Frequency and characterization of the accessory heads of the biceps brachii: A multicentric cadaveric study.

PURPOSE: The biceps brachii muscle (BBM) is a large and thick muscle on the ventral portion of the upper arm. The scientific literature reports the existence of extra heads. OBJECTIVE: The present work investigated the frequency of occurrence of BBM accessory head(s) in four different Anatomy Laboratories at universities in Northeast Brazil. MATERIAL AND METHODS: Once the upper limbs with an anatomical variation of the BBM heads were identified, the accessory head was evaluated for morphometric characterization (the length, width, and thickness). RESULTS: The sample consisted of 249 upper limbs and the outcomes were 26 members with BBM accessory heads (10.44% of the total sample). Among the 26 members studied was found a single accessory head in 22 (84.62%), two accessory heads in 3 (11.54%), and three accessory heads in 1 (3.85%). BBMs with one, two, and three accessory heads were found, with different origins. The average length, width, and thickness of these accessory heads were 169.39mm, 10.25mm, and 3.39mm, respectively. CONCLUSION: The frequency of BBM accessory heads in a population of northeastern Brazil in this cadaveric study was 10.44%.

Suspected intoxication by Kikuyu grass (Cenchrus clandestinus) of dairy cattle in the Azores, Portugal.

CASE HISTORY: An outbreak of suspected Kikuyu grass (Cenchrus clandestinus) intoxication among dairy cattle occurred on the island of Terceira in the Azores (Portugal), in October 2022. The animals affected were non-lactating dairy cows and heifers from five small farms grazing (free or tethered) a Kikuyu-dominant pasture. Of the 29 animals exposed, 17 were affected, and eight (five heifers and three adult cows) died, resulting in a morbidity rate of 58%, a mortality rate of 28% and a case mortality rate of 47%. CLINICAL FINDINGS AND TREATMENT: The clinical signs were non-specific and inconsistent, and included dry faeces, some with dark red blood; apathy and prostration; abdominal dilatation; tachycardia; tachypnoea; pale or jaundiced mucous membranes; sham drinking; sialorrhoea; and moderate to severe dehydration. Symptomatic treatment was provided but was ineffective. Haematology and serum biochemistry revealed an acute inflammatory leukogram, increased alkaline phosphatase (ALP) activity, decreased gamma-glutamyl transferase (GGT) activity, and azotaemia.The most consistent necropsy findings were haemorrhages in the epicardium and endocardium, an enlarged liver with rounded edges, non-perforated abomasal ulcers, and haemorrhagic lesions in the small and large intestines. Histopathology indicated myocarditis, hepatitis, interstitial nephritis, enteritis and colitis.Several fungal species were isolated from grass samples taken from affected pastures including several Fusarium spp., the genus implicated in Kikuyu toxicosis. Immediate removal of the animals from the pasture with Kikuyu was the only measure that prevented new cases and resulted in the recovery of some of the less affected animals. DIAGNOSIS: The epidemiological features of this outbreak and the clinical signs and micro- and macroscopic lesions observed were highly suggestive of Kikuyu grass poisoning. CLINICAL RELEVANCE: Although the weather conditions varied from other published cases, the grazing conditions (almost exclusive Kikuyu grass) and the post-mortem findings were very similar to those described in the literature, particularly the haemorrhages in the epicardium and endocardium. Kikuyu grass is very invasive and presents many desirable characteristics as cattle feed. Thus, an increase in cases of intoxication may be expected. Practitioners and farmers in areas where Kikuyu grass is abundant should be aware of the potential risks of grazing cattle exclusively on these pastures. They should also be aware of the early and subtle signs of Kikuyu intoxication to allow for timely removal of the animals from pasture.

Transabdominal preperitoneal (TAPP) repair for emergency groin hernia: a systematic review.

PURPOSE: Laparoscopic groin hernia repair has evolved and gained popularity and laparoscopic transabdominal preperitoneal (TAPP) procedure provides an opportunity to evaluate the peritoneal cavity and both inguinal areas without the need for additional dissection. There is still a paucity of evidence to support TAPP repair in the emergency setting. In this systematic review, we aim to evaluate the feasibility and safety of TAPP repair for incarcerated and strangulated groin hernias. METHODS: PRISMA guidelines were followed for literature search and established inclusion and exclusion criteria were applied. Data were extracted and analyzed for the outcomes of interest. RESULTS: Overall, 8 studies were included in the review, comprising 316 patients. Patients characteristics and outcomes were limitedly reported. Only 3 cases of conversion to open approach were reported and 2 recurrences were diagnosed. Postoperative complications are inconsistently reported but mostly refer to minor complications. There were no mortality cases. Visceral resections were performed in 25 cases due to ischemia, mostly extracorporeally. CONCLUSION: Laparoscopy is a game changer and TAPP approach is a feasible, safe, and effective technique for the emergent repair of groin hernias. Further studies and prospective randomized data are needed to establish its role in the emergent groin hernia management.

Dynamics of blaOXA-23 gene transmission in Acinetobacter spp. from contaminated veterinary environmental surfaces: an emerging One Health threat?

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii is a common pathogen associated with healthcare-acquired infections, and robust infection prevention and control protocols exist in human healthcare settings. In contrast, infection prevention and control (IPC) standards are limited in veterinary medicine, necessitating further investigation. AIM: Examine the possible transmission of carbapenem-resistant Acinetobacter spp. in a veterinary practice where a cat was diagnosed with an OXA-23-producing A. baumannii ST2 strain. METHODS: Environmental samples together with nasal and hand swabs from the veterinary personnel were collected. All swabs were screened for the presence of extended-spectrum-ß-lactamase- and carbapenemase-producing Enterobacterales, meticillin-resistant staphylococcus and multi-drug-resistant Acinetobacter spp. Whole-genome sequencing was performed for carbapenemase-producing strains. RESULTS: Of the veterinary staff, 60% carried meticillin-resistant Staphylococcus epidermidis. Environmental evaluation showed that 40% (N=6/15) of the surfaces analysed by contact plates and 40% (N=8/20) by swabs failed the hygiene criteria. Assessment of the surfaces revealed contamination with five OXA-23-producing Acinetobacter spp. strains: an OXA-23-producing Acinetobacter schindleri on the weight scale in the waiting room; and four OXA-23-producing Acinetobacter lwoffii strains, on different surfaces of the treatment room. The blaOXA-23 gene was located on the same plasmid-carrying Tn2008 across the different Acinetobacter spp. strains. These plasmids closely resemble a previously described OXA-23-encoding plasmid from a human Portuguese nosocomial Acinetobacter pittii isolate. Distinctly, the OXA-23-producing A. baumannii ST2 clinical strain had the resistant gene located on Tn2006, possibly inserted on the chromosome. CONCLUSION: The detection of an OXA-23-producing A. baumannii ST2 veterinary clinical strain is of concern for companion animal health and infection, prevention and control. This study established the dynamic of transmission of the plasmid-mediated blaOXA-23 gene on critical surfaces of a small animal veterinary practice. The genetic resemblance to a plasmid found in human nosocomial settings suggests a potential One Health link.

Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

Potential breeding containers of Aedes aegypti (Linnaeus, 1762) and Aedes albopictus (Skuse, 1894) at strategic points in a city in the eastern region of Maranhão.

Potential breeding containers for Aedes aegypti and Aedes albopictus mosquitoes are found in different environments, these places are considered by the National Dengue Control Program in Brazil as strategic points (SP), which have favorable conditions for the development of those insects. The aim of this study is to identify potential breeding containers for A. aegypti and A. albopictus at strategic points in the city of Codó, Maranhão. This study was conducted in five districts, one in each administrative area of the city. A survey of the types and quantity of existing strategic points in each neighborhood was carried out, and surveys of these properties were carried out to inspect the potential breeding containers, with the collection of the vectors' number of immatures found at them. 125 properties were inspected of which 76.91% and 81.25% were vacant lots in the dry and rainy seasons, respectively. There was a difference between the median of the different strategic points (H = 21.96; p < 0.0001), For A. aegypti, there was no difference between the medians of number of immatures regarding the strategic points (H = 3.71; p = 0.28). The total number of immature A. albopictus was higher in vacant lots than in workshops (H = 9.41; p = 0.02, p < 0.05). 4,356 and 4,911 potential breeding containers were found in the dry and rainy seasons, respectively. Regarding the potential breeding containers, 7 (0.16%) and 47 (0.96%) were found with immature vectors, in the dry and rainy seasons, respectively. There were more positive containers in the rainy season for which there was a difference between the median of the number of mosquitoes per positive container (H = 15.66; p = 0.01), the number of immatures for the tires group was greater than Vases and Fixed groups (p < 0.05); the same result was observed in the analyses of the species in the separate form. The impressive number of potential breeding containers found in the SP in both seasons highlights the importance of developing control strategies for these vectors, with emphasis on places such as vacant lots, workshops, tire shops and junkyards, which are serving as dispersal urban sites of vectors.

Retraction Note: Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model.

The article "Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model", by N.D. Suarez Uribe, M.F. Pezzini, J. Dall'Agnol, N. Marroni, S. Benitez, D. Benedetti, J. Da Silva, C.T. Cerski, E. Dallegrave, S. Macedo, S.C.W.S.E.F. de Oliveira, D. Joveleviths, published in Eur Rev Med Pharmacol Sci 2023; 27 (13): 6374-6383-DOI: 10.26355/eurrev_202307_32997-PMID: 37458654 has been retracted by the Editor in Chief for the following reasons: After publication, concerns were raised by an unidentified reader who underlined some similarities between this publication and a previous publication published in the Journal of Clinical and Experimental Gastroenterology. After being informed, the authors claimed the previous journal published the article without consent, and, therefore, the authors promptly withdrew the previous publication. The retraction published by the other journal does not contain any information regarding the reason for withdrawal. As a matter of fact, the journal does not have any evidence about the authors' claim and still considers this research a duplicate publication. For the above-mentioned reasons, the Editor in Chief decided to withdraw the manuscript. This manuscript has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32997.

Effects of Hydrofluoric Acid Concentrations, Commercial Brands, and Adhesive Application on the Bond Strength of a Resin Luting Agent to Lithium Disilicate Glass Ceramic.

OBJECTIVES: To evaluate the surface topography/roughness and bond strength of a resin luting agent to a lithium disilicate glass ceramic after etching with different concentrations of hydrofluoric acid (HF) and commercial brands. METHODS: For bond strength evaluation, 260 lithium disilicate glass ceramic (EMX) discs were randomly distributed into 13 groups based on concentrations of HF and commercial brands (n=20): 5% and 10%, Lysanda (LY5 and LY10); 5% and 10%, Maquira (MA5 and MA10); 5% and 10%, FGM (FG5 and FG10); 4.8%, Ivoclar Vivadent (IV5); 5% and 10%, PHS do Brasil (PH5 and PH10); 5% and 10%, BM4 (BM5 and BM10); 9%, Ultradent Inc (UL10); and Dentsply (DE10). A further random distribution (n=10) was made based on the application (+) or absence (-) of an adhesive layer. Resin luting agent cylinders (1 mm in diameter) were added on EMX surfaces, light-cured, and stored for 24 hours in deionized water at 37°C. On a universal testing machine (DL 500, EMIC), specimens were submitted to a microshear bond strength test at a crosshead speed of 1 mm/min until failure. A representative etched EMX disc from each group underwent surface topography analysis using field-emission scanning electron microscopy (n=1), and five (n=5) etched EMX discs from each group were tested for surface roughness. Data were statistically analyzed using analysis of variance and Tukey test (α=0.05). RESULTS: A less conditioned and smoother surface was observed for 5% HF compared to 10%. Additionally, commercial brands of HF were shown to affect bond strength. When the adhesive layer was not used (-), a 10% concentration promoted higher bond strengths to EMX. However, when adhesive was applied (+), the concentrations of HF and commercial brands had no effect on bond strength results. CONCLUSIONS: A 10% concentration of HF results in higher bond strength than a 5% concentration. If an adhesive layer is applied, neither this distinction nor the influence of commercial brands is observed.

The geographical distribution and socioeconomic risk factors of COVID-19, tuberculosis and leprosy in Fortaleza, Brazil.

BACKGROUND: Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. METHODS: The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. RESULTS: COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. CONCLUSIONS: Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.

Cotransplantation of marginal mass allogeneic islets with 3D culture-derived adult human skin cells improves glycemia in diabetic mice.

Islet transplantation represents a therapeutic option for type 1 diabetes (T1D). Long-term viability of transplanted islets requires improvement. Mesenchymal stromal cells (MSCs) have been proposed as adjuvants for islet transplantation facilitating grafting and functionality. Stem cell aggregation provides physiological interactions between cells and enhances the in situ concentration of modulators of inflammation and immunity. We established a hanging-drop culture of adult human skin fibroblast-like cells as spheroids, and skin spheroid-derived cells (SphCs) were characterized. We assessed the potential of SphCs in improving islet functionality by cotransplantation with a marginal mass of allogeneic islets in an experimental diabetic mouse model and characterized the secretome of SphCs by mass spectrometry-based proteomics. SphCs were characterized as multipotent progenitors and their coculture with anti-CD3 stimulated mouse splenocytes decreased CD4+ T cell proliferation with skewed cytokine secretion through an increase in the Th2/Th1 ratio profile. SphCs-conditioned media attenuated apoptosis of islets induced by cytokine challenge in vitro and importantly, intratesticular SphCs administration did not show tumorigenicity in immune-deficient mice. Moreover, SphCs improved glycemic control when cotransplanted with a marginal mass of allogeneic islets in a diabetic mouse model without pharmacological immunosuppression. SphCs' protein secretome differed from its paired skin fibroblast-like counterpart in containing 70% of up- and downregulated proteins and biological processes that overall positively influenced islets such as cytoprotection, cellular stress, metabolism, and survival. In summary, SphCs improved the performance of transplanted allogeneic islets in an experimental T1D model, without pharmacological immunosuppression. Future research is warranted to identify SphCs-secreted factors responsible for islets' endurance.

Proceedings of the 2022 UAB CRRT Academy: Non-Invasive Hemodynamic Monitoring to Guide Fluid Removal with CRRT and Proliferation of Extracorporeal Blood Purification Devices.

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.

In situ Raman spectroscopy and synchrotron X-ray diffraction studies on maleic acid under high pressure conditions.

Maleic acid was studied by Raman spectroscopy and powder synchrotron X-ray diffraction (XRD) under high pressure conditions by using a diamond anvil cell. The Raman spectroscopy measurements were performed from ambient pressure up to 9.2 GPa in the 100-3200 cm-1 spectral range. While the XRD measurements were performed up to 10.1 GPa. Here we present the pressure-dependence behavior from both the Raman modes and cell parameters. Maleic acid lattice parameters decrease anisotropically as a function of pressure and a reduction of 27% in the volume of the unit cell was observed. Modifications in the material's compressibility were observed at around 2 and 6 GPa.

Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model.

OBJECTIVE: Mancozeb is one of the most widely used Ethylenebisdithiocarbamates fungicides in Brazil. A pilot experimental model was created to evaluate its potential hepatotoxic effect. MATERIALS AND METHODS: An experimental study was performed with 27 male Wistar rats (3 groups). The Control Group received a saline solution, while Intervention Groups I and II received 250 mg/kg and 500 mg/kg of Mancozeb respectively, once a week, for 12 weeks. Anthropometric measurements were carried out, and the marker of biological exposure in urine was dosed. Biochemical tests, evaluation micronucleus count, comet and oxidative stress markers assay, and histological assessment of the liver were also performed. RESULTS: The hepatotoxic effect of Mancozeb was confirmed by anthropometric measurements, genotoxicity, and oxidative stress. Statistically significant results were found when the exposed groups were compared to the control group. CONCLUSIONS: These results were supported by inflammatory infiltration and balloonization in the treated groups. The experimental model effectively demonstrated the deleterious effect of Mancozeb on the liver.

The REWRITE Study - REal-WoRld effectIveness of TrifluridinE/tipiracil in Patients with Previously Treated Metastatic Colorectal Cancer.

AIMS: In the pivotal RECOURSE trial, trifluridine/tipiracil improved survival outcomes in refractory metastatic colorectal cancer (mCRC), while demonstrating an acceptable toxicity profile. Routine clinical practice evidence is important to support the ongoing value of recently approved medicines. Our objective was to assess the utilisation patterns and real-world effectiveness of trifluridine/tipiracil in previously treated mCRC patients. MATERIALS AND METHODS: This was a retrospective observational study including consecutive patients who started trifluridine/tipiracil between 1 April 2018 and 30 September 2019 in the medical oncology departments of three major public hospitals in Portugal. The primary outcome measure was overall survival. Associations between overall survival and patient and tumour characteristics were assessed using multivariate Cox regression analyses. RESULTS: In total, 111 patients were included in the study, with a mean age of 64 years. From these, 45.9% received two prior lines of treatment, 47.8% had three or more previous lines of treatment and 83.6% had Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at baseline. The median duration of trifluridine/tipiracil treatment was 3.7 cycles (95% confidence interval 3.4-4.1). Most patients (80.4%) remained on their planned dose throughout the trifluridine/tipiracil treatment period, fulfilling 100% relative dose intensity. The median overall survival in the total study cohort was 7.9 months (95% confidence interval 6.4-9.8) and the median progression-free survival was 3.4 months (95% confidence interval 3.2-3.9). The median overall survival was significantly higher in patients with a normal serum lactate dehydrogenase (LDH) level (median overall survival 11.2 months for [135, 205] IU/l LDH [95% confidence interval 8.2-NR] and 13.6 months for [205, 251] IU/l LDH [95% confidence interval 8.2-NR]) and in better fitted (ECOG = 0-1) patients (median overall survival 8.0 months; 95% confidence interval 6.7-10.0). The median time to worsening performance status was 6.2 months (95% confidence interval 5.0-8.0). Treatment discontinuation due to adverse events was low (3.1%). CONCLUSION: Our study confirms the effectiveness of trifluridine/tipiracil in real-life mCRC patients. Overall survival and progression-free survival outcomes are consistent with the efficacy profile reported in the earlier randomised RECOURSE clinical trial. Like other real-world studies, we found no additional safety concerns in the use of trifluridine/tipiracil.

Comparing Prevalence of Sarcopenia Using Twelve Sarcopenia Definitions in a Large Multinational European Population of Community-Dwelling Older Adults.

OBJECTIVES: Multinational prevalence data on sarcopenia among generally healthy older adults is limited. The aim of the study was to assess prevalence of sarcopenia in the DO-HEALTH European trial based on twelve current sarcopenia definitions. SETTING AND PARTICIPANTS: This is an analysis of the DO-HEALTH study including 1495 of 2157 community-dwelling participants age 70+ years from Germany, France, Portugal, and Switzerland with complete measurements of the sarcopenia toolbox including muscle mass by DXA, grip strength, and gait speed. MEASUREMENTS: The twelve sarcopenia definitions applied were Asian Working Group on Sarcopenia (AWGS1), AWGS2, Baumgartner, Delmonico, European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, EWGSOP2-lower extremities, Foundation for the National Institutes of Health (FNIH1), FNIH2, International Working Group on Sarcopenia in Older People (IWGS), Morley, and Sarcopenia Definitions and Outcomes Consortium (SDOC). RESULTS: Mean age was 74.9 years (SD 4.4); 63.3% were women. Sarcopenia prevalence ranged between 0.7% using the EWGSOP2 or AWGS2 definition, up to 16.8% using the Delmonico definition. Overall, most sarcopenia definitions, including Delmonico (16.8%), Baumgartner (12.8%), FNIH1(10.5%), IWGS (3.6%), EWGSOP1 (3.4%), SDOC (2.0%), Morley (1.3%), and AWGS1 (1.1%) tended to be higher than the prevalence based on EWGSOP2 (0.7%). In contrast, the definitions AWGS2 (0.7%), EWGSOP2-LE (1.1%), FNIH2 (1.0%) - all based on muscle mass and muscle strength - showed similar lower prevalence as EWGSOP2 (0.7%). Moreover, most sarcopenia definitions did not overlap on identifying sarcopenia on an individual participant-level. CONCLUSION: In this multinational European trial of community-dwelling older adults we found major discordances of sarcopenia prevalence both on a population- and on a participant- level between various sarcopenia definitions. Our findings suggest that the concept of sarcopenia may need to be rethought to reliably and validly identify people with impaired muscle health.

Parent anion radical formation in coenzyme Q0: Breaking ubiquinone family rules.

We report electron attachment (EA) measurements for the parent anion radical formation from coenzyme Q0 (CoQ0) at low electron energies (<2 eV) along with quantum chemical calculations. CoQ0 may be considered a prototype for the electron withdrawing properties of the larger CoQ n molecules, in particular ubiquinone (CoQ10), an electron carrier in aerobic cell respiration. Herein, we show that the mechanisms for the parent anion radical formation of CoQ0 and CoQ n (n = 1,2,4) are remarkably distinct. Reported EA data for CoQ1, CoQ2, CoQ4 and para-benzoquinone indicated stabilization of the parent anion radicals around 1.2-1.4 eV. In contrast, we observe for the yield of the parent anion radical of CoQ0 a sharp peak at âˆ¼ 0 eV, a shoulder at 0.07 eV and a peak around 0.49 eV. Although the mechanisms for the latter feature remain unclear, our calculations suggest that a dipole bound state (DBS) would account for the lower energy signals. Additionally, the isoprenoid side chains in CoQ n (n = 1,2,4) molecules seem to influence the DBS formation for these compounds. In contrast, the side chains enhance the parent anion radical stabilization around 1.4 eV. The absence of parent anion radical formation around 1.4 eV for CoQ0 can be attributed to the short auto-ionization lifetimes. The present results shed light on the underappreciated role played by the side chains in the stabilization of the parent anion radical. The isoprenoid tails should be viewed as co-responsible for the electron-accepting properties of ubiquinone, not mere spectators of electron transfer reactions.

Protective effect of sex steroid hormones on morphological and cellular outcomes after neonatal hypoxia-ischemia: A meta-analysis of preclinical studies.

Sex steroid hormones play an important role in fetal development, brain functioning and neuronal protection. Growing evidence highlights the positive effects of these hormones against brain damage induced by neonatal hypoxia-ischemia (HI). This systematic review with meta-analysis aims to verify the efficacy of sex steroid hormones in preventing HI-induced brain damage in rodent models. The protocol was registered at PROSPERO and a total of 22 articles were included. Moderate to large effects were observed in HI animals treated with sex steroid hormones in reducing cerebral infarction size and cell death, increasing neuronal survival, and mitigating neuroinflammatory responses and astrocyte reactivity. A small effect was evidenced for cognitive function, but no significant effect for motor function; moreover, a high degree of heterogeneity was observed. In summary, data suggest that sex steroid hormones, such as progesterone and 17ß estradiol, improve morphological and cellular outcomes following neonatal HI. Further research is paramount to examine neurological function during HI recovery and standardization of methodological aspects is imperative to reduce the risk of spurious findings.

Non-Status Epilepticus female rats show seizure-like behaviors in the chronic phase of Pilocarpine experimental model

Abstract Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the models chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non-castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.

Resumo Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.