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1.
Clin Transl Allergy ; 14(1): e12325, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38282193

ABSTRACT

INTRODUCTION: Information and communication technologies (ICTs) improve patient-centered care and are routinely used in Allergic Rhinitis (AR), but patients' preferences and attitudes are unexplored. This study examines AR-related information preferences and ICT use by AR patients. METHODS: A survey-based cross-sectional study was carried out in Ecuador from July to September 2019 in seven centers of reference for allergic disease. Participants were 18 years or older, diagnosed with AR and had access to ICT and the Internet. Descriptive and binomial logistic regressions were performed. A value of less than 0.05 was considered statistically significant. RESULTS: 217 patients were included. 47% (n = 102) used ICTs to learn about AR, of which 38.2% (n = 83) found it useful. Most of participants (75%, n = 164) did not think that ICTs reduce their need to see a doctor. Individuals with poorer quality of life were more likely to utilize ICTs to contact their doctor (OR 1.27, 95% CI 1.04-1.55), and more likely to be interested in AR-related content (OR 1.23, 95% CI 1.00-1.52). Patients with long-term AR or other allergies were less likely to use ICTs (OR 0.92 and OR 0.40 respectively). Higher education and lower quality of life may increase AR apps adoption (OR 4.82, 95% CI 1.11-21.00). Academic preparation five-fold increased ICT use for health provider communication (OR 5.29, 95% CI 1.18-23.72). Mild-persistent AR enhanced the probabilities of using ICTs to share experiences and communicate with other patients (OR 12.59, 95% CI 1.32-120.35). CONCLUSIONS: Our study emphasizes the importance of tailoring digital resources to patient needs by considering factors such as quality of life, education, and specific subgroups within the AR patient population. Additionally, the findings suggest that while ICTs can play a valuable role in patient education and support, they should complement, rather than replace, traditional medical care for many AR patients.

2.
Gynecol Endocrinol ; 39(1): 2235427, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37478894

ABSTRACT

Objective: To determine the prevalence of menopausal symptoms and factors related to severity in mid-aged women.Methods: Cross-sectional study in which 216 urban-living women from Asunción-Paraguay (40-60 years) were surveyed with the 10 item Cervantes Scale (CS-10) and a general questionnaire (personal and partner data).Results: Median (interquartile range [IQR]) age of the sample was 48 [9] years, 48.1% were postmenopausal, 8.8% used menopausal hormone therapy, 39.4% psychotropic drugs, 43.5% had hypertension, 6.5% diabetes, 51.9% abdominal obesity, and 89.3% had a partner (n = 193). A history of sexual abuse was present in 2.8%. Median total CS-10 score was 8.5 [9.75]. Overall, 93.3% (180/193) of women having a partner were sexually active, with a median coital frequency of 8 times per month. According to the CS-10, the three most prevalent menopausal symptoms were: aching in muscles and/or joints (70.8%), anxiety and nervousness (70.8%) and hot flashes/night sweats (54.2%). Factors associated with higher CS-10 scores were: female age and educational level, marital status, menopausal status, and marital sexual aspects. Partner educational level was inversely correlated (rho Spearman coefficient) with CS-10 total scores. However, multiple linear regression analysis found that higher total CS-10 scores (more severe menopausal symptoms) negatively correlated to coital frequency and positively correlated with peri- and postmenopausal status, parity, sedentary lifestyle and a history of sexual abuse.Conclusion: Menopausal symptoms in this mid-aged urban female Paraguayan sample were related to hormonal, sexual and other female aspects.


Subject(s)
Menopause , Sexual Behavior , Pregnancy , Female , Humans , Middle Aged , Child , Paraguay , Prevalence , Cross-Sectional Studies , Menopause/physiology , Hot Flashes/epidemiology , Surveys and Questionnaires
3.
Endocr Relat Cancer ; 30(10)2023 10 01.
Article in English | MEDLINE | ID: mdl-37428642

ABSTRACT

The relationship between growth hormone (GH) excess and cancer is a controversial matter. Until 2016, most studies in patients with acromegaly found links with colon and thyroid neoplasms. However, recent studies found increased risks in gastric, breast, and urinary tract cancer also. Concordantly, clinical situations where GH and insulin-like growth facto-I deficits exist are indeed associated with diminished malignancy incidence. In line with these observations, gain-of-function mutations of various enzymes belonging to the GH and IGF-I signaling pathways have been associated with increased carcinogenesis; similarly, loss-of-function mutations of other enzymes that usually work as tumor repressors are also associated with augmented cancer risk. In a study performed in Ecuador, it was demonstrated that subjects in the Ecuadorian cohort with Laron syndrome (ELS), who have a mutant GH receptor and greatly diminished GH and IGF-I signaling, display diminished incidence of cancer. Along with absent action of GH and IGF-I, ELS individuals also have low serum insulin levels and decreased insulin resistance. Furthermore, hyperglycemia and hyperinsulinemia are indispensable for fast cell mitosis, including that of those cells present in the benign and malignant neoplasms. Notably, and despite their obesity, subjects with the ELS display normoglycemia and hypo-insulinemia, along with diminished incidence of malignancies. We believe that the dual low-IGF-I/low insulin serum levels are responsible for the cancer protection, especially considering that the insulin/INSR signaling is a central site for energy generation in the form of ATP and GDP, which are indispensable for all and every GH/IGF-I physiologic as well as pathologic events.


Subject(s)
Acromegaly , Human Growth Hormone , Neoplasms , Humans , Growth Hormone/metabolism , Insulin-Like Growth Factor I/metabolism , Insulin
4.
Endocr Relat Cancer ; 30(6)2023 06 01.
Article in English | MEDLINE | ID: mdl-36971780

ABSTRACT

Meta-analyses from 2018-2022 have shown that obesity increases the risk of various cancers such as acute myeloid lymphoma, chronic myeloid lymphoma, diffuse beta cell lymphoma, Hodgkin's lymphoma, leukemia, multiple myeloma, non-Hodgkin's lymphoma, bladder, breast, cholangiocarcinoma, colorectal, ovarian, esophageal, kidney, liver, prostate, thyroid, and uterus. Contextually, obesity, and its comorbidities, is the largest, most lethal pandemics in the history of mankind; hence, identification of underlying mechanisms is needed to adequately address this global health threat. Herein, we present the metabolic and hormonal mechanisms linked to obesity that might etiologically contribute to neoplasia, including hyperinsulinemia and putative places in the insulin-signaling pathway. Excess insulin, acting as a growth factor, might contribute to tumorigenesis, while abundant ATP and GDP supply the additional energy needed for proliferation of rapidly dividing cells. Our observations in the Ecuadorian cohort of subjects with Laron syndrome (ELS) prove that obesity does not always associate with increased cancer risk. Indeed, despite excess body fat from birth to death, these individuals display a diminished incidence of cancer when compared to their age- and sex-matched relatives. Furthermore, in cell cultures exposed to potent oxidizing agents, addition of ELS serum induces less DNA damage as well as increased apoptosis. ELS individuals have absent growth hormone (GH) counter-regulatory effects in carbohydrate metabolism due to a defective GH receptor. The corresponding biochemical phenotype includes extremely low basal serum concentrations of insulin and insulin-like growth factor-I, lower basal glucose and triglyceride (TG) levels, and diminished glucose, TG, and insulin responses to orally administered glucose or to a mixed meal.


Subject(s)
Laron Syndrome , Neoplasms , Male , Female , Humans , Laron Syndrome/genetics , Ecuador , Insulin-Like Growth Factor I , Insulin , Neoplasms/epidemiology , Neoplasms/complications , Obesity/epidemiology , Obesity/complications , Glucose
5.
Pediatr Pulmonol ; 58(2): 550-555, 2023 02.
Article in English | MEDLINE | ID: mdl-36324233

ABSTRACT

AIM: To verify the added value of respiratory function monitor (RFM) to assess ventilation and the heart rate (HR) changes during stabilization of preterm infants. METHODS: Preterm infants <32 weeks' gestation, bradycardic at birth and in need for positive pressure ventilation (PPV) were included. The first 15 min of stabilization was monitored with RFM. Three time points were identified according to HR values (T0 the start of mask PPV; T1 the HR rise >100 bpm; T2 the delivery of the last PPV). For each inflation, PIP, PEEP, MAP, expired tidal volume/kg (Vte/kg), and mean dynamic compliance (Cdyn) were analyzed. RESULTS: PIP and MAP values were significantly higher at T1 (27.09 ± 5.37 and 17.47 ± 3.85 cmH2 O) and at T2 (24.7 ± 3.86 and 15.2 ± 3.78 cmH2 O) compared to T0 (24.05 ± 2.27 and 15.85 ± 2.77 cmH2 O). PEEP at T1 was significantly higher (6.27 ± 2.17 cmH2 O) compared to T2 (5.61 ± 1.50 cmH2 O). Vte/kg showed significantly lower T0 values (3.57 ± 2.14 ml/kg) compared to T1 (6.18 ± 2.51 ml/kg) and T2 (6.89 ± 2.40 ml/kg). There was a significant effect of time on Cdyn. CONCLUSIONS: A clear correspondence between HR rise and adequate Vte/kg during stabilization of very preterm infants was highlighted. RFM might be useful to tailor ventilation, following real-time changes of lung compliance.


Subject(s)
Infant, Premature, Diseases , Infant, Premature , Infant , Infant, Newborn , Humans , Infant, Premature/physiology , Tidal Volume/physiology , Heart Rate , Respiration , Positive-Pressure Respiration
6.
Diabetes Res Clin Pract ; 196: 110228, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36549505

ABSTRACT

AIMS: We examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS). METHODS: Adults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP). RESULTS: Both syndromic cohorts displayed DIS during OGTT. LS subjects had higher serum concentrations of total and HMW adiponectin, and lower levels of IGF-I, IGF-II, and IGF-Binding Protein-3 than individuals in other study groups. Furthermore, they displayed normal glycemic responses during OGTT with the lowest IAPP secretion. In contrast, individuals with GRS had higher levels of protein glycation, deficient glucose control during OGTT, and increased secretion of IAPP. CONCLUSIONS: A distinct metabolic phenotype depending on GH counter-regulatory status, associates with diabetes development and excess glucose-induced IAPP secretion.


Subject(s)
Adiponectin , Human Growth Hormone , Humans , Insulin Secretion , Syndrome , Insulin , Human Growth Hormone/metabolism , Glucose , Islet Amyloid Polypeptide/metabolism , Phenotype , Insulin-Like Growth Factor I/metabolism
7.
Arch Osteoporos ; 18(1): 15, 2022 12 27.
Article in English | MEDLINE | ID: mdl-36574063

ABSTRACT

We aimed at comparing the incidence of hip fractures in older adults from Ecuador before and during the COVID-19 pandemic. There was a significant reduction in the number of hip fractures, with no change in the length of hospital stay, mortality, and case-fatality rate, during the period of social isolation. INTRODUCTION: The impact that the COVID-19 pandemic has had on fragility fractures is being recently evaluated in the literature. Despite this, data from Latin America in this regard is scarce. PURPOSE: This study aims to compare the incidence rate of hip fractures before and during the COVID-19 pandemic in older adults who received care in the public and private health system of Ecuador. METHODS: This was a descriptive and retrospective study that analyzed data of individuals aged 60 years and older who had hip fractures before and during the COVID-19 pandemic. The information was obtained from the National Hospital Discharge Yearbook. We calculated the incidence, average length of hospital stay, mortality, and case-fatality rate associated with hip fractures. RESULTS: There was a significant reduction in the incidence of hip fractures in adults 60 or older during the period of social isolation due to COVID-19. Between March and December 2019, there was an incidence of 152 hip fractures per 100,000 inhabitants, whereas during the same period but in 2020 in the incidence was 110 per 100,000 inhabitants (p < 0.0001). The main decrease was observed in women aged 80 or more. The average length of hospital stay did not show significant changes. Mortality displayed a non-significant decrease (p = 0.14), although this decrease was significant among women (p = 0.02). Case-fatality rate showed a non-significant increase for the whole group (p = 0.68) and for men (p = 0.09). CONCLUSION: Hip fracture rates decreased significantly in adults aged 60 and older in 2020 compared to 2019. This decrease of hip fracture incidence rates was mainly due to the reductions observed in older people and women. The average length of hospital stay, mortality, and case-fatality rate associated with hip fractures did not show significant changes during the pandemic.


Subject(s)
COVID-19 , Hip Fractures , Osteoporotic Fractures , Male , Humans , Female , Middle Aged , Aged , Incidence , Pandemics , Ecuador/epidemiology , Retrospective Studies , COVID-19/epidemiology , Hip Fractures/epidemiology , Osteoporotic Fractures/epidemiology
8.
Crit Care Res Pract ; 2022: 4333345, 2022.
Article in English | MEDLINE | ID: mdl-35966802

ABSTRACT

Background: Bilevel positive airway pressure in spontaneous/time and average volume-assured pressure support (BiPAP·S/T-AVAPS) could maintain an adequate tidal volume by reducing the patient's inspiratory effort; however, this ventilatory strategy has not been compared with other ventilatory modes, especially the conventional BiPAP S/T mode, when noninvasive mechanical ventilation (NIMV) is used. The primary objective of this study was to determine the rate of success and failure of the use of BiPAP·S/T-AVAPS versus BiPAP·S/T alone in patients with mild-to-moderate "de novo" hypoxemic respiratory failure. Methods: This was a matched-cohort study. Subjects with mild-to-moderate de novo hypoxemic respiratory failure were divided into two groups according to the ventilatory strategy used. The subjects in the BiPAP·S/T group were paired with those in the BiPAP·S/T-AVAPS group. Results: A total of 58 subjects were studied. Twenty-nine subjects in the BiPAP·S/T group were paired with 29 subjects in the BiPAP·S/T-AVAPS group. Twenty patients (34.5%) presented with "failure of NIMV," while 38 (65.5%) patients did not. In addition, 13 (22.4%) patients died, while 45 (77.6%) recovered. No differences were found in the percentage of intubation (P=0.44) and mortality (P=0.1). Conclusion: The BiPAP S/T-AVAPS ventilator mode was not superior to the BiPAP·S/T mode. A high mortality rate was observed in patients with NIMV failure in both modes. This trial is registered with https://doi.org/10.1186/ISRCTN17904857.

9.
Mitochondrion ; 65: 113-123, 2022 07.
Article in English | MEDLINE | ID: mdl-35623560

ABSTRACT

Prion diseases encompass a group of incurable neurodegenerative disorders that occur due to the misfolding and aggregation of infectious proteins. The most well-known prion diseases are Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (also known as mad cow disease), and kuru. It is estimated that around 1-2 persons per million worldwide are affected annually by prion disorders. Infectious prion proteins propagate in the brain, clustering in the cells and rapidly inducing tissue degeneration and death. Prion disease alters cell metabolism and energy production damaging mitochondrial function and dynamics leading to a fast accumulation of damage. Dysfunction of mitochondria could be considered as an early precursor and central element in the pathogenesis of prion diseases such as in sporadic CJD. Preserving mitochondria function may help to resist the rapid spread and damage of prion proteins and even clearance. In the war against prions and other degenerative diseases, studying how to preserve the function of mitochondria by using antioxidants and even replacing them with artificial mitochondrial transfer/transplant (AMT/T) may bring a new hope and lead to an increase in patients' survival. In this perspective review, we provide key insights about the relationship between the progression of prion disease and mitochondria, in which understanding how protecting mitochondria function and viability by using antioxidants or AMT/T may help to develop novel therapeutic interventions.


Subject(s)
Encephalopathy, Bovine Spongiform , Prion Diseases , Prions , Animals , Antioxidants , Cattle , Female , Mitochondria/pathology , Prion Diseases/pathology , Prion Proteins
10.
Mitochondrion ; 64: 125-135, 2022 05.
Article in English | MEDLINE | ID: mdl-35337984

ABSTRACT

Alzheimer's disease (AD) is a leading neurodegenerative pathology associated with aging worldwide. It is estimated that AD prevalence will increase from 5.8 million people today to 13.8 million by 2050 in the United States alone. AD effects in the brain are well known; however, there is still a lack of knowledge about the cellular mechanisms behind the origin of AD. It is known that AD induces cellular stress affecting the energy metabolism in brain cells. During the pathophysiological advancement of AD, damaged mitochondria enter a vicious cycle, producing reactive oxygen species (ROS), harming mitochondrial DNA and proteins, leading to more ROS and cellular death. Additionally, mitochondria are interconnected with the plaques formed by amyloid-ß in AD and have underlying roles in the progression of the disease and severity. For years, the biomedical field struggled to develop new therapeutic options for AD without a significant advancement. However, mitochondria are striking back existing outside cells in a new mechanism of intercellular communication. Extracellular mitochondria are exchanged from healthy to damaged cells to rescue those with a perturbed metabolism in a process that could be applied as a new therapeutic option to repair those brain cells affected by AD. In this review we highlight key aspects of mitochondria's role in CNS' physiology and neurodegenerative disorders, focusing on AD. We also suggest how mitochondria strikes back as a therapeutic target and as a potential agent to be transplanted to repair neurons affected by AD.


Subject(s)
Alzheimer Disease , Alzheimer Disease/genetics , Amyloid beta-Peptides/metabolism , DNA, Mitochondrial/genetics , Humans , Mitochondria/metabolism , Reactive Oxygen Species/metabolism
11.
Mitochondrion ; 64: 34-44, 2022 05.
Article in English | MEDLINE | ID: mdl-35218960

ABSTRACT

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, worldwide. PD neuro-energetically affects the extrapyramidal system, by the progressive loss of striatal dopaminergic neurons in the substantia nigra pars compacta, leading to motor impairment. During the progression of PD, there will be an increase in mitochondrial dysfunction, reactive oxygen species (ROS), stress and accumulation of α-synuclein in neurons. This results in mitochondrial mutations altering their function and fission-fusion mechanisms and central nervous system (CNS) degeneration. Intracellular mitochondrial dysfunction has been studied for a long time in PD due to the decline of mitochondrial dynamics inside neurons. Mitochondrial damage-associated molecular patterns (DAMPs) have been known to contribute to several CNS pathologies especially PD pathogenesis. New and exciting evidence regarding the exchange of mitochondria between healthy to damaged cells in the central nervous system (CNS) and the therapeutic use of the artificial mitochondrial transfer/transplant (AMT) marked a return of this organelle to develop innovative therapeutic procedures for PD. The focus of this review aims to shed light on the role of mitochondria, both intra and extracellularly in PD, and how AMT could be used to generate new potential therapies in the fight against PD. Moreover, we suggest that mitochondrial therapy could work as a preventative measure, motivating the field to move towards this goal.


Subject(s)
Parkinson Disease , Dopaminergic Neurons/pathology , Humans , Mitochondria/genetics , Mitochondria/pathology , Mitochondrial Dynamics , Parkinson Disease/pathology , Reactive Oxygen Species/metabolism
12.
Front Pediatr ; 9: 742916, 2021.
Article in English | MEDLINE | ID: mdl-34869100

ABSTRACT

Pediatric Intensive Care Units (PICUs) provide multidisciplinary care to critically ill children and their families. Grief is present throughout the trajectory of illness and can peak around the time of death or non-death losses. The objective of this study was to assess how PICUs around the world implement grief and bereavement care (GBC) as part of an integrated model of care. This is a multicenter cross-sectional, prospective survey study. Questionnaires with multiple-choice and open-ended questions focusing on unit infrastructure, personnel, policies, limited patient data, and practices related to GBC for families and health care professionals (HCPs) were completed by on-site researchers, who were HCPs on the direct care of patients. PICU fulfillment of GBC goals was evaluated using a custom scoring based on indicators developed by the Initiative for Pediatric Palliative Care (IPPC). We compared average total and individual items fulfillment scores according to the respective country's World Bank income. Patient characteristics and details of unit infrastructure were also evaluated as potential predictors of total GBC fulfillment scores. Statistical analysis included multilevel generalized linear models (GLM) with a Gaussian distribution adjusted by child age/gender and clustering by center, using high income countries (HICs) as the comparative reference. Additionally, we applied principals of content analysis to analyze and summarize open-ended answers to contextualize qualitative data. The study included 34 PICUs from 18 countries: high-income countries (HICs): 32.4%, upper middle-income countries (UMICs): 44.1%, low middle-income and low-income countries (LMI/LICs): 23.5%. All groups reported some compliance with GBC goals; no group reported perfect fulfillment. We found statistically significant differences in GBC fulfillment scores between HICs and UMICs (specifically, HCP grief support), and between HICs and LMICs (specifically, family grief support and HCP grief support). PICUs world-wide provide some GBC, independent of income, but barriers include lack of financial support, time, and training, overall unit culture, presence of a palliative care consultation service, and varying cultural perceptions of child death. Disparities in GBC for families and HCPs exist and were related to the native countries' income level. Identifying barriers to support families and HCPs, can lead to opportunities of improving GBC in PICUs world-wide.

13.
Crit Care Res Pract ; 2021: 7793657, 2021.
Article in English | MEDLINE | ID: mdl-34873453

ABSTRACT

INTRODUCTION: This study intends to determine the Apnea-Hypopnea Index in patients hospitalized with acute hypercapnic respiratory failure from chronic obstructive pulmonary disease exacerbation, who require noninvasive ventilation with average volume-assured pressure support (AVAPS), as well as describes the clinical characteristics of these patients. MATERIALS AND METHODS: We designed a single-center prospective study. The coexistence of Apnea-Hypopnea Index and clinical, gasometric, spirometric, respiratory polygraphy, and ventilatory characteristics were determined. The clinical characteristics found were categorized and compared according to the Apnea-Hypopnea Index (AHI) < 5, AHI 5-15, and AHI >15. A p value <0.05 was considered statistically significant. RESULTS: During the study period, a total of 100 patients were admitted to the ICU with a diagnosis of acute hypercapnic respiratory failure due to COPD exacerbation. 72 patients presented with acute respiratory failure and fulfilled criteria for ventilatory support. Within them, 24 received invasive mechanical ventilation and 48 NIV. After applying the inclusion criteria for this study, 30 patients were eligible. An AHI >5 was present in 24 of the 30 patients recruited (80%). Neck circumference (cm), Epworth scale, and Mallampati score evidenced significant differences when compared to the patient's AHI <5, AHI 5-15, and AHI >15 (p < 0.05). Furthermore, patients with an AHI >5 had longer hospital admissions, prolonged periods on mechanical ventilation, and a higher percentage of intubation rates. CONCLUSION: Apnea-Hypopnea Index and chronic obstructive pulmonary disease exacerbation are a frequent association found in patients with acute hypercapnic respiratory failure and COPD exacerbations that require NIV. This association could be a determining factor in the response to NIV, especially when AVAPS is used as a ventilatory strategy.

14.
Front Pediatr ; 9: 746489, 2021.
Article in English | MEDLINE | ID: mdl-34778135

ABSTRACT

The adequate assessment and management of pain remains a challenging task in the Pediatric Intensive Care Unit (PICU). Our goal is to describe how pain is assessed and managed in PICUs around the world and to examine how human and material resources impact achievement of this goal. An international multicenter cross-sectional observational study was designed with the participation of 34 PICUs located in urban, suburban, and rural areas of 18 countries. We evaluated how PICUs around the world assessed and managed pain according to the Initiative for Pediatric Palliative Care recommendations, and how human and material resources impacted achievement of this goal. Data was collected for this study from 2016 to 2018 using questionnaires completed by medical doctors and nurses. In this paper, we focus on the indicators related to how pain is managed and assessed. The average achievement of the goal of pain relief across all centers was 72.2% (SD: 21.1). We found a statistically significant trend of more effective pain management scores, routine assessment, proper documentation, and involvement of pain management experts by increasing country income. While there are efforts being made worldwide to improve the knowledge in pain assessment and management, there is a lack of resources to do so appropriately in low-middle-income countries. There is a mismatch between the existing guidelines and policies, which are mainly designed in high income countries, and the resources available in lower resourced environments.

15.
Mitochondrion ; 58: 255-269, 2021 05.
Article in English | MEDLINE | ID: mdl-33662579

ABSTRACT

The cerebrospinal fluid (CSF) has an important role in the transport of nutrients and signaling molecules to the central nervous and immune systems through its circulation along the brain and spinal cord tissues. The mitochondrial activity in the central nervous system (CNS) is essential in processes such as neuroplasticity, neural differentiation and production of neurotransmitters. Interestingly, extracellular and active mitochondria have been detected in the CSF where they act as a biomarker for the outcome of pathologies such as subarachnoid hemorrhage and delayed cerebral ischemia. Additionally, cell-free-circulating mitochondrial DNA (ccf-mtDNA) has been detected in both the CSF of healthy donors and in that of patients with neurodegenerative diseases. Key questions arise as there is still much debate regarding if ccf-mtDNA detected in CSF is associated with a diversity of active or inactive extracellular mitochondria coexisting in distinct pathologies. Additionally, it is of great scientific and medical importance to identify the role of extracellular mitochondria (active and inactive) in the CSF and the difference between them being damage associated molecular patterns (DAMPs) or factors that promote homeostasis. This review analyzes the different types of extracellular mitochondria, methods for their identification and their presence in CSF. Extracellular mitochondria in the CSF could have an important implication in health and disease, which may lead to the development of medical approaches that utilize mitochondria as therapeutic agents.


Subject(s)
Cerebrospinal Fluid/metabolism , Biomarkers/metabolism , Humans , Mitochondria/metabolism
16.
Pediatr Cardiol ; 42(1): 1-18, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33373013

ABSTRACT

Congenital heart defects (CHD) is one of the most common types of birth defects. Thanks to advances in surgical techniques and intensive care, the majority of children with severe forms of CHD survive into adulthood. However, this increase in survival comes with a cost. CHD survivors have neurological functioning at the bottom of the normal range. A large spectrum of central nervous system dysmaturation leads to the deficits seen in critical CHD. The heart develops early during gestation, and CHD has a profound effect on fetal brain development for the remainder of gestation. Term infants with critical CHD are born with an immature brain, which is highly susceptible to hypoxic-ischemic injuries. Perioperative blood flow disturbances due to the CHD and the use of cardiopulmonary bypass or circulatory arrest during surgery cause additional neurological injuries. Innate patient factors, such as genetic syndromes and preterm birth, and postoperative complications play a larger role in neurological injury than perioperative factors. Strategies to reduce the disability burden in critical CHD survivors are urgently needed.


Subject(s)
Brain Diseases/epidemiology , Heart Defects, Congenital/epidemiology , Postoperative Complications/epidemiology , Adult , Brain/growth & development , Brain Injuries/epidemiology , Cardiopulmonary Bypass/methods , Child , Female , Heart Defects, Congenital/surgery , Humans , Hypoxia-Ischemia, Brain/epidemiology , Infant , Infant, Newborn , Neurodevelopmental Disorders/epidemiology , Pregnancy , Premature Birth/epidemiology , Survivors
17.
Rev Endocr Metab Disord ; 22(1): 59-70, 2021 03.
Article in English | MEDLINE | ID: mdl-33047268

ABSTRACT

The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80's. We have learned about migration of Sephardic Jews to our country, their isolation in remote hamlets and further inbreeding. These geographical, historical and social determinants induced dissemination of a growth hormone (GH) receptor mutation which widely occurred in those almost inaccessible villages. Consequently, the world's largest Laron syndrome (LS) cohort emerged in Loja and El Oro, two of the southern provinces of Ecuador. We have been fortunate to study these patients since 1987. New clinical features derived from GH insensitivity, their growth patterns as well as treatment with exogenous insulin-like growth factor I (IGF-I) have been reported. Novel biochemical characteristics in the field of GH insensitivity, IGFs, IGF binding proteins (BP) and their clinical correlates have also been described. In the last few years, studies on the morbidity and mortality of Ecuadorian LS adults surprisingly demonstrated that despite obesity, they had lower incidence of diabetes and cancer than their relatives. These events were linked to their metabolic phenotype of elevated but ineffective GH concentrations and low circulating IGF-I and IGFBP-3. It was also noted that absent GH counter-regulation induces a decrease in insulin resistance (IR), which results in low but highly efficient insulin levels which properly handle metabolic substrates. We propose that the combination of low IGF-I signaling, decreased IR, and efficient serum insulin concentrations are reasonable explanations for the diminished incidence of diabetes and cancer in these subjects.


Subject(s)
Laron Syndrome , Ecuador/epidemiology , Humans , Insulin-Like Growth Factor Binding Proteins , Insulin-Like Growth Factor I/metabolism , Laron Syndrome/epidemiology , Laron Syndrome/genetics , Phenotype , Receptors, Somatotropin/genetics
18.
Growth Horm IGF Res ; 53-54: 101339, 2020.
Article in English | MEDLINE | ID: mdl-32763832

ABSTRACT

Individuals affected with two genetic syndromes identified in Ecuador have severe short stature and diminished insulin secretion, along with essentially different GH counterregulatory effects on insulin action, which leads to the appearance of opposing metabolic phenotypes. In the case of Laron syndrome, subjects have enhanced insulin sensitivity and diminished incidence of type 2 diabetes mellitus. In the other clinical entity, individuals have innate insulin resistance, a varying degree of carbohydrate metabolism disturbances, glucose intolerance, and eventually insulin-resistant diabetes mellitus. Since both groups have diminished insulin secretion, the standard homeostatic minimal models for assessment of insulin sensitivity and resistance were used to see if they could properly identify the metabolic status, especially considering that these methodologies are simple and non-invasive procedures. METHODS: Fasting insulin concentrations, fasting glucose/fasting insulin ratio and various minimal models were determined in individuals from the two syndromic cohorts, as well as in a control group made of first-degree normal relatives of the insulin-resistant phenotype subjects. RESULTS: The metabolic characteristics of enhanced insulin sensitivity in one of the syndromes and innate insulin resistance in the other could not be properly ascertained by the selected methodology. Furthermore, results were confusing and even discrepant with the clinical findings. CONCLUSIONS: The standard homeostatic minimal models could not properly identify or discriminate insulin sensitivity and resistance in subjects with inherently diminished secretion. It is thereby suggested that these models should be used with caution in clinical situations where reduced secretion of the metabolic peptide is found or suspected.


Subject(s)
Dwarfism/complications , Glucose Intolerance/pathology , Growth Disorders/complications , Human Growth Hormone/deficiency , Insulin Resistance , Laron Syndrome/complications , Case-Control Studies , Glucose Intolerance/etiology , Humans , Prognosis , Syndrome
19.
BMC Oral Health ; 20(1): 146, 2020 05 19.
Article in English | MEDLINE | ID: mdl-32429887

ABSTRACT

BACKGROUND: The use of information and communication technologies (ICTs) provide the tools for enabling fast and reliable real-time communications, as well as the transfer of information between dental professionals and their patients. However, little is known about the frequency and preference of ICTs among Latin-American dentists. Our study aims to fill this gap by assessing different aspects related to ICTs, mainly the frequency of use, perceptions, and barriers among Ecuadorian dentists. METHODS: An anonymous, cross-sectional survey-based study was conducted among 342 Ecuadorian dentists. The final questionnaire included 13 items related to the frequency of use, perceptions, and barriers of ICTs. Bivariate analysis was performed by using chi-squared testing to explore the association between the independent variables and the intended use of ICTs, as well as to characterize the perceptions and barriers related to ICTs. RESULTS: In general, most participants reported the use of ICTs to communicate with colleagues (99.7%), and patients (96.2%), while only 63.5% reported using ICTs to obtain academic information in their daily practice. WhatsApp was rated as the most used ICT for communicating with colleagues and patients. A majority of participants considered that ICTs can be useful for facilitating continuing dental education (92.1%), searching new work opportunities (91.5%), promoting health (90.1%), working with colleagues and other health professionals (91.2%), promoting their professional services (90.6%), and for resolving clinical cases (87.7%). On the subject of barriers, privacy and security concerns about personal and/or patient information was the biggest concern among dentists (65%), followed by lack of time to learn how to use and/or use ICTs (48%), lack of mobile internet access (28.1%), and lack of internet access at work (24.9%). CONCLUSION: In our study, we found that Ecuadorian dentists had a high usage rate of ICTs, mainly for communicating with other colleagues and patients, while the academic use of technology remains a comparatively underused application. Most of the participants surveyed had a positive perception towards ICTs, while privacy and security concerns were identified as the main barrier. Older age was associated with a less favourable perception toward ICTs, as well as an increased likelihood of reporting barriers related to the use of technology.


Subject(s)
Communication , Dentists/psychology , Information Technology , Aged , Cross-Sectional Studies , Ecuador , Female , Humans , Latin America , Male , Medical Informatics/methods , Social Media , Surveys and Questionnaires
20.
PLoS One ; 15(5): e0233387, 2020.
Article in English | MEDLINE | ID: mdl-32437382

ABSTRACT

Real-time reverse transcription PCR (qPCR) normalized to an internal reference gene (RG), is a frequently used method for quantifying gene expression changes in neuroscience. Although RG expression is assumed to be constant independent of physiological or experimental conditions, several studies have shown that commonly used RGs are not expressed stably. The use of unstable RGs has a profound effect on the conclusions drawn from studies on gene expression, and almost universally results in spurious estimation of target gene expression. Approaches aimed at selecting and validating RGs often make use of different statistical methods, which may lead to conflicting results. Based on published RG validation studies involving hypoxia the present study evaluates the expression of 5 candidate RGs (Actb, Pgk1, Sdha, Gapdh, Rnu6b) as a function of hypoxia exposure and hypothermic treatment in the neonatal rat cerebral cortex-in order to identify RGs that are stably expressed under these experimental conditions-using several statistical approaches that have been proposed to validate RGs. In doing so, we first analyzed RG ranking stability proposed by several widely used statistical methods and related tools, i.e. the Coefficient of Variation (CV) analysis, GeNorm, NormFinder, BestKeeper, and the ΔCt method. Using the Geometric mean rank, Pgk1 was identified as the most stable gene. Subsequently, we compared RG expression patterns between the various experimental groups. We found that these statistical methods, next to producing different rankings per se, all ranked RGs displaying significant differences in expression levels between groups as the most stable RG. As a consequence, when assessing the impact of RG selection on target gene expression quantification, substantial differences in target gene expression profiles were observed. Altogether, by assessing mRNA expression profiles within the neonatal rat brain cortex in hypoxia and hypothermia as a showcase, this study underlines the importance of further validating RGs for each individual experimental paradigm, considering the limitations of the statistical methods used for this aim.


Subject(s)
Brain/metabolism , Gene Expression Profiling/methods , Genes, Essential , Hypothermia/genetics , Hypoxia, Brain/genetics , Animals , Animals, Newborn , Gene Expression , Hypothermia/metabolism , Hypoxia, Brain/metabolism , Rats , Real-Time Polymerase Chain Reaction/methods , Reproducibility of Results
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