Pulmonary function changes in asymptomatic smokers - a community survey in Udupi, Karnataka, India

Background: Smoking has been labeled the most important preventable cause of a respiratory disease and its effects in a smoker are well established. A better understanding on the pulmonary function impairments in an asymptomatic smoker is the need of the hour. Objective: To study the pulmonary function changes in asymptomatic smokers and non- smokers and to establish the dose -effect relationship amongst asymptomatic smokers.Methods: A cross sectional survey was conducted in Udupi district of Karnataka, India. 140 men aged between 20 to 45 years with a BMI ranging from 18.5 to 29.9 Kg2 /m was enrolled in to the study. 70 subjects were asymptomatic smokers and the other 70 were non-smokers. Outcomes measured were standard spirometric measures for pulmonary function and symptoms like breathlessness, cough and sputum using a Breathlessness Cough Sputum scale.Results: The mean age (mean ± SD) of non-smokers and asymptomatic smokers enrolled was 34.7±5 and 33.8±5 years respectively. The mean smoking dose amongst the asymptomatic smokers was 15.74±5.5 pack years. FEV1 amongst the asymptomatic smokers showed a negative correlation with smoking dose (p<0.05) and there was a significant difference in FEV1, FVC, PEFR, MVV and FEF 25- 75 % (p<0.001) amongst the asymptomatic smokers and non-smokers.Conclusions: Asymptomatic smokers showed low values of pulmonary function parameters compared to those in non-smokers

A Transgenic Rat for Investigating the Anatomy and Function of Corticotrophin Releasing Factor Circuits.

Corticotrophin-releasing factor (CRF) is a 41 amino acid neuropeptide that coordinates adaptive responses to stress. CRF projections from neurons in the central nucleus of the amygdala (CeA) to the brainstem are of particular interest for their role in motivated behavior. To directly examine the anatomy and function of CRF neurons, we generated a BAC transgenic Crh-Cre rat in which bacterial Cre recombinase is expressed from the Crh promoter. Using Cre-dependent reporters, we found that Cre expressing neurons in these rats are immunoreactive for CRF and are clustered in the lateral CeA (CeL) and the oval nucleus of the BNST. We detected major projections from CeA CRF neurons to parabrachial nuclei and the locus coeruleus, dorsal and ventral BNST, and more minor projections to lateral portions of the substantia nigra, ventral tegmental area, and lateral hypothalamus. Optogenetic stimulation of CeA CRF neurons evoked GABA-ergic responses in 11% of non-CRF neurons in the medial CeA (CeM) and 44% of non-CRF neurons in the CeL. Chemogenetic stimulation of CeA CRF neurons induced Fos in a similar proportion of non-CRF CeM neurons but a smaller proportion of non-CRF CeL neurons. The CRF1 receptor antagonist R121919 reduced this Fos induction by two-thirds in these regions. These results indicate that CeL CRF neurons provide both local inhibitory GABA and excitatory CRF signals to other CeA neurons, and demonstrate the value of the Crh-Cre rat as a tool for studying circuit function and physiology of CRF neurons

Blood Flow Improvement Trial: Design and Enrollment Developing Topics

Background Midlife insulin resistance (IR) has previously been shown to be associated with lower cerebral blood flow (CBF), and is a potentially modifiable risk factor for dementia. The Blood Flow Improvement Trial (BFiT), NCT03117829 , tested a 12 week carbohydrate restricted diet (CRD) and exercise behavioral intervention to reverse IR, and aimed to 1) determine the extent to which improving or normalizing glucose homeostasis improves CBF and cognitive function in individuals with IR, 2) determine whether participants continue to maintain improved or normalized glycemic control for 6 months, and 3) determine changes in the human metabolome as individuals improve or normalize IR and glucose homeostasis through diet and exercise. Method Participants were recruited from the Wisconsin Alzheimer’s Disease Research Center and screened for metabolic risk factor eligibility based on the criteria shown in Table 1. The design involved a 12 week diet and exercise intervention focused on self‐monitoring to promote adherence. Exercise was conducted in a supervised group setting 3 days/week for 50 minutes and participants were instructed to exercise on their own an additional 2 days/week. Participants followed a CRD and monitored their own blood glucose with the goal of achieving and maintaining fasting blood glucose/dL. Participants underwent baseline, 12 week, and 6 month procedures including urine and blood labs/metabolomics, cognitive testing, fitness testing, and blood flow imaging via MRI (Table 2). Result The enrollment goal was 40 participants. 118 individuals were screened for eligibility, and 72.5% of the target enrollment was met; of those participants, nearly 80% completed the 12 week intervention. Of the 23 participants that completed the intervention, mean attendance was 70% for supervised exercise sessions and 81% for weekly behavioral coaching sessions. Figure 1 summarizes screening, enrollment, and procedure completion. Conclusion IR may be a modifiable risk factor for dementia. The BFiT pilot trial was designed to test the feasibility of exercise and CRD to reduce IR and improve brain blood flow in middle‐aged adults. Reasonable enrollment and completion N were achieved. Future analysis will center on barriers to enrollment and adherence, as well as analysis of the primary and secondary outcome measures

Interaction of porphyrins with concanavalin a and pea lectin

Currently porphyrins are used as photosensitizers in photodynamic therapy for the treatment of cancer. However, this approach suffers due to the inability of many porphyrin-based drugs to accumulate preferentially in tumours. In view of this, we considered if the carbohydrate-binding proteins, lectins, which preferentially recognize malignant cells, could be used for the targeting of porphyrins to tumour cells. In the present study, we have investigated the interaction of a free base porphyrin, meso-tetrasulphonatophenylporphyrin and the corresponding metal derivative, meso-zinc-tetrasulphonatophenylporphyrin with two legume lectins, concanavalin A and pea (Pisum sativum) lectin. Each lectin subunit was found to bind one porphyrin molecule and the association constant, Ka, estimated from absorption and fluorescence titrations at room temperature (28 +/- 1 degree centigrade) was in the range of 1.2 X 10 to the power of 4 M to the power of -1 to 6.3 X 10 to the power of 4 M to the power of -1. Both free lectin and lectin saturated with the specific saccharide were found to bind the porphyrin with comparable binding strength, indicating that porphyrin binding takes place at a site different from the sugar-binding site. These results indicate that lectins may potentially serve as drug-delivery agents for porphyrin sensitizers in photodynamic therapy

Continuous-wave second-harmonic generation in the far-UVC pumped by a blue laser diode

Far-UVC light in the wavelength range of 200-230 nm has attracted renewed interest because of its safety for human exposure and effectiveness in inactivating pathogens. Here we present a compact solid-state far-UVC laser source based on second-harmonic generation (SHG) using a low-cost commercially-available blue laser diode pump. Leveraging the high intensity of light in a nanophotonic waveguide and heterogeneous integration, our approach achieves Cherenkov phase-matching across a bonded interface consisting of a silicon nitride (SiN) waveguide and a beta barium borate (BBO) nonlinear crystal. Through systematic investigations of waveguide dimensions and pump power, we analyze the dependencies of Cherenkov emission angle, conversion efficiency, and output power. Experimental results confirm the feasibility of generating far-UVC, paving the way for mass production in a compact form factor. This solid-state far-UVC laser source shows significant potential for applications in human-safe disinfection, non-line-of-sight free-space communication, and deep-UV Raman spectroscopy

Oxygen-permeable ceramic membranes for gas separation

Mixed-conducting oxides have a wide range of applications, including fuel cells, gas separation systems, sensors, and electrocatalytic equipment. Dense ceramic membranes made of mixed-conducting oxides are particularly attractive for gas separation and methane conversion processes. Membranes made of Sr-Fe-Co oxide, which exhibits high combined electronic and oxygen ionic conductivities, can be used to selectively transport oxygen during the partial oxidation of methane to synthesis gas (syngas, i.e., CO + H{sub 2}). The authors have fabricated tubular Sr{sub 2}Fe{sub 2}CoO{sub 6+{delta}} membranes and tested them (some for more than 1,000 h) in a methane conversion reactor that was operating at 850--950 C. An oxygen permeation flux of {approx} 10 scc/cm{sup 2} {center_dot} min was obtained at 900 C in a tubular membrane with a wall thickness of 0.75 mm. Using a gas-tight electrochemical cell, the authors have also measured the steady-state oxygen permeability of flat Sr{sub 2}Fe{sub 2}CoO{sub 6+{delta}} membranes as a function of temperature and oxygen partial pressure(pO{sub 2}). Steady-state oxygen permeability increases with increasing temperature and with the difference in pO{sub 2} on the two sides of the membrane. At 900 C, an oxygen permeability of {approx} 2.5 scc/cm{sup 2} {center_dot} min was obtained in a 2.9-mm-thick membrane. This value agrees with that obtained in methane conversion reactor experiments. Current-voltage (I-V) characteristics determined in the gas-tight cell indicate that bulk effect, rather than surface exchange effect, is the main limiting factor for oxygen permeation of {approx} 1-mm-thick Sr{sub 2}Fe{sub 2}CoO{sub 6+{delta}} membranes at elevated temperatures (> 650 C)

Separation of gases with solid electrolyte ionic conductors

The authors have developed a novel method of gas separation based on electrolyte ionic membrane technology. Separation of one gas from another occurs through an ion-conducting membrane by the passage of selected ions. Most systems studied have focused on oxygen ion conduction for the separation of oxygen from air, although protonic and halide-conducting solid materials also exist. As an example of this system, this paper concentrates on a study of a membrane reactor used in the production of syngas (CO + H{sub 2}) from methane. The membrane material is a modified perovskite-type oxide exhibiting mixed (electronic/ionic) conductivity. Mixed-conductivity oxides are promising materials for oxygen-permeating membranes that can operate without electrodes or external electrical circuitry. Extruded tubes of this material have been evaluated in a reactor operating at {approx} 850 C for partial oxidation of methane into syngas in the presence of a reforming catalyst. Separated oxygen on one side of the reactor wall was obtained from air on the other side. Methane conversion efficiencies of > 99% were observed, and some of the reactor tubes have been operated for > 1,000 h. Membrane tubes were fabricated from calcined powders by a plastic extrusion technique. Characterization of the mechanical, physical, and chemical properties of this material confirmed the stability exhibited in the reactor

A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men

Background Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). Methods We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. Results The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32–4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50–6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. Conclusions To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD