Optimizing Clinical Diabetes Diagnosis through Generative Adversarial Networks: Evaluation and Validation.

The escalating prevalence of Type 2 Diabetes (T2D) represents a substantial burden on global healthcare systems, especially in regions such as Mexico. Existing diagnostic techniques, although effective, often require invasive procedures and labor-intensive efforts. The promise of artificial intelligence and data science for streamlining and enhancing T2D diagnosis is well-recognized; however, these advancements are frequently constrained by the limited availability of comprehensive patient datasets. To mitigate this challenge, the present study investigated the efficacy of Generative Adversarial Networks (GANs) for augmenting existing T2D patient data, with a focus on a Mexican cohort. The researchers utilized a dataset of 1019 Mexican nationals, divided into 499 non-diabetic controls and 520 diabetic cases. GANs were applied to create synthetic patient profiles, which were subsequently used to train a Random Forest (RF) classification model. The study's findings revealed a notable improvement in the model's diagnostic accuracy, validating the utility of GAN-based data augmentation in a clinical context. The results bear significant implications for enhancing the robustness and reliability of Machine Learning tools in T2D diagnosis and management, offering a pathway toward more timely and effective patient care.

Mobility and postural limitations perceived by transtibial amputees undertaking agricultural activities: a qualitative study.

PURPOSE: In Colombia, 98% of landmines occur in rural areas, where the main victims of amputation are farmers. The challenges these amputees face in their agricultural work remain unknown. The aim of this study is to determine the mobility and postural limitations these farmers face in carrying out their daily activities. METHOD: Forty-nine participants meeting the following criteria were interviewed: transtibial amputee, 18 years and over, performs agricultural labour and wears the prosthesis daily. Subsequently, the interview transcripts were subjected to a content conventional analysis and responses were organized according to the abstraction process to identify categories and subcategories of the problems. RESULTS: Main problems reported were walking on sloping, uneven and wet terrain, problems associated with the stump skin, squatting, kneeling, using vehicles or animals for transportation and carrying objects over 30 kg. Postures such as sitting, running, jumping, and standing on tiptoes were mentioned less frequently. CONCLUSIONS: In conclusion, the prostheses worn by transtibial amputee farmers are not suitable for working on sloping and uneven terrain, nor for performing postures such as kneeling or squatting. These postures are very common in agricultural and livestock tasks in countries with mountainous areas such as Latin American countries. The recognition of problems reported by farmers transtibial amputees, may help to improve the design of prostheses so that they meet the needs of this population and decrease secondary injuries associated with prosthetic use. This information is useful to identify compensatory postures that facilitate prosthetic adaptation and rehabilitation for amputees.

Proteome of Agave angustifolia Haw.: Uncovering metabolic alterations, over-accumulation of amino acids, and compensatory pathways in chloroplast-deficient albino plantlets.

Amino acids (AA) are essential molecules for plant physiology, acting as precursor molecules for proteins and other organic compounds. Chloroplasts play a vital role in AA metabolism, yet little is known about the impact on AA metabolism of albino plants' lack of chloroplasts. In this study, we conducted a quantitative proteome analysis on albino and variegated somaclonal variants of Agave angustifolia Haw. to investigate metabolic alterations in chloroplast-deficient plants, with a focus on AA metabolic pathways. We identified 82 enzymes involved in AA metabolism, with 32 showing differential accumulation between the somaclonal variants. AaCM, AaALS, AaBCAT, AaIPMS1, AaSHMT, AaAST, AaCGS, and AaMS enzymes were particularly relevant in chloroplast-deficient Agave plantlets. Both variegated and albino phenotypes exhibited excessive synthesis of AA typically associated with chloroplasts (aromatic AAs, BCAAs, Asp, Lys, Pro and Met). Consistent trends were observed for AaBCAT and AaCM at mRNA and protein levels in albino plantlets. These findings highlight the critical activation and reprogramming of AA metabolic pathways in plants lacking chloroplasts. This study contributes to unraveling the intricate relationship between AA metabolism and chloroplast absence, offering insights into survival mechanisms of albino plants.

Mechanisms of adaptive hypertrophic cardiac remodeling in a large animal model of premature ventricular contraction-induced cardiomyopathy.

Frequent premature ventricular contractions (PVCs) promoted eccentric cardiac hypertrophy and reduced ejection fraction (EF) in a large animal model of PVC-induced cardiomyopathy (PVC-CM), but the molecular mechanisms and markers of this hypertrophic remodeling remain unexplored. Healthy mongrel canines were implanted with pacemakers to deliver bigeminal PVCs (50% burden with 200-220 ms coupling interval). After 12 weeks, left ventricular (LV) free wall samples were studied from PVC-CM and Sham groups. In addition to reduced LV ejection fraction (LVEF), the PVC-CM group showed larger cardiac myocytes without evident ultrastructural alterations compared to the Sham group. Biochemical markers of pathological hypertrophy, such as store-operated Ca2+ entry, calcineurin/NFAT pathway, ß-myosin heavy chain, and skeletal type α-actin were unaltered in the PVC-CM group. In contrast, pro-hypertrophic and antiapoptotic pathways including ERK1/2 and AKT/mTOR were activated and/or overexpressed in the PVC-CM group, which appeared counterbalanced by an overexpression of protein phosphatase 1 and a borderline elevation of the anti-hypertrophic factor atrial natriuretic peptide. Moreover, the potent angiogenic and pro-hypertrophic factor VEGF-A and its receptor VEGFR2 were significantly elevated in the PVC-CM group. In conclusion, a molecular program is in place to keep this structural remodeling associated with frequent PVCs as an adaptive pathological hypertrophy.

Δ9-Tetrahydrocannabinol Treatment Modifies Insulin Secretion in Pancreatic Islets from Prediabetic Mice Under Hypercaloric Diet.

Background: The endocannabinoid system over-activation is associated with type-2 diabetes mellitus onset, involving physiological, metabolic, and genetic alterations in pancreatic islets. The use of Δ9-Tetrahydrocannabinol (THC) as treatment is still controversial since its effects and mechanisms on insulin secretion are unclear. The aim of this study was to evaluate the effects of THC treatment in pancreatic islets from prediabetic mice. Methods: Prediabetes was induced in mice by hypercaloric diet, and then treated with THC for 3 weeks. Blood glucose and body weight were determined, after behavior tests. Histological changes were evaluated in whole pancreas; in isolated islets we analyzed the effect of THC exposure in glucose-stimulated insulin secretion (GSIS), gene expression, intracellular cyclic adenosine monophosphate (cAMP), and cytosolic calcium changes. Results: THC treatment in prediabetic mice enhanced anxiety and antidepressive behavior without changes in food ingestion, decreased oral-glucose tolerance test, plasma insulin and weight, with small alterations on pancreatic histology. In isolated islets from healthy mice THC increased GSIS, cAMP, and CB1 receptor (CB1r) expression, meanwhile calcium release was diminished. Small changes were observed in islets from prediabetic mice. Conclusions: THC treatment improves some clinical parameters in prediabetic mice, however, in isolated islets, modifies GSIS, intracellular calcium and gene expression, suggesting specific effects related to diabetes evolution.

Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

Rate of onset of dopamine transporter inhibitors assessed with intracranial self-stimulation and in vivo dopamine photometry in rats.

Drug self-administration and intracranial self-stimulation (ICSS) are two preclinical behavioral procedures used to predict abuse potential of drugs, and abuse-related drug effects in both procedures are thought to depend on increased mesolimbic dopamine (DA) signaling. Drug self-administration and ICSS yield concordant metrics of abuse potential across a diverse range of drug mechanisms of action. The "rate of onset," defined as the velocity with which a drug produces its effect once administered, has also been implicated as a determinant of abuse-related drug effects in self-administration procedures, but this variable has not been systematically examined in ICSS. Accordingly, this study compared ICSS effects produced in rats by three DA transporter inhibitors that have different rates of onset (fastest to slowest: cocaine, WIN-35428, RTI-31) and that produced progressively weaker metrics of abuse potential in a drug self-administration procedure in rhesus monkeys. Additionally, in vivo photometry using the fluorescent DA sensor dLight1.1 targeted to the nucleus accumbens (NAc) was used to assess the time course of extracellular DA levels as a neurochemical correlate of behavioral effects. All three compounds produced ICSS facilitation and increased DA levels assessed by dLight. In both procedures, the rank order of onset rate was cocaine > WIN-35428 > RTI-31; however, in contrast to monkey drug self-administration results, maximum effects did not differ across compounds. These results provide additional evidence that drug-induced increases in DA drive ICSS facilitation in rats and illustrate the utility of both ICSS and photometry to evaluate the time course and magnitude of abuse-related drug effects in rats.

[Prescriptions of statins in the elderly according to the type of healthcare establishment: An example of the usefulness of territorial hospital groups]. / Utilisations des statines chez le sujet âgé selon le type de prise en charge : un exemple de l'intérêt des groupements hospitaliers de territoire.

INTRODUCTION: The challenge of territorial hospital groups is to develop coherent care pathways for optimal patient care. Following the creation of a territorial pharmaceutical team, a common prescription review process was initiated in our health area. The objective of this study is to analyze the uses of statins in the elderly. METHOD: The study included all statin-treated patients older than 75 years at the five participating institutions (including long-term nursing homes). In a prospective multicenter study, the benefit/risk ratio of statin prescription has been assessed up. Depending on the clinical situation, a proposal to stop or adjust the dosage could be made. RESULTS: Nine hundred and forty-seven patients were included. Among them, 184 were treated with a statin. Forty-seven patients (26%) are treated in primary prevention and 137 patients (74%) in secondary prevention. Dosages are lower for long stays. Fifteen treatments interruption were accepted out of 44 proposals, mostly for long stays. The reasons given to continue treatment are the need for a new evaluation by a cardiologist or a high cardiovascular risk. CONCLUSION: The variability of results according to the type healthcare institution makes territorial medical and pharmaceutical collaboration relevant. The challenge is to develop a coherent care pathway for optimal care of elderly patients, with congruent objectives.

Prevalence of clozapine-induced sialorrhea and its effect on quality of life.

RATIONALE: Clozapine has proven to be superior to other antipsychotic drugs in the treatment of schizophrenia but is under-prescribed due to its potentially severe side effects. Clozapine-induced sialorrhea (CIS) is a frequent and extremely uncomfortable side effect, which remains understudied. OBJECTIVES: To examine the prevalence of diurnal and nocturnal CIS in a sample of patients treated with clozapine, and to evaluate its impact on quality of life. METHODS: We conducted a cross-sectional, observational study of 130 patients with schizophrenia spectrum disorders treated with clozapine. The prevalence of CIS was evaluated via specific sialorrhea scales. None of the patients included in the study was receiving a specific treatment for hypersalivation during the study period. Possible associations between sialorrhea and clinical and quality of life variables were analyzed. RESULTS: Of 130 subjects, 120 (92.3%) suffered from CIS. Eighty-one (62.31%) suffered from diurnal CIS, 115 (88.56%) from nocturnal CIS, and 85 (65.38%) suffered from both. Significant positive associations between quality of life and diurnal CIS (B = 0.417; p = 2.1e - 6, R2 = 0.156) and nocturnal CIS (B = 0.411; p = 7.7e - 6, R2 = 0.139) were detected. Thirty per cent of the subjects reported a moderate to severe negative impact of sialorrhea on their quality of life. CONCLUSIONS: The present study suggests that CIS is highly prevalent in patients with schizophrenia and has an important impact on quality of life in one-third of our sample. Therefore, the inclusion of a systematic evaluation and treatment of CIS in standard clinical practice is highly recommended. TRIAL REGISTRATION: Clinical Trials ( https://clinicaltrials.gov ) under reference NCT04197037.

Alterations of sarcoplasmic reticulum-mediated Ca2+ uptake in a model of premature ventricular contraction (PVC)-induced cardiomyopathy.

Premature ventricular contractions (PVCs) are the most frequent ventricular arrhythmias in the overall population. PVCs are known to acutely enhance contractility by the post-extrasystolic potentiation phenomenon, but over time persistent PVCs promote PVC-induced cardiomyopathy (PVC-CM), characterized by a reduction of the left ventricular (LV) ejection fraction. Ca2+ cycling in myocytes commands muscle contraction and in this process, SERCA2 leads the Ca2+ reuptake into the sarcoplasmic reticulum (SR) shaping cytosolic Ca2+ signal decay and muscle relaxation. Altered Ca2+ reuptake can contribute to the contractile dysfunction observed in PVC-CM. To better understand Ca2+ handling using our PVC-CM model (canines with 50% PVC burden for 12 weeks), SR-Ca2+ reuptake was investigated by measuring Ca2+ dynamics and analyzing protein expression. Kinetic analysis of Ca2+ reuptake in electrically paced myocytes showed a ~ 21 ms delay in PVC-CM compared to Sham in intact isolated myocytes, along with a ~ 13% reduction in SERCA2 activity assessed in permeabilized myocytes. Although these trends were not statistically significant between groups using hierarchical statistics, relaxation of myocytes following contraction was significantly slower in PVC-CM vs Sham myocytes. Western blot analyses indicate a 22% reduction in SERCA2 expression, a 23% increase in phospholamban (PLN) expression, and a 50% reduction in PLN phosphorylation in PVC-CM samples vs Sham. Computational analysis simulating a 20% decrease in SR-Ca2+ reuptake resulted in a ~ 22 ms delay in Ca2+ signal decay, consistent with the experimental result described above. In conclusion, SERCA2 and PLB alterations described above have a modest contribution to functional adaptations observed in PVC-CM.

Characteristics, as a shield against ionizing photons, of concrete blocks used in the construction industry.

INEGI reports that 81% of new constructions are built with durable materials, such as concrete blocks, including rooms where ionizing radiation is used, such as clinics and hospitals. The volume ratios used in the manufacture of concrete blocks have a 1: 5: 2 ratio of: portland cement, sand and crushed gravel. The percentage mass content of each atom in the sample is obtained with the energy-dispersed X-ray fluorescence, these results are used to calculate the characteristics such as shielding of the concrete blocks, which have been partially reported, in this work several characteristics are presented for photons from 1 keV to 100 GeV, such as linear attenuation coefficients, the hemireductive layer, the effective, atomic and electronic sections, the effective atomic number (Zef). The exposure of accumulation and energy absorption factors (EBF, EABF) of 0.5-40 mfp are reported, using the Photon Shielding and Dosimetry (PSD) software. These characteristics are compared to those of NBS concrete. The concrete blocks have an attenuation capacity for energies used in radiological equipment such as mammography, 20-35 keV; dental, 50-90 keV and for conventional radiography equipment, 70-150 keV, so the block and lightened concrete block must be considered in the calculations of primary and secondary shielding walls.

Radiation shielding and dosimetric parameters of mexican artisanal bricks.

In this work, were determined some radiation shielding and dosimetric parameters of three types of bricks for photons energy from 1 keV to 100 GeV photons using the Phy-X/PSD software, and for comparison also has been calculated the same parameters for NBS concrete. The parameters calculated are the linear attenuation coefficients (LAC), effective atomic numbers (Zeff), half value layers (HVL), the energy absorption buildup factors (EABF) and the exposure buildup factors (EBF), as well as the coefficients to use the geometric progression (G-P) fitting method. Obtained results show that the three types of bricks can be used safely for the design of medical facilities housing mammography units (less than 30 keV).

Decreased mortality among patients with catheter-related bloodstream infections at Catalan hospitals (2010-2019).

BACKGROUND: The incidence of catheter-related bloodstream infections (CRBSIs) has fallen over the last decade, especially in intensive care units (ICUs). AIM: To assess the existence of concomitant trends in outcomes and to analyse the current risk factors for mortality. METHODS: A multicentre retrospective cohort study was conducted at 24 Catalan hospitals participating in the Surveillance of healthcare-associated infections in Catalonia (VINCat). All hospital-acquired CRBSI episodes diagnosed from January 2010 to December 2019 were included. A common protocol including epidemiological, clinical, and microbiological data was prospectively completed. Mortality at 30 days after bacteraemia onset was analysed using the Cox regression model. FINDINGS: Over the study period, 4795 episodes of CRBSI were diagnosed. Among them, 75% were acquired in conventional wards and central venous catheters were the most frequently involved (61%). The 30-day mortality rate was 13.8%, presenting a significant downward trend over the study period: from 17.9% in 2010 to 10.6% in 2019 (hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.92-0.98). The multivariate analysis identified age (HR: 1.03; 95% CI: 1.02-1.04), femoral catheter (1.78; 1.33-2.38), medical ward acquisition (2.07; 1.62-2.65), ICU acquisition (3.45; 2.7-4.41), S. aureus (1.59; 1.27-1.99) and Candida sp. (2.19; 1.64-2.94) as risk factors for mortality, whereas the mortality rate associated with episodes originating in peripheral catheters was significantly lower (0.69; 0.54-0.88). CONCLUSION: Mortality associated with CRBSI has fallen in recent years but remains high. Intervention programmes should focus especially on ICUs and medical wards, where incidence and mortality rates are highest.

Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

[Correlation among tests and functional assessment scales in the follow-up of prosthetic adaptation in people with lower limb amputation]. / Correlación entre pruebas y escalas de valoración funcional en el seguimiento a la adaptación protésica de personas con amputación de miembro inferior.

INTRODUCTION: There is a wide variety of functional tests and scales for the assessment of different aspects in the adaptation of amputees, but there is still no consensus on which are the most appropriate. OBJECTIVES: To describe the measures of correlation and association among three functional tests for lower-limb amputees and to define the most appropriate for this assessment. To assess general satisfaction in lower-limb prostheses users and its association with the functional tests. METHODS: We included 83 unilateral lower-limb amputees who were users of low-cost exoskeletal prostheses. The instruments employed were the Houghton scale, the Prosthesis Evaluation Questionnaire - Mobility Scale (PEQ-MS) and the 2-minute walk test (2MWT). The statistical analysis was performed using the chi-square test and Spearman's correlation coefficient. RESULTS: The functional tests evaluated had an acceptable correlation and association with each other, but the Spearman correlation between the Houghton scale and the 2MWT was of greater significance (whole sample: r=0.56; below-knee amputees: r=0.53). The association measures did not achieve statistically significant results for above-knee amputees or for general satisfaction. CONCLUSIONS: The Houghton Scale and the 2MWT showed a good correlation and association with each other, becoming possible first-line instruments for the follow-up of exoskeletal lower limb prosthesis users. No significant association was identified between satisfaction and the instruments measured.

Geriatric Choosing Wisely choice of recommendations in France: a pragmatic approach based on clinical audits.

BACKGROUND: The international Choosing Wisely campaign seeks to improve the appropriateness of care, notably through large campaigns among physicians and users designed to raise awareness of the risks inherent in overmedication. METHODS: In deploying the Choosing Wisely campaign, the French Society of Geriatrics and Gerontology chose early operationalization via a tool for clinical audit over a limited area before progressive dissemination. This enabled validation of four consensual recommendations concerning the management of urinary tract infections, the prolonged use of anxiolytics, the use of neuroleptics in dementia syndromes, and the use of statins in primary prevention. The fifth recommendation concerns the importance of a dialogue on the level of care. It was written by patient representatives directly involved in the campaign. RESULTS: The first cross-regional campaign in France involved 5337 chart screenings in 43 health facilities. Analysis of the results showed an important variability in practices between institutions and significant percentage of inappropriate prescriptions, notably of psychotropic medication. DISCUSSION: The high rate of participation of target institutions shows that geriatrics professionals are interested in the evaluation and optimization of professional practices. Frequent overuse of psychotropic medication highlights the need of campaigns to raise awareness and encourage deprescribing.

Rotavirus gastroenteritis hospitalizations in provinces with different vaccination coverage rates in Spain, 2013-2018.

BACKGROUND: Rotavirus (RV) vaccines are available in Spain since 2006 but are not included in the National Immunization Program. RV vaccination has reached an intermediate vaccination coverage rate (VCR) but with substantial differences between provinces. The aim of this study was to assess the ratio of RV gastroenteritis (RVGE) admissions to all-cause hospitalizations in children under 5 years of age in areas with different VCR. METHODS: Observational, multicenter, cross-sectional, medical record-based study. All children admitted to the study hospitals with a RVGE confirmed diagnosis during a 5-year period were selected. The annual ratio of RVGE to the total number of all-cause hospitalizations in children < 5 years of age were calculated. The proportion of RVGE hospitalizations were compared in areas with low (< 30%), intermediate (31-59%) and high (> 60%) VCR. RESULTS: From June 2013 to May 2018, data from 1731 RVGE hospitalizations (16.47% of which were nosocomial) were collected from the 12 study hospitals. RVGE hospital admissions accounted for 2.82% (95 CI 2.72-3.00) and 43.84% (95% CI 40.53-47.21) of all-cause and Acute Gastroenteritis (AGE) hospitalizations in children under 5 years of age, respectively. The likelihood of hospitalization due to RVGE was 56% (IC95%, 51-61%) and 27% (IC95%, 18-35%) lower in areas with high and intermediate VCR, respectively, compared to the low VCR areas. CONCLUSIONS: RVGE hospitalization ratios are highly dependent on the RV VCR. Increasing VCR in areas with intermediate and low coverage rates would significantly reduce the severe burden of RVGE that requires hospital management in Spain. Clinical trial registration Not applicable.