A minimally-invasive method for profiling volatile organic compounds within postmortem internal gas reservoirs

International Journal of Legal Medicine - In forensic casework, non-invasive and minimally-invasive methods for postmortem examinations are extremely valuable. Whole body postmortem computed...     

国际淋巴瘤放射治疗协作组(ILROG)现代放射治疗靶区勾画及剂量指南——结内NHL

本指南反映了ILROG指导委员会在NHL现代放疗时代的共识,阐述了缩小照射野、降低剂量的作用,并且整合了现代三维计划图像技术和先进的放疗技术。在现代治疗条件下,应采用包含全身化疗在内的综合治疗。本指南明确定义了ISRT的CTV范围。对于惰性NHL,单纯放疗常作为根治手段,因此应考虑更大的照射野。为了既实现肿瘤LC这一主要目标,又降低正常组织损伤的风险,IMRT、呼吸门控、IGRT、四维图像等先进治疗技术都应使用于临床。     

PIWI-interacting RNAs as novel regulators of pancreatic beta cell function

Aims/hypothesis

P-element induced Wimpy testis (PIWI)-interacting RNAs (piRNAs) are small non-coding RNAs that interact with PIWI proteins and guide them to silence transposable elements. They are abundantly expressed in germline cells and play key roles in spermatogenesis. There is mounting evidence that piRNAs are also present in somatic cells, where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta cell activities.

Methods

piRNA profiling of rat pancreatic islets was performed by microarray analysis. The functions of piRNAs were investigated by silencing the two main Piwi genes or by modulating the level of selected piRNAs in islet cells.

Results

We detected about 18,000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet postnatal development. Moreover, we identified changes in the level of several piRNAs in the islets of Goto–Kakizaki rats, a well-established animal model of type 2 diabetes. Silencing of Piwil2 or Piwil4 genes in adult rat islets caused a reduction in the level of several piRNAs and resulted in defective insulin secretion and increased resistance of the cells to cytokine-induced cell death. Furthermore, overexpression in the islets of control animals of two piRNAs that are upregulated in diabetic rats led to a selective defect in glucose-induced insulin release.

Conclusions/interpretation

Our results provide evidence for a role of PIWI proteins and their associated piRNAs in the control of beta cell functions, and suggest a possible involvement in the development of type 2 diabetes.

Data availability

Data have been deposited in Gene Expression Omnibus repository under the accession number GSE93792. Data can be accessed via the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ojklueugdzehpkv&acc=GSE93792

     

Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark

Objective: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission.

Materials and methods: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc.

Results: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission.

Conclusion: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.     

Transcranial Doppler screening in sickle cell disease: The implications of using peak systolic criteria

AIM: To compare time average maximum mean velocity(TAMV) and peak systolic velocity(PSV) criteria of Trans Cranial Doppler(TCD) in their ability to predict abnormalities on magnetic resonance imaging(MRI)/magnetic resonance angiogram(MRA) in patients with sickle cell disease. METHODS: A retrospective evaluation was performed of the outcomes in all patients with a Transcranial Doppler examination at our institution since the implementation of the hospital picture archiving and communication system(PACS) system in January 2003 through December 2012. All ultrasound imaging exams were performed by the same technologist with a 3 MHz transducer. Inclusion criteria was based upon the Transcranial Doppler procedure code in our PACS which had an indication of sickle cell disease in the history. The patient’s age and gender along with the vessel with the highest time averaged mean velocity as well as the highest peak systolic velocity was recorded for analysis. A subset of the study cohort also had subsequent MR imaging and Angiograms performed within 6 mo of the TCD examination. MRI results were categorized as having a disease related abnormality(vessel narrowing, collateral formation/moya-moya, or abnormal fluid attenuation inversion recovery signal in parenchyma indicative of prior stroke) or normal. The MRI results formed the comparison standards for TCD exams in evaluating intracranial injury. Sensitivity and specificity for the two TCD criteria(TAMV and PSV) were calculated to determine which could be a better predictor for intracranial vasculopathy /clinically occult strokes.RESULTS: The study cohort for our institution was 110patients with a total of 291 TCD examinations. These patients had a mean age of 7.6 years with a range from 2-18 years of age. Sixty-two of the 110 patients(56%) had two or more TCD exams. Thirty-seven patients(34%) had at least one MRI following a TCD examination. Of the 291 TCD examinations, 46(16%) were conditional or abnormal by TAMV criteria. One hundred and sixteen(40%) were conditional or abnormal by PSV criteria. All studies that were abnormal by TAMV were also abnormal by PSV criteria. Seventy of the 116(60%) studies which were conditional or abnormal by peak systolic criteria would not have been identified by time averaged mean maximum velocity criteria. The most frequent location of highest velocity measurement was noted to be in the middle cerebral artery regardless of whether it was measured by PSV or TAMV. From the 37 patients having one or more MRIs, 43 MRI exams were performed within 6 mo of a TCD examination. Twenty two(51%) MRIs had a disease related abnormality reported. When evaluating conditional or abnormal exams by PSV criteria against follow-up MRI/MRA, the sensitivity was 73% [16/(16 + 6)] and specificity was 81% [17/(4 + 17)]. When evaluating conditional or abnormal exams by TAMV criteria by follow-up MRI/MRA as the gold standard, the sensitivity was 41% [9/(9 + 13)] and the specificity was 100% [21/(21 + 0)]. In using conditional or abnormal criteria from PSV and TAMV to predict abnormalities on followup MRI/MR Angiogram, PSV was more sensitive(73% vs 41%) while TAMV was more specific(100% vs 81%). CONCLUSION: Based on the data obtained at our institution and using the assumption that the best screening test is the one with the highest sensitivity, the peak systolic velocity could be the measurement of choice for TCD screening.     

Periodontal conditions, oral Candida albicans and salivary proteins in type 2 diabetic subjects with emphasis on gender

Background  

The association between periodontal conditions, oral yeast colonisation and salivary proteins in subjects with type 2 diabetes (T2D) is not yet documented. The present study aimed to assess the relationship between these variables in type 2 diabetic subjects with reference to gender.     

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma

Background Metastasis is a hallmark of cancer and responsible for most cancer deaths. Migrastatics were defined as drugs interfering with all modes of cancer cell invasion and thus cancers’ ability to metastasise. First anti-metastatic treatments have recently been approved.Methods We used bioinformatic analyses of publicly available melanoma databases. Experimentally, we performed in vitro target validation (including 2.5D cell morphology analysis and mass spectrometric analysis of RhoA binding partners), developed a new traceable spontaneously metastasising murine melanoma model for in vivo validation, and employed histology (haematoxylin/eosin and phospho-myosin II staining) to confirm drug action in harvested tumour tissues.Results Unbiased and targeted bioinformatic analyses identified the Rho kinase (ROCK)-myosin II pathway and its various components as potentially relevant targets in melanoma. In vitro validation demonstrated redundancy of several RhoGEFs upstream of RhoA and confirmed ROCK as a druggable target downstream of RhoA. The anti-metastatic effects of two ROCK inhibitors were demonstrated through in vivo melanoma metastasis tracking and inhibitor effects also confirmed ex vivo by digital pathology.Conclusions We proposed a migrastatic drug development pipeline. As part of the pipeline, we provide a new traceable spontaneous melanoma metastasis model for in vivo quantification of metastasis and anti-metastatic effects by non-invasive imaging.Subject terms: Skin cancer, Cancer models, Drug discovery, Metastasis     

Fast-track anesthesia in lateral mini-thoracotomy for transapical transcatheter valve implantation

BackgroundPatients who undergo transapical transcatheter aortic/mitral valve implantation are at higher risk of morbidity and mortality than those undergoing transvascular procedures. In addition, these patients have prolonged intensive care and hospital courses. Fast-track anesthesia could reduce perioperative complications and admission stays in such patients.MethodsThis retrospective single-center study, evaluates six high-risk patients undergoing transapical valve implantation between 01/2020 till 01/2021. All patients received a paravertebral block (PVB) as part of a fast-track approach. The airway was secured with a Gastro-double-lumen laryngeal mask which includes one orifice was for ventilation and one for the transesophageal echocardiography probe. Anesthesia was maintained with a volatile anesthetic (Sevoflurane MAC 1%). Immediately post procedure, all patients were awakened and admitted to the intermediate/intensive-care unit.ResultsThree patients were females, mean age =71±6 years, patients’ risk profiles were high (mean Log. EuroSCORE-I 22% & STS-PROM 10%). No incidents of re-intubation, atelectasis/pneumonia, low output syndrome, stroke, dialysis, pacemaker implantation or operative mortality were reported. One patient (16.7%) underwent re-exploration for bleeding and developed a wound infection. Postoperative pain scores showed that no patient required additional analgesics after the initial eight hours post procedure. Mean postoperative intermediate/intensive-care stay was 13.8±3.2 hours and patients were mobilized early and discharged to the normal ward.ConclusionsFast-track anesthesia using paravertebral-blockade for transcatheter transapical valve replacement in high-risk patients is a possible anesthetic approach. An effective PVB, in addition to a double-lumen laryngeal mask, provide an alternative strategy to conventional general anesthesia. These promising results could encourage further consideration of this approach in similar cardiac surgery patients.