Nevin Manimala

PLoS Comput Biol. 2022 Apr 11;18(4):e1010051. doi: 10.1371/journal.pcbi.1010051. Online ahead of print.

ABSTRACT

Understanding of the pairing statistics in solutions populated by a large number of distinct solute species with mutual interactions is a challenging topic, relevant in modeling the complexity of real biological systems. Here we describe, both experimentally and theoretically, the formation of duplexes in a solution of random-sequence DNA (rsDNA) oligomers of length L = 8, 12, 20 nucleotides. rsDNA solutions are formed by 4L distinct molecular species, leading to a variety of pairing motifs that depend on sequence complementarity and range from strongly bound, fully paired defectless helices to weakly interacting mismatched duplexes. Experiments and theory coherently combine revealing a hybridization statistics characterized by a prevalence of partially defected duplexes, with a distribution of type and number of pairing errors that depends on temperature. We find that despite the enormous multitude of inter-strand interactions, defectless duplexes are formed, involving a fraction up to 15% of the rsDNA chains at the lowest temperatures. Experiments and theory are limited here to equilibrium conditions.

PMID:35404933 | DOI:10.1371/journal.pcbi.1010051

PLoS One. 2022 Apr 11;17(4):e0261972. doi: 10.1371/journal.pone.0261972. eCollection 2022.

ABSTRACT

BACKGROUND: Tuberculosis is among the leading causes of death among infectious diseases. Regions with a high incidence of tuberculosis, such as sub-Saharan Africa, are disproportionately burdened by stillbirth and other pregnancy complications. Active tuberculosis increases the risk of pregnancy complications, but the association between latent tuberculosis infection (LTBI) and pregnancy outcomes is unknown. We explored the effect of latent tuberculosis infection on the risk of stillbirth in women attending antenatal care clinics in Ethiopia, a country with >170 000 annual cases of active tuberculosis.

METHOD: Pregnant women were enrolled from antenatal care at three health facilities in Adama, Ethiopia, during 2015-2018, with assessment for previous and current active tuberculosis and testing for LTBI using QuantiFERON-TB-GOLD-PLUS. Proportions of stillbirth (≥ 20 weeks of gestation) and neonatal death (< 29 days of birth) were compared with respect to categories of maternal tuberculosis infection (tuberculosis-uninfected, LTBI, previous-, and current active tuberculosis). Multivariable logistic regression was performed for stillbirth.

RESULTS: Among 1463 participants enrolled, the median age was 25 years, 10.2% were HIV-positive, 34.6% were primigravidae, and the median gestational age at inclusion was 18 weeks. Four (0.3%) were diagnosed with active tuberculosis during pregnancy, 68 (4.6%) reported previous treatment for active tuberculosis, 470 (32.1%) had LTBI, and 921 (63.0%) were tuberculosis-uninfected. Stillbirth was more frequent in participants with LTBI compared to tuberculosis-uninfected participants, although not reaching statistical significance (19/470, 4.0% vs 25/921, 2.7%, adjusted [for age, gravidity and HIV serostatus] odds ratio 1.38, 95% confidence interval 0.73-2.57, p = 0.30). Rates of neonatal death (5/470, 1.1% vs 10/921, 1.1%) were similar between these categories.

CONCLUSION: Latent tuberculosis infection was not significantly associated with stillbirth or neonatal death in this cohort. Studies based on larger cohorts and with details on causes of stillbirth, as well as other pregnancy outcomes, are needed to further investigate this issue.

PMID:35404930 | DOI:10.1371/journal.pone.0261972

Gac Med Mex. 2022;158(1):3-10. doi: 10.24875/GMM.M22000633.

ABSTRACT

INTRODUCTION: The population living in conditions of poorness has a heavier pathological burden than social strata with better economic possibilities.

OBJECTIVE: To determine the influence of socioeconomic and demographic factors on COVID-19 morbidity, mortality and lethality in municipalities and states of Mexico.

METHODS: Morbidity, mortality and lethality associated with COVID-19 were analyzed according to the human development index and its indicators, and type of population. Descriptive statistical analyses, correlations between developmental variables and morbidity, mortality and lethality, association tests and hierarchical groupings were carried out.

RESULTS: Positive correlations were observed between morbidity and mortality and the human development index; COVID-19 fatality increased as the values of said index decreased. There was a significantly higher risk of elevated mortality in localities with moderate and low development, and in those with less than 49,999 inhabitants. The main factors associated with fatality were lack of access to health services, income vulnerability and social deprivation.

CONCLUSIONS: The evidence generated should lead to decisions aimed at improving the quality of life of the population with social deprivations and vulnerabilities, which needs to be protected against the consequences of current COVID-19 pandemic.

PMID:35404927 | DOI:10.24875/GMM.M22000633

Gac Med Mex. 2022;158(1):16-22. doi: 10.24875/GMM.M22000635.

ABSTRACT

INTRODUCTION: In the care of patients with medically unexplained physical symptoms (MUPS) it is important what they think about their symptoms.

OBJECTIVE: To validate the psychometric properties of a symptom attribution scale in patients with MUPS and to verify its reliability.

METHODS: A non-probabilistic sample of 400 male and female adult patients were interviewed in the outpatient services of a family medicine hospital, 200 with MUPS and 200 with a defined organic pathology. Each group was diagnosed with defined criteria, and a scale with content and construct validity was applied by means of principal component analysis with varimax rotation.

RESULTS: The scale was made up of 12 items with two factors, one of symptom psychosocial attribution and other with organic attribution. The psychosocial-origin factor showed a variance of 49.7%. The goodness-of-fit test demonstrated that the correlation matrix was adequate, and Bartlett’s sphericity test indicated statistical significance (p < 0.0001); Cronbach’s alpha was 0.841.

CONCLUSION: The scale showed acceptable construct validity and good reliability and stability. The implications of these results for future measurement research are discussed.

PMID:35404921 | DOI:10.24875/GMM.M22000635

Gac Med Mex. 2022;158(1):23-30. doi: 10.24875/GMM.M22000636.

ABSTRACT

INTRODUCTION: Neonates with congenital heart disease can develop neurological problems, which is why it is important to know the time and extent at which these lesions occur in order to elucidate their causes and implications.

OBJECTIVE: To describe brain morphological alterations in autopsies of neonates with congenital heart disease.

METHODS: The cases of neonates with congenital heart disease and complete autopsy registered in the pathology department from 2009 to 2019 were included. Descriptive statistics were used with the calculation of frequencies and percentages.

RESULTS: Of a total of 21 patients, 61.9% were full-term males; median weight and age at admission were 2500 g and five days, respectively; mean hospital stay was seven days. The predominant heart disease was aortic arch pathology. Fifteen patients (71.3%) underwent surgery; 50% died of cardiogenic shock, 100% had hypoxic-ischemic brain lesions, 71% had incipient lesions, and 33.3%, parenchymal hemorrhage.

CONCLUSIONS: There are various risk factors for neurological damage in patients with complex congenital heart disease, which is impossible to be entirely controlled. This study allows us to know, for the first time in our milieu, the changes in the central nervous system that could exist in these patients.

PMID:35404920 | DOI:10.24875/GMM.M22000636

Biomech Model Mechanobiol. 2022 Apr 10. doi: 10.1007/s10237-022-01568-3. Online ahead of print.

ABSTRACT

Plastic (permanent) deformations were earlier, modeled by a phenomenological model in Peng and Vermolen (Biomech Model Mechanobiol 19(6):2525-2551, 2020). In this manusctipt, we consider a more physics-based formulation that is based on morphoelasticity. We firstly introduce the morphoelasticity approach and investigate the impact of various input variables on the output parameters by sensitivity analysis. A comparison of both model formulations shows that both models give similar computational results. Furthermore, we carry out Monte Carlo simulations of the skin contraction model containing the morphoelasticity approach. Most statistical correlations from the two models are similar, however, the impact of the collagen density on the severeness of contraction is larger for the morphoelasticity model than for the phenomenological model.

PMID:35403944 | DOI:10.1007/s10237-022-01568-3

Mol Biol Rep. 2022 Apr 11. doi: 10.1007/s11033-022-07415-z. Online ahead of print.

ABSTRACT

BACKGROUND: The hematological phenotype and genotype analysis of hemoglobin New York (Hb New York) combined with α or β thalassemia has been rarely reported, and whether there is any effect of Hb New York on thalassemia has not been well explored.

METHODS AND RESULTS: In this study, peripheral blood samples from 346 Hb New York carriers were collected for blood cell parameter analysis. When comparing Hb New York heterozygotes, Hb New York combined with α⁰ thalassemia or α⁺ thalassemia, we found that the differences in hemoglobin (HGB), MCV and MCH values were statistically significant (P < 0.05). The HGB, MCV and MCH values of α thalassemia patients were not different from Hb New York combined with α thalassemia group (P > 0.05). When Hb New York heterozygotes were compared to Hb New York combined with β⁰ thalassemia or β⁺ thalassemia, the differences in MCV and MCH values were statistically significant (P < 0.05). However, the differences in MCV and MCH values were not statistically significant between Hb New York combined with β thalassemia and β thalassemia (P > 0.05).

CONCLUSIONS: Our study shows that the hematological characteristics of Hb New York combined with thalassemia are similar to the corresponding thalassemia, and Hb New York does not aggravate the clinical manifestations of thalassemia.

PMID:35403941 | DOI:10.1007/s11033-022-07415-z

Mol Biol Rep. 2022 Apr 11. doi: 10.1007/s11033-022-07388-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Autism spectrum disorder (ASD) is an increasing concern among the Iraqi Arab population. The genetic alterations that cause ASD are likely to converge at the synapse. This study investigated polymorphisms in the GABA_A receptor subunit (GABRG3) and the RELN gene as putative biomarkers of ASD in a pediatric population in Iraq.

METHODS: The case control study included 60 patients with a clinical diagnosis of ASD (mild, moderate, or severe) according to DSM-IV criteria and matched healthy controls (n = 60). Blood samples were collected for DNA genotyping of SNPs rs736707 and rs208129 for RELN and GABRG3 using allele specific PCR. Assessment of genotype and allele distributions in patient groups used odd ratios (OR) with 95% confidence intervals and the Chi-square test. All statistical analysis was performed used SPSS software.

RESULT: The patient cohort was highly consanguineous, with increased ratio (p > 0.05) of males to females (3:1) in both ASD (mean age, 6.66 ± 3.05) and controls (mean age, 5.76 ± 2.3). Both GABRG3 rs208129 genotypes TT (OR 4.33, p = 0.0015) and TA (OR 0.259, P = 0.008), and the T and A alleles were significantly associated with ASD. The RELN rs736707 TC genotype (OR 2.626, P = 0.034) was the only significant association with ASD.

CONCLUSION: GABRG3 SNP rs208129 is a leading biomarker to predict genetic vulnerability to ASD in Iraqi Arabs. Expanded SNP panels and increased sample sizes are required for future GABRG3 studies, and to reach a consensus on RELN utility. Future ASD screening programs in Iraq should include genetic metrics in addition to clinical phenotype assessments.

PMID:35403940 | DOI:10.1007/s11033-022-07388-z

Environ Monit Assess. 2022 Apr 11;194(5):355. doi: 10.1007/s10661-022-10032-9.

ABSTRACT

Microbiological air contamination in the desert environment is becoming an essential subject for the health of office building occupants and public health. In this study, the concentrations and compositions of airborne microorganisms (bacteria and fungi) were assessed in indoor and outdoor environments using a multistory building complex in Kuwait as a case study. Airborne microorganism samples were collected from 12 sites within the building complex containing nineteen stories over four seasons. Culturable airborne bacteria and fungi were impacted on selected media to determine their concentrations and compositions with a Biolog Omnilog GEN III system and Biolog MicroStation. The indoor mean airborne bacterial count concentrations ranged from 35 to 18,463 CFU/m³, concentrations that are higher than 2,000 CFU/m³, demonstrating high-very high contamination levels in all seasons. Fungal contamination was high in winter and summer, with detected concentrations > 2,000 CFU/m³. Indoor-to-outdoor (I/O) ratios showed that airborne microbial contamination inside building floors originated from indoor air contamination. All the building floors showed bacterial and fungal concentrations ranging from less than 2,000 to more than 2,000 CFU/m³, indicative of a high to very high air contamination level. Statistical analysis showed no correlation between bacterial and fungal concentrations, demonstrating that they originated from unrelated sources. In the indoor building air, the most prevalent bacterial isolate was Bacillus pseudomycoides/cereus, whereas the most dominant fungal isolate was Aspergillus spp. The low count for indoor air bacterial species suggested no particular health risk for the occupants. In contrast, the high count of indoor air fungal species in the winter samples and the presence of potentially allergenic genera detected may suggest possible health risks for the occupants. The results obtained are the basis for the recommendation that the maintenance activities of the HVAC system and the periodical cleaning operation program be revised and preplanned as protective measures.

PMID:35403921 | DOI:10.1007/s10661-022-10032-9

Ann Surg Oncol. 2022 Apr 11. doi: 10.1245/s10434-022-11700-3. Online ahead of print.

ABSTRACT

BACKGROUND: This study analyzed the long-term survival after pathological complete response (pCR) with and without nodal metastases and associated recurrence following multimodal treatment of esophageal cancer. The recurrence pattern after pCR is of importance for different postoperative surveillance strategies.

METHODS: A cohort of 890 patients with esophageal cancer received neoadjuvant therapy followed by transthoracic esophagectomy. Only patients with pCR of the primary tumor with and without nodal metastasis were analyzed. A clinicopathological database was set up and completed with long-term follow up information on recurrent disease.

RESULTS: The specimen of 201 patients (23%) demonstrated pCR, 84% without (ypT0N0) and 16% with residual nodal disease (ypT0N+). For ypT0N0 patients, the 5-year overall survival was significantly higher than for patients with metastatic nodes (77% vs. 24%) (p < 0.0001). Sixty-eight percent of patients had no evidence of tumor recurrence, whereas 32% had proven relapse. For patients with and without tumor recurrence, 5-year survival rates were 14% and 93%, respectively (p < 0.0001). For patients with recurrent disease, median survival time was 27 for locoregional, 44 for distant, and 24 months for combined recurrence (p = 0.302). In the multivariable Cox-regression analysis, node-positive disease predicted both locoregional and metastatic recurrence.

CONCLUSIONS: Pathological CR offers long-term survival in patients without nodal metastases but outcome significantly deteriorates with the presence of nodal metastases. Follow-up recommendations may therefore be adopted in patients with pCR. Furthermore, “watch-and-wait” surveillance strategies with suspected clinical complete response have to be considered with caution.

PMID:35403919 | DOI:10.1245/s10434-022-11700-3