Advanced glycation end products of dietary origin and their association with inflammation in diabetes - A minireview.

Advanced glycation end products (AGEs) are a diverse group of compounds that are formed as a result of the non-enzymatic reaction between a reducing sugar such as glucose and the free NH2 groups of an amino acid in a protein or other biomolecule. The chemical reaction, by which these products are generated, is known as the Maillard reaction and occurs as a part of the body's normal metabolism. Such a reaction is enhanced during diabetes due to hyperglycemia, but it can also occur during the preparation, processing, and preservation of certain foods. Therefore, AGEs can also be obtained from the diet (d-AGE) and contribute to an increase of the total serum pool of these compounds. They have been implicated in a wide variety of pathological processes, mainly because of their ability to induce inflammatory responses and oxidative stress increase. They are extensively accumulated as a part of the normal aging, especially in tissues rich in long half-life proteins, which can compromise the physiology of these tissues. d-AGEs are abundant in diets rich in processed fats and sugars. This review is addressed to the current knowledge on these products and their impact on the immunomodulation of various mechanisms that may contribute to exacerbation of the diabetes pathophysiology.

Robotic kidney transplantation.

Kidney transplantation is the best treatment option for patients with end-stage renal disease owing to improved survival and quality of life compared with dialysis. The surgical approach to kidney transplantation has been somewhat stagnant in the past 50 years, with the open approach being the only available option. In this scenario, evidence of reduced surgery-related morbidity after the introduction of robotics into several surgical fields has induced surgeons to consider robot-assisted kidney transplantation (RAKT) as an alternative approach to these fragile and immunocompromised patients. Since 2014, when the RAKT technique was standardized thanks to the pioneering collaboration between the Vattikuti Urology Institute and the Medanta hospital (Vattikuti Urology Institute-Medanta), several centres worldwide implemented RAKT programmes, providing interesting results regarding the safety and feasibility of this procedure. However, RAKT is still considered an alternative procedure to be offered mainly in the living donor setting, owing to various possible drawbacks such as prolonged rewarming time, demanding learning curve, and difficulties in carrying out this procedure in challenging scenarios (such as patients with obesity, severe atherosclerosis of the iliac vessels, deceased donor setting, or paediatric recipients). Nevertheless, the refinement of robotic platforms through the implementation of novel technologies as well as the encouraging results from multicentre collaborations under the umbrella of the European Association of Urology Robotic Urology Section are currently expanding the boundaries of RAKT, making this surgical procedure a real alternative to the open approach.

Oncologic surveillance intensity after endoscopic treatment of upper tract urothelial carcinoma.

BACKGROUND: The optimal oncologic surveillance in patients with upper tract urothelial carcinoma (UTUC) elected for conservative treatment is still a matter of debate. METHODS: Patients elected for endoscopic treatment of UTUC were followed up according to EAU guidelines recommendations after treatment. Bladder cancer recurrence-free survival (BCa-RFS), UTUC recurrence-free survival (UTUC-RFS), radical nephroureterectomy-free survival (RNU-FS), and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. The crude risks of BCa and UTUC recurrences over time were estimated with the Locally Weighted Scatterplot Smoothing method. RESULTS: Overall, 54 and 55 patients had low- and high-risk diseases, respectively. Median follow-up was 46.9 (IQR: 28.7-68.7) and 36.9 (IQR: 19.8-60.1) months in low and high-risk patients, respectively. In low-risk patients, BCa recurrence risk was more than 20% at 24 months follow-up. At 60 months, time point after which cystoscopy and imaging should be interrupted, the risk of BCa recurrence and UTUC recurrence were 14% and 7%, respectively. In high-risk patients, the risk of BCa and UTUC recurrence at 36 months was approximately 40% and 10%, respectively. Conversely, at 60 months, the risk of bladder recurrence and UTUC recurrence was 28% and 8%, respectively. CONCLUSIONS: For low-risk patients, cystoscopy should be performed semi-annually until 24 months, while upper tract assessment should be obtained up to 60 months, as per current EAU guidelines recommendations. For high-risk patients, upper tract assessment should be intensified to semi-annually up to 36 months, then obtained yearly. Conversely, cystoscopy should be ideally performed semi-annually until 60 months and yearly thereafter.

Defining the role of multiparametric MRI in predicting prostate cancer extracapsular extension.

OBJECTIVES: To identify the predictive factors of prostate cancer extracapsular extension (ECE) in an institutional cohort of patients who underwent multiparametric MRI of the prostate prior to radical prostatectomy (RP). PATIENTS AND METHODS: Overall, 126 patients met the selection criteria, and their medical records were retrospectively collected and analysed; 2 experienced radiologists reviewed the imaging studies. Logistic regression analysis was conducted to identify the variables associated to ECE at whole-mount histology of RP specimens; according to the statistically significant variables associated, a predictive model was developed and calibrated with the Hosmer-Lomeshow test. RESULTS: The predictive ability to detect ECE with the generated model was 81.4% by including the length of capsular involvement (LCI) and intraprostatic perineural invasion (IPNI). The predictive accuracy of the model at the ROC curve analysis showed an area under the curve (AUC) of 0.83 [95% CI (0.76-0.90)], p < 0.001. Concordance between radiologists was substantial in all parameters examined (p < 0.001). Limitations include the retrospective design, limited number of cases, and MRI images reassessment according to PI-RADS v2.0. CONCLUSION: The LCI is the most robust MRI factor associated to ECE; in our series, we found a strong predictive accuracy when combined in a model with the IPNI presence. This outcome may prompt a change in the definition of PI-RADS score 5.

Simultaneous Bilateral Video-Endoscopic Inguinal Lymphadenectomy for Penile Carcinoma: Surgical Setting, Feasibility, Safety, and Preliminary Oncological Outcomes.

INTRODUCTION: Inguinal lymph node dissection (ILND) plays an important role for both staging and treatment purposes in patients diagnosed with penile carcinoma (PeCa). Video-endoscopic inguinal lymphadenectomy (VEIL) has been introduced to reduce complications, and in those patients elected for bilateral ILND, a simultaneous bilateral VEIL (sB-VEIL) has also been proposed. This study aimed to investigate the feasibility, safety, and preliminary oncological outcomes of sB-VEIL compared to consecutive bilateral VEIL (cB-VEIL). MATERIAL AND METHODS: Clinical N0-2 patients diagnosed with PeCa and treated with cB-VEIL and sB-VEIL between 2015 and 2023 at our institution were included. Modified ILND was performed in cN0 patients, while cN+ patients underwent a radical approach. Intra- and postoperative complications, operative time, time of drainage maintenance, length of hospital stay and readmission within 90 days, as well as lymph node yield, were compared between the two groups. RESULTS: Overall, 30 patients were submitted to B-VEIL. Of these, 20 and 10 patients underwent cB-VEIL and sB-VEIL, respectively. Overall, 16 (80%) and 7 (70%) patients were submitted to radical ILND due to cN1-2 disease in the cB-VEIL and sB-VEIL groups, respectively. No statistically significant difference emerged in terms of median nodal yield (13.5 vs. 14, p = 0.7) and median positive LNs (p = 0.9). sD-VEIL was associated with a shorter operative time (170 vs. 240 min, p < 0.01). No statistically significant difference emerged in terms of intraoperative estimated blood loss, length of hospital stay, time to drainage tube removal, major complications, and hospital readmission in the cB-VEIL and sB-VEIL groups, respectively (all p > 0.05). CONCLUSIONS: Simultaneous bilateral VEIL is a feasible and safe technique in patients with PeCA, showing similar oncological results and shorter operative time compared to a consecutive bilateral approach. Patients with higher preoperative comorbidity burden or anesthesiological risk are those who may benefit the most from this technique.

A new machine-learning model to predict long-term renal function impairment after minimally invasive partial nephrectomy: the Fundació Puigvert predictive model.

PURPOSE: To provide a new model to predict long-term renal function impairment after partial nephrectomy (PN). METHODS: Data of consecutive patients who underwent minimally invasive PN from 2005 to 2022 were analyzed. A minimum of 12 months of follow-up was required. We relied on a machine-learning algorithm, namely classification and regression tree (CART), to identify the predictors and associated clusters of chronic kidney disease (CKD) stage migration during follow-up. RESULTS: 568 patients underwent minimally invasive PN at our center. A total of 381 patients met our inclusion criteria. The median follow-up was 69 (IQR 38-99) months. A total of 103 (27%) patients experienced CKD stage migration at last follow-up. Progression of CKD stage after surgery, ACCI and baseline CKD stage were selected as the most informative risk factors to predict CKD progression, leading to the creation of four clusters. The progression of CKD stage rates for cluster #1 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI 1-4), #2 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI ≥ 5), #3 (no progression of CKD stage after surgery and baseline CKD stage 3-4-5) and #4 (progression of CKD stage after surgery) were 6.9%, 28.2%, 37.1%, and 69.6%, respectively. The c-index of the model was 0.75. CONCLUSION: We developed a new model to predict long-term renal function impairment after PN where the perioperative loss of renal function plays a pivotal role to predict lack of functional recovery. This model could help identify patients in whom functional follow-up should be intensified to minimize possible worsening factors of renal function.

Sequential Treatment With Bacillus Calmette-Güerin (BCG) and Mitomycin C Administered With Electromotive Drug Administration (EMDA) in Patients With High-Risk Nonmuscle Invasive Bladder Cancer After BCG Failure.

BACKGROUND: Nowadays, there is no standard non-surgical treatment for patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Güerin (BCG) therapy has failed. OBJECTIVES: To assess the clinical and oncological outcomes of sequential treatment with Bacillus Calmette-Guerin (BCG) and Mitomycin C (MMC) administered with Electromotive Drug Administration (EMDA) in patients with high-risk NMIBC who fail BCG immunotherapy. MATERIAL AND METHODS: We retrospectively studied patients with NMIBC who failed BCG and received alternating BCG and Mitomycin C with EMDA between 2010 and 2020. Treatment schedule consisted in an induction therapy with 6 instillations (BCG, BCG, MMC + EMDA, BCG, BCG, MMC + EMDA) and a 1-year maintenance. Complete response (CR) was defined as the absence of high-grade (HG) recurrences during follow-up, and progression was defined as the occurrence of muscle invasive or metastatic disease. CR rate was estimated at 3, 6, 12, and 24 months. Progression rate and toxicity were also assessed. RESULTS: Twenty-two patients were included with a median age of 73 years. Fifty percent of tumors were single, 90% were smaller than 1.5cm, 40% were GII (HG) and 40% were Ta. CR rate was 95.5%, 81% and 70% at 3 and 6 months, 12 months and 24 months, respectively. With a median follow-up of 28.8 months, 6 patients (27%) presented HG recurrence and only 1 patient (4.5%) progressed and ended in cystectomy. This patient died due to metastatic disease. Treatment was well tolerated and 22% of the patients presented adverse effects, being dysuria the most frequent one. CONCLUSION: Sequential treatment with BCG and Mitomycin C with EMDA achieved good responses and low toxicity in selected patients who did not respond to BCG. Only 1 patient ended in cystectomy and died due to metastatic disease, therefore, cystectomy was avoided in most cases.

Prevalencia de hipotiroidismo subclínico y biomarcadores de riesgo cardiovascular en pacientes del Hospital General de Riobamba / Prevalence of subclinical hypothyroidism and biomarkers of cardiovascular risk in patients of the General Hospital of Riobamba

El Hipotiroidismo subclínico (HSC) es definido bioquímicamente por una elevación en la concentración sérica de la hormona TSH con niveles normales de T4 libre. El objetivo de este estudio fue determinar la prevalencia de HSC en los pacientes que asistieron a la consulta de medicina interna del Hospital General IESS de Riobamba. Así como, analizar la correlación entre los parámetros hormonales y ciertos marcadores bioquímicos asociados con el incremento de riesgo cardiovascular. Se realizó una investigación de tipo descriptiva, observacional, con un diseño no experimental de corte transversal, que abarcó el periodo comprendido desde enero de 2019 hasta septiembre de 2021. 245 pacientes fueron diagnosticados con HSC, lo cual representó el 10.58 % del universo poblacional estudiado, 61.2% eran del sexo femenino, mientras que el 38.8% del sexo masculino. El mayor número de casos (59.61 %) se observó en el grupo etario mayor de 65 años, distribuidos de la siguiente manera: (22.86% hombres y 36.75% mujeres), también se encontró que el HSC está asociado con un perfil lipídico aterogénico, caracterizado por un incremento en la concentración de colesterol total y LDL los cuales se correlacionaron positivamente con las concentraciones de TSH.

Subclinical hypothyroidism (SH) is biochemically defined by an elevation in the serum concentration of TSH hormone with normal levels of free T4. The aim of this study was to determine the prevalence of SH in patients attending the internal medicine clinic of the General Hospital IESS of Riobamba. Also, to analyze the correlation between hormonal parameters and certain biochemical markers associated with increased cardiovascular risk. A descriptive, observational, non-experimental cross-sectional design was performed, covering the period from January 2019 to September 2021. 245 patients were diagnosed with SH, which represented 10.58 % of the population universe studied, 61.2% were female, while 38.8% were male. The highest number of cases (59.61 %) was observed in the age group over 65 years, distributed as follows: (22.86% men and 36.75% women), it was also found that SH is associated with an atherogenic lipid profile, characterized by an increase in the concentration of total cholesterol and LDL which correlated positively with TSH concentrations.

Diabetes, heart damage, and angiotensin II. What is the relationship link between them? A minireview.

Cardiovascular complications are the main cause of mortality and morbidity in the diabetic patients, in whom changes in myocardial structure and function have been described. Numerous molecular mechanisms have been proposed that could contribute to the development of a cardiac damage. In this regard, angiotensin II (Ang II), a proinflammatory peptide that constitutes the main effector of the renin-angiotensin system (RAS) has taken a relevant role. The aim of this review was to analyze the role of Ang II in the different biochemical pathways that could be involved in the development of cardiovascular damage during diabetes. We performed an exhaustive review in the main databases, using the following terms: angiotensin II, cardiovascular damage, renin angiotensin system, inflammation, and diabetes mellitus. Classically, the RAS has been defined as a complex system of enzymes, receptors, and peptides that help control the blood pressure and the fluid homeostasis. However, in recent years, this concept has undergone substantial changes. Although this system has been known for decades, recent discoveries in cellular and molecular biology, as well as cardiovascular physiology, have introduced a better understanding of its function and relationship to the development of the diabetic cardiomyopathy.

Sobrepeso y obesidad en los adolescentes / Overweight and obesity in adolescents / Sobrepeso e obesidade em adolescentes

El sobrepeso y la obesidad en los adolescentes se ha convertido en un problema grave de salud pública, que afecta a países industrializados y aquellos en vías de desarrollo. Lo cual altera la salud con excesos en el tejido adiposo, analizados con el Índice de Masa Corporal, el cual es un indicador antropométrico de gran valía. Objetivo. Analizar los aportes de investigaciones sobre el sobrepeso y obesidad en adolescentes con sus repercusiones. Metodología. Se realizó una revisión bibliográfica, recolectando artículos originales de revistas indexadas y que se encontraron en la base de datos científicas como Scopus, Scielo, y Google académico. Resultados. La prevalencia en adolescentes aumenta progresivamente y de no ser corregido se presentará en el adulto, aumentando los riesgos de padecer patologías como: hipertensión, alteraciones cardiovasculares y diabetes alterando la esperanza como la calidad de vida. Conclusión. Los factores causales son la mala alimentación tanto de los adolescentes como de sus padres; nivel socioeconómico, nivel educativo, la disminución de la actividad física junto con horas excesivas de televisión y uso de tecnología. Acompañado de factores genéticos. En los adolescentes el problema de sobrepeso y obesidad puede relacionarse con alteraciones emocionales, provocando un bajo autoestima, depresión y ansiedad. Para su tratamiento es necesario la intervención dietética buscando cambiar conductas, aumentando la actividad física, evitando el sedentarismo. El uso de tratamientos farmacológicos y quirúrgicos es también válido, sobre todo como alternativa para aquellos que no han logrado cambiar los hábitos alimentario saludables evitando la mortalidad.

Overweight and obesity in adolescents has become a serious public health problem, affecting both industrialized and developing countries. This alters health with excesses in adipose tissue, analyzed with the Body Mass Index, which is an anthropometric indicator of great value. Objective. To analyze the contributions of research on overweight and obesity in adolescents with its repercussions. Methodology. A bibliographic review was carried out, collecting original articles from indexed journals and found in scientific databases such as Scopus, Scielo, and Google Scholar. Results. The prevalence in adolescents increases progressively and if it is not corrected, it will be present in adults, increasing the risks of suffering pathologies such as hypertension, cardiovascular alterations and diabetes, altering life expectancy and quality of life. Conclusion. The causal factors are poor nutrition of both adolescents and their parents; socioeconomic level, educational level, decreased physical activity together with excessive hours of television and use of technology. Accompanied by genetic factors. In adolescents, the problem of overweight and obesity can be related to emotional alterations, causing low self-esteem, depression and anxiety. For its treatment, dietary intervention is necessary in order to change behaviors, increasing physical activity and avoiding sedentary lifestyles. The use of pharmacological and surgical treatments is also valid, especially as an alternative for those who have not been able to change healthy eating habits, avoiding mortality.

O excesso de peso e a obesidade em adolescentes tornou-se um grave problema de saúde pública, afetando tanto os países industrializados quanto os países em desenvolvimento. Isto altera a saúde com excessos de tecido adiposo, analisado com o Índice de Massa Corporal, que é um indicador antropométrico de grande valor. Objetivo. Analisar as contribuições da pesquisa sobre excesso de peso e obesidade em adolescentes com suas repercussões. Metodologia. Foi realizada uma revisão bibliográfica, coletando artigos originais de periódicos indexados e encontrados em bancos de dados científicos como Scopus, Scielo e Google Scholar. Resultados. A prevalência em adolescentes aumenta progressivamente e, se não for corrigida, estará presente em adultos, aumentando os riscos de sofrer patologias como: hipertensão, alterações cardiovasculares e diabetes, alterando a expectativa de vida e a qualidade de vida. Conclusão. Os fatores causais são a má alimentação tanto dos adolescentes quanto de seus pais; nível socioeconômico, nível educacional, a diminuição da atividade física junto com o excesso de horas de televisão e o uso de tecnologia. Acompanhados por fatores genéticos. Nos adolescentes, o problema de excesso de peso e obesidade pode estar relacionado a alterações emocionais, causando baixa auto-estima, depressão e ansiedade. Para seu tratamento, a intervenção dietética é necessária, procurando mudar o comportamento, aumentando a atividade física e evitando um estilo de vida sedentário. O uso de tratamentos farmacológicos e cirúrgicos também é válido, especialmente como uma alternativa para aqueles que não conseguiram mudar hábitos alimentares saudáveis e evitar a mortalidade.

Elevación del índice neutrófilo/linfocito y su relación con la proteína C reactiva en pacientes con diabetes mellitus tipo 2 / Elevation of the neutrophil/lymphocyte ratio and its relationship to C-reactive protein in patients with type 2 diabetes mellitus

Introducción: la proporción entre el recuento absoluto de neutrófilos y el recuento absoluto de linfocitos (índice de neutrófilos/linfocitos, INL) se ha convertido en los últimos años en un marcador crucial de inflamación sistémica, y se ha descrito que su elevación se relaciona con numerosas enfermedades inflamatorias crónicas. Objetivos: determinar el índice de neutrófilos/linfocitos (INL) en pacientes con diabetes mellitus tipo 2 (DM2), comparar con no diabéticos y establecer su correlación con la concentración de proteína C reactiva ultrasensible en una población de la localidad de Riobamba, Ecuador. Materiales y métodos: se realizó una investigación de tipo descriptiva, correlacional, de corte transversal, en el período comprendido desde julio de 2019 a febrero de 2020. Se seleccionaron 80 individuos para participar en el proyecto: 25 sujetos controles y 55 pacientes con diagnóstico de DM2. A cada sujeto se le extrajo una muestra de sangre en ayunas para la determinación de glucosa, colesterol total, triglicéridos, HDL colesterol, LDL colesterol, proteína C reactiva ultrasensible (PCR-us), hemoglobina glicosilada (HbA1c), recuento total de leucocitos, neutrófilos y linfocitos. Resultados: se encontró un incremento significativo en la concentración de glucosa (p<0,0001), HbA1c (p<0,0001), índice de masa corporal (IMC) (p<0,0001), PCR-us (p<0,0001), recuento absoluto de neutrófilos (p=0,001), recuento absoluto de linfocitos (p=0,04) e INL (p=0,0005), y una reducción significativa del HDL colesterol (p=0,02) en los pacientes con DM2 vs los controles. Se observó una correlación positiva (p<0,0001; r=0,7774) entre el INL y la PCR-us en los pacientes con DM2. Conclusiones: los pacientes con DM2 experimentaron elevación en el INL que se correlacionó con el incremento en la concentración de la PCR-us.

Introduction: the ratio between the absolute neutrophil count and the absolute lymphocyte count (neutrophil/lymphocyte ratio, NLR) has become a crucial marker of systemic inflammation in recent years, and its elevation has been described as being related to numerous chronic inflammatory diseases. Objectives: to determine the neutrophil/lymphocyte ratio (NLR) in patients with type 2 diabetes mellitus (T2DM), to compare with non-diabetics and to establish its correlation with the concentration of ultrasensitive C-reactive protein in a population of the town of Riobamba, Ecuador. Materials and methods: a descriptive, correlational, crosssectional, research was conducted from July 2019 to February 2020. Eighty individuals were selected to participate in the project, 25 control subjects and 55 patients with a diagnosis of T2DM. Each subject had a fasting blood sample drawn for the determination of glucose, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, ultrasensitive C-reactive protein (hs-CRP), glycosylated hemoglobin (HbA1c), total leukocyte count, neutrophils and lymphocytes. Results: a significant increase in glucose concentration (p<0.0001), HbA1c (p<0.0001), body mass index (BMI) (p<0.0001), hs-CRP (p<0.0001), absolute neutrophil count (p=0.001), absolute lymphocyte count (p=0.04), and NLR (p=0.0005), and a significant reduction in HDL cholesterol (p=0.02), were found in patients with T2DM vs controls. A positive correlation (p<0.0001; r=0.7774) was observed between NLR and hs-CRP in patients with T2DM. Conclusions: patients with T2DM experience elevation in NLR which correlates with increase in hs-CRP concentration.

La desventaja de los hombres frente a la Covid-19: análisis de la influencia del sexo sobre la respuesta inmunitaria ante la infección por SARS-Cov-2 / The disadvantage of men against COVID-19: analysis of the influence of sex on the immune response to SARS-CoV-2 infection

mundo se encuentra en medio de la pandemia de la enfermedad por coronavirus 2019 (COVID-19). En la mayoría de los países, la tasa de mortalidad, así como, la severidad de la enfermedad es más alta en hombres que en mujeres. Este sesgo sexual sugiere que los hombres son más propensos a desarrollar complicaciones graves o a sucumbir a las mismas, lo que conduce a la muerte. Por lo tanto, es importante comprender los elementos biológicos basados en el sexo que inciden en la respuesta inmunitaria. El objetivo de ésta revisión fue hacer un análisis en relación a la evidencia disponible sobre los diferentes factores que permitirían explicar esta disparidad sexual. Abordamos las diferencias en la respuesta inmunitaria en ambos sexos tomando en cuenta el aspecto genético, hormonal y el papel del sistema renina-angiotensina. Para ello, se realizó una búsqueda minuciosa en diferentes bases de datos utilizando las siguientes palabras clave: (Diferencia de sexo, genética, hormonas sexuales, COVID-19, SARS-CoV-2, respuesta inmunitaria, inflamación, hombres, mujeres). Los resultados de nuestro análisis ofrecen una comprensión más clara sobre la influencia de las diferencias sexuales en la capacidad de respuesta a una infección, con especial énfasis en la infección por SARS-CoV-2. Conocer estos factores no solo ayudará a comprender mejor la patogenia de la COVID-19, sino, además, guiará el diseño de terapias efectivas para la medicina personalizada basada en las diferencias sexuales

The world is during the 2019 coronavirus disease pandemic (COVID-19). In most countries, the mortality rate, as well as, the severity of the disease is higher in men than in women. This sex bias suggests that men are more likely to develop severe complications or succumb to severe complications, leading to death. Therefore, it is important to understand the sex-based biological elements that influence the immune response. The aim of this review was to review the available evidence on the different factors that could explain this sex disparity. We addressed the differences in the immune response in both sexes taking into account genetic, hormonal and the role of the renin-angiotensin system. For this purpose, a thorough search was performed in different databases using the following keywords: (Sex difference, genetics, sex hormones, COVID-19, SARS-CoV-2, immune response, inflammation, men, women). The results of our analysis provide a clearer understanding on the influence of sex differences on the ability to respond to an infection, with special emphasis to SARS-CoV-2 infection. Knowing these factors will not only help to better understand the pathogenesis of COVID-19, but will also guide the design of effective therapies for personalized medicine based on sex differences.

Nanoantibodies: small molecules, big possibilities.

Camelids (camels, dromedaries, alpacas, llamas, and vicuñas) contain in their serum conventional heterodimeric antibodies as well as antibodies with no light chains (L) in their structure and composed of only heavy chains (H), called as HcAbs (heavy chain antibodies). Variable fragments derived from these antibodies, called as VHH or nanoantibodies (Nbs), have also been described. Since their discovery, Nbs have been widely used in the fields of research, diagnostics, and pharmacotherapy. Despite being approximately one-tenth the size of a conventional antibody, they retain similar specificity and affinity to conventional antibodies and are much easier to clone and manipulate. Their unique properties such as small size, high stability, strong antigen binding affinity, water solubility, and natural origin make them suitable for the development of biopharmaceuticals and nanoreagents. The present review aims to describe the main structural and biochemical characteristics of these antibodies and to provide an update on their applications in research, biotechnology, and medicine. For this purpose, an exhaustive search of the biomedical literature was performed in the following databases: Medline (PubMed), Google Scholar, and ScienceDirect. Meta-analyses, observational studies, review articles, and clinical guidelines were reviewed. Only original articles were considered to assess the quality of the evidence.