Despite previous successes of RNA-based medicines, including the knockout of HPV oncogenes, the use of CRISPR activation is yet to be investigated as a promising potential therapy. This short review summarises key developments on attempts that have been made to increase p53 expression in the context of HPV cancer therapy, but leaves open the possibility for other cancers bearing a p53 wild-type gene.Rodents and shrews live in close proximity to humans and have been identified as important hosts of zoonotic pathogens. This study aimed to detect Group A rotavirus (RVA) and its potential risk factors in rodents and shrews in Bangladesh. We captured 417 small mammals from 10 districts with a high degree of contact between people and domestic animals and collected rectal swab samples between June 2011 and October 2013. We tested the swab samples for RVA RNA, targeting the NSP3 gene segment using real-time reverse transcription-polymerase chain reaction (rRT-PCR). Overall, RVA prevalence was the same (6.7%) in both rodents and shrews. We detected RVA RNA in 5.3% of Bandicota bengalensis (4/76; 95% CI 1.4-12.9), 5.1% of B. indica (4/79; 95% CI 1.4-12.4), 18.2% of Mus musculus (4/22; 95% CI 5.2-40.3), 6.7% of Rattus rattus (6/90; 95% CI 2.5-13.9), and 6.7% of Suncus murinus (10/150; 95% CI 3.2-11.9). We found significantly more RVA in males (10.4%; OR 3.4; P = 0.007), animals with a poor body condition score (13.9%; OR 2.7; P = 0.05), during wet season (8.3%; OR 4.1; P = 0.032), and in urban land gradients (10.04%; OR 2.9; P = 0.056). These findings form a basis for understanding the prevalence of rotaviruses circulating among rodents and shrews in this region. We recommend additional molecular studies to ascertain the genotype and zoonotic potential of RVA circulating in rodents and shrews in Bangladesh.Nutritional supplementation with medium-chain triglycerides (MCTs) has the potential to increase memory function in elderly patients with frailty and dementia. Our aim was to investigate the effects of MCT on cognitive and gait functions and their relationships with focal brain metabolism and functional connectivity even in healthy older adults. Participants were blindly randomized and allocated to two groups 18 g/day of MCT oil and matching placebo formula (control) administered as a jelly stick (6 g/pack, ingested three times a day). Gait analysis during the 6-m walk test, cognition, brain focal glucose metabolism quantified by 18F-fluorodeocyglucose positron emission tomography, and magnetic resonance imaging-based functional connectivity were assessed before and after a 3-month intervention. Sixty-three healthy, normal adults (females and males) were included. Compared with the control group, the MCT group showed better balance ability, as represented by the lower Lissajous index (23.1 ± 14.4 vs. 31.3 ± 18.9; P  less then  0.01), although no time × group interaction was observed in cognitive and other gait parameters. Moreover, MCT led to suppressed glucose metabolism in the right sensorimotor cortex compared with the control (P  less then  0.001), which was related to improved balance (r = 0.37; P = 0.04) along with increased functional connectivity from the ipsilateral cerebellar hemisphere. In conclusion, a 3-month MCT supplementation improves walking balance by suppressing glucose metabolism, which suggests the involvement of the cerebro-cerebellar network. This may reflect, at least in part, the inverse reaction of the ketogenic switch as a beneficial effect of long-term MCT dietary treatment.Functional neuroimaging has become a widely used tool in obesity and eating disorder research to explore the alterations in neurobiology that underlie overeating and binge eating behaviors. Current and traditional neurobiological models underscore the importance of impairments in brain systems supporting reward, cognitive control, attention, and emotion regulation as primary drivers for overeating. Due to the technical limitations of standard field strength functional magnetic resonance imaging (fMRI) scanners, human neuroimaging research to date has focused largely on cortical and basal ganglia effects on appetitive behaviors. The present review draws on animal and human research to highlight how neural signaling encoding energy regulation, reward-learning, and habit formation converge on hypothalamic, brainstem, thalamic, and striatal regions to contribute to overeating in humans. We also consider the role of regions such as the mediodorsal thalamus, ventral striatum, lateral hypothalamus and locus coeruleus in supporting habit formation, inhibitory control of food craving, and attentional biases. Through these discussions, we present proposals on how the neurobiology underlying these processes could be examined using functional neuroimaging and highlight how ultra-high field 7-Tesla (7 T) fMRI may be leveraged to elucidate the potential functional alterations in subcortical networks. Focus is given to how interactions of these regions with peripheral endocannabinoids and neuropeptides, such as orexin, could be explored. Technical and methodological aspects regarding the use of ultra-high field 7 T fMRI to study eating behaviors are also reviewed.Abdominal compartment syndrome (ACS) is defined as any organ dysfunction caused by intra-abdominal hypertension (IAH), referred as intra-abdominal pressure (IAP) ≥ 12 mm Hg according to the World Society of Abdominal Compartment Syndrome. Abdominal compartment syndrome develops in most cases when IAP rises above 20 mmHg. Abdominal compartment syndrome, while being a treatable and even preventable condition if detected early in the stage of intra-abdominal hypertension, is associated with high rates of morbidity and mortality if diagnosis is delayed therefore, early detection is essential. Acute kidney injury (AKI) is a common comorbidity, affecting approximately one in every five hospitalized patients, with a higher incidence in surgical patients. AKI in response to intra-abdominal hypertension develops as a result of a decline in cardiac output and compression of the renal vasculature and renal parenchyma. In spite of the high incidence of intra-abdominal hypertension, especially in surgical patients, its potential role in the pathophysiology of AKI has been investigated in very few clinical studies and is commonly overlooked in clinical practice despite being potentially treatable and reversible. Aim of the present review is to illustrate the current evidence on the pathophysiology, diagnosis and therapy of intra-abdominal hypertension and abdominal compartment syndrome in the context of AKI.

Prior work identified optimal outcomes at 2years following selective thoracic fusion (STF) for adolescent idiopathic scoliosis (AIS) but it is unclear whether these published predictors represent what is required to achieve an optimal outcome with further time and potential growth. The purpose of this study was to determine the preoperative factors associated with optimal outcome of STF for AIS at 5years.

Patients with primary thoracic AIS (Lenke 1-4C curves) who underwent a STF and had minimum 5years of follow-up were included. Optimal postoperative outcomes for a STF included a deformity-flexibility quotient (DFQ) < 4, lumbar curve < 26°, lumbar correction > 37%, C7-CSVL < 2cm, lumbar prominence < 5°, and trunk shift < 1.5cm. These outcomes were used to determine whether adhering to published recommendations for STF increased the likelihood of obtaining an optimal outcome at 5years, which included preoperative lumbar curve < 45°, lumbar bend < 25°, apical vertebral translation ratio > 1.2, and thoracic/thoracolumbar Cobb ratio > 1.2.

127 patients met inclusion. A preoperative lumbar curve < 45° was associated with an increased likelihood of achieving three of the optimal outcomes DFQ < 4, lumbar curve < 26°, and lumbar prominence < 5°. Following the 25° bend rule resulted in two optimal outcomes, while Cobb ratio > 1.2 was only associated with one optimal outcome. AVT > 1.2 was not significantly associated with any optimal outcome measures.

This study found that at 5years, performing a STF when there is a preoperative lumbar Cobb < 45° remained the best guideline for increasing the likelihood of an optimal outcome.

This study found that at 5 years, performing a STF when there is a preoperative lumbar Cobb  less then  45° remained the best guideline for increasing the likelihood of an optimal outcome.

Accurate prediction of survival outcomes after hanging is a crucial and challenging issue in comatose survivors. In this preclinical study, we evaluated the potential utility of using brain glucose metabolism as measured by fluorine-18-fluorodeoxyglucose (

F-FDG) positron emission tomography (PET) for survival prediction in a rat model of hanging-induced hypoxic brain injury (HBI).

HBI was induced by mechanical hanging using Sprague Dawley rats.

F-FDG brain PET images were acquired in 26 HBI rats three hours post-injury (3h post-injury) and 4 controls. During the 1month follow-up period, HBI rats were further classified as survivors (n = 15) and nonsurvivors (n = 11). Between-group regional (standardized uptake values normalized to the reference whole brain = SUVR

, cerebellum = SUVR

, and pons = SUVR

) and voxel-based analyses were performed. The prognostic value of the SUVR was tested for overall survival (OS). In addition, diffusion-weighted imaging (DWI) was performed in 2 controls and 5 HBI ratof

F-FDG brain PET for predicting survival in hanging-induced HBI.

These results suggest the potential utility of 18F-FDG brain PET for predicting survival in hanging-induced HBI.

The aim of this study was to compare the recent Positron emission tomography (PET) Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for evaluating the response of osteosarcoma to neoadjuvant chemotherapy of the extremities.

We retrospectively reviewed patients with osteosarcoma of the extremities who received neoadjuvant chemotherapy and then surgical resection at Peking University People’s Hospital. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (

F-FDG PET/CT) and magnetic resonance imaging (MRI) were performed prior to chemotherapy and before surgical resection. Therapeutic response was assessed separately by the PERCIST and RECIST 1.1 criteria. The association between the data acquired by the PERCIST and RECIST 1.1 criteria was then analyzed by Wilcoxon’s signed-rank test. The association between the PERCIST criteria and the pathological necrosis rate was analyzed by Fisher’s exact test. Finally, the im the PERCIST criteria are significantly more sensitive than RECIST 1.1 criteria to identify more responders when evaluating the response of osteosarcoma to neoadjuvant chemotherapy.The majority of patients undergoing Orthotopic Liver Transplantation (OLT) have increased in age, therefore chronological age may have become an unreliable parameter for supporting clinical decisions. The age-related deficit accumulation model measuring frailty proposed by Rockwood et al., may propose an alternative in providing an estimate of an individual’s biological age. No Frailty Index (FI) tailored specifically for OLT patients exists to date. Forty-three consecutive OLT patients with ≥ 20 years of survival with a functioning graft were included in our study. The FI was computed taking to account 39 items (FI-39), meeting the standard criteria for internal validation. Endpoints were polypharmacy, and recent Emergency Room admission. The mean age of our population was 69 (sd 9) years. The mean FI-39 was 0.23 (sd 0.1). The FI-39 was associated with polypharmacy [odds ratio (OR) 1.13; Confidence interval (95%CI) 1.03-1.24; p = 0.01], and recent Emergency Room admission [beta coefficient + 1.98; 95%CI + 0.