m6 A modification of HSATIII lncRNAs regulates temperature-dependent splicing.

Nuclear stress bodies (nSBs) are nuclear membraneless organelles formed around stress-inducible HSATIII architectural long noncoding RNAs (lncRNAs). nSBs repress splicing of hundreds of introns during thermal stress recovery, which are partly regulated by CLK1 kinase phosphorylation of temperature-dependent Ser/Arg-rich splicing factors (SRSFs). Here, we report a distinct mechanism for this splicing repression through protein sequestration by nSBs. Comprehensive identification of RNA-binding proteins revealed HSATIII association with proteins related to N6 -methyladenosine (m6 A) RNA modification. 11% of the first adenosine in the repetitive HSATIII sequence were m6 A-modified. nSBs sequester the m6 A writer complex to methylate HSATIII, leading to subsequent sequestration of the nuclear m6 A reader, YTHDC1. Sequestration of these factors from the nucleoplasm represses m6 A modification of pre-mRNAs, leading to repression of m6 A-dependent splicing during stress recovery phase. Thus, nSBs serve as a common platform for regulation of temperature-dependent splicing through dual mechanisms employing two distinct ribonucleoprotein modules with partially m6 A-modified architectural lncRNAs.

Serum keratin 19 (CYFRA21-1) is a prognostic biomarker in severe alcoholic hepatitis.

BACKGROUND AND AIMS: Up to 30% of patients with severe alcoholic hepatitis (sAH) die within 3 months of presentation. The degree of ductular reaction, characterized by accumulation of biliary and liver progenitor cells, confers a poor prognosis. Keratin fragments are established serological surrogates of liver injury and keratin 19 (K19) is a histological marker of the ductular reaction. We assessed the relationship between serum K19 levels (viz. CYFRA21-1), histology and outcome in patients with sAH. METHODS: Serum CYFRA21-1 was quantified in pre-treatment serum samples from 824 patients enrolled in the STOPAH trial. The cohort was randomly divided into two groups to test mortality associations; histological analyses were performed using the 87 cases with suitable samples. RESULTS: CYFRA21-1 levels were elevated in sAH and strongly predicted alcoholic steatohepatitis (ASH) on biopsy (area under the receiver operated characteristic [AUROC] 0.785 [95% Confidence Interval 0.602-0.967]) and 90-day survival (AUROC 0.684/0.693). The predictive ability of CYFRA21-1 was comparable with the model of end-stage liver disease (MELD) score and was independently associated with survival in multivariable analysis. CYFRA21-1 moderately correlated with hepatocellular injury markers M30/M65 but displayed a more robust predictive ability. A combination of MELD and CYFRA21-1 conferred a modest improvement in the AUROC value (0.731/0.743). CONCLUSIONS: In sAH serum, CYFRA21-1 levels associate with the presence of ASH on biopsy and independently predict 90-day survival. As a single marker performance is comparable to established scoring systems. Therefore, CYFRA21-1, which is available in many clinical laboratories, may become a useful component of prognostic models.

Influence of dietary supplementation of marigold flower powder and extract (Calendula officinalis L.) on performance, nutrient digestibility, serum biochemistry, antioxidant parameters and immune responses of growing Japanese quail.

This study aimed to investigate the effects of Marigold flower powder (MFP) and marigold flower extract (MFEx) as feed additives on the performance, blood parameters, antioxidant capacity, immunological parameters, microbial content, digestive enzymes and digestibility in growing Japanese quail. A total number of 350 birds randomly distributed into seven groups, with five replicates of 10 birds each, control diet (control group), the second, third and fourth groups were fed on a basal diet within MFP 0.6%, 0.9% and 1.2% respectively. Fifth, sixth and seventh groups received the basal diet plus MFEx 150, 200 and 250 ppm respectively. Quails fed on a diet supplemented with MFEx 200 ppm had significantly higher lipase levels (p ≤ 0.001) compared to the control and MFP 0.6% without any significant difference with other experimental groups. Moreover, all digestibility coefficients (DC) of nutrients except for nitrogen-free extract were significantly (p ≤ 0.001) affected by all dietary treatments. Quails fed on the diet supplemented with MFEx 200 ppm significantly (p ≤ 0.001) presented the best body weight, body weight gain, feed conversion ratio and the lowest feed intake over all groups. Total lipid profile, kidney functions and liver functions were significantly affected by both MFP and MFEx diets. The group treated with MFEx 250 ppm had lowest E. coli and Salmonella population and the highest Lactobacilli population number. Antioxidant parameters and immune response (except for lymphocytes) were significantly affected (p ≤ 0.001) by different levels of MFP and MFEx. In conclusion, the addition of MFEx and MFP at 200 ppm followed by 250 ppm and 1.2% MFP, respectively, to the basal diet improved product productive performance, blood parameters, antioxidant capacity, immunological parameters, microbial content and digestibility in growing Japanese quail.

Serum keratin 19 (CYFRA21-1) links ductular reaction with portal hypertension and outcome of various advanced liver diseases.

BACKGROUND: Keratins (Ks) represent tissue-specific proteins. K18 is produced in hepatocytes while K19, the most widely used ductular reaction (DR) marker, is found in cholangiocytes and hepatic progenitor cells. K18-based serum fragments are commonly used liver disease predictors, while K19-based serum fragments detected through CYFRA21-1 are established tumor but not liver disease markers yet. Since DR reflects the severity of the underlying liver disease, we systematically evaluated the usefulness of CYFRA21-1 in different liver disease severities and etiologies. METHODS: Hepatic expression of ductular keratins (K7/K19/K23) was analyzed in 57 patients with chronic liver disease (cohort i). Serum CYFRA21-1 levels were measured in 333 Austrians with advanced chronic liver disease (ACLD) of various etiologies undergoing hepatic venous pressure gradient (HVPG) measurement (cohort ii), 231 French patients with alcoholic cirrhosis (cohort iii), and 280 hospitalized Germans with decompensated cirrhosis of various etiologies (cohort iv). RESULTS: (i) Hepatic K19 levels were comparable among F0-F3 fibrosis stages, but increased in cirrhosis. Hepatic K19 mRNA strongly correlated with the levels of other DR-specific keratins. (ii) In ACLD, increased serum CYFRA21-1 associated with the presence of clinically significant portal hypertension (CSPH; HVPG ≥ 10 mmHg) (OR = 5.87 [2.95-11.68]) and mortality (HR = 3.02 [1.78-5.13]; median follow-up 22 months). (iii) In alcoholic cirrhosis, elevated serum CYFRA21-1 indicated increased risk of death/liver transplantation (HR = 2.59 [1.64-4.09]) and of HCC (HR = 1.74 [1.02-2.96]) over the long term (median follow-up 73 months). (iv) In decompensated cirrhosis, higher serum CYFRA21-1 predicted 90-day mortality (HR = 2.97 [1.92-4.60]) with a moderate accuracy (AUROC 0.64), independently from established prognostic scores. CONCLUSIONS: Hepatic K19 mRNA and serum CYFRA21-1 levels rise in cirrhosis. Increased CYFRA21-1 levels associate with the presence of CSPH and reliably indicate mortality in the short and long term independently of conventional liver biochemistry markers or scoring systems. Hence, the widely available serum CYFRA21-1 constitutes a novel, DR-related marker with prognostic implications in patients with different settings of advanced liver disease.

Two distinct nuclear stress bodies containing different sets of RNA-binding proteins are formed with HSATIII architectural noncoding RNAs upon thermal stress exposure.

Nuclear stress bodies (nSBs) are thermal stress-inducible membrane-less nuclear bodies that are formed on highly repetitive satellite III architectural noncoding RNAs (HSATIII arcRNAs). Upon thermal stress exposure, HSATIII expression is induced to sequestrate specific sets of RNA-binding proteins and form nSBs. The major population of nSBs contain SAFB as a marker, whereas the minor population are SAFB-negative. Here, we found that HNRNPM, which was previously reported to localize in nuclear foci adjacent to SAFB-positive foci upon thermal stress, localizes in a minor population of HSATIII-dependent nSBs. Hence, we used the terms nSB-S and nSB-M to distinguish the SAFB foci and HNRNPM foci, respectively. Analysis of the components of the nSBs revealed that each set contains distinct RNA-binding proteins, including SLTM and NCO5A in nSB-Ss and HNRNPA1 and HNRNPH1 in nSB-Ms. Overall, our findings indicate that two sets of nSBs containing HSATIII arcRNAs and distinct sets of RNA-binding proteins are formed upon thermal stress exposure.

Unusual rotavirus genotypes among children with acute diarrhea in Saudi Arabia.

BACKGROUND: Human rotavirus A (human RV-A) is the most common cause of viral gastroenteritis in infants. The objective of the study was to characterize the G and P genotypes among clinical rotavirus isolates from children with acute diarrhea admitted to a tertiary care hospital in Riyadh, Saudi Arabia. METHODS: From 2011 to 2012, 541 pediatric patients with acute diarrhea were tested for rotavirus infection. RNA extractions from the fecal specimens were done by commercial kit. RT-PCR and sequencing techniques were used to detect the prevalent genotypes. Phylogenetic analysis by Maximum Likelihood method was used to study the clustering of the circulating genotypes. RESULTS: The data showed that 171/541 (31.6%) faecal samples were positive for human RVA and majority were children aged below 2 years. From the G and P [types] detected it was seen that (a) 171 minus 43 ie. 128 rotavirus positives were G typed successfully (b) 171 minus 20 ie. 151 rotavirus positives were P typed successfully; (c) overall G [P] nature was determined for 113 rotavirus positives out of 171. VP4 genotyping showed that majority of the positives 146/151 (96.7%) were P [8]; 4/151 (2.6%) were P [4]; 1/151 (0.66%) was P [6]. The dominant strains included G1P [8] 70/113 (61.9%); G9P [8] 19/113 (16.8%); G12P [8] 7/113 (6.2%) and G3P [8] 5/113 (4.4%) while the uncommon strains detected from Saudi Arabia during the study were G1P [4] 1/113 (0.88%) and G12P [6] 1/113 (0.88%). Phylogenetic tree, based on VP4/VP7 sequence analysis, revealed that G1P [8] was distinctly related to homologous strains included in human RV-A vaccine strains. Nevertheless, the uncommon genotypes G1P [4] and G12P [6] were clustered with isolates from other countries such as Bangladesh, China, Japan, Thailand and Philippines. CONCLUSIONS: More studies will be required to further focus on newly emerging genotypes in our region together with the seasonality of rotavirus infection in the region, especially after January 2013 when the rotavirus vaccination has become part of routine childhood immunizations.

Spontaneous Perforation of Meckel's Diverticulum in a Young Adult Male: A Case Report and Review of the Literature.

Meckel's diverticulum, a congenital defect that affects about 2% of the population, is a remnant of the embryologic vitelline duct. Perforated Meckel's diverticulum, a rare consequence of an already rare disease process, frequently presents and is diagnosed as a perforated appendix. We report a case of a 28-year-old male who presented with a two-day history of right-sided lower abdominal pain associated with nausea. The abdominal examination revealed a soft, nondistended abdomen with tenderness in the right iliac fossa. A CT scan of the abdomen showed a normal appendix and inflammation of Meckel's diverticulum without any signs of perforation. Bowel exploration through a small midline incision indicated the presence of a highly inflamed Meckel's diverticulum with localized perforation 75 cm from the ileocecal valve. A resection of 15 cm of the small bowel and an end-to-end primary anastomosis were performed. The patient had an uncomplicated recovery and was discharged after a five-day admission to a surgical ward. This case report illustrates the significance of keeping Meckel's diverticulum as a differential diagnosis in all the patients who present with an acute abdomen.

Outcomes of Percutaneous Image-Guided and Laparoscopic Cholecystostomies in High-Risk Patients With Acute Calculus Cholecystitis: A Five-Year District General Hospital Experience.

Introduction Acute cholecystitis (AC), inflammation of the gall bladder, is one of the most common emergency surgical presentations. In the UK, approximately 15% of the population is estimated to have gallstones, and approximately 20% of them can develop AC. Laparoscopic cholecystectomy (LC) is considered the definitive management of AC. However, cholecystectomy carries a very high risk of morbidity and mortality in high-risk frail patients with multiple comorbidities who are deemed unfit for surgery. Percutaneous cholecystostomy (PC), both image-guided and laparoscopic, is generally acknowledged as an interim treatment measure before definitive management, which is the LC. Materials and methods This is a retrospective study from the Royal Albert Edward Infirmary, a district general hospital (DGH) based in Wigan, UK. The medical records of all the patients who were admitted to the surgical department and underwent PC between January 2017 and December 2022 were analyzed. Patients with previous hepato-pancreato-biliary (HPB) malignancy, who underwent open cholecystostomy, or those with abdominal ascites were excluded from the study. Information was collected regarding the age, gender, American Society of Anaesthesiologists (ASA) grades, success rates of both procedures as temporary or definitive management, duration of hospital stay, 30-day and 1-year mortality after the procedure, timing of the procedure, and long-term complications after the procedure, particularly those related to cholecystostomy tube dislodgment or blockage. Results Twenty-seven patients who underwent PC were divided into two groups: group A, consisting of 10 patients who underwent laparoscopic cholecystostomies, and group B, consisting of 17 patients who had ultrasound (US)-guided cholecystostomies. The mean age of the patients in group A was 66.7 as compared to 75.1 in group B. Most of the patients were in ASA groups III (14) and IV (10). About 74% of patients had procedures done during the day and 26% had PC at night time. The mean hospital stay was 13.5 days. About 55% of patients had planned elective LC as a definitive management. Following the treatment, two patients died within 30 days, and eight patients passed away within a year. About 40% of the patients had complications related to the tube dislodgment and blockage. Conclusion This study concludes that PC, using both laparoscopic and US-guided techniques, can serve as an interim as well as a definitive measure, particularly in patients who are at high risk for anesthesia and the procedure itself and have multiple comorbidities.

Application of ZnO NPs, SiO2 NPs and Date Pollen Extract as Partial Substitutes to Nitrogen, Phosphorus, and Potassium Fertilizers for Sweet Basil Production.

The reduction in mineral fertilizer usage is crucial to the production of medicinal and aromatic products for safety and health purposes. Presently, nanotechnology and the utilization of natural extracts have been extensively studied due to their significant contribution. Ocimum basilicum is commonly employed for various medicinal and aromatic applications. Therefore, randomized complete block design field experiments containing 10 treatments were conducted during the 2021 and 2022 seasons to investigate the effect of nanoparticles (NPs) of ZnO (1.5 and 2.0 g/L) and SiO2 (100 and 150 mg/L) and date palm pollen extract (DPPE) at 10 and 20 g/L either alone or in combination with the ¾ or ½ NPK recommended dose (RD). The NPK RD was served as a control treatment on basil plant production in each season. The effectiveness of ZnO NPs, SiO2 NPs, and DPPE for the decrease in NPK utilization was evaluated. Meanwhile, the most effective treatment for vegetative traits (except for plant height), essential oil %, and yield was ½ NPK RD + 20 g/L DPPE + 2.0 g/L ZnO NPs. Such a treatment increased the branch number/plant, main stem diameter, relevant chlorophyll content, fresh weight/plant, dry weight/plant, essential oil %, and essential oil yield/plant by 21.00 and 9.94%, 58.70 and 40.00%, 20.69 and 15.83%, 68.83 and 58.28%, 48.70 and 56.16%, 45.71 and 35.53%, and 113.22 and 110.32% over the control in the two seasons, respectively. For total phenol and antioxidant activity, the most effective treatments were the ¾ NPK +1.5 g/L ZnO NPs and ½ NPK +2.0 g/L ZnO NPs, respectively. Simultaneously, essential oil composition (with their compound numbers identified (11-29 for control and ¾ NPK RD + 1.5 g/L ZnO NPs)) and the percentage of total compounds, monoterpene hydrocarbons, sesquiterpene hydrocarbons, and oxygenated hydrocarbons were varied among the used applications. The major observed compounds (>8%) estragole, methyl eugenol, linalool, cineole, and caryophyllene were found in different treatments. Thus, the findings of this study indicate the favorable utilization of ZnO NPs, SiO2 NPs, and DPPE in reducing the application of NPK, which may present a novel strategy and beneficial approach.

Triple injection peri-sartorius (TIPS) block for postoperative analgesia after total knee arthroplasty: Randomised controlled study.

Background and Aims: Motor-sparing analgesia after total knee arthroplasty (TKA) is crucial. The primary endpoint was the postoperative visual analogue scale (VAS) score after triple injection peri-sartorius (TIPS) block after TKA. Secondary endpoints were postoperative morphine consumption, 24-h postoperative ambulation distances and the degrees of active knee extension. Methods: After general anaesthesia or spinal anaesthesia administration and before surgical incision, 80 patients undergoing TKA were randomised into group TIPS (received ultrasound-guided TIPS block where 40 ml 0.25% bupivacaine and 4 mg dexamethasone were injected: 10 ml at the distal femoral triangle, 10 ml above the sartorius and 20 ml at the distal adductor canal) and group FNB (femoral nerve block; received ultrasound-guided FNB with 20 ml 0.25% bupivacaine mixed with 4 mg dexamethasone). Postoperative pain score was noted and compared. Results: Dynamic VAS scores were lower in the TIPS group than in FNB, while the resting VAS scores were not significantly different. Mean (standard deviation [SD]) postoperative morphine consumption was 5.82 (2.47) mg in the TIPS group (95% confidence interval [CI] 5.03,6.61) versus 9.87 (2.99) mg in the FNB group (95% CI 8.91,10.83). Ambulation distances and active postoperative knee extension in the TIPS group showed greater significance than in the FNB group (TIPS: 18.0 [7.37] m, 95% CI 15.64,20.35] vs. FNB: 8.95 [5.93] m, 95% CI 7.05,10.84) and (TIPS: 52.12 [16.39], 95% CI 46.88,57.33 vs. FNB: 26.05 [11.10], 95% CI 22.501,29.59). Nausea was more evident in FNB patients. Conclusion: TIPS block provides superior analgesia than FNB with motor sparing of the quadriceps after TKA.

Single puncture combined lumbar erector spinae plane and quadratus lumborum block (SEQ block) in acetabular fracture surgeries: randomized clinical trial.

BACKGROUND: Acetabular fracture surgery can cause severe postoperative pain. A combined lumbar erector spinae plane block and paraspinous sagittal shift quadratus lumborum block may augment analgesia. METHODS: Fifty two patients undergoing posterior column acetabular surgery were divided into: Group Single puncture combined lumbar Erector spinae and Quadratus lumborum block (SEQ), patients who received SEQ block before anesthesia; and Group morphine (MOR), those who received general anesthesia (GA) and morphine. RESULTS: Demographic characteristics were comparable. The heart rate and mean arterial blood pressure were significantly lower in the SEQ group than in the MOR group between 60 and 180 min intraoperatively (P < 0.001). Postoperative resting and dynamic visual analogue scale scores in the SEQ group were significantly lower than those in the MOR group at all studied periods (P = 0.022-0.001), except at 20 and 24 h postoperatively. Fentanyl was required in all MOR group patients at a mean dose of 110.0 ± 28.42 µg while 18 patients required fentanyl in SEQ group at a mean dose of 60.55 ± 25.54 µg. Postoperative morphine consumption was significantly less in SEQ group (6.33 ± 2.37 mg) than MOR group (17.0 ± 2.55 mg). Postoperative nausea and vomiting were recorded in eight and four patients in MOR and SEQ group, respectively. No complications associated with the block technique were observed. CONCLUSIONS: The SEQ block reduces the postoperative opioid consumption and provides stable intra and postoperative hemodynamics without observed complications in posterior column acetabular surgery.

Biomarkers of hepatocellular synthesis in patients with decompensated cirrhosis.

BACKGROUND AND AIM: Since hepatocytes produce majority of serum proteins, patients with cirrhosis display substantial alterations in the serum proteome. The aim of the current study was to characterize these changes and to study the prognostic utility of hepatocellular proteins available in routine clinical testing. METHODS: Sera from 29 healthy controls and 43 patients with cirrhosis were subjected to untargeted proteomic analysis. Unsupervised hierarchical clustering was performed with Perseus software and R. Ingenuity pathway analysis (IPA) suggested upstream regulators that were validated in liver tissues. The behavior and prognostic usefulness of selected biomarkers was investigated in 61 controls and 285 subjects with decompensated cirrhosis. RESULTS: Proteomics uncovered 65 and 16 hepatocellular serum proteins that are significantly downregulated or upregulated in patients with cirrhosis vs. controls. Hierarchical clustering revealed two main clusters and six sub-clusters. IPA identified HNF4α and IL-6 as the two major upstream regulators that were confirmed by hepatic gene expression analyses. Among pseudocholinesterase, transferrin, transthyretin, albumin, and apolipoprotein AI (Apo-AI), Apo-AI was the best predictor of 90-days transplant-free survival (AUROC 0.678; p = 0.0001) and remained an independent predictor in multivariable Cox independently of the presence of acute-on-chronic liver failure. CONCLUSION: Our study reveals cirrhosis-associated changes in hepatocellular serum proteins and underlying transcription factors. Serum apolipoprotein AI may constitute a useful prognostic adjunct in patients with decompensated cirrhosis.

Recent advances in three-dimensional ultrasound virtual cystoscopy in modeling and local staging for urothelial carcinoma with histopathological correlation: a cohort prospective study.

Background: Bladder urothelial carcinoma is an alarming urologic malignancy. Complex factors like modelling and local staging can affect treatment strategy. However, local staging, particularly the muscle invasion status, significantly influences decisions regarding treatment strategies. Therefore, this study aims to evaluate the novel advances of three-dimensional (3D) ultrasound (US) imaging to assess local staging in comparison with conventional cystoscopy. Methods: Forty-three patients with painless haematuria and conventional cystoscopy findings of bladder mass underwent 3D US virtual cystoscopy. All specimens from conventional cystoscopy were processed histologically. Results: Out of 43 participants, 18 (41.9%) patients proved to have invasive urothelial carcinoma by histopathology. The 3D US had a sensitivity of 97.5% and a specificity of 100%; however conventional cystoscopy was accurate in only 53.5% of the studied cases. Furthermore, in the case of malignant ulcers, mural extension into both the submucosal and the muscle layers was more readily appreciated in multiplanar images. Conclusion: 3D US updates are promising for use in bladder tumour modelling and local staging; however, they can be of value in evaluating mural and extramural tumour extent and have proven accuracy.

A rare case of arterial tortuosity syndrome in an adult.

Arterial tortuosity syndrome (ATS) is rare autosomal recessive connective tissue disorder. It affects large and medium-sized arteries inducing tortuosity and elongation. Typical skeletal manifestations are dysmorphic features, hyperextensible skin, hypermobile joints, and congenital contractures. We present a case of a 33-year-old female, with history of multiple abdominal wall hernias, who was diagnosed with ATS by preoperative investigations based on typical vascular manifestations. We will present the radiological findings of this rare condition.

Effect of Pilates Exercises on Standing, Walking, and Balance in Children With Diplegic Cerebral Palsy.

OBJECTIVE: To analyze how Pilates exercises affect standing, walking, and balance in children with diplegic cerebral palsy throughout a 10-week program. METHODS: We included 40 children aged 7-9 years with diplegic cerebral palsy, and randomly allocated them into two groups of the same size: conventional therapy group (group A) and conventional therapy+Pilates group (group B). We administered the same conventional physical therapy program to both groups for 45 minutes, with group B receiving additional Pilates exercises for 45 minutes. Both groups attended the intervention program three times/week for 10 weeks. We used the Growth Motor Function Measure Scale (GMFM-88) to evaluate standing and walking (Dimensions D and E), and the Pediatric Balance Scale to evaluate balance function before and after treatment. RESULTS: Comparison of the average values of all measured variables before and after therapy showed a statistically significant difference (p<0.05) between the two groups. All measured variables showed a significant difference between groups A and B, in favor of group B (p<0.05). CONCLUSION: Pilates exercise in addition to conventional therapy is more effective in improving balance and gross motor function in children with diplegic cerebral palsy than the conventional therapy alone.

Comparison Between Ultrasound-guided Caudal Analgesia versus Peripheral Nerve Blocks for Lower Limb Surgeries in Pediatrics: A Randomized Controlled Prospective Study.

Background and Aim: Ultrasound (US) guided regional analgesia is a safe and effective method in providing perioperative analgesia in pediatrics with a high success rate rapid onset and fewer side effects. The aim of this study was to compare the efficacy of US-guided caudal block versus US-guided peripheral nerve blocks (femoral and sciatic nerve blocks) in providing perioperative analgesia in pediatrics undergoing unilateral lower limb surgery. Methods: Children aged 1-12 years scheduled for unilateral lower limb surgery during the period from January 2020 to December 2021 were randomly allocated into two groups. Group C where pediatrics received US-guided caudal block, while in group P, pediatrics received US-guided femoral and sciatic nerve blocks after the induction of general anesthesia (GA). The primary aim was to compare the postoperative pain (evaluated by the COMFORT pain score) between the two groups. Secondary aims were to compare perioperative opioids used parents' satisfaction and occurrence of side effects. Results: Pediatrics who underwent unilateral lower limb surgeries were allocated into two groups (group C and group P). There was no significant difference between patients' baseline characteristics and the postoperative pain score at 2, 4, 16, and 20 h.' However there was a statistical significance at 6, 8, 12, and 24 h postoperatively, frequency of analgesia as well as the total postoperative dose of opiates (nalbuphine). Time to first analgesic (nalbuphine) requirement was significantly less in group C with a mean of (9.6±2.9 h) than in group P with a mean of (15.1±3.5 h). Parents of children in group P were more satisfied than those in group C with no recorded complications for both techniques. Conclusion: US-guided lower limb peripheral nerve block is a simple and safe method to provide adequate and more prolonged analgesia compared to US-guided caudal block for lower limb surgeries in pediatrics.

Volumetric parameters from [18 F]FDG PET/CT predicts survival in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms.

A positive fluorine-18 labelled 2-deoxy-2-fluoroglucose ([18 F]FDG) positron emission tomography/computed tomography (PET/CT) has been associated with more aggressive disease and less differentiated neuroendocrine neoplasms (NEN). Although a high maximum standardized uptake value (SUVmax ) predicts poor outcome in NEN, volumetric parameters from [18 F]FDG PET have not been evaluated for prognostication in a pure high-grade gastroenteropancreatic (GEP) NEN cohort. In this retrospective observational study, we evaluated the volumetric PET parameters total metabolic tumour volume (tMTV) and total total lesion glycolysis (tTLG) for independent prognostication of overall survival (OS). High-grade GEP NEN patients with [18 F]FDG PET/CT examination and biopsy within 90 days were included. Total MTV and tTLG were calculated using an adaptive thresholding software. Patients were dichotomised into low and high metabolic groups based on median tMTV and tTLG. OS was compared using Kaplan-Meier estimator and log-rank test. Uni and multivariable Cox regression was used to estimate effect sizes and adjust for tumour differentiation and SUVmax . Sixty-six patients (median age 64 years) were included with 14 NET G3 and 52 NEC cases after histological re-evaluation. Median tMTV was 208 cm3 and median tTLG 1899 g. Median OS in the low versus high tMTV-group was 21.2 versus 5.7 months (HR 2.53, p = 0.0007) and 22.8 versus 5.7 months (HR 2.42, p = 0.0012) in the tTLG-group. Adjusted for tumour differentiation and SUVmax , tMTV and tTLG still predicted for poor OS, and both tMTV and tTLG were stronger prognostic parameters than SUVmax . Both regression models showed a strong association between volumetric parameters and OS for both neuroendocrine tumours (NET) G3 and neuroendocrine carcinomas (NEC). OS for the tTLG low metabolic NEC was much higher than for the tTLG high metabolic NET G3 (18.3 vs. 5.7 months). High-grade GEP NEN patients with high tMTV or tTLG had a worse OS regardless of tumour differentiation (NET G3 or NEC). Volumetric PET parameters were stronger prognostic parameters than SUVmax .

Determination of optimal concentration of vitamin E in polyethylene liners for producing minimal biological response to prosthetic wear debris.

The introduction of vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) for use in prosthetic components of hip implants has resulted in the production of implants that have excellent mechanical properties and substantially less adverse cellular responses. Given the importance of a biological response to wear in the survival of a prosthesis, we generated wear debris from UHMWPE that had been prepared with different concentrations of vitamin E of 0.1, 0.3, 0.5, and 1% and evaluated their biological reaction in vitro and in vivo. All types of VE-UHMWPE debris promoted a significantly lower expression of Tnf-α in murine peritoneal macrophages than that induced by conventional UHMWPE debris. However, levels of Tnf-α were not significantly different among the macrophages that were stimulated with VE-UHMWPE wear at the concentrations tested. The ability of wear debris to induce inflammatory osteolysis was assessed in a mouse calvarial osteolysis model. The expressions of Tnf-α, Il-6, and Rankl in granulomatous tissue formed around the wear debris were significantly reduced in mice that had been implanted with 0.3%VE-UHMWPE debris as compared to the corresponding values for mice that had been implanted with UHMWPE debris. Consistent with this finding, 0.3%VE-UHMWPE debris showed the lowest osteolytic activity, as evidenced by the reduced bone resorption area, the degree of infiltration of inflammatory cells and the TRAP staining area. Our results suggested that a 0.3% vitamin E concentration is the most appropriate concentration for use in prosthetic components with a reduced adverse cellular response for prolonging the life-span of the implant.

MicroRNAs as biomarkers in spontaneous intracerebral hemorrhage: A systematic review of recent clinical evidence.

OBJECTIVES: Spontaneous intracerebral hemorrhage (SICH) is a subtype of stroke associated with high mortality and devastating disabilities. Therefore, identifying non-invasive biomarkers for SICH would have a tremendous clinical impact. MicroRNAs (miRNAs) are non-coding single-stranded RNAs containing 21-23 nucleotides that control the activity of various protein-coding genes through post-transcriptional repression. In this systematic review, we report the recent clinical evidence on the role of miRNAs as biomarkers for the prediction, prognosis, early detection, and risk stratification of SICH. METHODS: We conducted a systematic search of PubMed, PubMed Central, MEDLINE, and Embase databases and included only full-text peer-reviewed articles published in English. RESULTS: We included 10 studies comprising seven case-control studies, two cohort studies, and one cross-sectional study, among which we found 27 altered miRNAs, suggesting their role as biomarkers for the early detection of ICH. Additionally, the expression of 34 miRNAs was associated with poor prognosis of ICH; miR-126 and miR-23a-3p expression correlated with relative perihematomal edema (PHE) volume, and using a subset of 10 miRNA signatures had an accuracy of 100% in predicting hematoma in patients with ICH. Moreover, miR-4317 and miR-4325 profiling predicted the development of late seizures. Thirty-nine miRNAs were associated with the incidence of all types of strokes, while 10 miRNAs correlated with the predicted risk of stroke but were not specific to a stroke subtype. The altered miRNA signatures contributed to endothelial dysfunction, hematoma, and PHE through leukocyte activation, oxidative stress response, programmed cell death, smooth muscle cell proliferation, and apoptosis of cerebrovascular endothelial cells. The current data had limitations and gaps, especially the human studies, and there may have been selection bias in the prospective studies. There were also some limitations regarding the methods for obtaining miRNAs and identifying target RNAs specific to SICH pathology. Additionally, there may have been correlations between the outcomes and other factors, such as therapeutic interventions and ICH severity, the circulating miRNA profiles and gene expression profiles, and other pathological conditions and patients' age. Finally, the prediction and risk stratification of SICH could not be calculated separately from ischemic stroke. CONCLUSIONS: Following our literature retrieval, we noted alterations in various miRNA signatures, suggesting their potential role as biomarkers for the early detection and differentiation of SICH. Indeed, miRNA expression was associated with a poor prognosis of SICH and correlated with the predicted risk of stroke but was not specific to a stroke subtype. Further studies are needed, especially on the therapeutic potential of miRNAs and their target RNAs in SICH.

Evaluation and Haematological Profile of an Inactivated RVF Vaccine Locally Produced in Egypt.

<b>Background and Objective:</b> The RVF virus cause diseases in newborn puppies, kittens, sheep, goats, cattle, camels, buffaloes and also humans. The RVF disease was first detected among livestock by veterinary officers. The disease causes abortions in animals. The goal of this study was to evaluate the immune response and the haematological profile associated with inactivated RFV vaccine locally produced in Egypt in young puppies and sheep. <b>Materials and Methods:</b> Through vaccination, both young puppies and sheep with local produced inactivated RVF vaccine with 2 doses with 2 weeks interval and evaluate the immune response by SNT and ELISA as well as haematological parameters at 0, 7, 14, 21 and 28 days post-vaccination. The variance between vaccinated groups and also non-vaccinated groups were compared by using a one-way Analysis of Variance (ANOVA). <b>Results:</b> The findings showed that young puppies had a strong response to antibodies after two doses of the RVF vaccine within the 2 week interval. The neutralization indices (NI) values in young puppies at different periods after RVF vaccination reported the value of 1.08±0.03, 1.23±0.04, 1.30±0.03 and 1.45±0.02 after 7, 14, 21 and 28 days post-vaccination, respectively. Parallel to this the ELISA OP values were 0.30±0.00, 0.39±0.03, 0.52±0.05 and 0.75±0.02 after 7, 14, 21 and 28 days post-vaccination, respectively. Nearly similar immune response was noticed in sheep with NI values of 1.15±0.02, 1.27±0.02, 1.42±0.05 and 1.55±0.03 at 7, 14, 21 and 28 days post-vaccination, respectively. In the same site the ELISA OP values were 0.34±0.00, 0.47±0.01, 0.68±0.00, 0.77±0.00. After 7, 14, 21 and 28 days post-vaccination respectively that are also similar to that in puppies. The haematological profile reported a significant decrease after the 1st week followed by a transient increase after booster dose at 2nd week except for the monocytes that increase after 1st week then decreases after 2nd week post-vaccination. <b>Conclusion:</b> Young puppies are similar to sheep in developing antibodies after vaccination with the RFV vaccine with no statistically significant effect within different batches. In addition, ELISA can replace the SNT for evaluation of the immune response. Young puppies are quite equal to sheep for the illustration of neutralizing antibodies for RFV vaccine. Sero-negative puppies can be easily obtained because dogs are not included in the vaccination program of RVF and so they can be used as a good model to determine the efficacy of the RVF vaccine.