Nevin Manimala

Neurosci Lett. 2023 Aug 4:137426. doi: 10.1016/j.neulet.2023.137426. Online ahead of print.

ABSTRACT

BACKGROUND: The synaptic vesicle glycoprotein 2 (SV2) has been implicated in synaptic function throughout the brain. Accumulating evidence investigated that SV2C contributed to dopamine release and the disrupted expression of SV2C was considered to be a unique feature of PD that may facilitate dopaminergic neuron dysfunction.

OBJECTIVE: This study aimed to examine the relationship between the SV2C rs1423099 single nucleotide polymorphism and sporadic Parkinson’s disease (PD) in the Chinese Han population.

MATERIALS AND METHODS: This study enrolled 351 patients with sporadic PD and 240 normal controls in Chinese Han population. Peripheral blood DNA was extracted by DNA extraction kits and the rs1423099 genotype was analyzed by Agena MassARRAY DNA mass spectrometry. The differences in genotype and allele distribution frequencies between PD patients and control groups were compared using chi-squared tests or Fisher’s exact tests.

RESULTS: No statistical difference was revealed in age and sex distribution between the cases and control groups, and the distribution of genotype and allele frequencies was consistent with the Hardy-Weinberg equilibrium test. In SV2C rs1423099 dominant model, the frequency of the CC/CT genotype was significantly higher in the PD group compared to the control group (OR =4.065,95% CI: 2.801-10.870, p=0.002). Nevertheless, in the recessive model, CC or CT/TT genotypes have no statistical difference in the two groups (p=0.09). Additionally, in allelic analysis, the C allele was investigated to increase the risk of PD (OR =1.346, 95% CI: 1.036-1.745, p=0.026); Furthermore, subgroup analysis suggested that those carrying the C allele in the male subgroup were at a higher risk to afflicted with PD (OR =1.637, 95% CI: 1.147-2.336, p=0.006).

CONCLUSION: SV2C rs1423099 single nucleotide polymorphism was associated with sporadic Parkinson’s disease in the Chinese Han population, particularly in males.

PMID:37544580 | DOI:10.1016/j.neulet.2023.137426

Neuroscience. 2023 Aug 4:S0306-4522(23)00341-X. doi: 10.1016/j.neuroscience.2023.07.032. Online ahead of print.

ABSTRACT

Mapping variability in cortical spontaneous activity (CSA) is an essential goal of understanding various sources of dark brain energy in human neuroscience. CSA was traditionally characterized using resting-state functional MRI (rfMRI) at 1.5T or 3T magnets while recently with 7T-rfMRI. However, the utility and interpretability of 7T-rfMRI must first be established for its variability. By leveraging rfMRI data from the Human Connectome Project (HCP), we derived CSA metrics with 3T-rfMRI and 7T-rfMRI for the same 84 healthy participants (52 females). The 7T-rfMRI produces different CSA metrics at multiple spatial-scales and their variability from the 3T-rfMRI. These differences were spatially dependent and varied according to specific cortical organization. For the amplitude metric, 7T-rfMRI enhanced its spatial contrasts in the anterior cortex but weakened it in the posterior cortex. An opposite pattern was observed for the connectivity metrics. The reliability changes of these metrics were scale dependent, indicating enhanced reliability for connectivity but weakened reliability for amplitude by 7T-rfMRI. These effects were primarily located in the high-order associate cortex, parsing the corresponding changes in individual differences with respect to 7T-rfMRI: 1) higher connectivity variability between participants and the lower connectivity variability within individual participants, and 2) lower amplitude variability between participants and higher amplitude variability within participants. Our work, for the first time, demonstrated the variability of the human CSA across space, rfMRI settings/platforms, and individuals. We discussed the statistical implications of our findings on CSA-based experimental designs and reproducible neuroscience as well as their translational value for personalized applications.

PMID:37544577 | DOI:10.1016/j.neuroscience.2023.07.032

Contraception. 2023 Aug 4:110138. doi: 10.1016/j.contraception.2023.110138. Online ahead of print.

ABSTRACT

OBJECTIVE(S): To characterize awareness of a 2017 Massachusetts (MA) law that ensures access to a 12-month supply of short-acting contraceptive methods (e.g., pill, patch, vaginal ring) among short-acting contraceptive users in MA and to identify perceived benefits and concerns of a 12-month-supply.

STUDY DESIGN: An online survey was administered to a Qualtrics® panel of MA women who were using short-acting contraceptive methods and were insured by an eligible health plan. The survey’s primary outcome was general awareness of the law; interest in, receipt of, and perceived benefits and risks of a 12-month-supply supply were also elicited. Analysis included descriptive statistics and bivariate and multivariable analyses examining factors associated with awareness of the law.

RESULTS: Among the 207 survey respondents 76% were aware of the law and 93% expressed interest in receiving a 12-month supply of a short-acting method; however, only 9% received it. Respondents identified as White (66%), privately insured (59%), and pill users (44%). Concerns about a 12-monthsupply included privacy, product expiration, and change in personal medical status. Perceived benefits included avoiding multiple trips to pharmacy and increased compliance. Multivariable analyses showed general awareness of the law was only associated with employer-based insurance with those respondents having 75% lower odds of being aware of the law than respondents with Medicaid coverage.

CONCLUSION: Although a high percentage of women surveyed were aware of the law and most were interested in receiving a 12-monthsupply of their short-acting method, the low percentage who have received a 12-monthsupply suggests barriers to policy uptake.

IMPLICATIONS: This study describes perceptions of the 12-monthsupply provision of the contraception ACCESS law. Addressing consumer concerns may be important to improve implementation and dissemination of this state policy change.

PMID:37544574 | DOI:10.1016/j.contraception.2023.110138

J Pain Symptom Manage. 2023 Aug 4:S0885-3924(23)00618-8. doi: 10.1016/j.jpainsymman.2023.07.020. Online ahead of print.

ABSTRACT

INTRODUCTION: Goals of care conversations for seriously ill hospitalized patients are associated with high quality patient-centered care. We aimed to assess the prevalence of documented goals of care conversations for rural hospitalized patients compared to nonrural hospitalized patients.

METHODS: We retrospectively assessed goals of care documentation using a template note for adult patients with predicted 90-day mortality greater than 30% admitted to eight rural and nine nonrural community hospitals between July 2021 and April 2023. We compared predictors and prevalence of goals of care documentation among rural and nonrural hospitals.

RESULTS: Of the 31,098 patients admitted during the study period, 21% were admitted to a rural hospital. Rural patients were more likely than nonrural patients to be > 65 years old (89% vs. 86%, P=<0.0001), more likely to live in a neighborhood classified in the highest quintile of socioeconomic disadvantage (40% vs. 16%, P=<0.0001), and less likely to receive a palliative care consult (8% vs. 18%, p=<0.0001). Goals of care documentation occurred less often for patients admitted to rural versus nonrural community hospitals (2% vs. 7%, p<0.0001). In the base multivariable logistic regression model adjusting for patient characteristics, the odds of goals care documentation was lower in rural versus nonrural community hospitals (aOR 0.4, p=0.0232). In a second multivariable logistic regression model including both patient characteristics and severity of illness, the odds of goals of care documentation in rural community hospitals was no longer statistically different than nonrural community hospitals (aOR 0.5, p=0.1080). Patients who received a palliative care consult had lower prevalence of goals of care documentation in rural versus nonrural hospitals (16% vs. 37%, P=<0.0001).

CONCLUSION: In this study of seventeen rural and nonrural community hospitals, we found low overall prevalence of goals of care documentation with particularly infrequent documentation occurring within rural hospitals. Future study is needed to assess barriers to goals of care documentation contributing to low prevalence of goals of care conversations in rural hospital settings.

KEY MESSAGE: This retrospective study assesses prevalence of goals of care documentation in rural community hospitals. The results indicate goals of care documentation is particularly infrequent in rural community hospitals when compared to nonrural community hospitals.

PMID:37544552 | DOI:10.1016/j.jpainsymman.2023.07.020

Urology. 2023 Aug 4:S0090-4295(23)00671-4. doi: 10.1016/j.urology.2023.07.028. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the feasibility and safety of delayed primary closure (DPC) in Fournier’s gangrene (FG) patients with large genital defects.

METHODS: A single institution retrospective review was performed from October 2020 to December 2022 of adult males that underwent DPC for FG. All patients underwent standard medical management and were assessed for DPC eligibility by the urology service. Clinical data on patient factors and outcomes were collected, and descriptive statistics were assessed.

RESULTS: Of 16 patients that underwent DPC, the average age was 61.1 years and BMI was 34.6 kg/m². Median Charlson Comorbidity Index was 3.5 (IQR 2-5.3) and Fournier’s Gangrene Severity Index was 6.5 (IQR 4.8-8). Median number of debridements was 2.5 (IQR 2-3), with a time to closure of 6.5 days (IQR 3-11) and length of stay of 13 days (IQR 9-16.3). Mean genital defect size was 119 cm² (range 44-346 cm²). Eight patients (50%) were closed using scrotal flaps alone while other patients had advancement flaps using the inner thigh, lower abdomen, and perineum. The majority of patients were discharged home directly (63%). There were four Clavien-Dindo III complications: two partial flap necrosis, one wound dehiscence, and one instance of bleeding. Of patients with follow-up, 6/15 (40.0%) had no known complications.

CONCLUSIONS: DPC is safe and effective for a range of patients presenting with FG. Patients with large defects may benefit from less complex wound management and direct discharge home.

PMID:37544517 | DOI:10.1016/j.urology.2023.07.028

Theor Popul Biol. 2023 Aug 4:S0040-5809(23)00049-7. doi: 10.1016/j.tpb.2023.07.004. Online ahead of print.

ABSTRACT

Recombination is a powerful evolutionary process that shapes the genetic diversity observed in the populations of many species. Reconstructing genealogies in the presence of recombination from sequencing data is a very challenging problem, as this relies on mutations having occurred on the correct lineages in order to detect the recombination and resolve the ordering of coalescence events in the local trees. We investigate the probability of reconstructing the true topology of ancestral recombination graphs (ARGs) under the coalescent with recombination and gene conversion. We explore how sample size and mutation rate affect the inherent uncertainty in reconstructed ARGs, which sheds light on the theoretical limitations of ARG reconstruction methods. We illustrate our results using estimates of evolutionary rates for several organisms; in particular, we find that for parameter values that are realistic for SARS-CoV-2, the probability of reconstructing genealogies that are close to the truth is low.

PMID:37544486 | DOI:10.1016/j.tpb.2023.07.004

J Affect Disord. 2023 Aug 4:S0165-0327(23)00989-8. doi: 10.1016/j.jad.2023.08.013. Online ahead of print.

ABSTRACT

BACKGROUND: People with mental illness have a reduced life expectancy, but the extent of the mortality gap and the contribution of natural and unnatural causes to excess mortality among people with mental illness in South Africa are unknown.

METHODS: We analysed reimbursement claims from South African medical insurance scheme beneficiaries aged 15-85 years. We estimated excess life years lost (LYL) associated with organic, substance use, psychotic, mood, anxiety, eating, personality, developmental or any mental disorders.

RESULTS: We followed 1,070,183 beneficiaries for a median of three years, of whom 282,926 (26.4 %) received mental health diagnoses. Men with a mental health diagnosis lost 3.83 life years (95 % CI 3.58-4.10) compared to men without. Women with a mental health diagnosis lost 2.19 life years (1.97-2.41) compared to women without. Excess mortality varied by sex and diagnosis, from 11.50 LYL (95 % CI 9.79-13.07) among men with alcohol use disorder to 0.87 LYL (0.40-1.43) among women with generalised anxiety disorder. Most LYL were attributable to natural causes (men: 3.42, women: 1.94). A considerable number of LYL were attributable to unnatural causes among men with bipolar (1.52) or substance use (2.45) disorder.

LIMITATIONS: Mental diagnoses are based on reimbursement claims.

CONCLUSIONS: Premature mortality among South African individuals with mental disorders is high. Our findings support interventions for the prevention, early detection, and treatment of physical comorbidities in this population. Targeted programs for suicide prevention and substance use treatment, particularly among men, can help reduce excess mortality from unnatural causes.

PMID:37544483 | DOI:10.1016/j.jad.2023.08.013

J Fluency Disord. 2023 Jul 26;77:105996. doi: 10.1016/j.jfludis.2023.105996. Online ahead of print.

ABSTRACT

PURPOSE: Using word- and nonword-reading passages in Kannada, which has a transparent orthography, we attempted to determine (a) whether orthographic differences between English and Kannada may explain the observed differences in stutter rates on nonwords, and (b) whether longer nonwords, like words, incur higher rates of stutters.

METHODS: Stutters are defined as sound or syllable repetitions, sound prolongations, broken words or nonwords (a pause within a word or nonword), abnormal pauses, and intrusive vowel-like sounds. Twenty-six persons, who stutter, read the word and nonword passages. The nonwords were created by changing the first syllable of each word; otherwise words and nonwords were equivalent in length and syllable structure. Stutters were counted from audio-recordings and statistically analyzed.

RESULTS: PWS stuttered on words in varying amounts and in significantly larger amounts on nonwords. Stutter frequency increased roughly in proportion to the increase in the length of phonological words (previously known) and nonwords (reported for the first time here).

CONCLUSION: The results cannot be attributed to the difficulty of pronouncing nonwords because Kannada orthography has a one-to-one relationship between the written and spoken forms of words. Speech production is a multi-stage process consisting of ideation, lemma selection, phonological word creation, and the articulatory planning and execution. Because nonwords lack meaning and clearly identifiable part of speech, it appears that stutters arise late in the speech production process at the phonological word formation and articulatory planning stages. Meaning, lexicality, and morphosyntax may not contribute significantly to the occurrence of stutters.

PMID:37544029 | DOI:10.1016/j.jfludis.2023.105996

J Med Virol. 2023 Aug;95(8):e29023. doi: 10.1002/jmv.29023.

ABSTRACT

An increasing trend of sapovirus (SaV) infections in Japanese children during 2009-2019, particularly after the introduction of the voluntary rotavirus (RV)-vaccination program has been observed. Herein, we investigated the epidemiological situation of SaV infections from 2019 to 2022 when people adopted a precautionary lifestyle due to the emergence of the COVID-19 pandemic, and RV vaccines had been implemented as routine vaccines. Stool samples were collected from children who attended outpatient clinics with acute gastroenteritis and analyzed by reverse transcriptase-polymerase chain reaction to determine viral etiology. Among 961 stool samples, 80 (8.3%) were positive for SaV: 2019-2020 (6.5%), 2020-2021 (0%), and 2021-2022 (12.8%). The trend of SaV infection in Japanese children yet remained upward with statistical significance (p = 0.000). The major genotype was GI.1 (75%) which caused a large outbreak in Kyoto between December 2021 and February 2022. Phylogenetic, gene sequence and deduced amino acid sequence analyses suggested that these GI.1 strains detected in the outbreak and other places during 2021-2022 or 2019-2020 remained genetically identical and widely spread. This study reveals that SaV infection is increasing among Japanese children which is a grave concern and demands immediate attention to be paid before SaV attains a serious public health problem.

PMID:37543991 | DOI:10.1002/jmv.29023

J Appl Clin Med Phys. 2023 Aug 6:e14112. doi: 10.1002/acm2.14112. Online ahead of print.

ABSTRACT

PURPOSE: To develop a prediction model (PM) for target positioning using diaphragm waveforms extracted from CBCT projection images.

METHODS: Nineteen patients with lung cancer underwent orthogonal rotational kV x-ray imaging lasting 70 s. IR markers placed on their abdominal surfaces and an implanted gold marker located nearest to the tumor were considered as external surrogates and the target, respectively. Four different types of regression-based PM were trained using surrogate motions and target positions for the first 60 s, as follows: Scenario A: Based on the clinical scenario, 3D target positions extracted from projection images were used as they were (PM_CL ). Scenario B: The short-arc 4D-CBCT waveform exhibiting eight target positions was obtained by averaging the target positions in Scenario A. The waveform was repeated for 60 s (W_4D-CBCT ) by adapting to the respiratory phase of the external surrogate. W_4D-CBCT was used as the target positions (PM_4D-CBCT ). Scenario C: The Amsterdam Shroud (AS) signal, which depicted the diaphragm motion in the superior-inferior direction was extracted from the orthogonal projection images. The amplitude and phase of W_4D-CBCT were corrected based on the AS signal. The AS-corrected W_4D-CBCT was used as the target positions (PM_AS-4D-CBCT ). Scenario D: The AS signal was extracted from single projection images. Other processes were the same as in Scenario C. The prediction errors were calculated for the remaining 10 s.

RESULTS: The 3D prediction error within 3 mm was 77.3% for PM_4D-CBCT , which was 12.8% lower than that for PM_CL . Using the diaphragm waveforms, the percentage of errors within 3 mm improved by approximately 7% to 84.0%-85.3% for PM_AS-4D-CBCT in Scenarios C and D, respectively. Statistically significant differences were observed between the prediction errors of PM_4D-CBCT and PM_AS-4D-CBCT .

CONCLUSION: PM_AS-4D-CBCT outperformed PM_4D-CBCT , proving the efficacy of the AS signal-based correction. PM_AS-4D-CBCT would make it possible to predict target positions from 4D-CBCT images without gold markers.

PMID:37543990 | DOI:10.1002/acm2.14112