Tag: pubmed

Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):e2114679118. doi: 10.1073/pnas.2114679118.

ABSTRACT

An important idea underlying a plausible dynamical theory of circulation in three-dimensional turbulence is the so-called area rule, according to which the probability density function (PDF) of the circulation around closed loops depends only on the minimal area of the loop, not its shape. We assess the robustness of the area rule, for both planar and nonplanar loops, using high-resolution data from direct numerical simulations. For planar loops, the circulation moments for rectangular shapes match those for the square with only small differences, these differences being larger when the aspect ratio is farther from unity and when the moment order increases. The differences do not exceed about 5% for any condition examined here. The aspect ratio dependence observed for the second-order moment is indistinguishable from results for the Gaussian random field (GRF) with the same two-point correlation function (for which the results are order-independent by construction). When normalized by the SD of the PDF, the aspect ratio dependence is even smaller ( < 2%) but does not vanish unlike for the GRF. We obtain circulation statistics around minimal area loops in three dimensions and compare them to those of a planar loop circumscribing equivalent areas, and we find that circulation statistics match in the two cases only when normalized by an internal variable such as the SD. This work highlights the hitherto unknown connection between minimal surfaces and turbulence.

PMID:34663734 | DOI:10.1073/pnas.2114679118

Neurosciences (Riyadh). 2021 Oct;26(4):366-371. doi: 10.17712/nsj.2021.4.20210070.

ABSTRACT

OBJECTIVES: To assess depression and its relation with different factors among people with epilepsy in wider range of ages.

METHODS: A cross-sectional study was conducted in Taif city. The sample size was 150; the inclusion criteria were ≥18-year-old patients diagnosed with epilepsy. The data were collected by interviewing patients following up from rural and urban areas of Taif in neurology clinics at King Faisal Medical Complex (KFMC) and King Abdul-Aziz Specialist Hospital (KAASH). The PHQ-9 score was used to screen for depression.

RESULTS: Our study showed that approximately 76.7% (n=115) of the patients had some form of depression. A severe form of depression was identified in 8.7% (n=13) of the patients, and a moderately severe form was observed in 13.3% (n=20) of the patients. There was no significant association between depression and gender, duration of epilepsy, type of epilepsy, and medications for epilepsy, while there was a statistical association between depression and age, stress level, and employment status (p<0.044, p<0.001, p<0.008, respectively).

CONCLUSION: Depression is common in people with epilepsy. Regular screening for depression is recommended in people with epilepsy for early detection and treatment.

PMID:34663709 | DOI:10.17712/nsj.2021.4.20210070

Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):e2105666118. doi: 10.1073/pnas.2105666118.

ABSTRACT

Fire is a common ecosystem process in forests and grasslands worldwide. Increasingly, ignitions are controlled by human activities either through suppression of wildfires or intentional ignition of prescribed fires. The southeastern United States leads the nation in prescribed fire, burning ca. 80% of the country’s extent annually. The COVID-19 pandemic radically changed human behavior as workplaces implemented social-distancing guidelines and provided an opportunity to evaluate relationships between humans and fire as fire management plans were postponed or cancelled. Using active fire data from satellite-based observations, we found that in the southeastern United States, COVID-19 led to a 21% reduction in fire activity compared to the 2003 to 2019 average. The reduction was more pronounced for federally managed lands, up to 41% below average compared to the past 20 y (38% below average compared to the past decade). Declines in fire activity were partly affected by an unusually wet February before the COVID-19 shutdown began in mid-March 2020. Despite the wet spring, the predicted number of active fire detections was still lower than expected, confirming a COVID-19 signal on ignitions. In addition, prescribed fire management statistics reported by US federal agencies confirmed the satellite observations and showed that, following the wet February and before the mid-March COVID-19 shutdown, cumulative burned area was approaching record highs across the region. With fire return intervals in the southeastern United States as frequent as 1 to 2 y, COVID-19 fire impacts will contribute to an increasing backlog in necessary fire management activities, affecting biodiversity and future fire danger.

PMID:34663728 | DOI:10.1073/pnas.2105666118

Neurosciences (Riyadh). 2021 Oct;26(4):346-356. doi: 10.17712/nsj.2021.4.20200050.

ABSTRACT

OBJECTIVES: To investigate the association between mannose-binding lectin 2 (MBL2) codon 54 polymorphism and clinical features of patients diagnosed with schizophrenia (SCZ) or bipolar disorder (BD).

METHODS: One hundred and eighteen patients with SCZ, 100 patients with BD, and 100 healthy volunteers were included in the case-control study. The patients consecutively admitted to the outpatient clinic in December 2017-May 2018 and were evaluated with some scales for clinical parameters. Polymerase chain reaction and RFLP were used to determine MBL2 polymorphism in DNA material.

RESULTS: The MBL2 gene polymorphism distributions in SCZ or BD patients were significantly different from the control group. The heterozygous genotype percentages were significantly higher in the control group than in the SCZ or BD patients (OR: 0.450; 95% Cl: 0.243-0.830; p=0.010; OR: 0.532; 95%Cl: 0.284-0.995; p=0.047, respectively), and there were statistically significant differences in the MBL2 polymorphism distributions between treatment-responsive SCZ or BD patients and treatment-resistant patients diagnosed with SCZ or BD. The heterozygous genotype percentages were also significantly higher in the treatment-responsive group than in the treatment-resistant group in SCZ or BD patients (OR: 7.857; 95% Cl: 1.006-61.363; p=0.023; OR: 8.782; 95% Cl: 1.114-69.197; p=0.016, respectively).

CONCLUSION: The presence of a heterozygous MBL2 genotype seems to be favorable both in terms of the absence of SCZ and BD in the healthy population and treatment response for Turkish patients.

PMID:34663707 | DOI:10.17712/nsj.2021.4.20200050

Neurosciences (Riyadh). 2021 Oct;26(4):357-365. doi: 10.17712/nsj.2021.4.20210075.

ABSTRACT

OBJECTIVES: To evaluate the efficacy of valproic acid (VPA) in a cohort of children below 2 years of age. We also aim to review the characteristics of such patients and the role and safety of VPA for this age group.

METHODS: A retrospective chart review conducted at King Abdulaziz University Hospital, Jeddah, Kingdome of Saudi Arabia, for children below 2 years of age diagnosed with epilepsy and treated with valproic acid from January 2016 to January 2020.

RESULTS: The cohort for this study includes 50 children below the age of 2 years (25 males, 25 females). Aged 3 months to 23 months at commencing valproic acid. The mean age of seizure onset was 9 months and the mean age of starting valproic acid was 16 months. Thirty-two patients (64%) had more than 50% seizure improvement after valproic acid. Eleven patients (22%) were seizure-free. No statistical significance abnormalities in blood count indices and ammonia were seen during the treatment period. Two patients had dose-related lethargy that improved after decreasing their dosage. Asymptomatic mild elevation in glutamate dehydrogenase was noticed in 18% of patients.

CONCLUSION: Using valproic acid in infants and children below the age of 2 years can be considered as a safe and effective treatment option for epilepsy in this age group.

PMID:34663708 | DOI:10.17712/nsj.2021.4.20210075

Pharmacol Rev. 2021 Oct;73(4):1-32. doi: 10.1124/pharmrev.121.000317.

ABSTRACT

Brain cancer is a formidable challenge for drug development, and drugs derived from many cutting-edge technologies are being tested in clinical trials. We manually characterized 981 clinical trials on brain tumors that were registered in ClinicalTrials.gov from 2010 to 2020. We identified 582 unique therapeutic entities targeting 581 unique drug targets and 557 unique treatment combinations involving drugs. We performed the classification of both the drugs and drug targets based on pharmacological and structural classifications. Our analysis demonstrates a large diversity of agents and targets. Currently, we identified 32 different pharmacological directions for therapies that are based on 42 structural classes of agents. Our analysis shows that kinase inhibitors, chemotherapeutic agents, and cancer vaccines are the three most common classes of agents identified in trials. Agents in clinical trials demonstrated uneven distribution in combination approaches; chemotherapy agents, proteasome inhibitors, and immune modulators frequently appeared in combinations, whereas kinase inhibitors, modified immune effector cells did not as was shown by combination networks and descriptive statistics. This analysis provides an extensive overview of the drug discovery field in brain cancer, shifts that have been happening in recent years, and challenges that are likely to come. SIGNIFICANCE STATEMENT: This review provides comprehensive quantitative analysis and discussion of the brain cancer drug discovery field, including classification of drug, targets, and therapies.

PMID:34663683 | DOI:10.1124/pharmrev.121.000317

Neurosciences (Riyadh). 2021 Oct;26(4):331-338. doi: 10.17712/nsj.2021.4.20210063.

ABSTRACT

OBJECTIVES: To perform screening of dysphagia in Montenegrin multiple sclerosis (MS) patients. Dysphagia is often neglected problem in patients with MS.

METHODS: We included 104 patients with relapsing-remitting MS who completed 3 questionnaires: dysphagia in multiple sclerosis (DYMUS), eating assessment tool-10 (EAT-10) and swallowing disturbance questionnaire (SDQ). Our study was performed in the clinic for neurology of the Clinical Center of Montenegro (Podgorica, Montenegro) and Polyclinic Neuron (Bijelo Polje, Montenegro) between November 2020 and December 2020.

RESULTS: Self-reported prevalence of this symptom in our group was simmilar to previously reported results. We did not find correlation between DYMUS and expanded disability status scale (EDSS), as it was reported before. Time spent from disease onset to diagnosis is strongly correlated with reported SDQ results. The population of dysphagia-patients is statistically significantly older compared to the non-dysphagia patients, and statistically higher mean values in this population of our subjects were proven on all 3 questionnaires used.

CONCLUSION: The importance of this issue is not just because it warns of potientially malnutrion in MS patients, but also important factor in therapy choosing algorithm in the era of orally used immunomodulatory drugs.

PMID:34663705 | DOI:10.17712/nsj.2021.4.20210063

BMJ Open. 2021 Oct 18;11(10):e049595. doi: 10.1136/bmjopen-2021-049595.

ABSTRACT

INTRODUCTION: Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%-20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.

METHODS AND ANALYSIS: This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12-18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work.

ETHICS AND DISSEMINATION: This trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018.The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences.

TRIAL REGISTRATION NUMBER: ISRCTN14274380.

PMID:34663658 | DOI:10.1136/bmjopen-2021-049595

Neurol Neuroimmunol Neuroinflamm. 2021 Oct 18;8(6):e1089. doi: 10.1212/NXI.0000000000001089. Print 2021 Nov.

ABSTRACT

BACKGROUND AND OBJECTIVES: Neuromyelitis optica (NMO) is a CNS inflammatory disease that predominantly affects the optic nerves and the spinal cord. It is more frequent in Asian and African populations than in European ones. Data on epidemiology, clinical presentation, additional investigations, and treatment in the African continent are scarce. We aim to (1) collect and analyze published data on neuromyelitis optica spectrum disorder (NMOSD), (2) indicate challenges in the diagnosis and management, and (3) discuss opportunities for future research, education, and policy making, specifically on the African continent.

METHODS: A systematic review was performed in January 2021 with the search terms “Neuromyelitis optica and Africa,” “Devic Disease and Africa,” and “NMOSD and Africa.” We included all study types except case reports, correspondence, or conference abstracts on NMO or NMOSD. Extracted data included study design, country, study period, demographic and clinical characteristics, results of paraclinical investigations, and outcome. Data analysis was performed with descriptive statistics.

RESULTS: We retrieved a total of 79 records, of which 19 were included. Ten of 54 African countries reported a total of 410 cases. Almost half of them were from North African countries. The mean age at diagnosis was 33 years (range 7-88 years), and 75% were female. Transverse myelitis followed by optic neuritis were the most frequent symptoms at the time of presentation. One hundred nineteen patients experienced at least 1 previous relapse, and 106 had a relapsing course after diagnosis. Relapses were treated with IV methylprednisolone. Azathioprine and steroids were used most often as maintenance treatments. Outcomes were rarely described.

DISCUSSION: The majority of studies on NMOSD from the African continent are retrospective, and most countries do not report any data. Our systemic review shows that data derived from patients living in Africa correspond well to what has been previously published in meta-analyses on patients of African ancestry with NMOSD who live outside of Africa, except for a younger age at onset and a lower proportion of females. We advocate for systematic data collection to adequately capture and monitor the burden of NMOSD, for expansion of research efforts and facilities to perform fundamental and clinical research, and for improved access to health care including diagnostics, treatments, and rehabilitation services for people affected by NMOSD in the African continent.

PMID:34663674 | DOI:10.1212/NXI.0000000000001089

BMJ Open. 2021 Oct 18;11(10):e048299. doi: 10.1136/bmjopen-2020-048299.

ABSTRACT

INTRODUCTION: Older adults (age ≥65 years) are pursuing increasingly complex, elective surgeries; and, are at higher risk for intraoperative and postoperative complications. Patients and their caregivers frequently struggle with the postoperative recovery process at home, which may contribute to complications. We aim to identify opportunities to intervene during the preoperative period to improve postoperative outcomes by understanding the preparatory behaviours of older adults and their caregivers before a complex, elective surgery.

METHODS AND ANALYSIS: As a result of the COVID-19 pandemic, we will conduct this study via telephone and videoconferencing. Using a multiphase mixed-methods research design, we will collect data on 10-15 patient-caregiver dyads from a pool of older adults (across a spectrum of cognitive abilities) scheduled for an elective colorectal surgery between 1 July 2020 and 30 May 2021. We will collect quantitative and qualitative data before (T1, T2) and after (T3, T4) surgery. Preoperatively, participants will each complete a cognitive assessment and a semi-structured qualitative interview that focuses on their preparatory behaviours (T1). They will then answer questionnaires about mood, self-efficacy and home environment (T2). Three weeks following hospital discharge, participants will complete another qualitative interview focusing on a comparison of preoperative and postoperative preparedness (T3). Researchers will also collect information about the patient’s medical conditions, the postoperative complications and healthcare utilisation from the patient’s chart 30 days following discharge (T4). We will code and conduct thematic analysis of the qualitative data to identify salient themes. Quantitative data will be analysed using basic descriptive statistics to characterise the participants. We will integrate the qualitative and quantitative findings using results from the quantitative scales to group participants and with use of joint display analysis.

ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Michigan IRB. Study findings will be disseminated through peer-reviewed journals and presentations at conferences.

PMID:34663655 | DOI:10.1136/bmjopen-2020-048299