Caenorhabditis elegans Rab escort protein (REP‐1) differently regulates each Rab protein function and localization in a tissue‐dependent manner

Rab proteins play a critical role in intracellular vesicle trafficking and require post‐translational modification by adding lipids at the C‐terminus for proper functions. This modification is preceded by the formation of a trimeric protein complex with the Rab escort protein (REP) and the Rab geranylgeranyltransferase (RabGGTase). However, the genetic hierarchy among these proteins and the tissue‐specificity of each protein function are not yet clearly understood. Here we identified the Caenorhabditis elegans rep‐1 gene and found that a rep‐1 mutant showed a mild defect in synaptic transmission and defecation behaviors. Genetic analyses using the exocytic Rab mutants rab‐3 or rab‐27 suggested that rep‐1 functions only in the RAB‐27 pathway, and not in the RAB‐3 pathway, for synaptic transmission at neuromuscular junctions. However, the disruption of REP‐1 did not cause defecation defects compared to severe defects in either RAB‐27 or RabGGTase disruption, suggesting that REP‐1 is not essential for RAB‐27 signaling in defection. Some Rab proteins did not physically interact with REP‐1, and localization of these Rab proteins was not severely affected by REP‐1 disruption. These findings suggest that REP‐1 functions are required in specific Rab pathways and in specific tissues, and that some Rab proteins are functionally prenylated without REP‐1.     

Identification of cembratriene-4,6-diol as antitumor-promoting agent from cigarette smoke condensate

Cigarette smoke condensate (CSC) was separated into severalfractions and each was tested for an inhibitory effect on theearly antigen (EA) of Epstein-Barr virus (EBV) which can beinduced by 12-0-tetradecanoylphorbol-13-acetate (TPA) in Rajicells. Two diastereoisomers of 2,7,11-cembratriene-4,6-diol(- and ß-CBT) were isolated from the neutral fractionsof CSC and these showed potent inhibitory effects on the inductionof EBV-EA by TPA. The doses of - and ß-CBT requiredfor 50% inhibition of EBV-EA induction by TPA were 7.7 and 6.7µg/ml, respectively, which are comparable with those ofretinoic acid, a potent inhibitor of induction of epideral ornithinedecarboxylase (ODC) activity and tumor promotion by TPA in mice.Application of - and ß-CBT to mouse skin prior totreatment with TPA inhibited TPA-induced ODC activity. The degreeof inhibition was dependent on the dose and application of 16.5µmol/mouse of - and ß-CBT resulted in a 50 and40% reduction, respectively, of the maximum of the ODC activityinduced as a result of treatment with TPA. In initiation-promotionexperiments, -CBT markedly inhibited the promoting effect ofTPA on skin tumor formation in mice which were initiated with7,12-dimethylbenz[a]anthracene, but ß-CBT was foundto be less effective. Application of 3.3 µmol of -CBT40 min prior to treatment with TPA (1 µg) resulted ina 53% reduction in the number of papillomas per mouse. Our presentdata suggest that EBV-EA inhibition assay using Raji cells iseffective for the first screening of inhibitors of tumor promotion,and provide evidence that CSC contains antitumor-promoting agentsin addition to carcinogenic and tumor-promoting agents alreadyreported.     

Nutritional Assessment in Adult Patients with Dysphagia: A Scoping Review

Malnutrition negatively affects the quality of life of patients with dysphagia. Despite the need for nutritional status assessment in patients with dysphagia, standard, effective nutritional assessments are not yet available, and the identification of optimal nutritional assessment items for patients with dysphagia is inadequate. We conducted a scoping review of the use of nutritional assessment items in adult patients with oropharyngeal and esophageal dysphagia. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched to identify articles published in English within the last 30 years. Twenty-two studies met the inclusion criteria. Seven nutritional assessment categories were identified: body mass index (BMI), nutritional screening tool, anthropometric measurements, body composition, dietary assessment, blood biomarkers, and other. BMI and albumin were more commonly assessed in adults. The Global Leadership Initiative on Malnutrition (GLIM), defining new diagnostic criteria for malnutrition, includes the categories of BMI, nutritional screening tool, anthropometric measurements, body composition, and dietary assessment as its required components, but not the blood biomarkers and the “other” categories. We recommend assessing nutritional status, including GLIM criteria, in adult patients with dysphagia. This would standardize nutritional assessments in patients with dysphagia and allow future global comparisons of the prevalence and outcomes of malnutrition, as well as of appropriate interventions.     

ASO Visual Abstract: Influence of Damaged Stomach on Anastomotic Leakage After Cervical Esophagogastrostomy for Patients with Esophageal Cancer

Annals of Surgical Oncology -     

High HNRNPA3 expression is associated with lymph node metastasis and poor prognosis in patients treated with radical cystectomy

ObjectiveWe sought to identify heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) expression in bladder cancer and its relationship to clinicopathological findings and prognosis.MethodsImmunohistochemical staining for HNRNPA3 was performed on 122 archived radical cystectomy specimens, with immunoreactivity being stratified on a 0 to 3 scale. The percentage of HNRNPA3 expressing tumor cells was calculated and multiplied by the staining score over an average of 5 areas to obtain a semiquantitative H-score (maximum value: 300). HNRNPA3 expression was categorized as high (≥80) or low (<80).ResultsThe patients’ median age was 70 years, and the median follow-up period was 39.4 months. High HNRNPA3 expression was significantly associated with lymph node metastasis (P= 0.014) and S100A8, S100A9 and uroplakin III expression (P= 0.028, 0.002, and 0.047, respectively). Log-rank tests indicated that high HNRNPA3 expression was significantly associated with disease progression and cancer-specific death (P= 0.013 and 0.006, respectively). In the Cox proportional hazards regression analysis, only lymph node metastasis was associated with disease progression and cancer-specific survival.ConclusionHNRNPA3 may be a new biomarker to predict biologically aggressive cancers and determine the appropriate treatment modality in patients after radical cystectomy.     

Measurement of self-propulsion distance of wheelchair using cycle computer excluding assistance distance by touch switch: A pilot study

Objective: Although the propulsion distance of a wheelchair is measured by some devices, measuring self-propulsion distance, excluding assistance propulsion distance by the caregiver, is difficult. This is a pilot study conducted to verify whether the propulsion distance of wheelchair users, excluding the assistance propulsion distance, can be measured using a cycle computer by attaching the touch switch.Methods: The wheelchair propulsion distance was measured using a cycle computer. We connected the touch switch and the cycle computer to the wheelchair to exclude assistance propulsion distance. We set the cycle computer to stop recording while the caregiver was touching the sensor. To confirm the propulsion distance using the cycle computer, the volunteer propelled the wheelchair on a rectangular facility with a total distance of 181 m, and the examiner confirmed the propulsion distance. The validation test to confirm the accuracy of the touch switch attached to the cycle computer was performed on a 50-m straight runway. The volunteer and caregiver propelled the wheelchair alternately by 10 m and continued until 50 m. The examiner confirmed the distance after 50-m propulsion.Results: In the 181-m rectangular facility, the propulsion distance that the volunteer propelled the wheelchair with the cycle computer was 180 m. In the 50-m straight runway, the propulsion distance was 30 m with caregiver assistance for 20 m.Conclusion: The present study showed that our modified device could measure the self-propulsion distance, excluding assistance propulsion distance in wheelchair users.     

Clinical and experimental approaches for imaging of acute kidney injury

Clinical and Experimental Nephrology - Complex molecular cell dynamics in acute kidney injury and its heterogeneous etiologies in patient populations in clinical settings have revealed the...     

A digest of the Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020

Clinical and Experimental Nephrology -     

The N-Methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enfturane-induced opisthotonus in mice

We determined whether enflurane-induced opisthotonus in ddN mice is mediated by N-methyl-D-aspartate (NMDA) receptor using NMDA receptor antagonists dizocilpine (MK-801) and ketamine. Animals were given intraperitoneal injections of 0.2ml saline (control), 2.5 or 5.0mg·kg^–1 dizocilpine in saline, or 20 or 40mg·kg^–1 ketamine is saline 20min prior to exposure to 2.0% enflurane. Incidence of opisthotonus measured during exposure to enflurane for 20min was 49% (n = 51) in saline (control) group, 6.7 (P 0.01 vs control, n = 30) and 15.0% (P 0.01, n = 40) in 2.5 and 5.0mg·kg^–1 dizocilpine group, respectively, and 43.9 (NS, n = 41) and 40.0% (NS, n = 40) in 20 and 40mg·kg^–1 ketamine group, respectively. These results strongly suggest that enflurane-induced opisthotonus is mediated by NMDA receptor. Ketamine failed to suppress significantly due to possibly small dosages. Further, dizocilpine itself produced severe seizures during preenflurane period (30.0 and 40.0% in 2.5 and 5.0mg·kg^–1, respectively), which may be a novel finding.(Komatsu H, Nogaya J, Anabuki D, et al.: The N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enflurane-induced opisthotonus in mice. J Anesth 7: 519–522, 1993)