Control of motivation for sucrose in the paraventricular hypothalamic nucleus by dynorphin peptides and the kappa opioid receptor.

The dynorphin peptides are the endogenous ligands for the kappa opioid receptor (KOR) and regulate food intake. Administration of dynorphin-A1-13 (DYN) in the paraventricular hypothalamic nucleus (PVN) increases palatable food intake, and this effect is blocked by co-administration of the orexin-A neuropeptide, which is co-released with DYN in PVN from neurons located in the lateral hypothalamus. While PVN administration of DYN increases palatable food intake, whether it increases food-seeking behaviors has yet to be examined. We tested the effects of DYN and norBNI (a KOR antagonist) on the seeking and consumption of sucrose using a progressive ratio (PR) and demand curve (DC) tasks. In PVN, DYN did not alter the sucrose breaking point (BP) in the PR task nor the elasticity or intensity of demand for sucrose in the DC task. Still, DYN reduced the delay in obtaining sucrose and increased licks during sucrose intake in the PR task, irrespective of the co-administration of orexin-A. In PVN, norBNI increased the delay in obtaining sucrose and reduced licks during sucrose intake in the PR task while increasing elasticity without altering intensity of demand in the DC task. However, subcutaneous norBNI reduced the BP for sucrose and increased the delay in obtaining sucrose in the PR task while reducing the elasticity of demand. Together, these data show different effects of systemic and PVN blockade of KOR on food-seeking, consummatory behaviors, and incentive motivation for sucrose and suggest that KOR activity in PVN is necessary but not sufficient to drive seeking behaviors for palatable food.

Postural control strategies are revealed by the complexity of fractional components of COP.

The complexity of the center of pressure (COP) provides important information regarding the underlying mechanisms of postural control. The relationships between COP complexity and balance performance are not fully established and might depend on the task constraints and the filtering decomposition of the COP signal. This study assessed COP complexity under different task constraints and it was assessed if emergent dynamics of COP fluctuations differ according to fractional components of COP related to peripheral or central adjustments. One hundred and sixty-two participants performed two sitting balance tasks. Accuracy was required by following a target that moved in the mediolateral (ML) or in the anteroposterior (AP) axis. Complexity dynamics of COP were addressed through detrended fluctuation analysis (DFA) in the axis constrained by accuracy requirements and in the one nonconstrained. Decomposition of COP components was applied by low-pass, band-pass, and high-pass filters. DFA of low-pass and band-pass components of COP in the constrained axis were small-to-moderately related (r = 0.190-0.237) to balance performance. DFA of the high-pass component of the COP exhibited the opposite relationship (r = -0.283 to -0.453) in both axes (constrained and nonconstrained). This study evidences that COP complexity is linked to better performance. This positive relationship complexity/performance is observed in the low- and mid-frequency components of the COP. These components might be related to central mechanisms of postural control. The lack of relationships between the different frequencies analyzed in the study suggests that they are capturing different components of postural control.NEW & NOTEWORTHY The relationship between the complexity of the center of pressure (COP) and balance performance is not fully established. The task constraints and the filtering decomposition of the COP could influence this relationship. COP complexity is related to a better balance performance only in low frequencies and midfrequencies of the COP. The different frequencies measure different postural control components. Filtering decomposition should be explored in future studies to address the underlying mechanisms of postural control.

Personalized biomarker-based treatment strategy for patients with squamous cell carcinoma of the head and neck: EORTC position and approach.

The molecular landscape of squamous cell carcinoma of the head and the neck (SCCHN) has been characterized and actionable or targetable genomic alterations have been identified. However, targeted therapies have very limited activity in unselected SCCHN, and the current treatment strategy is still based on tumor location and disease stage and not on tumor biology. Trying to select upfront the patients who will benefit from a specific treatment might be a way to improve patients' outcome. With the objective of optimizing the activity of targeted therapies and immunotherapy, we have designed an umbrella biomarker-driven study dedicated to recurrent and/or metastatic SCCHN patients (EORTC-1559-HNCG, NCT03088059). In this article, we review not only the different trial designs for biomarker-driven studies with their respective advantages and opportunities but also the potential pitfalls that led to the design of the EORTC-1559-HNCG protocol. We also discuss the scientific and logistic challenges of biomarker-driven trials.

Approaches for the successful isolation and cell culture of American Rickettsia species.

Rickettsia are intracellular vector-borne bacteria, which are the etiologic agent of severe infections that could inflict death to their host. The intracellular behaviour of Rickettsia makes the study of its genetics, proteomics and cellular processes very difficult. Hence, isolation remains an important experimental technique that permits the obtention of important yields of bacteria, useful for a broad range of experiments. Isolation of Rickettsia using passages in animals or embryonated eggs has been described for long time; however, it was until the 1990s that faster and more feasible approaches for cell culture were developed. Current isolation approaches are mainly based on shell vial culture, that varies according to the media, atmosphere or temperature conditions. These variations have allowed the establishment of isolates from different pathogenic and non-pathogenic Rickettsia species, using arthropod, animal or human samples. Purification method of bacteria has also witnessed changes alongside the quantification of its load in the resulting isolates, from the laborious and time consuming plaque assays, to the routinary use of real-time polymerase chain reaction (qPCR), which is faster and more accurate. This review discusses various approaches that have been used for the isolation and purification of different Rickettsia species along with the mention of some successful examples. It indicated that a successful strategy for the isolation of Rickettsia requires a careful selection of media, cell lines and culture conditions which now are not as time consuming as used to be.

Pathogen removal from domestic and swine wastewater by experimental constructed wetlands.

This study examined the performance of subsurface flow horizontal wetlands in total coliforms, faecal coliforms, enterococci and Salmonella removal from swine and domestic wastewaters. The effects of organic loading rate, contact time (CT) and the presence of aquatic macrophytes, Typha dominguensis and Typha latifolia, on treatment performance were evaluated. In general, chemical oxygen demand (COD) and total suspended solids (TSS) were reduced by 66 and 72% after 24 h and 75 and 84% after 48 h in domestic wastewaters, and 73 and 71% after 24 h and 72 and 78% after 48 h in swine wastewater. Total coliform and faecal coliform reductions of 70-83% and 65-78% were observed in the vegetated systems after 24 h of CT, while after 48 h, total coliform and faecal coliform reductions of 80-82% and 86-91% were noted.

Infective endocarditis in congenital heart disease: a frequent community-acquired complication.

BACKGROUND: Infective endocarditis (IE) is a severe complication in patients with congenital heart disease (CHD). Epidemiology, etiology, and outcome in this group are different to those of patients with acquired heart disease. METHODS: We reviewed all cases of proven and probable IE (Duke's criteria) diagnosed in our center during the last two decades. RESULTS: We observed 45 cases of IE in patients with CHD (age range 8 months to 35 years); these represented 5.5 % of all the episodes of IE in our institution during the study period. The most frequent CHD were ventricular septal defect (31 %), tetralogy of Fallot (19 %), and atrioventricular septal defect (11 %). Twenty cases of IE (44 %) were recorded in patients with non-corrected native-valve CHD. Of the 24 patients with prosthetic-valve IE, post-operative acquisition during the first 6 months was confirmed in 11 patients (range 4-110 days). IE was community-acquired in 62 % of cases. Streptococcus spp. were the most frequent etiologic agents (33 %), followed by Staphylococcus spp. (32 %). Surgery was required to treat IE in 47 % of patients (52 % in prosthetic-valve IE and 41 % in native-valve IE, p = ns). In comparison to native-valve IE, prosthetic-valve IE was significantly more nosocomial-acquired (61 vs. 14 %, p = 0.002), presented a higher heart failure rate at diagnosis (39 vs. 9 %, p = 0.035), and developed more breakthrough bacteremia episodes (19 vs. 0 %, p = 0.048). Global mortality was 24 % (75 % in patients with prosthetic-valve IE who required surgery and 0 % in patients with native-valve IE who required surgery, p = 0.001). Multivariate analysis excluding breakthrough bacteremia (100 % mortality in this condition) confirmed that nosocomial IE [odds ratio (OR), 23.7; 95 % confidence interval (CI), 2.3-239.9] and the presence of heart failure at diagnosis of IE (OR, 25.9; 95 % CI, 2.5-269.6) were independent factors associated with mortality. CONCLUSION: Half of all cases of IE in patients with CHD occurred in patients with non-corrected native-valve CHD and two-thirds were community-acquired. Streptococcus spp. were the most frequent etiological agents. Patients with prosthetic-valve IE present a worse outcome, especially those requiring surgery. Breakthrough bacteremia, nosocomial IE, and heart failure are independent factors of mortality in patients with CHD presenting IE.

Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial.

BACKGROUND: Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. PATIENTS AND METHODS: Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. RESULTS: The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). CONCLUSIONS: Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.

Variations in the definition and perceived importance of positive resection margins in patients with colorectal cancer - an EYSAC international survey.

INTRODUCTION: Microscopically positive resection margins (R1) are associated with poorer outcomes in patients with colorectal cancer. However, different definitions of R1 margins exist. It is unclear to what extent the definitions used in everyday clinical practice differ within and between nations. This study sought to investigate variations in the definition of R1 margins in colorectal cancer and the importance of margin status in clinical decision-making. MATERIALS AND METHODS: A 14-point survey was developed by members of The European Society of Surgical Oncology (ESSO) Youngs Surgeons and Alumni Club (EYSAC) Research Academy targeting all members of the multidisciplinary team (MDT) treating patients with colorectal cancer. The survey was distributed on social media, in ESSO's monthly newsletter and via national societies. RESULTS: In total, 137 responses were received. Most respondents were from Europe (89.7%), with the majority from Denmark (56.9%). Less than 2/3 of respondents defined R1 margins as the presence of viable cancer cells ≤1 mm of the margin. Only 60% reported that subdivisions of R1 margins (primary tumour vs tumour deposit vs metastatic lymph node) are routinely available. More than 20% of respondents reported that pathology reports are not routinely reviewed at MDT meetings. Less than half of respondents considered margin status in decision-making for type and duration of adjuvant chemotherapy in Stage III colon cancer. CONCLUSION: The definitions and perceived clinical importance of microscopically positive margins in patients with colorectal cancer appear to vary. Adoption of an international dataset for pathology reporting may help to standardise current practices.

Meta-analysis of pre-clinical studies on the effects of opioid receptor ligands on food intake, motivation, and choice.

The opioid receptors (OR) regulate food intake. Still, despite extensive pre-clinical research, the overall effects and individual contribution of the mu (MOR), kappa (KOR), and delta (DOR) OR subtypes to feeding behaviors and food intake remain unclear. To address this, we conducted a pre-registered systematic search and meta-analysis of rodent dose-response studies to evaluate the impact of central and peripheral administration of non-selective and selective OR ligands on intake, motivation, and choice of food. All studies had a high bias risk. Still, the meta-analysis confirmed the overall orexigenic and anorexigenic effects of OR agonists and antagonists, respectively. Our results support a larger orexigenic role for central MOR agonists among OR subtypes and that peripheral OR antagonists reduce motivation for and intake of preferred foods. In binary food choice studies, peripheral OR agonists selectively increase the intake of fat-preferred foods; in contrast, they did not increase the intake of sweet carbohydrate-preferred foods. Overall, these data support that OR regulation of intake, motivation, and choice is influenced by food macronutrient composition.

Socio-ecological determinants of rickettsial seroprevalence in a rural community of Yucatán, Mexico.

Rickettsial diseases have seen a re-emergence in the Americas in the last few decades, with concerning morbidity, mortality and economic implications that result from loss of productivity, income, curbs in liberal trade agreements, and reduction in agricultural practices. The aim of this study is to determine the socioecological determinants and seroprevalence for Rickettsia typhi and Rickettsia rickettsii among residents of Teabo, a rural community of Yucatán, Mexico. Sociodemographic data and serum samples were obtained from 180 consenting participants. Antibody titers for R. typhi and R. rickettsii were determined by indirect immunofluorescence assay (IFA). Participants also submitted tick samples collected from their residential area. We conducted logistic regression models to evaluate the association between exposure variables and seroprevalence. Rhipicephalus sanguineus s.l. (37%; n = 65), and Amblyomma cajennense Fabricius (17%; n = 29) were the predominant tick species in peri-domestic areas. Out of the 180 participants, there was significantly higher seroprevalence of R. typhi (n = 77; 46%) compared to R. rickettsii [n = 27, 15%, (p < 0.05)]. Pearson's chi-square test of independence revealed significant differences in R. rickettsii seroprevalence by gender (X2 [n = 175, df = 4, (p < 0.001)] = 180.26), level of education, (X2 [n = 180, df = 4, (p < 0.001)] = 44.0), and by tick species found in residential area, (X2 [n = 180, df = 4, (p = 0.050)] = 9.48). After adjusting for other variables in a logistic regression model, for each unit increase in the number of dogs present in the residential area, there was a 27% increase in the odds of human seroprevalence for R. typhi IgG (AOR = 1.27, 95% CI: 1.01-1.63). Compared to study participants living in residential areas with a 'low' height of vegetation, those living in residential areas with a 'medium' height of vegetation had 2.5 times greater odds of human seroprevalence for R. typhi IgG (AOR = 2.51, 95% CI: 1.19-5.40). Potentially modifiable existing factors in the peri-domestic area may constitute a high-risk source of seroprevalence for rickettsial antibodies among residents of the rural community of Teabo, Yucatán, Mexico.

Can wrecks serve as exploitable surrogate habitats for degraded natural reefs?

Overfishing is a key stressor in many coral reefs, affecting their function and ecosystem services. In the Gulf of California, 50 years of artisanal and recreational fishing have removed most of the largest and most vulnerable fish species, the Espiritu Santo Archipelago (ESA) is a marine protected area (MPA) where artisanal and recreational fishing are allowed in most of the natural reefs, while the artificial reefs (wrecks) are fully protected. An important question under such circumstances is whether artificial reefs can serve as surrogate habitats for the natural reefs. To address this question, we characterized the fish community (species richness, abundance, differences in taxonomic structure) and analyzed the obtained data by multivariate ordination and similarity analysis. The highest species richness was found in the artificial reefs, with total of 83 species, of which 21 species were exclusive. Contrary to the species richness, the total fish abundance was 20% higher at the natural reefs. The fish assemblages of the artificial reefs differ significantly from those of the natural reefs. The natural reefs of the ESA are dominated by few fish species from families of lower trophic levels. In contrast, the studied shipwrecks provide refuge to commercially important fish species (such as Snappers, Triggerfish, Jacks, and Groupers) including threatened species. The different fish compositions on the natural and artificial reefs is likely to be the outcome of differential fishing pressure. The non-fished areas (wrecks) of the ESA may represent a good strategy for reef restoration, enhanced fishing grounds (via spillover) and fishing management. However, the fish community structure of the artificial reefs differs from natural rocky reefs of the ESA, and therefore, should not be considered as surrogate habitats for natural reefs. The results point out the need to reassess the management effectiveness of the natural reefs of the ESA.

Major liver trauma post-mechanical cardiopulmonary resuscitation-the first reported case of survival with normal cardiovascular and neurological outcome.

Cardiopulmonary resuscitation (CPR) is often conducted with mechanical devices, such as Lund University Cardiac Arrest System in the setting of cardiac arrest during coronary catheterization, to enable effective chest compressions for a prolonged period. Certain injuries from such devices are common such as skin lesions, sternal and rib fractures. Others are rarer, such as visceral injury to the heart, major vessels, lung, liver, spleen and stomach. Major liver injuries have been previously reported but were universally fatal. Here, we report the first case of a capsular liver tear post-mechanical CPR, requiring immediate laparotomy and primary repair, resulting in patient survival with a normal cardiovascular and neurological and outcome.

Identification through exome sequencing of the first PMM2-CDG individual of Mexican mestizo origin.

Congenital Disorders of Glycosylation (CDG) are scarcely reported from Latin America. We here report on a Mexican mestizo with a multi-systemic syndrome including neurological involvement and a type I transferrin (Tf) isoelectric focusing (IEF) pattern. Clinical exome sequencing (CES) showed known compound missense variants in PMM2 c.422G > A (p.R141H) and c.395 T > C (p.I132T), coding for the phosphomanomutase 2 (PMM2). PMM2 catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. This is the third reported Mexican CDG patient and the first with PMM2-CDG. PMM2 has been recently identified as one of the top 10 genes carrying pathogenic variants in a Mexican population cohort.

[Evaluation of compliance with the antibiotic prophylaxis protocol in hysterectomy. Prospective cohort study]. / Evaluación de la adecuación al protocolo de profilaxis antibiótica en histerectomías. Estudio de cohortes prospectivo.

OBJECTIVE: Health care-related infections are a public health problem, among them surgical site infection (SSI) are the most frequent in hospitals. The objetive of this study was to assess the effect of the compliance to antibiotic prophylaxis protocol on the incidence of surgical site infection in hysterectomized patients. METHODS: A prospective cohort study was carried out between October 2009 and December 2018. The incidence of SSI was studied after a maximum period of 30 days from the moment of surgery. The degree of adequacy of antibiotic prophylaxis in hysterectomy and the effect of its inadequacy on the incidence of infection was evaluated using relative risk (RR) adjusted with a logistic regression model. RESULTS: A total of 1,025 interventions were studied in 1,022 women. The cumulative incidence of SSI was 2,1% (n = 22). The most frequent etiology of infection was Escherichia coli (23.1%) and Proteus mirabilis (23.1%). Antibiotic prophylaxis was indicated in 1,014 interventions (98.9%) being administered in 1,009 of them (99.5%). The adherence to the protocol was 92,5%. The main cause of non-compliance was the time of onset (40.9%), followed by the choice of the antibiotic (35.2%). The effect of inadequate prophylaxis on the incidence of infection was RR = 0.9; 95% CI 0.2-3.9; p> 0.05. CONCLUSIONS: The adequacy of antibiotic prophylaxis was very high, with a low incidence of surgical site infection. No association was found between adequacy of prophylaxis and incidence of infection in hysterectomy. The continuous improvement of epidemiological surveillance in gynecology should be emphasized.

Comparative study between cold air analgesia and supraorbital and supratrochlear nerve block for the management of pain during photodynamic therapy for actinic keratoses of the frontotemporal zone.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratoses, Bowen's disease and basal cell carcinoma. The main drawback of PDT is pain during application. OBJECTIVES: To compare the efficacy of supratrochlear and supraorbital nerve block with cold air analgesia to control the pain experienced during PDT. METHODS: A controlled open clinical trial was conducted in 34 patients having multiple actinic keratoses in the frontal region treated with PDT. On one side of the frontal region the supratrochlear and supraorbital nerves were blocked, while on the other side cold air was used as the method of analgesia. Pain was recorded on a visual analogue scale after treatment. RESULTS: Thirty-one of 34 patients reported less pain in the zone treated with nerve block. This difference was statistically significant. CONCLUSIONS: Nerve block is superior to cold air and is an easy, safe, effective means of controlling the pain associated with PDT.

Analysis of the elderly patient population in a tertiary-care university hospital.

A progressively ageing population and the high association between advanced age and cancer has resulted in an increased interest in the field of geriatric oncology with the objective being a more effective diagnosis and treatment of these patients. We performed an epidemiological analysis on an intent-to-treat of elderly population within our healthcare unit. This is a retrospective study of all patients attended in our Medical Oncology Department during the year 2002. A total 667 patients were assessed, 42% older than 70 years of age. The most frequent tumour sites were lung, colorectal and breast. The most frequent histology was adenocarcinoma. The diagnosis in advanced stages was significantly higher in older age group (76% vs. 59%). The use of symptom-control follow-up and palliative-care, compared with radio- and chemo-therapy, was higher in older age group. However, we observed no statistically significant differences with respect to inclusion in clinical trials. In conclusion, the elderly represents an important percentage of patients receiving cancer care. The distributions by sites and histology types are similar in both groups of age. Although the election of palliative treatment is more frequent in elderly population, the most frequently used treatments in both groups, were radiotherapy and chemotherapy. We didn't observe any significant differences about the inclusion in clinical trials.

[Symptomatic xanthogranuloma of the lateral ventricle]. / Xantogranuloma sintomático del ventrículo lateral. A propósito de un caso.

Xanthogranulomas of the choroid plexus is a benign tumour of uncertain etiology, usually asymptomatic. We report a case of symptomatic xanthogranuloma of the left lateral ventricle with edema in adjacent white matter, in a 62-year-old man with seizures.

SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018).

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.

European Society of Surgical Oncology's strategy for clinical research: Paving the way for a culture of research in cancer surgery.

As part of its mission to promote the best surgical care for cancer patients, the European Society of Surgical Oncology (ESSO) has been developing multiple programmes for clinical research along with its educational portfolio. This position paper describes the different research activities of the Society over the past decade and an action plan for the upcoming five years to lead innovative and high quality surgical oncology research. ESSO proposes to consider pragmatic research methodologies as a complement to randomised clinical trials (RCT), advocates for increased funding and operational support in conducting research and aims to enable young surgeons to be active in research and establish partnerships for translational research activities.