Nevin Manimala

Mol Biol Rep. 2022 Sep 10. doi: 10.1007/s11033-022-07707-4. Online ahead of print.

ABSTRACT

BACKGROUND: Long non-coding RNAs (LncRNAs) are known to have regulatory consequences for aberrant gene expression in cancers. The aim of this study was to evaluate the expression levels of long non-encoding RNAs, BACE1 (β-secretase1) and LINC-PINT (Long Intergenic Non-Protein Coding RNA, P53 Induced Transcript), in colorectal cancer (CRC) with clinicopathological parameters.

METHODS AND RESULTS: Bioinformatics analysis defining effectual signalling pathways Wnt. A total of 130 tissue samples (50 fresh CRC tissues with parallel adjacent normal tissues (ADJ) accompanied with 30 normal healthy control tissue samples) were collected from the Iranian population. mRNA expression analysis was performed via Real Time Q-PCR. Statistical analysis for comparing CRC expression levels with ADJ and normal healthy tissues were carried out using Kruskal-Wallis tests. The Receiver Operating Characteristic (ROC) curve was plotted for each LNC, separately. We discovered that PINT and BACE1 expression levels were decreased and increased respectively in CRC tumour samples compared with ADJ normal and healthy tissues. Clinicopathological parameter assessment revealed a significant relationship between PINT expression, tumour location, staging and distant metastasis (p < 0.009, p < 0.014, p < 0.008, respectively). Also, BACE1 over expression was significantly associated with tumour site (p < 0.009), metastasis (p < 0.017) and histological differentiation (p < 0.028) and staging (p < 0.017). Furthermore, ROC curve plotting showed LINC-PINT LNC-BACE1 may distinguish between early and late-stage of CRC, highlighting the value of both BACE1 and PINT as CRC progression biomarkers.

CONCLUSION: We investigated two LNCRNAs (PINT and BACE1) as potential CRC prognostic biomarkers, which are imperative for early and effective medical intervention in CRC. Expression levels of PINT and BACE1 in CRC tissue samples may serve to identify metastasis earlier, increasing patient survival rates and expediating clinical treatment options.

PMID:36087249 | DOI:10.1007/s11033-022-07707-4

Clin Pharmacol Ther. 2022 Sep 10. doi: 10.1002/cpt.2745. Online ahead of print.

ABSTRACT

High saturated fat diets have been shown to raise blood levels of cholecystokinin (CCK) and induce nonalcoholic steatohepatitis (NASH). CCK receptors are expressed on stellate cells and responsible for hepatic fibrosis when activated. The purpose of this study was to test the safety and dose of a CCK receptor antagonist, proglumide, in human subjects with NASH. An open-labeled single ascending dose study was conducted in 18 subjects with clinical NASH based upon steatosis by liver ultrasound, elevated hepatic transaminases, and a component of the metabolic syndrome. Three separate cohorts (N=6 each) were treated with oral proglumide for 12 weeks in a sequential ascending fashion with 800 (cohort-1), 1200 (cohort-2), and 1600 (cohort-3) mg/day, respectively. Blood hematology, chemistries, proglumide levels, a biomarker panel for fibrosis, and symptom surveys were determined at baseline and every four weeks. Abdominal ultrasounds and transient elastography utilizing FibroScan® were obtained at baseline and at week-12. Proglumide was well tolerated at all doses without any serious adverse events. There was no change in body weight from baseline to week-12. For Cohorts-1, -2, and -3, the median percent change in alanine aminotransferase was 8.42, -5.05, and -22.23 and median percent change in fibrosis score by FibroScan® was 8.13, -5.44, and -28.87 (kPa), respectively. Hepatic steatosis as measured by CAP score significantly decreased with proglumide, (P<0.05). Blood microRNA biomarkers and serum 4-hydroxyproline were consistent with decreased fibrosis at week-12 compared to baseline. These findings suggest proglumide exhibits anti-inflammatory and anti-fibrotic properties and this compound is well tolerated in subjects with NASH.

PMID:36087237 | DOI:10.1002/cpt.2745

Clin Rheumatol. 2022 Sep 10. doi: 10.1007/s10067-022-06370-1. Online ahead of print.

ABSTRACT

OBJECTIVES: Although most of the autoinfammatory disorders have a confirmed genetic cause, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome still has an unknown genetic background. However, familial cases of PFAPA syndrome have been reported suggesting a genetic its basis. PFAPA syndrome may also be considered an infammasome disorder as variants in infammasome-associated genes such as CARD8, NLRP3, and MEFV have been reported to contribute to the disease.

METHODS: Polymerase chain reaction (PCR)/Sanger sequencing analysis was performed for the detection of the variations in 71 PFAPA patients and 71 healthy controls. NLRP3 concentrations in serum were measured in 71 PFAPA patients and 71 healthy controls.

RESULTS: No statistically significant differences were observed in the allele or genotype frequencies of the NLRP3 polymorphisms between the controls and patients (P > 0.05). We found no significant differences for NLRP3 serum levels between PFAPA patients and controls (p > 0.05). Mutations in the MEFV gene were detected in 32.5% of our patients (13/40).

CONCLUSIONS: It seems that the synergistic effect of different genes plays a role in the formation of PFAPA syndrome. For this reason, it may be useful to examine the presence of mutations in genes such as NLRP3, MEFV, and CARD8 together while investigating the genetics of PFAPA syndrome. Key points • Familial cases of PFAPA syndrome have been reported suggesting a genetic basis for this syndrome. • Elevated serum or plasma levels of IL-1β, IL-6, and IL-18 have been demonstrated during PFAPA flares in several studies. • It seems that the synergistic effect of different genes plays a role in the formation of PFAPA syndrome.

PMID:36087224 | DOI:10.1007/s10067-022-06370-1

J Nephrol. 2022 Sep 10. doi: 10.1007/s40620-022-01448-0. Online ahead of print.

ABSTRACT

BACKGROUND: People with kidney failure treated with dialysis are at increased risk of SARS-CoV-2 infection, and severe COVID-19 outcomes such as hospitalization and death. Though there are well-defined sex differences in outcomes for the general population with COVID-19, we do not know whether this translates into kidney failure populations. We aimed to estimate the differences in COVID-19 symptoms and clinical outcomes between males and females treated with maintenance dialysis.

METHODS: In this prospective observational cohort study, we included adults treated with maintenance dialysis in Southern Alberta, Canada that tested positive for COVID-19 between March 2020 and February 2022. We examined the association between sex (dichotomized as male and female) with COVID-19 symptoms including fever, cough, malaise, shortness of breath, muscle joints/aches, nausea and/or vomiting, loss of appetite, diarrhea, headache, sore throat, and loss of smell/taste using chi-square or Fisher’s exact tests. Secondary outcomes included 30-day hospitalization, ICU admission, and death.

RESULTS: Of 1,329 cohort participants, 246 (18.5%) tested positive for SARS-CoV-2 and were included in our study, including 95 females (39%). Of 207 participants with symptoms assessed, females had less frequent fever (p = 0.003), and more nausea or vomiting (p = 0.003) compared to males, after correction for multiple testing. Males exhibited no symptoms 25% of the time, compared with 10% of females (p = 0.01, not significant when corrected for multiple testing). We did not identify statistically significant differences in clinical outcomes between the sexes, though vaccinated patients had lower odds of hospitalization.

CONCLUSIONS: Sex differences in COVID-19 symptoms were identified in a cohort of patients treated with maintenance dialysis, which may inform sex-specific screening strategies in dialysis units. Further work is necessary to examine mechanisms for identified sex differences.

PMID:36087218 | DOI:10.1007/s40620-022-01448-0

Methods Mol Biol. 2022;2574:309-366. doi: 10.1007/978-1-0716-2712-9_16.

ABSTRACT

Paired- and single-chain T cell receptor (TCR) sequencing are now commonly used techniques for interrogating adaptive immune responses. TCRs targeting the same epitope frequently share motifs consisting of critical contact residues. Here we illustrate the key features of tcrdist3, a new Python package for distance-based TCR analysis through a series of three interactive examples. In the first example, we illustrate how tcrdist3 can integrate sequence similarity networks, gene-usage plots, and background-adjusted CDR3 logos to identify TCR sequence features conferring antigen specificity among sets of peptide-MHC-multimer sorted receptors. In the second example, we show how the TCRjoin feature in tcrdist3 can be used to flexibly query receptor sequences of interest against bulk repertoires or libraries of previously annotated TCRs based on matching of similar sequences. In the third example, we show how the TCRdist metric can be leveraged to identify candidate polyclonal receptors under antigenic selection in bulk repertoires based on sequence neighbor enrichment testing, a statistical approach similar to TCRNET and ALICE algorithms, but with added flexibility in how the neighborhood can be defined.

PMID:36087210 | DOI:10.1007/978-1-0716-2712-9_16

Environ Sci Pollut Res Int. 2022 Sep 10. doi: 10.1007/s11356-022-22903-2. Online ahead of print.

ABSTRACT

Global warming in the twenty-first century has gradually made high temperatures a major threat to the global population. Health problems associated with extreme temperatures have become a growing public health concern worldwide. This study aimed to estimate road injuries stratified by sex, age, geographic location, and sociodemographic status attribute to high, low, and non-optimal temperatures in 21 regional and global. We used the Global Burden of Disease (GBD) Study Results Tool to examine the age-standardized death rates (ASDR) and disability-adjusted life years (DALYs) due to road injuries in 2019 by Joinpoint regression. In addition, we reported high, low, and non-optimal temperature exposures for road injuries across different groups by gender, age, region, and disease. Moreover, we examined temporal trends in the burden of road disease caused by high, low, and non-optimum temperatures from 1990 to 2019. Trend analyzes were conducted for five sociodemographic index (SDI) regions. Globally, both ASDR and DALY declined from 1990 to 2019, with average annual percent change (AAPC) values of – 1.3% and – 1.2%, respectively. In 2019, the indicators (death and DALYs) steadily declined, while SDI quintile increased in most regions. Road injuries related to death and DALYs rate attributed to high temperatures were 0.17 and 8.50, respectively, in 2019. From 1990 to 2019, DALYs for road injuries caused by low temperatures showed the most significant upward trend in most regions, especially in low-latitude countries. This study provides a comprehensive understanding of the road injury burden caused by high, low, and non-optimum temperatures, which remains high in regions with low SDI. Therefore, special attention should be paid to road injuries in poor countries or in areas with extreme temperatures.

PMID:36087177 | DOI:10.1007/s11356-022-22903-2

Environ Monit Assess. 2022 Sep 10;194(10):764. doi: 10.1007/s10661-022-10449-2.

ABSTRACT

Sea level rise is one of the serious aftermaths of global warming on the hydrosphere. The scientific community often depends on global climate models (GCMs) for projection of future sea levels. Numerous GCMs are available; thus, selecting the most appropriate GCM/GCMs is a critical task to be performed prior to downscaling. In this study, multi-criteria decision-making (MCDM) techniques, namely, Preference Ranking Organisation Method of Enrichment Evaluation (PROMETHEE-II), Elimination Et Choice Translating Reality (ELECTRE-II), and compromise programming, were used to identify appropriate GCMs whose projections can be used to downscale sea level projections at Ernakulam, Kerala, India. Support vector machine was employed to statistically downscale the sea level projections from the projections of GCMs. Five statistical metrics, namely, correlation coefficient ([Formula: see text]), normalized root mean square error, absolute normalized average bias, mean absolute relative error, and skill score, were adopted in this study as the performance criteria. The weightage of each criterion was computed using the entropy method. Six GCMs (GISS-E2-H, CanESM2, ACCESS1-0, CNRM-CM5, GFDL-CM3, and CMCC-CM) were considered for the analysis based on the availability of predictors. GISS-E2-H, CanESM2, and ACCESS1-0 occupied the first three positions respectively in all three MCDM techniques.

PMID:36087169 | DOI:10.1007/s10661-022-10449-2

Neurol Sci. 2022 Sep 10. doi: 10.1007/s10072-022-06372-6. Online ahead of print.

ABSTRACT

BACKGROUND: People often ignore the usefulness of stroke prevention, the typical onset symptoms, and the efficacy of the new therapies. In order to attempt to correct this situation, we performed a wide educational campaign addressed to students of high schools in Liguria and Piedmont Italian regions.

METHOD: The campaign consisted in two phases: (1) compilation of a simple questionnaire on stroke, followed by a scientific lecture on the disease, distribution of didactic materials, and final open discussion; (2) re-filling and sending by participants of the same questionnaire for the statistical evaluation of the improvement of stroke awareness.

RESULTS: The global initial percentage of wrong answers (number of subjects 2,264) was 33.4%: (A) stroke general knowledge 23.5%, (B) stroke risk factors 37.6%, (C) stroke early symptoms 34.1%). At the end of the campaign, the total percentage of wrong answers (number of subjects 1883) attained the 11.4%.: (A) stroke general knowledge 3.7%, (B) stroke risk factors 11.7%, (C) stroke early symptoms 12.5%). All these differences were strongly significant.

DISCUSSION AND CONCLUSION: We demonstrated that our educational campaign obtained an important improvement of stroke awareness in our sample. Girl students, Lyceum students, and less young students attained significant better knowledge improvement. We hope that the enhanced awareness might induce a more frequent diffusion of prevention strategies, an increased capacity of recognizing onset stroke symptoms with shortening of patients’ presentation in the emergency room of the hospitals when they can undergo reperfusion treatments.

PMID:36087147 | DOI:10.1007/s10072-022-06372-6

Brain Struct Funct. 2022 Sep 10. doi: 10.1007/s00429-022-02556-0. Online ahead of print.

ABSTRACT

The functional roles of the precuneus are unclear. Focal precuneus lesions are rare, making it difficult to identify robust brain-behavior relationships. Distinct functional subdivisions of the precuneus have been proposed based on unique connectivity profiles. This includes an association of the anterior division with bodily awareness, the central region with complex cognition, and the posterior division with visual processing. Our goal was to test the hypothesis that the central precuneus is preferentially involved (compared to the other sectors of the precuneus) in executive function, as estimated from performance on the trail-making test (TMT). 35 patients with focal brain lesions involving the precuneus were included from the University of Iowa and Montpellier University. Multivariate lesion symptom mapping of TMT performance was performed to evaluate whether lesion location was associated with impaired task performance. Lesion symptom mapping revealed a statistically significant association of central precuneus lesions with impaired TMT performance (r = 0.43, p < 0.01). Further, a functional network derived from this precuneus region showed connectivity to other cortical areas implicated in executive function, including the dorsolateral prefrontal cortex and inferior parietal lobe. This analysis provides support for the role of the central precuneus in executive function, consistent with the unique connectivity pattern of the central precuneus with a broader network implicated in cognitive control and executive function.

PMID:36087124 | DOI:10.1007/s00429-022-02556-0

Dysphagia. 2022 Sep 10. doi: 10.1007/s00455-022-10515-4. Online ahead of print.

ABSTRACT

Either effortful swallowing exercise or repetitive transcranial magnetic stimulation (rTMS) is considered as an effective method to treat dysphagia after stroke. Thus, synchronizing these two interventions may improve the efficiency of treatment. This trial intended to explore the effects of rTMS and effortful swallowing exercise on the recovery of swallowing function in patients after stroke. A total of 56 patients with post-stroke dysphagia who were able to actively cooperate with the training were analyzed in this study. We experimented with different intervention effects of rTMS synchronization with effortful swallowing training (group 1), rTMS (group 2), and traditional swallowing training alone (group 3). Every patient completed conventional swallowing training 5 days a week for 2 weeks. Patients in group 1 and group 2 underwent 10 consecutive sessions of 5 Hz rTMS over the affected mylohyoid cortical region. Fiberoptic endoscopic dysphagia severity scale (FEDSS), penetration/aspiration scale (PAS), standardized swallowing assessment (SSA), and functional oral intake scale (FOIS) were assessed and compared across the groups. No significant difference in FEDSS, PAS, SSA, or FOIS scores was found at baseline among the three groups. The mean change values of the FEDSS score, PAS score, SSA score, and FOIS score between baseline and post-intervention of the three groups (H = 16.05, P < 0.001; H = 21.70, P < 0.001; F (2, 53) = 9.68, P < 0.001; H = 18.26, P < 0.001; respectively) were statistically significant. In addition, the mean change values of FEDSS, PAS, SSA, and FOIS scores in participants in group 1 (all P < 0.001) and group 2 (P = 0.046; P = 0.045; P = 0.028; P = 0.032; respectively) were significantly higher than in group 3. Similarly, the mean change values of FEDSS, PAS, SSA, and FOIS scores were significantly higher in participants in group 1 than in group 2 (P = 0.046; P = 0.038; P = 0.042; P = 0.044; respectively). The results revealed that the conjunction of rTMS and effortful swallowing training was an effective method to facilitate the recovery of swallowing function in stroke patients. The present clinical trial provided a new treatment method for the functional restoration of swallowing in stroke patients, which may further facilitate the recovery of swallowing function in stroke patients with swallowing disorders.

PMID:36087120 | DOI:10.1007/s00455-022-10515-4