Pregnancy outcomes of antibody negative and untreated subclinical hypothyroidism.

AIM: Subclinical hypothyroidism is thought to be associated with adverse pregnancy outcomes but the data is conflicting and generally depends on antibody positivity and treatment. We evaluated the pregnancy outcomes in Turkish population with untreated, antibody negative subclinical hypothyroidism for the first time. METHODS: We searched for 30 015 patients between January 2016 and May 2017 retrospectively. Finally, a total of 930 pregnant women with untreated, antibody negative subclinical hypothyroidism and 7986 controls were included. Demographic characteristics, laboratory findings and pregnancy outcomes, including pregnancy loss, impaired glucose tolerance, gestational diabetes, hypertensive disorders of pregnancy, preterm birth, neonatal intensive care unit admission, placenta previa and abruption, cesarean delivery, low birthweight, Apgar score <7 and premature rupture of membranes were recorded. RESULTS: Demographic and laboratory characteristics were similar between two groups except thyroid stimulating hormone levels and previous uterine surgery rates. Subclinical hypothyroidism group had an increased risk of pregnancy loss (odds ratio [OR] 2.583; 95% confidence interval [CI] 1.982-3.365; P < 0.001), impaired glucose tolerance (OR 1.952; 95% CI 1.450-2.627; P < 0.001), hypertensive disorders of pregnancy (OR 1.476; 95% CI 1.113-1.923; P = 0.004), neonatal intensive care unit admission (OR 1.620; 95% CI 1.084-2.420; P = 0.019), placenta previa (OR 12.581; 95% CI 5.046-31.363; P < 0.001) and cesarean delivery (OR 1.263; 95% CI 1.091-1.462; P = 0.002). CONCLUSION: Subclinical hypothyroidism has worse pregnancy outcomes as compared to euthyroid pregnant women even in antibody negativity. Therefore, we suggest that all pregnant women should routinely be screened in their first antenatal visits for thyroid functions.

Effect of main pancreatic duct suture ligation on the prevention of clinically relevant pancreatic fistula after distal pancreatectomy: analysis of 82 consecutive patients.

OBJECTIVE: This study aimed to examine the factors linked to the development of clinically significant pancreatic fistulas following distal pancreatectomy (DP) and to assess the efficacy of suture ligation of the main pancreatic duct. PATIENTS AND METHODS: A single-center retrospective study was performed on the medical records of 82 patients who underwent DP in our institution between January 2011 and December 2019. RESULTS: There were 28 males (34.1%) and 54 females (65.9%). The patients' age ranged from 18 to 86 years (median: 55.5 years). Indications for DP included primary pancreatic disease (n=63, 76.8%) and non-pancreatic disease (n=19, 23.2%). Postoperative mortality and morbidity rates were 3.7% and 48%, respectively. Pancreatic parenchymal closure was accomplished by a hand-sewn technique or mechanical stapling in 89 and 13 patients, respectively. Identification of the pancreatic duct and suture ligation was performed in 46 patients (56.1%). Pancreatic fistula was developed in 20 patients (24.4%); 12 fistulas were classified as Grade B, and 8 as Grade C. Biochemical leaks (Grade A) were identified in 8 patients (9.8%). Multivariate analysis indicated that failure to ligate the main pancreatic duct was the only variable associated with an increased risk for pancreatic leak (p=0.031; odds ratio=0.233; 95% confidence interval, 0.062-0.879). CONCLUSIONS: Pancreatic leak remains a common complication after DP. The incidence of leaks is reduced significantly when the main pancreatic duct is identified and directly ligated during DP.

Multimodal Treatment of Chylous Fistula: A Retrospective Case-Control Study.

Chylous fistulas (CF) are rare surgical complications and there is no standard treatment. This study presents the treatment modalities performed on patients who developed CF over a 10-year period. During the observation period, CF developed in 29 patients, 16 of whom were women. The mean age was 55.76± 13.48. Lymphatic duct injury was mostly seen in the abdomen (58.6%) and the most common reason was nephrectomy (20.7%). Extended lymphatic dissection due to malignancy was performed in 82.7% of all cases. Chylous leakage started postoperatively on 3.78±3.94 days (range: 1-19 days). Fasting, total parenteral nutrition (TPN), and somatostatin treatment were applied to all patients, and 75.8% of the fistulas were resolved completely with medical treatment. Surgical ligation of the lymphatic canal was performed in 7 patients. One was not successful and underwent percutaneous embolization of the thoracic lymphatic leakage cavity. All fistulas were resolved in 18.18±10.4 days. The resolution time and hospital stay were significantly higher in thoracic fistulas (p=0.017; p=0.003, respectively). In addition, malignant cases had longer resolution time (32.40±28.72 vs 16.27±11.25, p=0.036) and hospital stay (35.0±29.74 vs 16.25±14.05p= 0.002 respectively) than non-malignant. There was no chylothorax, chylous ascites, or recurrence at 20.55±22.88 months follow-up. Treatment of CF with fasting, TPN, and somatostatin analogs are effective. Other interventions such as surgical ligation with or without fibrin glue and interventional radiology treatments may be considered when conservative treatments fail.

Extreme Concentrations of Nitric Oxide Control Daytime Oxidation and Quench Nocturnal Oxidation Chemistry in Delhi during Highly Polluted Episodes.

Delhi, India, suffers from periods of very poor air quality, but little is known about the chemical production of secondary pollutants in this highly polluted environment. During the postmonsoon period in 2018, extremely high nighttime concentrations of NOx (NO and NO2) and volatile organic compounds (VOCs) were observed, with median NOx mixing ratios of ∼200 ppbV (maximum of ∼700 ppbV). A detailed chemical box model constrained to a comprehensive suite of speciated VOC and NOx measurements revealed very low nighttime concentrations of oxidants, NO3, O3, and OH, driven by high nighttime NO concentrations. This results in an atypical NO3 diel profile, not previously reported in other highly polluted urban environments, significantly perturbing nighttime radical oxidation chemistry. Low concentrations of oxidants and high nocturnal primary emissions coupled with a shallow boundary layer led to enhanced early morning photo-oxidation chemistry. This results in a temporal shift in peak O3 concentrations when compared to the premonsoon period (12:00 and 15:00 local time, respectively). This shift will likely have important implications on local air quality, and effective urban air quality management should consider the impacts of nighttime emission sources during the postmonsoon period.

NIR Fluorescence lifetime macroscopic imaging with a time-gated SPAD camera.

The performance of SwissSPAD2 (SS2), a large scale, widefield time-gated CMOS SPAD imager developed for fluorescence lifetime imaging, has recently been described in the context of visible range and fluorescence lifetime imaging microscopy (FLIM) of dyes with lifetimes in the 2.5 - 4 ns range. Here, we explore its capabilities in the NIR regime relevant for small animal imaging, where its sensitivity is lower and typical NIR fluorescent dye lifetimes are much shorter (1 ns or less). We carry out this study in a simple macroscopic imaging setup based on a compact NIR picosecond pulsed laser, an engineered diffuser-based illumination optics, and NIR optimized imaging lens suitable for well-plate or small animal imaging. Because laser repetition rates can vary between models, but the synchronization signal frequency accepted by SS2 is fixed to 20 MHz, we first checked that a simple frequency-division scheme enables data recording for different laser repetition rates. Next, we acquired data using different time gate widths, including gates with duration longer than the laser period, and analyzed the resulting data using both standard nonlinear least-square fit (NLSF) and phasor analysis. We show that the fixed synchronization rate and large gate widths characterizing SS2 (10 ns and over) are not an obstacle to accurately extracting lifetime in the 1 ns range and to distinguishing between close lifetimes. In summary, SS2 and similar very large gated SPAD imagers appear as a versatile alternative to other widefield time-resolved detectors for NIR fluorescence lifetime imaging, including preclinical molecular applications.

Existence of SARS-CoV-2 RNA on ambient particulate matter samples: A nationwide study in Turkey.

Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus and has been affecting the world since the end of 2019. The disease led to significant mortality and morbidity in Turkey, since the first case was reported on March 11th, 2020. Studies suggest a positive association between air pollution and SARS-CoV-2 infection. The aim of the present study was to investigate the role of ambient particulate matters (PM), as potential carriers for SARS-CoV-2. Ambient PM samples in various size ranges were collected from 13 sites including urban and urban-background locations and hospital gardens in 10 cities across Turkey between 13th of May and 14th of June 2020 to investigate the possible presence of SARS-CoV-2 RNA on ambient PM. A total of 203 daily samples (TSP, n = 80; PM2.5, n = 33; PM2.5-10, n = 23; PM10µm, n = 19; and 6 size segregated PM, n = 48) were collected using various samplers. The N1 gene and RdRP gene expressions were analyzed for the presence of SARS-CoV-2, as suggested by the Centers for Disease Control and Prevention (CDC). According to real time (RT)-PCR and three-dimensional (3D) digital (d) PCR analysis, dual RdRP and N1 gene positivity were detected in 20 (9.8%) samples. Ambient PM-bound SARS-CoV-2 was analyzed quantitatively and the air concentrations of the virus ranged from 0.1 copies/m3 to 23 copies/m3. The highest percentages of virus detection on PM samples were from hospital gardens in Tekirdag, Zonguldak, and Istanbul, especially in PM2.5 mode. Findings of this study have suggested that SARS-CoV-2 may be transported by ambient particles, especially at sites close to the infection hot-spots. However, whether this has an impact on the spread of the virus infection remains to be determined.

Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma.

BACKGROUND: Scarce data are available comparing outcomes of hepatic resection vs orthotopic liver transplantation (OLT) for localized hepatocellular carcinoma (HCC) patients both meeting and exceeding the Milan criteria. This study compared the clinical and oncological outcomes of patients undergoing hepatic resection vs transplantation localized HCC. METHOD: Between January 2005 and February 2017, clinical and oncological outcomes of patients who underwent liver resection (n = 38) vs OLT (n = 28) for localized HCC were compared using a prospectively maintained database. RESULTS: A total of 66 patients (with a median age of 62) who met the study criteria were analyzed. Comparable postoperative complications (13.2% vs 28.6%, P = .45) and perioperative mortality rates (7.9% vs 10.7%, P = .2) were noted for the resection vs OLT groups. While Child-Pugh Class A patients were more prevalent in the resection group (78.9% vs 7.1%, P = .0001), the rate of patients who met the Milan criteria was higher in the OLT group (89.3% vs 34.25, P = .0001). Recurrence rates were 36.8% in the resection group and 3.6% in the OLT group at the end of the median follow-up period (32 vs 39 months, respectively). The HCC-related mortality rate was significantly higher in the resection group (39.5% vs 10.7%, P = .034). However, a subgroup analysis of patients who met the Milan criteria revealed similar rates of recurrence and HCC-related mortality (15.4% vs 8%, P = .63). Based on logistic regression analysis, number of tumors (P = .034, odds ratio: 2.1) and "resection"-type surgery (P = .008, odds ratio: 20.2) were independently associated with recurrence. CONCLUSION: Compared to liver transplantation, hepatic resection for localized hepatocellular carcinoma is associated with a higher rate of recurrence and disease-related mortality.

The breast lesion excision system procedure: An optimal solution for the management of indeterminate BI-RADS category 3 breast lesions in women with severe anxiety.

OBJECTIVES: To evaluate the efficacy of the Breast lesion excision system (BLES) procedure as a primary excisional biopsy for the management of breast imaging-reporting and data system (BI-RADS) category 3, small, and solid breast lesions in women having severe breast cancer anxiety. METHODS: A retospective study was conducted on 68 patients who underwent a BLES procedure. The study protocol was approved by the local ethical committee of Yeni Yuzyil University in Istanbul, Turkey. The study was carried out according to the principles of the Helsinki Declaration. Small breast lesions removed using a (12, 15 or 20 mm) wand from September 2011 to November 2014. These were category 3 lesions as determined by ultrasound (US) imaging according to BI-RADS. The radiological and pathological sizes of these lesions, the complete excision rates, the procedure durations, the pathological diagnosis, the complications, and the imaging findings before and after the procedure were all recorded. RESULTS: All the patients had a benign pathology. The mean duration of procedure was 12 (range=8-22) minutes. There was no major complication during the procedure and in the following period. Only some small hematomas were determined in 3 (4.2%) patients, and no additional surgical intervention was performed. Conclusion: The BLES procedure is an optimal solution for the management of indeterminate BI-RADS category 3 breast lesions in women with severe anxiety.

Oncogenic Ras blocks anoikis by activation of a novel effector pathway independent of phosphatidylinositol 3-kinase.

Activated Ras, but not Raf, causes transformation of RIE-1 rat intestinal epithelial cells, demonstrating the importance of Raf-independent effector signaling in mediating Ras transformation. To further assess the contribution of Raf-dependent and Raf-independent function in oncogenic Ras transformation, we evaluated the mechanism by which oncogenic Ras blocks suspension-induced apoptosis, or anoikis, of RIE-1 cells. We determined that oncogenic versions of H-, K-, and N-Ras, as well as the Ras-related proteins TC21 and R-Ras, protected RIE-1 cells from anoikis. Surprisingly, our analyses of Ras effector domain mutants or constitutively activated effectors indicated that activation of Raf-1, phosphatidylinositol 3-kinase (PI3K), or RalGDS alone is not sufficient to promote Ras inhibition of anoikis. Treatment of Ras-transformed cells with the U0126 MEK inhibitor caused partial reversion to an anoikis-sensitive state, indicating that extracellular signal-regulated kinase activation contributes to inhibition of anoikis. Unexpectedly, oncogenic Ras failed to activate Akt, and treatment of Ras-transformed RIE-1 cells with the LY294002 PI3K inhibitor did not affect anoikis resistance or growth in soft agar. Thus, while important for Ras transformation of fibroblasts, PI3K may not be involved in Ras transformation of RIE-1 cells. Finally, inhibition of epidermal growth factor receptor kinase activity did not overcome Ras inhibition of anoikis, indicating that this autocrine loop essential for transformation is not involved in anoikis protection. We conclude that a PI3K- and RalGEF-independent Ras effector(s) likely cooperates with Raf to confer anoikis resistance upon RIE-1 cells, thus underscoring the complex nature by which Ras transforms cells.

Effect of Dosage and Type of Hepatitis B Immunoglobulin on Hepatitis Antibody Levels in Liver Transplant Recipients.

BACKGROUND: The current study aimed to evaluate the effect of dosage and type (intramuscular [IM] vs intravenous [IV]) of hepatitis B immunoglobulin (HBIG) on hepatitis antibody level in liver transplant recipients. METHODS: Between September 2000 and August 2016, patients who underwent orthotropic liver transplantation for chronic liver failure or hepatocellular carcinoma secondary to chronic hepatitis B virus (HBV) were retrospectively reviewed from a prospectively maintained database. The analyses of risk factors for postoperative short- and long-term anti-hepatitis B surface antibody levels (as classified level I: 0 to 100 U; II: 100 to 500 U; III: 500 to 1000 U; IV: >1000 U) were performed based on demographic characteristics, hepatitis B envelope antigen, hepatitis B core antibody, HBV DNA, delta antigen, HBIG administration dosage during unhepatic phase (5000 or 10,000 I/U; IM or IV), and type of administration in post-transplant period. Patients who were followed for less than 12 months were excluded from long-term analysis. RESULTS: The mean follow-up of 58 orthotropic liver transplant patients was 72 (±45) months. No adverse events were observed during both IM and IV type of administration. Compared with IM type, IV administration was associated with a significantly higher HBV antibody level in the short term (for IM and IV: level I: 24% vs 6%; II: 49% vs 18%; III: 12% vs 35%; IV: 15% vs 41%, respectively, P = .007). In the long term, IV administration of hepatitis B immunoglobulin (HBIG) was reported as the sole factor causing higher antibody level (P = .002). Longer follow-up was associated with decreased levels of anti-hepatitis B surface antibody. CONCLUSION: IV HBIG administration in preoperative anhepatic phase and postoperative prophylaxis is associated with higher antibody level both the short and long term without any adverse event.

Antiviral Combination Therapy With Low-Dose Hepatitis B Immunoglobulin for the Prevention of Hepatitis B Virus Recurrence in Liver Transplant Recipients: A Single-Center Experience.

OBJECTIVES: This study presents the overall long-term hepatitis B virus (HBV) recurrence rate with possible associated factors after hepatitis B immunoglobulin (HBIG) was given in combination with 4 different antiviral (lamivudine, adefovir, entecavir, and tenofovir) drugs. PATIENTS AND METHODS: Between September 2000 and October 2013, the medical records of 42 adult patients who underwent liver transplantation at the Cukurova University Medical Hospital for chronic liver failure or hepatocellular carcinoma (HCC) secondary to chronic HBV were reviewed retrospectively. The analyses of risk factors for recurrence were performed based on the efficacy of hepatitis B envelope antigen (HBeAg), hepatitis B core antibody (anti-HBc), HBV DNA, preoperative prophylaxis, and the presence of HCC. Posttransplantation HBV recurrence was defined as persistence of hepatitis B surface antigen (HBsAg) positivity after orthotopic liver transplantation, or the reappearance of HBsAg and HBV DNA after initial HBsAg undetectability despite prophylaxis. RESULTS: The mean follow-up of 28 patients having HBIG and lamivudine prophylaxis was 73.25 ± 37.5 months with a recurrence rate of 3.5%. The mean follow-up of 2 patients having HBIG and adefovir prophylaxis was 90 ± 46.6 months with a 50% recurrence rate. The mean follow-up of each 6 patients who received prophylaxis with entecavir and tenofovir groups were 27.5 ± 16.1 and 16.17 ± 5.3 respectively, with no posttransplantation recurrence for both groups. On univariate analysis, preoperative factors such as anti-HBc, HBV DNA, preoperative prophylaxis, and the presence of HCC did not show any correlation with recurrence. However, HBeAg showed statistical significance for recurrence. CONCLUSIONS: Low-dose HBIG in combination with antiviral agents (lamivudine, entecavir, and tenofovir) is efficacious in preventing recurrence of HBV in posttransplantation patients.

Effects of enteral and parenteral glutamine on intestinal mucosa and on levels of blood glutamine, tumor necrosis factor-alpha, and interleukin-10 in an experimental sepsis model.

OBJECTIVE: To investigate the effects of enteral and parenteral glutamine (Gln) usage on rats in sepsis. METHODS: This study was conducted in Istanbul University Experimental Medical Research Institution (DETAE) laboratory, Istanbul University, Istanbul, Turkey between June and September 2009. The levels of blood Gln, tumor necrosis-alpha (TNF-alpha) and interleukin (IL)-10 was measured. Samples of tissue were obtained from the mesenteric lymph nodes, liver, and lower lobe of the right lung to evaluate the reproduction of bacteria, and samples of tissue were also obtained from the small intestine to evaluate blood and villus atrophy. RESULTS: Bacteremia of Group EP (combined group) were found lower than Group C (control) (p=0.007). Villous atrophy rates of all groups were lower than Group C: between Group E (enteral) and C (p=0.003); between Group P (parenteral alanine) and C (p=0.019); and between Group EP and C (p=0.001). The values of serum TNF-alpha and IL-10 of Group EP and P were lower than the other groups at the 24th and 96th hours (p=0.000). CONCLUSION: In this study we found that the most efficient Gln administration technique in sepsis was enteral administration together with parenteral administration due to trophic effect on the intestinal mucosa, decrease of reproduction in tissue and blood cultures, immunomodulator effect, and approximately the same cost as parenteral application.

Effects of intra-abdominal pressure increase on intestinal ischemia and bacterial translocation in experimental sepsis model.

OBJECTIVE: To investigate the safety of laparoscopic intervention for diagnosis and treatment at 8 mm Hg pressure in one-hour period on acute peritonitis related intra-abdominal sepsis model. METHODS: In this study, we included 32 female Wistar-Albino rats, weighing 250 +/- 20 g, and divided them into 4 groups. This study was conducted in Istanbul University Experimental Medical Research Institution (DETAE) laboratory from April to May 2009. Intra-abdominal sepsis was created with intraperitoneal (i.p.) one mL (109 CFU/mL) Escherichia coli (E. coli) injection, and pneumoperitoneum was formed with CO2 insufflation at 8 mm Hg pressure for one hour i.p. The rats were administered with: Group 1 - one mL i.p. isotonic saline; Group 2 - one mL i.p. isotonic saline + pneumoperitoneum; Group 3 - i.p E. coli; and Group 4 - i.p. E.coli + pneumoperitoneum. Data were analyzed using the Statistical Package for Social Sciences version 15 for Windows (SPSS Inc, Chicago, IL, USA). RESULTS: Fever and leukocyte values were considered high in Groups 3 and 4 compared with Groups 1 and 2 (p=0.001). The administered reproduction ratio of the E. coli strain was determined as 0% in Groups 1 and 2, and 100% in Groups 3 and 4. CONCLUSION: In this study, as pneumoperitoneum was formed for one hour at 8 mm Hg pressure, in case of intra-abdominal derived sepsis where emergency intervention is needed, we consider that laparoscopic approaches with low pressure may be used safely for diagnosis and treatment.

Friedreich's ataxia: a clinical review of 20 childhood cases.

The authors report the clinical review of 20 childhood cases with Friedreich's ataxia. The mean age at onset of symptoms was 6.1 years. The main presenting symptom was abnormal gait (100%). Ataxia of gait and limbs and depressed or absent tendon reflexes were found in all cases. Clinical findings are in accordance with the findings of Harding and Werdelin. Neurophysiological studies (especially sensory) are important in the confirmation of the diagnosis. Of the 10 cases in which sensory nerve conduction velocity measurements were performed, 7 had absent sensory action potentials, 2 had decreased potentials and one was normal. In our study, it is shown that in patients having ataxic gait, ataxia of limbs and tendon reflexes depression or loss, Friedreich's ataxia may be diagnosed with the help of electrophysiological studies.

Early-onset cerebellar ataxia with retained tendon reflexes.

The authors report a clinical review of 16 childhood cases with early-onset cerebellar ataxia with retained tendon reflexes. The preservation of tendon reflexes distinguishes this disorder from Friedreich's ataxia. The mean age of onset of symptoms was 7.1 years. The main presenting symptom was abnormal gait (100%). Ataxia of gait and limbs and normal or increased tendon reflexes were found in all cases. This disorder is associated with dysarthria, pyramidal signs in the limbs, and in some instances, sensory loss. Other important differences from Friedreich's ataxia are absence of optic atrophy, diabetes mellitus, cardiomyopathy and severe skeletal deformity. Sensory nerve conduction was found to be normal, excluding one case. This finding constitutes another aspect of the syndrome different from Freidreich's ataxia. CT scans were normal in 2 of the 4 cases. The remaining two cases showed cerebellar atrophy. Inheritance is probably autosomal recessive in the majority of cases.

X-linked spastic paraplegia.

This paper describes a family with 10 males affected by x-linked spastic paraplegia. X-linked inheritance is rarely encountered in pure and complicated forms of hereditary spastic paraplegia. The disease was characterized by hyperreflexia, progressive spastic gait disorder, extensor plantar responses and mental retardation in all of the affected members of the family we studied. In addition to these symptoms, the older patients had cerebellar findings, severe disability and contractures. This is the 13th family manifesting x-linked spastic paraplegia reported in the literature.

Parallel-stranded linear homoduplexes of d(A+-G)n > 10 and d(A-G)n > 10 manifesting the contrasting ionic strength sensitivities of poly(A+.A+) and DNA.

In contrast to shorter homologs which only form a single-stranded nucleic acid alpha-helix in acid solution at [Na+]/=0.2 M) the protonated base-backbone interactions are so weakened that duplex stability becomes increasingly dependent upon H-bonded base pairing and stacking and almost independent of pH. Between pH 6 and 8 this duplex structure is devoid of protonated dA residues and shows positive dependence of T m on ionic strength similar to that of DNA.