Valence opponency in peripheral olfactory processing.

A hallmark of complex sensory systems is the organization of neurons into functionally meaningful maps, which allow for comparison and contrast of parallel inputs via lateral inhibition. However, it is unclear whether such a map exists in olfaction. Here, we address this question by determining the organizing principle underlying the stereotyped pairing of olfactory receptor neurons (ORNs) in Drosophila sensory hairs, wherein compartmentalized neurons inhibit each other via ephaptic coupling. Systematic behavioral assays reveal that most paired ORNs antagonistically regulate the same type of behavior. Such valence opponency is relevant in critical behavioral contexts including place preference, egg laying, and courtship. Odor-mixture experiments show that ephaptic inhibition provides a peripheral means for evaluating and shaping countervailing cues relayed to higher brain centers. Furthermore, computational modeling suggests that this organization likely contributes to processing ratio information in odor mixtures. This olfactory valence map may have evolved to swiftly process ethologically meaningful odor blends without involving costly synaptic computation.

Effective and alternative treatment of anastomotic leak after gastrojejunal bypass: endoluminal vacuum therapy.

Anastomotic leak (AL) after with Roux-en-Y gastric bypass (RYGB) has a morbidity rate to 53% and it can be potentially lethal (mortality rate from 0.5 to 10%). In these cases, surgery is usually a challenge, so in recent years minimally invasive endoscopic treatment is gaining ground. Endoluminal vacuum therapy (EVAC) is a promising treatment that is being used in esophagogastric and rectal surgery for the management of AL. We present the case of a patient on his 5th postoperative day of bariatric surgery (RYGB) with an acute abdomen. He was diagnosed of dehiscence of gastrojejunal anastomosis and he needed urgent surgery twice. Subsequently, in control CT, a new anastomotic leak is evidenced. However, given the clinical stability of the patient, it was decided to start EVAC type ESO-Sponge® placed by endoscopy. A total of 4 changes are made every 3-4 days with a total duration of treatment of 15 days. EVAC was removed when the defect presented a 1 mm sized.

Endoscopic vacuum therapy: management of upper gastrointestinal anastomotic leaks and esophageal perforations.

BACKGROUND AND STUDY AIMS: Upper gastrointestinal tract (UGT) leaks are associated with severe morbidity and mortality. Endoluminal vacuum (EVAC) therapy is a promising approach for repairing effectively these defects. Our study describes the results obtained from a series of cases treated with EVAC for the management of esophageal anastomotic (EA) leak following esophagectomy for cancer, gastroenteric (GE) anastomoses leak after bariatric surgery and esophageal perforation (EP). PATIENTS AND METHODS: We retrospectively analyzed ten patients who had an EA and GE anastomoses leaks and EP treated with EVAC. We described the results of the sample in terms of treatment failure, treatment duration, and number of EVAC replacements. RESULTS: Five patients underwent esophagectomy with neoadjuvant radio-chemotherapy, one patient underwent gastrojejunal bypass bariatric surgery and there were four EP. The median size of mucosal defects was 6,9 mm. The median duration of treatment was thirteen days with 3,6 interventions performed, every three to four days. Treatment success rate was 70%. Treatment failure was 30%: two patients required surgery and in one case an endoluminal prosthesis. CONCLUSIONS: EVAC therapy is an appropriate treatment for the management of postoperative fistulas in the UGT. Longer treatments are associated with neoadjuvant chemoradiotherapy and larger fistulas.

Giant sigmoid diverticulum.

Unlike acute diverticulitis, giant diverticulum larger than 4 cm is a rare entity with few cases described in the literature. We present a case of a 66-year-old male patient diagnosed with colonic diverticulosis. He presented to the emergency department with symptoms of acute abdomen and was diagnosed by CT scan with a 13x14 cm giant diverticulum showing signs of complication. Given the findings, an urgent surgical intervention was decided, and diverticulectomy at the diverticular neck was performed using an endostapler. The etiology of giant diverticula is related to a mechanism of one-way valve at the diverticular neck. Diagnosis poses a challenge as the clinical presentation is nonspecific. The imaging modality of choice is CT scan, which reveals a large cystic image dependent on the sigmoid colon. Definitive treatment is surgical, either by resecting the affected segment including the lesion or by performing a simple diverticulectomy in uncomplicated cases.

An uncommon cause of intestinal obstruction: Vanek's tumor.

Vanek's Tumor, also known as Inflammatory Fibroid Polyp (IFP), is a rare submucosal mesenchymal lesion with spindle cells and eosinophilic infiltration. Its etiology is unknown but linked to chronic cellular damage. IFP can develop in various gastrointestinal segments, most commonly in the gastric antrum (70%), small intestine (18-20%), colon, and rectum (4-7%). IFP are usually symptomless and are often found incidentally during colonoscopies or gastroscopies. Most cases can be treated with simple endoscopic resection. In rare cases where larger lesions over 1 cm are identified through endoscopic ultrasound without deeper layer involvement, submucosal endoscopic dissection can be done with good outcomes and minimal risk. Some polyps may cause dyspeptic, hemorrhagic, or obstructive symptoms based on size and location. We report a case of a 56-year-old patient with a 24-hour history of obstructive symptoms, including bowel cessation and vomiting. The patient also had abdominal pain and gradual weight loss over the past two months. Notably, the patient had a prior diagnosis of Crohn's disease 12 years ago, without treatment or continuous medical monitoring.

Conversational avoidance during existential interviews with patients with progressive illness.

We examined patterns of avoidance when existential emotional topics were raised during conversations with patients with pulmonary arterial hypertension (PAH), an incurable life-limiting disease. 30 adult outpatients with PAH were recruited for a 20 to 60-minute interview about their illness experience. Qualitative content analysis was used to identify avoidance strategies that patients employed. Participants averaged 58 years in age (SD = 18), 77% were female, and mean length of illness was 6.3 years (SD = 5.3). We found four avoidance strategies: (1) Reversal, when individuals would begin discussing a negative concern and then backtrack to more positive sentiments; (2) Diversion for when patients would sidetrack the conversation to a different and less uncomfortable topic; (3) Diminishment for when a concern is raised and then made to seem unimportant; and (4) Obstruction, when patients refuse to discuss a concern further. Exploration of existential concerns can elicit distress but may be necessary to promote adaptation to progressive illness and to the foreseeable challenges that may affect the sense of life meaning and value. By recognizing when existential concerns may be present but not adequately discussed, clinicians may be better able to assist patients to cope and prepare for the future.

Predator swamping reduces predation risk during nocturnal migration of juvenile salmon in a high-mortality landscape.

Animal migrations are costly and are often characterized by high predation risk for individuals. Three of the most oft-assumed mechanisms for reducing risk for migrants are swamping predators with high densities, specific timing of migrations and increased body size. Assessing the relative importance of these mechanisms in reducing predation risk particularly for migrants is generally lacking due to the difficulties in tracking the fate of individuals and population-level characteristics simultaneously. We used acoustic telemetry to track migration behaviour and survival of juvenile sockeye salmon (Oncorhynchus nerka) smolts released over a wide range of conspecific outmigration densities in a river associated with poor survival. The landscape was indeed high risk; smolt survival was poor (˜68%) over 13·5 km of river examined even though migration was rapid (generally <48 h). Our results demonstrate that smolts largely employ swamping of predators to reduce predation risk. Increased densities of co-migrant conspecifics dramatically improved survival of smolts. The strong propensity for nocturnal migration resulted in smolts pausing downstream movements until the next nightfall, greatly increasing relative migration durations for smolts that could not traverse the study area in a single night. Smolt size did not appear to impact predation risk, potentially due to unique characteristics of the system or our inability to tag the entire size range of outmigrants. Movement behaviours were important in traversing this high-risk landscape and provide rare evidence for swamping to effectively reduce individual predation risk.

Regulation of endothelin-converting enzyme-1 (ECE-1) by the calcimimetic R-568.

Although calcimimetics were developed to block parathyroid hormone synthesis, some reports suggest that they may also reduce blood pressure by unknown mechanisms. Calcimimetic-induced changes in the synthesis of endothelial vasoactive factors could be involved. Wistar rats were treated with the calcimimetic R-568, and systolic blood pressure (SBP) was registered with a tail-cuff sphygmomanometer, the content of endothelial nitric oxide synthase (eNOS) and endothelin-converting enzyme (ECE-1) in tissue was evaluated by immunohistochemistry and Western blot, circulating levels of endothelin-1 (ET-1) were measured by ELISA. R-568 reduced SBP and circulating levels of ET-1, without changes in eNOS expression. In contrast, R-568 increased the lung and vascular content of ECE-1. In order to analyze the mechanisms involved, we studied the effect of R-568 on human endothelial cells. R-568 did not modify neither eNOS protein content nor pre-pro-ET-1 mRNA expression, but increased ECE-1 protein content, and decreased ET-1 synthesis and ECE-1 activity. The inhibition of ECE-1 activity was very strong, similar to the classic ECE inhibitor phosphoramidon, the addition of exogenous zinc restored enzymatic activity. Moreover, the amount of zinc in immunoprecipitated ECE from R-568 treated cells was 3-fold less than in control cells. In conclusion, R-568 inhibits ECE by expelling zinc from the enzyme, with the subsequent decrease in enzymatic activity and reducing circulating levels of ET-1, which may be responsible for the lower SBP observed in R-568-treated rats. This descent would be partially compensated by the increased synthesis of the ECE-1 itself, and by other homeostatic mechanisms that regulate SBP.

High Hepatitis E Virus (HEV) Seroprevalence and No Evidence of HEV Viraemia in Vietnamese Blood Donors.

The prevalence of hepatitis E virus (HEV) in the Vietnamese population remains underestimated. The aim of the present study was to investigate the seroprevalence of HEV IgG/IgM antibodies and the presence of HEV RNA in blood donors as a part of epidemiological surveillance for transfusion-transmitted viruses. Serum samples from blood donors (n = 553) were analysed for markers of past (anti-HEV IgG) and recent/ongoing (anti-HEV IgM) HEV infections. In addition, all serum samples were subsequently tested for HEV RNA positivity. The overall prevalence of anti-HEV IgG was 26.8% (n = 148/553), while the seroprevalence of anti-HEV IgM was 0.5% (n = 3/553). Anti-HEV IgG seroprevalence in male and female donors was similar (27.1% and 25.5%, respectively). A higher risk of hepatitis E exposure was observed with increasing age. None of the blood donors were HEV RNA positive, and there was no evidence of HEV viraemia. Although the absence of HEV viraemia in blood donors from Northern Vietnam is encouraging, further epidemiological surveillance in other geographical regions is warranted to rule out transfusion-transmitted HEV.

Impact of COVID-19 Confinement on the Health-Related Habits of People at High Risk of Type 2 Diabetes.

The general lockdown decreed in Spain due to the COVID-19 pandemic interrupted the ALAS health promotion intervention aimed at the population at high risk of suffering from type 2 diabetes. We conducted a descriptive study in 2020 through a telephone survey and a comparison with baseline data to determine the impact of confinement on the lifestyles of the participants. We collected sociodemographic variables and conducted assessments before/after confinement on general health status and lifestyle (sleep, physical activity and diet). Additionally, weight, BMI and adherence to a Mediterranean diet were assessed. Descriptive statistical analyses, comparisons of pre-post confinement data and logistic regression were carried out. A total of 387 individuals responded. Among them, 31.8% reported a worse perception of health after confinement, and 63,1% reported no change. Regarding exercise, 61.1% reduced their weekly physical activity time. Regarding diet, 34,4% perceived worse quality, and 53.4% reported no change, despite the fact that 89.4% declared changes in their eating practices. Weight and BMI decreased by 3,1%, and adherence to the Mediterranean diet improved from baseline. Confinement had a negative impact on the general health, diet, sleep and physical activity of this population (at risk of diabetes); however, weight and BMI decreased, and adherence to a Mediterranean diet improved.

Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection and is associated with poor prognosis. There is controversy regarding the clinical benefit of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. Objective: To assess the efficacy and safety of intraoperative HIPEC in patients with locally advanced colon cancer. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial was conducted in 17 Spanish centers from November 15, 2015, to March 9, 2021. Enrolled patients were aged 18 to 75 years with locally advanced primary colon cancer diagnosed preoperatively (cT4N02M0). Interventions: Patients were randomly assigned 1:1 to receive cytoreduction plus HIPEC with mitomycin C (30 mg/m2 over 60 minutes; investigational group) or cytoreduction alone (comparator group), both followed by systemic adjuvant chemotherapy. Randomization of the intention-to-treat population was done via a web-based system, with stratification by treatment center and sex. Main Outcomes and Measures: The primary outcome was 3-year locoregional control (LC) rate, defined as the proportion of patients without peritoneal disease recurrence analyzed by intention to treat. Secondary end points were disease-free survival, overall survival, morbidity, and rate of toxic effects. Results: A total of 184 patients were recruited and randomized (investigational group, n = 89; comparator group, n = 95). The mean (SD) age was 61.5 (9.2) years, and 111 (60.3%) were male. Median duration of follow-up was 36 months (IQR, 27-36 months). Demographic and clinical characteristics were similar between groups. The 3-year LC rate was higher in the investigational group (97.6%) than in the comparator group (87.6%) (log-rank P = .03; hazard ratio [HR], 0.21; 95% CI, 0.05-0.95). No differences were observed in disease-free survival (investigational, 81.2%; comparator, 78.0%; log-rank P = .22; HR, 0.71; 95% CI, 0.41-1.22) or overall survival (investigational, 91.7%; comparator, 92.9%; log-rank P = .68; HR, 0.79; 95% CI, 0.26-2.37). The definitive subgroup with pT4 disease showed a pronounced benefit in 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; log-rank P = .003; HR, 0.09; 95% CI, 0.01-0.70). No differences in morbidity or toxic effects between groups were observed. Conclusions and Relevance: In this randomized clinical trial, the addition of HIPEC to complete surgical resection for locally advanced colon cancer improved the 3-year LC rate compared with surgery alone. This approach should be considered for patients with locally advanced colorectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02614534.

Association between use of enhanced recovery after surgery protocols and postoperative complications after gastric surgery for cancer (POWER 4): a nationwide, prospective multicentre study.

INTRODUCTION: The effectiveness of the Enhanced Recovery After Surgery (ERAS) protocols in gastric cancer surgery remains controversial. METHODS: Multicentre prospective cohort study of adult patients undergoing surgery for gastric cancer. Adherence with 22 individual components of ERAS pathways were assessed in all patients, regardless of whether they were treated in a self-designed ERAS centre. Each centre had a three-month recruitment period between October 2019 and September 2020. The primary outcome was moderate-to-severe postoperative complications within 30 days after surgery. Secondary outcomes were overall postoperative complications, adherence to the ERAS pathway, 30 day-mortality and hospital length of stay (LOS). RESULTS: A total of 743 patients in 72 Spanish hospitals were included, 211 of them (28.4 %) from self-declared ERAS centres. A total of 245 patients (33 %) experienced postoperative complications, graded as moderate-to-severe complications in 172 patients (23.1 %). There were no differences in the incidence of moderate-to-severe complications (22.3% vs. 23.5%; OR, 0.92 (95% CI, 0.59 to 1.41); P = 0.068), or overall postoperative complications between the self-declared ERAS and non-ERAS groups (33.6% vs. 32.7%; OR, 1.05 (95 % CI, 0.70 to 1.56); P = 0.825). The overall rate of adherence to the ERAS pathway was 52% [IQR 45 to 60]. There were no differences in postoperative outcomes between higher (Q1, > 60 %) and lower (Q4, ≤ 45 %) ERAS adherence quartiles. CONCLUSIONS: Neither the partial application of perioperative ERAS measures nor treatment in self-designated ERAS centres improved postoperative outcomes in patients undergoing gastric surgery for cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03865810.

Evaluation under real-life conditions of a lifestyle intervention for diabetes prevention developed by the municipal health services of Madrid, Spain.

The Diet, Physical Activity and Health (Alimentación, Actividad física y Salud, ALAS) program is an intervention implemented by the municipal health services of Madrid with the objective of reducing weight and preventing diabetes in high-risk population by improving diet and physical activity. The ALAS program combines individual visits with a 10-session group workshop that takes place over a 6-month period. This study evaluated the effectiveness of the ALAS intervention implemented under real-life conditions between 2016 and 2019. The intervention was evaluated with a pre- and post-intervention study with follow-up performed 6 and 12 months from the start of the program. The analyzed outcomes were a 5-10% reduction in the initial weight, body mass index (BMI), waist circumference and a change in glycemic status in prediabetic participants. Statistical models were adjusted by sociodemographic variables. The participants were recruited from municipal community health centers or referred by municipal occupational health services. Between 2016 and 2019, 1629 people participated in the program. At 6 months, 85% of the participants had lost weight; 43% had lost 5% or more of their initial weight, and 12% had lost 10% or more. Regarding BMI, 22.3% of participants who were initially obese were no longer obese, and 15.2% of the overweight participants achieved normal weight. A total of 35.1% of the prediabetic participants reverted to normoglycemic status. The intervention was found to be more effective for men, for those who completed the intervention and those who accessed the program through the occupational health route. Among the participants who accessed the intervention via the community, the intervention was more effective in those with a high educational level. The evaluation demonstrated the effectiveness of the ALAS program for reducing weight and the risk of developing Type 2 diabetes when applied under real-life conditions. The effectiveness of the intervention differed according to gender, access route and educational level of the participants.

Investigation of clade B New World arenavirus tropism by using chimeric GP1 proteins.

Clade B of the New World arenaviruses contains both pathogenic and nonpathogenic members, whose surface glycoproteins (GPs) are characterized by different abilities to use the human transferrin receptor type 1 (hTfR1) protein as a receptor. Using closely related pairs of pathogenic and nonpathogenic viruses, we investigated the determinants of the GP1 subunit that confer these different characteristics. We identified a central region (residues 85 to 221) in the Guanarito virus GP1 that was sufficient to interact with hTfR1, with residues 159 to 221 being essential. The recently solved structure of part of the Machupo virus GP1 suggests an explanation for these requirements.

Identification of Species and Subspecies of Lactic Acid Bacteria Present in Spanish Cheeses Type "Torta" by MALDI-TOF MS and pheS gene Analyses.

Several artisanal cheeses are elaborated in European countries, being commonly curdled with rennets of animal origin. However, in some Spanish regions some cheeses of type "Torta" are elaborated using Cynara cardunculus L. rennets. Two of these cheeses, "Torta del Casar" and "Torta de Trujillo", are elaborated in Cáceres province with ewe's raw milk and matured over at least 60 days without starters. In this work, we identified the lactic acid bacteria present in these cheeses using MALDI-TOF MS and pheS gene analyses, which showed they belong to the species Lactobacillus curvatus, Lactobacillus diolivorans, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactococcus lactis and Leuconostoc mesenteroides. The pheS gene analysis also allowed the identification of the subspecies La. plantarum subsp. plantarum, La. paracasei subsp. paracasei and Le. mesenteroides subsp. jonggajibkimchii. Low similarity values were found in this gene for some currently accepted subspecies of Lc. lactis and for the two subspecies of La. plantarum, and values near to 100% for the subspecies of Le. mesenteroides and La. paracasei. These results, which were confirmed by the calculated ANIb and dDDH values of their whole genomes, showed the need to revise the taxonomic status of these species and their subspecies.

New world clade B arenaviruses can use transferrin receptor 1 (TfR1)-dependent and -independent entry pathways, and glycoproteins from human pathogenic strains are associated with the use of TfR1.

Arenaviruses are rodent-borne viruses, with five members of the family capable of causing severe hemorrhagic fevers if transmitted to humans. To date, two distinct cellular receptors have been identified that are used by different pathogenic viruses, alpha-dystroglycan by Lassa fever virus and transferrin receptor 1 (TfR1) by certain New World clade B viruses. Our previous studies have suggested that other, as-yet-unknown receptors are involved in arenavirus entry. In the present study, we examined the use of TfR1 by the glycoproteins (GPs) from a panel of New World clade B arenaviruses comprising three pathogenic and two nonpathogenic strains. Interestingly, we found that TfR1 was only used by the GPs from the pathogenic viruses, with entry of the nonpathogenic strains being TfR1 independent. The pathogenic GPs could also direct entry into cells by TfR1-independent pathways, albeit less efficiently. A comparison of the abilities of TfR1 orthologs from different species to support arenavirus entry found that the human and feline receptors were able to enhance entry of the pathogenic strains, but that neither the murine or canine forms were functional. Since the ability to use TfR1 is a characteristic feature of the human pathogens, this interaction may represent an important target in the treatment of New World hemorrhagic fevers. In addition, the ability to use TfR1 may be a useful tool to predict the likelihood that any existing or newly discovered viruses in this family could infect humans.

Nasogastric feeding for infants who have undergone palatoplasty for a cleft palate.

Almost 1,000 babies are born each year with some form of cleft, whether it is a palate, lip or a combination. However, with the advent of new regional cleft centres and specialist professionals caring for larger numbers of children with a cleft lip and palate, the long-term outcomes of these patients should show improvement. The nursing care on paediatric wards will make an important contribution to these outcomes. In this article, post-operative feeding, analgesia and inpatient stays following cleft palate repair are examined. In a post-palatoplasty study of 68 babies, 34 who were fed orally and 34 nasogastrically, the babies who were fed nasogastrically were more settled, needed less analgesia and were discharged earlier. The parents of these babies were more relaxed knowing their child was fed and had adequate analgesia, and nurses believed they were able to give these babies a better quality of care.

Facklamia Species as an Underrecognized Pathogen.

Facklamia species are a rarely reported etiology of clinical infection with few cases described in literature. However, the prevalence of infection may be underestimated due to challenges in species identification. We describe 3 cases of Facklamia species bacteremia and the unique microbiologic aspects inherent to this genus that make it particularly challenging to identify. In addition, given the unique susceptibility profile of Facklamia species, we discuss the importance of fully identifying this organism when it is a suspected as a pathogen, to optimize therapy based on its distinct antibiotic resistance profile.