Exome and Tissue-Associated Microbiota as Predictive Markers of Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer

The clinical and pathological responses to multimodal neoadjuvant therapy in locally advanced rectal cancers (LARCs) remain unpredictable, and robust biomarkers are still lacking. Recent studies have shown that tumors present somatic molecular alterations related to better treatment response, and it is also clear that tumor-associated bacteria are modulators of chemotherapy and immunotherapy efficacy, therefore having implications for long-term survivorship and a good potential as the biomarkers of outcome. Here, we performed whole exome sequencing and 16S ribosomal RNA (rRNA) amplicon sequencing from 44 pre-treatment LARC biopsies from Argentinian and Brazilian patients, treated with neoadjuvant chemoradiotherapy or total neoadjuvant treatment, searching for predictive biomarkers of response (responders, n = 17; non-responders, n = 27). In general, the somatic landscape of LARC was not capable to predict a response; however, a significant enrichment in mutational signature SBS5 was observed in non-responders (p = 0.0021), as well as the co-occurrence of APC and FAT4 mutations (p < 0.05). Microbiota studies revealed a similar alpha and beta diversity of bacteria between response groups. Yet, the linear discriminant analysis (LDA) of effect size indicated an enrichment of Hungatella, Flavonifractor, and Methanosphaera (LDA score ≥3) in the pre-treatment biopsies of responders, while non-responders had a higher abundance of Enhydrobacter, Paraprevotella (LDA score ≥3) and Finegoldia (LDA score ≥4). Altogether, the evaluation of these biomarkers in pre-treatment biopsies could eventually predict a neoadjuvant treatment response, while in post-treatment samples, it could help in guiding non-operative treatment strategies.Fil: Takenaka, Isabella Kuniko T. M.. No especifíca;Fil: Bartelli, Thais F.. No especifíca;Fil: Defelicibus, Alexandre. No especifíca;Fil: Sendoya, Juan Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Golubicki, Mariano. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Robbio, Juan. No especifíca;Fil: Serpa, Marianna S.. No especifíca;Fil: Branco, Gabriela P.. No especifíca;Fil: Santos, Luana B. C.. No especifíca;Fil: Claro, Laura C. L.. No especifíca;Fil: Oliveira dos Santos, Gabriel. No especifíca;Fil: Kupper, Bruna E. C.. No especifíca;Fil: da Silva, Israel T.. No especifíca;Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: de Mello, Celso A. L.. No especifíca;Fil: Riechelmann, Rachel P.. No especifíca;Fil: Dias Neto, Emmanuel. Universidade de Sao Paulo; BrasilFil: Iseas, Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Aguiar, Samuel. No especifíca;Fil: Nunes, Diana Noronha. No especifíca

Assessment of the risk of burnout and its associated factors in healthcare professionals during the COVID-19 pandemic: A prospective cohort study

IntroductionThe COVID-19 pandemic resulted in tremendous physical and psychological pressure on healthcare professionals, especially on those working in intensive care units (ICUs) and Emergency Departments (EDs). The present study intended to characterize the profile of these professionals which is associated with burnout and determine the potential predictors of such condition.MethodsA Prospective cohort study was carried out in a tertiary hospital between March 2020 and March 2021, in Salvador, Brazil. A standardized and validated version of the Oldenburg Burnout inventory (OLBI) was applied to assess risk of burnout together with data forms designed to collect information on sociodemographic characteristics and religious beliefs. ICU and ED healthcare professionals were evaluated during off-hours at two distinct periods of the COVID-19 pandemic, in 2020 and in 2021. Differences in the results obtained from each study participant between the timepoints were compared. A binary logistic regression analysis was performed to identify the predictors of burnout development independent of other confounding factors.ResultsSeventy-seven healthcare professionals with a median age of 33 (interquartile range [IQR]: 31–37.5) years and predominantly female (72.7%; n = 56) were enrolled. There were 62 professionals at risk of developing burnout through the OLBI. Those had a median age of 33 (IQR: 31–37) and female predominance (71%, n = 44). Disengagement and burnout were the only features which frequencies significantly changed over time, with increasing detection at the latest timepoint. Alcohol consumption was found to be an important risk factor for burnout development [adjusted odds ratio (aOR): 10.8 (95% CI: 1.8–64.2)]. Importantly, working in the ICU [aOR: 0.04 (95%CI: 0.01–0.32)] and the habit of praying daily [aOR: 0.07 (95%CI: 0.01–0.41)] were characteristics linked to reduced odds of burnout.DiscussionDisengagement substantially increased during the COVID-19 pandemic in healthcare professionals. Alcohol consumption favors the onset of burnout whereas habit of praying daily and working in the ICU are protective against such outcome. Institutional policies aimed at minimizing etilism may positively impact mental health of these professionals

Observational study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers - protocol study

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) is a respiratory disease characterized by the collapse of the extrathoracic airway and has important social implications related to accidents and cardiovascular risk. The main objective of the present study was to investigate whether the drop in expiratory flow and the volume expired in 0.2 s during the application of negative expiratory pressure (NEP) are associated with the presence and severity of OSA in a population of professional interstate bus drivers who travel medium and long distances.</p> <p>Methods/Design</p> <p>An observational, analytic study will be carried out involving adult male subjects of an interstate bus company. Those who agree to participate will undergo a detailed patient history, physical examination involving determination of blood pressure, anthropometric data, circumference measurements (hips, waist and neck), tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep apnea and excessive daytime sleepiness will be administered. Data acquisition will be completely anonymous. Following the medical examination, the participants will perform a spirometry, NEP test and standard overnight polysomnography. The NEP test is performed through the administration of negative pressure at the mouth during expiration. This is a practical test performed while awake and requires little cooperation from the subject. In the absence of expiratory flow limitation, the increase in the pressure gradient between the alveoli and open upper airway caused by NEP results in an increase in expiratory flow.</p> <p>Discussion</p> <p>Despite the abundance of scientific evidence, OSA is still underdiagnosed in the general population. In addition, diagnostic procedures are expensive, and predictive criteria are still unsatisfactory. Because increased upper airway collapsibility is one of the main determinants of OSA, the response to the application of NEP could be a predictor of this disorder. With the enrollment of this study protocol, the expectation is to encounter predictive NEP values for different degrees of OSA in order to contribute toward an early diagnosis of this condition and reduce its impact and complications among commercial interstate bus drivers.</p> <p>Trial registration</p> <p><it>Registro Brasileiro de Ensaios Clinicos </it>(local acronym RBEC) [Internet]: Rio de Janeiro (RJ): <it>Instituto de Informaçao Cientifica e Tecnologica em Saude </it>(Brazil); 2010 - Identifier RBR-7dq5xx. Cross-sectional study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers; 2011 May 31 [7 pages]. Available from <url>http://www.ensaiosclinicos.gov.br/rg/RBR-7dq5xx/</url>.</p

Sleep study, respiratory mechanics, chemosensitive response and quality of life in morbidly obese patients undergoing bariatric surgery: a prospective, randomized, controlled trial

<p>Abstract</p> <p>Background</p> <p>Obesity is a major public health problem in both developed and developing countries alike and leads to a series of changes in respiratory physiology. There is a strong correlation between obesity and cardiopulmonary sleep disorders. Weight loss among such patients leads to a reduction in these alterations in respiratory physiology, but clinical treatment is not effective for a long period of time. Thus, bariatric surgery is a viable option.</p> <p>Methods/Design</p> <p>The present study involves patients with morbid obesity (BMI of 40 kg/m²or 35 kg/m²to 39.9 kg/m²with comorbidities), candidates for bariatric surgery, screened at the Santa Casa de Misericórdia Hospital in the city of Sao Paulo (Brazil). The inclusion criteria are grade III morbid obesity, an indication for bariatric surgery, agreement to participate in the study and a signed term of informed consent. The exclusion criteria are BMI above 55 kg/m², clinically significant or unstable mental health concerns, an unrealistic postoperative target weight and/or unrealistic expectations of surgical treatment. Bariatric surgery candidates who meet the inclusion criteria will be referred to Santa Casa de Misericórdia Hospital and will be reviewed again 30, 90 and 360 days following surgery. Data collection will involve patient records, personal data collection, objective assessment of HR, BP, neck circumference, chest and abdomen, collection and analysis of clinical preoperative findings, polysomnography, pulmonary function test and a questionnaire on sleepiness.</p> <p>Discussion</p> <p>This paper describes a randomised controlled trial of morbidly obese patients. Polysomnography, respiratory mechanics, chemosensitive response and quality of life will be assessed in patients undergoing or not undergoing bariatric surgery.</p> <p>Trial Registration</p> <p>The protocol for this study is registered with the Brazilian Registry of Clinical Trials - ReBEC (RBR-9k9hhv).</p

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

STING regulates metabolic reprogramming in macrophages via HIF-1α during Brucella infection.

Macrophages metabolic reprogramming in response to microbial insults is a major determinant of pathogen growth or containment. Here, we reveal a distinct mechanism by which stimulator of interferon genes (STING), a cytosolic sensor that regulates innate immune responses, contributes to an inflammatory M1-like macrophage profile upon Brucella abortus infection. This metabolic reprogramming is induced by STING-dependent stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), a global regulator of cellular metabolism and innate immune cell functions. HIF-1α stabilization reduces oxidative phosphorylation and increases glycolysis during infection with B. abortus and, likewise, enhances nitric oxide production, inflammasome activation and IL-1β release in infected macrophages. Furthermore, the induction of this inflammatory profile participates in the control of bacterial replication since absence of HIF-1α renders mice more susceptible to B. abortus infection. Mechanistically, activation of STING by B. abortus infection drives the production of mitochondrial reactive oxygen species (mROS) that ultimately influences HIF-1α stabilization. Moreover, STING increases the intracellular succinate concentration in infected macrophages, and succinate pretreatment induces HIF-1α stabilization and IL-1β release independently of its cognate receptor GPR91. Collectively, these data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during B. abortus infection that is orchestrated by STING via HIF-1α pathway and highlight the metabolic reprogramming of macrophages as a potential treatment strategy for bacterial infections

Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on the masticatory system and the impact on sleep variables in cerebral palsy patients: a randomized, five arms clinical trial

<p>Abstract</p> <p>Background</p> <p>Few studies demonstrate effectiveness of therapies for oral rehabilitation of patients with cerebral palsy (CP), given the difficulties in chewing, swallowing and speech, besides the intellectual, sensory and social limitations. Due to upper airway obstruction, they are also vulnerable to sleep disorders. This study aims to assess the sleep variables, through polysomnography, and masticatory dynamics, using electromiography, before and after neuromuscular electrical stimulation, associated or not with low power laser (Gallium Arsenide- Aluminun, =780 nm) and LED (= 660 nm) irradiation in CP patients.</p> <p>Methods/design</p> <p>50 patients with CP, both gender, aged between 19 and 60 years will be enrolled in this study. The inclusion criteria are: voluntary participation, patient with hemiparesis, quadriparesis or diparetic CP, with ability to understand and respond to verbal commands. The exclusion criteria are: patients undergoing/underwent orthodontic, functional maxillary orthopedic or botulinum toxin treatment. Polysomnographic and surface electromyographic exams on masseter, temporalis and suprahyoid will be carry out in all sample. Questionnaire assessing oral characteristics will be applied. The sample will be divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation; Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical stimulation and laser therapy and Group 5: neuromuscular electrical stimulation and LED therapy. All patients will be treated during 8 consecutive weeks. After treatment, polysomnographic and electromiographic exams will be collected again.</p> <p>Discussion</p> <p>This paper describes a five arm clinical trial assessing the examination of sleep quality and masticatory function in patients with CP under non-invasive therapies.</p> <p>Trial registration</p> <p>The protocol for this study is registered with the Brazilian Registry of Clinical Trials - ReBEC RBR-994XFS</p> <p>Descriptors</p> <p>Cerebral Palsy. Stomatognathic System. Electromyography. Transcutaneous Electric Nerve Stimulation. Phototherapy. Sleep Disorders. Polysomnography.</p