Category: Nevin Manimala

PLoS One. 2022 Apr 25;17(4):e0265380. doi: 10.1371/journal.pone.0265380. eCollection 2022.

ABSTRACT

Blebs, pressure driven protrusions of the cell membrane, facilitate the movement of eukaryotic cells such as the soil amoeba Dictyostelium discoideum, white blood cells and cancer cells. Blebs initiate when the cell membrane separates from the underlying cortex. A local rupture of the cortex, has been suggested as a mechanism by which blebs are initiated. However, much clarity is still needed about how cells inherently regulate rupture of the cortex in locations where blebs are expected to form. In this work, we examine the role of membrane energy and the motor protein myosin II (myosin) in facilitating the cell driven rupture of the cortex. We perform under-agarose chemotaxis experiments, using Dictyostelium discoideum cells, to visualize the dynamics of myosin and calculate changes in membrane energy in the blebbing region. To facilitate a rapid detection of blebs and analysis of the energy and myosin distribution at the cell front, we introduce an autonomous bleb detection algorithm that takes in discrete cell boundaries and returns the coordinate location of blebs with its shape characteristics. We are able to identify by microscopy naturally occurring gaps in the cortex prior to membrane detachment at sites of bleb nucleation. These gaps form at positions calculated to have high membrane energy, and are associated with areas of myosin enrichment. Myosin is also shown to accumulate in the cortex prior to bleb initiation and just before the complete disassembly of the cortex. Together our findings provide direct spatial and temporal evidence to support cortex rupture as an intrinsic bleb initiation mechanism and suggests that myosin clusters are associated with regions of high membrane energy where its contractile activity leads to a rupture of the cortex at points of maximal energy.

PMID:35468148 | DOI:10.1371/journal.pone.0265380

PLoS One. 2022 Apr 25;17(4):e0267047. doi: 10.1371/journal.pone.0267047. eCollection 2022.

ABSTRACT

COVID-19 is a disease characterized by its seemingly unpredictable clinical outcomes. In order to better understand the molecular signature of the disease, a recent multi-omics study was done which looked at correlations between biomolecules and used a tree- based machine learning approach to predict clinical outcomes. This study specifically looked at patients admitted to the hospital experiencing COVID-19 or COVID-19 like symptoms. In this paper we examine the same multi-omics data, however we take a different approach, and we identify stable molecules of interest for further pathway analysis. We used stability selection, regularized regression models, enrichment analysis, and principal components analysis on proteomics, metabolomics, lipidomics, and RNA sequencing data, and we determined key molecules and biological pathways in disease severity, and disease status. In addition to the individual omics analyses, we perform the integrative method Sparse Multiple Canonical Correlation Analysis to analyse relationships of the different view of data. Our findings suggest that COVID-19 status is associated with the cell cycle and death, as well as the inflammatory response. This relationship is reflected in all four sets of molecules analyzed. We further observe that the metabolic processes, particularly processes to do with vitamin absorption and cholesterol are implicated in COVID-19 status and severity.

PMID:35468151 | DOI:10.1371/journal.pone.0267047

PLoS One. 2022 Apr 25;17(4):e0266185. doi: 10.1371/journal.pone.0266185. eCollection 2022.

ABSTRACT

BACKGROUND: Maternal mortality is a persistent public health problem worldwide. The maternal mortality ratio of Myanmar was 250 deaths per 100,000 live births in 2017 which was the second-highest among ASEAN member countries in that year. Myanmar’s infant mortality rate was twice the average of ASEAN member countries in 2020. This study examined factors influencing institutional maternity service utilization and identified the need for improved maternal health outcomes.

METHODS: A cross-sectional study design was used to examine the experience of 3,642 women from the 2015-16 Myanmar Demographic and Health Survey by adapting Andersen’s Behavioral Model. Both descriptive and inferential statistics were applied. Adjusted odds ratios and 95% confidence interval were reported in the logistic regression results.

RESULTS: The findings illustrate that the proportion of women who delivered their last child in a health/clinical care facility was 39.7%. Women live in rural areas, states/regions with a high levels of poverty, poor households, experience with financial burden and the husband’s occupation in agriculture or unskilled labor were negatively associated with institutional delivery. While a greater number of ANC visits and level of the couple’s education had a positive association with institutional delivery.

CONCLUSION: The determinants of institutional delivery utilization in this study related to the institutional facilities environment imply an improvement of the institutional availability and accessibility in rural areas, and different states/regions, particularly Chin, Kayah and Kachin States- the poorest states in Myanmar. The poverty reduction strategies are urgently implemented because problems on health care costs and household economic status played important roles in institutional delivery utilization. The ANC visits indicated a significant increase in institutional delivery. The government needs to motivate vulnerable population groups to seek ANC and institutional delivery. Moreover, education is crucial in increasing health knowledge, skills, and capabilities. Thus, improving access to quality, formal, and informal education is necessary.

PMID:35468140 | DOI:10.1371/journal.pone.0266185

PLoS Negl Trop Dis. 2022 Apr 25;16(4):e0010394. doi: 10.1371/journal.pntd.0010394. Online ahead of print.

ABSTRACT

Murine typhus is a flea-borne zoonotic disease with acute febrile illness caused by Rickettsia typhi and is distributed widely throughout the world, particularly in port cities and coastal regions. We observed that murine typhus was an endemic disease (number of annual indigenous cases = 29.23±8.76) with a low incidence rate (0.13±2.03*10-4 per 100,000 person-years) in Taiwan from 2007-2019. Most (45.79%, 174/380) indigenous infections were reported in May, June, and July. The incidence rates in both May and June were statistically higher than those in other months (p<0.05). Correspondingly, sera collected from small mammals (rodents and shrews) trapped in airports and harbors demonstrated anti-R. typhi antibody responses (seropositive rate = 8.24±0.33%). Interestingly, the ports with the highest seropositivity rates in small mammals are all inside/near the areas with the highest incidence rates of indigenous murine typhus. In addition, incidence rates in humans were positively correlated with the 1-month and 2-month prior seropositive rates in small mammals (R = 0.31 and 0.37, respectively). As early treatment with appropriate antibiotics for murine typhus could effectively shorten the duration of illness and reduce the risk of hospitalization and fatality, flea-related exposure experience should be considered in clinics during peak seasons and the months after a rise in seropositivity rates in small mammals. Surveillance in small mammals might be helpful for the development of real-time reporting or even early reminders for physicians of sporadic murine typhus cases based on the delayed correlation observed in this study.

PMID:35468137 | DOI:10.1371/journal.pntd.0010394

PLoS Comput Biol. 2022 Apr 25;18(4):e1009885. doi: 10.1371/journal.pcbi.1009885. eCollection 2022 Apr.

ABSTRACT

B cells undergo rapid mutation and selection for antibody binding affinity when producing antibodies capable of neutralizing pathogens. This evolutionary process can be intermixed with migration between tissues, differentiation between cellular subsets, and switching between functional isotypes. B cell receptor (BCR) sequence data has the potential to elucidate important information about these processes. However, there is currently no robust, generalizable framework for making such inferences from BCR sequence data. To address this, we develop three parsimony-based summary statistics to characterize migration, differentiation, and isotype switching along B cell phylogenetic trees. We use simulations to demonstrate the effectiveness of this approach. We then use this framework to infer patterns of cellular differentiation and isotype switching from high throughput BCR sequence datasets obtained from patients in a study of HIV infection and a study of food allergy. These methods are implemented in the R package dowser, available at https://dowser.readthedocs.io.

PMID:35468128 | DOI:10.1371/journal.pcbi.1009885

PLoS Comput Biol. 2022 Apr 25;18(4):e1010048. doi: 10.1371/journal.pcbi.1010048. Online ahead of print.

ABSTRACT

Tumors often harbor orders of magnitude more mutations than healthy tissues. The increased number of mutations may be due to an elevated mutation rate or frequent cell death and correspondingly rapid cell turnover, or a combination of the two. It is difficult to disentangle these two mechanisms based on widely available bulk sequencing data, where sequences from individual cells are intermixed and, thus, the cell lineage tree of the tumor cannot be resolved. Here we present a method that can simultaneously estimate the cell turnover rate and the rate of mutations from bulk sequencing data. Our method works by simulating tumor growth and finding the parameters with which the observed data can be reproduced with maximum likelihood. Applying this method to a real tumor sample, we find that both the mutation rate and the frequency of death may be high.

PMID:35468135 | DOI:10.1371/journal.pcbi.1010048

Bol Med Hosp Infant Mex. 2022;79(2):91-99. doi: 10.24875/BMHIM.21000075.

ABSTRACT

BACKGROUND: Initial publications of COVID-19 (2019 coronavirus disease) focused on the adult population until March 2020, when the first series in children was reported. Our objective was to analyze the spatiotemporal behavior of the pediatric population with COVID-19 in the state of Jalisco.

METHODS: We conducted a cross-sectional study including subjects < 18 years of age with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection confirmed by reverse transcription-polymerase chain reaction, registered in the RADAR platform. We investigated the prevalence, incidence rate, age, sex, outpatient or inpatient status, distribution of cases by time, municipality of residence, and geographical region. Descriptive statistics were used for data analysis.

RESULTS: Of 58,231 subjects studied, 1,515 were children (3%): 768 males (51%) and 747 females (49%). The mean age was 12 ± 5 years; outpatients predominated (94%). The Central region concentrated the largest cases with 1,257 (82%) and was the second-highest incidence rate, behind the Occidental Coastal-Mountain region. The most affected municipality was Guadalajara. The distribution of new cases increased proportionally to mobility: after the holiday weekend in May, it rose from 28 to 161 cases; after the opening of beaches and recreational sites in June and July, to 539; and after the opening of movie theaters in August, to 673 cases.

CONCLUSIONS: Although with a lower incidence, the pediatric population is not exempt from SARS-CoV-2 infection. We observed an increase in cases as restrictions on social activities diminished.

PMID:35468124 | DOI:10.24875/BMHIM.21000075

J Trauma Acute Care Surg. 2022 May 1;92(5):848-854. doi: 10.1097/TA.0000000000003543. Epub 2022 Jan 25.

ABSTRACT

BACKGROUND: Rates of posttraumatic stress disorder (PTSD) among injury survivors are higher relative to the general population, supporting the need to identify those most at risk for PTSD following injury given negative impact of PTSD on recovery. Perceived life threat and assaultive trauma are consistent risk factors for subsequent PTSD development, although less work has explored them in combination. The current study evaluated whether trauma type (assaultive vs. nonassaultive) and perceived life threat, together, led to greater PTSD symptoms 1 month and 6 months postinjury.

METHODS: Participants included adult injured trauma survivors admitted to a level 1 trauma center. While hospitalized, perceived life threat during trauma was assessed and mechanism of injury was collected via record review and was collapsed into two categories: assaultive and nonassaultive. The Clinician-Administered PTSD Scale (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) was administered at 1 month (N = 137) and 6 months (N = 220) after injury.

RESULTS: The four symptoms clusters of PTSD (intrusions, avoidance, hyperarousal, and negative mood/cognitions) were examined using four 2 (time) × 2 (life threat) × 2 (trauma type) mixed methods analyses of variance to assess differences based on risk factors and time. Results showed significant interaction effects of life threat, trauma type, and time for intrusive symptoms and avoidance symptoms. Individuals with life threat during assaultive traumas maintained heightened intrusive symptoms across time and increased avoidance at 6 months. On the other hand, participants with either life threat or assaultive traumas had decreased symptoms at 6 months.

CONCLUSION: Experiencing assaultive trauma and life threat led to greater symptoms of PTSD. Individuals with assaultive traumas who experienced life threat may represent a specific at-risk group following injury. Avoidance can protract functional impairment and impede access to care, negatively impacting recovery. This study highlights a need to assess for these peritrauma factors during hospitalization and supports early intervention targeting avoidance and intrusive symptoms in this group.

LEVEL OF EVIDENCE: Prognostic/Epidemiologic, Level IV.

PMID:35468115 | DOI:10.1097/TA.0000000000003543

Rev Esp Cir Ortop Traumatol. 2022 Apr 21:S1888-4415(22)00051-0. doi: 10.1016/j.recot.2021.09.013. Online ahead of print.

ABSTRACT

INTRODUCTION: The fifth metacarpal neck fracture is traditionally treated with closed reduction and intrinsic plus cast immobilisation. Another alternative and more functional treatment is the syndactylia. The aim of our study is to compare both treatments searching for any differences in their functional outcomes.

METHOD: We did a prospective, controlled, masked, randomised cohort study with patients over 18 years old attended from May 2019 to May 2020 in Vigo’s Sanitary Area with this injure and an angle below 40°. The collected data was: sex, age, fracture angle, range of motion of the metacarpophalangeal articulation (MCFA), grip strength, pain, fracture consolidation, Quick DASH and comfort 4 and 6 weeks after the injury.

RESULTS: 39 men and 1 woman were included in the sample. 36.1 years old as the age average. 90% of the injuries affected the right hand, being all the patients right-handed, finding statistically significant differences in MCFA flexion within 4 weeks and in grade of discomfort, both in favour of the syndactylia (p<.05). Any of the other collected data was statistically significant. Every fracture achieved consolidation at the end of the follow-up.

CONCLUSION: Following the results, we consider both immobilizations good treatment options of these fractures; nevertheless, syndactylia has proven an earlier MCFA flexion recovery and a better tolerance.

PMID:35466074 | DOI:10.1016/j.recot.2021.09.013

Eur Urol Focus. 2022 Apr 21:S2405-4569(22)00081-5. doi: 10.1016/j.euf.2022.04.004. Online ahead of print.

ABSTRACT

BACKGROUND: No clear recommendations are available on whether retrograde intrarenal surgery (RIRS) via flexible ureterorenoscopy or shockwave lithotripsy (SWL) should be preferred for kidney stones ≤2 cm, except for lower-pole stones.

OBJECTIVE: To compare outcomes between RIRS and SWL.

DESIGN, SETTING, AND PARTICIPANTS: This was a single-center randomized controlled trial from March 2015 to May 2018. Patients with a single 6-20-mm kidney stone were enrolled (NCT02645058).

INTERVENTION: Patients were randomized to RIRS or SWL.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the single-procedure stone-free rate (SFR) at 1 mo. Two levels of success were set: fragments ≤4 mm (SFR-4) and no residual fragments (SFR-0). Secondary endpoints were the SFR at 6 mo and 1 yr and rates of complications and further treatments.

RESULTS AND LIMITATIONS: A total of 138 patients underwent treatment (70 RIRS vs 68 SWL). In comparison to SWL, RIRS SFR results were higher at 1 mo (SFR-4 70.0% vs 45.6%; p = 0.004; SFR-0 50.0% vs 26.5%; p = 0.004) and 6 mo (SFR-4 79.7% vs 63.6%; p = 0.038; SFR-0 59.4% vs 40.9%; p = 0.032). There was no difference in SFR measures between the groups at 1 yr (SFR-4 p = 0.322; SFR-0 p = 0.392). Overall complications were comparable (p = 0.207), but the complication rate for stones >10 mm was higher for the SWL group (p = 0.021). The need for further treatment was comparable (p = 0.368). In terms of patient satisfaction, 86.8% and 77.1% of patients would choose SWL and RIRS again, respectively (p = 0.24).

CONCLUSIONS: RIRS achieved better SFRs in comparison to SWL at 1 and 6 mo, but not at 1 yr. The RIRS complication rate was lower for stones >10 mm. SWL remains a viable alternative, especially for 6-10-mm stones, providing comparable results to RIRS in the long term.

PATIENT SUMMARY: We compared outcomes for the treatment of kidney stones ≤2 cm with two techniques: flexible ureteroscopy, in which a flexible telescope is passed through the urethra and bladder to reach the ureter between the bladder and kidney; and shockwave lithotripsy, in which shockwaves are applied to the skin over the location of the kidney stone. Ureteroscopy achieved better stone-free results at 1 and 6 months, but not at 1 year.

PMID:35466071 | DOI:10.1016/j.euf.2022.04.004