Inducible nitric oxide synthase in T cells regulates T cell death and immune memory

The progeny of T lymphocytes responding to immunization mostly die rapidly, leaving a few long-lived survivors functioning as immune memory. Thus, control of this choice of death versus survival is critical for immune memory. There are indications that reactive radicals may be involved in this death pathway. We now show that, in mice lacking inducible nitric oxide synthase (iNOS), higher frequencies of both CD4 and CD8 memory T cells persist in response to immunization, even when iNOS(+/+) APCs are used for immunization. Postactivation T cell death by neglect is reduced in iNOS(-/-) T cells, and levels of the antiapoptotic proteins Bcl-2 and Bcl-xL are increased. Inhibitors of the iNOS-peroxynitrite pathway also enhance memory responses and block postactivation death by neglect in both mouse and human T cells. However, early primary immune responses are not enhanced, which suggests that altered survival, rather than enhanced activation, is responsible for the persistent immunity observed. Thus, in primary immune responses, iNOS in activated T cells autocrinely controls their susceptibility to death by neglect to determine the level of persisting CD4 and CD8 T cell memory, and modulation of this pathway can enhance the persistence of immune memory in response to vaccination.     

Umbilical Coiling Index Assessment During Routine Fetal Anatomic Survey: A Screening Tool for Fetuses at Risk

Background

The umbilical cord is the lifeline of the foetus as it supplies water, nutrients, and oxygen. Protection of these blood vessels is needed and provided by Wharton’s Jelly, amniotic fluid and the helical pattern, or coiling, of the umbilical cord vessels.

Aim

To establish the relationship between antenatal umbilical cord coiling index (aUCI) measured at 18–20 weeks along with level II USG and adverse perinatal outcomes.

Methods

A cross-sectional study was conducted on 408 antenatal women, enrolled at the time of fetal anatomic survey, and their cord coiling index (aUCI) was measured, and its association with perinatal outcomes was observed. Umbilical coiling index was classified as Hypocoiled if UCI <10th percentile, hypercoiled >90th percentile, normocoiled between 10th and 90th percentile.

Results

408 antenatal women were enrolled for the study. Mean aUCI was 0.43 ± 0.30 (normocoiled group), 0.18 ± 0.4 (hypocoiled), and 0.53 ± 0.05 (hypercoiled group). The average gestational age at delivery in hypocoiled group was 36.8 ± 2.34 weeks, and it was shorter than 38.3 ± 1.82 weeks of the normocoiled group and 38.9 ± 1.72 weeks of the hypercoiled group. Mean birth weight observed was 2055 ± 744 (hypocoiled group), 3049 ± 564 (hypercoiled), and 3102 ± 564 (normocoiled) p < 0.001. Preterm births 52 (59%) and low birth weight 76 (69%) were significantly associated with hypocoiling.

Conclusion

Abnormal umbilical cord coiling index, detected at the fetal ultrasound anatomic survey in the second trimester (18–20 weeks), can be used potentially as a screening or as a predictive tool for adverse antenatal or perinatal events.

     

Effect of Orlistat Versus Metformin in Various Aspects of Polycystic Ovarian Syndrome: A Systematic Review of Randomized Control Trials

Background

Polycystic ovarian syndrome (PCOS), a commonly prevalent endocrinopathy among reproductive age group women, is most often associated with obesity. Increased insulin resistance appears to be the central pathophysiologic mechanism responsible for various complications of PCOS. This makes ‘weight loss’ as the first-line treatment approach in PCOS. So various trials have tried to compare metformin (an insulin-sensitizing agent) and orlistat (an anti-obesity drug) aiming to achieve weight loss and hence higher ovulation rate for the group of obese PCOS patients. Keeping an eye on all these background facts, we designed this systematic review and metaanalysis to compare the effects of metformin and orlistat on various aspects of PCOS and to pick the better among the two drugs.

Materials and Methods

This is a systemic review of randomized control trials that studied the effectiveness of orlistat versus metformin in terms of improvement in ovulation rate, weight loss, lipid profile, etc. Systematic literature search over the period January 2000–December 2016 was performed in the following electronic databases: Medline, embase, google scholar, pubmed and The Cochrane Library and only randomized controlled clinical trials were included in our study. All authors carefully went through all sources of information independently.

Results

According to this study, weight loss, testosterone level after 4 weeks of treatment, total serum cholesterol and triglyceride level showed significant fall in orlistat-treated group.

Conclusion

Our review shows that orlistat is a more effective drug than metformin and should be the preferred drug in obese PCOS in combination with weight loss.

     

Stacking interactions of W271 and H275 of SeMV serine protease with W43 of natively unfolded VPg confer catalytic activity to protease

N-terminal serine protease domain of Sesbania mosaic virus polyprotein, requires fused VPg for its activity. W43 of VPg mediates aromatic stacking interactions (characterized by 230 nm positive CD peak) with protease. A stretch of aromatic residues (F269, W271, Y315, and Y319) exposed in the protease domain were mutated to identify the interacting partner of W43. W271A Protease-VPg mutant showed absence of cleavage activity both in vivo and in trans, with concomitant loss of the 230 nm CD peak. F269A Protease-VPg mutant was partially active. Mutations of the tyrosines did not result in loss of protease activity or the CD peak. Interestingly, H275, though not a part of the exposed aromatic stretch, was shown to be essential for protease activity and contributed significantly to the CD peak. Hence, we conclude that W271 and H275 of the protease domain mediate aromatic stacking interactions with W43 of VPg thereby rendering the protease active.     

Primary renal fibrosarcoma: a rare case report and review of literature

Primary renal fibrosarcoma is a rare tumor. We describe a case of primary renal fibrosarcoma in a 54-year-old male who presented with abdominal lump and intermittent hematuria.     

Health care utilization by adult Hispanic long-term survivors of hematopoietic stem cell transplantation: report from the Bone Marrow Transplant Survivor Study

BACKGROUND: Long-term hematopoietic cell transplantation (HCT) survivors have a high prevalence of severe and chronic health conditions, placing significant demands on the healthcare system. The objective of the current study was to evaluate and compare the healthcare utilization by adult Hispanic and non-Hispanic white long-term survivors of HCT. METHODS: A mailed questionnaire was used to assess self-reported healthcare utilization in 3 domains: general contact with healthcare system, general physical examination outside cancer center (GPE), and cancer/HCT center visit. Eligible individuals had undergone HCT between 1974 and 1998, at age > or =21 years, and had survived > or =2 years after HCT. RESULTS: The cohort included 681 non-Hispanic white and 137 Hispanic survivors. The median age at HCT was 38.3 years, and the median length of follow-up was 6.6 years. Hispanic survivors had lower family income and education and were more likely to lack health insurance. The prevalence of GPE increased significantly over time among non-Hispanic whites (67% at 2-5 years to 76% at 11+ years) but remained unchanged among Hispanics (66% to 61%). Cancer/HCT center visits declined over time among both Hispanics and non-Hispanic whites, but a higher proportion of Hispanics reported cancer/HCT center visits at 11+ years after HCT (81% vs 54%). CONCLUSIONS: Compared with non-Hispanic whites, Hispanic survivors are less likely to establish contact with primary care providers years after HCT and to continue to receive care at cancer/HCT centers. Future studies of this population are needed to establish the factors responsible for this pattern of healthcare utilization.     

Comparison of on-call radiology resident and faculty interpretation of 4- and 16-row multidetector CT pulmonary angiography with indirect CT venography

RATIONALE AND OBJECTIVES: On-call radiology residents frequently interpret computed tomography (CT) pulmonary angiography and CT venography studies outside of routine working hours. The purpose of this study was to compare resident and faculty interpretation concordance rates and to see if concordance rates differed depending on the number of CT detectors used. MATERIALS AND METHODS: The study population included 122 consecutive CT pulmonary angiography (CTPA) and CT venography (CTV) examinations performed on a four-row multidetector CT (MDCT) and 125 consecutive CTPA examinations performed using a 16-row MDCT scanner with CTV performed in 124 patients. Preliminary resident reports and final faculty reports were compared. Discrepant cases were independently reviewed by three cardiothoracic radiologists who were unaware of the initial interpretations. Interpretation concordance rates were calculated for both 4- and 16- row MDCT studies and compared using Fisher's exact test. RESULTS: Resident and faculty CTPA and CTV interpretations were concordant in 80% of the 4-row cases and 94% of the 16-row cases. When comparing resident interpretation to the final expert reference standard, the corrected resident error rate was 11% and 2% for 4-row CTPA and CTV, respectively and 4% and 2% for 16-row CTPA and CTV, respectively. Overall CTPA and CTV concordance was significantly lower for 4-row MDCT (80% versus 94%, P < .001 [two-sided] by Fisher's exact test). CONCLUSIONS: Radiology resident interpretation of CTPA and CTV studies demonstrates a high level of agreement with radiology faculty interpretation. Concordance rates are significantly higher for 16-row MDCT than 4-row MDCT which may be due to improved image quality.