disability/functioning. The two groups did not differ in their propensity to drop out of the clinical trials, nor in overall symptom improvement associated with participation in those trials.
These data suggest that gambling disorder has a relatively long DUI and highlight the need to raise awareness and foster early intervention for affected and at-risk individuals. Because earlier age at first gambling in any form was strongly linked to longer DUI, this highlights the need for more rigorous legislation and education to reduce exposure of younger people to gambling.

UNASSIGNED: Duration of untreated psychosis (DUP) is an important modifiable factor affecting schizophrenia outcomes. A dearth of research in India on untreated versus treated schizophrenia warrants further research.
UNASSIGNED: This was a longitudinal study in a tertiary hospital over 2 years. Inpatients diagnosed with schizophrenia (N = 116), aged 18-45, were divided into untreated and treated groups. Diagnostic confirmation, severity assessment, and clinical outcome were done using ICD-10 criteria, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (CGI) scale. Follow-up was done at 12 and 24 weeks. DUP was measured, and its association with the outcome was assessed.
UNASSIGNED: Final analysis included 100 patients, 50 each of previously untreated and treated. Untreated patients had lower age and duration of illness (DOI), but higher DUP (p < .001). Treated patients showed much improvement on CGI-I at 12 weeks (p = .029), with no difference at 24 weeks. PANSS severity comparison showed no difference, and both groups followed a declining trend. In untreated patients, age of onset (AoO) was negatively correlated with severity (except general symptoms at baseline) at all follow-ups (\'r\' range = -0.32 to -0.49, p < .05), while DOI showed a positive correlation with negative and general symptoms at 12 weeks (r ~ 0.3, p < .05). Treated patients showed inconsistent and lower negative correlation between AoO and PANSS, with no correlation between severity and DOI. The mean sample DUP was 17.9 ± 31.6 weeks; it negatively correlated with education (r = -0.25, p = .01) and positively with PANSS severity (\'r\' range = 0.22 to 0.30, p < .05) at all follow-ups, especially negative symptoms. Patients with no or minimal improvement on CGI at 24 weeks had higher DUP (Quade\'s ANOVA F[1,98] = 6.24, p = .014).
UNASSIGNED: Illness variables in untreated schizophrenia affect severity, which has delayed improvement than treated schizophrenia. Higher DUP is associated with negative symptoms of schizophrenia.

Lymph nodes with acellular mucin harvested from treated colorectal cancers (CRC) are staged as pN0. However, there is variability among pathologists while reporting the pN stage when acellular mucin is found within nodes of untreated CRCs. While the UICC guidelines suggest staging them as pN1, the AJCC and CAP do not offer any recommendations. In order to characterize their clinicopathologic features and outcome, we compared 16 untreated CRCs (study group; mean age: 68 years) harboring nodes with acellular mucin with 34 pN0 and 25 pN1 untreated CRC controls. All tumors were unifocal; 12 (75%) were right-sided lesions. Most cases (75%) showed one node with acellular mucin (range: 1-3). MMR-deficient tumors were significantly more common in the study group (83%) compared to pN0 (33%; p = 0.006) and pN1 controls (8%; p < 0.001). The overall survival of study group patients was closer to pN0 compared to pN1 controls; however, this difference was not statistically significant. In conclusion, untreated CRC that harbor acellular mucin within lymph nodes commonly present as right-sided, MMR-deficient tumors in older women that show a non-mucinous phenotype. While the limited number of cases precludes us from making any formal recommendations about staging, we suggest that the finding of acellular mucin in a node should prompt evaluation of deeper levels (with or without cytokeratin immunohistochemistry) and submission of all pericolonic fat for additional lymph node harvest. Whether acellular mucin in nodes of untreated CRCs is related to the indolent biology of the disease, a robust local immune response or MMR deficiency requires further investigation.

Phenylketonuria (PKU) is an inborn error of metabolism caused by variants in the phenylalanine hydroxylase (PAH) gene and it is characterized by excessively high levels of phenylalanine in body fluids. PKU is a paradigm for a genetic disease that can be treated and majority of developed countries have a population-based newborn screening. Thus, the combination of early diagnosis and immediate initiation of treatment has resulted in normal intelligence for treated PKU patients. Although PKU is a monogenic disease, decades of research and clinical practice have shown that the correlation between the genotype and corresponding phenotype is not simple at all. Attempts have been made to discover modifier genes for PKU cognitive phenotype but without any success so far. We conducted whole genome sequencing of 4 subjects from unrelated non-consanguineous families who presented with pathogenic mutations in the PAH gene, high blood phenylalanine concentrations and near-normal cognitive development despite no treatment. We used cross sample analysis to select genes common for more than one patient. Thus, the SHANK gene family emerged as the only relevant gene family with variants detected in 3 of 4 analyzed patients. We detected two novel variants, p.Pro1591Ala in SHANK1 and p.Asp18Asn in SHANK2, as well as SHANK2:p.Gly46Ser, SHANK2:p.Pro1388_Phe1389insLeuPro and SHANK3:p.Pro1716Thr variants that were previously described. Computational analysis indicated that the identified variants do not abolish the function of SHANK proteins. However, changes in posttranslational modifications of SHANK proteins could influence functioning of the glutamatergic synapses, cytoskeleton regulation and contribute to maintaining optimal synaptic density and number of dendritic spines. Our findings are linking SHANK gene family and brain plasticity in PKU for the first time. We hypothesize that variant SHANK proteins maintain optimal synaptic density and number of dendritic spines under high concentrations of phenylalanine and could have protective modifying effect on cognitive development of PKU patients.

The dynamic nature of the SIV population during disease progression in the SIV/macaque model of AIDS and the factors responsible for its behavior have not been documented, largely owing to the lack of sufficient spatial and temporal sampling of both viral and host data from SIV-infected animals. In this study, we detail Bayesian coalescent inference of the changing collective intra-host viral effective population size (Ne ) from various tissues over the course of infection and its relationship with what we demonstrate is a continuously changing immune cell repertoire within the blood. Although the relative contribution of these factors varied among hosts and time points, the adaptive immune response best explained the overall periodic dynamic behavior of the effective virus population. Data exposing the nature of the relationship between the virus and immune cell populations revealed the plausibility of an eco-evolutionary mathematical model, which was able to mimic the large-scale oscillations in Ne through virus escape from relatively few, early immunodominant responses, followed by slower escape from several subdominant and weakened immune populations. The results of this study suggest that SIV diversity within the untreated host is governed by a predator-prey relationship, wherein differing phases of infection are the result of adaptation in response to varying immune responses. Previous investigations into viral population dynamics using sequence data have focused on single estimates of the effective viral population size (Ne ) or point estimates over sparse sampling data to provide insight into the precise impact of immune selection on virus adaptive behavior. Herein, we describe the use of the coalescent phylogenetic frame- work to estimate the relative changes in Ne over time in order to quantify the relationship with empirical data on the dynamic immune composition of the host. This relationship has allowed us to expand on earlier simulations to build a predator-prey model that explains the deterministic behavior of the virus over the course of disease progression. We show that sequential viral adaptation can occur in response to phases of varying immune pressure, providing a broader picture of the viral response throughout the entire course of progression to AIDS.