Teenage Pregnancy and Associated Risk Factors and Outcome in Nepal From 2000-2020: A Systematic Review and Meta-Analysis.

Background Teenage pregnancy is considered a high-risk pregnancy in terms of reproductive outcome and the subsequent financial constraint. Objective To assess the prevalence of teenage pregnancy, associated risk factors, and outcomes in the context of Nepal. Method We searched electronic databases to search relevant articles published from January 2000 till October 2020 using the keywords with appropriate Boolean operators. All the data were extracted into a standardized form designed in Excel. We conducted a statistical analysis using Comprehensive Meta-Analysis Software (CMA) version 3. Data pooled for proportion with 95% confidence interval (CI). A Forest plot was used to visualize the degree of variation between studies. Result Fourteen studies were included in the analysis after the rigorous screening of 4425 studies. Prevalence of teenage pregnancy was 13.2% (Proportion, 0.132; CI, 0.077- 0.215). Among teenage pregnancies, 11.8% were already multigravida (Proportion, 0.118; CI, 0.029-0.374). Among teen pregnancies, 18.6% were illiterate; among the literate, only 25.9% were of education above grade 10,31.9% were unaware of contraceptive methods, and only 3.2% reported using any contraception methods. 75.4% of teenage pregnancies had a vaginal delivery with or without episiotomy, 6.5% by instrumental deliveries, and 21.5% by cesarean section. Preterm delivery was 12.0%, and post-term delivery was 8.2%. Abortion was reported in 11.1% of teenage pregnancies. Major tears were reported in 52.9%, obstructed labor was in 4%, and pre-labor rupture of the membrane was in 7.0% of teenage pregnancies. The low birth weight of newborns was 19.4%. Stillbirth and neonatal deaths were 1.7% and 1.4%, respectively. Conclusion The prevalence of teenage pregnancy in Nepal was 13.2%. The majority of them did not use any form of contraceptives; and had low education. Several maternal and neonatal complications were reported among teenage pregnancies.

Clinical evaluation of acute phase nystagmus associated with cerebellar lesions.

OBJECTIVES: To determine the characteristics of acute phase nystagmus in patients with cerebellar lesions, and to identify a useful indicator for differentiating central lesions from peripheral lesions. METHODS: Acute phase nystagmus and the appearance of neurological symptoms were retrospectively investigated in 11 patients with cerebellar stroke. RESULTS: At the initial visit, there were no patients with vertical nystagmus, direction-changing gaze evoked nystagmus or pure rotatory nystagmus. There were four cases with no nystagmus and seven cases with horizontal nystagmus at the initial visit. There were no neurological symptoms, except for vertigo and hearing loss, in any cases at the initial visit. The direction and type of nystagmus changed with time, and neurological symptoms other than vertigo appeared subsequently to admission. CONCLUSION: It is important to observe the changes in nystagmus and other neurological findings for the differential diagnosis of central lesions.

Clinical study of tympanostomy tube placement for patients with intractable Ménière's disease.

OBJECTIVE: To evaluate the effectiveness of tympanostomy tube placement in controlling symptoms of intractable Ménière's disease. METHODS: Fifteen patients with intractable Ménière's disease underwent tympanostomy tube placement in the affected ear. Post-operative changes in vertigo attacks and hearing level were recorded, and were evaluated according to American Academy of Otolaryngology-Head and Neck Surgery criteria. RESULTS: At 12 months after treatment, 3 patients (20 per cent) showed complete control of vertigo, 7 (47 per cent) showed substantial control and 2 (13 per cent) showed limited control; 3 patients (20 per cent) required other treatment. At 24 months after treatment, 7 patients (47 per cent) showed complete control of vertigo, 3 (20 per cent) showed substantial control and 1 (7 per cent) showed limited control; 1 patient required other treatment 15 months after tympanostomy tube placement. CONCLUSION: There is no definite pathophysiological explanation for the effect of tympanostomy tube placement in reducing vertigo attacks. This treatment is not effective for all patients with intractable Ménière's disease. However, tympanostomy tube placement might be an additional surgical therapeutic option to consider prior to contemplating other, more invasive treatments.

Single timepoint models of dynamic systems.

Many interesting studies aimed at elucidating the connectivity structure of biomolecular pathways make use of abundance measurements, and employ statistical and information theoretic approaches to assess connectivities. These studies often do not address the effects of the dynamics of the underlying biological system, yet dynamics give rise to impactful issues such as timepoint selection and its effect on structure recovery. In this work, we study conditions for reliable retrieval of the connectivity structure of a dynamic system, and the impact of dynamics on structure-learning efforts. We encounter an unexpected problem not previously described in elucidating connectivity structure from dynamic systems, show how this confounds structure learning of the system and discuss possible approaches to overcome the confounding effect. Finally, we test our hypotheses on an accurate dynamic model of the IGF signalling pathway. We use two structure-learning methods at four time points to contrast the performance and robustness of those methods in terms of recovering correct connectivity.

Learning cyclic signaling pathway structures while minimizing data requirements.

Bayesian network structure learning is a useful tool for elucidation of regulatory structures of biomolecular pathways. The approach however is limited by its acyclicity constraint, a problematic one in the cycle-containing biological domain. Here, we introduce a novel method for modeling cyclic pathways in biology, by employing our newly introduced Generalized Bayesian Networks (GBNs). Our novel algorithm enables cyclic structure learning while employing biologically relevant data, as it extends our cycle-learning algorithm to permit learning with singly perturbed samples. We present theoretical arguments as well as structure learning results from realistic, simulated data of a biological system. We also present results from a real world dataset, involving signaling pathways in T-cells.

Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes.

Based on available evidence, we would propose the following. (i) Excesses of glucose and free fatty acids cause insulin resistance in skeletal muscle and damage to the endothelial cell by a similar mechanism. (ii) Key pathogenetic events in this mechanism very likely include increased fatty acid esterification, protein kinase C activation, an increase in oxidative stress (demonstrated to date in endothelium) and alterations in the inhibitor kappa B kinase/nuclear factor kappa B system. (iii) Activation of AMP-activated protein kinase (AMPK) inhibits all of these events and enhances insulin signalling in the endothelial cell. It also enhances insulin action in muscle; however, the mechanism by which it does so has not been well studied. (iv) The reported beneficial effects of exercise and metformin on cardiovascular disease and insulin resistance in humans could be related to the fact that they activate AMPK. (v) The comparative roles of AMPK in regulating metabolism, signalling and gene expression in muscle and endothelial cells warrant further study.

Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle.

Numerous studies have shown a correlation between changes in protein kinase C (PKC) distribution and/or activity and insulin resistance in skeletal muscle. To investigate which PKC isoforms might be involved and how they affect insulin action and signaling, studies were carried out in rat soleus muscle incubated with phorbol esters. Muscles preincubated for 1 h with 1 microM phorbol 12,13-dibutyrate (PDBu) showed an impaired ability of insulin to stimulate glucose incorporation into glycogen and a translocation of PKC-alpha, -betaI, -theta, and -epsilon, and probably -betaII, from the cytosol to membranes. Preincubation with 1 microM PDBu decreased activation of the insulin receptor tyrosine kinase by insulin and to an even greater extent the phosphorylation of Akt/protein kinase B and glycogen synthase kinase-3. However, it failed to diminish the activation of phosphatidylinositol 3'-kinase by insulin. Despite these changes in signaling, the stimulation by insulin of glucose transport (2-deoxyglucose uptake) and glucose incorporation into lipid and oxidation to CO2 was unaffected. The results indicate that preincubation of skeletal muscle with phorbol ester leads to a translocation of multiple conventional and novel PKC isoforms and to an impairment of several, but not all, events in the insulin-signaling cascade. They also demonstrate that these changes are associated with an inhibition of insulin-stimulated glycogen synthesis but that, at the concentration of PDBu used here, glucose transport, its incorporation into lipid, and its oxidation to CO2 are unaffected.

Increased protein kinase C theta in skeletal muscle of diabetic patients.

In this study we have investigated whether protein kinase C (PKC) protein and activity are increased in skeletal muscle of human diabetic patients. The protein content of different PKC isoforms (beta, Theta, epsilon, delta, mu, and zeta) in the particulate fraction was measured, using Western analysis, in human rectus abdominus skeletal muscle from obese (hyperinsulinemic, normoglycemic) and obese diabetic (hyperinsulinemic, hyperglycemic) subjects. PKC Theta protein content was significantly higher in the particulate fraction of muscle from diabetic patients compared with the nondiabetic controls. PKC Theta was immunoprecipitated and its activity was measured in muscle from diabetic and nondiabetic controls. There was a significant increase in PKC Theta activity in muscle from diabetic patients compared with muscle from nondiabetic controls. Therefore, both PKC Theta protein content and activity were significantly increased in the particulate fraction in muscle from diabetic patients, suggesting the involvement of this isoform in diabetes. Most of the PKC Theta protein was found in the cytosol. There was no change in cytosolic PKC Theta protein content in muscle from diabetic patients compared with muscle from nondiabetic controls. Thus, the increase in particulate-associated PKC Theta was likely due to translocation and activation rather than an increase in protein mass.

Involvement of protein kinase C in human skeletal muscle insulin resistance and obesity.

This study was conducted to investigate the possible involvement of protein kinase C (PKC) and serine/threonine phosphorylation of the insulin receptor in insulin resistance and/or obesity. Insulin receptor tyrosine kinase activity was depressed in muscle from obese insulin-resistant patients compared with lean insulin-responsive control subjects. Alkaline phosphatase treatment resulted in a significant 48% increase in in vitro insulin-stimulated receptor tyrosine kinase activity in obese but not lean muscle. To investigate the involvement of PKC in skeletal muscle insulin resistance and/or obesity, membrane-associated PKC activity and the protein content of various PKC isoforms were measured in human skeletal muscle from lean, insulin-responsive, and obese insulin-resistant patients. Membrane-associated PKC activity was not changed; however, PKC-beta protein content, assayed by Western blot analysis, was significantly higher, whereas PKC-theta, -eta, and -mu were significantly lower in muscle from obese patients compared with muscle from lean control subjects. Incubation of muscle strips with insulin significantly increased membrane-associated PKC activity in muscle from obese but not lean subjects. PKC-delta, -beta, and -theta were translocated from the cytosol to the membrane fraction in response to insulin treatment. These results suggest that in skeletal muscle from insulin-resistant obese patients, insulin receptor tyrosine kinase activity was reduced because of hyperphosphorylation on serine/threonine residues. Membrane-associated PKC-beta protein was elevated under basal conditions, and membrane-associated total PKC activity was increased under insulin-stimulated conditions in muscle from obese insulin-resistant patients. Thus, we postulate that the decreased tyrosine kinase activity of the insulin receptor may be caused by serine/threonine phosphorylation by PKC.

Protein kinase C modulates insulin action in human skeletal muscle.

There is good evidence from cell lines and rodents that elevated protein kinase C (PKC) overexpression/activity causes insulin resistance. Therefore, the present study determined the effects of PKC activation/inhibition on insulin-mediated glucose transport in incubated human skeletal muscle and primary adipocytes to discern a potential role for PKC in insulin action. Rectus abdominus muscle strips or adipocytes from obese, insulin-resistant, and insulin-sensitive patients were incubated in vitro under basal and insulin (100 nM)-stimulated conditions in the presence of GF 109203X (GF), a PKC inhibitor, or 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), a PKC activator. PKC inhibition had no effect on basal glucose transport. GF increased (P < 0.05) insulin-stimulated 2-deoxyglucose (2-DOG) transport approximately twofold above basal. GF plus insulin also increased (P < 0.05) insulin receptor tyrosine phosphorylation 48% and phosphatidylinositol 3-kinase (PI 3-kinase) activity approximately 50% (P < 0.05) vs. insulin treatment alone. Similar results for GF on glucose uptake were observed in human primary adipocytes. Further support for the hypothesis that elevated PKC activity is related to insulin resistance comes from the finding that PKC activation by dPPA was associated with a 40% decrease (P < 0.05) in insulin-stimulated 2-DOG transport. Incubation of insulin-sensitive muscles with GF also resulted in enhanced insulin action ( approximately 3-fold above basal). These data demonstrate that certain PKC inhibitors augment insulin-mediated glucose uptake and suggest that PKC may modulate insulin action in human skeletal muscle.

Strategies of antiretroviral therapy in adults.

Recent progress in antiretroviral treatment has led to dramatic improvements in HIV-related morbidity and mortality. These improvements have been fostered by advances in our understanding of HIV-related pathogenesis, the use of plasma HIV RNA levels to monitor patients, and the availability of 13 licensed antiretroviral drugs. Numerous drug combinations, especially those containing three or more agents, can suppress plasma HIV RNA levels below the lower limit of detection in the majority of treated patients. Urologists should be familiar with the limitations of this therapeutic response: patient adherence, drug resistance, a residual burden of chronically infected cells which are refractory to treatment, an unknown impact on HIV in genital secretions, and potential transmissibility through sexual contact.

Evaluation of nicotine, cotinine, thiocyanate, carboxyhemoglobin, and expired carbon monoxide as biochemical tobacco smoke uptake parameters.

In a cross-sectional study on 236 individuals in Japan (174 males, 62 females; 149 smokers, 87 non-smokers) plasma nicotine (pnic), cotinine (pcot) and thiocyanate (pSCN), urinary creatinine ratios of nicotine (unic), cotinine (ucot) and thiocyanate (uSCN) as well as carboxyhemoglobin (COHb) and expired carbon monoxide (COex) were determined. All tobacco smoke uptake parameters (TSUP) were significantly elevated in smokers as compared to nonsmokers. The discriminant power (smokers vs nonsmokers) rank in the following order: ucot approximately pcot approximately unic greater than pSCN approximately COHb approximately pnic greater than COex approximately uSCN. All parameters except for pnic are significantly correlated with the self-reported number of cigarettes smoked per day. The reason for the poor correlation of pnic with daily cigarette consumption is the short half-life of pnic coupled with the arbitrary time of blood drawing in relation to the last time of smoking.