Risk factors for therapeutic failure in adults with methicillin-resistant Staphylococcus aureus (MRSA) infection treated with vancomycin in a high-complexity hospital in Cali, Colombia.

Objective: To determine the risk factors associated with therapeutic failure of vancomycin in hospitalized adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Design: Case-control study. Setting: Conducted in a high complexity hospital in Cali, Colombia. Participants: Adult hospitalized from January 1, 2015, to December 31, 2021, with MRSA infections with confirmed microbiological isolation. Methods: Cases were patients with therapeutic failure of vancomycin (mortality, poor clinical improvement, change of antibiotic used, early relapse, or persistence of positive blood cultures) and control patients were those who did not present failure. Significant variables from the bivariate analysis were included in a multiple analysis with an asymmetric logistic regression model. Results: A total of 105 patients were included in the study, 28 in the treatment group and 77 in the control group. The median age was 49 years and 59 (56%) of participants were men. The following variables: age (OR 1.034; 95% CI 1.007-1.061, p=0.011), osteomyelitis/ septic arthritis (OR 6.035; 95% CI 2.282-15.956, p=0.000) and minimum inhibitory concentration (MIC) (OR 5.971; 95% CI 1.321-26.979, p=0.020) were found to be independent risk factors associated with therapeutic failure of vancomycin. Vancomycin trough levels were not different between cases and controls (OR 0.976; 95% CI 0.911-1.044, p=0.478). Conclusions: When a multiple analysis was performed to control for confounding factors, only 3 variables were found to be significant and were considered risk factors for therapeutic failure of vancomycin in adult patients with MRSA infection: age, MIC, and osteomyelitis/ septic arthritis.

The Effects of Fucoidan Derived from Sargassum filipendula and Fucus vesiculosus on the Survival and Mineralisation of Osteogenic Progenitors.

Osteosarcoma is a bone cancer primarily affecting teenagers. It has a poor prognosis and diminished quality of life after treatment due to chemotherapy side effects, surgical complications and post-surgical osteoporosis risks. The sulphated polysaccharide fucoidan, derived from brown algae, has been a subject of interest for its potential anti-cancer properties and its impact on bone regeneration. This study explores the influence of crude, low-molecular-weight (LMW, 10-50 kDa), medium-molecular-weight (MMW, 50-100 kDa) and high-molecular-weight (HMW, >100 kDa) fractions from Sargassum filipendula, harvested from the Colombian sea coast, as well as crude fucoidan from Fucus vesiculosus, on a specific human osteoprogenitor cell type, human embryonic-derived mesenchymal stem cells. Fourier transform infrared spectroscopy coupled with attenuated total reflection (FTIR-ATR) results showed the highest sulphation levels and lowest uronic acid content in crude extract from F. vesiculosus. There was a dose-dependent drop in focal adhesion formation, proliferation and osteogenic differentiation of cells for all fucoidan types, but the least toxicity was observed for LMW and MMW. Transmission electron microscopy (TEM), JC-1 (5,50,6,60-tetrachloro-1,10,3,30-tetraethylbenzimi-dazolylcarbocyanine iodide) staining and cytochrome c analyses confirmed mitochondrial damage, swollen ER and upregulated autophagy due to fucoidans, with the highest severity in the case of F. vesiculosus fucoidan. Stress-induced apoptosis-like cell death by F. vesiculosus fucoidan and stress-induced necrosis-like cell death by S. filipendula fucoidans were also confirmed. LMW and MMW doses of <200 ng/mL were the least toxic and showed potential osteoinductivity. This research underscores the multifaceted impact of fucoidans on osteoprogenitor cells and highlights the delicate balance between potential therapeutic benefits and the challenges involved in using fucoidans for post-surgery treatments in patients with osteosarcoma.

Bruton's Tyrosine Kinase Inhibitors: Recent Updates.

Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the landscape for the treatment of hematological malignancies, solid tumors, and, recently, autoimmune disorders. The BTK receptor is expressed in several hematopoietic cells such as macrophages, neutrophils, mast cells, and osteoclasts. Similarly, the BTK receptor is involved in signaling pathways such as chemokine receptor signaling, Toll-like receptor signaling, and Fc receptor signaling. Due to their unique mechanism, these agents provide a diverse utility in a variety of disease states not limited to the field of malignant hematology and are generally well-tolerated.

Clinical features of patients with hands arthralgia referred from primary care physicians to rheumatologists: A cohort study.

PURPOSE: Early referral of patients with suspicious of rheumatoid arthritis (RA) has an impact on prognosis. Our study aimed to evaluate the clinical characteristics of patients with hands arthralgia who were referred from primary care physicians (PCP) to the rheumatologist. METHODS: A descriptive, observational, prospective cohort study was performed. We included patients who visited a PCP for the first time for hands arthralgia. Demographics and the European Alliance of Associations for Rheumatology criteria for arthralgia suspicious for progression to RA plus seven complementary questions, the time to referral, the pressure needed to provoke pain with an automatic squeeze test machine in the metacarpophalangeal joints of both hands, and the diagnoses established at the last review of medical charts from patients on follow-up were documented. The primary outcome was the referral to a rheumatologist. RESULTS: A total of 109 patients were included. The mean age was 49.9 years, 81.6% were women. 30.3% were referred to the rheumatologist. The time to referral was a median of 38 days. The main clinical characteristics associated with referral to the rheumatologist were the "most severe symptoms are present after midnight" (OR=6.29) and the "difficulty with making a fist" (OR=3.67). An isolated "positive squeeze test of metacarpophalangeal joints" was not associated with a referral to the rheumatologist. CONCLUSIONS: Among patients with hands arthralgia who attended PCP, those with most severe symptoms after midnight and difficulty making a fist were more likely to be referred to the rheumatology clinic. Isolated positive squeeze tests are not a parameter for referral, it should only be performed if arthralgia is clinically suspected.

Clinical features of patients with hands arthralgia referred from primary care physicians to rheumatologists: A cohort study / Características clínicas de los pacientes con artralgia de manos que son referidos a la clínica de reumatología por médicos de atención primaria: un estudio de cohorte

Purpose: Early referral of patients with suspicious of rheumatoid arthritis (RA) has an impact on prognosis. Our study aimed to evaluate the clinical characteristics of patients with hands arthralgia who were referred from primary care physicians (PCP) to the rheumatologist.Methods: A descriptive, observational, prospective cohort study was performed. We included patients who visited a PCP for the first time for hands arthralgia. Demographics and the European Alliance of Associations for Rheumatology criteria for arthralgia suspicious for progression to RA plus seven complementary questions, the time to referral, the pressure needed to provoke pain with an automatic squeeze test machine in the metacarpophalangeal joints of both hands, and the diagnoses established at the last review of medical charts from patients on follow-up were documented. The primary outcome was the referral to a rheumatologist. Results: A total of 109 patients were included. The mean age was 49.9 years, 81.6% were women. 30.3% were referred to the rheumatologist. The time to referral was a median of 38 days. The main clinical characteristics associated with referral to the rheumatologist were the “most severe symptoms are present after midnight” (OR=6.29) and the “difficulty with making a fist” (OR=3.67). An isolated “positive squeeze test of metacarpophalangeal joints” was not associated with a referral to the rheumatologist. Conclusions: Among patients with hands arthralgia who attended PCP, those with most severe symptoms after midnight and difficulty making a fist were more likely to be referred to the rheumatology clinic. Isolated positive squeeze tests are not a parameter for referral, it should only be performed if arthralgia is clinically suspected.(AU)

Objetivo: Derivar tempranamente a los pacientes con sospecha de artritis reumatoide (AR) tiene un impacto en su pronóstico. Nuestro estudio tuvo como objetivo evaluar las características clínicas de los pacientes con artralgia de manos que fueron remitidos desde médicos de atención primaria (MAP) al reumatólogo. Métodos: Se realizó un estudio de cohorte descriptivo, observacional, y prospectivo. Incluimos pacientes que acudieron con un MAP por artralgia de manos. Se documentaron criterios demográficos y de la European Alliance of Associations for Rheumatology (EULAR) para artralgia con sospecha de progresión a AR más siete preguntas complementarias, el tiempo de derivación, la presión necesaria para provocar dolor con una máquina automática que comprime las articulaciones metacarpofalángicas, y los diagnósticos establecidos en la última revisión documentados en los expedientes médicos de los pacientes en seguimiento. El resultado principal fue la referencia al reumatólogo. Resultados: Un total de 109 pacientes fueron incluidos. El promedio de edad fue de 49,9 años, 81,6% fueron mujeres, 30,3% fueron referidos al reumatólogo. El tiempo de derivación al reumatólogo tuvo una mediana de 38 días. Las principales características clínicas asociadas con lo anterior fueron: «síntomas más severos presentes después de la medianoche» (OR=6,29) y «dificultad para hacer un puño» (OR=3,67). Una «prueba de compresión positiva de las articulaciones metacarpofalángicas» aislada no se asoció con una derivación al reumatólogo. Conclusión: Entre los pacientes que acudieron con MAP por artralgia de manos, aquellos con síntomas más severos después de la medianoche y que refirieron dificultad para realizar un puño fueron más frecuentemente referidos a una clínica de reumatología. Sin embargo, una prueba de compresión aislada no fue útil para la derivación temprana.(AU)

Indocyanine green and iohexol loaded hydroxyapatite in poly(L-lactide-co-caprolactone)-based composite for bimodal near-infrared fluorescence- and X-ray-based imaging.

This study aimed to develop material for multimodal imaging by means of X-ray and near-infrared containing FDA- and EMA-approved iohexol and indocyanine green (ICG). The mentioned contrast agents (CAs) are hydrophilic and amphiphilic, respectively, which creates difficulties in fabrication of functional polymeric composites for fiducial markers (FMs) with usage thereof. Therefore, this study exploited for the first time the possibility of enhancing the radiopacity and introduction of the NIR fluorescence of FMs by adsorption of the CAs on hydroxyapatite (HAp) nanoparticles. The particles were embedded in the poly(L-lactide-co-caprolactone) (P[LAcoCL]) matrix resulting in the composite material for bimodal near-infrared fluorescence- and X-ray-based imaging. The applied method of material preparation provided homogenous distribution of both CAs with high iohexol loading efficiency and improved fluorescence signal due to hindered ICG aggregation. The material possessed profound contrasting properties for both imaging modalities. Its stability was evaluated during in vitro experiments in phosphate-buffered saline (PBS) and foetal bovine serum (FBS) solutions. The addition of HAp nanoparticles had significant effect on the fluorescence signal. The X-ray radiopacity was stable within minimum 11 weeks, even though the addition of ICG contributed to a faster release of iohexol. The stiffness of the material was not affected by iohexol or ICG, but incorporation of HAp nanoparticles elevated the values of bending modulus by approximately 70%. Moreover, the performed cell study revealed that all tested materials were not cytotoxic. Thus, the developed material can be successfully used for fabrication of FMs.

Determination of 45 Pesticides in Avocado Varieties by the QuEChERS Method and Gas Chromatography-Tandem Mass Spectrometry.

Gas chromatography (GC) tandem mass spectrometry (MS/MS) stands as a preeminent analytical instrument extensively employed for the surveillance of pesticide residues in food. Nevertheless, these methods are vulnerable to matrix effects (MEs), which can potentially affect accurate quantification depending on the specific combination of analyte and matrix. Among the various strategies to mitigate MEs, matrix-matched calibration represents the prevailing approach in pesticide residue applications due to its cost-effectiveness and straightforward implementation. In this study, a total of 45 representative pesticides were analyzed in three different varieties of avocado (i.e., Criollo, Hass, and Lorena) using the Quick-Easy-Cheap-Effective-Rugged-Safe (QuEChERS) method with ammonium formate and GC-MS/MS. For this purpose, 5 g of the avocado sample was extracted with 10 mL of acetonitrile, and then 2.5 g of ammonium formate was added to induce phase separation. Subsequently, the supernatant underwent a cleanup process via dispersive solid-phase extraction employing 150 mg of anhydrous MgSO4, 50 mg of primary-secondary amine, 50 mg of octadecylsilane, 10 mg of graphitized carbon black, and 60 mg of a zirconium oxide-based sorbent (Z-Sep+). The GC-MS/MS analysis was successfully performed in less than 25 min. Rigorous validation experiments were carried out to assess the performance of the method. The examination of a matrix-matched calibration curve for each variety of avocado revealed that the ME remained relatively consistent and less than 20% (considered as a soft ME) for most pesticide/variety combinations. Furthermore, the method´s limits of quantification were lower than 5 µg/kg for all three varieties. Finally, the recovery values for most pesticides fell within the acceptable range of 70-120%, with relative standard deviation values below 20%.

Hypertrophic Cardiomyopathy Diagnosis and Treatment in High- and Low-Income Countries: A Narrative Review.

Hypertrophic cardiomyopathy (HCM) is a hereditary cardiac condition characterized by unexplained left ventricular hypertrophy without a hemodynamic cause. This condition is prevalent in the United States, resulting in various clinical manifestations, including diastolic dysfunction, left ventricular outflow obstruction, cardiac ischemia, and atrial fibrillation. HCM is associated with several genetic mutations, with sarcomeric mutations being the most common and contributing to a more complex disease course. Early diagnosis of HCM is essential for effective management, as late diagnosis often requires invasive treatments and creates a substantial financial burden. Disparities in HCM diagnosis and treatment exist between high-income and low-income countries. High-income countries have more resources to investigate and implement advanced diagnostic and treatment modalities. In contrast, low-income countries face challenges in accessing diagnostic equipment, trained personnel, and affordable medications, leading to a lower quality of life and life expectancy for affected individuals. Diagnostic tools for HCM include imaging studies such as 2D echocardiography, cardiovascular magnetic resonance (CMR), and electrocardiograms (ECGs). CMR is considered the gold standard but remains inaccessible to a significant portion of the world's population, especially in low-income countries. Genetics plays a crucial role in HCM, with numerous mutations identified in various genes. Genetic counseling is essential but often limited in low-income countries due to resource constraints. Disparities in healthcare access and adherence to treatment recommendations exist between high-income and low-income countries, leading to differences in patient outcomes. Addressing these disparities is essential to improve the overall management of HCM on a global scale. In conclusion, this review highlights the complex nature of HCM, emphasizing the importance of early diagnosis, genetic counseling, and access to appropriate diagnostic and therapeutic interventions. Addressing healthcare disparities is crucial to ensure that all individuals with HCM receive timely and effective care, regardless of their geographic location or socioeconomic status.

Fusariosis in Mexico: A 10-year retrospective series.

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.

This study describes the epidemiological characteristics of patients with fusariosis from a multicenter cohort in Mexico. These findings provide information from this invasive fungal disease that threatens different countries in Latin America.

[Conocimiento de las madres de niños menores de 5 años sobre la vacunación en la Unidad de Medicina Familiar 1, Orizaba, Veracruz].

Objective: Determine the level of knowledge and acceptance that mothers of children under 5 years of age have about vaccination. Methods: Statistical analysis was performed using the GraphPad Prism statistical program. Absolute frequencies and percentages were estimated for the qual- itative variables, and measures of central tendency and dispersion for numerical variables. The level of knowledge and acceptance of vaccination was associated with the variables using Pearson's Chi-square. Results: The level of knowledge that prevailed was high (70.3%) and was associated with age (p=0.00), education (p=0.00) and occupation (p=0.03). The most frequent occupation was housewife (47.1%), the most frequent schooling was professional education (3.5%), the majority were married women (60.2%) and Catholics (81.2%). Conclusions: The null hypothesis of our study is confirmed, obtaining that 70.3% of the population has high knowledge about vaccination in children under 5 years of age, it was also found that this knowledge is associated with age, schooling and occupation of the mothers participating in this study.

Objetivo: Determinar el nivel de conocimiento y aceptación que tienen las madres de niños menores de 5 años sobre la vacunación. Métodos: Se realizo el análisis estadístico en el programa estadístico GraphPad Prism. Se estimaron frecuencias absolutas y porcentajes para las variables cualitativas, y medidas de tendencia central y dispersión para variables numéricas. Se asocio el nivel de conocimiento y aceptación sobre la vacunación con las variables mediante de Chi cuadrada de Pearson. Resultados: El nivel de conocimiento que predomino fue alto (70.3%) y se encontró asociado a la edad (p=0.00), escolaridad (p=0.00) y ocupación (p=0.03). La ocupación más frecuente fue ama de casa (47.1%), la escolaridad con mayor frecuencia fue educación profesional (3.5%), la mayoría fueron mujeres casadas (60.2%) y católicas (81.2%). Conclusiones: Se confirma la hipótesis nula de nuestro estudio obteniendo que el 70.3% de la población tiene un conocimiento alto acerca de la vacunación en niños menores de 5 años, además se encontró que este conocimiento se encuentra asociado a la edad, escolaridad y ocupación de las madres participantes en este estudio.

Chlorphenamine adsorption on commercial activated carbons: Effect of Operating Conditions and Surface Chemistry.

Chlorphenamine (CPA) adsorption onto three activated carbons (ACs), namely, Megapol M (MM), Micro 10 (M10), and GAMA B (GB), was studied in this work. The textural properties, concentrations of active sites, surface charge and point of zero charge of the ACs were assessed. The surface areas (SBET) of MM, GB and M10 were 1107, 812 and 766 m2/g, respectively. The MM surface had an acidic character, while the surfaces of M10 and GB were basic. The adsorption capacity of MM, M10, and GB towards CPA was studied at pH 7 and 11, and the adsorption capacity decreased in the order MM > M10 ≈ GB, which was ascribed to the magnitude of SBET and the concentration of acidic sites. The solution pH significantly increased the adsorption capacity of MM towards CPA by raising the solution pH from 5 to 9, and this behavior was attributed to the electrostatic attraction between the negatively charged surface of MM and the cationic species of CPA. The maximum uptake of CPA adsorbed on MM was 574.6 mg/g at pH = 11 and T = 25 °C. The adsorption capacity of MM was slightly raised by incrementing the temperature. Lastly, the zeta potential measurements of pristine MM and MM saturated with CPA confirmed that the electrostatic attraction predominated in the pH range of 5-9, and the π-π stacking interactions were the principal mechanism of CPA adsorption on MM at pH 11.

Paraventricular nucleus projections to the nucleus tractus solitarii are essential for full expression of hypoxia-induced peripheral chemoreflex responses.

The hypothalamic paraventricular nucleus (PVN) is essential to peripheral chemoreflex neurocircuitry, but the specific efferent pathways utilized are not well defined. The PVN sends dense projections to the nucleus tractus solitarii (nTS), which exhibits neuronal activation following a hypoxic challenge. We hypothesized that nTS-projecting PVN (PVN-nTS) neurons contribute to hypoxia-induced nTS neuronal activation and cardiorespiratory responses. To selectively target PVN-nTS neurons, rats underwent bilateral nTS nanoinjection of retrogradely transported adeno-associated virus (AAV) driving Cre recombinase expression. We then nanoinjected into PVN AAVs driving Cre-dependent expression of Gq or Gi designer receptors exclusively activated by designer drugs (DREADDs) to test the degree that selective activation or inhibition, respectively, of the PVN-nTS pathway affects the hypoxic ventilatory response (HVR) of conscious rats. We used immunohistochemistry for Fos and extracellular recordings to examine how DREADD activation influences PVN-nTS neuronal activation by hypoxia. Pathway activation enhanced the HVR at moderate hypoxic intensities and increased PVN and nTS Fos immunoreactivity in normoxia and hypoxia. In contrast, PVN-nTS inhibition reduced both the HVR and PVN and nTS neuronal activation following hypoxia. To further confirm selective pathway effects on central cardiorespiratory output, rats underwent hypoxia before and after bilateral nTS nanoinjections of C21 to activate or inhibit PVN-nTS terminals. PVN terminal activation within the nTS enhanced tachycardic, sympathetic and phrenic (PhrNA) nerve activity responses to hypoxia whereas inhibition attenuated hypoxia-induced increases in nTS neuronal action potential discharge and PhrNA. The results demonstrate the PVN-nTS pathway enhances nTS neuronal activation and is necessary for full cardiorespiratory responses to hypoxia. KEY POINTS: The hypothalamic paraventricular nucleus (PVN) contributes to peripheral chemoreflex cardiorespiratory responses, but specific PVN efferent pathways are not known. The nucleus tractus solitarii (nTS) is the first integration site of the peripheral chemoreflex, and the nTS receives dense projections from the PVN. Selective GqDREADD activation of the PVN-nTS pathway was shown to enhance ventilatory responses to hypoxia and activation (Fos immunoreactivity (IR)) of nTS neurons in conscious rats, augmenting the sympathetic and phrenic nerve activity (SSNA and PhrNA) responses to hypoxia in anaesthetized rats. Selective GiDREADD inhibition of PVN-nTS neurons attenuates ventilatory responses, nTS neuronal Fos-IR, action potential discharge and PhrNA responses to hypoxia. These results demonstrate that a projection from the PVN to the nTS is critical for full chemoreflex responses to hypoxia.

Binary fluoride and As(V) adsorption in water using pleco fish bone chars.

The present work studied individual and binary adsorption of fluorides and As(V) in water on pleco fish bone chars (BC), as well as the effect of BC mass variation on the adsorption capacity of fluoride and As(V) in water for human consumption. The results of individual adsorption indicated that the adsorption of fluoride and As(V) on BC depends on solution pH. The adsorption capacity of fluorides at an initial concentration of 30 mg L-1 increases approximately 3 times, from 5.9 to 15.3 mg g-1, when decreasing the pH of the solution from 9 to 5, however, for the case of As(V) an antagonistic effect is observed, the adsorption capacity increases 7 times when raising the pH from 5 to 9, from 18.4 to 132.1 µg g-1 at an initial As(V) concentration of 300 µg L-1. Besides, in the binary adsorption, BC showed a higher affinity to adsorb fluoride since its adsorption capacity decreased from 16.55 to 12.50 mg g-1 as the As(V) concentration increased from 0 to 800 µg L-1 in solution. In contrast, As(V) adsorption was severely affected, decreasing from 140.2 to 32.7 µg g-1 when the fluoride concentration in the solution increased from 0 to 100 mg L-1. On the other hand, in the adsorption of groundwater contaminated with fluoride and As(V), it was determined that increasing the mass of BC from 0.5 to 20 g increases the removal percentage, reaching 99.3 and 75.7% removal for fluoride and As(V), respectively, due to the fact that increasing the mass of the adsorbent leads to a larger area and a greater number of sites that allow the adsorption of these contaminants. The thermodynamic study revealed the spontaneity of fluoride and As(V) adsorption, better affinity for fluoride but higher adsorption rate of As(V) on BC. Characterization techniques such as XRD and EDS allowed identifying hydroxyapatite as the mineral phase of BC, which is responsible for the adsorption of BC. By studying the effect of solution pH on the adsorption capacities and the characterization of BC such as XRD, EDS and TGA, it was determined that the mechanisms of fluoride adsorption are by electrostatic attractions and ion exchange, and for As(V) it is by coprecipitation and ion exchange. It was concluded that BC from pleco fish could be an alternative for treating water contaminated by fluorides and As(V).

Effects of a high salt diet on blood pressure dipping and the implications on hypertension.

High blood pressure, also known as hypertension, is a major risk factor for cardiovascular disease. Salt intake has been shown to have a significant impact on BP, but the mechanisms by which it influences the blood pressure dipping pattern, and 24-h blood pressure remains controversial. This literature review aims to both summarize the current evidence on high salt diet induced hypertension and discuss the epidemiological aspects including socioeconomic issues in the United States and abroad. Our review indicates that a high salt diet is associated with a blunted nocturnal blood pressure dipping pattern, which is characterized by a reduced decrease in blood pressure during the nighttime hours. The mechanisms by which high salt intake affects blood pressure dipping patterns are not fully understood, but it is suggested that it may be related to changes in the sympathetic nervous system. Further, we looked at the association between major blood pressure and circadian rhythm regulatory centers in the brain, including the paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN) and nucleus tractus solitarius (nTS). We also discuss the underlying social and economic issues in the United States and around the world. In conclusion, the evidence suggests that a high salt diet is associated with a blunted, non-dipping, or reverse dipping blood pressure pattern, which has been shown to increase the risk of cardiovascular disease. Further research is needed to better understand the underlying mechanisms by which high salt intake influences changes within the central nervous system.

Karyotype Anomalies in Patients with Disorders of Sexual Development.

OBJECTIVES: Objectives Disorders of sex development(DSD)can result in discordance between the chromosomal and anatomicand/orphenotypic sex of a patient. Reporting patients with uncommon karyotypes associated with DSD is important for clinical comparison of developmental outcomes, and management. Methods We describe three female patients with karyotypes resulting in DSD and the use of a combination of chromosomes and FISH techniques to identify potential causes. Results The first patient was mosaic for idic(Y) that was negative for SRY by FISH. The second patient had idic(Y) that was positive for SRY by FISH. The third patient had an unbalanced translocation between the X chromosome and chromosome 2 [der(2)(X;2)] and XY. These three patients illustrate three different genetic mechanisms underlying DSD. Conclusion Our findings expand the list of abnormal karyotypes that can be associated with DSD and highlight the importance of SRY and DAX1 in phenotypic and functional sexual development.

Surgical Management of Tophaceous Gout in the Upper Limb.

PURPOSE: Gouty tophi are a clinical manifestation of hyperuricemia in advanced stages. They can produce pain, functional limitation, and severe deformities. Patients with severe symptoms require short-term symptomatic solutions that standard medical management is not able to provide. The objective of this study was to present the results obtained with the surgical management of tophaceous gout in the upper limb, as well as present a detailed characterization of the disease in the upper limb. METHODS: Databases of the hand surgery service of a quaternary care hospital were reviewed to identify patients aged >18 years old undergoing tophi resection in the upper limbs between 2014 and 2020. Medical history records were reviewed retrospectively, and the relevant data were extracted to establish demographic profile, clinical presentation, anatomic distribution, postoperative outcomes, and additional procedures required. RESULTS: The most frequent symptom was pain (83%), followed by limited range of motion (56%), deformity (50%), and daily living/occupational activity limitation (28%). The main indications for surgical management were the presence of deformity, pain, and/or limited range of motion. The most frequently affected anatomic sites were the metacarpophalangeal joints, followed by the elbows, proximal interphalangeal joints, and proximal phalanges. The postoperative complication rate was 28%. The most common complications were operative site infections and wound dehiscence. Decreased pain was associated with surgical resection. Additional procedures, such as extensor tenorrhaphy and local flaps, were required in 47.2% of patients. CONCLUSION: Surgical resection of tophi can decrease pain. Although surgery is associated with a high rate of complications, most are minor. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Tratamiento de la enfermedad de Pompe

Introducción: La enfermedad de Pompe es un trastorno de origen genético causado por la deficiencia de la enzima alfa-glucosidasa ácida, que se caracteriza por el acumulo anormal de glucógeno en los músculos y otros tejidos, generando una debilidad muscular progresiva, la cual debe ser diagnosticada y tratada de forma oportuna, ya que de esto dependerá el pronóstico, la sobrevida y la funcionalidad de los pacientes con esta condición. Contenidos: El abordaje multidisciplinario incluye tanto una adecuada valoración y soporte nutricional como el inicio del tratamiento modificador de enfermedad a través de la terapia de reemplazo enzimático, que a su vez dependerá de la forma de presentación, la variante genética, el perfil inicial del paciente, las condiciones especiales que puedan existir y las metas propias para cada paciente. Para garantizar un manejo adecuado, se deben realizar estudios de seguimiento con parámetros objetivos, evaluar posibles eventos secundarios e instaurar su manejo en caso de presentarlos. Conclusiones: El pronóstico de esta enfermedad dependerá del inicio oportuno del tratamiento, la implementación de pautas nutricionales adecuadas y el establecimiento del seguimiento de los parámetros clínicos y paraclínicos para cada uno de los pacientes.

Introduction: Pompe disease is a disorder of genetic origin caused by the deficiency of the acid alpha-glucosidase enzyme, which is characterized by the abnormal accumulation of glycogen in the muscles and other tissues, generating progressive muscle weakness, which must be diagnosed and treated in a timely manner, since the prognosis, survival, and functionality of patients with this condition will depend on this. Contents: The multidisciplinary approach includes both an adequate evaluation and nutritional support as well as the initiation of disease-modifying treatment through enzyme replacement therapy, which in turn will depend on the form of presentation, the genetic variant, the initial profile of the patient, the special conditions that may exist and the specific goals for each patient. To guarantee adequate management, follow-up studies must be carried out with objective parameters, evaluate possible secondary events and establish their management in case of presenting them. Conclusions: The prognosis of this disease will depend on the timely initiation of treatment, the implementation of adequate nutritional guidelines and the establishment of monitoring of clinical and paraclinical parameters for each of the patients.

Racial differences in COVID-19 severity associated with history of substance use disorders and overdose: Findings from multi-site electronic health records in New York City.

Substance use disorders (SUD) are associated with increased risk of worse COVID-19 outcomes. Likewise, racial/ethnic minority patients experience greater risk of severe COVID-19 disease compared to white patients. Providers should understand the role of race and ethnicity as an effect modifier on COVID-19 severity among individuals with SUD. This retrospective cohort study assessed patient race/ethnicity as an effect modifier of the risk of severe COVID-19 disease among patients with histories of SUD and overdose. We used merged electronic health record data from 116,471 adult patients with a COVID-19 encounter between March 2020 and February 2021 across five healthcare systems in New York City. Exposures were patient histories of SUD and overdose. Outcomes were risk of COVID-19 hospitalization and subsequent COVID-19-related ventilation, acute kidney failure, sepsis, and mortality. Risk factors included patient age, sex, and race/ethnicity, as well as medical comorbidities associated with COVID-19 severity. We tested for interaction between SUD and patient race/ethnicity on COVID-19 outcomes. Findings showed that Non-Hispanic Black, Hispanic/Latino, and Asian/Pacific Islander patients experienced a higher prevalence of all adverse COVID-19 outcomes compared to non-Hispanic white patients. Past-year alcohol (OR 1.24 [1.01-1.53]) and opioid use disorders (OR 1.91 [1.46-2.49]), as well as overdose history (OR 4.45 [3.62-5.46]), were predictive of COVID-19 mortality, as well as other adverse COVID-19 outcomes. Among patients with SUD, significant differences in outcome risk were detected between patients of different race/ethnicity groups. Findings indicate that providers should consider multiple dimensions of vulnerability to adequately manage COVID-19 disease among populations with SUDs.

In vitro and in vivo degradation behavior of Mg-0.45Zn-0.45Ca (ZX00) screws for orthopedic applications.

Magnesium (Mg) alloys have become a potential material for orthopedic implants due to their unnecessary implant removal, biocompatibility, and mechanical integrity until fracture healing. This study examined the in vitro and in vivo degradation of an Mg fixation screw composed of Mg-0.45Zn-0.45Ca (ZX00, in wt.%). With ZX00 human-sized implants, in vitro immersion tests up to 28 days under physiological conditions, along with electrochemical measurements were performed for the first time. In addition, ZX00 screws were implanted in the diaphysis of sheep for 6, 12, and 24 weeks to assess the degradation and biocompatibility of the screws in vivo. Using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), micro-computed tomography (µCT), X-ray photoelectron spectroscopy (XPS), and histology, the surface and cross-sectional morphologies of the corrosion layers formed, as well as the bone-corrosion-layer-implant interfaces, were analyzed. Our findings from in vivo testing demonstrated that ZX00 alloy promotes bone healing and the formation of new bone in direct contact with the corrosion products. In addition, the same elemental composition of corrosion products was observed for in vitro and in vivo experiments; however, their elemental distribution and thicknesses differ depending on the implant location. Our findings suggest that the corrosion resistance was microstructure-dependent. The head zone was the least corrosion-resistant, indicating that the production procedure could impact the corrosion performance of the implant. In spite of this, the formation of new bone and no adverse effects on the surrounding tissues demonstrated that the ZX00 is a suitable Mg-based alloy for temporary bone implants.

The impact of preexisting psychiatric disorders and antidepressant use on COVID-19 related outcomes: a multicenter study.

Pre-existing mental disorders are linked to COVID-19-related outcomes. However, the findings are inconsistent and a thorough analysis of a broader spectrum of outcomes such as COVID-19 infection severity, morbidity, and mortality is required. We investigated whether the presence of psychiatric diagnoses and/or the use of antidepressants influenced the severity of the outcome of COVID-19. This retrospective cohort study evaluated electronic health records from the INSIGHT Clinical Research Network in 116,498 individuals who were diagnosed with COVID-19 between March 1, 2020, and February 23, 2021. We examined hospitalization, intubation/mechanical ventilation, acute kidney failure, severe sepsis, and death as COVID-19-related outcomes. After using propensity score matching to control for demographics and medical comorbidities, we used contingency tables to assess whether patients with (1) a history of psychiatric disorders were at higher risk of more severe COVID-19-related outcomes and (2) if use of antidepressants decreased the risk of more severe COVID-19 infection. Pre-existing psychiatric disorders were associated with an increased risk for hospitalization, and subsequent outcomes such as acute kidney failure and severe sepsis, including an increased risk of death in patients with schizophrenia spectrum disorders or bipolar disorders. The use of antidepressants was associated with significantly reduced risk of sepsis (p = 0.033), death (p = 0.026). Psychiatric disorder diagnosis prior to a COVID-19-related healthcare encounter increased the risk of more severe COVID-19-related outcomes as well as subsequent health complications. However, there are indications that the use of antidepressants might decrease this risk. This may have significant implications for the treatment and prognosis of patients with COVID-19.