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The most prominent host response to viral infection is the production of type 1 interferons (T1 IFNs). One host regulator of the T1 IFNs is the serine-threonine kinase, tumor progression locus 2 (TPL2). We have previously demonstrated that Tpl2

Extensive research in chemistry, manufacturing, controls, preclinical science, and clinical trials is required when developing a novel biological medication. Drug reviewers in regulatory bodies throughout the world and all regulatory bodies are entrusted with determining whether research evidence establishes new drug product safety, effectiveness, and quality control in order to protect public health. Among the world every province has its own regulatory organization in charge of enforcing laws and regulations and developing guidelines for drug marketing. There are some particular requirements sets by regulatory authority that must be satisfied when submitting in the particular nation. The world is split into various approval procedures, it is pivotal for manufacturers to carefully assess market interest, expenditures, target zones, and regulatory standards before establishing biologics. Despite the existence and widespread adoption of an ICH-CTD standard format, some limitations are included. This article discusses the comparison considerations used for biological product approval in the United States, Canada, Europe, Australia, and Singapore.

Rifampicin (RIF) is one of the most valued drugs in the treatment of tuberculosis. TB treatment relies on a combination therapy and for multidrug-resistant strains may include β-lactams.

A proof-of-concept of colloidal surface-enhanced Raman scattering (SERS) substrate for rapid selective detection of overexpressed CA 15-3 biomarker in breast cancer serum (BCS) is suggested using PEGylated gold nanourchins (GNUs) conjugated with anti-CA 15-3 monoclonal antibody (mAb). UV-vis spectroscopy provided conformational information about mAb where the initial aromatic amino acid peak was red-shifted from 271 to 291 nm. The fluorescence peak of tyrosine in mAb was reduced by ≈ 77%, and red-shifted by ≈ 3 nm after incubation in BCS. Fourier transform near-infrared spectroscopy and SERS were used to study the composition and the molecular structure of the mAb and BCS. Some of the most dominant Raman shifts after GNU-PEG-mAb interaction with BCS are 498, 736, 818, 1397, 1484, 2028, 2271, and 3227 cm

Proper synthesis and maintenance of a multilayered cell envelope is critical for bacterial fitness. However, whether mechanisms exist to coordinate synthesis of the membrane and peptidoglycan layers is unclear. InBacillus subtilis, synthesis of peptidoglycan (PG) during cell elongation is mediated by an elongasome complex acting in concert with class A PBPs (aPBPs). We previously described mutant strains limited in their capacity for PG synthesis due to a loss of aPBPs and an inability to compensate by upregulation of elongasome function. Growth of these PG-limited cells can be restored by suppressor mutations predicted to decrease membrane synthesis. One suppressor mutation leads to an altered function repressor, FapR*, that functions as a super-repressor and leads to decreased transcription of fatty acid synthesis (FAS) genes. Consistent with fatty acid limitation mitigating cell wall synthesis defects, inhibition of FAS by cerulenin also restored growth of PG-limited cells. Moreover, cerulenin can counteract the inhibitory effect of β-lactams in some strains. These results imply that limiting PG synthesis results in impaired growth, in part, due to an imbalance of PG and cell membrane synthesis and thatB. subtilislacks a robust physiological mechanism to reduce membrane synthesis when PG synthesis is impaired.ImportanceUnderstanding how a bacterium coordinates cell envelope synthesis is essential to fully appreciate how bacteria grow, divide, and resist cell envelope stresses such as β-lactam antibiotics. Balanced synthesis of the peptidoglycan cell wall and the cell membrane is critical for cells to maintain shape, turgor pressure and resist external cell envelope threats. UsingBacillus subtilis, we show that cells deficient in peptidoglycan synthesis can be rescued by compensatory mutations that decrease the synthesis of fatty acids. Further, we show that inhibiting fatty acid synthesis with cerulenin is sufficient to restore growth of cells deficient in peptidoglycan synthesis. Understanding the coordination of cell wall and membrane synthesis may provide insights relevant to antimicrobial treatment.

Background: Vascular closure devices have replaced mechanical compression for closure of femoral access sites after endovascular procedures. Case: We present an 87-year-old male with symptomatic infrarenal aortic aneurysm measuring 4.8 cm presenting for elective endovascular repair of the aortic aneurysm. A Perclose ProGlide Suture-Mediated Closure was used for closure. The closure was complicated by a separation of the ProGlide device resulting in the migration of the footplate to the descending aorta. Correction required snare retrieval via radial access, and the patient recovered without complications. Discussion: We highlight an important complication of the Perclose ProGlide Suture-Mediated Closure device that is rare but important to know when performing endovascular closures with this device.

Bacteria can adapt to stressful conditions through mutations affecting the RNA polymerase core subunits that lead to beneficial changes in transcription. In response to selection with rifampicin (RIF), mutations arise in the RIF resistance determining region (RRDR) ofrpoBthat reduce antibiotic binding. These changes can also alter transcription and thereby have pleiotropic effects on bacterial fitness. Here, we studied the evolution of resistance inBacillus subtilisto the synergistic combination of RIF and the β-lactam cefuroxime (CEF). Two independent evolution experiments led to the recovery of a singlerpoBallele (S487L) that was able to confer resistance to RIF and CEF through a single mutation. Two other common RRDR mutations made the cells 32x more sensitive to CEF (H482Y) or led to only modest CEF resistance (Q469R). The diverse effects of these three mutations on CEF resistance are correlated with differences in the expression of peptidoglycan (PG) synthesis genes and in the levels of two metabolites crucial in regulating PG synthesis, glucosamine-6-phosphate (GlcN-6-P) and UDP-N-acetylglucosamine (UDP-GlcNAc). We conclude that RRDR mutations can have widely varying effects on pathways important for cell wall biosynthesis, and this may restrict the spectrum of mutations that arise during combination therapy.ImportanceRifampicin (RIF) is one of the most valued drugs in the treatment of tuberculosis. TB treatment relies on a combination therapy, and for multidrug resistant strains may include β-lactams. Mutations inrpoBpresent a common route for emergence of resistance to RIF. In this study, usingB. subtilisas a model, we evaluate the emergence of resistance for the synergistic combination of RIF and the β-lactam cefuroxime (CEF). One clinically-relevantrpoBmutation conferred resistance to both RIF and CEF, whereas two others increased CEF sensitivity. We were able to link these phenotypes to accumulation of specific PG precursors. Mainly, UDP-GlcNAc through its GlmR mediated influence on GlmS activity has a strong impact on CEF resistance. Since these mutations are clinically relevant, these effects on CEF sensitivity may help refine the use of β-lactams in TB therapy.

We describe the fabrication of plasmonic-active nanostructured thin film substrate as a label-free surface-enhanced Raman scattering (SERS)-based biosensor immobilized covalently with monoclonal HER-II antibody (mAb) to detect overexpressed HER-II as a biomarker in breast cancer serum (BCS). Oriented conjugation of mAb via hydrazone linkage to provide higher mAb accessibility was characterized by UV-vis and reflective Fourier transform near-infrared (FT-NIR) spectroscopic techniques. The interaction of BCS with mAb was studied by FT-NIR and nonresonant SERS at 637 nm. The results showed detection of glycoprotein content at different laser powers including a rise in amino acid and glycan content with varying results at higher power. With nonresonant SERS we observed nonlinear behavior of peak intensity. Analysis of variance was implemented to determine the effect of laser power which was found not to be a contributing factor. However, at the nanoscale, factors including the heating effect and aggregation of molecules can contribute to the nonlinearity of peak intensity.

Obesity affects over 40% of the US population and predisposes individuals to metabolic syndrome, which is associated with a 50% increase in the risk of cardiovascular events. A documented clinical manifestation of obesity is a procoagulant and anti-fibrinolytic state. Elevated levels of circulating plasminogen activator inhibitor (PAI) -1 are correlated with metabolic syndrome, and PAI-1-deficient mice are protected from diet-induced obesity (DIO) . However, an unresolved question is whether plasminogen itself influences the development of obesity and associated disease sequelae? Here, we analyzed the impact of genetically-imposed plasminogen deficiency on the development of DIO and associated pathologies. Over the course of 20 weeks, plasminogen-deficient (Plg-) mice gained as much weight as the control mice (Plg+) on HFD, although HFD-fed Plg- mice had larger epididymal white adipose tissues than those of HFD-fed Plg+ mice. In contrast, while HFD-fed Plg+ animals displayed a fatty liver disease phenotype characterized by histological evidence of steatosis, elevated triglyceride content, and hepatocellular injury, HFD-fed Plg- mice were protected from developing each of these pathologies. HFD-fed Plg+ mice also developed hypercholesterolemia, whereas circulating cholesterol levels in Plg- mice were comparable to LFD-fed mice. Intriguingly, while the brown adipose tissue mass was comparable between diet and genotype, there was an upregulation of uncoupling protein-1 (Ucp1) expression in BAT of HFD-fed Plg- mice. Notably, whereas HFD-fed Plg+ mice showed evidence of insulin resistance as revealed by compromised glucose clearance, HFD-fed Plg- mice were partially protected. Collectively, our data suggest that plasmin (ogen) contributes to HFD-induced fatty liver disease and insulin resistance, and that plasminogen deficiency imposes a state of metabolically healthy obesity. Disclosure W.S.Hur: None. Y.Nguyen: None. Y.Patel: None. K.C.King: None. M.J.Flick: None. Funding National Institutes of Health (RDK112778)

With the emergence of smart devices, the antennas that can fulfil the requirements of such devices are very much in demand. As the devices should be connected to the internet, antennas that are aesthetically good and easy to interface anywhere on the routers or repeaters are needed. One of the solutions to this problem is by using transparent antennas that are visibly neutral and can be placed anywhere in the system. Transparent antennas integrated with dielectric resonator (DR) elements lead to fewer conduction losses due to the high dielectric constant of DR, and so an antenna resonating in the frequency band of 2.4 GHz (IEEE 802.11) WLAN applications is proposed that was simulated using Ansys High-Frequency Structure Simulator (HFSS) software. The optical transparency along with wide impedance bandwidth (31.26%), directional radiation pattern, gain and efficiency values greater than 1.5 dBi, and 75%, respectively makes the antenna suitable for smart wireless applications. The DRA fabricated using transparent material AgHT-8, Plexiglas, and Borosilicate glass show good agreement with the simulated results.

This work describes the observation of multi-wavelengths due to stimulated Raman scattering from deep red to near-infrared (NIR) induced by plasmon-enhanced fluorescence (PEF) of fluorescein isothiocyanate (FITC) conjugated gold nanoparticles (F-AuNP) excited by 488 nm diode laser. Coupling between the near-field of localized surface plasmons of AuNP with molecules amplifies the fluorescence signal i.e. brightness hence the quantum yield by several orders of magnitude. Resonance Rayleigh scattering and PEF conditions are satisfied due to the overlapping of 488 nm of the laser beam with the maximum absorbance of FITC, and the SPR of AuNP with FITC emission spectrum at ≈525 nm. PEF acts as Stoke sand secondary pump beam for further optical excitation. Surface-enhanced Raman scattering (SERS) showed FITC molecular bonds at 600, 1680, and a weak deviation at 1280 cm−1, respectively. Longer wavelengths with higher output power were observed between 180° and 270°, and shorter wavelengths with lower power between 90° and 0° respectively. F-AuNPs were incubated and up taken by the oyster mushroom (OM) grown in the lab for bioimaging purposes and studied by phase-contrast microscope (PCM), and fluorescence microscope (FM). The FM results revealed visible colours, which can be utilized for in vitro and in vivo biosensing applications.

Background We previously found that African Americans and Native Hawaiians were at highest lung cancer risk compared with Japanese Americans and Latinos; whites were midway in risk. These differences were more evident at relatively low levels of smoking intensity, fewer than 20 cigarettes per day (CPD), than at higher intensity. Methods We apportioned lung cancer risk into three parts: age-specific background risk (among never smokers), an excess relative risk term for cumulative smoking, and modifiers of the smoking effect: race and years-quit smoking. We also explored the effect of replacing self-reports of CPD with a urinary biomarker—total nicotine equivalents—using data from a urinary biomarker substudy. Results Total lung cancers increased from 1979 to 4993 compared to earlier analysis. Estimated excess relative risks for lung cancer due to smoking for 50 years at 10 CPD (25 pack-years) ranged from 21.9 (95% CI = 18.0 to 25.8) for Native Hawaiians to 8.0 (95% CI = 6.6 to 9.4) for Latinos over the five groups. The risk from smoking was higher for squamous cell carcinomas and small cell cancers than for adenocarcinomas. Racial differences consistent with earlier patterns were seen for overall cancer and for cancer subtypes. Adjusting for predicted total nicotine equivalents, Japanese Americans no longer exhibit a lower risk, and African Americans are no longer at higher risk, compared to whites. Striking risk differences between Native Hawaiians and Latinos persist. Conclusions Racial differences in lung cancer risk persist in the Multiethnic Cohort study that are not easily explained by variations in self-reported or urinary biomarker-measured smoking intensities.

A dual-function nanocomposite agent (NCA) was prepared for deep tissue fluorescence and thermal imaging. The results showed that a combination of some agents such as gold nanourchins (GNU) and indocyanine green (ICG) can have spectral overlapping and hence some peak broadening. Despite 83% and 92% loss of NCA fluorescence after tissue layers L1 and L2, respectively, there was sufficient signal detected for imaging the target buried under the tissue. No fluorescence was detected after L3. A significant contribution was made by GNU for both the fluorescence signal due to the plasmon-enhanced fluorescence (PEF) effect and the thermal heating because of local surface plasmon resonance (LSPR) due to its sharp tips. In the first case, PEF occurred within the first 40 s then followed by a gradual quenching by 23% in 4 min and 72% in the following 6 min. During the second quenching time, the emission signal was blue shifted by 10 nm. Of the three samples, sample 2 (S2) indicated the highest temperature rise ≈ 60 °C in 50 s; sample 3 (S3) produced the lowest temperature of ≈ 33 °C in 250 s after the first layer, thus showing BSA acting as a heat sink. Both the heating and cooling time are determined by the thermal properties of the material such as conductivity and diffusivity. Finally, despite the advantages of PEF, the photostability and quenching rate of a dye molecule must be considered in a dynamic detection monitoring system to account and compensate for the effect of contrast agent quality variation.

In this article, a retail management system (RMS) called Shopwell is developed which keeps track of the expiry date of products along with the total expenditure analysis through Python, MySQL, and Android Studio where customers can keep track of the budget utilized for buying the products like groceries, cosmetics, and medication and it alerts when the product expiry is near while shopping online or offline. The customers hardly keep track of expiry dates on products and sometimes it is hard to keep track of total spending over a while. The proposed system can be linked with any retail business and comes in handy in the form of an app that can be installed on mobiles, tablets, and laptops. Once the retail business ties up with Shopwell, the bill which is created after shopping generates a link which directly links to the app once clicked by the customer when shopping online otherwise the link is established once the cashier scans the QR code available in the customer's app after scanning the products over offline mode. Once the app has the required data of the purchased items, it assists the customers to keep a record of the purchase details chiefly on the expiration date and the total expenditure thus avoiding consumers to stop using out of date products while keeping the daily budgets within stipulated limits.

Summary: Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the TGFB1 gene (rs11466334, risk allele frequency (RAF) = 6.8%, odds ratio [OR] = 1.27, p = 2.06 × 10−8), which replicated in independent studies of African ancestry (p = 6.26 × 10−23). We identified a multiethnic risk variant in the BACE2 gene (rs13052926, RAF = 14.1%, OR = 1.08, p = 5.75 × 10−9), which also replicated in independent studies (p = 3.45 × 10−4). We also observed a significant difference in the performance of a multiethnic genetic risk score (GRS) across population groups (pheterogeneity = 3.85 × 10−20). Comparing individuals in the top GRS risk category (40%–60%), the OR was highest in Asians (OR = 3.08) and European (OR = 2.94) ancestry populations, followed by Hispanic (OR = 2.39), Native Hawaiian (OR = 2.02), and African ancestry (OR = 1.57) populations. These findings underscore the importance of genetic discovery and risk characterization in diverse populations and the urgent need to further increase representation of non-European ancestry individuals in genetics research to improve genetic-based risk prediction across populations.

The work describes the application of photoacoustic (PA), fluorescence spectroscopy, and Fourier transform near-infrared spectroscopy as non-destructive optical techniques to examine the quality of milk. The amplitude of the acoustic wave was linearly proportional to the absorbed fluence. The acoustic velocity and the fluence threshold for onset of non-linearity were decreased as the fat % increased. Initially, the PA pressure was increased with fluence but it exhibited non-linearity and occurred earlier i.e. faster as the fat % was increased. The peak pressures of 120, 160, and 180 kPa were determined for 1%, 2%, and 3.5% respectively. The corresponding acoustic transient times of 0.5, 0.44, and 0.36 µs were calculated for 1%, 2%, and 3.5% milk respectively. The absorption coefficient of milk samples was determined using the pressure-fluence slope and Grüneisen constant, which increased with fat %. The bandwidths between 350–450 nm and 450–550 nm correspond to tryptophan or valine, and Methionine amino acids respectively, and the peak at ≈315 nm is thought to be due to tyrosine. The fluorescence intensity of the sample day 1 (D1-open) decreased with time more significantly due to variations in the environmental condition. The bands between 4000 and 4500 cm−1 correspond to CH-stretch, and day 4 (D4-closed) showed the highest peak amplitudes compared to the others. Combination of N–H and O–H stretch was mainly observed between 4500 and 5000 cm−1, and the bands at 4581, 4655 cm−1 in fresh sample disappeared in D1-open and D1-closed. New bands of 4717, 4792, and 4829 cm−1 were observed.

We describe studies of the interaction of a pulsed Nd:YAG laser with bovine serum albumin (BSA) solution (i.e., S0) and S0 containing gold nanourchin (GNU) (i.e., S1: S0 + 0.1 ml GNU) using combined photoacoustic (PA) and probe beam deflection (PBD) techniques. The changes in absorbance and chemical bonds are studied by UV–Vis and near-FTIR spectroscopy. The results showed a decrease in absorbance of the bio-plasmonic solution, which further decreased by increasing the concentration. The PA pressure increased with fluence in the order of GNU > S0 > S1, and all exhibited a non-linear response at ≈9.5 J cm−2and reached a maximum at 12.5 J cm−2. No PBD was observed in S0 indicating the role of GNU in producing the heating effect. ∂n/∂T increased in the order of S2 > S1 > S0, respectively, where S2 is (S0 + 0.2 ml GNU). The absorbance of S0 and S1 increased after heating due to protein denaturation. For S1, surface-enhanced FTIR showed an increase in the intensity of most bands between 6320 and 6630 cm−1, and the band at 5264 cm−1, which likely corresponds to β-sheet structure, significantly diminished after heating. The collapse of cavitation and plasma shock waves produced significant acoustic transients, hence some photomechanical effects. The acoustic energy released after the collapse of bubbles at 1.8 and 12.5 J cm−2was calculated to be ≈140 μJ and 7 mJ, respectively, corresponding to 4% and 28% of the input optical energy being converted to sound energy in the early phase of the expansion.

1,3-Butadiene (BD) is a known human carcinogen used in the synthetic polymer industry and also found in cigarette smoke, automobile exhaust and wood burning smoke. BD is metabolically activated by cytochrome P450 monooxygenases (CYP) 2E1 and 2A6 to 3,4-epoxy-1-butene (EB), which can be detoxified by GST-catalyzed glutathione conjugation or hydrolysis. We have previously observed ethnic differences in urinary levels of EB–mercapturic acids in white, Japanese American and Native Hawaiian smokers. In the present study, similar analyses were extended to urinary BD–DNA adducts. BD-induced N7-(1-hydroxy-3-buten-2-yl) guanine (EB–GII) adducts were quantified in urine samples obtained from smokers and non-smokers belonging to three racial/ethnic groups: white, Japanese American and Native Hawaiian. After adjusting for sex, age, nicotine equivalents, body mass index and batch, we found that Japanese American smokers excreted significantly higher amounts of urinary EB–GII than whites [1.45 (95% confidence interval: 1.12–1.87) versus 0.68 (95% confidence interval: 0.52–0.85) fmol/ml urine, P = 4 × 10−5]. Levels of urinary EB–GII in Native Hawaiian smokers were not different from those in whites [0.67 (95% confidence interval: 0.51–0.84) fmol/ml urine, P = 0.938]. There were no racial/ethnic differences in urinary EB–GII adduct levels in non-smokers. Racial/ethnic differences in urinary EB–GII adduct levels in smokers could not be explained by GSTT1 gene deletion or CYP2A6 enzymatic activity. Urinary EB–GII adduct levels in smokers were significantly associated with concentrations of BD metabolite dihyroxybutyl mercapturic acid. Overall, our results reveal that urinary EB–GII adducts in smokers differ across racial/ethnic groups. Future studies are required to understand genetic and epigenetic factors that may be responsible for these differences.

Purpose To describe current practice of pediatric sternal precautions (PSPs) and prone positioning restrictions (PPRs) in infants after median sternotomy. Methods A Web-based survey with 21 questions was developed on the basis of a review of current literature and expert consultation. Snowball sampling resulted in 68 participants well represented by profession throughout the United States. Results Approximately 80% of participants reported having institutional protocols for PSPs. Most common reported PSPs were no lifting at the axillae and no pulling of arms to achieve sitting. PSPs also included PPRs. The opinions of participants supported no PPRs or modified PPRs compared with strict PPRs. Conclusions Types of PPRs varied across participants, with the majority of participants in favor of modified PPRs while PSPs were less varied. Research is needed to examine the effects of PSPs and PPRs in infants post-median sternotomy.

PURPOSE In studies of men of European ancestry, rare pathogenic variants in DNA repair pathway genes have been shown to be associated with risk of aggressive prostate cancer. The contribution of rare coding variation to prostate cancer risk in men of African ancestry has not been established. METHODS We sequenced a panel of 19 DNA repair and cancer predisposition genes in 2,453 African American and 1,151 Ugandan cases and controls with prostate cancer. Rare variants were classified as pathogenic or putatively functionally disruptive and examined in association with prostate cancer risk and disease aggressiveness in gene and pathway-level association analyses. RESULTS Pathogenic variants were found in 75 of 2,098 cases (3.6%) and 31 of 1,481 controls (2.1%; odds ratio [OR], 1.82; 95% CI, 1.19 to 2.79; P = .0044), with the association being stronger for more aggressive disease phenotypes (OR, 3.10; 95% CI, 1.54 to 6.23; P = .0022). The highest risks for aggressive disease were observed with pathogenic variants in the ATM, BRCA2, PALB2, and NBN genes, with ORs ranging from approximately 4 to 15 in the combined study sample of African American and Ugandan men. Rare, nonpathogenic, nonsynonymous variants did not have a major impact on risk of overall prostate cancer or disease aggressiveness. CONCLUSION Rare pathogenic variants in DNA repair genes have appreciable effects on risk of aggressive prostate cancer in men of African ancestry. These findings have potential implications for panel testing and risk stratification in this high-risk population.

Bacteria surround themselves with peptidoglycan, an adaptable enclosure that contributes to cell shape and stability. Peptidoglycan assembly relies on penicillin-binding proteins (PBPs) acting in concert with SEDS-family transglycosylases RodA and FtsW, which support cell elongation and division respectively. InBacillus subtilis, cells lacking all four PBPs with transglycosylase activity (aPBPs) are viable. Here, we show that the alternative sigma factor σIis essential in the absence of aPBPs. Defects in aPBP-dependent wall synthesis are compensated by σI-dependent upregulation of an MreB homolog, MreBH, which localizes the LytE autolysin to the RodA-containing elongasome complex. Suppressor analysis reveals that cells unable to activate this σIstress response acquire gain-of-function mutations in the essential histidine kinase WalK, which also elevates expression ofsigI,mreBHandlytE. These results reveal compensatory mechanisms that balance the directional peptidoglycan synthesis arising from the elongasome complex with the more diffusive action of aPBPs.

Coronary artery fistulas (CAF) are rare congenital or acquired coronary artery anatomic anomalies. They can develop from any of the three coronary arteries and drain into any of the cardiac chambers and great vessels thus creating an anatomic bypass of the myocardial capillary network. In our case, we present an 81-year-old who was referred for left heart catheterization after having found myocardial ischemia on perfusion imaging. Incidentally, he was found to have a fistula connection between the left circumflex coronary artery with the pulmonary artery. We present an atypical case of a circumflex coronary artery as a rare point of origin for a fistula with an incidence of about 18%.

A smart parking system using Raspberry Pi and android app access is proposed in this article. An automated smart parking system which provides the user to pre-book along with on the spot booking facility of parking spaces available around the area is implemented. The system also helps to store the user’s information in database which enables for fast parking access thus reducing the traffic congestion. The hardware is realized using Raspberry Pi and IR sensor. In addition, the system is controlled through an app which is made using Kodular App Development tool, that helps the user to keep track of the updates about available parking spaces. The scalable and precise database can be created on firebase and host it on an application in real-time which is useful to store data in a json format (bucket format). The system is a perfect partner for people to book the parking spaces at their ease from remote locations without wasting time and avoiding traffic congestion.

Factor Xa inhibitors are approved for the prevention of clot formation in non-valvular atrial fibrillation and for treating deep venous thromboembolism and pulmonary embolism. This class of medications are known CYP3A4 and CYP2J2 inhibitors vulnerable to drug-drug interactions and are known to be risk factors for GI bleeding. Although not a common finding, these medications are possible risk factors for acute liver injury, as seen in our patient. We present an uncommon case of persistent Factor Xa Inhibitor induced liver injury in an Eastern Asian male.

The systemic illness associated with SARS-CoV-2 infection results in hospitalization rate of 380.3 hospitalizations per 100,000 population, overwhelming health care systems. Vitamin D regulates expression of approximately 11,000 genes spanning many physiologic functions that include regulation of both innate and adaptive immune function. We investigate potential benefit of calcitriol therapy given to patients hospitalized with COVID-19. This was an open label, randomized clinical trial of calcitriol or no treatment given to hospitalized adult patients with COVID-19. Subjects were randomly assigned treatment with calcitriol 0.5 μg daily for 14 days or hospital discharge; or no treatment (1:1) at time of enrollment. We enrolled 50 consecutive patients, 25 per trial arm. The change in peripheral arterial oxygen saturation to the inspired fraction of oxygen (SaO2/FIO2 ratio) was calculated on admission and discharge between the groups. The control group had an average increase of +13.2 (±127.7) on discharge and the calcitriol group had an increase of +91.04 (±119.08) (p = .0305), suggesting an improvement in oxygenation among subjects who received calcitriol. Additionally, 12 patients in the control group required oxygen supplementation on admission and 21 of them were discharged on room air. 14 subjects needed oxygen supplementation in the calcitriol group on admission while all 25 were discharged on room air. Other clinical markers showed the average length of stay was 9.24 (±9.4) in the control group compared to 5.5 (±3.9) days in the calcitriol group (p = .14). The need for ICU transfer was 8 in the control group and 5 in the calcitriol group. There were 3 deaths and 4 readmissions in the control group and 0 deaths and 2 readmissions in the calcitriol group. This pilot study illustrates improvement in oxygenation among hospitalized patients with COVID-19 treated with calcitriol and suggests the need for a larger randomized trial.

The Multiethnic Cohort Study has demonstrated that African Americans and Native Hawaiians have a higher risk for lung cancer due to cigarette smoking than Whites while Latinos and Japanese Americans have a lower risk. These findings are consistent with other epidemiologic studies in the literature. In this review, we summarize tobacco carcinogen and toxicant biomarker studies and genetic analyses which partially explain these differences. As determined by measurement of total nicotine equivalents in urine, which account for about 85% of the nicotine dose, African Americans take up greater amounts of nicotine than Whites per cigarette while Japanese Americans take up less. There are corresponding differences in the uptake of tobacco smoke carcinogens such as tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, 1,3-butadiene, and other toxic volatiles. The lower nicotine uptake of Japanese Americans is clearly linked to the preponderance of low activity forms of the primary nicotine metabolizing enzyme CYP2A6 in this ethnic group, leading to more unchanged nicotine in the body and thus lower smoking intensity. But the relatively high risk of Native Hawaiians and the low risk of Latino smokers for lung cancer are not explained by these factors. The possible role of epigenetics in modifying lung cancer risk among smokers is also discussed here. The results of these published studies may lead to a better understanding of susceptibility factors for lung cancer in cigarette smokers thus potentially identifying biomarkers that can detect those individuals at highest risk so that preventive approaches can be initiated at an early stage of the lung cancer development process.

Over the past years, thermoelectric refrigeration has attracted considerable attention due to its compact size, reliability, and environmental friendliness. Traditional refrigeration systems use greenhouse gases, which significantly impacts our environment. Therefore, in this work, a thermoelectric cooler prototype refrigeration system, a solid-state device causing no harm to the environment, was constructed and tested experimentally. A heat sink was attached to the cold side of the thermoelectric cooler (TEC) to cool the air passing through the heat sink. In contrast, a cold plate was attached to the hot side of TEC to remove the generated heat with the help of the liquid circulating in the aluminium cold plate. Experiments were carried out by varying parameters such as input current to the TEC module, inlet air flow rate, water flow rate through the cold plate, etc. The experimental results indicate that the cooling effect is increased by approximately 40%, increasing current from 2A to 8A. However, the cooling effect was decreased with increasing inlet airflow rate by 58% when airflow rate increased from 2.25 m/s to 3.55 m/s. However, the system performance shows approximately 35% increment with an increase in fan speed. Furthermore, a decrease in the water flow rate from 3.04 L/m to 1.80 L/m showed a slight increment in the cooling by 15%.

Background ART-associated weight gain, metabolic disorders, and co-morbidities such as cardiovascular disease are challenges in long-term human immunodeficiency virus (HIV) care. We explore the effects of different ART classes on lipids at The Ohio State University Medical Center Infectious Diseases Clinic. Methods This was a retrospective, cohort study of adult PWH on ART for ≥ 3 months seen at our clinic from 1/1/2015 to 1/1/2017. Patients with CD4+ count < 200 cells/mm3 and viral load >200 copies/mL, history of malignancy, or pregnancy were excluded. Lipid values were collected over the study period. The primary outcome was change in total cholesterol (TC), high density lipoprotein (HDL) cholesterol, and non-HDL cholesterol over the study period. Multivariable regression was used to model these outcomes. Results Among 411 PWH who met criteria, 87.4% were male, and 43.3% had a baseline diagnosis of hyperlipidemia. 21.1% were on a protease inhibitor (PI), 45% were on a non-nucleoside reverse transcriptase inhibitor (NNRTI), and 37% were on an integrase strand transfer inhibitor (INSTI). 70.1% were on tenofovir disoproxil fumarate (TDF)/ emtricitabine (FTC), 20.7% were on abacavir (ABC)/ lamivudine (3TC), and 4.4% were on TAF/FTC. The mean population (MP) difference in TC was -1.54 ± 1.34 mg/dL (p=0.25), the MP difference in non-HDL cholesterol was -1.78 ± 1.26 mg/dL (p=0.16), and the MP difference in HDL cholesterol was 0.24 ± 0.43 mg/dL (p=0.6). In multivariable linear regression models (Table 1), TAF/FTC was associated with a change of TC of 18.2 ± 6.4 mg/dL (P= 0.005), a change of non-HDL cholesterol of 12.0 ± 6.0 mg/dL (p=0.046), and a change of HDL cholesterol of 6.2 ± 2.1 mg/dL (p=0.003). These models included terms for months of follow up, male gender and baseline hyperlipidemia. Though race, diabetes mellitus, and ethnicity were not significant in the model, after adjustments for them, PWH on TAF/FTC showed a change of TC of 18.0 ± 6.4 mg/dL (p=0.005), a change of non-HDL cholesterol of 11.8 ± 6.0 mg/dL (P=0.051), and a change of HDL of 6.2 ± 2.1 (p=0.03). Multivariable Linear Regression Models for Change in Total Cholesterol and Non-HDL Cholesterol Conclusion Prior studies have shown an increase in lipid levels associated with TAF compared to TDF. This study shows that TAF is an independent risk factor for increased TC, non-HDL cholesterol, and HDL cholesterol in the PWH population as a whole. Disclosures Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)