Effect of spatiotemporal variables on abundance, biting activity and parity of Nyssorhynchus darlingi (Diptera: Culicidae) in peri-Iquitos, Peru.

BACKGROUND: In malaria endemic regions of the Peruvian Amazon, rainfall together with river level and breeding site availability drive fluctuating vector mosquito abundance and human malaria cases, leading to temporal heterogeneity. The main variables influencing spatial transmission include location of communities, mosquito behaviour, land use/land cover, and human ecology/behaviour. The main objective was to evaluate seasonal and microgeographic biting behaviour of the malaria vector Nyssorhynchus (or Anopheles) darlingi in Amazonian Peru and to investigate effects of seasonality on malaria transmission. METHODS: We captured mosquitoes from 18:00 to 06:00 h using Human Landing Catch in two riverine (Lupuna, Santa Emilia) and two highway (El Triunfo, Nuevo Horizonte) communities indoors and outdoors from 8 houses per community, during the dry and rainy seasons from February 2016 to January 2017. We then estimated parity rate, daily survival and age of a portion of each collection of Ny. darlingi. All collected specimens of Ny. darlingi were tested for the presence of Plasmodium vivax or Plasmodium falciparum sporozoites using real-time PCR targeting the small subunit of the 18S rRNA. RESULTS: Abundance of Ny. darlingi varied across village, season, and biting behaviour (indoor vs outdoor), and was highly significant between rainy and dry seasons (p < 0.0001). Biting patterns differed, although not significantly, and persisted regardless of season, with peaks in highway communities at ~ 20:00 h in contrast to biting throughout the night (i.e., 18:00-06:00) in riverine communities. Of 3721 Ny. darlingi tested for Plasmodium, 23 (0.62%) were infected. We detected Plasmodium-infected Ny. darlingi in both community types and most (20/23) were captured outdoors during the rainy season; 17/23 before midnight. Seventeen Ny. darlingi were infected with P. vivax, and 6 with P. falciparum. No infected Ny. darlingi were captured during the dry season. Significantly higher rates of parity were detected in Ny. darlingi during the rainy season (average 64.69%) versus the dry season (average 36.91%) and by community, Lupuna, a riverine village, had the highest proportion of parous to nulliparous females during the rainy season. CONCLUSIONS: These data add a seasonal dimension to malaria transmission in peri-Iquitos, providing more evidence that, at least locally, the greatest risk of malaria transmission is outdoors during the rainy season mainly before midnight, irrespective of whether the community was located adjacent to the highway or along the river.

Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial.

INTRODUCTION: Seasonal malaria chemoprevention (SMC) involves repeated administrations of sulfadoxine-pyrimethamine plus amodiaquine to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. While highly impactful in reducing Plasmodium falciparum malaria burden in controlled research settings, the impact of SMC on infection prevalence is moderate in real-life settings. It remains unclear what drives this efficacy decay. Recently, the WHO widened the scope for SMC to target all vulnerable populations. The Ministry of Health (MoH) in Burkina Faso is considering extending SMC to children below 10 years old. We aim to assess the impact of SMC on clinical incidence and parasite prevalence and quantify the human infectious reservoir for malaria in this population. METHODS AND ANALYSIS: We will perform a cluster randomised trial in Saponé Health District, Burkina Faso, with three study arms comprising 62 clusters of three compounds: arm 1 (control): SMC in under 5-year-old children, implemented by the MoH without directly observed treatment (DOT) for the full course of SMC; arm 2 (intervention): SMC in under 5-year-old children, with DOT for the full course of SMC; arm 3 (intervention): SMC in under 10-year-old children, with DOT for the full course of SMC. The primary endpoint is parasite prevalence at the end of the malaria transmission season. Secondary endpoints include the impact of SMC on clinical incidence. Factors affecting SMC uptake, treatment adherence, drug concentrations, parasite resistance markers and transmission of parasites will be determined. ETHICS AND DISSEMINATION: The London School of Hygiene & Tropical Medicine's Ethics Committee (29193) and the Burkina Faso National Medical Ethics Committee (Deliberation No 2023-05-104) approved this study. The findings will be presented to the community; disease occurrence data and study outcomes will also be shared with the Burkina Faso MoH. Findings will be published irrespective of their results. TRIAL REGISTRATION NUMBER: NCT05878366.

Sexual-biased necroinflammation is revealed as a predictor of bevacizumab benefit in Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a highly malignant brain tumor that affects men more often than women. In addition, the former shows a poorer survival prognosis. To date the reason for this sex-specific aggressiveness remains unclear. Therefore, the aim of this study is to investigate tumor processes that explain these sex differences. METHODS: This was a retrospective study of GBM patients which was stratified according to sex. Cohort with 73 tumors were analyzed with immunohistochemistry, RNA-seq and RT-qPCR to characterize differences in vascular and immunological profiles. Transcriptomic profiling, GSEA and pathway enrichment analysis were used for discovery molecular pathways predominant in each group. We further investigated the therapeutic effect of Bevacizumab (VEGFA blocking antibody) in retrospective GBM cohort (36 tumors) based on sex differences. RESULTS: We found that under hypoxic tumor conditions, two distinct tumor immuno-angiogenic ecosystems develop linked to sex differences and ESR1 expression are generated. One of these subgroups, which includes male patients with low ESR1 expression, is characterized by vascular fragility associated with the appearance of regions of necrosis and high inflammation (called necroinflamed tumors). This male-specific tumor subtype shows high inflammation related to MDSC infiltration. Using this stratification, we identified a possible group of patients who could respond to bevacizumab (BVZ) and revealed a genetic signature that may find clinical applications as a predictor of those who may benefit most from this treatment. CONCLUSIONS: This study provides a stratification based on the sexual differences in GBM, which associates the poor prognosis with the presence of immunosuppressive myeloid cells in the necrotic areas. This new stratification could change the current prognosis of GBM and identifies those who respond to BVZ treatment.

Maternal and obstetric outcomes after Ex-Utero Intrapartum Treatment (EXIT): a single center experience.

BACKGROUND: The Ex-utero Intrapartum Treatment (EXIT) is a procedure developed to manage a range of fetal conditions, aiming to ensure the maintenance of neonatal airway and preserving the feto-placental circulation. Its goal is to enhance the neonatal ability to successfully transition and adapt to postnatal life, thereby reducing perinatal morbidity and mortality. However, EXIT has been associated with a high risk of maternal complications. This paper provides an overview of the indications and characteristics of the EXIT procedure, as well as the obstetric outcomes and maternal complications. METHODS: A retrospective analysis was conducted on a cohort of patients undergoing EXIT at our center between January 2007 and December 2022. Maternal outcomes, including demographic information, data related to the surgical procedure, surgical complications, and postoperative complications were analyzed. To assess the severity of the surgical complications, a modified Clavien-Dindo classification was used. Comparative analysis was performed by randomly selecting a sample from elective cesarean deliveries performed at our center. RESULTS: A total of 34 EXIT procedures were performed. According to the modified Clavien-Dindo classification, we observed no major complications, while minor maternal complications were present in 2.94% of cases. Compared to elective cesarean deliveries (n = 350), there were no significant differences in terms of maternal complications, highlighting the similarity observed in the mean decrease in postoperative hemoglobin (1.15 g/dL in EXIT vs. 1.2 g/dL in elective cesarean deliveries, p = 0.94). In EXIT group, there was a higher rate of polyhydramnios (26.47% vs 6.59%, p < 0.001), as well as the need for amnioreduction (14.71% vs 0%, p = 0.001) and preterm delivery (32.35% vs 6.02%, p = 0.001). There were no cases of endometritis, post-procedural fever, or abruptio placentae following EXIT. CONCLUSIONS: EXIT can be considered a safe procedure when performed under adequate conditions, including appropriate uterine access and proper anesthetic management. In our series, EXIT procedure was not associated with a higher incidence of maternal complications when compared to elective cesarean delivery. TRIAL REGISTRATION: Retrospectively registered.

Human Hemoglobin-Based Zinc-Air Battery in a Neutral Electrolyte.

The use of human hemoglobin (Hb) as a catalytic component of the air electrode in a primary zinc-air battery with a neutral electrolyte has been investigated. Three different electrode modifications, using the drop-casting method, with Hb and Nafion were first tested in a three-electrode cell, obtaining the best oxygen electroreduction (ORR) performance and long-term stability with a Hb plus Nafion (Hb-Nafion)-modified electrode. The latter Hb-Nafion-based air electrode provided a higher specific capacity and discharge time than the opposite order (Nafion-Hb).

The prelude to industrial whaling: identifying the targets of ancient European whaling using zooarchaeology and collagen mass-peptide fingerprinting.

Taxonomic identification of whale bones found during archaeological excavations is problematic due to their typically fragmented state. This difficulty limits understanding of both the past spatio-temporal distributions of whale populations and of possible early whaling activities. To overcome this challenge, we performed zooarchaeology by mass spectrometry on an unprecedented 719 archaeological and palaeontological specimens of probable whale bone from Atlantic European contexts, predominantly dating from ca 3500 BCE to the eighteenth century CE. The results show high numbers of Balaenidae (many probably North Atlantic right whale (Eubalaena glacialis)) and grey whale (Eschrichtius robustus) specimens, two taxa no longer present in the eastern North Atlantic. This discovery matches expectations regarding the past utilization of North Atlantic right whales, but was unanticipated for grey whales, which have hitherto rarely been identified in the European zooarchaeological record. Many of these specimens derive from contexts associated with mediaeval cultures frequently linked to whaling: the Basques, northern Spaniards, Normans, Flemish, Frisians, Anglo-Saxons and Scandinavians. This association raises the likelihood that early whaling impacted these taxa, contributing to their extirpation and extinction. Much lower numbers of other large cetacean taxa were identified, suggesting that what are now the most depleted whales were once those most frequently used.

How, when, and to what degree do people with alcohol dependence recover their psychological wellbeing and quality of life? The Madrid Recovery Project.

Introduction: The consensus on recovery from alcohol use disorder (AUD) has shifted toward encompassing psychological wellbeing and quality of life dimensions. However, few studies have explored the long-term recovery process and its dimensions, timing, styles, and modes. The aim of this study was to investigate the extent, timing, and process of psychological wellbeing and quality of life recovery in alcohol use disorder (AUD) patients, as well as the relationship with classic dimensions of AUD recovery. Method: A cross-sectional study has been carried out with 348 participants with AUD, in different abstinence periods (1 month-28 years), and 171 control subjects. Participants underwent a psychological evaluation, which included self-informed measures of psychological wellbeing, quality of life, negative emotionality, and coping strategies related to alcohol consumption avoidance. Statistical analysis included linear and non-linear regression models between psychological dimensions and maintenance of abstinence, as well as matching the scores of the sample with AUD to those of controls. Scatter plots were used to explore inflection points. In addition, mean comparison tests were performed between participants with AUD and controls and by gender. Results: In general, according to the regression models, there were pronounced increases in indices of wellbeing and coping strategies (and pronounced decreases in negative emotionality) during the first 5 years of abstinence, followed by less pronounced improvements. The matching of AUD subjects in wellbeing and negative emotionality indices with controls occurs at different times: (a) 1 year or less: physical health; (b) 1-4 years: psychological health; (c) 4-10 years: social relationships, wellbeing, and negative emotionality; and (d) more than 10 years: autonomy and self-acceptance. There are statistically significant differences by gender for the negative emotionality and physical health variables. Conclusion: Recovery from AUD is a long process that involves improvements in wellbeing and quality of life. Four stages can be described in this process, with the most pronounced changes occurring during the first 5 years of abstinence. However, AUD patients take more time to obtain similar scores to controls in several psychological dimensions.

Transcription and FACT facilitate the restoration of replication-coupled chromatin assembly defects.

Genome duplication occurs through the coordinated action of DNA replication and nucleosome assembly at replication forks. Defective nucleosome assembly causes DNA lesions by fork breakage that need to be repaired. In addition, it causes a loss of chromatin integrity. These chromatin alterations can be restored, even though the mechanisms are unknown. Here, we show that the process of chromatin restoration can deal with highly severe chromatin defects induced by the absence of the chaperones CAF1 and Rtt106 or a strong reduction in the pool of available histones, and that this process can be followed by analyzing the topoisomer distribution of the 2µ plasmid. Using this assay, we demonstrate that chromatin restoration is slow and independent of checkpoint activation, whereas it requires the action of transcription and the FACT complex. Therefore, cells are able to "repair" not only DNA lesions but also chromatin alterations associated with defective nucleosome assembly.

Maternal and Neonatal Outcomes After Ex-Utero Intrapartum Treatment for Congenital Diaphragmatic Hernia: A Case Series.

INTRODUCTION: Despite advances in neonatal intensive care, fetuses with congenital diaphragmatic hernia (CDH) remain to have a poor prognosis. Exclusive postnatal treatment is inadequate in patients with moderate CDH (observed than expected lung-to-head ratio [O/E LHR] 26-45%) and can lead to respiratory failure at birth, requiring extracorporeal membrane oxygenation in 75% of cases. An ex-utero intrapartum treatment (EXIT) procedure may be beneficial in these cases, improving the fetal-neonatal transition. MATERIAL AND METHODS: We review all pregnancies with fetal isolated left CDH with moderate O/E LHR delivered by EXIT in our center from January 2007 to December 2022. Maternal and neonatal variables were analyzed. As primary outcomes, we included neonatal survival and mortality rates, surgical and infectious complications, uterine scar dehiscence, and blood loss during EXIT. As secondary outcomes, we studied recurrences of the diaphragmatic defect, long-term evolution, subsequent pregnancies, and mode of delivery. RESULTS: A total of 14 patients were delivered by the EXIT procedure, with a neonatal survival rate of 85.7%. All these children had optimal physical and neurocognitive development and no pulmonary morbidity. We found no major complications and 7.1% of minor maternal complications. There were no cases of surgical wound infection or endometritis. The median decrease in hemoglobin during the EXIT procedure was 1.9 mg/dL, and only one case required postoperative transfusion. Two out of the 14 women became pregnant again, and both pregnancies were uneventful. CONCLUSIONS: In our series, the EXIT procedure allows for adequate airway management associated with a high neonatal survival rate in patients with moderate O/E LHR CDH, with a low rate of neonatal and maternal complications.

Gender bias in clinical trials of biological agents for migraine: A systematic review.

Migraine is considered one of the most disabling diseases. Currently, there are few studies on clinical migraine treatment based on sex-related differences, despite the important role of sex in migraine. Our aim was to evaluate gender bias in published clinical trials on monoclonal antibodies (erenumab, galcanezumab, fremanezumab and eptinezumab). We performed a systematic review of controlled clinical trials of erenumab, galcanezumab, fremanezumab and eptinezumab, searching the PubMed/MEDLINE database for articles published before December 2021. The search identified 760 articles, 25 of which met the inclusion criteria. Of all the patients included in these trials, 85.1% were women. Only one study had female lead authors. Two of the 25 studies included a sex-based analysis of the primary endpoint. None of the articles discussed the results separately for men and for women. The proportion of men recruited in trials is scarce and more studies are needed to guarantee the safety and tolerability of monoclonal antibodies used in male migraine. As observed in our study, despite the high number of women recruited, only 2 studies analysed the results separately by sex. Thus, a potential risk of gender bias was found in these clinical trials.

Anaplastic large cell lymphomas with the 6p25.3 rearrangement are a heterogeneous group of tumours with a diverse molecular background.

ALK-negative anaplastic large cell lymphoma (ALCL) cases with 6p25.3 rearrangement are characterized by peculiar morphological and immunohistochemical features compare to 6p25.3-negative ALK-negative ALCL cases. A subgroup of 6p25.3-positive ALK-negative ALCL cases show the t(6,7) (p25.3;q32.3) rearrangement. Aims: To analyse the differences between 6p25.3-rearranged cases with and without t(6,7) (p25.3;q32.3). Using RNA-sequencing we studied a series of 17 samples showing 6p25.3-rearrangement, identified by FISH, consisting of seven systemic and eight primary cutaneous cases including two examples of secondary skin involvement by systemic ALCL. RNA-sequencing exclusively detected a translocation involving a gene in the 6p25.3 region (either IRF4 or DUSP22) in 7/14 cases (50%). In six of these seven cases the partner proved to be the LINC-PINT region in chromosome 7, while an EXOC2::DUSP22 rearrangement was found in one case. All cases but one were primary cutaneous ALCLs. They all were CD3 positive and BCL2 negative, while most of them expressed p-STAT3. On the contrary, cases without the t(6,7) (p25.3;q32.3) were mainly systemic (71%, 5/7) against just two pcALCL. In general, they lose CD3 (50% positive) and p-STAT3 (25% positive) expression, being all of them BCL2 positive. Moreover, in 60% of them other gene fusions were found. At the transcriptional level, they were characterized by the overexpression of TCF3 (TCF7L1/E2A), DLL3, CD58 and BCL2 genes 75%(6/8) of pcALCL with 6p25.3 rearrangement featured the so-called "biphasic morphologic pattern, which was not found in cutaneous involvement from systemic ALCL. 83% (5/6) of the pcALCL cases with the "biphasic morphologic pattern" showed the t(6,7) (p25.3;q32.3) rearrangement. ALK-negative ALCL cases with 6p25.3 rearrangement are a subgroup of tumours that are heterogeneous with respect to the presence or absence of the t(6,7) (p25.3;q32.3) translocation.

Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators.

Glial-origin brain tumors, including glioblastomas (GBM), have one of the worst prognoses due to their rapid and fatal progression. From an oncological point of view, advances in complete surgical resection fail to eliminate the entire tumor and the remaining cells allow a rapid recurrence, which does not respond to traditional therapeutic treatments. Here, we have reviewed new immunotherapy strategies in association with the knowledge of the immune micro-environment. To understand the best lines for the future, we address the advances in the design of neoantigen vaccines and possible new immune modulators. Recently, the efficacy and availability of vaccine development with different formulations, especially liposome plus mRNA vaccines, has been observed. We believe that the application of new strategies used with mRNA vaccines in combination with personalized medicine (guided by different omic's strategies) could give good results in glioma therapy. In addition, a large part of the possible advances in new immunotherapy strategies focused on GBM may be key improving current therapies of immune checkpoint inhibitors (ICI), given the fact that this type of tumor has been highly refractory to ICI.

Consumption of ultra-processed foods is associated with depression, mesocorticolimbic volume, and inflammation.

BACKGROUND: The consumption of ultra-processed foods and drinks (UPF) has been associated with depression and inflammation and preclinical studies showed that some UPF components disrupt the amygdala-hippocampal complex. We combine diet, clinical and brain imaging data to investigate the relationship between the UPF consumption, depressive symptoms, and brain volumes in humans, considering interactions with obesity, and the mediation effect of inflammation biomarkers. METHODS: One-hundred fifty-two adults underwent diet, depressive symptoms, anatomic magnetic resonance imaging assessments and laboratory tests. Relationships between the % of UPF consumption (in grams) of the total diet, depressive symptoms, and gray matter brain volumes were explored using several adjusted regression models, and in interaction with the presence of obesity. Whether inflammatory biomarkers (i.e., white blood cell count, lipopolysaccharide-binding protein, c-reactive protein) mediate the previous associations was investigated using R mediation package. RESULTS: High UPF consumption was associated with higher depressive symptoms in all participants (ß = 0.178, CI = 0.008-0.261) and in those with obesity (ß = 0.214, CI = -0.004-0.333). Higher consumption was also associated with lower volumes in the posterior cingulate cortex and the left amygdala, which in the participants with obesity also encompassed the left ventral putamen and the dorsal frontal cortex. White blood count levels mediated the association between UPF consumption and depressive symptoms (p = 0.022). LIMITATIONS: The present study precludes any causal conclusions. CONCLUSIONS: UPF consumption is associated with depressive symptoms and lower volumes within the mesocorticolimbic brain network implicated in reward processes and conflict monitoring. Associations were partially dependent on obesity and white blood cell count.

Outcomes and bioethical implications of lymphadenectomy in mastectomized patients: Importance and indication of ultrasound-guided fine-needle aspiration biopsy / Resultados e implicaciones bioéticas de la linfadenectomía en pacientes mastectomizadas: Importancia y recomendación de biopsia por aspiración con aguja fina guiada por ecografía / Resultados e implicações bioéticas da linfadenectomia em pacientes mastectomizadas: Importância e recomendação da biópsia aspirativa com agulha fina guiada por ultrassom

Introduction: Lymph node involvement is the main prognostic factor in breast cancer. Mastectomized patients usually undergo lymphadenectomy (LA) of micrometastatic sentinel lymph nodes (SLNs) despite the evidence of AMAROS trial to replace this therapy with radiotherapy in select cases. Objective: Demonstrate the ability of ultrasonography to detect non-metastatic or micrometastatic SLNs. Materials and methods: 132 patients who underwent mastectomy were evaluated. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was indicated for suspicious lymph nodes. LA and SNL biopsy (SLNB) were performed in patients with positive and negative FNAB, respectively. LA was performed in FNAB positive or SLNB positive cases, except in the presence of isolated tumor cells and micrometastatic SLNs. The tumor burden after LA in patients with negative FNAB and positive SLNB was measured; the presence of two or fewer positive SLNs was considered a low burden. Results: Sensitivity of FNAB for detecting positive lymph nodes in patients with a high tumor burden was 93% and specificity was 84%. Positive (PPV) and negative predictive value (NPV) were 60% and 79%, respectively. Conclusions: LA could have been avoided in 90% of mastectomized patients with negative FNAB and a low tumor burden who met the AMAROS criteria with a high NPV (79%).

Introducción: La afectación ganglionar es el principal factor pronóstico en cáncer de seno. Generalmente, pacientes mastectomizadas se somenten a linfadenectomia (LA) de ganglios linfáticos centinela micrometastásicos (GLCs), a pesar de la evidencia del ensayo AMAROS en ciertos casos para reemplazarla con radioterapia. Objetivo: Demostrar la importancia de la ecografía para detectar GLCs no metastásicos o micrometastásicos. Materiales y métodos: Se evaluaron132 pacientes sometidas a mastectomía. Se recomendó biopsia aspirativa con aguja fina (BAAF) por ultrasonido para ganglios linfáticos sospechosos. Se realizó Biopsia LA y biopsia de GLCs (BGLC) en pacientes con BAAF positiva y negativa, respectivamente. En casos positivos de BAAF o BGLC se ejecutó LA, excepto en presencia de células tumorales aisladas y GLCs. Se evaluó la carga tumoral posterior a LA en pacientes con BAAF negativa y BGLC positiva. La presencia de dos o menos GLC positivos se consideró carga baja. Resultados: La sensibilidad de BAAF para detectar nódulos linfáticos positivos en pacientes con alta carga tumoral fue del 93%; la especificidad fue del 79%. Valores predictivos positivo (60%) y negativo (79%). Conclusiones: Se podría haber evitado LA en 90% de pacientes mastectomizadas con BAAF negativa y baja carga tumoral que cumplían criterios AMAROS con alto VPN (79%).

Introdução: O comprometimento dos gânglios é o principal fator prognóstico no câncer de mama. Geralmente, pacientes mastectomizadas são submetidas a linfadenectomia (LA) de gânglios linfáticos sentinelas de micrometástases (GLSs), apesar da evidência do estudo AMAROS em certos casos para substituí-la por radioterapia. Objetivo: Demonstrar a importância da ultrassonografia na detecção de GLSs não metastáticos ou micrometástase. Materiais e métodos: Foram avaliadas 132 pacientes submetidas à mastectomia. A biópsia aspirativa com agulha fina (BAAF) ultrassônica foi recomendada para gânglios linfáticos suspeitos. A biópsia LA e a biópsia do GLSs (BGLS) foram realizadas em pacientes com BAAF positivo e negativo, respectivamente. Nos casos positivos de BAAF ou BGLS, a LA foi realizada, exceto na presença de células tumorais isoladas e GLSs. A carga tumoral após a LA foi avaliada em pacientes com BAAF negativa e BGLS positiva. A presença de dois ou menos GLS positivos foi considerada carga baixa. Resultados: A sensibilidade do BAAF para detectar linfonodos positivos em pacientes com alta carga tumoral foi de 93%; a especificidade foi de 79%. Valores preditivos positivos (60%) e negativos (79%). Conclusões: a LA poderia ter sido evitada em 90% das pacientes mastectomizadas com BAAF negativa e baixa carga tumoral que preencheram os critérios AMAROS com alto VPN (79%).

Inguinal Sentinel Lymph Node in a Patient With Recurrent Breast Cancer.

ABSTRACT: Sentinel lymph node biopsy is the standard of care for axillary staging in early, clinically node-negative breast cancer. The lymphatic pathways could be altered after receiving axillary treatments such as radiation and/or axillary lymph node dissection. We report a case of inguinal and contralateral axilla SLNs in breast cancer recurrence.

Tauopathies: The Role of Tau in Cellular Crosstalk and Synaptic Dysfunctions.

Tauopathies are a group of neurodegenerative diseases among which are many of the most prevalent and with higher incidence worldwide, such as Alzheimer's disease (AD). According to the World Health Organization, this set of diseases will continue to increase their incidence, affecting millions of people by 2050. All of them are characterized by aberrant aggregation of tau protein in neurons and glia that are distributed in different brain regions according to their susceptibility. Numerous studies reveal that synaptic regulation not only has a neuronal component, but glia plays a fundamental role in it beyond its neuroinflammatory role. Despite this, it has not been emphasized how the glial inclusions of tau in this cell type directly affect this and many other essential functions, whose alterations have been related to the development of tauopathies. In this way, this review shows how tau inclusions in glia influence the synaptic dysfunctions that result in the cognitive symptoms characteristic of tauopathies. Thus, the mechanisms affected by inclusions in neurons, astrocytes, and oligodendrocytes are unraveled.

A Rare Case of Drug-induced Erectile Dysfunction with Adalimumab and Certolizumab Solved after Switch to Ustekinumab in a Crohn's Disease Patient.

BACKGROUND: Crohn Disease (CD) is an intestinal inflammatory condition characterized by a complex pathogenesis, with elevated levels of inflammatory cytokines. Adalimumab and certolizumab are two biologic drugs inhibiting TNF-α. OBJECTIVE: We report the first case of a probable relationship, according to Naranjo causality assessment score, between two consecutive treatments with TNF-α inhibitors and induced erectile dysfunction (ED), that disappeared after switching to another biologic drug (ustekinumab). CASE PRESENTATION: This case report describes a possible and important association of two TNF-α inhibitors (certolizumab and adalimumab) and ED in a male patient with CD, with resolution after switching to Ustekinumab (anti-interleukin 12 and 23 biologic drug). A 65 years old man experienced erectile dysfunction during treatment with an anti-TNF. The adverse effect disappeared after discontinuation of the drug. All necessary urologic exams were carried out. Adalimumab was replaced by certolizumab and sexual disfunction symptoms appeared again, improving typically at the end of treatment periods and getting worse with each new dose. RESULTS: Switching to ustekinumab lead to a resolution of the erectile dysfunction. CONCLUSION: We describe for the first time a sexual dysfunction possibly due to two similar anti TNF drugs and its resolution after the switch to another similar but different drug, highlighting the potential difference between biologic drugs.

Unlocking Hidden Awareness: Repurposing fMRI to Detect Levels of Consciousness.

Determining the state of consciousness in patients with disorders of consciousness is a challenging task because for someone to be deemed conscious, both wakefulness and awareness are required. Awareness has traditionally been assessed by examining physical responsiveness but in 2010, Monti et al. explored how using fMRI to measure brain activity in humans could help reclassify the state of consciousness in these patients. The findings, published in The New England Journal of Medicine, show that some brain regions are active when patients respond to an imagery or communication task. This is a seminal study because it demonstrates that patients who behaviourally appear to be in a vegetative or minimally conscious state may still have residual brain functions that would not be apparent from a clinical examination alone. Notably, it exemplified how fMRI can be repurposed as a communication tool for this subset of aware, but 'locked in', patients who appear unresponsive. From an educator's perspective, this paper is valuable because it is relevant to a broad audience, both introductory and advanced level undergraduate students. It introduces key concepts in cognitive and clinical neuroscience and encourages students to consider the connections between social issues and technology development in neuroscience. Finally, educators may use this paper to discuss and debate the nature of consciousness and the ethical implications that the use of fMRI for determining consciousness may have on medical ethics.