First clinical data on artificial intelligence-guided catheter ablation in long-standing persistent atrial fibrillation.

INTRODUCTION: Despite advanced ablation strategies and major technological improvements, treatment of persistent atrial fibrillation (AF) remains challenging and the underlying pathophysiology is not fully understood. This study analyzed the multiple procedure outcome and safety of catheter ablation of spatiotemporal dispersions (DISPERS) detected by artificial intelligence (AI)-guided software in patients with long-standing persistent AF. METHODS AND RESULTS: The Volta VX1 software was used for 50 consecutive patients undergoing catheter ablation for persistent AF. First, high-density mapping (78% biatrial) with a multipolar mapping catheter was performed. In addition to pulmonary vein isolation (PVI), ablation of DISPERS was performed aiming at homogenizing, dissecting, isolating, or connecting DISPERS areas to nonconducting anatomical structures. Follow-up contained regular visits at our outpatient clinic at 1, 3, 6, and 12 months including 7-day Holter electrocardiograms. Patients were mainly suffering from long-standing persistent AF (mean AF duration 50.30 ± 54.28 months). Following PVI, ablation of left atrial and right atrial DISPERS areas led to AF cycle length prolongation (mean of 162.0 ± 16.6 to 202.2 ± 21.6 ms after) and AF termination to atrial tachycardia (AT) or sinus rhythm (SR) in 12 patients (24%). No stroke or pericardial effusion occurred; major groin complications (pseudoaneurysm n = 1, atrioventricular fistula n = 1) were detected in two patients. After a blanking period of 6 weeks, recurrence of any atrial arrhythmia was documented in 26 patients (52%). The majority of patients presented with organized AT (n = 15) while AF was present in n = 9 patients and AT/AF was observed in n = 2 patients. Twenty-two patients underwent reablation. During a mean follow-up of 363.14 ± 187.42 days and after an average of 1.46 ± 0.68 procedures, 82% of patients remained in stable SR. CONCLUSION: DISPERS-guided ablation using machine learning software (the Volta VX1 software) in addition to PVI in long-standing persistent AF ablation resulted in high long-term success rates regarding AF and AT elimination. Most arrhythmia recurrences were reentrant AT. After a total of 1.46 ± 0.68 procedures, freedom from AF/AT was 82%. Despite prolonged procedure times complication rates were low. Randomized studies are necessary to evaluate long-term efficacy of dispersion-guided ablation using AI.

Novel Species of Brucella Causing Human Brucellosis, French Guiana.

Human brucellosis is a zoonoses caused by bacteria of the genus Brucella. Infection results in subacute or chronic debilitating disease with nonspecific clinical manifestations and is often associated with consuming unpasteurized dairy products. We report 2 cases of brucellosis in male patients who were hospitalized in distinct towns of French Guiana, an overseas territory of France located on the northeastern shore of South America. Both men were citizens of Brazil working as clandestine goldminers in the deep Amazonian rainforest. Characterization of the 2 bacterial isolates revealed that they represent a potential new species of Brucella. Medical practitioners working in contact with wildlife in this region of the world should be aware of the existence of these pathogens and the potential for human infection.

A Fenton Approach to Aromatic Radical Cations and Diarylmethane Synthesis.

Manipulating carbon-centered radicals to add to electron-deficient systems is a well-precedented process. By coupling the Fe(II)-mediated Fenton reaction with the Fe(III)-mediated single-electron oxidation of anisolic compounds, we demonstrate how electron-rich carbon-centered radicals can react with electron-rich arenes through a radical-polar cascade pathway. This bioinspired approach produces diarylmethane derivatives from simple unfunctionalized precursors.

Demystifying normalized difference vegetation index (NDVI) for greenness exposure assessments and policy interventions in urban greening.

Most nature and health research use the normalized difference vegetation index (NDVI) for measuring greenness exposure. However, little is known about what NDVI measures in terms of vegetation types (e.g., canopy, grass coverage) within certain analysis zones (e.g., 500 m buffer). Additionally, exploration is needed to understand how to interpret changes in average NDVI (e.g., per 0.1 increments) exposure in relation to changes in vegetation amount and types. In this study, we aimed to explore what vegetation types and amounts best explain the average NDVI and how changes in average NDVI values indicate changes in different vegetation coverages. We used spatial modeling to sample mean NDVI and percentages of vegetation for sample locations within the Greater Manchester case study area. We fitted linear, nonlinear, and mixed multivariate and univariate generalized additive models (GAMs) for multiple spatial scales to identify the relationships between NDVI and vegetation amount and types. Our results showed that the relationships between NDVI and individual vegetation types mostly follow nonlinear trends. We found that canopy and shrubs coverage exhibited a greater influence on mean NDVI exposure values than grass coverage at 300 and 500 m indicating that NDVI values are sensitive to certain types and amounts of vegetation within various buffer zones. We also identified increment in mean NDVI exposure values at lower, mid, and high ranges might be associated with varying changes in total greenspace percentage and individual vegetation types. For instance, at 300 m buffer, an increment of mean NDVI in the lower range (e.g., from 0.2 to 0.3) is associated with an about 17% increase in greenspace percentage. Overall, interpreting changes in NDVI values for urban greening interventions would require careful evaluation of the relative changes in types and quantities of vegetation for different buffer zones.

Economic burden of locoregional and metastatic relapses in resectable early-stage non-small cell lung cancer in Spain.

BACKGROUND: There are scarce data of the costs of non-small cell lung cancer (NSCLC) recurrence in Spain. The objective of this study is to assess the economic burden of disease recurrence, for both locoregional and/or metastatic relapses, after appropriate early-stage NSCLC treatment in Spain. MATERIALS AND METHODS: A two-round consensus panel of Spanish oncologists and hospital pharmacists was conducted to collect information on patient's flow, treatments, use of healthcare resources and sick leaves in patients with relapsed NSCLC. A decision-tree model was developed to calculate the economic burden of disease recurrence after appropriate early-stage NSCLC. Both direct and indirect costs were considered. Direct costs included drug acquisition and healthcare resources costs. Indirect costs were estimated using the human-capital approach. Unit costs were obtained from national databases (euros of 2022). A multi-way sensitivity analysis was performed to provide a range to the mean values. RESULTS: Among a cohort of 100 patients with relapsed NSCLC, 45 patients would have locoregional relapse (36.3 would eventually progress to metastasis and 8.7 would be considered in remission) and 55 patients would have metastatic relapse. Over time, 91.3 patients would experience a metastatic relapse (55 as first relapse and 36.6 after previous locoregional relapse). The overall cost incurred by the 100-patients cohort is €10,095,846 (€9,336,782 direct costs, €795,064 indirect costs). The average cost of a locoregional relapse is €25,194 (€19,658 direct costs, €5536 indirect costs), while the average cost a patient with metastasis who receives up to 4 lines of treatment is €127,167 (€117,328 direct, €9839 indirect). CONCLUSIONS: To our knowledge, this is the first study that specifically quantifies the cost of relapse in NSCLC in Spain. Our findings shown that the overall cost of a relapse after appropriate treatment of early-stage NSCLC patients is substantial, and it increases considerably in the metastatic relapse setting, mainly due to the high cost and long duration of first-line treatments.

Comparative genomics analysis of two Helcococcus kunzii strains co-isolated with Staphylococcus aureus from diabetic foot ulcers.

Helcococcus kunzii is a commensal Gram-positive bacterial species recovered from the human skin microbiota and considered as an opportunistic pathogen. Although little is known about its clinical significance, its increased abundance has been reported in infected wounds, particularly in foot ulcers in persons with diabetes. This species is usually detected in mixed cultures from human specimens and frequently isolated with Staphylococcus aureus. Modulation of staphylococci virulence by H. kunzii has been shown in an infection model of Caenorhabditis elegans. The aim of this study was to compare the genomes of two H. kunzii strains isolated from foot ulcers -isolate H13 and H10 showing high or low impact on S. aureus virulence, respectively- and the H. kunzii ATCC51366 strain. Whole genome analyses revealed some differences between the two strains: length (2.06 Mb (H13) and 2.05 Mb (H10) bp), GC content (29.3% (H13) and 29.5% (H10)) and gene content (1,884 (H13) and 1,786 (H10) predicted genes). The core-proteome phylogenies within the genus characterised H. kunzii H13 and H10 as genetically similar to their ancestor. The main differences between the strains were mainly in sugar-associated transporters and various hypothetical proteins. Five targets were identified as potentially involved in S. aureus virulence modulation in both genomes: the two-component iron export system and three autoinducer-like proteins. Moreover, H13 strain harbours a prophage inserted in 1,261,110-1,295,549 (attL-attR), which is absent in H10 strain. The prophage PhiCD38_2 was previously reported for its ability to modulate secretion profile, reinforcing the autoinducer-like hypothesis. In the future, transcriptomics or metaproteomics approaches could be performed to better characterize the H13 strain and possibly identify the underlying mechanism for S. aureus virulence modulation.

Oxidative Stress, Inflammatory, Angiogenic, and Apoptotic molecules in Proliferative Diabetic Retinopathy and Diabetic Macular Edema Patients.

The aim of this study is to evaluate molecules involved in oxidative stress (OS), inflammation, angiogenesis, and apoptosis, and discern which of these are more likely to be implicated in proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) by investigating the correlation between them in the plasma (PLS) and vitreous body (VIT), as well as examining data obtained from ophthalmological examinations. Type 2 diabetic (T2DM) patients with PDR/DME (PDRG/DMEG; n = 112) and non-DM subjects as the surrogate controls (SCG n = 48) were selected according to the inclusion/exclusion criteria and programming for vitrectomy, either due to having PDR/DME or macular hole (MH)/epiretinal membrane (ERM)/rhegmatogenous retinal detachment. Blood samples were collected and processed to determine the glycemic profile, total cholesterol, and C reactive protein, as well as the malondialdehyde (MDA), 4-hydroxynonenal (4HNE), superoxide dismutase (SOD), and catalase (CAT) levels and total antioxidant capacity (TAC). In addition, interleukin 6 (IL6), vascular endothelial growth factor (VEGF), and caspase 3 (CAS3) were assayed. The VITs were collected and processed to measure the expression levels of all the abovementioned molecules. Statistical analyses were conducted using the R Core Team (2022) program, including group comparisons and correlation analyses. Compared with the SCG, our findings support the presence of molecules involved in OS, inflammation, angiogenesis, and apoptosis in the PLS and VIT samples from T2DM. In PLS from PDRG, there was a decrease in the antioxidant load (p < 0.001) and an increase in pro-angiogenic molecules (p < 0.001), but an increase in pro-oxidants (p < 0.001) and a decline in antioxidants (p < 0.001) intravitreally. In PLS from DMEG, pro-oxidants and pro-inflammatory molecules were augmented (p < 0.001) and the antioxidant capacity diminished (p < 0.001), but the pro-oxidants increased (p < 0.001) and antioxidants decreased (p < 0.001) intravitreally. Furthermore, we found a positive correlation between the PLS-CAT and the VIT-SOD levels (rho = 0.5; p < 0.01) in PDRG, and a negative correlation between the PSD-4HNE and the VIT-TAC levels (rho = 0.5; p < 0.01) in DMEG. Integrative data of retinal imaging variables showed a positive correlation between the central subfield foveal thickness (CSFT) and the VIT-SOD levels (rho = 0.5; p < 0.01), and a negative correlation between the CSFT and the VIT-4HNE levels (rho = 0.4; p < 0.01) in PDRG. In DMEG, the CSFT displayed a negative correlation with the VIT-CAT (rho = 0.5; p < 0.01). Exploring the relationship of the abovementioned potential biomarkers between PLS and VIT may help detecting early molecular changes in PDR/DME, which can be used to identify patients at high risk of progression, as well as to monitor therapeutic outcomes in the diabetic retina.

Tau protein in cerebrospinal fluid: a novel biomarker of the time of death?

BACKGROUND: Tau proteins are recognized biomarkers of neurodegeneration and neuronal damage in the cerebrospinal fluid (CSF). It has also been suggested that these CSF proteins could increase post-mortem due to neuronal death. The aim of this study was to investigate the changes in CSF total and phosphorylated tau (p-tau) levels in the early post-mortem interval (PMI), to determine whether these proteins could be relevant biomarkers of time since death. METHODS: Tau and p-tau levels were measured by ELISA in lumbar and cisternal CSF samples from 82 corpses (46 men, 36 women, mean age: 72.4 ± 15.2 years) with a PMI < 12 h. Forty-eight of them were considered neurologically healthy at the time of death. Rectal and tympanic temperatures were also measured in 37 individuals, and two validated temperature-based methods of PMI estimation were applied (Henssge's nomogram and Baccino's method). RESULTS: CSF tau and p-tau levels were significantly increased, with respective median values of 3315 pg/mL and 68.5 pg/mL in the whole cohort, while lower but still increased levels were observed in neurologically healthy patients. Sub-occipital punctures systematically provided higher tau and p-tau values (p < 0.0001). Despite a great inter-individual variability, the concentrations of both biomarkers were positively correlated with the early PMI, with the highest correlation for cisternal p-tau (r = 0.50, p < 0.0001 in the whole cohort; r = 0.58, p = 0.0003 in the neurologically healthy patients). Higher levels of CSF biomarkers were observed for PMI > 6 h versus PMI ≤ 6 h, the discriminatory power of the biomarkers being higher in the subgroup of neurologically healthy patients. Based on cut-off values obtained by ROC curve analysis, the CSF biomarkers could rectify or adjust the time interval provided by the temperature-based methods in a significant number of cases. A predictive model combining tympanic temperature and cisternal tau values was found to be particularly accurate to assign individuals according to their PMI (≤ or > 6 h), with a Se of 83% and a Sp of 100% (AUC = 0.95). CONCLUSION: Our findings suggest that CSF tau and p-tau proteins could serve as potential biomarkers of time since death, in association with tympanic temperature. The practical applicability of such an integrated approach has to be assessed by further studies.

Investigating Pathogenicity and Virulence of Staphylococcus pettenkoferi: An Emerging Pathogen.

Staphylococcus pettenkoferi is a coagulase-negative Staphylococcus identified in 2002 that has been implicated in human diseases as an opportunistic pathogenic bacterium. Its multiresistant character is becoming a major health problem, yet the pathogenicity of S. pettenkoferi is poorly characterized. In this study, the pathogenicity of a S. pettenkoferi clinical isolate from diabetic foot osteomyelitis was compared with a Staphylococcus aureus strain in various in vitro and in vivo experiments. Growth kinetics were compared against S. aureus, and bacteria survival was assessed in the RAW 264.7 murine macrophage cell line, the THP-1 human leukemia monocytic cell line, and the HaCaT human keratinocyte cell line. Ex vivo analysis was performed in whole blood survival assays and in vivo assays via the infection model of zebrafish embryos. Moreover, whole-genome analysis was performed. Our results show that S. pettenkoferi was able to survive in human blood, human keratinocytes, murine macrophages, and human macrophages. S. pettenkoferi demonstrated its virulence by causing substantial embryo mortality in the zebrafish model. Genomic analysis revealed virulence factors such as biofilm-encoding genes (e.g., icaABCD; rsbUVW) and regulator-encoding genes (e.g., agr, mgrA, sarA, saeS) well characterized in S. aureus. This study thus advances the knowledge of this under-investigated pathogen and validates the zebrafish infection model for this bacterium.

Assessing Feed-Forward Backpropagation Artificial Neural Networks for Strain-Rate-Sensitive Mechanical Modeling.

The manufacturing processes and design of metal and alloy products can be performed over a wide range of strain rates and temperatures. To design and optimize these processes using computational mechanics tools, the selection and calibration of the constitutive models is critical. In the case of hazardous and explosive impact loads, it is not always possible to test material properties. For this purpose, this paper assesses the efficiency and the accuracy of different architectures of ANNs for the identification of the Johnson-Cook material model parameters. The implemented computational tool of an ANN-based parameter identification strategy provides adequate results in a range of strain rates required for general manufacturing and product design applications. Four ANN architectures are studied to find the most suitable configuration for a reduced amount of experimental data, particularly for cases where high-impact testing is constrained. The different ANN structures are evaluated based on the model's predictive capability, revealing that the perceptron-based network of 66 inputs and one hidden layer of 30 neurons provides the highest prediction accuracy of the effective flow stress-strain behavior of Ti64 alloy and three virtual materials.

Gastrocnemius tendon strain in a dog treated with autologous mesenchymal stem cells and a custom orthosis.

OBJECTIVE: To report clinical findings and outcome in a dog with gastrocnemius tendon strain treated with autologous mesenchymal stem cells and a custom orthosis. STUDY DESIGN: Clinical report. ANIMAL: A 4-year-old spayed female Border Collie. METHODS: Bone-marrow derived, autologous mesenchymal stem cells were transplanted into the tendon core lesion. A custom, progressive, dynamic orthosis was fit to the tarsus. Serial orthopedic examinations and ultrasonography as well as long-term force-plate gait analysis were utilized for follow up. RESULTS: Lameness subjectively resolved and peak vertical force increased from 43% to 92% of the contralateral pelvic limb. Serial ultrasonographic examinations revealed improved but incomplete restoration of normal linear fiber pattern of the gastrocnemius tendon. CONCLUSIONS: Findings suggest that autologous mesenchymal stem cell transplantation with custom, progressive, dynamic orthosis may be a viable, minimally invasive technique for treatment of calcaneal tendon injuries in dogs.

[Primary hyperaldosteronism by unilateral adrenal hyperplasia: a report of two cases]. / Hiperaldosteronismo primario (HAP) por hiperplasia suprarrenal unilateral (HSU). Reporte de dos casos.

Primary aldosteronism (PA) is actually the main cause of adrenal-endocrine hypertension. This syndrome is characterized by hypertension, hypokalemia, suppressed plasma renin activity, and increased aldosterone excretion. The most common causes of this syndrome are bilateral idiopathic hyperaldosteronism and aldosterone producing adenoma (Conn's syndrome) and less frequently unilateral adrenal hyperplasia, adrenal carcinoma, or familial hyperaldosteronism. Unilateral adrenal hyperplasia (UAP) constitutes 2% of the causes of PA. We present the case of two patients with UAP.

Plasma Rich in Growth Factors (PRGF) in the Treatment of Patients With Chronic Cervical and Lumbar Pain: A Prospective Observational Clinical Study.

BACKGROUND: Chronic back pain is a long-lasting disorder, whose main source of pain is often the intervertebral disc that undergoes a degenerative process associated with low-grade inflammation, leading to a reduced quality of life. OBJECTIVES: The aim of our study was to assess the efficacy of intradiscal and epidural injections of plasma rich in growth factors (PRGF) in patients with chronic clinical symptoms due to intervertebral disc (IVD) degeneration. STUDY DESIGN: Prospective observational study. SETTING: A single spine unit in a private clinic. METHODS: Thirty-two patients with cervical and lumbar chronic pain due to IVD degeneration were treated with 2 or 3 series of intradiscal and epidural PRGF infiltrations with 2 weeks between each procedure. The procedures were performed under fluoroscopic guidance and grade 3 sedation in an operating theater. Treatment efficacy was evaluated using the Spine Tango Core Outcome Measure Index questionnaire, Numeric Rating Scale for back pain, and the Oswestry Disability Index questionnaire. In addition, the number of patients who successfully achieved the minimal clinically important change was also determined. These assessments were evaluated at pretreatment (baseline) and at one, 3, and 6 months posttreatment. RESULTS: The Oswestry Disability Index, COMI Spine Tango Core Outcome Measure Index total score, and Numeric Rating Scale showed a statistically significant reduction from the baseline level to the posttreatment first month, third month, and sixth month (P < 0.001). Moreover, 78.1% of the patients reached a pain reduction superior to 30% one month posttreatment, and 87.5% at 6 months posttreatment, which is considered as a clinically significant improvement. LIMITATIONS: This study was prospective and did not have a control group. Only patient-reported outcomes were evaluated. CONCLUSIONS: This observational, prospective study of patients with chronic back pain showed that 2-3 intradiscal and epidural injections of PRGF significantly decreased pain and disability at one month posttreatment and this improvement was maintained, and in some patients even improved, at 3, and 6 months posttreatment.

Ranibizumab for the treatment of retinopathy of prematurity: systematic review and meta-analysis.

Anti-VEGF drugs like ranibizumab can be used to treat retinopathy of prematurity (ROP) by halting the formation of abnormal blood vessels, or lasers can be used to burn the edges of the retina where these vessels are present. The objective is to compare the efficacy for ROP between ranibizumab and laser therapy. Material and methods: Electronic searches will be carried out in medical databases with key words and controlled vocabulary terms. Randomized controlled trials (RCT) will be assessed. The primary outcome will be the full ROP regression. Two reviewers will extract the data using predefined forms and, to assess the quality of the study, we will use RoB 2.0, the tool for randomized controlled trials developed by the Cochrane Collaboration. We used a combination of the inverse-variance approach and random-effects models for the meta-analysis. Results: The eyes of 182 preterm infants who had ranibizumab treatment were assessed in a total of 364 eyes, and 135 infants received laser therapy. The follow-up period was between 6 and 24 months. Ranibizumab was not associated with greater regression of ROP compared to laser therapy in preterm infants (RR: 1.09, CI 95%: 0.95-1.24; p: 0.22). Also, ranibizumab was not associated with recurrence of ROP compared to laser therapy in preterm infants (RR: 3.77, CI 95%: 0.55-25.81; p: 0.22). Conclusions: The efficacy of ranibizumab compared to laser is very uncertain in terms of ROP regression and decreased ROP recurrence in preterm infants. Systematic Review Registration: identifier PROSPERO (CRD42022324150).

Examining the Role of Quality of Institutionalized Healthcare on Maternal Mortality in the Dominican Republic.

The main study objective was to determine the extent to which the quality of institutionalized healthcare, sociodemographic factors of obstetric patients, and institutional factors affect maternal mortality in the Dominican Republic. COM-Poisson distribution and the Pearson correlation coefficient were used to determine the relationship of predictor factors (i.e., hospital bed rate, vaginal birth rate, teenage mother birth rate, single mother birth rate, unemployment rate, infant mortality rate, and sex of child rate) in influencing maternal mortality rate. The factors hospital bed rate, teenage mother birth rate, and unemployment rate were not correlated with maternal mortality. Maternal mortality increased as vaginal birth rates and infant death rates increased whereas it decreased as single mother birth rates increased. Further research to explore alternate response variables, such as maternal near-misses or severe maternal morbidity is warranted. Additionally, the link found between infant death and maternal mortality presents an opportunity for collaboration among medical specialists to develop multi-faceted solutions to combat adverse maternal and infant health outcomes in the DR.

Cost-effectiveness of adjuvant atezolizumab versus best supportive care in the treatment of patients with resectable early-stage non-small cell lung cancer and overexpression of PD-L1.

AIMS: To assess the cost-effectiveness of adjuvant atezolizumab in the treatment of early-stage NSCLC patients (stage II-IIIA) with expression PD-L1 ≥ 50% without mutations in EGFR or ALK rearrangements in Spain. MATERIALS AND METHODS: A 5-states Markov model (DFS, locoregional recurrence, 1 L-metastatic recurrence, 2 L-metastatic recurrence, and death states) was adapted to the Spanish setting. Demographic characteristics of the hypothetical cohort, transition probabilities from the DFS state, and safety parameters were obtained from IMpower010 study (GO29527). Transition probabilities from locoregional and metastatic health states were obtained from the literature. The usual clinical practice in Spain (use of health resources, management of the disease, etc.) was obtained from a previous analysis carried out by the authors of this study. A societal perspective was considered so both direct and indirect costs were included (expressed in € of 2021). A lifetime horizon was used, so costs and health outcomes were discounted at 3% per year. Sensitivity analyses were performed to evaluate uncertainty. RESULTS: Over a lifetime horizon, treatment with adjuvant atezolizumab provided greater effectiveness (+2.61 life years [LY] and +1.95 quality-adjusted life years [QALY]) and higher cost (€+22,538) than BSC. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratios (ICUR) of the analysis were €8,625/LY gained and €11,583/QALY gained, respectively. Robustness of these base-case results was confirmed by the sensitivity analyses performed. In the probabilistic sensitivity analysis, 90% of the simulations performed showed that adjuvant atezolizumab is cost-effective versus BSC, considering a threshold of €30,000/QALY. CONCLUSIONS: Our results showed that adjuvant treatment with atezolizumab in patients with early-stage resected NSCLC with overexpression of PD-L1 and without EGFR and ALK mutations is cost-effective versus BSC as the ICERs and ICURs obtained are below the cost-effectiveness thresholds commonly considered in Spain, thus offering a new treatment alternative for these patients.

Epidemiologic Situation of HIV and Monkeypox Coinfection: A Systematic Review.

The most recent monkeypox (Mpox) outbreak is mostly affecting men who have sex with men (MSM) who participate in high-risk sexual behaviors, which is typically the case among human immunodeficiency virus (HIV) carriers, according to clinical and epidemiological statistics. The objective of this research is to determine the epidemiological situation of HIV and smallpox co-infection. Until 1 October 2022, a thorough evaluation of the literature was conducted utilizing the databases PubMed, Embase, Scopus, and Web of Science. Studies were evaluated based on the criteria for selection. Fifty-three studies met the selection criteria. A total of 6345 confirmed cases of monkeypox were recorded, and 40.32% (n = 2558) of these cases also had HIV co-infection. In addition, 51.36% (n = 3259) of the men (91.44%; n = 5802), whose ages ranged from 18 to 71 years, exhibited MSM-specific sexual behaviors. Co-infection with these two viruses can be especially dangerous because it can exacerbate the symptoms of both diseases and make them more difficult to treat. People with HIV are more vulnerable to certain infections, including monkeypox, because their immune systems are weakened. Therefore, it is important that they take measures to prevent infection, such as avoiding contact with infected animals, risky behaviors, and maintaining good hygiene.

Severity of Fatigue and Its Relationship with TSH before and after Levothyroxine Replacement Therapy in Patients with Primary Hypothyroidism.

BACKGROUND: Fatigue is a common symptom in hypothyroidism; however, the effect of levothyroxine on fatigue has been little studied. The aim of this study was to evaluate the effect of levothyroxine on fatigue in Latino patients with primary hypothyroidism, as well as the association of TSH and free T4 (FT4) with the severity and persistence of fatigue. METHODS: A prospective study was performed in 92 patients with primary hypothyroidism. Fatigue severity scale (FSS) scores and clinical and biochemical characteristics before and at 6 months of levothyroxine were evaluated. RESULTS: After 6 months of levothyroxine, a reduction in FSS (53 (47-57) vs. 36 (16-38); p = 0.001) and fatigue frequency (45.7% vs. 26.1%; p = 0.008) was evident. Both before and after 6 months of levothyroxine, there was a positive correlation of the FSS score with TSH and a negative correlation with FT4. Persistent fatigue was associated with a pretreatment FSS score (r = 0.75; p = 0.001) and diabetes (r = 0.40; p = 0.001). An FSS > 34 (RR 3.9 (95% CI 1.43-10.73; p = 0.008)), an FSS > 36 (RR 3.23 (95% CI 1.21-8.6; p = 0.019)), and diabetes (RR 5.7 (95% CI 1.25-9.6; p = 0.024)) before treatment were risk factors for persistent fatigue. CONCLUSIONS: Levothyroxine improved fatigue in most patients. Diabetes and an FSS score >34 or >36 before treatment were risk factors for persistent fatigue.

Biochemical-molecular-genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients.

Introduction: Glaucoma is a chronic neurodegenerative disease, which is the leading cause of irreversible blindness worldwide. As a response to high intraocular pressure, the clinical and molecular glaucoma biomarkers indicate the biological state of the visual system. Classical and uncovering novel biomarkers of glaucoma development and progression, follow-up, and monitoring the response to treatment are key objectives to improve vision outcomes. While the glaucoma imaging field has successfully validated biomarkers of disease progression, there is still a considerable need for developing new biomarkers of early glaucoma, that is, at the preclinical and initial glaucoma stages. Outstanding clinical trials and animal-model study designs, innovative technology, and analytical approaches in bioinformatics are essential tools to successfully uncover novel glaucoma biomarkers with a high potential for translation into clinical practice. Methods: To better understand the clinical and biochemical-molecular-genetic glaucoma pathogenesis, we conducted an analytical, observational, and case-comparative/control study in 358 primary open-angle glaucoma (POAG) patients and 226 comparative-control individuals (CG) to collect tears, aqueous humor, and blood samples to be processed for identifying POAG biomarkers by exploring several biological pathways, such as inflammation, neurotransmitter/neurotrophin alteration, oxidative stress, gene expression, miRNAs fingerprint and its biological targets, and vascular endothelial dysfunction, Statistics were done by using the IBM SPSS 25.0 program. Differences were considered statistically significant when p ≤ 0.05. Results: Mean age of the POAG patients was 70.03 ± 9.23 years, and 70.62 ± 7.89 years in the CG. Malondialdehyde (MDA), nitric oxide (NO), interleuquin (IL)-6, endothelin-1 (ET-1), and 5 hydroxyindolacetic acid (5-HIAA), displayed significantly higher levels in the POAG patients vs. the CG (p < 0.001). Total antioxidant capacity (TAC), brain derived neurotrophic factor (BDNF), 5-hydroxy tryptamine (5-HT), solute carrier family 23-nucleobase transporters-member 2 (SLC23A2) gene, and the glutathione peroxidase 4 (GPX4) gene, showed significantly lower levelsin the POAG patients than in the CG (p < 0.001). The miRNAs that differentially expressed in tear samples of the POAG patients respect to the CG were the hsa miR-26b-5p (involved in cell proliferation and apoptosis), hsa miR-152-3p (regulator of cell proliferation, and extracellular matrix expression), hsa miR-30e-5p (regulator of autophagy and apoptosis), and hsa miR-151a-3p (regulator of myoblast proliferation). Discussion: We are incredibly enthusiastic gathering as much information as possible on POAG biomarkers to learn how the above information can be used to better steer the diagnosis and therapy of glaucoma to prevent blindness in the predictable future. In fact, we may suggest that the design and development of blended biomarkers is a more appropriate solution in ophthalmological practice for early diagnosis and to predict therapeutic response in the POAG patients.

Oxidative Stress Mediates Epigenetic Modifications and the Expression of miRNAs and Genes Related to Apoptosis in Diabetic Retinopathy Patients.

Knowledge on the underlying mechanisms and molecular targets for managing the ocular complications of type 2 diabetes mellitus (T2DM) remains incomplete. Diabetic retinopathy (DR) is a major cause of irreversible visual disability worldwide. By using ophthalmological and molecular-genetic approaches, we gathered specific information to build a data network for deciphering the crosslink of oxidative stress (OS) and apoptosis (AP) processes, as well as to identify potential epigenetic modifications related to noncoding RNAs in the eyes of patients with T2DM. A total of 120 participants were recruited, being classified into two groups: individuals with T2MD (T2MDG, n = 67), divided into a group of individuals with (+DR, n = 49) and without (-DR, n = 18) DR, and a control group (CG, n = 53). Analyses of compiled data reflected significantly higher plasma levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and significantly lower total antioxidant capacity (TAC) in the +DR patients compared with the -DR and the CG groups. Furthermore, the plasma caspase-3 (CAS3), highly involved in apoptosis (AP), showed significantly higher values in the +DR group than in the -DR patients. The microRNAs (miR) hsa-miR 10a-5p and hsa-miR 15b-5p, as well as the genes BCL2L2 and TP53 involved in these pathways, were identified in relation to DR clinical changes. Our data suggest an interaction between OS and the above players in DR pathogenesis. Furthermore, potential miRNA-regulated target genes were identified in relation to DR. In this concern, we may raise new diagnostic and therapeutic challenges that hold the potential to significantly improve managing the diabetic eye.