Gene co-expression network and differential expression analyses of subcutaneous white adipose tissue reveal novel insights into the pathological mechanisms underlying ketosis in dairy cows.

Ketosis is a common nutritional metabolic disease during the perinatal period in dairy cows. Although various risk factors have been identified, the molecular mechanism underlying ketosis remains elusive. In this study, subcutaneous white adipose tissue (sWAT) was biopsied for transcriptome sequencing on 10 Holstein cows with type II ketosis [blood ß-hydroxybutyric acid (BHB) >1.4 mmol/L; Ket group] and another 10 cows without type II ketosis (BHB ≤1.4 mmol/L; Nket group) at d 10 after calving. Serum concentrations of nonesterified fatty acids (NEFA) and BHB, as indicators of excessive fat mobilization and circulating ketone bodies, respectively, were significantly higher in the Ket group than in the Nket group. Aspartate transaminase (AST) and total bilirubin (TBIL), as indicators of liver damage, were higher in the Ket group than in the Nket group. Weighted gene co-expression network analysis (WGCNA) of the sWAT transcriptome revealed modules significantly correlated with serum BHB, NEFA, AST, TBIL, and total cholesterol. The genes in these modules were enriched in the regulation of the lipid biosynthesis process. Neurotrophic tyrosine kinase receptor type 2 (NTRK2) was identified as the key hub gene by intramodular connectivity, gene significance, and module membership. Quantitative reverse transcription PCR analyses for these samples, as well as a set of independent samples, validated the downregulation of NTRK2 expression in the sWAT of dairy cows with type II ketosis. NTRK2 encodes tyrosine protein kinase receptor B (TrkB), which is a high-affinity receptor for brain-derived neurotrophic factor, suggesting that abnormal lipid mobilization in cows with type II ketosis might be associated with impaired central nervous system regulation of adipose tissue metabolism, providing a novel insight into the pathogenesis underlying type II ketosis in dairy cows.

Ketosis Alters Transcriptional Adaptations of Subcutaneous White Adipose Tissue in Holstein Cows during the Transition Period.

Ketosis is a common nutritional, metabolic disease during the perinatal period in dairy cows characterized by elevated blood ß-hydroxybutyrate (BHBA). In this study, RNA sequencing (RNA-seq) was performed to investigate adaptive changes in adipose tissue during the perinatal period of dairy cows. Blood and tailhead subcutaneous white adipose tissue (sWAT) were obtained from ketotic cows (Ket = 8, BHBA ≥ 1.4 mmol/L) and non-ketotic cows (Nket = 6, BHBA < 1.4 mmol/L) 21 d pre-partum and 10 d post-partum. Compared with pre-partum, decreased lipid synthesis due to down-regulation of PCK1 may be in a strong association with clinical ketosis. Simultaneously, PCK2 was downregulated in the Ket postnatally compared to its expression prenatally, and the expression of PCK2 was 2.7~4.2 times higher than that of PCK1, implying a more severe lipid storage impairment in the Ket. Moreover, compared to pre-partum, the upregulated differentially expressed genes post-partum in the Ket were enriched in the inflammatory response biological process. The higher expression of TNC (tenascin C) in the post-partum Ket relative to the Nket suggested that the adipose tissue of ketotic cows might also be accompanied by tissue fibrosis. Notably, pre-partum CD209 was higher in the Ket than in the Nket, which might be used as a candidate marker for the pre-partum prediction of ketosis. Combined with published gene expression traits, these results suggested that inflammation leads to a more widespread downregulation of the lipid synthesis gene network in adipose tissue in ketotic cows. Additionally, sWAT in post-partum cows with ketosis might also be accompanied by tissue fibrosis which could make the treatment of ketosis more difficult.

Value of computed tomography scores in complicated acute diverticulitis.

BACKGROUND: Diverticular disease remains one of the most common conditions in the western world. Up to 25% of patients with diverticular disease require hospitalization, 15-30% of those of which require surgical intervention. CT scoring systems have been proposed as means to drive assessment and stratify patients necessitating hospital intervention. To assess and correlate CT scoring systems with clinical and surgical outcomes. METHODS: Retrospective cohort analysis at a single institution. Single institutional assessment with patients presenting to emergency with a CT diagnosed episode of acute diverticulitis. One hundred and eighty-nine patients were included in the study, 61% of which were male. Patient demographics, comorbidities, medications, biochemistry and inflammatory markers, type of complication following acute diverticulitis, operative/procedural intervention, hospital outcome and mortality were measured. CT scoring systems assessed included modified Hinchey, modified Neff, World Society of Emergency Surgery (WSES) and modified Siewert scoring systems. RESULTS: Majority of patients had left-sided diverticulitis (91%) with localized air (88%) and pericolic abscess (49%) the most common radiological findings. 28% of patients required radiological and/or surgical management with 12% requiring intensive care unit (ICU) admission. There was a general trend for surgical/radiological intervention as the scores increased in severity. The four scoring systems were found to be statistically significant predictors of any intervention and of ICU admission with minimal statistical differences across the different scoring systems. CONCLUSION: Radiological CT scores for complicated diverticulitis are at best, moderate predictors of clinical and surgical outcomes and may serve to guide management with minimal statistical differences across different scores.

Clinical outcomes of patients with two small hepatocellular carcinomas.

BACKGROUND: Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear. AIM: To define the outcomes of patients presenting with two small HCC. METHODS: Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC ≤ 3 cm between January 2000 and March 2018. Primary outcomes were overall survival (OS) and transplant-free survival (TFS). RESULTS: 104 patients were identified (male n = 89). Median age was 63 years (interquartile range 58-67.75) and the most common aetiology of liver disease was hepatitis C (40.4%). 59 (56.7%) had synchronous HCC and 45 (43.3%) had sequential. 36 patients died (34.6%) and 25 were transplanted (24.0%). 1, 3 and 5-year OS was 93.0%, 66.1% and 62.3% and 5-year post-transplant survival was 95.8%. 1, 3 and 5-year TFS was 82.1%, 45.85% and 37.8%. When synchronous and sequential groups were compared, OS (1,3 and 5 year synchronous 91.3%, 63.8%, 61.1%, sequential 95.3%, 69.5%, 64.6%, P = 0.41) was similar but TFS was higher in the sequential group (1,3 and 5 year synchronous 68.5%, 37.3% and 29.7%, sequential 93.2%, 56.6%, 48.5%, P = 0.02) though this difference did not remain during multivariate analysis. CONCLUSION: TFS in patients presenting with two HCC ≤ 3 cm is poor regardless of the timing of the second tumor. All patients presenting with two small HCC should be considered for transplantation.

Incidental detection of prostate cancer with computed tomography scans.

Prostate cancer (PCa) is the second most frequent type of cancer found in men worldwide, with around one in nine men being diagnosed with PCa within their lifetime. PCa often shows no symptoms in its early stages and its diagnosis techniques are either invasive, resource intensive, or has low efficacy, making widespread early detection onerous. Inspired by the recent success of deep convolutional neural networks (CNN) in computer aided detection (CADe), we propose a new CNN based framework for incidental detection of clinically significant prostate cancer (csPCa) in patients who had a CT scan of the abdomen/pelvis for other reasons. While CT is generally considered insufficient to diagnose PCa due to its inferior soft tissue characterisation, our evaluations on a relatively large dataset consisting of 139 clinically significant PCa patients and 432 controls show that the proposed deep neural network pipeline can detect csPCa patients at a level that is suitable for incidental detection. The proposed pipeline achieved an area under the receiver operating characteristic curve (ROC-AUC) of 0.88 (95% Confidence Interval: 0.86-0.90) at patient level csPCa detection on CT, significantly higher than the AUCs achieved by two radiologists (0.61 and 0.70) on the same task.

Reflective temperature sensor based on a fiber Bragg grating combined with a fiber loop ringdown technique.

In this paper, a reflective fiber sensing system combined with a fiber loop ringdown technique for temperature detection is proposed. A fiber Bragg grating (FBG) with an initial center wavelength of 1543.33 nm was set as the sensor head. The experimental results showed that the average sensitivity of temperature was 1.003 µs/°C in the temperature range of 30-38°C, and the resolution was 0.007°C, which is 14 times better than the current FBG sensing demodulator. In addition, the system has the advantages of simple structure, low cost, and insensitivity to optical power fluctuation.

The association between maternal renal function and pregnancy outcomes in type 1 and type 2 diabetes.

AIMS: To investigate the prognostic value of estimated glomerular filtration rate (eGFR) and albuminuria in determining pregnancy outcomes in women with type 1 and type 2 diabetes. METHODS: An observational study of pregnant women with type 1 (n = 92) and type 2 diabetes (n = 106) who delivered between 2004 and 2014 at a single tertiary obstetric centre. Clinical and biochemical characteristics were determined and related to major obstetric outcomes: preeclampsia, preterm birth <32 and <37 weeks, and neonatal intensive care admission. We used univariate analyses and multivariable logistic regression models with eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albuminuria as covariates. RESULTS: In the pooled diabetes cohort, multivariable logistic regression with eGFR and albuminuria status demonstrated that the presence of albuminuria (albumin-to-creatinine ratio ≥ 3.5 mg/mmol) (OR, 2.7; 95% CI, 1.42-4.99; P = 0.002) was associated with preeclampsia, whilst an eGFR of < 120 mL/min/1.73 m2 was associated with preterm birth < 32 weeks (OR, 1.04; 95% CI, 1.00-1.09; P = 0.02). CONCLUSIONS: Despite its recognized limitations in pregnancy, lower eGFR values were associated with increased risk of adverse outcomes. Our exploratory data suggest eGFR, along with albuminuria, can aid in identifying women at high risk of developing adverse obstetric outcomes.

Combined Vertebral Augmentation and Radiofrequency Ablation in the Management of Spinal Metastases: an Update.

OPINION STATEMENT: Spinal metastases are the most commonly encountered tumour of the spine, occurring in up to 40% of patients with cancer. Each year, approximately 5% of cancer patients will develop spinal metastases. This number is expected to increase as the life expectancy of cancer patients increases. Patients with spinal metastases experience severe and frequently debilitating pain, which often decreases their remaining quality of life. With a median survival of less than 1 year, the goals of treatment in spinal metastases are reducing pain, improving or maintaining level of function and providing mechanical stability. Currently, conventional treatment strategies involve a combination of analgesics, bisphosphonates, radiotherapy and/or relatively extensive surgery. Despite these measures, pain management in patients with spinal metastases is often suboptimal. In the last two decades, minimally invasive percutaneous interventional radiology techniques such as vertebral augmentation and radiofrequency ablation (RFA) have shown progressive success in reducing pain and improving function in many patients with symptomatic spinal metastases. Both vertebral augmentation and RFA are increasingly being recognised as excellent alternative to medical and surgical management in carefully selected patients with spinal metastases, namely those with severe refractory pain limiting daily activities and stable pathological vertebral compression fractures. In addition, for more complicated lesions such as spinal metastasis with soft tissue extension, combined treatments such as vertebral augmentation in conjunction with RFA may be helpful. While combined RFA and vertebral augmentation have theoretical benefits, comparative trials have not been performed to establish superiority of combined therapy. We believe that a multidisciplinary approach as well as careful pre-procedure evaluation and imaging will be necessary for effective and safe management of spinal metastases. RFA and vertebral augmentation should be considered during early stages of the disease so as to maintain the remaining quality of life in this patient population group.