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Resumen Introduccion Las variantes C1236T, G2677T/A y C3435T del gen ABCB1 alteran la funcion de la glicoproteina P y el transporte de sustancias endogenas y exogenas en la barrera hematoencefalica; ademas, actuan como factores de susceptibilidad para algunas enfermedades neurodegenerativas. El objetivo del estudio fue determinar la asociacion de polimorfismos ABCB1 (C1236T, G2677T/A y C3435T), sus haplotipos y sus combinaciones de genotipos con la enfermedad desmielinizante. Metodo Se genotipifico a 199 pacientes con enfermedad desmielinizante y a 200 controles mestizos mexicanos mediante PCR-RFLP y secuenciacion Sanger para comparar las frecuencias de alelos, genotipos, haplotipos y combinaciones de genotipos entre pacientes y controles. El analisis estadistico se realizo con regresion logistica y χ2 de Pearson al 95% de confianza; se calculo la OR y se evaluo la asociacion con enfermedad desmielinizante. Resultados Los haplotipos TTT y CGC fueron los mas frecuentes en pacientes y controles. El alelo G2677 (OR = 1,79; IC 95%: 1,12-2,86; p = 0,015) muestra asociacion con enfermedad desmielinizante, asi como los genotipos GG2677 (OR = 2,72; IC 95% = 1,11-6,68; p = 0,025) y CC3435 (OR = 1,82; IC 95%: 1,15-2,90; p = 0,010) y su combinacion GG2677/CC3435 (OR = 2,02; IC 95%: 1,17-3,48; p = 0,010) y el haplotipo CAT (OR = 0,21; IC 95%: 0,05-0,66; p = 0,001). Los portadores TTTTTT presentaron la edad de inicio mas temprana (23,0 ± 7,7 vs. 31,6 ± 10,7; p = 0,0001). Conclusiones La combinacion de genotipos GG2677/CC3435 esta asociada al desarrollo de enfermedad desmielinizante en esta muestra, principalmente en el sexo masculino, en el cual puede darse acumulacion toxica de sustratos de glicoproteina P. En este estudio, la edad de inicio de la enfermedad desmielinizante podria ser modulada diferencialmente entre sexos por el alelo G2677 del gen ABCB1.

Background: Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds of stings yearly without developing systemic reactions. Objective: This study aims to analyze the mechanisms underlying bee venom tolerance in beekeepers. Methods: A cross-sectional study was conducted. Participants were recruited and classified into 3 groups: allergic patients (APs), who experienced systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBKs), who received ≥50 stings/year; and healthy nonexposed controls (HCs). We measured serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5, and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T cells (Treg), and IL-10 production. Results: Compared with TBKs, APs had high levels of sIgE to AmV and all its allergic components (P

Background Intraosseous ganglia of the carpal bones are uncommon with sparse publications to guide treatment. The purpose of this study was to review a single-institution experience to determine the outcomes of patients with surgically treated intraosseous carpal ganglia. Methods Skeletally mature patients with intraosseous carpal ganglia between 1995 and 2016 treated operatively were identified. Demographic information, clinical data, and radiographic studies were evaluated. Results Thirty-three ganglia in 31 patients were identified. Intraosseous ganglia were located in the lunate (23), scaphoid (9), and trapezoid (1). Patients who presented with pathologic fracture or collapse had larger intraosseus ganglia than those presenting with pain alone. Surgery significantly improved pain. Patients treated with debridement with autograft bone graft had a higher consolidation rate compared with allograft bone but no difference in pain. Conclusions Patients with large or symptomatic lesions can be treated successfully with curettage and debridement, which leads to relief of pain. The use of bone grafting remains controversial.

Family history of thyroid disease (FHTD) constitutes a possible risk factor for congenital hypothyroidism (CH) in the general population; however, FHTD possible relationship with CH in subjects with Down syndrome (DS) has not yet been explored.To determine whether FHTD is associated with an increased incidence of CH in neonates with DS.Hospital-based case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and positive FHTD (cases) were compared with those of 183 newborns with DS without FHTD (control group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated.Nine newborns with DS in our sample had CH (4.1 %). In the multivariate analysis, FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8).Newborns with DS and FHTD have an eight-fold higher risk for CH, particularly when the index case is male. FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada.Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD.Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %).Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8).La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

Background: Poly (ADP-ribose) polymerase-inhibitors (PARPis) showed antitumour activity in BRCA1/2-mutated cancers, with more heterogeneous outcomes in tumours harbouring mutations that impair other genes involved in the DNA homologous recombination repair (HRR) or wild-type (wt). Methods: We conducted a systematic review and meta-analysis to better assess the role of PARPis in the treatment of metastatic solid tumours, with and without BRCA1/2 mutations. The primary end-point was progression-free survival (PFS). The secondary end-points were overall response rate (ORR) and overall survival (OS). A random-effects model was applied. Results: Twenty-nine studies (8,839 patients) were included. PFS was significantly improved (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.51-0.68, p < 0.001), without being affected by BRCA mutational status (p = 0.65). Significant subgroup differences were observed with regard to the tumour site (p = 0.001), line of therapy (p = 0.002), control arm (p < 0.001), type of PARPi (p < 0.001) and trials' phase (p = 0.006). PARPis were associated with ORR (relative risk: 1.35, 95% CI: 1.16-1.56, p < 0.001), with significant subgroup differences observed with regard to treatment line (p = 0.03), control arm (p = 0.04) and PARPis (p < 0.001) and independent of mutational status (p = 0.44), tumour site (p = 0.86) and trials' phase (p = 0.09). OS was significantly improved by PARPis (HR: 0.86, 95% CI: 0.80-0.92, p < 0.001), regardless of mutational status (p = 0.57), tumour site (p = 0.82), treatment line (p = 0.22), control arm (p = 0.21), PARPis (p = 0.30) and trials' phase (p = 0.26). Finally, an exploratory subgroup analysis showed a significant PFS improvement (HR: 0.51, 95% CI: 0.43-0.60, p < 0.001) with PARPis in BRCA-wt/HRR-deficient tumours. Conclusion: Our results confirm the efficacy of already approved PARPi-based treatments in BRCA1/2-mutant solid tumours, support their role also in BRCA-independent HRR-deficient tumours and suggest a potentially broader efficacy in some wt tumours, perhaps with appropriate therapeutic partners. Prospective studies are warranted.

Resumen Introduccion Las infecciones neonatales por Candida spp. son eventos graves por su morbimortalidad, sin embargo, en paises en vias de desarrollo la informacion epidemiologica es insuficiente. El objetivo de este estudio fue describir la incidencia y los factores asociados a la infeccion invasiva por Candida spp. en una unidad de cuidados intensivos neonatales de Mexico. Metodos Estudio de casos y controles anidado en una cohorte y apareado por el peso al nacer. Se estimo la incidencia de infeccion neonatal invasiva por Candida spp., y para el analisis bivariado de los factores estudiados se uso la prueba de McNemar para contraste de hipotesis y analisis multivariado con regresion logistica. Resultados La incidencia de la infeccion fue de 2,27 eventos/1.000 RN vivos. Las especies identificadas fueron C. albicans 35,3% (n: 30), C. parapsilosis 30,6% (n: 26), C. glabrata 31,8% (n: 27) y 2 eventos con C. lipolytica. Los factores asociados a mayor riesgo fueron la ventilacion mecanica (OR: 3,04; IC 95%: 1,13-8,14), los antibioticos sistemicos (OR: 7,48; IC 95%: 1,30-42,9), el numero de esquemas antimicrobianos (OR: 2,02; IC 95%: 1,01-4,03) y los dias con nutricion parenteral total (OR: 1,14; IC 95%: 1,04-1,25) o con cateter venoso central (OR: 1,11; IC 95%: 1,02-1,20). La profilaxis con fluconazol disminuyo el riesgo (OR: 0,32; IC 95%: 0,12-0,84). Conclusiones Las intervenciones invasivas (cateter central, ventilacion mecanica y nutricion parenteral) y el uso de antimicrobianos incrementan el riesgo de infeccion neonatal por Candida spp., mientras que el fluconazol profilactico es protector.

Background Women who were born overseas represent an increasing proportion of women giving birth in the Australian healthcare system. Problem Women from migrant and refugee backgrounds have an increased risk of poor pregnancy and birth outcomes, including experiences of care. Aim To understand how women from migrant and refugee backgrounds perceive and experience the continuum of maternity care (pregnancy, birth, postnatal) in Australia. Methodology We conducted a qualitative evidence synthesis, searching MEDLINE, CIHAHL, and PsycInfo for studies published from inception to 23/05/2020. We included studies that used qualitative methods for data collection and analysis, that explored migrant/refugee women’s experiences or perceptions of maternity care in Australia. We used a thematic synthesis approach, assessed the methodological limitations of included studies, and used GRADE-CERQual to assess confidence in qualitative review findings. Results 27 studies met the inclusion criteria, representing women in Australia from 42 countries. Key themes were developed into 24 findings, including access to interpreters, structural barriers to service utilisation, experiences with health workers, trust in healthcare, experiences of discrimination, preferences for care, and conflicts between traditional cultural expectations and the Australian medical system. Conclusion This review can help policy makers and organisations who provide care to women from migrant and refugee backgrounds to improve their experiences with maternity care. It highlights factors linked to negative experiences of care as well as factors associated with more positive experiences to identify potential changes to practices and policies that would be well received by this population.

Right ventricular function has prognostic significance in patients with pulmonary hypertension. We evaluated whether cardiac magnetic resonance-derived strain and strain rate parameters could reliably reflect right ventricular systolic and diastolic function in precapillary pulmonary hypertension. End-systolic elastance and the time constant of right ventricular relaxation tau, both derived from invasive high-fidelity micromanometer catheter measurements, were used as gold standards for assessing systolic and diastolic right ventricular function, respectively. Nineteen consecutive precapillary pulmonary hypertension patients underwent cardiac magnetic resonance and right heart catheterization prospectively. Cardiac magnetic resonance data were compared with those of 19 control subjects. In pulmonary hypertension patients, associations between strain- and strain rate-related parameters and invasive hemodynamic parameters were evaluated. Longitudinal peak systolic strain, strain rate, and early diastolic strain rate were lower in PAH patients than in controls; peak atrial-diastolic strain rate was higher in pulmonary hypertension patients. Similarly, circumferential peak systolic strain rate was lower and peak atrial-diastolic strain rate was higher in pulmonary hypertension. In pulmonary hypertension, no correlations existed between cardiac magnetic resonance-derived and hemodynamically derived measures of systolic right ventricular function. Regarding diastolic parameters, tau was significantly correlated with peak longitudinal atrial-diastolic strain rate ( r = −0.61), deceleration time ( r = 0.75), longitudinal systolic to diastolic time ratio ( r = 0.59), early diastolic strain rate ( r = −0.5), circumferential peak atrial-diastolic strain rate ( r = −0.52), and deceleration time ( r = 0.62). Strain analysis of the right ventricular diastolic phase is a reliable non-invasive method for detecting right ventricular diastolic dysfunction in PAH.

Background Mesentery thickening and enlarged lymphnodes are typical findings of Crohn's disease (CD), but their role is unknown. Aim of the present study was to evaluate their prevalence and significance on postoperative complications and long-term surgical recurrence after CD surgery. Methods 1272 consecutive, unselected patients were retrospectively reviewed, divided into 4 groups based on the presence or absence of a thickened mesentery and enlarged lymphnodes, and stratified for primary or recurrent surgical procedure. In all patients but those treated with strictureplasty the mesentery and lymphnodes were removed. Patients’ characteristics, peri-operative findings, and long-term recurrence were compared by univariate and multivariate analysis. Results Thickened mesentery and enlarged lymphnodes were not present in all cases, were typical of ileal location and penetrating behaviour, had a constant decrease over recurrences, were independent of either pre-operative medical therapy or surgical approach, did not increase the duration of surgery and complications, presented similar 20-years recurrence rate to normal mesentery and lymphnodes. Lymphopathy was associated to a worst nutritional status during disease recurrences. At multivariate analysis, age, location, and behaviour, but not mesenteric characteristics, were related to an increased risk of surgical recurrence. Conclusions This study provides new information on mesentery and lymphnodes in CD patients. Further studies are needed to clarify the appropriate surgical approach.

Objective Inhalant users may develop toluene leukoencephalopathy, a devastating neuropsychiatric disorder. We present a case of toluene-induced damage to the corticospinal and the corticonuclear tracts, which presented with involuntary emotional expression disorder. Methods Case study of a 20-year-old man with a 3-year history of frequent solvent abuse was admitted to the Neuropsychiatry Unit of the National Institute of Neurology and Neurosurgery because “he could not speak or walk” but would keep “laughing and crying without reason”. Results Neuropsychiatric examination revealed pathological laughter and crying, facial and speech apraxia, a bilateral pyramidal syndrome, and lack of control of urinary sphincter. Magnetic resonance imaging revealed a highly selective bilateral damage to the pyramidal system and the somatosensory pathway. SPECT imaging showed left fronto-parietal hypoperfusion. Conclusions This document provides support for the understanding of involuntary emotional expression disorders as a differential diagnosis in the clinical practice of psychiatrists, as well as the functional anatomy of these conditions.

espanolLa enfermedad del coronavirus 2019 (COVID-19), infeccion causada por el coronavirus 2 del sindrome respiratorio agudo grave (SARS-CoV-2), actualmente afecta al mundo en forma de una pandemia. Debido a que algunos reportes apuntan a que esta infeccion puede cursar tambien con manifestaciones neurologicas, en esta revision narrativa se abordan los aspectos basicos y clinicos concernientes a la afectacion del sistema nervioso por esta enfermedad. Mas de un tercio de los pacientes hospitalizados por COVID-19 pueden presentar manifestaciones neurologicas, tanto centrales como perifericas. Entre las primeras se encuentran el mareo y la cefalea; y entre las segundas, las alteraciones del gusto y el olfato. Otras manifestaciones neurologicas reportadas son la enfermedad vascular cerebral y las crisis epilepticas. Segun los informes publicados, los padecimientos neurologicos no son infrecuentes en COVID-19 y en ocasiones pueden representar la primera manifestacion de la enfermedad, de modo que los neurologos deberan considerar esta posibilidad diagnostica en su practica cotidiana. Dado que no todas las manifestaciones neurologicas de COVID-19 pudieran deberse a efectos directos de SARS-CoV-2, es importante monitorear el resto de los parametros clinicos, por ejemplo, la oxigenacion. De igual forma, es recomendable el seguimiento de los pacientes, ya que hasta el momento se ignora si las complicaciones neurologicas pueden desarrollarse tardiamente. EnglishCoronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently hitting the world in the form of a pandemic. Given that some reports suggest that this infection can also occur with neurologic manifestations, this narrative review addresses the basic and clinical aspects concerning the nervous system involvement associated with this disease. More than one third of patients hospitalized for COVID-19 can present with both central and peripheral neurological manifestations. The former include dizziness and headache, while the latter include taste and smell disturbances. Other reported neurological manifestations are cerebrovascular disease and epileptic seizures. According to published reports, neurological disorders are not uncommon in COVID-19 and can sometimes represent the first manifestation of the disease; therefore, neurologists should consider this diagnostic possibility in their daily practice. Since maybe not all COVID-19 neurological manifestations are due to SARS-CoV-2 direct effects, it is important to monitor the rest of the clinical parameters such as, for example, oxygen saturation. Similarly, follow-up of patients is advisable, since whether neurological complications may develop lately is thus far unknown.

espanolAntecedentes: Las deficiencias de anticuerpos abarcan un amplio espectro de patologias y constituyen aproximadamente 50 % de las inmunodeficiencias primarias; con la citometria es posible evaluar el estado inmunologico de forma rapida, efectiva y a bajo costo. objetivo: Evaluar mediante citometria de flujo, las celulas de pacientes con tres tipos de inmunodeficiencias primarias humorales. Metodo: Mediante citometria de flujo se analizaron muestras de sangre de pacientes y sujetos sanos con distintos anticuerpos monoclonales. resultados: Mediante diversas tinciones se demostro disminucion severa de linfoci- tos B en pacientes con agammaglobulinemia ligada al cromosoma X, la falta de expresion de CD154 en pacientes con sin- drome de hiperinmunoglobulina M y heterogeneidad de subpoblaciones de linfocitos B en pacientes con inmunodeficiencia comun variable. conclusion: Con la citometria de flujo es posible realizar el diagnostico temprano de inmunodeficiencias primarias con un nivel de confianza elevado y, en muchos casos, identificar los genes implicados. EnglishBackground: Antibody deficiencies encompass a wide spectrum of pathologies and constitute approximately 50 % of primary immunodeficiencies; with cytometry, it is possible to evaluate the immune status rapidly, effectively and at low cost. objective: To assess, by means of flow cytometry, the cells of patients with three types of primary humoral immunodeficiencies. Method: Us- ing flow cytometry, blood samples from patients and healthy subjects were analyzed with different monoclonal antibodies. results: Using various stains, a severe decrease in B lymphocytes was shown in patients with X-linked agammaglobulinemia, as well as a lack of CD154 expression in patients with hyper-immunoglobulin M syndrome, and heterogeneity of B lymphocyte subpopulations in patients with common variable immunodeficiency. conclusion: Flow cytometry enables early diagnosis of primary immunodeficiencies with a high level of confidence and, in many cases, identification of the genes involved.

RATIONALE AND OBJECTIVES Our study compared sensitivity, specificity, and accuracy of whole-body diffusion-weighted imaging (WB-DWI) using a b-value of 2000 s/mm2 with that of the commonly used b-value of 800 s/mm2 for depiction of active tumor sites in patients with plasma cell diseases. We introduced an ultrahigh b-value to reduce interfering signals from benign and post-therapeutic inactive lesions by suppressing T2-shine-through effects. MATERIALS AND METHODS The prospective single-center study included patients when they went through a whole-body MRI (WB-MRI) staging or response evaluation procedure. The apparent diffusion coefficient (ADC) and morphologic appearance served as reference for classifying focal lesions on WB-DWI as vital or post-therapeutic. Additionally, we compared our classification with patients' serological markers of disease activity. RESULTS One hundred participants (65 ± 10 years, 58 men) underwent WB-DWI between June and October 2019. The detection rate of vital focal lesions was similar for both b-values with a sensitivity of 0.99 using b = 800 s/mm2 and 0.98 using b = 2000 s/mm2. By contrast, specificity and accuracy were 0.09 and 0.71 when using a b-value of 800 s/mm2, and 0.96 and 0.98 when using a b-value of 2000 s/mm2, respectively. The difference in specificity and accuracy was statistically significant (p < 0.001). CONCLUSION Using a b-value of 2000 s/mm2 significantly improved the specificity of lesion detection with WB-DWI as compared to the commonly used b-value of 800 s/mm2. The high b-value significantly reduced signal intensities of post-therapeutic or benign lesions and provided a significantly more accurate representation of active tumor load.

Background: Allium sativum L., or garlic, is one of the most studied plants worldwide within the field of traditional medicine. Current interests lie in the potential use of garlic as a preventive measure and adjuvant treatment for viral infections, e.g., SARS-CoV-2. Even though it cannot be presented as a single treatment, its beneficial effects are beyond doubt. The World Health Organization has deemed it an essential part of any balanced diet with immunomodulatory properties. Objective: The aim of the study was to review the literature on the effects of garlic compounds and preparations on immunomodulation and viral infection management, with emphasis on SARS-CoV- -2. Method: Exhaustive literature search has been carried out on electronic databases. Conclusion: Garlic is a fundamental part of a well-balanced diet which helps maintain general good health. The reported information regarding garlic’s ability to beneficially modulate inflammation and the immune system is encouraging. Nonetheless, more efforts must be made to understand the actual medicinal properties and mechanisms of action of the compounds found in this plant to inhibit or diminish viral infections, particularly SARS-CoV-2. Based on our findings, we propose a series of innovative strategies to achieve such a challenge in the near future.

Background Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated. Objective To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19. Design We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial. Participants We recruited 116 hospitalized patients with severe COVID-19 in Mexico. Interventions Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment. Main Measures The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients. Key Results Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35–1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66–3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A. Conclusions Colchicine is safe but not effective in the treatment of severe COVID-19. Trial Registration ClinicalTrials.gov Identifier: NCT04367168.

This chapter deals with the mechanics of inelastic bending in the presence of tension. Bending a circular tube ovalizes its cross sections and leads to a limit-load instability. Bending in the presence of tension can aggravate the growth of ovalization. Two types of combined bending-tension loading have been identified. The first is encountered in a suspended line, where the tension is used to control the shape of the suspended section. In this case, the tension is reacted by a distributed force normal to the axis of the tube that occurs because of the weight of the pipe and the buoyancy force. The transverse force acts at the axis of the tube and thus does not influence ovality. In this type of loading, the tension interacts with the bending (and possibly pressure) through an inelastic action by aggravating the state of stress. In the second type of combined bending-tension loading, the pipe is bent over a rigid surface, in which case the tension is reacted by a distributed force acting on the surface of the bent tube. This type of loading is encountered, for example, by a pipeline passing over a curved stinger and when winding or unwinding a line on a reel.

The production of artisan gelato has always been a very important sector for the Italian economy, the aim of this work is to highlight the peculiarity of production in Sicily, in synergy with a young economic reality and the production reality that is expanding Gelateria Cappadonia, Caffè Morettino Srl Palermo and the academic world. The aim of this research is to solve the color change during the production of artisan coffee gelato.

We determine the prevalence and trends of open neural tube defects (ONTDs) during 1991 to 2019 at the "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara (Mexico). Also, details of potential risks were obtained in 662 newborns, including those 143 patients with anencephaly and open spina bifida (OSB) classified as isolated (cases) and 519 controls. Data were analyzed using multivariable logistic regression. Among 267 201 live births during the study period, 336 were born with ONTDs, yielding an overall prevalence of 12.6 per 10 000. After folic acid (FA)-related programs began in Mexico (2003-2019), only OSB showed a decline of 20.6%. For anencephaly, associated risks included relatives with neural tube defects (NTDs) (adjusted odds ratio [aOR]: 67.9, 95% confidence interval [95% CI]: 11.3-409.8), pre-pregnancy body mass index (BMI) ≥25 kg/m2 (aOR: 2.6, 95% CI: 1.1-6.0), insufficient gestational weight gain (aOR: 3.0, 95% CI: 1.3-7.1), parity ≥4 (aOR: 3.2, 95% CI: 1.3-7.7), and exposure to analgesic/antipyretic drugs (aOR: 9.0; 95% CI: 2.5-33.0). For OSB, associated risks included consanguinity (aOR: 14.0, 95% CI: 3.5-55.9), relatives with NTDs (aOR: 22.4, 95% CI: 4.5-112.9), BMI ≥25 kg/m2 (aOR: 2.5, 95% CI: 1.6-4.2), insufficient gestational weight gain (aOR: 1.9, 95% CI: 1.1-3.1), and exposures to hyperthermia (aOR: 2.3, 95% CI: 1.2-4.3), common cold (aOR: 6.8, 95% CI: 3.6-12.7), and analgesic/antipyretic drugs (aOR: 3.6, 95% CI: 1.3-10.0). Our high rate probably results from exposures to preventable risks, most related to FA, indicating a need for strengthening existing FA-related programs in Mexico.

The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health issue which has profound effects on most aspects of societal well-being, including physical and mental health. A plethora of studies globally have suggested the existence of a sex disparity in the severity and outcome of COVID-19 patients, mainly due to mechanisms of virus infection, immune response to the virus, development of systemic inflammation, and consequent systemic complications, particularly thromboembolism. Epidemiological data report a sex difference in the severity of COVID-19, with a more favorable course of the disease in women compared to men regardless of age, although the rate of SARS-CoV-2 infection seems to be similar in both sexes. Sex hormones, including androgens and estrogens, may not only impact virus entry and load, but also shape the clinical manifestations, complications, and ultimately the outcome of the disease. The current review comprehensively summarizes the current literature on sex disparities in susceptibility and outcome of COVID-19 as well as the literature underpinning the pathophysiological and molecular mechanisms, which may provide a rationale to a sex disparity. These mechanisms include sex hormone influence on factors that facilitate virus entry and priming, immune and inflammatory response, as well as coagulation and thrombosis diathesis. Based on present evidence, women appear to be relatively protected from COVID-19 because of a more effective immune response and a less pronounced systemic inflammation, with consequent moderate clinical manifestations of the disease, together with a lesser predisposition to thromboembolism. Conversely, men appear to be particularly susceptible to COVID-19 because of a less effective immune response with consequent severe clinical manifestations of the disease, together with a greater predisposition to thromboembolism. In the elderly, generally characterized by the phenomenon of inflammaging, sex disparities in overall mortality following SARS-CoV-2 infection are even more palpable as elderly men appear to be more prone to severe COVID-19 because of a greater predisposition to infections, a weaker immune defense, and an enhanced thrombotic state compared to women. The information revealed from the review highlights potential novel therapeutic approaches employing the administration of hormonal or antihormonal therapy in combination with antiviral drugs in COVID-19 patients.

Transient abnormal myelopoiesis (TAM) raises the risk for acute myeloid leukemia of Down syndrome (DS) (ML-DS), and both are related to GATA1 pathogenic variants. Here, we analyzed which findings on complete blood count (CBC) are associated with TAM in a cohort of neonates with DS screened for GATA1 pathogenic variants. The CBCs were compared among 70 newborns with DS, including 16 patients (22.9%) with TAM (cases), and 54 patients (77.1%) without TAM (controls). TAM was defined as peripheral circulating blasts (PCBs) ≥ 1%. PCR and direct sequencing were used to screen DNA samples from peripheral blood for GATA1 exon 2 mutations. Multivariate logistic regression analyses determined that the mean count of lymphocytes was significantly higher in DS infants with TAM (p = .035) and that lymphocytosis confers a risk for TAM (adjusted odds ratio = 7.23, 95% confidence intervals: 2.02-25.92). Pathogenic variants of GATA1 were identified in 2 of 70 analyzed DS neonates (2.9%), of which one had ML-DS and another had an asymptomatic TAM. Among those DS infants with TAM, the GATA1 pathogenic variant detection was 12.5%. Our results indicated that lymphocytosis is associated with TAM in neonates with DS. However, since not all infants with an abnormal CBC had TAM, and not all infants with TAM had GATA1 pathogenic variants, we emphasize that only the search for GATA1 pathogenic variants allows the proper identification of the subgroup of DS infants with a real increasing in risk for ML-DS.

Background Evidence regarding functional hypogonadism, previously referred to as 'late-onset' hypogonadism, has increased substantially during the last 10 year. Objective To update the European Academy of Andrology (EAA) guidelines on functional hypogonadism. Methods Expert group of academicians appointed by the EAA generated a series of consensus recommendations according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Results The diagnosis of functional hypogonadism should be based on both the presence of clinical symptoms supported by repeatedly low morning fasting serum total testosterone (T) measured with a well-validated assay, after exclusion of organic causes of hypogonadism. Lifestyle changes and weight reduction should be the first approach in all overweight and obese men. Whenever possible, withdrawal/modification of drugs potentially interfering with T production should be advised. Testosterone replacement therapy (TRT) is contraindicated in men with untreated prostate or breast cancer, as well as severe heart failure. Severe low urinary tract symptoms and haematocrit >48%-50% represent relative contraindications for TRT. Prostate-specific antigen and digital rectal examination of the prostate should be undertaken in men >40 years of age before initiating TRT to exclude occult prostate cancer. Transdermal T should be preferred for initiation of TRT, whereas gonadotrophin therapy is only recommended when fertility is desired in men with secondary hypogonadism. TRT is able to improve sexual function in hypogonadal men. Other potential positive outcomes of TRT remain uncertain and controversial. Conclusion TRT can reliably improve global sexual function in men with hypogonadism in the short term. Long-term clinical benefits, and safety of TRT in functional hypogonadism, remain to be fully documented. Clinicians should therefore explicitly discuss the uncertainties and benefits of TRT and engage them in shared management decision-making.

Introduction Patients with Peyronie's disease may experience significat distress. The choice of treatment depends on a variety of factors, including the stage of the disease, the presence of pain, severity and direction of the curvature, penile length and the quality of erectile function. Aim To review the evidence associated with surgical treatment of Peyronie‘s Disease and provide clinical recommendations on behalf of the European Society for Sexual Medicine. 131 peer-reviewed studies and systematic reviews, which were published from 2009 to 2019 in the English language, were included. Methods MEDLINE, Google Scholar and EMBASE were searched for randomized clinical trials, meta-analyses, open-label prospective and retrospective studies. Main Outcome Measure The panel provided statements on clinically relevant questions including patient involvement in the decision process, indications for surgery, choice of the approach, and the management of patient expectations. A comparison of the different grafts used in patients who have undergone plaque incision/excision and grafting in order to identify an ideal graft, has been carried out. The prevalence of postoperative complications has been summarized. Levels of evidence were provided according to the Oxford 2011 criteria and Oxford Centre for Evidence-Based Medicine recommendations. Results In order to allow shared decision making, a patient preoperative counselling regarding the pros and cons of each intervention is recommended. In particular, adverse effects of surgical treatments should be discussed to set realistic understanding and expectations of surgical outcomes and ultimately improve postoperative satisfaction rates. Surgical treatment should be only offered in the chronic phase of the condition, when the deformity and/or degree of erectile dysfunction, prevent patients from engaging in satisfying sexual interaction, or if the deformity is the cause of severe bother. Conclusions Current European Society for Sexual Medicine recommendations cover several aspects of Peyronie's disease treatment. These recommendations aim both to ensure patients and partners have accurate and realistic expectations of their treatment options, as well as to formulate algorithms to guide clinician management pathways. Osmonov D, Ragheb A, Ward S et al, ESSM Position Statement on Surgical Treatment of Peyronie's Disease. Sex Med 2022;10:100459.

The aim of this meta-analysis was to to determine the influence of obesity on patient outcome and implant survivorship after primary unicompartmental knee arthroplasty (UKA). A PRISMA systematic review was conducted by searching the Medline (PubMed), EMBASE, and Cochrane electronic databases to identify clinical studies investigating the effect of obesity on outcomes after UKA. Data were collected on aspecifically designed extraction form. Methodological quality was assessed using the Methodological Index for Nonrandomized Studies score. Quantitative meta-analysis was carried out using RevMan 5.4 software. A total of 17 studies were included; 43,845 primary UKA patients were classified by their BMI: on-obese (BMI 25 to 35 kg/m2). Pooled analysis showed no statistically significant difference in Knee Society Score (KSS) pain in the obese (n.s.) and the severely obese (n.s.) group compared to the non-obese group, while the KSS function score was lower in the severely obese (P = 0.0002) compared to the obese (P = 0.06) and the non-obese group. Postoperative Oxford Knee Score (OKS) was lower in the obese group (P = 0.01) but not in the severely obese group (P = 0.16). Postoperative Range of Motion (ROM) was comparable in the obese and non-obese group (P = 0.16). Implant survival at 10 years follow-up was significantly lower in the obese (82.5–95.3%; P

Objectives: This study sought to: 1) under­stand how the perceived food environment (availability, accessibility, and affordability) is associated with cardiometabolic health outcomes in predominately low-income Black residents in urban neighborhoods with limited healthy food access; and 2) examine the association of shopping at specific store types with cardiometabolic health outcomes. Methods: We report on cross-sectional data from 459 individuals participating in the Pittsburgh, PA Hill/Homewood Research on Neighborhoods and Health (PHRESH) study. Mean participant age was 60.7 (SD=13.9); 81.7% were female. We used logistic regression to examine associations between three factors (perceived fruit and vegetable availability, quality, and price; primary food shopping store characteristics; and frequency of shopping at stores with low or high access to healthy foods) and cardiometabolic and self-rated health. Results: Adjusting for sociodemographic characteristics, participants with higher perceived fruit and vegetable accessibility (AOR:.47, 95%CI: .28-.79, P=.004) and affordability (AOR:.59, 95%CI: .36-.96, P=.034) had lower odds of high blood pres­sure. Shopping often (vs rarely) at stores with low access to healthy foods was associated with higher odds of high total cholesterol (AOR:3.52, 95%CI: 1.09-11.40, P=.035). Finally, primary food shopping at a discount grocery (vs full-service supermarket) was as­sociated with lower odds of overweight/obe­sity (AOR:.51, 95%CI: .26-.99, P=.049). Conclusions: These results suggest that both perceived accessibility and affordability of healthy foods are associated with reduced cardiometabolic risk factors in this urban, low-income predominantly Black population. Additionally, discount grocery stores may be particularly valuable by providing access and affordability of healthy foods in this population. Ethn Dis. 2021;31(4):537-546; doi:10.18865/ed.31.4.537

Poplars are one of the most widespread fast-growing tree species used for forest plantations. Owing to their distinct features (fast growth and short rotation) and the dependency on the timber pric...

To evaluate the feasibility of non-contrast-enhanced three-dimensional ultrashort echo time (3D-UTE) MRI for pulmonary imaging in immunocompromised patients during hematopoietic stem cell transplantation (HSCT).MRI was performed using a stack-of-spirals 3D-UTE sequence (slice thickness: 2.34mm; matrix: 256 × 256; acquisition time: 12.7-17.6 seconds) enabling imaging of the entire thorax within single breath-holds. Patients underwent MRI before HSCT initiation, in the case of periprocedural pneumonia, before discharge, and in the case of re-hospitalization. Two readers separately assessed the images regarding presence of pleural effusions, ground glass opacities (GGO), and consolidations on a per lung basis. A T2-weighted (T2w) multi-shot Turbo Spin Echo sequence (BLADE) was acquired in coronal orientation during breath-hold (slice thickness: 6.00mm; matrix: 320 × 320; acquisition time: 3.1-5.5 min) and read on a per lesion basis. Low-dose CT scans in inspiration were used as reference and were read on a per lung basis. Only scans performed within a maximum of three days were included in the inter-method analyses. Interrater agreement, sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 3D-UTE MRI were calculated.67 MRI scans of 28 patients were acquired. A reference CT examination was available for 33 scans of 23 patients. 3D-UTE MRI showed high sensitivity and specificity regarding pleural effusions (n = 6; sensitivity, 92 %; specificity, 100 %) and consolidations (n = 22; sensitivity 98 %, specificity, 86 %). Diagnostic performance was lower for GGO (n = 9; sensitivity, 63 %; specificity, 84 %). Accuracy rates were high (pleural effusions, 98 %; GGO, 79 %; consolidations 94 %). Interrater agreement was substantial for consolidations and pleural effusions (κ = 0.69-0.82) and moderate for GGO (κ = 0.54). Compared to T2w imaging, 3D-UTE MRI depicted the assessed pathologies with at least equivalent quality and was rated superior regarding consolidations and GGO in ~50 %.Non-contrast 3D-UTE MRI enables radiation-free assessment of typical pulmonary complications during HSCT procedure within a single breath-hold. Yet, CT was found to be superior regarding the identification of pure GGO changes.· 3D-UTE MRI of the thorax can be acquired within a single breath-hold.. · 3D-UTE MRI provides diagnostic imaging of pulmonary consolidations and pleural effusions.. · 3D-UTE sequences improve detection rates of ground glass opacities on pulmonary MRI.. · 3D-UTE MRI depicts pulmonary pathologies at least equivalent to T2-weighted Blade sequence..· Metz C, Böckle D, Heidenreich JF et al. Pulmonary Imaging of Immunocompromised Patients during Hematopoietic Stem Cell Transplantation using Non-Contrast-Enhanced Three-Dimensional Ultrashort Echo Time (3D-UTE) MRI. Fortschr Röntgenstr 2022; 194: 39 - 48.ZIEL: Evaluation einer 3-dimensionalen MRT-Sequenz mit ultrakurzer Echozeit (3D-UTE) für die pulmonale Bildgebung immunsupprimierter Patienten unter Stammzelltransplantation. Die Datenaufnahme erfolgte mit einer 3D-UTE-Sequenz (Schichtdicke 2,34mm; Matrix 256 × 256; Akquisitionszeit 12,7–17,6 s) unter Verwendung einer Stack-of-spirals-Trajektorie innerhalb eines Atemstopps. Die Untersuchungen wurden vor Beginn der Stammzelltransplantation, bei periprozeduralen Pneumonien, vor Entlassung und im Falle einer Rehospitalisierung durchgeführt. Die Datensätze wurden auf vorliegende Pleuraergüsse, Milchglasinfiltrate und Konsolidierungen von 2 Radiologen auf Lungenbasis bewertet. Zum Vergleich wurde eine klinische T2-Bildgebung herangezogen (BLADE, Schichtdicke 6,00mm; Matrix 320 × 320; Akquisitionszeit 3,1–5,5 min) und im Atomstopp in koronarer Schichtführung akquiriert. Klinisch indizierte Low-Dose-CT-Untersuchungen in Inspiration wurden als Referenz herangezogen und auf Lungenbasis evaluiert. Es wurden nur Untersuchungen eingeschlossen, die innerhalb von maximal 3 Tagen angefertigt wurden. Interrater-Übereinstimmung, Sensitivität, Spezifität, positiver und negativer prädiktiver Wert sowie diagnostische Genauigkeit der 3D-UTE-MRT wurden ermittelt. 67 MR-Scans von 28 Patienten wurden akquiriert. Zu 33 MRT-Untersuchungen von 23 Patienten lag eine Referenz-CT vor. Die 3D-UTE zeigte eine hohe Sensitivität und Spezifität in der Detektion von Pleuraergüssen (n = 6; Sensitivität 92 %; Spezifität 100 %) und Konsolidierungen (n = 22; Sensitivität 98 %; Spezifität 86 %). Hinsichtlich Milchglasinfiltraten (n = 9; Sensitivität 63 %; Spezifität 84 %) war die diagnostische Leistungsfähigkeit geringer. Die Genauigkeit der 3D-UTE-MRT war hoch (Pleuraergüsse, 98 %; Milchglasinfiltrate, 79 %; Konsolidierungen, 94 %). Die Interrater-Übereinstimmung war für Pleuraergüsse und Konsolidierungen substanziell (κ = 0,69–0,82), für Milchglasinfiltrate moderat (κ = 0,54). Verglichen mit der T2-Sequenz zeigte die 3D-UTE-MRT die pulmonalen Pathologien in mindestens gleichwertiger Abbildungsqualität und wurde bei Konsolidierungen und Milchglasinfiltraten in ~50 % der Fälle als überlegen bewertet. Die kontrastmittelfreie 3D-UTE-MRT ermöglicht eine strahlungsfreie und diagnostische Darstellung typischer pulmonaler Komplikationen von Patienten unter Stammzelltransplantation. Die CT zeigte sich zur Erkennung reiner Milchglasinfiltrate überlegen. · Die 3D-UTE-MRT des gesamten Thorax kann innerhalb eines Atemstopps akquiriert werden.. · Die 3D-UTE-MRT ermöglicht die diagnostische Bildgebung von Pleuraergüssen und Konsolidierungen.. · Die 3D-UTE-MRT verbessert die Detektionsraten von Milchglasinfiltraten in der pulmonalen MRT.. · Die 3D-UTE-Bildgebung stellt pulmonale Pathologien mindestens gleichwertig zur T2-Blade dar..

This report presents the case of fissured subepicardial hematoma and cardiac tamponade after coronary artery perforation during a complex percutaneous intervention. Surgical therapy was required to achieve hemostasis because a percutaneous sealing result was insufficient. Prompt recognition and cardiac surgery availability are essential for patient survival in such situations. (Level of Difficulty: Beginner.), Central Illustration

3D-printed dielectric substrates are manufactured using additive manufacturing (AM) technology. With CAD/CAM, rapid, accurate, and automatic manufacturing of objects with different characteristics and almost any geometry is possible. With 3D printing processes, objects are formed layer by layer, and complicated shapes can easily be created. For this reason, in the last decade, AM has seen a great boom in the development of RF and microwave circuits. Some applications that benefit from AM are metamaterials [1]-[3], antennas [4]-[5], and selective surfaces [6], among others. Most of the RF and microwave circuits reported in previous works are designed considering the dielectric substrate as an isotropic material; therefore, large differences are found between the measured and the simulated results [6]-[8]. These variations are largely due to the fact that the manufacturing standards generally include a mixture of materials inside the substrates with a periodic arrangement [9], and this favors dielectric anisotropy in the substrates. Consequently, the study of these materials is of great importance to the scientific community. This article is intended for designers who wish to tailor the dielectric characteristics of a substrate for microwave circuits, noting that anisotropy will manifest itself at lower frequencies when the internal structure of the printed material is modified.

Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

Context The present summary of the European Association of Urology (EAU) guidelines is based on the latest guidelines on male sexual health published in March 2021, with a last comprehensive update in January 2021. Objective To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health. Evidence acquisition A literature review was performed up to January 2021. The guidelines were updated, and a strength rating for each recommendation was included based on either a systematic review of the evidence or a consensus opinion from the expert panel. Evidence synthesis Late-onset hypogonadism is a clinical condition in the ageing male combining low levels of circulating testosterone and specific symptoms associated with impaired hormone production and/or action. A comprehensive diagnostic and therapeutic work-up, along with screening recommendations and contraindications, is provided. Erectile dysfunction (ED) is the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Along with a detailed basic and advanced diagnostic approach, a novel decision-making algorithm for treating ED in order to better tailor therapy to individual patients is provided. The EAU guidelines have adopted the definition of premature ejaculation (PE), which has been developed by the International Society for Sexual Medicine. After the subtype of PE has been defined, patient’s expectations should be discussed thoroughly and pharmacotherapy must be considered as the first-line treatment for patients with lifelong PE, whereas treating the underlying cause must be the initial goal for patients with acquired PE. Haemospermia is defined as the appearance of blood in the ejaculate. Several reasons of haemospermia have been acknowledged; the primary goal over the management work-up is to exclude malignant conditions and treat any other underlying cause. Conclusions The 2021 guidelines on sexual and reproductive health summarise the most recent findings, and advise in terms of diagnosis and treatment of male hypogonadism and sexual dysfunction for their use in clinical practice. These guidelines reflect the multidisciplinary nature of their management. Patient summary Updated European Association of Urology guidelines on sexual and reproductive health are presented, addressing the diagnosis and treatment of the most prevalent conditions in men. Patients must be fully informed of all relevant diagnostic and therapeutic options and, together with their treating physicians, decide on optimal personalised management strategies.

Sometimes, the clinical presentation of a brain tumour mimics that of stroke or viceversa. In these cases it is useful to evaluate follow-up with MR. The coregistration of PET and MR images improves the diagnostic performance of both techniques. In the area of interest, FDG uptake of any degree, with reference to the adjacent brain tissue uptake, should be considered suggestive of tumor if it corresponds to brain injury in MR, even when the FDG uptake is equal to or lower than that of the normal cerebral cortex. We present a case in which coregistration of images from both techniques contributed to the differential diagnosis of stroke and high-grade glioma, whole-body PET/CT ruled out metastatic etiology, and the results led to surgery.

In March 2020, the Australian government introduced a raft of public health initiatives to curb the rising cases of coronavirus disease 2019 (COVID-19) including closing schools and work from home orders. As a group of female academics, we were immediately attuned to the potential of COVID-19 to dilute progress made towards reducing the academic gender gap. This study emerged in response and comprised a rapid gender impact assessment of Australian universities’ organisational responses to COVID-19. Our aim was to understand the nature of university policy responses and the extent to which they considered differential impacts for men and women. We searched for relevant communications pertaining to COVID-19 policies from all Australian universities published up to June 2020. Our final sample comprised 79 documents from 29 universities. Information collected was in relation to five key policy domains: support for higher degree research students, leave arrangements for staff, working remotely, managing staff and academic promotion. Overall, little attention was paid to how gender might impact on the need for, or access to, policies in response to COVID-19. Findings showed a reliance on existing workplace mechanisms including access to leave and flexible working arrangements. While the ability to work flexibly is considered a key enabler of gender equality, these approaches have been in place at Australian universities for decades but have, on their own, been inadequate to redress entrenched inequalities. While there is potential for social disruptions brought about by the pandemic to act as a catalyst for change, this will not happen without policies that are transformative in their approach to equality and inclusion.

Background. Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Methods. Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. Results. The RA + osteoporosis group had elevated sRANKL levels ( p = 0.005 ), higher sRANKL/OPG ratio ( p = 0.017 ), decreased DKK-1 ( p = 0.028 ), and lower SOST levels ( p < 0.001 ). Low total hip BMD correlated with high sRANKL ( p = 0.001 ) and sRANKL/OPG ratio ( p = 0.005 ). Total hip and lumbar spine BMD correlated with DKK-1 ( p = 0.009 and p = 0.05 , respectively) and SOST levels ( p < 0.001 and p < 0.001 , respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures ( p = 0.003 and p = 0.003 , respectively) and hip fracture ( p = 0.002 and p = 0.006 , respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture ( p = 0.003 ) and hip fracture ( p = 0.009 ). Conclusion. High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

BACKGROUND: The Mexican serviceberry, Malacomeles denticulata, have been used as a successful oral therapy by Mexican communities without enough scientific support. OBJECTIVE: To evaluate the M. denticulata extracts with selective antibacterial properties over dental biofilm bacteria. METHODS: Fruit, Leaf, and Stem of M. denticulata extracts were evaluated with micro-broth dilution method using ATCC bacteria. OD600 values had compared against each positive control (T-student-test). Anaerobically viability had confirmed by Colony-Forming-Units. Thin-Layer-Chromatography was used to identify the number of compounds and phytochemicals to identify secondary metabolites of the selected extracts. RESULTS: Streptococcus mutans showed Minimum-Bactericidal-Concentrations_(MBC) at 30 mg/mL to Fruit, Leaf, and Stem extracts. Periodontal-pathogens Aggregatibacter actinomycetemcomitans serotype b_(MBC = 30 mg/mL_NS); Fusobacterium nucleatum subsp. nucleatum_(MBC = 30 mg/mL_p

Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas2. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified. Multi-omics datasets are integrated to generate a unified and clinically informed molecular classification of meningiomas.

Background Current mitral bioprostheses are akin to the aortic valve and therefore abolish the left ventricular (LV) physiological vortex. We evaluated the hemodynamic performance and the effects on intraventricular flow dynamics (IFD) of a novel mitral bioprosthesis that presents an innovative design, mimicking the native valve. Methods A D-shaped self-expandable stent-bovine pericardium monoleaflet valve was designed to provide physiological asymmetric intraventricular flow. Twelve juvenile sheep were consecutively implanted transapically. Post-implant studies were obtained immediately after the implantation and at 3 months to assess the hemodynamic performance of the prostheses, using Doppler echocardiography and IFD using echo particle imaging velocimetry. Results Three deaths occurred during follow-up, one due to valve misplacement because of poor imaging visualization and 2 not valve related. Mean transvalvular gradient and effective orifice area after implantation and at 3 months were 2.2 ± 1.2 mmHg and 4.0 ± 1.1 cm2, and 3.3 ± 1.5 mmHg and 3.5 ± 0.5 cm2, respectively. LV vortex dimension, orientation and physiologic anti-clockwise rotation were preserved compared with pre-operative normal LV flow pattern. One animal showed a moderate paravalvular leak, others mild or none. LV outflow tract obstruction, valve thrombosis or hemolysis were not observed. Conclusions Our preclinical in vivo results, confirm the good hemodynamic performance of this new transcatheter bioprosthesis with preservation of the physiological IFD. Clinical studies are needed to document whether these characteristics will foster LV recovery and improve the clinical outcome of patients with mitral regurgitation.

A leiomyoma is a benign mesenchymal neoplasm that usually develops where smooth muscle is present. In this report, we present the case of a 75-year-old woman who sought medical attention due to pelvic organ prolapse and urinary incontinence, and without defecatory symptoms. Both pelvic floor ultrasound and magnetic resonance imaging (MRI) examination showed a well-defined mass in the ischioanal fossa, eventually diagnosed as a perianal leiomyoma. It is considered a rare entity because of its location involving the anal sphincter and clinical features. We describe the ultrasonographic and MRI findings of this perianal leiomyoma, together with differential diagnoses and immunohistochemical characterization.

Although breast conserving surgery is the standard of care for patients with localized breast cancer in high-income countries, little is known about its use in developing countries, where disparities in access to treatment may lead to an increased use of mastectomy. We examined the use of breast conserving surgery at a Mexican cancer center after the implementation of a public insurance program aimed at providing coverage for previously uninsured patients. Between 2006 and 2016, 4519 women received surgical treatment for breast cancer, of which 39% had early-stage disease. The proportion of patients treated with breast conserving surgery increased from 10% in the 2006-2009 period to 33% in the 2013-2016 period, with most of this increase occurring among women with early-stage disease (17-52%). Improving access to care and reducing the financial burden of breast cancer in developing countries may lead to an increased use of breast conserving surgery.

Objective Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. Design and methods In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. Results 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. Conclusions These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.

Resumo O aumento da demanda pelo pronto atendimento é um fenômeno mundial, e seu uso inapropriado é um dos principais problemas. Há necessidade de identificar os fatores relacionados para orientar a melhoria da qualidade dos serviços. O objetivo deste artigo é analisar os fatores associados ao uso inapropriado em serviços de Pronto Atendimento. Estudo transversal com dados de 384 prontuários de pacientes atendidos em dois serviços de pronto atendimento de um município do Centro-Sul do Paraná, Brasil, em 2013. A análise foi descritiva, bivariada pelo Qui-quadrado de Pearson para verificar associações entre uso inapropriado e variáveis independentes. Realizou-se Regressão Logística Múltipla. A proporção do uso inapropriado de pronto atendimento foi de 73,4% e apresentou associação com pessoas com alguma condição sensível à atenção primária, residentes em áreas sem cobertura desta atenção, pessoas entre 0 e 11 anos, e 12 a 17 anos, atendimento no primeiro trimestre do ano, doenças do aparelho respiratório, lesões e envenenamentos e doenças do sistema osteomuscular. Necessita-se fortalecer a atenção primária para redução do uso inapropriado do pronto atendimento, especialmente na atenção às condições sensíveis à atenção primária e ampliação da acessibilidade sócio-organizacional. Abstract The increase in the demand for Emergency Services is a worldwide phenomenon, and its inappropriate use is one of the main problems. Factors related to the inappropriate use must be investigated to guide improvement in the quality of services. This article aims at analyzing factors associated with the inappropriate use of emergency services. This is a cross-sectional study with secondary data from 384 medical records from two emergency services in a city in central-southern region of the state of Paraná, Brazil, in 2013. A descriptive, bivariate using Pearson’s chi-squared test was performed to verify associations between inappropriate use and independent variables. Multiple Logistic Regression was also performed. The proportion of inappropriate use of Emergency Services was 73.4% and was associated with people with some primary health care sensitive conditions, residents in areas without primary care coverage, people between 0 and 11 years old, and 12 to 17 years old, care in the first trimester of the year, respiratory diseases, lesions and poisonings and diseases of the musculoskeletal system. Primary care must be strengthened to reduce the inappropriate use of care, especially in the attention to primary health care sensitive conditions and to increase the socio-organizational accessibility.

The increase in production, consumption and inadequate disposition of plastics has generated an accumulation of these elements in marine ecosystems, which have become important microplastics sinks (< 5 mm). The objective of this research was to determine the temporal and spatial differences in the density, distribution, and type of microplastics in the sediments of Buenaventura Bay. For this purpose, sediment samples were collected in the internal estuary (close to the rivers) and in the external estuary (with a greater marine influence). Samples were obtained in the dry, transition, and rainy season for the years 2015 and 2019. Microplastics were extracted by density separation method, each particle was classified and measured by optical microscopy. Density ranged from 11 to 1,354 particles/kg, with averages of 194.9 ± 51.3 and 359.6 ± 88.0 particles/kg for the years 2015 and 2019, respectively, reporting an increase of 84.4 %. The internal estuary presented a higher density in both years and the fibers constituted the most common form of microplastic particles, with 63.7 % for 2015 and 56.03 % for 2019. The presence and increasing accumulation of microplastics generates risks and adverse effects for the marine communities; additionally it coul compromise the food safety for coastal human populations.

Objectives: To investigate the extent of synaptic loss, and the contribution of gray matter (GM) inflammation and demyelination to synaptic loss, in multiple sclerosis (MS) brain tissue. Methods: This study was performed on two different post-mortem series of MS and control brains, including deep GM and cortical GM. MS brain samples had been specifically selected for the presence of active demyelinating GM lesions. Over 1,000,000 individual synapses were identified and counted using confocal microscopy, and further characterized as glutamatergic/GABAergic. Synaptic counts were also correlated with neuronal/axonal loss. Results: Important synaptic loss was observed in active demyelinating GM lesions (−58.9%), while in chronic inactive GM lesions, synaptic density was only mildly reduced compared to adjacent non-lesional gray matter (NLGM) (−12.6%). Synaptic loss equally affected glutamatergic and GABAergic synapses. Diffuse synaptic loss was observed in MS NLGM compared to control GM (−21.2% overall). Conclusion: This study provides evidence, in MS brain tissue, of acute synaptic damage/loss during active GM inflammatory demyelination and of synaptic reorganization in chronically demyelinated GM, affecting equally glutamatergic and GABAergic synapses. Furthermore, this study provides a strong indication of widespread synaptic loss in MS NLGM also independently from focal GM demyelination.

Background Lactobacillus is a genus of Gram-positive non-spore-forming rods usually found in the microbiota of the oral cavity, gastrointestinal tract, and female genitourinary tract. Also, they are commonly used in the food industry as supplements and probiotics. Lactobacilli are normally considered non-pathogenic to the human body, however, under certain circumstances such as immunosuppression, they can cause severe infections, with only a few cases of bacteremia, infective endocarditis, pneumonia, meningitis, and intra-abdominal infections reported. Among these presentations, a pyogenic liver abscess is rather rare. Case presentation We describe the case of a 59-year-old man with a history of diabetes mellitus and multiple abdominal surgeries with the latest being in 2014 presenting with bacteremia and multiple large pyogenic liver abscesses due to Lactobacillus gasseri, which did not appear to be related to the use of probiotics or immunosuppression. Conclusions Given the high prevalence of diabetes mellitus and the increased use of probiotics, it is expected that in the future we will see an increase in infections caused by Lactobacilli. Medical management with antibiotics and percutaneous drainage were successful strategies for the treatment of this unusual case of pyogenic liver abscesses and bacteremia caused by Lactobacillus gasseri.

To identify the risk factors associated with patency loss after bailout stenting with third-generation hybrid heparin-bonded nitinol stent of the femoropopliteal segment. Prospective, multicenter, single-arm registry including 156 patients (50 females, mean age 72 ± 11 years) subjected, from February 2017 to December 2018, to provisional stenting with Gore Tigris vascular stent of the distal superficial femoral artery, with or without involvement of the popliteal artery, in 9 different centers. The 194 lesions, with Rutherford score ≥ 3, were stented in case of recoil, dissection or residual stenosis not responding to percutaneous trans-luminal angioplasty (PTA). The follow-up (FU) was performed with clinical evaluation and duplex ultrasound (DUS) at 1, 6 and 12 months. The primary patency rate was 99(95%CI 98–100)% at 1 month, 86(80–92)% at 6 months and 81(74–88)% at-12 months. After patency loss, 13/23 (56.5%) patients were re-treated, yielding a primary assisted patency of 91(86–96)% at 6 months and 88(82–94)% at 12 months and a secondary patency of 94(90–98)% at 6 months and 90(84–95)% at 12 months. Rutherford score ≥ 4 (p = 0.03) and previous severe treatments (p = 0.01) were identified as risk factors for early patency loss during FU. The involvement of the popliteal artery was not an independent risk factor for loss of patency. The bailout stenting of the femoropopliteal segment with third-generation nitinol stents is a safe and effective option in case of recoil, dissection or residual stenosis not responding to PTA. Critical limb ischemia and history of previous major treatment at the same level are significant prognostic factors for patency loss during FU.

Introduction There is an increased risk of thrombotic complications in patients with COVID‐19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new‐onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID‐19. Methods We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow‐up due to kidney transplantation or death from non‐thrombotic causes. Findings One‐hundred and eighty five prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS‐CoV‐2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID‐19 survivors compared to the non‐infected cohort (18.5% vs. 1.9%, p = 0.002) after a median follow‐up of 7 months. Multivariate regression analysis showed that COVID‐19 infection increased risk for late thrombotic events adjusted for age, sex, hypertension, diabetes, antithrombotic treatment, and previous thrombotic events (Odds Ratio (OR) 26.4, 95% confidence interval 2.5–280.6, p = 0.01). Clinical and laboratory markers did not predict thrombotic events. Conclusions There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID‐19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID‐19.