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1.
Nutr Hosp ; 2024 Feb 08.
Article in Spanish | MEDLINE | ID: mdl-38450493

ABSTRACT

AIM: assess the prescription of oral nutritional supplements (ONS) in the Northern Area of Gran Canaria in the period 2016-2021. MATERIALS AND METHODS: based on electronic prescription data, the first ONS prescription during 2016-2021 was analyzed considering age, gender, nutritional requirements (NR), body mass index (BMI), percentage of weight loss (%WL), albumin and number of prescribed ONS per patient. RESULTS: 10,595 prescriptions were identified corresponding to 6661 patients with the following characteristics: 46.3 % men, mean age 72.84 ± 15.93 years, BMI 20.60 ± 3.98 kg/m2, %WL 11.89 ± 8.32 %; albumin 3.08 ± 0.63 g/dl. The most frequent etiologies of DRE were: neoplasms 42.6 %; degenerative processes of the CNS 28.9 %; stroke 3.9 %; short intestine 6.9 %, and inflammatory bowel disease (IBD) 5.5 %. The percentages of NR covered by the prescribed ONS were: 100 % in 8.9 % of cases, 50 % in 36.9 %, and 25 % in 54.2 %; 40.4 % of patients received 1 unit of ONS daily, 36.3 % took 2 units of ONS, and 23 % received > 3 units of ONS per day. Greater NR were associated with a greater number of ONS (p < 0.001), but 40.8 % of patients who needed to cover > 50 % of NR received only one unit of ONS. CONCLUSION: a significant percentage of patients with DRM do not receive a number of ONS according to their NR.

2.
J Hand Surg Am ; 49(5): 432-442, 2024 May.
Article in English | MEDLINE | ID: mdl-38506782

ABSTRACT

PURPOSE: The purpose of this study was to compare clinical and radiologic outcomes of biological ligament reconstruction (BLR) versus nonbiological ligament reconstruction (NBLR) for chronic injuries involving the ulnar collateral ligament of the thumb's metacarpophalangeal joint. METHODS: Forty-two patients who underwent static BLR (n = 24) or NBLR (n = 18) were included in this retrospective analysis. Preoperative, postoperative, and contralateral thumb measurements (clinical evaluation, radiographs, and subjective outcome questionnaires) were compared over a mean of 38 months of follow-up. RESULTS: Average postoperative thumb metacarpophalangeal and interphalangeal joint ranges of motion were 2° to 54° and 0 to 71°, respectively, for BLR and 0° to 58° and 0° to 71°, respectively, for NBLR. Average grip and pinch strengths, relative to the unaffected hand, were 102% and 84% versus 103% and 89%, respectively. All patients demonstrated stability with a firm end point, compared with the unaffected thumb. The average Quick Disabilities of the Arm, Shoulder, and Hand score among all patients was 12 for the disability/symptom module, 0 for the sports module, and 17 for the work module. Stiffness was reported among four patients, and no patient sustained wound-related issues or other complications. CONCLUSIONS: Nonbiological ligament reconstruction of the thumb ulnar collateral ligament generates short-term outcomes comparable with those of BLR, potentially allowing for expedited recovery and rehabilitation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Subject(s)
Collateral Ligament, Ulnar , Metacarpophalangeal Joint , Range of Motion, Articular , Thumb , Humans , Thumb/surgery , Thumb/injuries , Metacarpophalangeal Joint/surgery , Retrospective Studies , Male , Female , Adult , Range of Motion, Articular/physiology , Collateral Ligament, Ulnar/surgery , Collateral Ligament, Ulnar/injuries , Middle Aged , Ulnar Collateral Ligament Reconstruction , Hand Strength , Treatment Outcome , Disability Evaluation , Young Adult , Plastic Surgery Procedures/methods , Collateral Ligaments/surgery , Collateral Ligaments/injuries
4.
Front Public Health ; 11: 995602, 2023.
Article in English | MEDLINE | ID: mdl-37608984

ABSTRACT

The underline hypothesis of this study was that SARS-CoV-2 can infect individuals regardless of health condition, sex, and age in opposition to the classical epidemiological assumption of an identifiable susceptible subpopulation for epidemic development. To address this issue, a population cohort with 24.4 million metadata associated with 226,089 official RT-qPCR positive and 283,450 negative cases, including 27,769 deceased, linked putatively to B.1. and B.1.1. SARS-CoV-2 lineages were analyzed. The analysis baseline was to determine the infection and mortality structure of the diseased cohort at the onset-exponential phase of the first epidemic wave in Mexico under the assumption of limited herd immunity. Individuals with nonchronic diseases (NOCDs) were compared with those exhibiting at least one of 10 chronic diseases (CDs) adjusted by age and sex. Risk factors for infection and mortality were estimated with classification and regression tree (CART) and cluster analysis based on Spearman's matrix of rho-values in RStudio®, complemented with two proposed mortality indices. SARS-CoV-2 infection was independent of health condition (52.8% NOCD vs. 47.2% CDs; p = 0.001-0.009) but influenced by age >46 in one risk analysis scenario (p < 0.001). Sex contributed 9.7% to the overall risk. The independent effect was supported by the health structure of negative cases with a similar tendency but a higher proportion of NOCDs (61.4%, p = 0.007). The infection probability in individuals with one CD was determined by the disease type and age, which was higher in those older individuals (≥56 years) exhibiting diabetes (12.3%, cp = 0.0006), hypertension (10.1%, cp < 0.0001), and obesity (7.8%, cp = 0.001). In contrast, the mortality risk was heavily influenced by CD conditioned by sex and age, accounting for 72.3% of total deaths (p = 0.001-0.008). Significant mortality risk (48%) was comprised of women and men (w, m) aged ≥56 years with diabetes (19% w and 27.9% m, cp < 0.0004), hypertension (11.5% w, cp = 0.0001), and CKD (3.5% w and 5.3% m, cp = 0.0009). Older people with diabetes and hypertension comorbidity increased the risk to 60.5% (p = 0.001). Based on a mortality-weighted index, women were more vulnerable to preexisting metabolic or cardiovascular diseases. These findings support our hypothesis and justify the need for surveillance systems at a communitarian level. This is the first study addressing this fundamental epidemiological question.


Subject(s)
COVID-19 , Hypertension , Male , Humans , Female , Aged , Middle Aged , COVID-19/epidemiology , SARS-CoV-2 , Mexico/epidemiology , Chronic Disease , Hypertension/epidemiology
5.
Foods ; 12(4)2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36832976

ABSTRACT

The present work describes the purification of an enzyme capable of degrading punicalagin. The enzyme was produced by Aspergillus niger GH1 by solid-state fermentation, and the enzyme production was induced by using ellagitannins as the sole carbon source. The purification steps included the concentration by lyophilization, desalting, anionic exchange, and gel filtration chromatography. The enzyme kinetic constants were calculated by using punicalagin, methyl gallate, and sugar beet arabinans. The molecular mass of the protein was estimated by SDS-PAGE. The identified bands were excised and digested using trypsin, and the peptides were submitted to HPLC-MS/MS analysis. The docking analysis was conducted, and a 3D model was created. The purification fold increases 75 times compared with the cell-free extract. The obtained Km values were 0.053 mM, 0.53% and 6.66 mM for punicalagin, sugar beet arabinans and methyl gallate, respectively. The optimal pH and temperature for the reaction were 5 and 40 °C, respectively. The SDS-PAGE and native PAGE analysis revealed the presence of two bands identified as α-l-arabinofuranosidase. Both enzymes were capable of degrading punicalagin and releasing ellagic acid.

6.
Eval Health Prof ; 46(2): 159-169, 2023 06.
Article in English | MEDLINE | ID: mdl-36821795

ABSTRACT

This study evaluates the psychometric properties of the Access of Older Adults to Outpatient Primary-Care Health Services Scale (AOAOPHSS), in research conducted among 707 Mexican older adults selected by convenience from 14 rural and one urban locations. The AOAOPHSS explores 10 dimensions of two integrated subscales: Accessibility and Personal Abilities. Data analysis was performed in five phases. First, potentially biased responses were identified. Second, the response efficiency of the items and their association with external variables were evaluated. Third, the basic properties of the scores for the subscales' dimensions of the AOAOPHSS were identified using non-parametric Mokken Scaling Analysis (MSA). Fourth, the Structural Equation Modeling methodology was used to identify the properties of the internal structure of the latent construct. Finally, reliability and internal consistency were evaluated at both score and item levels. The following findings emerged. 13 items with inefficient response options were removed, and 24 were retained using the MSA. The latent structure of the latter was defined based on 21 items of five Accessibility Subscale dimensions. Its internal consistency reliability ranged between 0.67 and 0.81 (omega coefficients) and between 0.61 and 0.78 (alpha coefficients). Accordingly, this paper discusses the overall implications of using the Accessibility Subscale.


Subject(s)
Outpatients , Primary Health Care , Humans , Aged , Psychometrics , Reproducibility of Results , Ambulatory Care , Surveys and Questionnaires
7.
Article in English | MEDLINE | ID: mdl-36011737

ABSTRACT

The objective of this work was to validate the content of a scale formulated in Spanish for older adults in Mexico, with the aim of comprehensively measuring the access of this population group to outpatient primary-care services. To this end, we carried out a methodological content-validity study in four stages: (1) construction of the scale; (2) evaluation of item legibility; (3) quantitative content evaluation by two groups of judges selected by convenience: participant-judges including older adults with adequate reading comprehension, surveyed in person (n = 23), and expert-judges comprised of researchers specialized in the fields of health services, psychometrics and aging, surveyed online (n = 7); and (4) collection of qualitative feedback from several of the participant-judges (older adults, n = 4). The content was validated both by sequentially examining the level of consensus in the responses of both groups of judges, using the Tastle and Wierman method, and by calculating Aiken's Validity Coefficient with a 90% confidence interval. The scale contained 65 items pertaining to 10 dimensions of two major constructs: accessibility (n = 39) and personal abilities (n = 26). Five items were eliminated in accordance with the minimum-consensus criterion (0.5). This is the first psychometric scale to be developed in Mexico with the view of integrating the characteristics of health-care services and the abilities of the older adults in a single questionnaire designed to measure the access of this population group to outpatient primary-care services.


Subject(s)
Ambulatory Care , Aged , Humans , Mexico , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
8.
SN Bus Econ ; 2(7): 68, 2022.
Article in English | MEDLINE | ID: mdl-35729876

ABSTRACT

2017-2020 data from Medical Examiner Offices of 19 large U.S. counties are collected to study how suicides evolved during the early stage of the COVID-19 pandemic. I use these data to obtain three key findings. First, I document that the total number of suicides per month was increasing during the early months of the pandemic but was below previous years' levels. Second, using a monthly event study design to account for seasonal trends and county-level differences in suicides, I find that during April through August 2020, monthly suicides were between 11.2 and 20.5% lower than previous years. Third, I explore whether school closures during the start of the pandemic might be associated with suicides among school-age individuals, and I find that monthly suicides increased relative to previous years for this age group, with the highest increases during the summer. Supplementary Information: The online version contains supplementary material available at 10.1007/s43546-022-00235-0.

9.
Article in English | MEDLINE | ID: mdl-35162294

ABSTRACT

This study provides a safe and low-cost in-house protocol for RT-qPCR-based detection of SARS-CoV-2 using mouthwash-saliva self-collected specimens to achieve clinical and epidemiological surveillance in a real-time web environment applied to ambulatory populations. The in-house protocol comprises a mouthwash-saliva self-collected specimen, heat virus inactivation, and primers to target virus N-gene region and the human RPP30-gene. Aligning with 209 SARS-CoV-2 sequences confirmed specificity including the Alpha variant from the UK. Development, validation, and statistical comparison with official nasopharyngeal swabbing RT-qPCR test were conducted with 115 specimens of ambulatory volunteers. A web-mobile application platform was developed to integrate a real-time epidemiological and clinical core baseline database with mouthwash-saliva RT-qPCR testing. Nine built-in algorithms were generated for decision-making on testing, confining, monitoring, and self-reports to family, social, and work environments. Epidemiological and clinical follow-up and SARS-CoV-2 testing generated a database of 37,351 entries allowing individual decision-making for prevention. Mouthwash-saliva had higher sensitivity than nasopharyngeal swabbing in detecting asymptomatic and mild symptomatic cases with 720 viral copy number (VCN)/mL as the detection limit (Ct = 37.6). Cycling threshold and viral loading were marginally different (p = 0.057) between asymptomatic (35 Ct ± 2.8; 21,767.7 VCN/mL, range 720-77,278) and symptomatic (31.3 Ct ± 4.5; 747,294.3 VCN/mL, range 1433.6-3.08 × 106). We provided proof-of-concept evidence of effective surveillance to target asymptomatic and moderate symptomatic ambulatory individuals based on integrating a bio-safety level II laboratory, self-collected, low-risk, low-cost detection protocol, and a real-time digital monitoring system. Mouthwash-saliva was effective for SARS-CoV-2 sampling for the first time at the community level.


Subject(s)
COVID-19 , Mouthwashes , COVID-19 Testing , Female , Humans , SARS-CoV-2 , Saliva , Specimen Handling
10.
J Hand Surg Am ; 47(1): 86.e1-86.e11, 2022 01.
Article in English | MEDLINE | ID: mdl-34016492

ABSTRACT

PURPOSE: We hypothesized that a vascularized ulnar periosteal pedicled flap (VUPPF) is a versatile graft applicable in adult patients that yields good outcomes and is a reliable alternative to other vascularized bone grafts to reduce both the technical demands and donor site morbidity of other options. METHODS: We reviewed 11 adult patients who underwent surgical treatment of forearm atrophic nonunion with a VUPPF. Patients' demographics, outcomes (measured by pain on the visual analog scale; Quick Disabilities of the Arm, Shoulder, and Hand score; range of motion; and grip strength), and associated complications were reported. RESULTS: Of the 11 patients, 5 had previous surgery in an attempt to treat the nonunion with an autologous cancellous bone graft from the iliac crest or olecranon. The average time from nonunion until the VUPPF was 9 months (SD, ±3 months; range, 6-14 months). The mean visual analog scale score improved considerably after surgery (8.7 vs 0.6), and considerable improvement was also noted in the Quick Disabilities of the Arm, Shoulder, and Hand score (50 vs 6). A notable improvement was seen in grip strength after surgery. Pronation/supination also improved considerably between the preoperative assessment and the final postoperative follow-up. CONCLUSIONS: A vascularized ulnar periosteal pedicled flap seems to be a useful and versatile option for a variety of bone union failures of the upper extremity in adults, either at initial presentation or as a salvage technique. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Subject(s)
Fractures, Ununited , Adult , Bone Transplantation , Follow-Up Studies , Forearm , Fractures, Ununited/surgery , Humans , Retrospective Studies , Surgical Flaps , Ulna/surgery
11.
Mod Rheumatol ; 32(2): 330-337, 2022 Feb 28.
Article in English | MEDLINE | ID: mdl-33853472

ABSTRACT

OBJECTIVES: We aimed to determine the prevalence of anti-carbamylated protein (anti-CarP) antibodies in Mexican Hispanics with established rheumatoid arthritis (RA) and to assess their relationship with disease activity. METHODS: A cohort study was conducted in 278 patients with established RA during an 18-month follow-up. We measured IgG/IgM/IgA rheumatoid factor (RF), IgG anticitrullinated protein antibodies (ACPA) and IgG/IgM/IgA anti-CarP antibodies using enzyme-linked immunosorbent assay (ELISA). For disease activity, we performed the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR). Repeated measures one-way ANOVA was used to test the association between anti-CarP IgG antibody status and longitudinal DAS28-ESR scores. Patients were evaluated at baseline and at 6, 12, and 18 months during follow-up. RESULTS: Anti-CarP IgG antibodies were positive in 47.8% of patients and, accounting for all isotypes, in 9.5% of patients with negative RF and ACPA. Triple antibody positivity was present in 42.6% of patients in our sample. Anti-CarP IgG antibody positivity did not show statistically significant differences in mean DAS28-ESR when compared to anti-CarP IgG antibody negative patients at baseline, 6, 12 or 18 months. CONCLUSION: Anti-CarP IgG antibodies are not associated to a higher disease activity in Hispanic patients with established RA. Our findings suggest that the clinical value of measuring anti-CarP antibodies in RA diminishes over time.


Subject(s)
Arthritis, Rheumatoid , Autoantibodies , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Hispanic or Latino , Humans , Immunoglobulin A , Immunoglobulin G , Immunoglobulin M , Peptides, Cyclic , Rheumatoid Factor
12.
Pediatrics ; 149(1)2022 01 01.
Article in English | MEDLINE | ID: mdl-34918158

ABSTRACT

OBJECTIVES: To inform next steps in pediatric diarrhea burden reduction by understanding the shifting enteropathogen landscape after rotavirus vaccine implementation. METHODS: We conducted a case-control study of 1788 medically attended children younger than 5 years, with and without gastroenteritis, after universal rotavirus vaccine implementation in Peru. We tested case and control stools for 5 viruses, 19 bacteria, and parasites; calculated coinfection-adjusted attributable fractions (AFs) to determine pathogen-specific burdens; and evaluated pathogen-specific gastroenteritis severity using Clark and Vesikari scales. RESULTS: Six pathogens were independently positively associated with gastroenteritis: norovirus genogroup II (GII) (AF 29.1, 95% confidence interval [CI]: 28.0-32.3), rotavirus (AF 8.9, 95% CI: 6.8-9.7), sapovirus (AF 6.3, 95% CI: 4.3-7.4), astrovirus (AF 2.8, 95% CI: 0.0-4.0); enterotoxigenic Escherichia coli heat stable and/or heat labile and heat stable (AF 2.4, 95% CI: 0.6-3.1), and Shigella spp. (AF 2.0, 95% CI: 0.4-2.2). Among typeable rotavirus cases, we most frequently identified partially heterotypic strain G12P[8] (54 of 81, 67%). Mean severity was significantly higher for norovirus GII-positive cases relative to norovirus GII-negative cases (Vesikari [12.7 vs 11.8; P < .001] and Clark [11.7 vs 11.4; P = .016]), and cases in the 6- to 12-month age range relative to cases in other age groups (Vesikari [12.7 vs 12.0; P = .0002] and Clark [12.0 vs 11.4; P = .0016]). CONCLUSIONS: Norovirus is well recognized as the leading cause of pediatric gastroenteritis in settings with universal rotavirus vaccination. However, sapovirus is often overlooked. Both norovirus and sapovirus contribute significantly to the severe pediatric disease burden in this setting. Decision-makers should consider multivalent vaccine acquisition strategies to target multiple caliciviruses in similar countries after successful rotavirus vaccine implementation.


Subject(s)
Gastroenteritis/microbiology , Gastroenteritis/prevention & control , Rotavirus Infections/prevention & control , Rotavirus Vaccines , Case-Control Studies , Child, Preschool , Diarrhea/microbiology , Diarrhea/prevention & control , Diarrhea/virology , Feces/microbiology , Feces/virology , Gastroenteritis/parasitology , Gastroenteritis/virology , Genotype , Humans , Norovirus/genetics , Peru , Prospective Studies , Rotavirus/genetics , Sapovirus/genetics , Severity of Illness Index
13.
Econ Lett ; 207: 110014, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34548722

ABSTRACT

This paper uses 2018-2020 prefecture-month-year, gender-month-year, and age group-month-year level data on suicide rates in Japan to document how suicide rates are evolving during the COVID-19 pandemic. I use a monthly event study design to study changes in suicide rates surrounding Japan's COVID-19 state of emergency and to trace out monthly changes in suicide rates during the first 11 months of 2020 relative to 2018-2019. I find that monthly suicide rates during the pandemic started increasing meaningfully in June-July 2020. I find that women experienced greater increases in suicide rates than men, relative to their 2018-2019 average suicide rate, and that women experienced the largest increase in suicide rates in October 2020. I also find descriptive evidence that in terms of suicide, individuals under 30 years old were faring worse during the pandemic.

14.
Bioresour Technol ; 337: 125462, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34320742

ABSTRACT

The role and mechanism of elagitannase is misunderstood because it exhibited different activities due to the low purity or complexity of substrates, and there is no available information about the biochemical, physicochemical and molecular characteristics of the enzyme. This study was aimed to obtain enzymatic extracts by Aspergillus niger GH1 in solid-state fermentation, using dextrose and ellagitannins as inducers of ellagitannase. Protein and bioinformatic analysis were performed to identify the protein sequence expressed in terms of culture conditions. The presence of ellagitannins increased ellagitannase activity 1143-fold compared to dextrose. The higher ellagitannase activity was found at 18 h of culture (1143.30 U g-1PE). Three groups of proteins were identified in both cultures: ß-glucosidase, phospholipase C, and triacylglycerol lipase. However, only phospholipase C was overexpressed with ellagitannins as inducers, showing the most spontaneous reaction with punicalagin (ΔG -8.56). These results suggest that phospholipase could be involved in ellagitannins biosynthesis.


Subject(s)
Ellagic Acid , Hydrolyzable Tannins , Aspergillus niger/metabolism , Fermentation , Hydrolyzable Tannins/metabolism
15.
J Clin Med ; 10(10)2021 May 14.
Article in English | MEDLINE | ID: mdl-34068891

ABSTRACT

BACKGROUND: When conservative management fails, patients with stress urinary incontinence (SUI) are considered for surgical treatment. Simpler, more economical and less invasive surgical techniques, such as the Remeex® system, have been developed. OBJECTIVES: To analyze the objective effectiveness of the Remeex® system in the treatment of male stress urinary incontinence. To study survival and complication rates of the Remeex® system in male SUI patients. MATERIALS AND METHODS: Prospective observational study between July 2015 and May 2020. Group A (n = 7; GA) patients with mild SUI. Group B (n = 22; GB) patients with moderate SUI. Group C (n = 18; GC) patients with severe SUI. Effectiveness was assessed by the number of patients achieving complete and partial dryness. Complete dryness was defined as patients using 0-1 safety pads per day; partial dryness as a >50% reduction in the number of pads used. Results were analyzed using descriptive statistics, Student's t-test. Chi2, Fisher's exact test, ANOVA, and multivariate analysis. Significance was set at p < 0.05. RESULTS: Mean age 69.76 years, mean follow-up 33.52 months. Objective effectiveness was observed in 89.36% of patients with incontinence. The effectiveness was 85.71% in GA, 90.91% in GB and 88.89% in GC. There were no significant differences among groups (p = 1.0000). 34.04% of patients with an implant required at least one readjustment, while 66.00% did not require any. There were no significant differences among groups (p = 0.113) Chi2 = 4.352. 95.74% of implants remained in place by the end of follow-up. We observed complications in 17.02% of patients. CONCLUSIONS: Remeex® system is an effective and safe method for male stress urinary incontinence treatment, regardless of the severity of the incontinence, with high survival and low complication and removal rates. System readjustments are required in one-third of the cases.

16.
Sci Rep ; 11(1): 6298, 2021 03 18.
Article in English | MEDLINE | ID: mdl-33737671

ABSTRACT

The advance of Next Generation Sequencing (NGS) technologies allows high-throughput genotyping at a reasonable cost, although, in the case of peach, this technology has been scarcely developed. To date, only a standard Genotyping by Sequencing approach (GBS), based on a single restriction with ApeKI to reduce genome complexity, has been applied in peach. In this work, we assessed the performance of the double-digest RADseq approach (ddRADseq), by testing 6 double restrictions with the restriction profile generated with ApeKI. The enzyme pair PstI/MboI retained the highest number of loci in concordance with the in silico analysis. Under this condition, the analysis of a diverse germplasm collection (191 peach genotypes) yielded 200,759,000 paired-end (2 × 250 bp) reads that allowed the identification of 113,411 SNP, 13,661 InDel and 2133 SSR. We take advantage of a wide sample set to describe technical scope of the platform. The novel platform presented here represents a useful tool for genomic-based breeding for peach.


Subject(s)
Genome, Plant , Genotype , High-Throughput Nucleotide Sequencing/methods , Prunus persica/enzymology , Prunus persica/genetics , Sequence Analysis, DNA/methods , Computational Biology/methods , DNA, Plant/genetics , DNA, Plant/isolation & purification , Deoxyribonucleases, Type II Site-Specific/genetics , Genetic Loci , Genotyping Techniques/methods , Plant Breeding , Polymorphism, Single Nucleotide
17.
Mol Cell ; 81(5): 922-939.e9, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33434505

ABSTRACT

R-2-hydroxyglutarate (R-2HG), a metabolite produced by mutant isocitrate dehydrogenases (IDHs), was recently reported to exhibit anti-tumor activity. However, its effect on cancer metabolism remains largely elusive. Here we show that R-2HG effectively attenuates aerobic glycolysis, a hallmark of cancer metabolism, in (R-2HG-sensitive) leukemia cells. Mechanistically, R-2HG abrogates fat-mass- and obesity-associated protein (FTO)/N6-methyladenosine (m6A)/YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated post-transcriptional upregulation of phosphofructokinase platelet (PFKP) and lactate dehydrogenase B (LDHB) (two critical glycolytic genes) expression and thereby suppresses aerobic glycolysis. Knockdown of FTO, PFKP, or LDHB recapitulates R-2HG-induced glycolytic inhibition in (R-2HG-sensitive) leukemia cells, but not in normal CD34+ hematopoietic stem/progenitor cells, and inhibits leukemogenesis in vivo; conversely, their overexpression reverses R-2HG-induced effects. R-2HG also suppresses glycolysis and downregulates FTO/PFKP/LDHB expression in human primary IDH-wild-type acute myeloid leukemia (AML) cells, demonstrating the clinical relevance. Collectively, our study reveals previously unrecognized effects of R-2HG and RNA modification on aerobic glycolysis in leukemia, highlighting the therapeutic potential of targeting cancer epitranscriptomics and metabolism.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Antineoplastic Agents/pharmacology , Glutarates/pharmacology , Glycolysis/genetics , Lactate Dehydrogenases/genetics , Leukemia, Myeloid, Acute/drug therapy , Phosphofructokinase-1, Type C/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/antagonists & inhibitors , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Fluorouracil/pharmacology , Gene Expression Regulation, Neoplastic , Glycolysis/drug effects , HEK293 Cells , Humans , K562 Cells , Lactate Dehydrogenases/antagonists & inhibitors , Lactate Dehydrogenases/metabolism , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oxidative Phosphorylation/drug effects , Phosphofructokinase-1, Type C/antagonists & inhibitors , Phosphofructokinase-1, Type C/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Signal Transduction , Survival Analysis , Xenograft Model Antitumor Assays
18.
EClinicalMedicine ; 27: 100561, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33043286

ABSTRACT

BACKGROUND: Norovirus (NV) causes acute gastroenteritis in infants. Humoral and fecal immunoglobulin A (IgA) responses have been correlated with protection against NV; however, the role of breast milk IgA against NV infection and associated diarrhea is still unknown. This study aimed to evaluate the protective role of NV-specific IgA (NV-IgA) in breast milk. METHODS: Ninety-five breast milk samples collected from mothers enrolled in a 2016-2017 Peruvian birth cohort study were tested for total IgA and NV-IgA by ELISA using GII·4 variants and non-GII·4 genotype virus-like particles (VLPs). Breast milk samples were grouped according to the NV infection and diarrheal status of infants: NV positive with diarrhea (NV+D+, n=18); NV positive without diarrhea (NV+D-, n=37); and NV negative without diarrhea (NV-D-, n=40). The percent positivity and titer of NV-IgA were compared among groups. The cross-reactivity was estimated based on the correlation of ratio between NV-IgA against GII·4 variants and non-GII·4 genotype VLPs. FINDINGS: NV-IgA had high positivity rates against different VLPs, especially against GII (89-100%). The NV+D- group had higher percent positivity (89% vs. 61%, p=0·03) and median titer (1:100 vs 1:50, p=0·03) of NV-IgA than the NV+D+ group against GI·1 VLPs. A relatively high correlation between different GII·4 variants (0·87) and low correlation between genogroups (0·23-0·37) were observed. INTERPRETATION: Mothers with high positivity rates and titers of NV-IgA in breast milk had NV infected infants with reduced diarrheal symptoms. Antigenic relatedness to the genetic diversity of human norovirus was suggested.Funding National Institute of Allergy and Infectious Diseases, National Institute of Health: 1R01AI108695-01A1 and the Japan Society for the Promotion of Science (Fostering Joint International Research B):19KK0241.

19.
Horiz. sanitario (en linea) ; 19(2): 175-184, may.-ago. 2020. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1134101

ABSTRACT

Resumen Objetivo Identificar los determinantes de acceso a los servicios de atención primaria en adultos mayores, residentes en áreas rurales y urbanas de diferentes regiones del mundo. Materiales y Métodos Se realizó una revisión sistemática de la literatura en bases electrónicas, a partir de publicaciones cualitativas y cuantitativas de fuente primaria o secundaria, descritas entre 2015 y 2019. Se determinaron palabras clave enmarcadas bajo el Modelo de Dimensiones y habilidades de Levesque, Harris y Russell. El análisis se efectuó utilizando una lista de chequeo con cinco criterios técnicos de evaluación, elegidos por conveniencia técnico-académica. Resultados La búsqueda inicial identificó 118 manuscritos para revisión. Los estudios fueron analizados y clasificados en cinco segmentos que involucran a cinco regiones del mundo. Los principales determinantes de acceso encontrados, fueron clasificados en habilidades personales de los adultos mayores y características propias del sistema de salud, tanto para el área rural como urbana. Conclusiones A nivel mundial el principal determinante de acceso a los servicios de atención primaria en adultos mayores, residentes de áreas rurales es la falta de disponibilidad de servicios; mientras los de población urbana, mantienen las barreras financieras como el principal obstáculo para su acceso a la salud.


Abstract Objective The determinants of access to primary care services in elderly people living in rural and urban areas of different regions of the world. Material and Method A systematic review of the literature in electronic databases was carried out from qualitative and quantitative publications, of primary or secondary source, described between 2015 and 2019. Key words were determined framed under the Levesque Dimensions and Skills Model, Harris and Russell. The analysis was carried out using a checklist with five technical evaluation criteria chosen for technical-academic convenience. Results The initial search identified 118 manuscripts for review. The studies were analyzed and classified in to five segments that involve five regions of the world. The main determinants of access found were classified in to personal skills of the elderly and characteristics of the health system for both rural and urban areas. Conclusions It is concluded that at the global level the main determinant of access to primary care services in elderly residents of rural areas is the lack of availability of services; while urban older adults maintain financial barriers as the main obstacle to their access to health.


Resumo Objetivo Identificar os determinantes do acesso aos serviços de atenção primária em idosos, residentes em áreas rurais e urbano de diferentes regiões do mundo. Material e Método Foi realizada uma revisão sistemática da literatura sobre bases eletrônicas com base em publicações qualitativas e quantitativas de fonte primária ou secundária descritas entre 2015 e 2019. Foram determinadas as palavras-chave enquadradas no Modelo de Dimensões e Habilidades de Levesque, Harrise Russell. A análise foi realizada pormeio de uma lista de verificação com cinco critérios de avaliação técnica, escolhidos por conveniência técnico-acadêmica. Resultados A pesquisa inicial identificou 118 manuscritos para revisão. Os estudos foram analisados e clasificados em cinco segmentos, envolvendo cinco regiões do mundo. Os principais determinantes de acesso encontrados foram classificados em habilidades pessoais dos idosos e características do sistema de saúde, tanto nas áreas rurais quanto nas urbanas. Conclusões O principal determinante do acesso a serviços de atenção primária a idosos residentes em áreas rurais é a falta de disponibilidade de serviços; enquanto a população urbana mantém as barreiras financeiras como o principal obstáculo ao acesso à saúde.


Résumé Objectif Identifier les déterminants de l'accès aux services de soins primaires de personnes âgées vivant en zone rurale et urbaine de différentes régions du monde. Matériel et Méthode Une revue systématique de la littérature a été réalisée en cherchant dans des bases de données électroniques des publications qualitatives et quantitatives, de source primaire ou secondaire, décrites entre 2015 et 2019. Les mots-clés ont été déterminés d'après le modèle de dimensions et compétences de Levesque, Harris et Russell. L'analyse a été effectuée à l'aide d'une liste de contrôle avec cinq critères techniques d'évaluation, choisis par convenance technique et académique. Résultats La recherche initiale a permis d'identifier 118 manuscrits à examiner. Ces études ont été analysées et classées en cinq segments correspondant à cinq régions du monde. Les principaux déterminants de l'accès trouvés ont été classés selon les capacités personnelles des personnes âgées et selon les caractéristiques propres du système de santé, tant pour les zones rurales que pour les zones urbaines. Conclusions Mondialement, le principal déterminant de l'accès aux services de soins primaires de la part des personnes âgées vivant en zone rurale est le manque de disponibilité des services; tandis que pour la population urbaine, il s'agit de barrières financières.

20.
PLoS Negl Trop Dis ; 14(4): e0008235, 2020 04.
Article in English | MEDLINE | ID: mdl-32287327

ABSTRACT

Brucellosis, caused by Brucella abortus, is a major disease of cattle and humans worldwide distributed. Eradication and control of the disease has been difficult in Central and South America, Central Asia, the Mediterranean and the Middle East. Epidemiological strategies combined with phylogenetic methods provide the high-resolution power needed to study relationships between surveillance data and pathogen population dynamics, using genetic diversity and spatiotemporal distributions. This information is crucial for prevention and control of disease spreading at a local and worldwide level. In Costa Rica (CR), the disease was first reported at the beginning of the 20th century and has not been controlled despite many efforts. We characterized 188 B. abortus isolates from CR recovered from cattle, humans and water buffalo, from 2003 to 2018, and whole genome sequencing (WGS) was performed in 95 of them. They were also assessed based on geographic origin, date of introduction, and phylogenetic associations in a worldwide and national context. Our results show circulation of five B. abortus lineages (I to V) in CR, phylogenetically related to isolates from the United States, United Kingdom, and South America. Lineage I was dominant and probably introduced at the end of the 19th century. Lineage II, represented by a single isolate from a water buffalo, clustered with a Colombian sample, and was likely introduced after 1845. Lineages III and IV were likely introduced during the early 2000s. Fourteen isolates from humans were found within the same lineage (lineage I) regardless of their geographic origin within the country. The main CR lineages, introduced more than 100 years ago, are widely spread throughout the country, in contrast to new introductions that seemed to be more geographically restricted. Following the brucellosis prevalence and the farming practices of several middle- and low-income countries, similar scenarios could be found in other regions worldwide.


Subject(s)
Brucella abortus/classification , Brucella abortus/isolation & purification , Brucellosis, Bovine/epidemiology , Brucellosis, Bovine/microbiology , Brucellosis/epidemiology , Brucellosis/microbiology , Genotype , Animals , Brucella abortus/genetics , Buffaloes , Cattle , Costa Rica/epidemiology , Humans , Molecular Epidemiology , Phylogeny , Population Dynamics , Prevalence , Whole Genome Sequencing
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