Tag: nevin manimala

J Sep Sci. 2023 Mar 25:e2200985. doi: 10.1002/jssc.202200985. Online ahead of print.

ABSTRACT

Astragali Radix is widely used because of its dual use in medicine and food, and its quality evaluation is of great importance. In this study, a pseudo-targeted metabolomics approach based on scheduled multiple reaction monitoring was developed, and a total of 114 compounds with good linearity, sensitivity and reproducibility were selected for relative quantification, and the chemical differences between Astragali Radix of different growth patterns were further compared by chemometric analysis. With the help of multivariate and univariate analysis, 26 differential compounds between wild/semi-wild Astragali Radix and cultivated Astragali Radix were determined. Then 5 marker compounds were screened out by lasso regression, and further verified by systematic clustering, random forest, support vector machine, and logistic regression. In addition, malonyl-substituted flavonoids showed relatively higher content in wild/semi-wild Astragali Radix. Thus, the malonyl-substitution was the characteristic for flavonoids in wild/semi-wild Astragali Radix. In conclusion, the application of pseudo-targeted metabolomics and various statistical methods could offer multi-dimensional information for the holistic quality evaluation of Astragali Radix. This article is protected by copyright. All rights reserved.

PMID:36965089 | DOI:10.1002/jssc.202200985

Cancer Med. 2023 Mar 25. doi: 10.1002/cam4.5842. Online ahead of print.

ABSTRACT

BACKGROUND: The first HPV-vaccine eligible cohorts in the Netherlands will enter the cervical screening program in 2023. However, a substantial number of young women already have had a cervical sample taken before entry into the regular screening program. This study was initiated to explore early effects of HPV vaccination on detection of cytological abnormalities in cervical samples of women younger than the screening age.

METHODS: Results of cervical samples were obtained from the Dutch National Pathology Databank (PALGA) and were linked to the women’s HPV vaccination status from the national vaccination registry (Praeventis) (N = 42,171). Occurrence of low-grade and high-grade squamous intraepithelial lesions or worse (LSIL and HSIL+) and high-risk HPV positive tests (hrHPV) in the first cervical sample were compared between vaccinated and unvaccinated women by multivariable logistic regression analysis, corrected for age at cervical sampling and age of vaccination (12/13 years, ≥ = 14 years).

RESULTS: For fully vaccinated women (three- or two-dose schedule), statistically significant reductions were seen for all outcomes compared to unvaccinated women (hrHPV: adjusted OR, 0.70, 95% CI, 0.63-0.79; LSIL: 0.70, 0.61-0.80; HSIL+: 0.39, 0.30-0.51).

CONCLUSIONS: By linking nation-wide registries on pathology and vaccination, we show significant beneficial early effects of HPV-vaccination on LSIL, HSIL+, CIN3/AIS/carcinoma and hrHPV detection in young women upto 24 years of age who have a cervical sample taken before entry into the cervical cancer screening program.

PMID:36965085 | DOI:10.1002/cam4.5842

J Physiol. 2023 Mar 25. doi: 10.1113/JP283986. Online ahead of print.

ABSTRACT

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) elegantly probes excitability and connectivity of the human brain. However, TMS-EEG signals inevitably also contain sensory evoked responses caused by TMS-associated auditory and somatosensory inputs, constituting a substantial confounding factor. Here we applied our recently established optimized SHAM protocol (Gordon et al., Neuroimage 2021:118708) to disentangle TMS-EEG responses caused by TMS vs. sensory input. One unresolved question is whether these responses superimpose without relevant interaction, a requirement for their disaggregation by the optimized SHAM approach. We applied in 20 healthy subjects a pharmacological intervention using a single oral dose of 20 mg of diazepam, a positive modulator of GABAA receptors. Diazepam decreased the amplitudes of the P60 and P150 components specifically in the ACTIVE TMS and/or the ACTIVE TMS minus SHAM conditions but not in the SHAM condition, pointing to a response caused by TMS. In contrast, diazepam suppressed the amplitude of the N100 component indiscriminately in the ACTIVE TMS and SHAM conditions but not in the ACTIVE TMS minus SHAM condition, pointing to a response caused by sensory input. Moreover, diazepam suppressed the beta-band response observed in the motor cortex specifically after ACTIVE TMS and ACTIVE TMS minus SHAM. These findings demonstrate lack of interaction of TMS-EEG responses caused by TMS vs. sensory input and validate optimized SHAM-controlled TMS-EEG as an appropriate approach to untangle these TMS-EEG responses. This gain of knowledge will enable the proficient use of TMS-EEG to probe physiology of human cortex. KEY POINTS: Optimized SHAM disentangles TMS-EEG responses caused by TMS vs. sensory input Diazepam modulates differentially TMS-EEG responses caused by TMS vs. sensory input Diazepam modulation of P60 and P150 indicate TMS-EEG responses caused by TMS Diazepam modulation of N100 indicate a TMS-EEG response caused by sensory input Abstract figure legend a. Representation of the TMS target on the scalp (marked as red “x”) indicating the left primary motor cortex (around the location of the C3 electrode). b. Representation of the SHAM TMS condition, which involved the delivery of auditory (masking nose and sham coil) and somatosensory stimuli (scalp electrical stimulation) of equivalent intensity compared to the ACTIVE TMS. To the right, topographical plots display the results from the statistical comparison between responses post vs. pre diazepam intake, using cluster-based dependent samples t-tests (electrodes that composed the significant clusters in cyan). Below, time course plot of the EEG responses to the stimuli before (green) and after (purple) the intake of diazepam. Plotted signal corresponds to the average across all significant electrodes, displayed in the topographical plots above. Shaded gray areas indicate the time windows of significant difference between the EEG responses. c. Representation of the ACTIVE TMS condition, which, in addition to auditory (masking noise and real coil) and somatosensory stimuli (scalp electrical stimulation and real coil), involved the direct activation of the underlying cortex. Time course plot of EEG responses and topographical plots as in “b”. d. By subtracting the individual EEG responses to sensory stimuli (SHAM) from the response to TMS (ACTIVE) we obtain the EEG response attributed solely to the direct cortical activation by TMS. Time course plot of EEG responses and topographical plots as in “b”. This article is protected by copyright. All rights reserved.

PMID:36965075 | DOI:10.1113/JP283986

NMR Biomed. 2023 Mar 25:e4937. doi: 10.1002/nbm.4937. Online ahead of print.

ABSTRACT

Chemical exchange saturation transfer (CEST) sensitively detects molecular alterations in the brain, such as relayed nuclear Overhauser effect (rNOE) CEST contrast at -3.5 ppm representing aliphatic protons in both lipids and proteins, and CEST contrast at 3.5 ppm correlates with protein amide protons. Myelin is rich in lipids, thus CEST could be explored as biomarkers for myelin pathology, which could contribute to multiple sclerosis (MS) diagnosis and prognosis. In this study, we aim to investigate the specificity of aliphatic rNOE and amide pool in myelin detection using cuprizone (CPZ) mouse model, which recapitulates the demyelination and remyelination of MS. In this study, preclinical 3T MRI was performed in nineteen male C57BL/6 mice. Mice in normal control group (NC, n=9) were fed with normal diet for the whole course, while mice in CPZ group (n=10) were fed with CPZ for 10 weeks followed by 4 weeks with normal diet. CEST contrasts of rNOE (-3.5 ppm) and amide (3.5 ppm) in brain regions of corpus callosum (CC) and caudate putamen were compared. Statistical differences among the groups were found with two-way ANOVA. We observed significant decreased rNOE (NC: 4.85 ± 0.09 %/s vs CPZ: 3.88 ± 0.18 %/s, p = 0.007) and amide pool (NC: 3.20 ± 0.10 %/s vs CPZ: 2.46 ± 0.16 %/s, p = 0.02) in CC after 8 weeks on CPZ diet (p < 0.05). Moreover, rNOE in CPZ recovered to a comparable level as NC at week 14 (p = 0.39), while amide remained at low level as NC (p = 0.051). Significant rNOE and amide changes validated with immunohistochemistry results of the demyelination and remyelination demonstrated great potential of CEST in revealing myelin pathology, which has implications in MS identification at the clinical-field strength 3T.

PMID:36965064 | DOI:10.1002/nbm.4937

J Obstet Gynaecol Res. 2023 Mar 25. doi: 10.1111/jog.15641. Online ahead of print.

ABSTRACT

AIM: To evaluate the associations between placental histopathology (signs of maternal and fetal vascular malperfusion, delayed villous maturation, villitis of unknown etiology) and subtypes of preeclampsia by onset, clinical aspects of the disease and neonatal outcome.

METHODS: Placental slides from preeclamptic pregnancies were retrospectively reviewed according to a uniform scheme. Information regarding obstetrical anamnesis, clinical data and perinatal outcome was collected from charts, and statistical analysis was performed in order to demonstrate associations between microscopic placental alterations and different aspects of preeclampsia.

RESULTS: A total of 49 cases were studied. Diffuse signs of maternal vascular malperfusion and avascular villi were more common in early-onset-preeclampsia associated with worse prognosis. Preeclampsia with fetal growth restriction had more often diffuse signs of maternal and fetal vascular malperfusion and villitis of unknown etiology. Recurring preeclampsia was associated with more common perivasculitis. Umbilical and uterine artery Doppler indices were associated with medial hypertrophy and/or acute atherosis of maternal decidual vessels. Large foci of avascular villi correlated with extent of maternal 24-h-proteinuria which itself correlated with outcome of preeclampsia. Rate of capillarisation of villi was significantly lower in case of hypertension requiring a three-drug combination of antihypertensive medications versus hypertension treated with one or two drugs, preeclampsia with growth restriction, and stillbirth versus live birth.

CONCLUSIONS: Early- versus late-onset-preeclampsia showed a markedly different profile of histopathological features and perinatal outcome, reflecting their distinguished pathogenesis and prognosis; preeclampsia complicated with fetal growth restriction also had distinctive features. Qualitative and quantitative changes define placental pathology of preeclampsia.

PMID:36965061 | DOI:10.1111/jog.15641

Acta Obstet Gynecol Scand. 2023 Mar 25. doi: 10.1111/aogs.14562. Online ahead of print.

ABSTRACT

INTRODUCTION: Pelvic girdle pain in pregnancy is a major public health concern. For too many women, the pain condition causes disability and sick leave, has a negative impact on daily life, and breeds doubt in their view as mother, partner, and worker. The pathophysiology is unknown and causal treatment is lacking. Depression in pregnancy is common, undertreated, and previously associated with pelvic girdle pain with unclear causal direction.

MATERIAL AND METHODS: A prospective inception cohort study of 356 Swedish women examined them in early and late pregnancy. Women with a positive Posterior Pelvic Pain Provocation test in early pregnancy were not included. The exposure, depressive symptoms in early pregnancy, was self-reported on the Hospital Anxiety and Depression Scale, depression part (0-21). Outcome measure in late pregnancy was a graded score on the Posterior Pelvic Pain Provocation test (0-8). Covariates for statistical adjustment were identified in a directed acyclic graph. Linear robust and logistic regression were used in the statistical analyses.

RESULTS: In early pregnancy, the 248 women with negative Posterior Pelvic Pain Provocation test had a mean score of 2.35 (± 2.3 standard deviation) on the Hospital Anxiety and Depression Scale, depression part. In a fully adjusted, multiple robust regression model a positive association was shown between Hospital Anxiety and Depression Scale score, depression part, and the Posterior Pelvic Pain Provocation test score in late pregnancy with an estimated effect of β = 0.32 (95% confidence interval [CI] 0.16-0.48, p < 0.001). Dichotomization of exposure (Hospital Anxiety and Depression Scale, depression part <8/≥8) and outcome (Posterior Pelvic Pain Provocation test score 0/>0) rendered adjusted odds ratio 1.71 (95% CI 0.38-7.7) and numbers needed to treat adjusted odds ratio 5.54 (95% CI -3.4-14.5).

CONCLUSIONS: Depressive symptoms in early pregnancy were associated with the development and intensity of pelvic girdle pain in late pregnancy. Considering the small sample size, screening and treatment for depressive symptoms in early pregnancy may enable a way to reduce and prevent disabling pelvic girdle pain in late pregnancy. Trials are needed to confirm the results.

PMID:36965059 | DOI:10.1111/aogs.14562

Colorectal Dis. 2023 Mar 25. doi: 10.1111/codi.16537. Online ahead of print.

ABSTRACT

AIM: Incisional hernia (IH) is a common complication of colorectal surgery, affecting up to 30% of patients at 2 years. Given the associated morbidity and high recurrence rates after attempted repair of IH, emphasis should be placed on prevention. There is an association between surgeon volume and outcomes in hernia surgery, yet there is little evidence regarding impact of the seniority of the surgeon performing abdominal wall closure on IH rate. The aim of our study was to assess the rates of IH at 1 year following abdominal wall closure between junior and senior surgeons in patients undergoing elective colorectal surgery.

METHODS: This was an exploratory analysis of patients who underwent elective surgery for colorectal cancer between 2014-2018 as part of the Hughes Abdominal Repair Trial (HART), a prospective, multicentre randomised control trial comparing abdominal wall closure methods. Grade of surgeon performing abdominal closure was categorised into “trainee” and “consultant” and compared to IH rate at one year.

RESULTS: A total of 663 patients were included in this retrospective analysis of patients in the HART trial. The rate of IH in patients closed by trainees was 20%, compared to 12% in those closed by consultants (p = <0.001). When comparing closure methods, IH rates were significantly higher in the Hughes closure arm between trainees and consultants (20% vs. 12%, p = 0.032), but not high enough in the mass closure arm to reach statistical significance (21% vs. 13%, p = 0.058). On multivariate analysis, age (p = 0.036, OR: 1.02, 95% CI: 1.00-1.04), Male sex (p = 0.049, OR: 1.61, 95% CI: 1.00-2.59) and closure by a trainee (p = 0.006, OR: 1.85, 95% CI: 1.20-2.85) were identified as risk factors for developing IH.

CONCLUSION: Patients who undergo abdominal wall closure by a surgeon in training have an increased risk of developing IH when compared to those closed by a consultant. Further work is needed to determine the impact of supervised and unsupervised trainees on IH rates, but abdominal wall closure should be regarded as a training opportunity in its own right.

PMID:36965056 | DOI:10.1111/codi.16537

Int J Cancer. 2023 Mar 25. doi: 10.1002/ijc.34524. Online ahead of print.

ABSTRACT

A concern of reverse causation exists about the association between nasopharyngeal carcinoma (NPC) prognosis and body mass index (BMI) at diagnosis, while the prognostic impact of BMI measured years before diagnosis is unknown. Therefore, we investigated associations of pre-diagnosis and pre-treatment BMI and body shape on NPC mortality. From a population-based patient cohort in southern China between 2010 and 2013, we included 2526 incident NPC cases with prospective follow-up through 2018. We assessed the associations of BMI and body shape at age 20 years, 10 years before diagnosis, and at diagnosis with NPC mortality, combining strategies of stratification and statistical adjustment to minimise reverse causation. We observed 25% lower all-cause mortality (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.64-0.89) and 28% lower NPC-specific mortality (HR 0.74, 95% CI: 0.51-1.03) among overweight vs normal-weight NPC cases at diagnosis. Lean body shapes 1 and 2 at diagnosis were associated with 68% and 23% higher all-cause mortality, respectively, compared with normal body shape 3. No effect modification by cancer stage was detected for associations with all-cause or NPC-specific mortality. Associations with BMI and body shape 10 years before diagnosis were similar but attenuated, while body size and shape at age 20 were not associated with mortality. Being overweight at diagnosis decreased mortality, and thinner body shape increased mortality, compared with normal weight/body shape. These associations may be due to poorer nutrition and treatment intolerance, resulting in treatment discontinuation and worse survival outcomes. This article is protected by copyright. All rights reserved.

PMID:36965052 | DOI:10.1002/ijc.34524

Stat Med. 2023 Mar 25. doi: 10.1002/sim.9715. Online ahead of print.

ABSTRACT

INTRODUCTION: When a study sample includes a large proportion of long-term survivors, mixture cure (MC) models that separately assess biomarker associations with long-term recurrence-free survival and time to disease recurrence are preferred to proportional-hazards models. However, in samples with few recurrences, standard maximum likelihood can be biased.

OBJECTIVE AND METHODS: We extend Firth-type penalized likelihood (FT-PL) developed for bias reduction in the exponential family to the Weibull-logistic MC, using the Jeffreys invariant prior. Via simulation studies based on a motivating cohort study, we compare parameter estimates of the FT-PL method to those by ML, as well as type 1 error (T1E) and power obtained using likelihood ratio statistics.

RESULTS: In samples with relatively few events, the Firth-type penalized likelihood estimates (FT-PLEs) have mean bias closer to zero and smaller mean squared error than maximum likelihood estimates (MLEs), and can be obtained in samples where the MLEs are infinite. Under similar T1E rates, FT-PL consistently exhibits higher statistical power than ML in samples with few events. In addition, we compare FT-PL estimation with two other penalization methods (a log-F prior method and a modified Firth-type method) based on the same simulations.

DISCUSSION: Consistent with findings for logistic and Cox regressions, FT-PL under MC regression yields finite estimates under stringent conditions, and better bias-and-variance balance than the other two penalizations. The practicality and strength of FT-PL for MC analysis is illustrated in a cohort study of breast cancer prognosis with long-term follow-up for recurrence-free survival.

PMID:36964996 | DOI:10.1002/sim.9715

J Psychiatr Ment Health Nurs. 2023 Mar 25. doi: 10.1111/jpm.12918. Online ahead of print.

ABSTRACT

WHAT IS KNOWN ON THE SUBJECT?: Home treatment teams help people in a mental health crisis to recover. The staff goes to the person’s home, avoiding the need to go to the hospital and providing care in the person’s environment. The teams have been created in our country in recent years, becoming part of the mental health care network. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The paper presents the functioning of a CRHTT, the type of care it provides, and the coordination with the rest of the care network. It also shows the clinical results obtained in the first two years since its creation, supporting the CRHTT’s effectiveness in accompanying people with mental health crises and reducing the need for hospital care. The outstanding factors in the team operation were coordination fluidity with referral services (facilitating accessibility), a prolonged care time (about two months), and continuity of care during the CRHTT intervention (the same CRHTT professionals visited the user and the family at home) and upon discharge (CRHTT staff organized joint visits with the professionals who would care for the user and the family after home treatment). The CRHTT followed a person-centered orientation based on horizontality and dialogue. The CRHTT fostered the inclusion of the family and social network in the treatment and a deep understanding of the crisis considering social determinants. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Flexibility, approach to the person’s environment, dialogue, shared decision-making, and the inclusion of the family and social network in the treatment are central factors in CRHTT functioning. It helps the person regain control over their life and enhance their resources to face possible future crises. Training in crisis management, community mental health and family care, and teamwork (which implies joint home visits and co-responsibility with the rest of the staff, user, and the family) are relevant for CRHTT professionals.

ABSTRACT: INTRODUCTION: Crisis resolution and home treatment teams (CRHTTs) provide intensive home care to people in a mental health crisis, becoming an increasingly widespread alternative to hospital admissions. However, there are wide variations in service delivery, organization, and outcomes, and little literature on how these teams work in clinical practice and different settings.

AIM: To share the organizational functioning, the therapeutic approach, and the outcomes obtained in a CRHTT in Catalonia, Spain.

METHOD: A descriptive analysis of the functioning of a home treatment team, the characteristics of the people served, and the clinical results from November 2017 to December 2019 are presented.

RESULTS: One hundred and five people were served, with an average stay of 57 days. And 55.24% were women, and the mean age was 41. Most people could overcome the crisis at home, and 5.71% required hospital admission during home care. A statistically significant improvement was observed in the results of the GAF and HoNOS scales at admission and discharge.

DISCUSSION: Despite reduced staff, home care was an alternative to hospital admission for most people treated.

IMPLICATIONS FOR PRACTICE: Flexibility, teamwork, and collaboration with the social network are relevant factors when accompanying the recovery process at home.

PMID:36964951 | DOI:10.1111/jpm.12918