A role for the carbon source of the cell and protein kinase A in regulating the S. pombe septation initiation network.

The septation initiation network (SIN) is a conserved signal transduction network, which is important for cytokinesis in Schizosaccharomyces pombe. The SIN component Etd1p is required for association of some SIN proteins with the spindle pole body (SPB) during anaphase and for contractile ring formation. We show that tethering of Cdc7p or Sid1p to the SIN scaffold Cdc11p at the SPB, rescues etd1-Δ. Analysis of a suppressor of the mutant etd1-M9 revealed that SIN signalling is influenced by the carbon source of the cell. Growth on a non-fermentable carbon source glycerol reduces the requirement for SIN signalling but does not bypass it. The decreased need for SIN signalling is mediated largely by reduction of protein kinase A activity, and it is phenocopied by deletion of pka1 on glucose medium. We conclude that protein kinase A is an important regulator of the SIN, and that SIN signalling is regulated by the carbon source of the cell.

Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia.

BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039).

Intermittent dilution of dietary digestible lysine lowers the incidence of white striping by suppressing the growth, lipid synthesis, and muscle damage in broiler chickens.

BACKGROUND: White striping (WS) is a myopathy of breast muscle (Pectoralis major) that affects the quality and consumer acceptance of breast fillets of broiler chickens. Previous studies have shown that intermittent dilution of dietary nutrients suppresses the development of WS on the breast muscle of broiler chickens. However, the mechanism by which these interventions reduce the occurrence of WS remains inconclusive. In this study, we adopted intermittent reduction of dietary digestible lysine (dLys) density or metabolizable energy (ME) and amino acid (AA) density using chemical and fatty acid composition of breast fillets, and blood metabolites to understand the mechanism while histopathology and immunohistochemistry of breast muscles were used for confirmation. RESULTS: Occurrence of WS was lower in broiler chickens fed 85% dLys diets in comparison with other groups. Crude protein and ether extract in breast meat of 85% dLys groups were greater (P < 0.001) and lower (P = 0.010), respectively. Serum concentrations of lipid metabolites and enzymes were lower in broiler chickens fed 85% dLys diets than control group (P < 0.05). Feeding 85% dLys diets had low degree of myodegeneration and necrosis, inflammation, lipid deposition, infiltration of T-lymphocyte (CD3+) and macrophages (Iba-1+), and low expression of heat-shock protein 70 (HSP70) than other groups (P < 0.001). CONCLUSION: Dilution of dietary dLys to 85% of the required quantities reduces the development of WS in broiler chickens by slowing the growth, lipid synthesis, and muscle damage confirmed by lower extent of histopathological lesions. © 2022 Society of Chemical Industry.

Comparison of prenatal central nervous system abnormalities with postmortem findings in fetuses following termination of pregnancy and clinical utility of postmortem examination.

OBJECTIVES: In this study, we aimed to compare prenatal ultrasound (USG) and postmortem examination findings of central nervous system (CNS) abnormalities in fetuses following termination of pregnancy (TOP). METHODS: A total of 190 fetuses with USG-confirmed fetal CNS abnormalities of terminated pregnancies between January 2001 and January 2017 were retrospectively analyzed and USG and postmortem examination findings were compared. RESULTS: The most frequent CNS abnormalities were acrania/anencephaly (n=45, 24%), spina bifida (n=43, 23%), and ventriculomegaly (n=35, 18%). In 144 of the 190 (76%) cases, there was total agreement between USG and postmortem examination diagnosis. Postmortem examination provided minor findings which did not change the major clinical diagnosis in two (1%) cases with spina bifida and ventriculomegaly. In six (3%) cases, the diagnosis changed after postmortem examination. In 25 of the 190 (13%) cases with multiple abnormalities as evidenced by USG, CNS abnormality was unable to be confirmed at postmortem examination. CONCLUSIONS: Our study results show an overall high agreement (76%) between USG and postmortem examination findings for CNS malformations. Due to autolysis and fluid structure, USG-confirmed CNS diagnosis cannot be always confirmed by postmortem examination. This potential discrepancy should be explained to patients before considering TOP. Postmortem examination is the gold standard to confirm prenatal diagnosis.

Fetal autopsy for the diagnosis of skeletal dysplasia and comparison with prenatal ultrasound findings over a 16-year period.

OBJECTIVES: To evaluate the relationship between prenatal ultrasonography (USG) and fetal autopsy findings. METHODS: Among 453 pregnancy terminations performed because of fetal anomalies on prenatal USG, 54 with skeletal dysplasia on fetal autopsy were included in this retrospective study. RESULTS: The most common diagnoses among the 54 fetal autopsies were osteogenesis imperfecta (n=12), dysostosis (n=10), achondroplasia (n=9), arthrogryposis (n=6), and thanatophoric dysplasia (n=6). The prenatal USG and fetal autopsy findings showed complete agreement in 35 cases (64.8%), partial agreement in nine cases (16.6%), and disagreement in 10 cases (18.5%). CONCLUSIONS: Fetal autopsy via perinatal pathology is essential for precise identification of the type of skeletal dysplasia; it should be routinely performed to confirm the diagnosis of prenatally detected fetal anomalies. Autopsy is vital for accurate prenatal diagnosis and the 'gold standard' technique for the identification of clinically important abnormalities.

Predictive value of prenatal ultrasound in foetal intraabdominal cystic lesions and evaluation of perinatal outcomes: a single-centre study results.

The prenatal diagnosis of intra-abdominal cystic lesions is relatively common and it can be due to a wide variety of clinical conditions. The aims of this study were to determine the accuracy of the prenatal ultrasound in identifying the aetiology of foetal intra-abdominal cysts and to describe the prenatal and postnatal outcomes. This study is a retrospective analysis of 137 foetuses diagnosed with intraabdominal cysts during the prenatal period, except those originating from the urinary system, conducted from April 2015 to August 2018. Among 137 intraabdominal cysts identified as antenatal, ovarian cysts had the highest rate of prenatal diagnosis. The most frequently misdiagnosed pathologies were gastrointestinal system obstructions with 6 cases. There were 129 (94.2%)cases of intraabdominal cysts born alive. Intrabdominal cystic lesions resolved spontaneously in 23(16.8%) cases in the intrauterine period and 28 cases within 12 (20.4%) months after birth during follow-up. Postpartum surgical treatment was performed in 44 (%32.1) cases. The overall neonatal mortality was 21/137 (15.3%),with no death in the intrauterine period; 8(5.8%) of these were death following termination of pregnancy, 6(4.4%) were postpartum, and 7(5.1%) were post-surgical death. Postnatal results of intraabdominal cysts are variable. Therefore, individual assessing and managing each case is of clear benefit due to cyst's variable course. IMPACT STATEMENTWhat is already known on this subject? The prenatal diagnosis of intra- abdominal cystic lesions is relatively common and prenatal ultrasound is the main screening tool. The diagnosis of a foetal intra-abdominal cyst might represent a diagnostic and management dilemma due to the wide variety of potential diagnosis.What the results of this study add? The accuracy of prenatal ultrasound in identifying the origin of a foetal intra-abdominal cyst seems to be high with detailed ultrasonographic examinations and the perinatal outcome of these foetuses is favourable in most of them.What the implications are of these findings for clinical practice and/or future research? Regardless of the cyst's origin, it should be kept in mind that prenatal and postnatal clinical courses can be variable in each case, and every pregnant woman with a foetus with an intraabdominal cyst must be managed individually in every aspect.

Effect of humate supplementation to feed and/or litter on performance, intestinal viscosity, litter quality, and occurrence of footpad dermatitis in broilers fed barley-based diets.

We investigated the effect of in-feed and/or in-litter supplemental humate against footpad dermatitis (FPD) in broilers fed diets based on barley. Three hundred and sixty 1-day-old Ross 308 broiler chickens were randomly distributed to 24 floor pens (4 treatments, each consisting of 6 replicate pens; 15 chickens per pen) as a completely randomized design with 2 × 2 factorial arrangement of two levels of supplemental humate in feed (0 and 1 g/kg feed) and litter (0 and 5 g/kg litter). Growth performance, intestinal viscosity, litter quality, and incidence and severity of FPD in broilers were measured. In addition, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined in blood and footpad tissues of broilers with different FPD scores. The results revealed that there was no interaction between humate supplementation to feed and litter. Neither dietary nor litter supplementation of humate had a significant effect on growth performance, intestinal viscosity, litter quality, and occurrence of FPD. And also, MDA and SOD levels in serum and footpad tissue did not affect by either dietary or litter supplementation of humate. The presence of FPD (score 1) had no effect on MDA and SOD levels in serum, however, increased the MDA and SOD levels (P < 0.001, P = 0.001, respectively) in footpad tissue of broilers. The intestinal viscosity did not differ between FPD scores 0 and 1. In conclusion, findings of this experiment suggest that humate supplementation to feed and litter did not alleviate FPD development in broilers fed diets based on barley. In addition, the presence of FPD lesions increases the MDA and SOD levels in the footpad tissues.

Evaluation of Microvascular Complications in Kidney Recipients With Posttransplant Diabetes Mellitus.

CONTEXT: The paucity of data on microvascular complications in patients with posttransplant diabetes (PTDM) is an obstacle to developing follow-up algorithms. OBJECTIVE: To evaluate diabetic microvascular complications in patients with long-standing PTDM. METHODS: In patients with ≥5-year history of PTDM and age-matched renal transplant recipients without PTDM (NDM), diabetic peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument, the CASE IV device, and in vivo corneal confocal microscopy (CCM). Cardiac autonomic neuropathy tests were performed using heart rate variability. Nephropathy screening was assessed using spot urine albumin/creatinine ratio and eGFR calculation. Diabetic retinopathy was evaluated by fundus examination and photography, and optical coherence tomography. RESULTS: This study included 41 patients with PTDM and 45 NDM patients. The median follow-up was 107.5 months in the PTDM group. Peripheral neuropathy was significantly higher in the PTDM group than in the NDM group (P = .02). In the PTDM patients with peripheral neuropathy, corneal nerve fiber density examined by CCM was significantly lower than in PTDM patients without neuropathy (P = .001). Parasympathetic involvement was observed in 58.5% of the PTDM group and 22% of the NDM group (P = .001). Sympathetic involvement was present in 65.9% of the PTDM group and 29.3% of the NDM group (P = .001). Retinopathy was observed in 19.5% of patients in the PTDM group and in none of the NDM patients (P < .001). Renal functions were similar between the study groups. CONCLUSION: Cardiac autonomic neuropathy and diabetic retinopathy can affect patients with PTDM at a high rate. Diabetic retinopathy is a threat to the vision of PTDM patients. Diabetic peripheral neuropathy can be detected early in PTDM patients by CCM.

Chronic otitis media and middle ear variants: Is there relation?

BACKGROUND: Chronic otitis media (COM) is an inflammatory disease that lasts for a long time. It is common in developing countries. Hearing loss can result from COM. The relationship between variations in middle ear anatomy and COM was investigated in our study. AIM: To compare the prevalence of middle ear anatomic variations between the cases with COM and healthy individuals. METHODS: This retrospective study included 500 patients with COM and 500 healthy controls. The presence of those variants was determined: Koerner's septum, facial canal dehiscence, high jugular bulb, jugular bulb dehiscence, jugular bulb diverticulum, sigmoid sinus anterior location and deep tympanic recesses. RESULTS: A total of 1000 temporal bones were examined. The incidences of these variants were respectively (15.4%-18.6%), (38.6%-41.2%), (18.2%-4.6%), (2.6%-1.2%), (1.2%-0%), (8.6%-0%), (0%-0%). It was observed that only high jugular bulb (P < 0.001) and anteriorly located sigmoid sinus frequencies (P = 0.002) in the case group were statistically significantly higher than the control groups. CONCLUSION: COM is a multifactorial disease and variants of middle ear have always been important in terms of potential risk for complication during surgery but rarely associated with COM as an etiology or as a consequence of the disease. We didn't find a positive correlation between COM and Koerner's septum and facial canal defect. We ended up with a significant conclusion with the variants of dural venous sinuses -high jugular bulb, dehiscence of jugular bulb, diverticulum of jugular bulb and anteriorly located sigmoid sinus- that have been studied less and frequently associated with inner ear illnesses.

Dilemma after termination of pregnancy due to urogenital fetal anomalies: Discrepancy between prenatal ultrasonographic diagnosis and autopsy.

OBJECTIVE: To evaluate the agreement and disagreement between prenatal ultrasound and fetal autopsy findings in pregnancy terminations due to urogenital anomalies. METHODS: Of 453 pregnancy terminations performed due to fetal anomalies, 82 cases with urogenital anomalies on either prenatal ultrasound or fetal autopsy were included in this retrospective study. The discrepancy between prenatal ultrasound and fetal autopsy findings on urogenital anomaly findings was evaluated. RESULTS: Complete agreement between prenatal ultrasound and fetal autopsy findings was noted in 33 (40.2%) cases (particularly for megacystis, bilateral renal agenesis, and infantile polycystic kidney), whereas partial agreement (anal atresia and horseshoe kidney as additional minor findings) and altered diagnosis were noted in 12 (14.6%) and 8 (9.8%) cases, respectively. Disagreement was noted in 29 (35.4%) cases including anomaly only on autopsy in 20 (24.3%) cases (renal agenesis, horseshoe kidney and multicystic dysplastic kidney in particular) and anomaly only on ultrasound in 9 (10.9%) cases. CONCLUSIONS: Accordingly, our findings indicate fetal autopsy to be a method of vital importance in complementing prenatal diagnosis; it may add valuable information that may improve future pregnancy management and counseling of parents, and hence prenatal ultrasound and fetal autopsy should be regarded as complementary techniques.

Maternal Serum Cripto-1 Levels in Pregnancies Complicated with Placenta Previa and Placenta Accreta Spectrum (PAS).

OBJECTIVE: To examine maternal serum Cripto-1 levels in placenta accreta spectrum (PAS) pregnancies and compare them with placenta previa (PP) cases and healthy pregnancies. STUDY DESIGN: A prospective case-control study. PLACE AND DURATION OF STUDY: Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey, from April to September 2021. METHODOLOGY: Sixty singleton pregnant patients with PP complicated with PAS were enrolled, 45 singleton pregnant women with a diagnosis of PP without PAS, and 48 healthy uncomplicated gestational age-matched singleton pregnant women. Cripto-1 levels were determined and evaluated. RESULTS: The median maternal serum concentrations of Cripto-1 were greater in pregnant women with PAS (3.11 ng/mL) than in the PP (2.52 ng/mL) and the control groups (2.01 ng/mL, p<0.001). Based on the Youden index, a 2.557 ng/mL cut-off value of maternal serum Cripto-1 level had a 76.7% sensitivity and 72.1% specificity to diagnose pregnancies complicated with PAS. A negative and statistically significant linear relationship was found between maternal serum Cripto-1 concentration and the gestational week at birth (r= -0.325, p<0.001). A positive and statistically significant linear relationship was found between maternal serum concentrations of Cripto-1 and maternal length of hospital stay after birth (r= 0.320, p<0.001). CONCLUSION: Serum Cripto-1 levels were significantly increased levels in pregnant women suffering from PAS than in pregnant women with PP and uncomplicated healthy pregnancies. Higher expression of Cripto-1 might be a crucial factor in the pathogenesis of PAS. KEY WORDS: Abnormal placental implantation, placenta accreta spectrum, Cripto-1, Placenta previa.

Growth performance, carcass yield and characteristics, meat quality, serum biochemistry, jejunal histomorphometry, oxidative stability of liver and breast muscle, and immune response of broiler chickens fed natural antioxidant alone or in combination with Bacillus licheniformis.

In this study, oxidative stability of liver and breast meat, and immune response were evaluated in broiler chickens fed supplemental phytogenic feed additive (PFA) alone or in combination with Bacillus licheniformis. Three experimental groups - control, PFA (60 mg kg - 1 ), and PFA (60 mg kg - 1 )  +  0.5 mg kg - 1 B. licheniformis (1.6  × â€¯10 12  cfu g - 1 ), each consisting of 5 replicates - were established with 20 one-day-old chickens per replicate (300 birds in total). Growth performance, carcass yield and characteristics, and meat quality remained unaffected. However, supplemental PFA and PFA  +  B. licheniformis improved the serum biochemistry and jejunal histomorphometry of broiler chickens ( P < 0.05 ). PFA and PFA  +  B. licheniformis groups had lower thiobarbituric acid reacting substances (TBARS) in liver, and freeze-thaw breast meat after 30, 60, and 90 d of storage ( P < 0.05 ). PFA and PFA  +  B. licheniformis supplementation lowered the carbonyl group in fresh and stored breast meat ( P < 0.05 ). Antibody titer against infectious bursal disease virus was higher in the PFA  +  B. licheniformis group than the control group ( P < 0.05 ). It can be concluded that PFA or PFA  +  B. licheniformis in broiler diets improves the health, oxidative stability of liver and breast meat, and immune response of broiler chickens.

A novel technique in the management of severe postpartum uterine atony bleeding: Three vertical uterine compression sutures.

OBJECTIVE: Postpartum hemorrhage is a leading cause of maternal morbidity and mortality worldwide. Uterine atony is the most common cause of bleeding accounting for ∼80 % of cases of postpartum hemorrhage. To reduce maternal morbidity and mortality due to bleeding caused by uterine atony even under limited resources, a simple and effective procedure that can be easily applied by all obstetricians and junior physicians is required. The aim of this study was to evaluate the efficacy of novel three vertical compression sutures for severe postpartum hemorrhage. DESIGN: Two vertical sutures are transfixed, one on each side of the lower uterine segment, from anterior to posterior over the bladder reflection avoiding the endometrial cavity, and tied over the fundus. The lateral sutures should be placed approximately 2 cm from the lateral edge of the lower uterus and approximately 4 cm from the cornual border, because the uterus widens upward from below. The third vertical suture is placed in the midline at the same level as the two vertical sutures, passing the endometrial cavity from anterior to posterior, and is tied in the middle of the fundus, where the three sutures are positioned side-by-side. RESULTS: We report 25 cases of postpartum hemorrhage secondary to life-threatening severe uterine atony treated with this novel approach of using three vertical compression sutures. Success was achieved in 24/25 (96 %) of cases treated with three vertical sutures, without requiring hysterectomy except one. CONCLUSIONS: To reduce maternal morbidity and mortality, three vertical compression sutures as a novel technique, can be attempted before applying other more complex interventions. It does not require any extra skill or training, and is an ideal option as its simplicity allows it to be performed by all obstetricians, including junior obstetric staff.

Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour in adults. Identification of accessible and cost-effective prognostic factors may better guide adjuvant treatment-related decisions. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of host inflammatory response, and their increase has recently been shown to be a poor prognostic factor in several malignancies. The aim of the present study was to investigate the prognostic value of preoperative NLR and PLR in GBM patients. Between 2012 and 2017, 104 patients who had undergone surgery for GBM were considered for adjuvant therapy in our institution. Of those, 80 patients with evaluable pre-corticosteroid full blood count results were identified and included in the final analysis. The Eastern Cooperative Oncology Group performance status, localization, radiochemotherapy and second-line systemic therapy were found to be independent prognostic indicators for progression-free and overall survival. The median overall survival was 13.2 months. Patients with NLR <4 had a better median overall survival of 10.7 vs. 7.8 months in patients with NLR >4; however, this difference was not statistically significant (P>0.05). Overall survival also did not differ significantly between patients with low and those with high PLR values (10.2 vs. 15.2 months, respectively; P=0.105). In conclusion, the results of the present study suggest that pre-treatment NLR and PLR do not have prognostic value in GBM patients; however, large-scale trials are required to confirm these findings.

Morphological and Histological Study on the Foot Pads of the Anatolian Bobcat (Lynx lynx).

This study was conducted to reveal the morphometric and morphological features of foot pads in the Anatolian bobcat (Lynx lynx). To achieve this objective, dissection, histological, and radiography techniques were applied to two dead materials obtained from the Republic of Turkey Ministry of Forest and Water Works Sivas Branch Manager. Digit I is radiographically rudimentary in the forepaw. The paws of the forelimb of the Anatolian bobcat have a carpal, a metacarpal, and four digital pads, while the hind feet have a metatarsal pad and four digital pads. The metacarpal pad is cone-like, while the metatarsal pad resembles a butterfly. The digital pads in the paws of the forelimb are longer and thinner than in the paws in the hind feet. The paws in both feet are situated as binary. Through histological examination, it was determined that the skin of the foot pads consists of epidermis, dermis, and pad cushion. The epidermis is subdivided into basal, spinous, granular, lucidum, and corneum layers. The dermis of each pad consists of papillar and reticular strata containing sweat glands, elastin, collagen, and reticular fibers. Anat Rec, 301:932-938, 2018. © 2017 Wiley Periodicals, Inc.

Prognostic significance of concomitant radiotherapy in newly diagnosed glioblastoma multiforme: a multivariate analysis of 116 patients.

BACKGROUND AND OBJECTIVES: Currently, radiotherapy with concomitant and adjuvant temozolomide has become the standard treatment for glioblastoma. The purpose of this study was to report our experience with radiation plus concomitant temozolomide in 116 patients with glioblastoma multiforme (GBM) and examine the value of different prognostic factors. DESIGN AND SETTING: Retrospective analysis of 116 patients with newly diagnosed GBM, who were treated at our department between January 1994 and March 2009. PATIENTS AND METHODS: Age, gender, Karnofsky performance scale (KPS) score, a preoperative history of seizures, extent of surgery, total radiotherapy dose, and use of concomitant and adjuvant temozolomide were evaluated in uni- and multivariate analyses. Survival was determined using the Kaplan-Meier method, and differences were compared using the log rank test. Cox regression analysis was conducted to identify the independent prognostic factors. RESULTS: The median overall survival time was 9 months, and the 1- and 2-year survival rates were 41.9% and 9.6%, respectively. The univariate analysis revealed that age, KPS score, presence of seizures, radiation doses, and use of concomitant and adjuvant temozolomide were significant prognostic factors. The multivariate analysis confirmed that the age, KPS score, presence of seizures, radiation doses, and use of concomitant and adjuvant temozolomide were independent, significant prognostic factors. CONCLUSIONS: The results of our analyses demonstrate that radiation with concomitant and adjuvant temozolomide yields encouraging outcomes in patients with GBM, validating the results published in research papers. In addition, age, KPS score, presence of seizures, and radiation doses were identified as prognostic factors.