Does early exercise intolerance effect time to return to play, symptom burden, neurocognition, Vestibular-Ocular-Motor (VOM) function and academic ability in acutely concussed student-athletes?

INTRODUCTION: Early Exercise Intolerance (EEI) is associated with delayed recovery and longer time to Return To Play (RTP), but this has not been established.Participants; (n = 52, male n = 30) UK university-aged rugby-union student-athletes. METHODS: Student-athletes completed baseline screening (July-October 2021 and 2022). The test battery was repeated within 48 h, 4, 8 and 14 days after a Sports-Related Concussion (SRC) with the Buffalo Concussion Bike or Treadmill Test to set sub-symptom heart rate threshold. Student-athletes then completed a controlled early exercise protocol in-between reassessment (days 3, 5-7 and 9-13). Those with EEI were compared to those with early-exercise tolerance. OUTCOME MEASURES: Post-Concussion Symptom Scale, Immediate Post-Concussion and Cognitive Test, Vestibular-Ocular Motor Screening Tool and the Revised Perceived Academic Impact Tool. RESULTS: EEI was seen throughout the initial 14-days post-SRC (23.8%, 22.4%, 25.5%. 25.0%). EEI was associated with a slower reaction time within 48 h (-0.01 (-0.030-0.043) Vs 0.06 (0.033-0.24), p = 0.004) and greater VOMS scores within 48 h; (0.00 (0.00-4.00) Vs 5.50 (2.75-9.00), p = 0.016) and 4 days (0.00 (0.00-2.00) Vs 5.00 (0.00-6.00), p = 0.044). RTP was 12.5 days longer in those with EEI at 14-days post-SRC. CONCLUSION: EEI is prevalent following an SRC in university-aged student-athletes and was associated with delayed recovery and RTP.

Musculoskeletal injury or Sports-Related Concussion (SRC) in a season of rugby union does not affect performance on concussion battery testing in university-aged student-athletes.

BACKGROUND: Sub-concussive and concussive impacts sustained during contact sports such as rugby may affect neurocognitive performance, vestibular-ocular-motor function, symptom burden and academic ability. METHOD: Student-athletes (n = 146) participating in rugby union British Universities or domestic competitions were assessed on the Immediate Post-Concussion and Cognitive Test, Post-Concussion Symptom Scale, vestibular-oculo-motor screening tool and revised perceived academic impact tool. Individual change from pre-season (July-September 2021) to 2-weeks following last exposure to contact (April-July 2022) was analysed. RESULTS: Symptom burden significantly worsened (p=0.016) over the season. Significant improvements on verbal memory (p=0.016), visual memory (p=0.008) and motor processing speed (p=0.001) suggest a possible learning effect. Surprisingly, the number of days lost to concussion significantly and positively affected performance on verbal memory (p = 0.018) and reaction time (p = 0.027). Previous concussive events significantly predicted a worsening in symptom burden (p < 0.028), as did in-season concussive events, predicting improved verbal memory (p = 0.033) and symptom burden change (p = 0.047). Baseline performance significantly affected change on several neurocognitive tests, with low-scorers showing more improvement over the season. CONCLUSION: Participation in rugby union was not associated with deleterious effects on brain function. Previous concussive events and in-season factors, possibly related to learning effects, may explain improvement in cognitive function across the season.

Establishment of patient-derived tumor organoids to functionally inform treatment decisions in metastatic colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (mCRC) patients tend to have modest benefits from molecularly driven therapeutics. Patient-derived tumor organoids (PDTOs) represent an unmatched model to elucidate tumor resistance to therapy, due to their high capacity to resemble tumor characteristics. MATERIALS AND METHODS: We used viable tumor tissue from two cohorts of patients with mCRC, naïve or refractory to treatment, respectively, for generating PDTOs. The derived models were subjected to a 6-day drug screening assay (DSA) with a comprehensive pipeline of chemotherapy and targeted drugs against almost all the actionable mCRC molecular drivers. For the second cohort DSA data were matched with those from PDTO genotyping. RESULTS: A total of 40 PDTOs included in the two cohorts were derived from mCRC primary tumors or metastases. The first cohort included 31 PDTOs derived from patients treated in front line. For this cohort, DSA results were matched with patient responses. Moreover, RAS/BRAF mutational status was matched with DSA cetuximab response. Ten out of 12 (83.3%) RAS wild-type PDTOs responded to cetuximab, while all the mutant PDTOs, 8 out of 8 (100%), were resistant. For the second cohort (chemorefractory patients), we used part of tumor tissue for genotyping. Four out of nine DSA/genotyping data resulted applicable in the clinic. Two RAS-mutant mCRC patients have been treated with FOLFOX-bevacizumab and mitomycin-capecitabine in third line, respectively, based on DSA results, obtaining disease control. One patient was treated with nivolumab-second mitochondrial-derived activator of caspases mimetic (phase I trial) due to high tumor mutational burden at genotyping, experiencing stable disease. In one case, the presence of BRCA2 mutation correlated with DSA sensitivity to olaparib; however, the patient could not receive the therapy. CONCLUSIONS: Using CRC as a model, we have designed and validated a clinically applicable methodology to potentially inform clinical decisions with functional data. Undoubtedly, further larger analyses are needed to improve methodology success rates and propose suitable treatment strategies for mCRC patients.

Recovery of symptoms, neurocognitive and vestibular-ocular-motor function and academic ability after sports-related concussion (SRC) in university-aged student-athletes: a systematic review.

BACKGROUND: Physiological differences between a maturing and matured brain alters how Sports-Related Concussion (SRC) affects different age groups; therefore, a review specific to university-aged student-athletes is needed. OBJECTIVES: Determine time to recovery for symptom burden, neurocognitive and Vestibular-Ocular-Motor (VOM) function and academic impact in university-aged student-athletes. METHODS: Searches were conducted in PubMed, SpringerLink, PsycINFO, Science Direct, Scopus, Cochrane, Web of Science and EMBASE. Articles were included if they contained original data collected within 30 days in university-aged student-athletes, analysed SRC associated symptoms, neurocognitive or VOM function or academic ability and published in English. Two reviewers independently reviewed sources, using the Oxford Classification of Evidence-Based Medicine (CEBM) and the Downs and Black checklist, and independently extracting data before achieving consensus. RESULTS: 58 articles met the inclusion criteria. Recovery of symptoms occurred by 7 and 3-5.3 days for neurocognition. The evidence base did not allow for a conclusion on recovery time for VOM function or academic ability. Few papers investigated recovery times at specified re-assessment time-points and have used vastly differing methodologies. CONCLUSIONS: To fully understand the implication of SRC on the university-aged student-athlete' studies using a multi-faceted approach at specific re-assessments time points are required.Systematic review registration number: CRD42019130685.

Diagnostic performance of LI-RADS in adult patients with rare hepatic tumors.

OBJECTIVE: The rare hepatic tumor can have a wide spectrum of radiologic features, representing a diagnostic challenge. Our purpose is to report the experience of a National Cancer Center, emphasizing the radiological features encountered and assessing the LR-M categories in the diagnostic performances for these lesions. PATIENTS AND METHODS: We assessed 113 patients who underwent surgical resection or biopsy for rare liver lesions from May 2010 to December 2020. For these patients a computerized search of radiological records was performed to identify which had been studied with MRI and CT. For each lesion, the radiologists recorded the attenuation on CT studies and signal intensity (SI) in T1 weighted (W), in T2-W, DWI and in the related map of the apparent diffusion coefficient (ADC). We assessed the presence and the type of contrast enhancement (CE) during contrast study on CT and MRI and the enhancement was categorized according to LI-RADS 2018. We also assessed the presence of other features in LR-M categories (ancillary LR-M features) in order to classify different subgroups. The lesions were classified according to LR categories, and the gold standard was histological analysis. RESULTS: The final study population included 95 patients (46 females and 49 males), with a mean age of 51 years (range 38-83 years). 83 patients had solid lesions, 12 patients had cystic lesions (simple or complex). According to histological analysis, we categorized 79 patients with malignant lesions and 16 patients with benign lesions. According to radiological features we assessed as malignant 82 patients (79 true malignant and 3 false malignant), as benign 13 patients (all true benign). Therefore, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiological features to identify benign and malignant lesions were 100.0%, 81.3%, 96.3%, 100.0% and 96.8%, respectively. We found no significant difference in signal and contrast enhancement appearance among all LR-M categories (p-value =0.34 at Chi square test). However, among LR-M categories the presence of satellite nodules was a feature typical of cHCC-CC (p-value < 0.05 at Chi square test). The presence of intra lesion necrosis and haemorrhage was suggestive of sarcoma (p-value < 0.05 at Chi square test). CONCLUSIONS: High diagnostic accuracy was obtained by LI-RADS classification between malignant and benign lesion. The presence of ancillary features could help the radiologist towards a correct diagnosis.

Prospective study with specific Re-Assessment time points to determine time to recovery following a Sports-Related Concussion in university-aged student-athletes.

BACKGROUND: Time to recovery for symptom burden and neurocognition following a Sports-Related Concussion (SRC) has previously been determined by consolidating varying re-assessment time points into a singular point, and has not been established for Vestibular-Ocular-Motor (VOM) function or academic ability. OBJECTIVES: Establish when recovery of symptom burden, neurocognition, VOM function, and academic ability occurs in university-aged student-athletes. METHODS: Student-athletes completed an assessment battery (Post-Concussion Symptom Scale (PCSS), Immediate Post-Concussion Assessment and Cognitive Test (ImPACT), Vestibular Ocular-Motor Screening (VOMS), Perceived Academic Impairment Tool (PAIT)) during pre-season (n = 140), within 48 hours, 4, 8 and 14 days post-SRC and prior to Return To Play (RTP) and were managed according to the Rugby Football Union' community pathway (n = 42). Student-athletes were deemed recovered or impaired according to Reliable Change Index' (RCI) or compared to their individual baseline. RESULTS: Symptom burden recovers by four days post-SRC on RCI and to baseline by eight days. VOM function and academic ability recovers by 8 days. Some student-athletes demonstrated worse performance at RTP on all tests by RCI and to baseline, except for on VOMS score and near point convergence by RCI change. CONCLUSIONS: Variation in individual university-aged student-athletes requires a multi-faceted approach to establish what dysfunctions post-SRC exist and when recovery occurs.

Liver resection and ablation for squamous cell carcinoma liver metastases.

BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

Pancreatic cancer detection and characterization: state of the art and radiomics.

Pancreatic ductal adenocarcinoma (PDAC) represents a challenge for a multidisciplinary oncology team. Diagnosis of PDAC remains challenging due to overlapping imaging features with benign lesions, notwithstanding great advances with computed tomography (CT) and magnetic resonance imaging (MRI). The term "Radiomics" has recently been introduced to define a mathematical process to extract countless quantitative features from medical images (including each diagnostic technique) with high throughput computing for diagnosis and prediction. This article is an updated overview of the imaging techniques to be employed during detection and characterization of pancreatic cancer diagnostic workup. Particularly, the limitations and advantages of the different imaging techniques are discussed, with a particular focus on functional imaging. This overview is the result of a self-study without protocol and registration number. Articles published in the English language from January 2000 to January 2021 were included. We analyzed 15 papers on radiomics. The possibility of functional imaging, such as CT, MRI, and radiomics has revolutionized pancreatic imaging, improving the detection and characterization of the lesions and allowing a prognosis related to radiological features, favoring the process of personalized medicine.

Uterine artery embolisation or myomectomy for women with uterine fibroids wishing to avoid hysterectomy: a cost-utility analysis of the FEMME trial.

OBJECTIVES: To assess the cost-effectiveness of uterine artery embolisation (UAE) and myomectomy for women with symptomatic uterine fibroids wishing to avoid hysterectomy. DESIGN: Economic evaluation alongside the FEMME randomised controlled trial. SETTING: 29 UK hospitals. POPULATION: Premenopausal women who had symptomatic uterine fibroids amenable to UAE or myomectomy wishing to avoid hysterectomy. 254 women were randomised to UAE (127) and myomectomy (127). METHODS: A within-trial cost-utility analysis was conducted from the perspective of the UK NHS. MAIN OUTCOME MEASURES: Quality-adjusted life years (QALYs) measured using the EuroQoL EQ-5D-3L, combined with costs to estimate cost-effectiveness over 2 and 4 years of follow-up. RESULTS: Over a 2-year time horizon, UAE was associated with higher mean costs (difference £645; 95% CI -1381 to 2580) and lower QALYs (difference -0.09; 95% CI -0.11 to -0.04) when compared with myomectomy. Similar results were observed over the 4-year time horizon. Thus, UAE was dominated by myomectomy. Results of the sensitivity analyses were consistent with the base case results for both years. Over 2 years, UAE was associated with higher costs (difference £456; 95% CI -1823 to 3164) and lower QALYs (difference -0.06; 95% CI -0.11 to -0.02). CONCLUSIONS: Myomectomy is a cost-effective option for the treatment of uterine fibroids. The differences in costs and QALYs are small. Women should be fully informed and have the option to choose between the two procedures. TWEETABLE ABSTRACT: Fully informed women with uterine fibroids should have a choice between uterine artery embolisation or myomectomy.

Electroporation-based treatments in minimally invasive percutaneous, laparoscopy and endoscopy procedures for treatment of deep-seated tumors.

Electroporation (EP) techniques, used alone (Irreversible Electroporation, IRE) or in combination with anti-cancer drugs (Electrochemotherapy, ECT), have been shown to be effective in the treatment of several types of cancers. The efficacy of ECT and IRE is well demonstrated for the treatment of non-superficial tumor metastases, and it depends on the applied electrical parameters. Particularly, ECT is an effective local therapy that uses electroporation to enhance the cytotoxic effect of bleomycin or cisplatin injected intravenously or intratumorally. Pre-clinical investigations to test alternative anti-cancer drugs, explore new combinations of treatment modalities, and evaluate different sets of pulse protocols for effective tissue electroporation, are ongoing. Further ECT developments include the treatment of deep-seated tumors with percutaneous, laparoscopy, and endoscopy approaches, with the aim of establishing a less invasive approach. ECT is highly effective in the treatment of tumors of any histology, in minimizing the damage of critical normal tissue or organs, and in reducing pain and muscular contractions. This work describes the new technological advances in the field of ECT treatment for deep-seated tumors.

Does Vestibular-Ocular-Motor (VOM) Impairment Affect Time to Return to Play, Symptom Severity, Neurocognition and Academic Ability in Student-Athletes following acute Concussion?

Introduction: Research indicates Sports-Related Concussion (SRC) impairs Vestibular-Ocular-Motor (VOM) function. The aim was to explore if VOM impairment correlates with longer Return To Play (RTP), symptom burden, neurocognitive performance and academic capability.Participants: 40 (61.4% male) Loughborough University, UK, rugby union student-athletes who sustained 42 SRCs.Methods: Student-athletes completed an assessment battery during pre-season (baseline), 2, 4, 8 and 14 days post-SRC and prior to RTP and were managed according to the rugby Football Union' community pathway.Outcome measures: Vestibular Ocular-Motor Screening (VOMS), Immediate Post-Concussion Assessment and Cognitive Test, Post-Concussion Symptom Scale, Perceived Academic Impairment Tool questionnaire and percentage of academic activities specifically missed due to SRC.Results: VOMS scores were significantly (p < 0.005) greater than baseline at all time points except RTP. Presence of VOM dysfunction at 14 days post-SRC significantly correlated with a longer RTP, greater symptom burden and increased odds ratio at 2, 4 and 8 days and academic time loss at 2, 4 and 8 days post-SRC.Conclusion: VOM impairment is associated with an increased symptom burden and impaired academic capability, and a longer time to RTP when present at 14 days post-SRC.

Mid-transverse colon cancer and extended versus transverse colectomy: Results of the Italian society of surgical oncology colorectal cancer network (SICO CCN) multicenter collaborative study.

INTRODUCTION: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. MATERIALS AND METHODS: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery. RESULTS: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). CONCLUSIONS: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.

Laparoscopic repeat liver resection for hepatocellular carcinoma: a multicentre propensity score-based study.

BACKGROUND: In the absence of randomized controlled data and even propensity-matched data, indications for, and outcomes of, laparoscopic repeat liver resection for hepatocellular carcinoma (HCC) remain uncertain. This study aimed to clarify the current indications for laparoscopic repeat liver resection for HCC, and to evaluate outcomes. METHODS: Forty-two liver surgery centres around the world registered patients who underwent repeat liver resection for HCC. Patient characteristics, preoperative liver function, tumour characteristics, surgical method, and short- and long-term outcomes were recorded. RESULTS: Analyses showed that the laparoscopic procedure was generally used in patients with relatively poor performance status and liver function, but favourable tumour characteristics. Intraoperative blood loss (mean(s.d.) 254(551) versus 748(1128) ml; P < 0·001), duration of operation (248(156) versus 285(167) min; P < 0·001), morbidity (12·7 versus 18·1 per cent; P = 0·006) and duration of postoperative hospital stay (10·1(14·3) versus 11·8(11·8) days; P = 0·013) were significantly reduced for laparoscopic compared with open procedures, whereas survival time was comparable (median 10·04 versus 8·94 years; P = 0·297). Propensity score matching showed that laparoscopic repeat liver resection for HCC resulted in less intraoperative blood loss (268(730) versus 497(784) ml; P = 0·001) and a longer operation time (272(187) versus 232(129); P = 0·007) than the open approach, and similar survival time (12·55 versus 8·94 years; P = 0·086). CONCLUSION: Laparoscopic repeat liver resection is feasible in selected patients with recurrent HCC.

ANTECEDENTES: Dado que no existen ensayos clínicos controlados ni estudios de datos emparejados por puntaje de propensión, todavía hay dudas sobre las indicaciones y los resultados de la resección iterativa laparocópica de un carcinoma hepatocelular (hepatocellular carcinoma, HCC). Este estudio tuvo como objetivo esclarecer las indicaciones actuales y los resultados de la resección hepática laparoscópica iterativa del HCC. MÉTODOS: Se incluyeron los pacientes de 42 centros de cirugía hepática a nivel mundial en los que se había realizado una resección hepática iterativa por HCC. Se analizaron las características del paciente, la función hepática preoperatoria, las características del tumor, el abordaje quirúrgico y los resultados a corto y largo plazo. RESULTADOS: El análisis demostró que la vía laparoscópica generalmente se utilizaba en pacientes con carácteristicas tumorales favorables, pero con estado funcional y función hepatica relativamente peores. La pérdida de sangre intraoperatoria (254,3 ± 551,2 versus 748,0 ± 1127,7 mL, P < 0,001), la duración de la intervención (247,6 ± 155,8 versus 285,1 ± 167,0 minutos, P < 0,001), la morbilidad (12,7 versus 18,1%, P = 0,005) y la estancia hospitalaria postoperatoria (10,07 ± 14,29 versus 11,80 ± 11,79 días, P = 0,010) fueron significativamente menores para los pacientes tratados por via laparoscópica en comparacion con la vía abierta, mientra que el tiempo de supervivencia fue comparable (mediana 10,04 versus 8,94 años, P = 0,297). El estudio de emparejamiento por puntaje de propensión mostró que la resección hepática iterativa por vía laparoscópica de un HCC (frente a la vía abierta) conllevaba una menor pérdida sanguínea intraoperatoria (268,0 ± 730,2 versus 496,5 ± 784,2 mL, P = 0,01), una mayor duración de la intervención (272,1 ± 187,2 versus 231,8 ± 129,1 minutos , P = 0,07) y un tiempo de supervivencia similar (mediana 12,55 versus 8,94 años, P = 0,0855). CONCLUSIÓN: La resección hepática iterativa por vía laparoscópica es factible en pacientes seleccionados con HCC recidivado.

Sudden unexpected death in epilepsy: Incidence at a Spanish epilepsy unit. / Muerte súbita en epilepsia: casuística de una unidad médica de epilepsia española.

INTRODUCTION: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with epilepsy. Most studies concerning this issue have been conducted in central and northern European countries and the United States. We conducted an epidemiologic study of SUDEP at our hospital's epilepsy unit. METHODS: This retrospective cohort study included all epileptic patients aged ≥14 years, regardless of epilepsy severity, who were treated at the outpatient epilepsy unit of our hospital between 2000 and 2013. The study included 2,309 patients. Deceased patients were identified using civil records. The cause of death was obtained from death certificates, autopsy reports, hospital reports, general practitioner records, and witnesses of the event. We calculated the incidence and proportional mortality of SUDEP based on our data. RESULTS: We identified 7 cases of definite SUDEP (2 patients with SUDEP plus), one case of probable SUDEP, and one case of possible SUDEP. Considering only cases of definite SUDEP, incidence was estimated at 0.44 cases per 1,000 patient-years and proportional mortality at 4.6%. Mean age of patients with definite SUDEP was 38.14 years; 4 were men and 3 were women. Most deaths occurred while patients were in bed and were therefore unwitnessed. Epilepsy in these patients was either remote symptomatic or cryptogenic. All patients but 2 had generalised seizures. None of the patients was in remission. CONCLUSIONS: SUDEP incidence and proportional mortality rates in our study are similar to those reported by population studies. This may be due to the fact that we did not select patients by severity. Risk factors for SUDEP in our sample are therefore consistent with those reported in the literature.

Evaluation of an antibody to α4ß7 in the control of SIVmac239-nef-stop infection.

Treatment of SIV-infected rhesus macaques with short-term antiretroviral therapy (ART) and partially overlapping infusions of antibody to integrin α4ß7 was reported to induce durable posttreatment viral suppression. In an attempt to replicate those observations, we treated macaques infected with the same virus and with the same ART and monoclonal antibody (mAb) regimens (anti-α4ß7 versus control mAb). Sequencing demonstrated that the virus used was actually SIVmac239-nef-stop, not wild-type SIVmac239. A positive correlation was found at 2 weeks after infection between the frequency of repair of attenuated Nef-STOP virus to pathogenic Nef-OPEN and plasma SIV RNA levels. Levels of plasma viremia before the first antibody infusion and preinfection levels of α4ß7 hi CD4+ T cells, but not treatment with antibody to α4ß7 , correlated with levels of viral replication upon discontinuation of all treatments. Follow-up plasma viremia, peripheral blood CD4+ T cell counts, and lymph node and rectal tissue viral load were not significantly different between anti-α4ß7 and control mAb groups.

Optical pupillometry in traumatic brain injury: neurological pupil index and its relationship with intracranial pressure through significant event analysis.

Primary Objective: Treatment paradigms for traumatic brain injury (TBI) rely on invasive monitoring of intracranial pressure (ICP) for planning intervention. Optical pupillometry is a non-invasive, objective monitoring method, measuring parameters of pupillary response and displaying a scalar value - a neurological pupil index (NPi). An impaired response on NPi has been tentatively correlated with ICP, through analysis of mean/peak NPi and ICP readings. We sought to evaluate this relationship more closely. Research Design: Prospective observational. Methods and Procedures: We obtained hourly pupillometry readings, alongside ICP values, from 40 patients with TBI requiring invasive ICP monitoring. Significant events were identified for analysis based on the significant aberration of ICP or NPi. Main Outcomes and Results: On average, individuals experienced a few significant events. There was a weak relationship between ICP events and a preceding NPi event. The results show that there is a weak but statistically insignificant relationship between NPi and ICP, where reduced pupil reactivity may indicate a raised ICP. The strength of this trend appears to diminish post-decompressive surgery. Conclusions: Whilst pupillometry may not be a reliable surrogate marker for ICP, NPi may still prove to be a useful tool in a multimodal prognostic assessment of the patient with acute brain injury.

Frequency of microorganisms isolated at different stages of lactation and milk production loss associated with somatic cell count and to mastitis-causing pathogens / Frequência de microrganismos isolados em diferentes fases da lactação e perda de produção de leite associada à contagem de células somáticas e aos patógenos causadores de mastite

The aim of this study was to evaluate the frequency of isolation of agents causing subclinical mastitis in a herd and to estimate production losses associated with SCC> 200,000cells/mL. Three 7-day interval microbiological cultures were performed in all lactating animals from the same farm that was evaluated from June to July. To evaluate the negative and positive isolation frequencies between the lactation phases, a Chi-square test was performed. Simple linear regressions were performed to evaluate the lactation curve of animals grouped by pathogens isolated from negative cows in the microbiological culture and with SCC <200,000cells/mL. To estimate the production losses between the groups, regression coefficients were used. Results found in this experiment were: Culture-negative cows with SCC ≥ 200,000cells/mL, cows testing positive in milk culture, with SCC <200,000cells/mL and cows testing positive in milk culture, with SCC ≥ 200,000cells/mL. Milk production was -3.5; -0.5 and -4.27kg, respectively, when compared to culture-negative cows with SCC <200,000cells/mL. Cows infected with yeast cells, Coagulase-negative staphylococci (CNS), Staphylococcus aureus and environmental streptococci produced -3.42; -0.5; -0.168 and -2.5kg of milk when compared to culture-negative cows with SCC <200,000cells/mL. SCC indicates an inflammatory reaction in the mammary gland and it is directly associated with milk production losses and with presence of microorganisms in the mammary gland.(AU)

O objetivo deste estudo foi avaliar a frequência de isolamento de agentes causadores de mastite subclínica em um rebanho e estimar as perdas de produção associadas com CCS>200.000 cél./mL. Três cultivos microbiológicos intervalados por sete dias foram realizados em todos os animais em lactação da propriedade avaliada, no período de junho a julho. Para avaliar as frequências de isolamento negativo e positivo entre as fases da lactação, foi realizado um teste de qui-quadrado. Foram realizadas regressões lineares simples para avaliar a curva de lactação dos animais agrupados por patógenos isolados em relação a vacas negativas na cultura microbiológica e com CCS < 200.000 cél./mL. Os coeficientes das regressões foram utilizados para estimar as perdas de produção entre os grupos. Vacas com resultado negativo na microbiologia, mas com CCS ≥ 200.000 cél./mL, positivas na microbiologia com CCS < 200.000 cél./mL e positivas com CCS ≥ 200.000 cél./mL, produziram por dia, respectivamente, -3,5; -0,5 e -4,27kg de leite em relação às vacas negativas com CCS < 200.000 cél./mL. Vacas infectadas com células leveduriformes, Staphylococcus coagulase negativa, Staphylococcus aureus e Streptococcus ambientais produziram, respectivamente, -3,42; -0,5; -0,168 e -2,5kg de leite, comparadas a vacas negativas com CCS < 200.000 cél./mL. A CCS, indicativa de reação inflamatória, encontra-se diretamente associada às perdas de produção de leite, assim como a presença do microrganismo na glândula mamária.(AU)

Time and laser ranging: a window of opportunity for geodesy, navigation and metrology.

Recent progress in the domain of time and frequency (T/F) standards requires important improvements of existing time distribution links. Among these, the accuracy of time transfer is actually an important part of the concerns in order to establish and maintain time & space references from ground and/or space facilities. Several time transfers by laser link projects have been carried out over the past 10 years with numerous scientific and metrological objectives. Satellite Laser ranging (SLR) has proven to be a fundamental tool, offering a straightforward, conceptually simple, highly accurate and unambiguous observable. Depending on the mission, LR is used to transmit time over two-way or one-way distances from 500 to several millions of km. The following missions and their objectives employed this technique: European Laser Timing (ELT) at 450 km, Time Transfer by Laser Link (T2L2) at 1,336 km, Laser Time Transfer (LTT) at 36,000 km, Lunar Reconnaissance Orbiter (LRO) at 350,000 km, and MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) at tens of million km. This article describes the synergy between SLR and T/F technologies developed on the ground and in space and as well as the state of the art of their exploitation. The performance and sources of limitation of such space missions are analyzed. It shows that current and future challenges lie in the improvement of the time accuracy and stability of the time for ground geodetic observatories. The role of the next generation of SLR systems is emphasized both in space and at ground level, from the point of view of GGOS and valuable exploitation of the synergy between time synchronization, ranging and data transfer.

Effects of treatment of preweaning dairy calves with recombinant bovine somatotropin on immune responses and somatotropic axis.

Weaning may be associated with negative energy balance and body weight loss when calves are still immunologically immature, predisposing them to infectious diseases. The aim of the present experiment was to investigate the effects of treatment of preweaning dairy calves with recombinant bovine somatotropin (rbST) on the somatotropic axis, selected immune parameters, and hematology of calves around weaning. Thirty-six Holstein female calves were randomly assigned to receive 1.5 to 1.8 mg of rbST (Posilac, Elanco Animal Health, Greenfield, IN) per kilogram of body weight or to receive injections of saline (saline solution 0.9%, Valley Vet Supply, Marysville, KS) every 7 d from 21 to 63 d of life. Calves were fed milk replacer ad libitum from birth to 38 d of age (d -11), when progressive weaning started, and calves were weaned at 49 d of age (d 0). Calves were weighed at birth and weekly from 21 to 63 d of age, when wither height also was measured. Calves were vaccinated with 0.5 mg of ovalbumin on study d -28 and -7. Blood samples were collected on d -28, -25, -21, -11, 0, 3, 7, and 14. Polymorphonuclear leukocytes were isolated and challenged ex vivo with Escherichia coli to determine phagocytosis and oxidative burst capacity. Additionally, expression of cluster of differentiation (CD)62L and CD18 by granulocyte, lymphocyte, and CD14+ monocyte were determined. Blood samples were also used to determine hematological parameters and concentrations of growth hormone, insulin-like growth factor-1, insulin, glucose, fatty acids, ß-hydroxybutyrate, haptoglobin, and anti-ovalbumin IgG. Calves treated with rbST had greater concentrations of growth hormone and insulin-like growth factor-1 from d -25 to 14 than control calves, whereas insulin, fatty acid, and ß-hydroxybutyrate concentrations did not differ. On d -11, glucose concentration was greater for rbST-treated calves. Treatment did not affect polymorphonuclear lymphocyte phagocytosis and oxidative burst, but intensity of expression of CD62L and CD18 by granulocytes tended to be increased by rbST treatment. Treatment did not affect the concentration of anti-ovalbumin IgG in serum. Haptoglobin concentration was reduced in rbST treated calves on d 3 and we noted a tendency for hematocrit to be lower in rbST-treated calves. Treatment did not affect body weight, wither height, and average daily gain, despite the fact that rbST-treated calves had lower daily milk replacer intake. The relatively minor improvements in immune responses resulting from rbST treatment of weaning calves may not be sufficient to reduce the incidence of infectious diseases.