The Impact of Implementation of a Commercial Inferior Vena Cava Filter Database Program on Filter Retrieval versus Physician Tracking over a 9-Year Period: A Retrospective, Observational Study.

PURPOSE: To compare the impact of a commercial tracking database on inferior vena cava filter retrievals with that of physician tracking and no tracking. MATERIALS AND METHODS: From January 2013 to December 2021, 532 filters were placed at a single institution and followed in 3 phases: (a) Phase 1, pretracking (January 1, 2013, to February 28, 2015); (b) Phase 2, commercial database tracking (March 1, 2015, to June 30, 2019); and (c) Phase 3, commercial database tracking with separate tracking by an interventional radiologist (July 1, 2019, to December 31, 2021). Patients excluded from the commercial database due to human error served as a control group. Outcomes of commercial database entry, 2-year filter retrieval rates, dwell times, and factors contributing to retrieval candidacy were collected. RESULTS: Two-year retrieval rates in Phases 1, 2 and 3 were 20%, 31%, and 46%, respectively (Phase 1 vs 2, P = .04; Phase 2 vs 3, P = .009). Median dwell times across Phases 1, 2, and 3 were 168 days (4-1,313 days), 140 days (3-1,988 days), and 188 days (13-734 days) (P = .33), respectively. There was no difference in retrieval rates (P = .86) and dwell times (P = .50) between patients enrolled in the database group and those enrolled in the control group. Across all phases, 48% of patients enrolled in the database were not successfully contacted, and only 6% were categorized as "likely to consult" filter retrieval. During Phase 3, 100% of patients achieved a retrieval disposition. CONCLUSIONS: A commercial tracking database had low success rates of contacting patients and did not increase filter retrieval rates relative to those in the control group; however, physician tracking increased retrieval rates.

Angiography with cone-beam CT versus contrast-enhanced MRI for living donor transplant imaging: Is MRI enough?

The purpose of this study is to compare the subjective and objective quality and confidence between conventional angiography with cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) for the preoperative evaluation of potential donors for living donor liver transplant. Seventeen patients undergoing preoperative donor evaluation for living donor liver transplantation that underwent angiography with CBCT and contrast-enhanced MRI for evaluation of hepatic vascular anatomy were included in the study. Four attending radiologists interpreted anonymized, randomized angiography with CBCT images and MRIs, rating the diagnostic quality and confidence of their interpretation (on a 3-point scale) for each element, as well as clinically relevant measurements. Overall, the readers rated the quality of angiography with CBCT to be higher than that of MRI (median [interquartile range] = 3 (2, 3) vs. 2 (1-3), p < 0.001) across all patients. Readers of angiography with CBCT had more confidence in their interpretations as an average of all elements evaluated than the MRI readers (3 (3) vs. 3 (2, 3), p < 0.001). When the same reader interpreted both MRI and CBCT, the right hepatic artery diameter (3.8 mm ± 0.72 mm vs. 4.5 mm ± 1.2 mm, p < 0.005) and proper hepatic artery diameter (4.43 mm ± 0.98 mm vs. 5.4 mm ± 1.05 mm, p < 0.003) were significantly different between MRI and CBCT. There was poor interrater reliability for determining segment IV arterial supply for both modalities (κ < 0.2). Angiography with CBCT provides higher subjective diagnostic quality and greater radiologist confidence than MRI. The difference in measurements between CBCT and MRI when the same reader reads both studies suggests CBCT adds additional information over MRI evaluation alone.

A case of stuck mechanical Tricuspid Valve.

A 34-year-old non hypertensive, non-diabetic and ill looking weak woman came to our emergency department with shortness of breath NYHA III-IV, severe bilateral pedal edema extending up to the thighs and gross ascites. Physical examination revealed 3mm pitting ankle and leg edema and hemodynamically was stable with raised jugular venous pressure. There was a closing and opening mechanical click on Cardiac auscultation. At the lower left sternal border, there was grade 2/6 holodiastolic rumble and a grade 2/6 systolic murmur. She had history of mitral valve replacement and tricuspid valve replacement in 2017 with mechanical valves then she had Redo tricuspid valve replacement with mechanical prosthesis again after four months. No known food or drug allergy and psychosocial issues. Her routine bloods Labs were normal and COVID-19 was negative. On chest X-ray P/A view images and echo showed markedly gross left sided pleural effusion. In Coronary angiogram showed normal coronaries and stuck tricuspid valve (Fig.1). Echocardiography report showed preserved LV systolic function (EF=57%), dilated left atrium and right atrium. Prosthetic mitral valve was seen at mitral position, well seated and well-functioning. The mechanical mitral valve was functioning well with normal disc motion with no thrombus formation. Prosthetic tricuspid valve was seen at tricuspid level with peak gradient of 22mmHg and shown stuck mechanical tricuspid discs stuck throughout the cardiac cycle, in a fully open position (Fig.2A and 2B). Atrial fibrillation was shown on ECG. The diagnosis was made as; pannus formation resulting in mechanical TV thrombosis.

Evaluation of Technical Performance of Ultrasound-Guided Procedures through Hand Motion Analysis: An Exploration of Motion Metrics.

PURPOSE: To evaluate the ability of hand motion analysis using conventional and new motion metrics to differentiate between operators of varying levels of experience for central venous access (CVA) and liver biopsy (LB). MATERIALS AND METHODS: In the CVA task, 7 interventional radiologists (experts), 10 senior trainees, and 5 junior trainees performed ultrasound-guided CVA on a standardized manikin; 5 trainees were retested after 1 year. In the LB task, 4 radiologists (experts) and 7 trainees biopsied a lesion on a manikin. Conventional motion metrics (path length and task time), a refined metric (translational movements), and new metrics (rotational sum and rotational movements) were calculated. RESULTS: In the CVA task, experts outperformed trainees on all metrics (P < .02). Senior trainees required fewer rotational movements (P = .02), translational movements (P = .045), and time (P = .001) than junior trainees. Similarly, on 1-year follow-up, trainees had fewer translational (P = .02) and rotational (P = .003) movements with less task time (P = .003). The path length and rotational sum were not different between junior and senior trainees or for trainees on follow-up. Rotational and translational movements had greater area under the curve values (0.91 and 0.86, respectively) than the rotational sum (0.73) and path length (0.61). In the LB task, experts performed the task with a shorter path length (P = .04), fewer translational (P = .04) and rotational (P = .02) movements, and less time (P < .001) relative to the trainees. CONCLUSIONS: Hand motion analysis using translational and rotational movements was better at differentiating levels of experience and improvement with training than the conventional metric of path length.

Selective Induction of Cell Death in Human M1 Macrophages by Smac Mimetics Is Mediated by cIAP-2 and RIPK-1/3 through the Activation of mTORC.

Inflammatory macrophages have been implicated in many diseases, including rheumatoid arthritis and inflammatory bowel disease. Therefore, targeting macrophage function and activation may represent a potential strategy to treat macrophage-associated diseases. We have previously shown that IFN-γ-induced differentiation of human M0 macrophages toward proinflammatory M1 state rendered them highly susceptible to the cytocidal effects of second mitochondria-derived activator of caspases mimetics (SMs), antagonist of the inhibitors of apoptosis proteins (IAPs), whereas M0 and anti-inflammatory M2c macrophages were resistant. In this study, we investigated the mechanism governing SM-induced cell death during differentiation into M1 macrophages and in polarized M1 macrophages. IFN-γ stimulation conferred on M0 macrophages the sensitivity to SM-induced cell death through the Jak/STAT, IFN regulatory factor-1, and mammalian target of rapamycin complex-1 (mTORC-1)/ribosomal protein S6 kinase pathways. Interestingly, mTORC-1 regulated SM-induced cell death independent of M1 differentiation. In contrast, SM-induced cell death in polarized M1 macrophages is regulated by the mTORC-2 pathway. Moreover, SM-induced cell death is regulated by cellular IAP (cIAP)-2, receptor-interacting protein kinase (RIPK)-1, and RIPK-3 degradation through mTORC activation during differentiation into M1 macrophages and in polarized M1 macrophages. In contrast to cancer cell lines, SM-induced cell death in M1 macrophages is independent of endogenously produced TNF-α, as well as the NF-κB pathway. Collectively, selective induction of cell death in human M1 macrophages by SMs may be mediated by cIAP-2, RIPK-1, and RIPK-3 degradation through mTORC activation. Moreover, blocking cIAP-1/2, mTORC, or IFN regulatory factor-1 may represent a promising therapeutic strategy to control M1-associated diseases.

TLR-4 Agonist Induces IFN-γ Production Selectively in Proinflammatory Human M1 Macrophages through the PI3K-mTOR- and JNK-MAPK-Activated p70S6K Pathway.

IFN-γ, a proinflammatory cytokine produced primarily by T cells and NK cells, activates macrophages and engages mechanisms to control pathogens. Although there is evidence of IFN-γ production by murine macrophages, IFN-γ production by normal human macrophages and their subsets remains unknown. Herein, we show that human M1 macrophages generated by IFN-γ and IL-12- and IL-18-stimulated monocyte-derived macrophages (M0) produce significant levels of IFN-γ. Further stimulation of IL-12/IL-18-primed macrophages or M1 macrophages with agonists for TLR-2, TLR-3, or TLR-4 significantly enhanced IFN-γ production in contrast to the similarly stimulated M0, M2a, M2b, and M2c macrophages. Similarly, M1 macrophages generated from COVID-19-infected patients' macrophages produced IFN-γ that was enhanced following LPS stimulation. The inhibition of M1 differentiation by Jak inhibitors reversed LPS-induced IFN-γ production, suggesting that differentiation with IFN-γ plays a key role in IFN-γ induction. We subsequently investigated the signaling pathway(s) responsible for TLR-4-induced IFN-γ production in M1 macrophages. Our results show that TLR-4-induced IFN-γ production is regulated by the ribosomal protein S6 kinase (p70S6K) through the activation of PI3K, the mammalian target of rapamycin complex 1/2 (mTORC1/2), and the JNK MAPK pathways. These results suggest that M1-derived IFN-γ may play a key role in inflammation that may be augmented following bacterial/viral infections. Moreover, blocking the mTORC1/2, PI3K, and JNK MAPKs in macrophages may be of potential translational significance in preventing macrophage-mediated inflammatory diseases.

Predicting Thermal Injury Patient Outcomes in a Tertiary-Care Burn Center, Pakistan.

INTRODUCTION: To explore candidate parameters for their ability to predict survival and length of hospital stay (LOS) in thermal burns patients, to prepare multivariate predictive models for these two outcomes, and to compare performance of native models to other models. METHODS: A retrospective cohort study was undertaken based on record review. Data was extracted from files of patients admitted to a tertiary-care burn center in Lahore, Pakistan from January 1, 2020 to October 31, 2020. After univariate preselection, we prepared multivariate logistic regression models for each outcome of interest (survival and LOS). Multivariate models were tested and compared to other models. RESULTS: Increasing total body surface area (TBSA) of burn was associated with reduced survival and prolonged length of hospital stay. Advancing age and full-thickness burns independently predicted decreased survival. Burn etiology showed prognostic value: petrol-flame burns predicted decreased survival and prolonged LOS; scald was associated with improved survival-odds and shorter LOS. The Survival-model consisted of (1) Baux score, (2) TBSA>40% and (3) serum albumin <3.5 g/dL (AUC = 0.968, Nagelkerke R2 = 0.797). The LOS-model consisted of (1) TBSA2 and (2) serum albumin concentration (AUC = 0.832, Nagelkerke R2 = 0.408). In tests of discrimination and calibration, native models prepared for survival and LOS outperformed other models applicable to our dataset. CONCLUSIONS: Data from a South Asian burn center has been used to explore factors influencing prognosis for their utility in predictive models for survival and the duration of hospital stay. The significant prognostic roles of TBSA, age, inhalational injury, burn-depth, etiology of burn, anatomic site of burn, hypoalbuminemia, and other biochemical parameters were observed. These tools hold significance in guiding healthcare policy and in communications with patients and their families.

4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response.

Deregulation of mRNA translation engenders many human disorders, including obesity, neurodegenerative diseases, and cancer, and is associated with pathogen infections. The role of eIF4E-dependent translational control in macrophage inflammatory responses in vivo is largely unexplored. In this study, we investigated the involvement of the translation inhibitors eIF4E-binding proteins (4E-BPs) in the regulation of macrophage inflammatory responses in vitro and in vivo. We show that the lack of 4E-BPs exacerbates inflammatory polarization of bone marrow-derived macrophages and that 4E-BP-null adipose tissue macrophages display enhanced inflammatory gene expression following exposure to a high-fat diet (HFD). The exaggerated inflammatory response in HFD-fed 4E-BP-null mice coincides with significantly higher weight gain, higher Irf8 mRNA translation, and increased expression of IRF8 in adipose tissue compared with wild-type mice. Thus, 4E-BP-dependent translational control limits, in part, the proinflammatory response during HFD. These data underscore the activity of the 4E-BP-IRF8 axis as a paramount regulatory mechanism of proinflammatory responses in adipose tissue macrophages.

Unmediated connection of mental health decline and suicide among medical and nonmedical undergraduates during the pandemic of COVID-19: A cross-sectional comparative study.

Background and Objectives: All medicine and healthcare undergraduates were encountered with terminations and delays of professional examinations. These alterations were on topmost of other tasks the COVID-19 pandemic carried out for instance not roaming, covered faces with masks and specifically segregation. This interruption of normal life was a major cause of mental health disaster and it is no surprise that medicine and healthcare undergraduate has had high rates of psychological effects including hopelessness, stress and suicidal thoughts. This study aimed to investigate the unmediated connection of anxiety and stress related mental health decline and suicide among medical and nonmedical undergraduates during the pandemic of covid-19. Methods: A multidiscipline online cross-sectional comparative study design was chosen for this study conducted from November 2020 to January 2021 with a pre-validated questionnaire to collect responses from sample size 1290. SPSS- 21 used for descriptive analysis of means, S.D, ANOVA and spearman's correlations. Forward step-wise model of linear regression applies for true significant bivariate relationship (p<.001). Results: The result shows that all three cohorts were affected. Among the non-medical cohorts, B-Pharmacy students had the high level (p<.001) of anxiety with suicide ideation response (n=200; 39.2%), along with lowest level of envisions care (19.5%; p<.001) in pandemic. Control and independent variable had a strong negative effects on B-Pharmacy and medical students with p<.000. Conclusions: This study offered more data that the concerns, anxieties and uncertainties caused by pandemic COVID-19, don't roll out alone but remain as long-lasting problems demanding ongoing attention.

Identification of novel genes involved in apoptosis of HIV-infected macrophages using unbiased genome-wide screening.

BACKGROUND: Macrophages, besides resting latently infected CD4+ T cells, constitute the predominant stable, major non-T cell HIV reservoirs. Therefore, it is essential to eliminate both latently infected CD4+ T cells and tissue macrophages to completely eradicate HIV in patients. Until now, most of the research focus is directed towards eliminating latently infected CD4+ T cells. However, few approaches have been directed at killing of HIV-infected macrophages either in vitro or in vivo. HIV infection dysregulates the expression of many host genes essential for the survival of infected cells. We postulated that exploiting this alteration may yield novel targets for the selective killing of infected macrophages. METHODS: We applied a pooled shRNA-based genome-wide approach by employing a lentivirus-based library of shRNAs to screen novel gene targets whose inhibition should selectively induce apoptosis in HIV-infected macrophages. Primary human MDMs were infected with HIV-eGFP and HIV-HSA viruses. Infected MDMs were transfected with siRNAs specific for the promising genes followed by analysis of apoptosis by flow cytometry using labelled Annexin-V in HIV-infected, HIV-exposed but uninfected bystander MDMs and uninfected MDMs. The results were analyzed using student's t-test from at least four independent experiments. RESULTS: We validated 28 top hits in two independent HIV infection models. This culminated in the identification of four target genes, Cox7a2, Znf484, Cstf2t, and Cdk2, whose loss-of-function induced apoptosis preferentially in HIV-infected macrophages. Silencing these single genes killed significantly higher number of HIV-HSA-infected MDMs compared to the HIV-HSA-exposed, uninfected bystander macrophages, indicating the specificity in the killing of HIV-infected macrophages. The mechanism governing Cox7a2-mediated apoptosis of HIV-infected macrophages revealed that targeting respiratory chain complex II and IV genes also selectively induced apoptosis of HIV-infected macrophages possibly through enhanced ROS production. CONCLUSIONS: We have identified above-mentioned novel genes and specifically the respiratory chain complex II and IV genes whose silencing may cause selective elimination of HIV-infected macrophages and eventually the HIV-macrophage reservoirs. The results highlight the potential of the identified genes as targets for eliminating HIV-infected macrophages in physiological environment as part of an HIV cure strategy.

Developing neck circumference growth reference charts for Pakistani children and adolescents using the lambda-mu-sigma and quantile regression method.

OBJECTIVE: Neck circumference (NC) is currently used as an embryonic marker of obesity and its associated risks. But its use in clinical evaluations and other epidemiological purposes requires sex and age-specific standardised cut-offs which are still scarce for the Pakistani paediatric population. We therefore developed sex and age-specific growth reference charts for NC for Pakistani children and adolescents aged 2-18 years. DESIGN: Cross-sectional multi-ethnic anthropometric survey (MEAS) study. SETTING: Multan, Lahore, Rawalpindi and Islamabad. PARTICIPANTS: The dataset of 10 668 healthy Pakistani children and adolescents aged 2-18 years collected in MEAS were used. Information related to age, sex and NC were taken as study variables. The lambda-mu-sigma (LMS) and quantile regression (QR) methods were applied to develop growth reference charts for NC. RESULTS: The 5th, 10th, 25th, 50th, 75th, 90th and 95th smoothed percentile values of NC were presented. The centile values showed that neck size increased with age in both boys and girls. During 8 and 14 years of age, girls were found to have larger NC than boys. A comparison of NC median (50th) percentile values with references from Iranian and Turkish populations reveals substantially lower NC percentiles in Pakistani children and adolescents compared to their peers in the reference population. CONCLUSION: The comparative results suggest that the uses of NC references of developed countries are inadequate for Pakistani children. A small variability between empirical centiles and centiles obtained by QR procedure recommends that growth charts should be constructed by QR as an alternative method.

Transfection of hard-to-transfect primary human macrophages with Bax siRNA to reverse Resveratrol-induced apoptosis.

Small interfering RNA (siRNA) is a critical loss-of-function tool for elucidating the role of genes in biomedical studies. The effective use of siRNA needs transfection technology that delivers siRNA into the correct location of target cells, especially those which are extremely difficult to transfect. Macrophages, which play an important role in the pathogenesis of many diseases, are known to be extremely hard to transfect. Thus, to elucidate the functions of genes in human macrophage biology, it is essential to devise technology for efficient siRNA transfection. However, a fast and efficient method for siRNA transfection in primary human macrophages has not been reported. The siRNA transfection is a tug-of-war between transfection rate and cytotoxicity. A higher transfection rate is generally accompanied with increased cytotoxicity, therefore, choosing a transfection reagent that limits cell death while maintain a desirable transfection rate is important. In this study, we employed auto-analysis function of the IncuCyte® to devise a fast and cost-saving technology for efficient transfection of adherent cells and particularly human macrophages. We show that DharmaFECT3 transfection reagent from Dharmacon was the most efficient in transfecting primary human monocyte-derived macrophages and PMA-differentiated U937 cells, whereas other transfection reagents tested were cytotoxic. This method exhibited approximately 85% transfection efficiency in human macrophages. Moreover, siRNA silencing of Bax with this technique effectively protected primary human macrophages and PMA-differentiated U937 cells against Resveratrol-induced cell death. In addition, this method inherently takes the balance between transfection rate and cytotoxicity of siRNA transfection reagents into consideration.

Evaluation of Primary Lymphedema with Intranodal Lymphangiography.

PURPOSE: There are limited existing data on the lymphatic anatomy of patients with primary lymphedema (LED), which is caused by aberrant development of lymphatic channels. In addition, there is a paucity of contemporary studies that use groin intranodal lymphangiography (IL) to evaluate LED anatomy. The purpose of this retrospective observational study was to better delineate the disease process and anatomy of primary LED using groin IL. MATERIALS AND METHODS: We identified common groin IL findings in a cohort of 17 primary LED patients performed between 1/1/2017 and 1/31/2022 at a single institution. These patients were clinically determined to have primary lymphedema and demonstrated associated findings on lower extremity MR and lymphoscintigraphy. RESULTS: Ten patients (59%) demonstrated irregular lymph node morphology or a paucity of lymph nodes on the more symptomatic laterality. Eight patients (47%) demonstrated lymphovenous shunting from pre-existing anastomoses between the lymphatic and venous systems. Eight patients (47%) demonstrated passage of contrast past midline to the contralateral lymphatics. Finally, 12 patients (71%) failed to opacify the cisterna chyli and thoracic duct on their initial lymphangiograms. Delayed computed tomography of 3 patients showed eventual central lymphatic opacification up to the renal veins, but none of these patients showed central lymphatic opacification to the thorax. CONCLUSION: This descriptive, exploratory study demonstrates common central groin IL findings in primary LED to highlight patterns interventional radiologists should identify and report when addressing primary LED.

Analyzing the Evolution of Needle and Ultrasound Probe Manipulation Skills of Interventional Radiology Trainees With Time and Experience.

PURPOSE: To test the hypothesis that hand motion analysis can measure the progression of needle and ultrasound probe manipulation skills of interventional radiology trainees in central venous line placement. MATERIALS AND METHODS: An expert cohort of 6 interventional radiologists and 4 anesthesiologists and a trainee cohort of 6 novice trainees (<50 central lines) and 5 experienced trainees (>50 central lines) performed simulated central venous access. Four novices and 1 experienced trainee repeated the task 1 year later. An electromagnetic motion tracking system tracked the needle hand and ultrasound probe. Path length, translational, and rotational movements were calculated separately for the needle hand and probe sensor. These metrics were used to calculate motion metrics based scores on a scale of 0 to 3 for each sensor. Nonparametric statistics were used, and the data are reported as median ± interquartile range. RESULTS: Comparing novice and experienced trainees, there was a significant difference in probe scores (experienced vs. novice: 1 ± 2 vs. 0 ± 0, P = 0.04) but not in needle-hand scores (1 ± 1.5 vs. 0 ± 1, P = 0.26). Trainees showed a significant increase in probe scores at the 1-year follow-up (baseline vs. follow-up: 0 ± 1 vs. 2.5 ± 1.8, P = 0.003), but no significant difference was observed in the needle manipulation metrics. Experts differed significantly from experienced trainees for all metrics for both sensors (P < 0.05), with the exception of the path length of the probe. CONCLUSIONS: Acquisition of improved dexterity of the probe may occur before improvement in the dexterity with the needle hand for interventional radiology trainees.

Dietary Fructose and Sodium Consumed during Early Mid-Life Are Associated with Hypertensive End-Organ Damage by Late Mid-Life in the CARDIA Cohort.

We aimed to investigate how dietary fructose and sodium impact blood pressure and risk of hypertensive target organ damage 10 years later. Data from n = 3116 individuals were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Four groups were identified based on the four possible combinations of the lower and upper 50th percentile for sodium (in mg) and fructose (expressed as percent of total daily calories). Differences among groups were ascertained and logistic regression analyses were used to assess the risk of hypertensive target organ damage (diastolic dysfunction, coronary calcification and albuminuria). Individuals in the low-fructose + low-sodium group were found to have lower SBP compared to those in the low-fructose + high-sodium and high-fructose + high-sodium groups (p < 0.05). The highest risk for hypertensive target organ damage was found for albuminuria only in the high-fructose + high-sodium group (OR = 3.328, p = 0.006) while female sex was protective across all groups against coronary calcification. Our findings highlight that sodium alone may not be the culprit for hypertension and hypertensive target organ damage, but rather when combined with an increased intake of dietary fructose, especially in middle-aged individuals.

Process Intensification of the Continuous Synthesis of Bio-Derived Monomers for Sustainable Coatings Using a Taylor Vortex Flow Reactor.

We describe the optimization and scale-up of two consecutive reaction steps in the synthesis of bio-derived alkoxybutenolide monomers that have been reported as potential replacements for acrylate-based coatings (Sci. Adv.2020, 6, eabe0026). These monomers are synthesized by (i) oxidation of furfural with photogenerated singlet oxygen followed by (ii) thermal condensation of the desired 5-hydroxyfuranone intermediate product with an alcohol, a step which until now has involved a lengthy batch reaction. The two steps have been successfully telescoped into a single kilogram-scale process without any need to isolate the 5-hydroxyfuranone between the steps. Our process development involved FTIR reaction monitoring, FTIR data analysis via 2D visualization, and two different photoreactors: (i) a semicontinuous photoreactor based on a modified rotary evaporator, where FTIR and 2D correlation spectroscopy (2D-COS) revealed the loss of the methyl formate coproduct, and (ii) our fully continuous Taylor Vortex photoreactor, which enhanced the mass transfer and permitted the use of near-stoichiometric equivalents of O2. The use of in-line FTIR monitoring and modeling greatly accelerated process optimization in the Vortex reactor. This led to scale-up of the photo-oxidation in 85% yield with a projected productivity of 1.3 kg day-1 and a space-time yield of 0.06 mol day-1 mL-1. Higher productivities could be achieved while sacrificing yield (e.g., 4 kg day-1 at 40% yield). The use of superheated methanol at 200 °C in a pressurized thermal flow reactor accelerated the second step, the thermal condensation of 5-hydroxyfuranone, from a 20 h batch reflux reaction (0.5 L, 85 g) to a space time of <1 min in a reactor only 3 mL in volume operating with projected productivities of >700 g day-1. Proof of concept for telescoping the two steps was established with an overall two-step yield of 67%, producing a process with a projected productivity of 1.1 kg day-1 for the methoxybutenolide monomer without any purification of the 5-hydroxyfuranone intermediate.

The impact of access to financial services on mitigating COVID-19 mortality globally.

The COVID-19 pandemic has disproportionately affected different social and demographic groups, deepening the negative health implications of social and economic inequalities and highlighting the importance of social determinants of health. Despite a deep literature on pandemic-related disparities, specifically regarding social determinants and health outcomes, the influence of the accessibility of financial services on health outcomes during COVID-19 remains largely unexplored. Modeling (pre-omicron) COVID-19 mortality across 142 nations, we assess the impact of national-level usage and access to formal financial services. Two financial access indexes constructed through principal component analysis capture (1) usage of and access to formal financial tools and (2) reliance on alternative and informal financial tools. On average, nations with higher pre-pandemic use of and access to formal financial services had substantially lower population mortality risk from COVID-19, controlling for key population health, demographic, and socioeconomic covariates. The scale of effect is similar in magnitude-but opposite in direction-to major risk factors identified in previous literature, such as lung cancer, hypertension, and income inequality. Findings suggest that financial services deserve greater attention both in the public health literature related to COVID-19 and more broadly in policy discussions about fostering better public health overall.

Evaluating the Sensitivity of Different Molecular Techniques for Detecting Mycobacterium tuberculosis Complex in Patients with Pulmonary Infection.

This study aimed to evaluate the accuracy of detecting drug-resistant Mycobacterium tuberculosis complex (MTBC)-specific DNA in sputum specimens from 48 patients diagnosed with pulmonary tuberculosis. The presence of MTBC DNA in the specimens was validated using the GeneXpert MTB/RIF system and compared with a specific PCR assay targeting the IS6110 and the mtp40 gene sequence fragments. Additionally, the results obtained by multiplex PCR assays to detect the most frequently encountered rifampin, isoniazid, and ethambutol resistance-conferring mutations were matched with those obtained by GeneXpert and phenotypic culture-based drug susceptibility tests. Of the 48 sputum samples, 25 were positive for MTBC using the GeneXpert MTB/RIF test. Nevertheless, the IS6110 and mtp40 single-step PCR revealed the IS6110 in 27 of the 48 sputum samples, while the mtp40 gene fragment was found in only 17 of them. Furthermore, multiplex PCR assays detected drug-resistant conferring mutations in 21 (77.8%) of the 27 samples with confirmed MTBC DNA, 10 of which contained single drug-resistant conferring mutations towards ethambutol and two towards rifampin, and the remaining nine contained double-resistant mutations for ethambutol and rifampin. In contrast, only five sputum specimens (18.5%) contained drug-resistant MTBC isolates, and two contained mono-drug-resistant MTBC species toward ethambutol and rifampin, respectively, and the remaining three were designated as multi-drug resistant toward both drugs using GeneXpert and phenotypic culture-based drug susceptibility tests. Such discrepancies in the results emphasize the need to develop novel molecular tests that associate with phenotypic non-DNA-based assays to improve the detection of drug-resistant isolates in clinical specimens in future studies.

Relationship between the ABO blood group and Rhesus factors with COVID-19 susceptibility.

INTRODUCTION: The molecular research has raised copious hypotheses about different molecular effects on the variable expression of the current virus on the human body. The present prospective study aims to determine clinically as well as statistically, the relation between ABO blood groups and Rhesus (Rh) factor and the severity of the Covid-19 virus. RESEARCH DESIGN AND METHODS: We conducted a prospective, single-centered study at The Combined Military Hospital Lahore, Pakistan. Details of only those patients who exhibit COVID-19 symptoms were included. The odds ratios with a 95% confidence interval and the chi-square test of blood groups and Rhesus factor was also conducted individually with the severity of disease, outcomes, and respiratory symptoms. P-values less than 0.05 was considered significant. RESULTS: The chi-square test and odd ratio yielded no significant results when the covid-19 status was compared with the Rhesus factor (p-value > 0.05). However, the results were found to be significant when associations were run between Covid-19 status and all the blood groups (p-value < 0.05). CONCLUSION: According to the analytical results of the present study, protective nature of all the blood antigens (A, B, AB, none) was observed in patients presenting with Covid-19 symptoms of varying severity.