Enhancing Kidney Transplant Outcomes: The Impact of Living Donor Programs.

INTRODUCTION: The protocol for deceased donor kidney transplants has been standardised. The procedure for a living donor has peculiarities derived from the differences in the graft. When a living kidney donor program is implemented, changes occur in both the profile of the kidney transplant candidate and in the postoperative treatments. AIMS: To discover whether a living donor program influences the functional outcomes of kidney grafts in a longstanding classical deceased donor kidney transplant program and to identify the factors associated with transplant outcomes. METHODS: Retrospective observational multicentre study. SAMPLE: Kidney transplant patients in two urology referral centres for renal transplant in Spain between 1994 and 2019. Groups: TV (living transplant): patients given kidney transplants from living donors (n = 150); TCpre11 (deceased transplant previous to 2011): patients given kidney transplants from deceased donors before the living donor program was implemented (n = 650); and TCpost11 (deceased transplant after 2011): patients given kidney transplants from deceased donors after the living donor program was implemented (n = 500). RESULTS: Mean age was 55.75 years (18-80 years), higher in TCpre11. There were 493 female patients (37.92%) and 1007 male patients (62.08%). Mean body mass index (BMI) was 26.69 kg/m2 (17.50-42.78 kg/m2), higher in TCpre11. Mean ischemia time was 17.97 h (6-29 h), higher in TCpost11. Median duration of urethral catheter: 8 days (6-98 days), higher in TCpost11. Median duration of double-J ureteral stent: 58 days (24-180 days), higher in TCpost11. Pretransplant UTIs: 17.77%, higher in TCpre11 (25.69%) than in TV (12%), higher in TV (12%) than TCpost11 (9.2%), and higher in TCpre11 (25.69%) than TCpost11 (9.2%). Acute renal rejection in 9.33% of TV, 14.77% of TCpre11, and 9.8% of TCpost11. Multivariate analysis: TCpost11 featured higher BMI, more smoking, and chronic renal failure progression time. Lower use of nonantibiotic prophylaxis to prevent recurrent urinary tract infections, increased duration of urethral catheters due to obstructive problems, and favoured deterioration of kidney function was observed in the deceased donor program. The living donor (LD) program had a strong influence on deceased donor transplants in the prelysis phase. Implementation of a LD program was associated with a decrease in the likelihood of acute rejection in TCpost11 and an increase in the tendency towards normal kidney function. CONCLUSIONS: Implementing living donor transplant programs affects functional outcomes in deceased donor transplants, reducing the probability of acute rejection and increasing the tendency towards normal kidney function. Preventing recurrent urinary tract infections with measures other than antibiotics, smoking cessation, delaying the removal of the double-J stent from the graft, and pre-emptive transplant (transplant prior to dialysis) are associated with improved renal function of the graft.

Impact of Pleural Lavage Cytology Positivity on Early Recurrence After Surgery for Non-Small Cell Lung Cancer.

OBJECTIVE: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). METHODS: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. RESULTS: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06-2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04-2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14-2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27-3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25-16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25-5.36, p<0.001). CONCLUSIONS: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.

The relationship between sperm nuclear DNA fragmentation, mitochondrial DNA fragmentation, and copy number in normal and abnormal human ejaculates.

BACKGROUND: While it is common to clinically evaluate sperm nuclear DNA fragmentation, less attention has been given to sperm mitochondrial DNA. Recently, a digital PCR assay has allowed accurate estimation of the proportion of fragmented mtDNA molecules and relative copy number. OBJECTIVES: To determine the correlation of classical sperm parameters, average mtDNA copies per spermatozoon and the level of mtDNA fragmentation (SDF-mtDNA) to that of nuclear DNA fragmentation (SDF-nDNA), measured as the proportion of global, single-strand DNA (SDF-SSBs) and double-strand DNA breaks (SDF-DSBs). To determine whether the level of nuclear and mitochondrial DNA fragmentation and/or copy number can differentiate normozoospermic from non-normozoospermic samples. MATERIALS AND METHODS: Ejaculates from 29 normozoospermic and 43 non-normozoospermic were evaluated. SDF was determined using the sperm chromatin dispersion assay. mtDNA copy number and SDF-mtDNA were analyzed using digital PCR assays. RESULTS: Relative mtDNA copy increased as sperm concentration or motility decreased, or abnormal morphology increased. Unlike SDF-mtDNA, mtDNA copy number was not correlated with SDF-nDNA. SDF-mtDNA increased as the concentration or proportion of non-vital sperm increased; the higher the mtDNA copy number, the lower the level of fragmentation. Non-normozoospermic samples showed double the level of SDF-nDNA compared to normozoospermic (median 25.00 vs. 13.67). mtDNA copy number per spermatozoon was 3× higher in non-normozoospermic ejaculates (median 16.06 vs. 4.99). Although logistic regression revealed SDF-Global and mtDNA copy number as independent risk factors for non-normozoospermia, when SDF-Global and mtDNA copy number were combined, ROC curve analysis resulted in an even stronger discriminatory ability for predicting the probability of non-normozoospermia (AUC = 0.85, 95% CI 0.76-0.94, p < 0.001). CONCLUSION: High-quality ejaculates show lower nuclear SDF and retain less mtDNA copies, with approximately half of them fragmented, so that the absolute number of non-fragmented mtDNA molecules per spermatozoon is extremely low.

Addendum to: The relationship between sperm nuclear DNA fragmentation, mitochondrial DNA fragmentation and copy number in normal and abnormal human ejaculates.

BACKGROUND: While the kinetics of human sperm nuclear DNA fragmentation (SDF-nDNA) following ejaculation have been described, the dynamics and relationships of mitochondrial DNA copy number per spermatozoon (mtDNAcn) and fragmentation (SDF-mtDNA) remain unexplored. OBJECTIVES: To compare post-ejaculatory kinetics of mtDNAcn, SDF-mtDNA and SDF-nDNA, global, single-strand DNA breaks (SDF-SSBs) and double-strand DNA breaks (SDF-DSBs) in normozoospermic and non-normozoospermic samples. MATERIALS AND METHODS: 28 normozoospermic and 43 non-normozoospermic ejaculates were evaluated at 0, 6, 24 and 48 h of incubation in vitro. SDF-nDNA was determined by sperm chromatin dispersion (SCD) assays. mtDNAcn and SDF-mtDNA were analysed by dPCR. RESULTS: SDF-nDNA-global values increased as a consequence of quadratic SDF-SSBs and linear SDF-DSBs kinetics. Non-normozoospermic samples showed a slower SDF-global rate between 6-24 h, due to lesser SSBs production. Regarding SDF-DSBs, non-normozoospermic samples exhibited a faster initial increase rate, followed by a slower final increment. The mtDNAcn median value decreased linearly, being 3.2× higher in non-normozoospermics at all time points; mtDNAcn in both cohorts reduced to half of the baseline by 48 h. mtDNAcn was identified as a risk factor for discriminating non-normozoospermia, a finding that was further strengthen when combined with SDF-Global or SDF-DSBs values. SDF-mtDNA frequencies were identical, increasing over time correspondingly in both cohorts. The mtDNA fragmentation rate was initially fast, decreasing progressively with time for both cohorts; half of the initially unfragmented copies were fragmented after 48 h. Rates of mtDNAcn loss and SDF-mtDNA increase were only marginally correlated with the rates of nuclear fragmentation. CONCLUSION: mtDNA fragmentation and loss occur post ejaculation. Their dynamics are likely to be associated with different and/or uncoupled mechanisms to that which cause nuclear DNA fragmentation. Our results indicate that while mtDNA fragmentation is not influenced by the sperm quality, the number of copies of sperm mtDNAcn can potentially serve as a risk factor for predicting non-normozoospermia.

Hospitalization burden related to herpes zoster infection during the COVID-19 pandemic in Spain (2020-2021).

Varicella-Zoster Virus (VZV) belongs to the family Herpesviridae. Herpes zoster (HZ) is caused by reactivation of latent VZV. It is associated with risk factors such as immunosenescence, immunosuppressive pathologies and pharmacological treatments. Patients with these risk factors are more likely to be hospitalized. Increases in HZ hospitalizations have been reported in many countries in recent years. The objective of this study is to estimate hospitalization rates, mortality rates and costs due to HZ during the worst years of the COVID-19 pandemic in Spain (2020-2021). This is a descriptive study based on an analysis of information from the Minimum Basic Dataset and coded according to the Spanish version of the 10th International Classification of Diseases (ICD-10-CM). Hospitalization, mortality and case-fatality rates, and median length of hospitalization were calculated.. The hospitalization rate was 14.4 cases per 100,000 inhabitants, and the mortality rate was 1.3 cases per 100,000 inhabitants. Both increased considerably with age. In this time period, 92.3% of the registered cases were people over 50 years of age. Nevertheless, during the COVID-19 pandemic period, hospitalization rate decreased and the mortality rate increased from previous years. HZ hospitalization and mortality rates are relevant issues in the public health of older people. It is highly recommended to evaluate new vaccination strategies against VZV to include the HZ vaccine for health care for elderly people, as well as to reduce the disease burden and associated risk factors. The estimation of HZ disease hospitalization costs were €100,433,904.

The Spanish Scientific Societies before the ESC 2021 guidelines on vascular disease prevention: Generalizing the measurement of albuminuria to identify vascular risk and prevent vascular disease.

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.

[Surgical management of primary spontaneous pneumothorax. A national survey of the Emerging Thoracic Surgery Group of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR)]. / Manejo quirúrgico del neumotórax espontáneo primario. Encuesta nacional del Grupo Emergente de Cirugía Torácica de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR).

Introduction: In February 2022, the Emerging Thoracic Surgery Group of the Spanish Society of Pneumology and Thoracic Surgery initiated a multicenter study on the surgical management of primary spontaneous pneumothorax (PSP). As a preliminary step, this survey was developed with the aim of finding out the current situation in our country to specify and direct this project. Method: A descriptive study was carried out based on the results of this survey launched through the Google Docs® platform. The survey was sent to all active national thoracic surgeons, a total of 319. It consisted of 20 questions including demographic, surgical and follow-up data. Results: We obtained 124 responses (39% of all specialists and doctors in training in the national territory). The most consistent indications were: homolateral recurrence for 124 (100%), lack of resolution of the episode for 120 (96.7%), risk professions for 104 (84%) and bilateral pneumothorax for 93 (75%). The approach of choice for 100% of respondents was videothoracoscopy. Of these, 96 contemplated pulmonary resection of obvious lesions (77%). Regarding the pleurodesis technique, pleural abrasion was the technique most used by 70 respondents (56.7%) while 49 (40%) performed chemical pleurodesis with talc either alone or in combination with mechanical pleurodesis. Conclusions: While there is some consistency in some aspects of surgical management of PSP, this survey makes evident the variability in pleurodesis techniques applied among surgeons in our country.

Identifying Hate Speech and Attribution of Responsibility: An Analysis of Simulated WhatsApp Conversations during the Pandemic.

BACKGROUND: During the COVID-19 pandemic, public confrontations between people who had agreed to be vaccinated and those who had not, highlighted the relevance of the deepening dissemination of violent and discriminatory expressions and determined a level of perception of hate discourses. METHOD: A cross-sectional observational study was carried out, based on an innovative methodology: simulations of WhatsApp conversations. In addition, the following variables were considered among others: level of empathy, personality traits and conflict resolution. RESULTS: The participants were 567 nursing students (413 females, 153 males and 1 person who did not identify with any gender). The results showed that, for the most part, the participants correctly identified hate speech, but were unable to discern the frame of reference. CONCLUSIONS: It is necessary to implement intervention strategies to minimize the impact of hate speech, which continues to be used on many levels to harass others, justify violence or undermine rights, generating an environment of prejudice and intolerance that encourages discrimination and violent attacks against certain individuals or collectives.

Invasive bacterial infection in children with fever and petechial rash in the emergency department: a national prospective observational study.

OBJECTIVE: To determine the incidence and clinical predictors of invasive bacterial infection (IBI) in well-appearing children who present to the emergency department (ED) with fever and petechiae. DESIGN: A prospective, observational, multicentre study was conducted in 18 hospitals between November 2017 and October 2019. PATIENTS: A total of 688 patients were recruited. MAIN OUTCOME MEASURES: The primary outcome was the presence of IBI. Clinical features and laboratory test results were described and related to the presence of IBI. RESULTS: Ten IBIs were found (1.5%), comprising eight cases of meningococcal disease and two of occult pneumococcal bacteraemia. Median age was 26.2 months (IQR 15.3-51.2). Blood samples were obtained from 575 patients (83.3%). Patients with an IBI had a shorter time from fever to ED visit (13.5 hours vs 24 hours) and between fever and rash onset (3.5 hours vs 24 hours). Values for absolute leucocyte count, total neutrophil count, C reactive protein and procalcitonin were significantly higher in patients with an IBI. Significantly fewer patients with a favourable clinical status while in the observation unit were found to have an IBI (2/408 patients, 0.5%) than when clinical status was unfavourable (3/18, 16.7%). CONCLUSIONS: The incidence of IBI among children with fever and petechial rash is lower than previously reported (1.5%). The time from fever to ED visit and to rash onset was shorter in patients with an IBI. Patients with a favourable clinical course during observation in the ED are at lower risk of IBI.

Clinical and microbiological characteristics of bacterial infections in patients with cirrhosis. A prospective cohort study from Argentina and Uruguay.

INTRODUCTION AND OBJECTIVES: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. MATERIALS AND METHODS: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. RESULTS: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. CONCLUSIONS: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).

Artículo especial por el Día Mundial del Riñón: Las sociedades científicas españolas ante la guía ESC 2021 de prevención de la enfermedad vascular: generalizar la medida de la albuminuria para identificar el riesgo vascular y prevenir la enfermedad vascular / The Spanish Scientific Societies before the ESC 2021 guidelines on vascular disease prevention: Generalising the measurement of albuminuria to identify vascular risk and prevent vascular disease

Las guías de 2021 sobre la prevención de la enfermedad vascular (EV) en la práctica clínica publicadas por la European Society of Cardiology (ESC) y apoyadas por otras 13 sociedades científicas europeas reconocen el papel clave de la detección de la enfermedad renal crónica (ERC) en la prevención de la EV. El riesgo vascular en la ERC se categoriza a partir de las medidas del filtrado glomerular estimado (FGe) y del cociente albúmina:creatinina en orina (ACRo). Así, la ERC moderada se asocia a un riesgo vascular alto y la ERC grave a un riesgo vascular muy alto, debiendo actuar en consecuencia desde el punto de vista terapéutico, sin que sea necesario aplicar otras puntuaciones de riesgo vascular cuando este ya es muy alto debido a la ERC. Es más, la ESC sitúa la medida del FGe y del ACRo en el inicio de la estimación del riesgo vascular y del algoritmo de decisión subsiguiente. A fin de optimizar la implementación de la guía 2021 de la ESC sobre la prevención de la EV en España, consideramos que: 1) El estudio de la orina para determinar la albuminuria mediante el ACRo debería formar parte de la rutina clínica al mismo nivel que el de la glucemia, la colesterolemia y la estimación del FG cuando estas se usan para tomar decisiones sobre el riesgo de EV. 2) Los servicios de salud públicos y privados españoles deberían disponer de los medios y recursos necesarios para implementar de forma óptima las Guías ESC 2021 de prevención de la EV en España, incluyendo la determinación del ACRo.(AU)

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies, recognise the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorised based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimise the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolaemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing. (AU)

New Perspective on Planar Inductive Sensors: Radio-Frequency Refractometry for Highly Sensitive Quantification of Magnetic Nanoparticles.

We demonstrate how resonant planar coils may be used as sensors to detect and quantify magnetic nanoparticles reliably. A coil's resonant frequency depends on the adjacent materials' magnetic permeability and electric permittivity. A small number of nanoparticles dispersed on a supporting matrix on top of a planar coil circuit may thus be quantified. Such nanoparticle detection has application detection to create new devices to assess biomedicine, food quality assurance, and environmental control challenges. We developed a mathematical model for the inductive sensor response at radio frequencies to obtain the nanoparticles' mass from the self-resonance frequency of the coil. In the model, the calibration parameters only depend on the refraction index of the material around the coil, not on the separate magnetic permeability and electric permittivity. The model compares favourably with three-dimensional electromagnetic simulations and independent experimental measurements. The sensor can be scaled and automated in portable devices to measure small quantities of nanoparticles at a low cost. The resonant sensor combined with the mathematical model is a significant improvement over simple inductive sensors, which operate at smaller frequencies and do not have the required sensitivity, and oscillator-based inductive sensors, which focus on just magnetic permeability.

Robotic versus Laparoscopic Partial Nephrectomy in the New Era: Systematic Review.

(1) Background: In recent years there have been advances in imaging techniques, in addition to progress in the surgery of renal tumors directed towards minimally invasive techniques. Thus, nephron-sparing surgery has become the gold standard for the treatment of T1 renal masses. The aim of this study is to investigate the benefits of robotic partial nephrectomy in comparison with laparoscopic nephrectomy. (2) Methods: We performed a systematic review according to the PRISMA criteria during September 2022. We included clinical trials, and cohort and case-control studies published between 2000 and 2022. This comprised studies performed in adult patients with T1 renal cancer and studies comparing robotic with open and laparoscopic partial nephrectomy. A risk of bias assessment was performed according to the Newcastle-Ottawa scale. (3) Results: We observed lower hot ischemia times in the robotic surgery groups, although at the cost of an increase in total operative time, without appreciating the differences in terms of serious surgical complications (Clavien III-V). (4) Conclusions: Robotic partial nephrectomy is a safe procedure, with a shorter learning curve than laparoscopic surgery and with all the benefits of minimally invasive surgery.

Fiordo / Fjord

Estas historias de la LIBRETA DE VIAJE DEL MÉDICO DE FAMILIA, que forman una biblioteca del médico caminante o viajero emocional, son hojas sueltas en las que se escribe sobre paisajes y emociones; son un atlas de geografía emocional. La evocación de un paisaje ante la asistencia a un paciente —montañas, ríos, valles, playas, mares, desiertos, mesetas, islas, pantanos, cascadas, dunas, bosques, salinas, lagos, etc.—, con las sensaciones sentidas por el médico, de calor, frescor, humedad, dificultad, agobio, serenidad, inmensidad, soledad, etc. No es un diario, solo una libreta de apuntes con las vivencias del médico sobre los patrones y procesos de la consulta en un cierto caso clínico, que, a su vez, puede ilustrar un prototipo de esa clase de casos.(AU)

These stories of THE FAMILY PHYSICIAN’S TRAVEL NOTEBOOK, which comprise a library of the nomadic doctor or emotional traveller, are loose-leaf pages with writings about landscapes and emotions. They are an emotional geography atlas. The suggestion of a landscape before treating a patient –mountains, rivers, valleys, beaches, seas, deserts, plateaus, islands, swamps, waterfalls, dunes, forests, salt marshes, lakes, etc.-, with the sensations felt by the doctor -heat, coolness, humidity, hardship, stress, serenity, vastness, loneliness, etc. It is not a journal, only a notebook with the physician’s experiences about the patterns and processes of consultation in a particular case study, which in turn may illustrate a prototype for these types of cases.(AU)

Bacterial DNase activity as a putative inductor of sperm DNA fragmentation in infected bull frozen-thawed semen samples.

The aim of this study was to investigate the relationship between DNase activity associated with bacterial contamination of incubated bovine frozen-thawed spermatozoa and elevated sperm DNA fragmentation. Electrophoresis analysis of plasmid PBR322 incubated for 30 min at 37 °C with the supernatant of the diluent of frozen-thawed centrifuged bovine semen straws infected with bacteria showed clear evidence of DNase activity when compared to plasmid incubated in similarly prepared non-infected bovine diluent supernatant (Experiment 1). This DNase activity was subsequently found to be time dependent (0-60 min) and its activity prevented in the presence of EDTA (10 and 20 mM; Experiment 2). Semen straws infected (n = 10) and not infected (n = 10) with bacteria where incubated at 37 °C for up to 48h post-thaw. Semen infected with bacteria showed an exponential increase in bacterial growth and a corresponding increase in sperm DNA fragmentation. Non-infected semen samples showed no change in the incidence of sperm DNA fragmentation over the same period of incubation (Experiment 3). Our experiments reinforce the idea that exogenous DNases present in the semen should be considered as one of the primary contributing causes of sperm DNA fragmentation post ejaculation. In the case of the bull, post-thaw incubation of commercial straws contaminated with bacteria, resulted in increased levels of sperm DNA fragmentation, most likely associated with DNase activity (potentially restriction endonucleases) derived from the bacteria. Such adverse changes in sperm DNA fragmentation, as described here in vitro, may be also operative after insemination in the female reproductive tract (in vivo) and highlight the importance of implementing high levels of hygiene practice during semen processing, especially in light of future trends of bacterial resistance to the common antibiotics used in semen diluents.

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.

Renal Failure Management in Patients with Metastatic Renal Cancer Receiving Nivolumab: Evaluation from Two Points of View.

INTRODUCTION: Immunotherapy is recommended as category 1 in first-line treatment in metastatic renal cancer (mRC), however the evidence on the management of toxicities in patients with chronic renal failure is limited. Description of the Cases: Case 1: Patient with mRC and renal failure on hemodialysis. After 25 months of treatment with Nivolumab, he presented a partial response, without toxicities. Case 2: Patient with mRC undergoing treatment with Nivolumab-Ipilimumab, who after 6 cycles was admitted for acute renal failure, compatible with grade 4 nephrotoxicity, requiring definitive suspension of treatment, corticosteroid therapy and hemodialysis. CONCLUSIONS: Nivolumab is a safe and effective therapy in hemodialysis patients, not increasing adverse events, nor requiring dose adjustment. Immunotherapy nephrotoxicity must be adequately managed in daily clinical practice in an interdisciplinary way with the nephrologist.

A meta-analysis indicates that the regulation of cell motility is a non-intrinsic function of chemoattractant receptors that is governed independently of directional sensing.

Chemoattraction, defined as the migration of a cell toward a source of a chemical gradient, is controlled by chemoattractant receptors. Chemoattraction involves two basic activities, namely, directional sensing, a molecular mechanism that detects the direction of a source of chemoattractant, and actin-based motility, which allows the migration of a cell towards it. Current models assume first, that chemoattractant receptors govern both directional sensing and motility (most commonly inducing an increase in the migratory speed of the cells, i.e. chemokinesis), and, second, that the signaling pathways controlling both activities are intertwined. We performed a meta-analysis to reassess these two points. From this study emerge two main findings. First, although many chemoattractant receptors govern directional sensing, there are also receptors that do not regulate cell motility, suggesting that is the ability to control directional sensing, not motility, that best defines a chemoattractant receptor. Second, multiple experimental data suggest that receptor-controlled directional sensing and motility can be controlled independently. We hypothesize that this independence may be based on the existence of separated signalling modules that selectively govern directional sensing and motility in chemotactic cells. Together, the information gathered can be useful to update current models representing the signalling from chemoattractant receptors. The new models may facilitate the development of strategies for a more effective pharmacological modulation of chemoattractant receptor-controlled chemoattraction in health and disease.