Value of sarcopenia in the resection of colorectal liver metastases-a systematic review and meta-analysis.

Introduction: Sarcopenia is defined as a decline in muscle function as well as muscle mass. Sarcopenia itself and sarcopenic obesity, defined as sarcopenia in obese patients, have been used as surrogates for a worse prognosis in colorectal cancer. This review aims to determine if there is evidence for sarcopenia as a prognostic parameter in colorectal liver metastases (CRLM). Methods: PubMed, Embase, Cochrane Central, Web of Science, SCOPUS, and CINAHL databases were searched for articles that were selected in accordance with the PRISMA guidelines. The primary outcomes were overall survival (OS) and disease-free survival (DFS). A random effects meta-analysis was conducted. Results: After eliminating duplicates and screening abstracts (n = 111), 949 studies were screened, and 33 publications met the inclusion criteria. Of them, 15 were selected after close paper review, and 10 were incorporated into the meta-analysis, which comprised 825 patients. No significant influence of sarcopenia for OS (odds ratio (OR), 2.802 (95% confidence interval (CI), 1.094-1.11); p = 0.4) or DFS (OR, 1.203 (95% CI, 1.162-1.208); p = 0.5) was found, although a trend was defined toward sarcopenia. Sarcopenia significantly influenced postoperative complication rates (OR, 7.905 (95% CI, 1.876-3.32); p = 0.001) in two studies where data were available. Conclusion: Existing evidence on the influence of sarcopenia on postoperative OS as well as DFS in patients undergoing resection for CRLM exists. We were not able to confirm that sarcopenic patients have a significantly worse OS and DFS in our analysis, although a trend toward this hypothesis was visible. Sarcopenia seems to influence complication rates but prospective studies are needed.

[Atypical femoral fracture : Pitfalls in surgical treatment]. / Atypische Femurfraktur : Fallstricke bei der chirurgischen Versorgung.

Atypical femoral fractures are a very rare complication after treatment with bisphosphonates. This case report describes the diagnostic criteria and some particularities of the surgical treatment. Atypical femoral fractures are typically stabilized with intramedullary nails but some pitfalls in surgical treatment, e.g. the choice of implant, have to be considered. Basically, these fractures can be treated using conventional intramedullary nails, which, however, must be used by being adapted depending on the morphology of the femur. The fact that atypical femoral fractures can occur under bisphosphonate treatment should in no way influence the indications for starting anti-osteoporotic treatment.

Use of LigaSure vessel sealing system versus conventional axillary dissection in breast cancer patients: a retrospective comparative study.

BACKGROUND: In locally advanced breast cancer, axillary lymph node dissection remains a pivotal component of surgical therapy. Apart from this, it has been mostly replaced by sentinel node biopsy. Complications after axillary dissection include wound infection, neuropathy, lymphedema and-most frequently-seroma. In this retrospective multi-centre study, we compared the use of LigaSureTM with monopolar electrocautery regarding perioperative outcome. METHODS: A retrospective data analysis from female breast cancer patients who underwent axillary dissection at two breast centres in Austria that are using two different surgical techniques was performed for this study. We compared the rate of complications and re-operations, length of hospital stay, time to drain removal, total drain fluid, seroma formation after drain removal, number of seroma aspirations and total seroma fluid. RESULTS: Seventy one female patients with a median age of 63 (30-83) were included in this study. In 35 patients LigaSureTM and in 36 monopolar cautery was used for axillary dissection. There was no significant difference regarding intraoperative complications and rate of re-operations between the two groups (2.9 vs. 5.6%; p = 1 and 2.9 vs. 13.9%; p = 0.199). The time to drain removal and the length of hospital stay was similar in both groups. A significant difference in the occurence of postoperative wound infection could also not be shown. However, we found a significantly smaller total drain fluid in the LigaSureTM-group compared to the cautery-group (364.6 ml vs. 643.4 ml; p = 0.004). Seroma formation after drain removal was more frequent in the LigaSureTM-group (68.6 vs. 41.7%; p = 0.032) with a higher number of outpatient seroma aspirations (2.0 vs. 0.9; p = 0.005). CONCLUSION: LigaSureTM and monopolar cautery provide equivalent techniques in axillary lymph node dissection with comparable postoperative outcomes.

[Potential effect of the stimulus threshold level of the nociceptive flexion reflex (NFRT) on mortality and delirium incidence in the critically ill patient: a retrospective cohort analysis]. / Potenzieller Einfluss der Reizschwellenhöhe des nozizeptiven Flexorenreflex (NFRT) auf die Mortalitäts- und Delirinzidenz beim kritisch kranken Patienten: eine retrospektive Kohortenanalyse.

BACKGROUND: Mortality and delirium in critically ill patients are affected by the provided analgesics and sedatives. The deeper the sedation and the higher the dose of analgesics applied, the more difficult it is to assess pain and the depth of sedation. Therefore, instrumental measurement methods, such as the measurement of the stimulus threshold of the nociceptive flexion reflex (NFRT), are becoming increasingly more important. OBJECTIVE: The aim of the present study is to investigate a potential association between the level of the nociceptive flexion reflex, mortality, and the occurrence of delirium. MATERIAL AND METHODS: By retrospectively analyzing a pilot data set of 57 ICU patients from the interdisciplinary surgical ICU of Ulm University Hospital surveyed between 11/2018 and 03/2020, a possible association between the NFRT, mortality, and the occurrence of delirium was calculated in an adjusted logistic regression model. Depending on the cut-off value, the stimulus threshold corridors result in the following comparison pairs: < 20 mA vs. 20-40 mA/20-50 mA/20-60 mA, > 40 mA vs. 20-40 mA, > 50 mA vs. 20-50 mA and > 60 mA vs. 20-60 mA. Results are presented as odds ratios (OR) adjusted for age, sex, height, TISS-28, SAPS II, RASS, BPS, and applied analgesics. Pain assessment was performed, in addition to the Behavioral Pain scale, ≥ 3 times daily by measuring NFRT. RESULTS: A statistically nonsignificant tendency for an increase in mortality incidence occurred with an NFRT > 50 mA, versus a stimulus threshold corridor of 20-50 mA (OR 3.3, CI: 0.89-12.43, p = 0.07). A trend toward a reduction in delirium incidence occurred at an NFRT < 20 mA, versus a stimulus threshold corridor of 20-40 mA (OR 0.40, CI: 0.18-0.92, p = 0.03). CONCLUSION: Based on the level of the NFRT, no recommendation can be made at this point to adjust the analgesic regimen of critically ill patients, who are unable to communicate. The observation of a tendency towards an increase in mortality at high stimulus thresholds or a reduction in the occurrence of delirium at low stimulus thresholds of the NFRT must be verified in standardized studies.

Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

OBJECTIVE: To investigate the role of Ca2+/calmodulin-dependent protein kinase 2 (CaMKK2) in post-traumatic osteoarthritis (PTOA). METHODS: Destabilization of the medial meniscus (DMM) or sham surgeries were performed on 10-week-old male wild-type (WT) and Camkk2-/- mice. Half of the DMM-WT mice and all other cohorts (n = 6/group) received tri-weekly intraperitoneal (i.p.) injections of saline whereas the remaining DMM-WT mice (n = 6/group) received i.p. injections of the CaMKK2 inhibitor STO-609 (0.033 mg/kg body weight) thrice a week. Study was terminated at 8- or 12-weeks post-surgery, and knee joints processed for microcomputed tomography imaging followed by histology and immunohistochemistry. Primary articular chondrocytes were isolated from knee joints of 4-6-day-old WT and Camkk2-/- mice, and treated with 10 ng/ml interleukin-1ß (IL)-1ß for 24 or 48 h to investigate gene and protein expression. RESULTS: CaMKK2 levels and activity became elevated in articular chondrocytes following IL-1ß treatment or DMM surgery. Inhibition or absence of CaMKK2 protected against DMM-associated destruction of the cartilage, subchondral bone alterations and synovial inflammation. When challenged with IL-1ß, chondrocytes lacking CaMKK2 displayed attenuated inflammation, cartilage catabolism, and resistance to suppression of matrix synthesis. IL-1ß-treated CaMKK2-null chondrocytes displayed decreased IL-6 production, activation of signal transducer and activator of transcription 3 (Stat3) and matrix metalloproteinase 13 (MMP13), indicating a potential mechanism for the regulation of inflammatory responses in chondrocytes by CaMKK2. CONCLUSIONS: Our findings reveal a novel function for CaMKK2 in chondrocytes and highlight the potential for its inhibition as an innovative therapeutic strategy in the prevention of PTOA.

Natural language processing of radiology reports to investigate the effects of the COVID-19 pandemic on the incidence and age distribution of fractures.

OBJECTIVE: During the COVID-19 pandemic, the number of patients presenting in hospitals because of emergency conditions decreased. Radiology is thus confronted with the effects of the pandemic. The aim of this study was to use natural language processing (NLP) to automatically analyze the number and distribution of fractures during the pandemic and in the 5 years before the pandemic. MATERIALS AND METHODS: We used a pre-trained commercially available NLP engine to automatically categorize 5397 radiological reports of radiographs (hand/wrist, elbow, shoulder, ankle, knee, pelvis/hip) within a 6-week period from March to April in 2015-2020 into "fracture affirmed" or "fracture not affirmed." The NLP engine achieved an F1 score of 0.81 compared to human annotators. RESULTS: In 2020, we found a significant decrease of fractures in general (p < 0.001); the average number of fractures in 2015-2019 was 295, whereas it was 233 in 2020. In children and adolescents (p < 0.001), and in adults up to 65 years (p = 0.006), significantly fewer fractures were reported in 2020. The number of fractures in the elderly did not change (p = 0.15). The number of hand/wrist fractures (p < 0.001) and fractures of the elbow (p < 0.001) was significantly lower in 2020 compared with the average in the years 2015-2019. CONCLUSION: NLP can be used to identify relevant changes in the number of pathologies as shown here for the use case fracture detection. This may trigger root cause analysis and enable automated real-time monitoring in radiology.

Deep learning for diagnosis and survival prediction in soft tissue sarcoma.

BACKGROUND: Clinical management of soft tissue sarcoma (STS) is particularly challenging. Here, we used digital pathology and deep learning (DL) for diagnosis and prognosis prediction of STS. PATIENTS AND METHODS: Our retrospective, multicenter study included a total of 506 histopathological slides from 291 patients with STS. The Cancer Genome Atlas cohort (240 patients) served as training and validation set. A second, multicenter cohort (51 patients) served as an additional test set. The use of the DL model (DLM) as a clinical decision support system was evaluated by nine pathologists with different levels of expertise. For prognosis prediction, 139 slides from 85 patients with leiomyosarcoma (LMS) were used. Area under the receiver operating characteristic (AUROC) and accuracy served as main outcome measures. RESULTS: The DLM achieved a mean AUROC of 0.97 (±0.01) and an accuracy of 79.9% (±6.1%) in diagnosing the five most common STS subtypes. The DLM significantly improved the accuracy of the pathologists from 46.3% (±15.5%) to 87.1% (±11.1%). Furthermore, they were significantly faster and more certain in their diagnosis. In LMS, the mean AUROC in predicting the disease-specific survival status was 0.91 (±0.1) and the accuracy was 88.9% (±9.9%). Cox regression showed the DLM's prediction to be a significant independent prognostic factor (P = 0.008, hazard ratio 5.5, 95% confidence interval 1.56-19.7) in these patients, outperforming other risk factors. CONCLUSIONS: DL can be used to accurately diagnose frequent subtypes of STS from conventional histopathological slides. It might be used for prognosis prediction in LMS, the most prevalent STS subtype in our cohort. It can also help pathologists to make faster and more accurate diagnoses. This could substantially improve the clinical management of STS patients.

Conservative versus tailored surgical treatment in patients with first time lateral patella dislocation: a randomized-controlled trial.

BACKGROUND: Patellar instability has a high incidence and occurs particularly in young and female patients. If the patella dislocates for the first time, treatment is usually conservative. However, this cautious approach carries the risk of recurrence and of secondary pathologies such as osteochondral fractures. Moreover, there is also risk of continuous symptoms apparent, as recurrent patella dislocation is related to patellofemoral osteoarthritis as well. An initial surgical treatment could possibly avoid these consequences of recurrent patella dislocation. METHODS: A prospective, randomized-controlled trial design is applied. Patients with unilateral first-time patella dislocation will be considered for participation. Study participants will be randomized to either conservative treatment or to a tailored patella stabilizing treatment. In the conservative group, patients will use a knee brace and will be prescribed outpatient physical therapy. The surgical treatment will be performed in a tailored manner, addressing the pathologic anatomy that predisposes to patella dislocation. The Banff Patellofemoral Instability-Instrument 2.0, recurrence rate, apprehension test, joint degeneration, and the Patella Instability Severity Score will serve as outcome parameters. The main analysis will focus on the difference in change of the scores between the two groups within a 2-year follow-up. Statistical analysis will use linear mixed models. Power analysis was done for the comparison of the two study arms at 2-year follow-up with regard to the BPII Score. A sample size of N = 64 per study arm (128 overall) provides 80% power (alpha = 0.05, two-tailed) to detect a difference of 0.5 standard deviations in a t-test for independent samples. DISCUSSION: Although several studies have already dealt with this issue, there is still no consensus on the ideal treatment concept for primary patellar dislocation. Moreover, most of these studies show a unified surgical group, which means that all patients were treated with the same surgical procedure. This is regarded as a major limitation as surgical treatment of patella dislocation should depend on the patient's anatomic pathologies leading to patellar instability. To our knowledge, this is the first study investigating whether patients with primary patella dislocation are better treated conservatively or operatively with tailored surgery to stabilize the patella. TRIAL REGISTRATION: The study will be prospectively registered in the publicly accessible database www.ClinicalTrials.gov .

[Nontuberculous Mycobacterial Pulmonary Disease - The New ATS/ERS/ESCMID/IDSA Guideline]. / Lungenerkrankung durch nicht-tuberkulöse Mykobakterien.

The new ATS/ERS/ESCMID/IDSA guideline answers 22 PICO questions on the treatment of lung diseases caused by Mycobacterium avium complex (MAC), M. kansasii, M. xenopi and M. abscessus. NON-TUBERCULOUS MYCOBACTERIA (NTM) LUNG DISEASE: Especially in patients with microscopic detection of acid-fast bacteria in sputum or with cavernous disease manifestation, the start of treatment should not be delayed. Treatment should be based on species-specific resistance testing (according to the CLSI guidelines). In selected patients, adjuvant surgical resection after consultation with an expert is recommended. MAC LUNG DISEASE: Therapy is based on a regimen with at least three drugs including a macrolide (rather azithromycin than clarithromycin) and ethambutol. For patients with cavitation, with pronounced nodular bronchiectatic disease or with macrolide resistance, daily oral therapy should be expanded by parenteral amikacin or streptomycin. Liposomally encapsulated amikacin for inhalation is recommended in patients with treatment failure. Patients with nodular-bronchiectatic disease manifestation should receive oral macrolide-based therapy, which - depending on the extent - can be given 3 times a week. The recommended duration is 12 months after conversion of the sputum culture. M. KANSASII LUNG DISEASE: The triple combination of rifampicin, ethambutol and macrolide (or isoniazid) is recommended for at least 12 months. In patients with rifampicin resistance or intolerance, moxifloxacin is recommended as a replacement. M. XENOPI LUNG DISEASE: The combination of rifampicin, ethambutol and macrolide (and/or moxifloxacin) is recommended for at least 12 months after conversion of the sputum culture. For patients with cavernous disease manifestation, it is recommended to add at least parenteral amikacin and to consult experts. M. ABSCESSUS LUNG DISEASE: At least 3, in the beginning rather 4 drugs are recommended for therapy. The choice of substance should be based on a in vitro resistance test. Macrolides are the basis, but should not be counted in patients with strains with inducible macrolide resistance. Due to the lack of data, no explicit recommendations are made regarding the duration of therapy; a consultation of experts is recommended.

[COVID-19 associated pneumonia despite repeatedly negative PCR-analysis from oropharyngeal swabs]. / COVID-19-assoziierte Pneumonie trotz persistierend negativen PCR-Tests aus oropharyngealen Abstrichen.

PATIENT HISTORY AND CLINICAL FINDINGS: A 46-year old construction worker presented at the emergency department with two orthostatic syncopes. The patient complained of prolonged fever and coughs for 7 days which had not improved after oral treatment with sultamicillin for 5 days, prescribed by the patient's general practitioner. Physical examination showed high blood pressure due to previously known hypertension. Other vital signs without pathological findings. Pulmonary auscultation showed basal soft crackling noises of the left lung. FINDINGS AND DIAGNOSIS: Laboratory examination showed increased values for LDH, pro-BNP and CRP and normal values for leucocytes and procalcitonin. Conventional X-Ray of the chest showed bipulmonal lateral atypical infiltrates. After the first PCR turned in negative another PCR-analysis for SARS-CoV-2 of a deep oral swab-sample was performed since the clinical, laboratory and radiological findings were typical for COVID-19. Again, SARS-CoV-2-RNA was not detected. A CT-scan of the chest showed bipulmonal lateral ground-glass attenuation, again typical for COVID-19 associated pneumonia. After a third attempt for a PCR-analysis of a deep oral swab-sample was negative, analysis of a sputum was performed which finally confirmed the diagnosis of COVID-19 associated pneumonia. THERAPY AND COURSE OF EVENTS: The patient was admitted for evaluation of syncopes and suspect of COVID-19 associated pneumonia. The patient was prophylactically isolated while the result of SARS-CoV-2-PCR from a deep oral swab was pending. Suspecting a possible secondary bacterial infection at the beginning, intravenous antibiotic treatment with ampicillin/sulbactam was initiated. While further examinations showed no indication for bacterial infection, antibiotics were discontinued after 3 days. Due to clinical recovery antiviral therapy was not performed after confirming the diagnosis. The patient was discharged 17 days after onset of first symptoms without any requirements for further isolation. CONCLUSION: This casuistic describes a case of COVID-19 associated pneumonia presenting with typical clinical features, laboratory and radiological findings. Detection of viral RNA was not successful from deep oral swab-samples despite repeated attempts. Finally, PCR-analysis of sputum confirmed the diagnosis. Analysis of deeper airway samples (sputum, bronchoalveolar lavage, tracheal secretions) or stool for SARS-CoV-2 should be performed in cases of evident clinical suspicion of COVID-19 and negative PCR results from deep oral swabs.

Genetic Algorithm Optimization of Core-Shell Nanowire Betavoltaic Generators.

Numerical optimization has been used to determine the optimum junction design for core-shell nanowires used in betavoltaic generators. A genetic algorithm has been used to calculate the relative thickness, height, and doping of each segment within silicon, gallium arsenide, and gallium phosphide nanowires. Using the simulated spectra and energy deposition of nickel-63, nickel citrate, tritium, and tritiated butyl, devices with power output and overall efficiency up to 8 µW.cm-2 and 12%, respectively, have been predicted. Compared to previously investigated axial nanowires, the core-shell structures simulated here have realized drastic improvements by reducing surface recombination for longer nanowires. In addition, core-shell nanowires are shown to be capable of nearly matching the ideal performance predicted for this device structure. A new approach for calculating the practical upper limit of betavoltaic performance is presented and additional methods for improvement are discussed.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Progress of instability in fragility fractures of the pelvis: An observational study.

Fragility fractures of the pelvis (FFP) are an increasing entity among elderly persons. Characteristics are different from high-energy pelvic trauma. Little is known about the natural course of FFP in conservative and after operative treatment. MATERIALS AND METHODS: Medical charts and radiologic data of 148 patients with an FFP, who were admitted in a 3-year period, were analysed retrospectively. Incidence and characteristics of fracture progression (FP) were noted. RESULTS: Patients presenting early after a traumatic event had more often non-displaced fractures, fractures with lower FFP Type classification and were more frequently treated conservatively. FP was observed in 21 cases (14.2%), twenty times after conservative and once after operative treatment. FP under conservative treatment occurred in female patients only. Patients with FP were younger than patients without. FP occurred in all fracture types, most frequently in FFP Type I. A second CT scan was positive for FP in 39.2% of patients with prolonged pain or restricted mobility. CONCLUSION: FP is a real phenomenon, occurring in a minority of FFP patients. Female patients are at highest risk. Repeated CT scan is positive in nearly 40% of patients with continuing pain or restricted mobility. Operative treatment is a good preventive measure of FP as FP does only exceptionally occur after operative fixation of FFP.

Comparison of a 2D iPad application and 3D body scanner to air displacement plethysmography for measurement of body fat percentage.

BACKGROUND: Novel and innovative imaging methods that rapidly estimate body fat percentage (%BF) are publicly available, yet little is known about their accuracy. The present study evaluated the test-retest reliability of a two-dimensional iPad (Apple, Inc., Cupertino, CA, USA) application (2D APP) and a three-dimensional body scanner (3D SCAN) for estimating %BF and compared both imaging methods with air displacement plethysmography (Bod Pod; Cosmed USA, Inc., Concord, CA, USA). METHODS: Seventy-nine adults (37 female, 42 male) varying widely in age [mean (SD), range] [32.9 (12.4), 18-65 years] and body mass index [25.0 (4.9), 18.2-41.8 kg m-2 ] were measured with the Bod Pod and twice with the 3D SCAN and the 2D APP in a repeated-measures design. RESULTS: Test-retest reliability was excellent for both the 2D APP (intraclass correlation = 0.993) and the 3D SCAN (intraclass correlation = 0.993) with the SEM <1% BF for both methods. Although the three methods were highly correlated with each other (r = 0.857-0.923), the mean %BF estimations were significantly different (P = 0.001). The 2D APP [19.9 (8.2)%BF] underestimated the Bod Pod value [21.9 (9.4)%BF] and the 3D SCAN [24.0 (6.8)%BF] overestimated. Additionally, the SE of estimate and total error exceeded 4% BF for both 2D APP and 3D SCAN, and both methods tended to overestimate lean participants and underestimate fat participants. CONCLUSIONS: Although highly reliable, neither the 2D APP, nor the 3D SCAN provided valid estimates of %BFBod Pod .

The effects of bolt length on penetration hole characteristics, brain damage and specified-risk material dispersal in finished cattle stunned with a penetrating captive bolt stunner.

The purpose of this study was to determine the effect of captive bolt lengths on penetration hole characteristics, brain damage, and specified risk material (SRM) dispersal. Cattle were stunned with a pneumatic captive bolt stunner using: standard (15.2 cm; STRD), medium (16.5 cm; MED), or long (17.8 cm; LON) bolts. Heads (N = 293) and exsanguination blood (N = 103) were collected for analyses. Penetration hole diameter and depth differed by treatment (P ≤ 0.004); both parameters were greatest for LON (P < 0.05). Presence of damage in frontal, parietal, and occipital lobes, olfactory bulb, and collective area including the corpus callosum, fornix and thalamus were impacted by treatment (P < 0.003). Treatment did not impact SRM dispersal (P = 0.33), determined by presence of glial acidic fibrillary protein. Data suggest that bolt length affects both the extent of brain damage and the specific structures damaged but all bolt lengths are successful in causing substantial brain damage and subsequent insensibility.

Pelvimetry of multiparous Nellore cows in the cycling and early puerperal stages / Pelvimetria de vacas pluríparas da raça Nellore em estágio cíclico e início do puerpério

Pelvis is an osteoligamentous complex, which is classified as dolichopellic in ruminants. Impairments linked to incompatibility of pelvic canal and fetal size is directly related to pelvic anatomy and disposition. Heritability of pelvic area characteristics varies from moderate to high, demonstrating its importance for animal selection. Pelvimetry can be performed through direct and indirect methods that were accessed in this study aiming to establish a correlation between internal and external pelvic dimensions in multiparous Nellore cows (26 animals) at cycling and early puerperal (up to 30 days postpartum) reproductive stages. Pelvic dimensions measured by descriptive analysis were higher at early puerperal stage. Strong Pearson's correlation was determined between internal and external pelvic dimensions, between reproductive stages, and between pelvic girdle area and internal pelvic area. Significant Tukey's test differences between animals in internal and external dimensions were also found. According to the results, the pelvic anatomy of Nellore cows varies according to their reproductive stage. We detach that and provide data regarding the use of internal pelvic area for animal selection studies on this breed is determined and should be measured using the proposed formula, since it can confirm statistical differences in the areas of pelvic components between animals in the cycling and early puerperal stages.(AU)

A pelve é considerada um complexo osteoligamentoso, classificada como dolicopélvica em ruminantes. Prejuízos ligados à incompatibilidade canal pélvico/tamanho fetal relacionam-se diretamente à anatomia e disposição pélvica. A característica de área pélvica apresenta herdabilidade variando de moderada a alta, indicando sua importância na seleção animal. A pelvimetria inclui formas direta e indireta. Neste estudo utilizaram-se vinte e seis vacas multíparas, da raça Nelore, agrupadas de acordo com o estágio reprodutivo, cíclico e em início de estágio puerperal (até 30 dias pós-parto). Através deste, objetivou-se evidenciar a relação das medidas pélvicas internas e externas nos diferentes períodos reprodutivos e coletar obter dados referentes a utilização da área interna do hexágono no estudo pelvimétrico dessa espécie em estágio cíclico ou puerperal. Para tanto, realizou-se, a pelvimetria direta e indireta. Os resultados obtidos, pela análise descritiva, foram maiores para animais em início de estágio puerperal. Por meio da correlação de Pearson podem-se observar fortes correlações entre mensurações pélvicas internas e externas, também entre os grupos propostos, e forte correlação entre elipse pélvica e área interna do hexágono. Pelo teste Tukey diferenças significativas tanto em medidas internas e externas puderam ser demonstradas. Conclui-se que as condições anatômicas da pelve variam de acordo com o estágio reprodutivo do animal, que aferição da área pélvica utilizando a formula proposta para área do hexágono interno é relevante pois foi possível comprovar a diferenças estatísticas de áreas nas fases cíclica e puerperal.(AU)

MCC950 blocks enhanced interleukin-1ß production in patients with NLRP3 low penetrance variants.

OBJECTIVE: To determine the role of the NLRP3 inflammasome by using the selective NLRP3 inhibitor MCC950 in patients with NLRP3 low penetrance variants and clinical symptoms suggestive for an autoinflammatory syndrome including central nervous system (CNS) involvement. METHODS: Nineteen symptomatic patients with low penetrance NLRP3 variants (Q703K n = 17, V198M n = 2) recruited between 2011 and 2017 were included in this monocentric study. A functional inflammasome activation assay was performed in patients in comparison to healthy controls (HC), including the determination of interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-α) secretion in the presence of the NLRP3 selective small-molecule inhibitor MCC950. Detailed clinical features were assessed and anti-IL-1 treatment response was determined. RESULTS: Peripheral blood mononuclear cells (PBMC) from patients with low penetrance NLRP3 variants displayed enhanced IL-1ß levels following inflammasome activation compared to HC. Furthermore, IL-1ß release was NLRP3-dependent as it was blocked by MCC950. The production of IL-6 and TNF-α was also increased in patients with low penetrance NLRP3 variants. Clinically, they presented with a heterogenous spectrum of neurological manifestations, while cranial nerve inflammation was the most common feature. Overall inflammasome activation did not correlate with disease severity. Eight of ten treated patients responded to anti IL-1 treatment, however a complete response was only documented in four patients. CONCLUSION: PBMC of several patients with NLRP3 low penetrance variants and CNS manifestation showed increased NLRP3-specific IL-1ß release upon stimulation and elevated NLRP3-independent IL-6 and TNF-α levels as those were not suppressed by MCC950. Our data suggest that beside the possible causal involvement of the NLRP3 inflammasome additional, yet unidentified genetic or environmental factors may contribute to the multi-organ inflammation in our patients and explain the partial response to IL-1 targeting therapies.

4-Deoxyraputindole C induces cell death and cell cycle arrest in tumor cell lines.

Several molecules extracted from natural products exhibit different biological activities, such as ion channel modulation, activation of signaling pathways, and anti-inflammatory or antitumor activity. In this study, we tested the antitumor ability of natural compounds extracted from the Raputia praetermissa plant. Among the compounds tested, an alkaloid, here called compound S4 (4-Deoxyraputindole C), showed antitumor effects against human tumor lineages. Compound S4 was the most active against Raji, a lymphoma lineage, promoting cell death with characteristics that including membrane permeabilization, dissipation of the mitochondrial potential, increased superoxide production, and lysosomal membrane permeabilization. The use of cell death inhibitors such as Z-VAD-FMK (caspase inhibitor), necrostatin-1 (receptor-interacting serine/threonine-protein kinase 1 inhibitor), E-64 (cysteine peptidases inhibitor), and N-acetyl- L-cysteine (antioxidant) did not decrease compound S4-dependent cell death. Additionally, we tested the effect of cellular activity on adherent human tumor cells. The highest reduction of cellular activity was observed in A549 cells, a lung carcinoma lineage. In this lineage, the effect on the reduction of the cellular activity was due to cell cycle arrest, without plasma membrane permeabilization, loss of the mitochondrial potential or lysosomal membrane permeabilization. Compound S4 was able to inhibit cathepsin B and L by a nonlinear competitive (negative co-operativity) and simple-linear competitive inhibitions, respectively. The potency of inhibition was higher against cathepsin L. Compound S4 promoted cell cycle arrest at G 0 and G 2 phase, and increase the expression of p16 and p21 proteins. In conclusion, compound S4 is an interesting molecule against cancer, promoting cell death in the human lymphoma lineage Raji and cell cycle arrest in the human lung carcinoma lineage A549.