Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of Macrolide Antibiotics and Transport into the Interstitial Fluid: Comparison among Erythromycin, Clarithromycin, and Azithromycin

Recent research has found higher levels and longer total exposure of azithromycin, a macrolide antibiotic agent, in the interstitial fluid of the skin than in the plasma. This unique distribution is expected to contribute to its antimicrobial activity at the primary infection site. However, it remains unclear whether this characteristic distribution in the extracellular tissue space is common to macrolide antibiotics or if it is azithromycin-specific, with most macrolides largely localized intracellularly. In this study, we investigated pharmacokinetic characteristics of erythromycin and clarithromycin in the interstitial fluid of the skin of rats after intravenous drug administration, and compared the results with our previously reported results on azithromycin. Interstitial fluid samples were directly collected from a pore on the skin using a dissolving microneedle array. We found that the total macrolide concentrations in the interstitial fluid were significantly different among three macrolides. The rank order of the interstitial fluid-plasma concentration ratio was azithromycin (3.8 to 4.9) > clarithromycin (1.2 to 1.5) > erythromycin (0.27 to 0.39), and this ratio was stable after dosing, whereas higher drug levels in the skin tissue than in the plasma were observed for all three macrolides. Our results suggest that lower erythromycin concentrations in the interstitial fluid than in the plasma contributes to the emergence of bacterial resistance in the extracellular tissue space. Monitoring of total macrolide concentrations in interstitial fluid may provide valuable information regarding antimicrobial effects and the emergence of bacterial resistance for the development of an appropriate pharmacokinetics–pharmacodynamics-based dosing strategy.
Acute Effect of the Timing of Resistance Exercise and Nutrient Intake on Muscle Protein Breakdown

Background: Combining resistance exercise (RE) with nutrient intake stimulates muscle protein net balance. However, it is still unclear whether the optimal timing of nutrient intake is before or after RE, especially on muscle protein breakdown (MPB) for an augmented muscle anabolic response. The aim of this study was to investigate the effect of a substantial mixed meal (i.e., nutrient- and protein-dense whole foods) before or after RE, compared with RE without a meal on the acute response of MPB in a crossover-design study. Methods: Eight healthy young men performed three trials: (1) meal intake before RE (Pre), (2) meal intake after RE (Post), and (3) RE without meal intake (No). Plasma insulin and 3-methylhistidine (3-MH), an MPB marker, were measured. Results: Time course change in plasma insulin level after RE was significantly higher in the Post condition than in the Pre and No conditions. The area under the curve of 3-MH concentration was significantly lower in the Post condition than in the Pre and No conditions. Conclusions: These results suggest that a substantial mixed meal immediately after RE may effectively suppress MPB in the morning.
Study of Drilling Process by Cooling Compressed Air in Reinforced Polyether-Ether-Ketone

This study is focused on the application of a cooling compressed air system in drilling processes; this environmentally friendly technique allows removing material at very low temperatures, approximately up to −22 °C in the cutting area. The main goals are to find the most improve cutting conditions with less energy consumption, for the drilling of reinforced polyether-ether-ketone with glass fiber at 30% (PEEK-GF30) with cooling compressed air by a Ranque-Hilsch vortex tube, and to find a balance between environmental conditions and adequate process performance. Drilling tests were carried out on plates of PEEK-GF30 to analyze the influence of cutting parameters and environmental temperature (–22, 0 and 22 °C) on variables such as thrust forces, energy and material removed rate by the use of statistical methods; analysis of variance, analysis of means, response surface, and desirability function were employed to identify the optimum region that provides the most improved values of the aforementioned variables. Drill bit diameter was also analyzed to determine the quality of drilled holes. During the drilling processes, force signals were detected by a piezoelectric dynamometer connected to multichannel amplifier and a pyrometer was used to control the temperature. The diameters of the drilled holes were measured by a coordinate measuring machine. Cooling compressed air can be considered an adequate technique to improve the results from an environmental and efficient perspective; in particular, the maximum desirability function was found at a spindle speed of 7000 rpm, a feedrate of 1 mm/rev and a temperature close to −22 °C.
External Cephalic Version: ACOG Practice Bulletin Number 221.

In Reply: We thank the authors for their interest in our recent commentary in the July 2020 issue1 and for drawing attention to the effects of the coronavirus disease 2019 (COVID-19) pandemic on women with substance use disorders, unstable housing, and histories of incarceration. The populations referred to in our commentary were by no means meant to be an exhaustive list of populations disproportionately affected by the COVID-19 pandemic or preexisting inequities in our country. We continue to encourage readers to identify at-risk populations in their communities and similarly be proactive in promoting equity. As beautifully illustrated in the letter by Isquick et al, this recent public health crisis is an opportunity to create equity beyond short-term solutions to the immediate problems created by COVID-19. We have demonstrated that our health systems and society can change and adapt quickly in the midst of crisis. This is a call to action to carry this momentum forward as we reimagine and redesign our systems of health care delivery and the ways in which our society supports the most vulnerable among us. We join Isquick et al in advocating for just and creative solutions to the challenges many of our patients face daily, such as housing insecurity and the effects of systemic racism, that inevitably affect their health and well-being.
SARS‐CoV‐2 infection presenting as a febrile rash

The World Health Organization (WHO) has declared that Coronavirus disease 2019 (Covid-19) is a public health emergency of international concern as it continues to spread worldwide.1 After a median incubation period of 4 days, fever and cough are the two most common manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
3D-printed Surgical Training Model Based on Real Patient Situations for Dental Education

Background: Most simulation models used at university dental clinics are typodonts. Usually, models show idealized eugnathic situations, which are rarely encountered in everyday practice. The aim of this study was to use 3D printing technology to manufacture individualized surgical training models for root tip resection (apicoectomy) on the basis of real patient data and to compare their suitability for dental education against a commercial typodont model. Methods: The training model was designed using CAD/CAM (computer-aided design/computer-aided manufacturing) technology. The printer used to manufacture the models employed the PolyJet technique. Dental students, about one year before their final examinations, acted as test persons and evaluated the simulation models on a visual analogue scale (VAS) with four questions (Q1–Q4). Results: A training model for root tip resection was constructed and printed employing two different materials (hard and soft) to differentiate anatomical structures within the model. The exercise was rated by 35 participants for the typodont model and 33 students for the 3D-printed model. Wilcoxon rank sum tests were carried out to identify differences in the assessments of the two model types. The alternative hypothesis for each test was: “The rating for the typodont model is higher than that for the 3D-printed model”. As the p-values reveal, the alternative hypothesis has to be rejected in all cases. For both models, the gingiva mask was criticized. Conclusions: Individual 3D-printed surgical training models based on real patient data offer a realistic alternative to industrially manufactured typodont models. However, there is still room for improvement with respect to the gingiva mask for learning surgical incision and flap formation.
A phase 2 study of ATRA, arsenic trioxide, and gemtuzumab ozogamicin in patients with high-risk APL (SWOG 0535).

High-risk acute promyelocytic leukemia (APL) remains a therapeutic challenge, with higher associated rates of early mortality and relapse than standard-risk APL. All-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) is a well-established treatment for patients with standard-risk APL, but it is not well defined for those with high-risk APL. In a prior study of patients with high-risk APL, the addition of gemtuzumab ozogamicin (GO) to ATO plus ATRA suggested benefit. The SWOG Cancer Research Network conducted a phase 2 study to confirm the efficacy and safety of the combination of ATRA plus ATO plus GO in treating high-risk APL patients. The primary end points were 3-year event-free survival (EFS) and early (6-week) death rates associated with this combination. Seventy patients were treated. With a median follow-up of 3.4 years, the 3-year EFS and overall survival estimates were 78% (95% confidence interval [CI], 67%-86%) and 86% (95% CI, 75%-92%), respectively. Overall, 86% of patients achieved complete response. The 6-week mortality rate was 11%. The most common treatment-emergent toxicities during the induction phase included febrile neutropenia, aspartate aminotransferase/alanine aminotransferase elevation, hyperglycemia, hypoxia, headache, and prolonged QT interval corrected for heart rate. Retinoic acid syndrome occurred in 9% of patients. Approximately 37% of patients did not complete all planned courses of postremission therapy. The combination of ATRA plus ATO plus GO in high-risk APL patients was effective and generally well tolerated, suggesting an opportunity to offer a chemotherapy-free induction platform for patients with this disease. This trial was registered at www.clinicaltrials. gov as #NCT00551460.
Application of polyetheretherketone cages through minimally invasive oblique retroperitoneal approach for the treatment of lumbar polymicrobial spondylodiscitis

Abstract Despite the plethora of evidence in support of the use of structural osseous autograft in lumbar spondylodiscitis, attention has recently been turned to the addition of synthetic materials such as polyetheretherketone (PEEK) to restore anterior vertebral column support. From January 2015 to April 2017, 7 patients with lumbar polymicrobial spondylodiscitis were surgically treated with a minimally invasive oblique retroperitoneal approach to the infected focus. The patients underwent a standard lateral minimally invasive oblique retroperitoneal approach using direct lateral interbody fusion system. The PEEK cages were loaded with autologous bone graft. All the patients underwent posterior fixation with percutaneous pedicle screw instrumentation. Lumbar function was measured using Oswestry Disability Index, and pain was measured with visual analog scale. Fusion and subsidence were also recorded. The study included 5 female and 2 male patients. The median age was 58.9 years. The duration of follow-up was 31.8 ± 6.1 months (range: 24–47). All patients recovered from the infection without relapse within 24-month follow-up. Visual analog scale significantly declined from 7.57 ± 0.53 before surgery to 1.57 ± 0.53 at 12-month follow-up. Mean Oswestry Disability Index decreased from 72.14 ± 6.82 before surgery to 22.28 ± 2.13 after surgery. All patients had solid fusion at 2-year follow-up. Fusion occurred at 6 to 15 months (mean 9.8 months). The specific use of PEEK cages in lumbar polymicrobial spondylodiscitis suggests reliable outcome in terms of clinical and imaging outcomes in our limited cases.
Resistance Mechanisms towards CD38−Directed Antibody Therapy in Multiple Myeloma

Antibodies targeting CD38 are rapidly changing the treatment landscape of multiple myeloma (MM). CD38−directed antibodies have several mechanisms of action. Fc−dependent immune effector mechanisms include complement-dependent cytotoxicity (CDC), antibody−dependent cell−mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and apoptosis. In addition, direct effects and immunomodulatory effects contribute to the efficacy of CD38−directed antibodies. Daratumumab, the first−in−class anti−CD38 monoclonal antibody, is now part of standard treatment regimens of both newly diagnosed as well as relapsed/refractory MM patients. The FDA has recently approved isatuximab in combination with pomalidomide and dexamethasone for relapsed/refractory MM patients after at least two prior therapies. Further, the other CD38−targeting antibodies (i.e., MOR202 and TAK-079) are increasingly used in clinical trials. The shift to front-line treatment of daratumumab will lead to an increase in patients refractory to CD38 antibody therapy already after first−line treatment. Therefore, it is important to gain insight into the mechanisms of resistance to CD38−targeting antibodies in MM, and to develop strategies to overcome this resistance. In the current review, we will briefly describe the most important clinical data and mechanisms of action and will focus in depth on the current knowledge on mechanisms of resistance to CD38-targeting antibodies and potential strategies to overcome this.
Association of early viral lower respiratory infections and subsequent development of atopy, a systematic review and meta-analysis of cohort studies

Introduction Existing evidence on the relationship between childhood lower respiratory tract infections (LRTI) and the subsequent atopy development is controversial. We aimed to investigate an association between viral LRTI at <5 years and the development of atopy at > 2 years. Methods We conducted a search at Embase, Pubmed, Web of Science, and Global Index Medicus. We collected data from the included articles. We estimated the odds ratio and the 95% confidence intervals with a random effect model. We determined factors associated with atopy development after childhood LRTI using univariate and multivariate meta-regression analyses. We recorded this systematic review at PROSPERO with the number CRD42018116955. Results We included 24 studies. There was no relationship between viral LRTI at <5 years and skin prick test-diagnosed-atopy (OR = 1.2, [95% CI = 0.7–2.0]), unknown diagnosed-atopy (OR = 0.7, [95% CI = 0.4–1.3]), atopic dermatitis (OR = 1.2, [95% CI = 0.9–1.6]), hyperreactivity to pollen (OR = 0.8, [95% CI = 0.3–2.7]), food (OR = 0.8, [95% CI = 0.3–2.5]), or house dust mite (OR = 1.1, [95% CI = 0.6–2.2]). Although not confirmed in all studies with a symmetric distribution of the 23 confounding factors investigated, the overall analyses showed that there was a relationship between childhood viral LRTI at < 5 years and serum test diagnosed-atopy (OR = 2.0, [95% CI = 1.0–4.1]), allergic rhinoconjunctivitis (OR = 1.7, [95% CI = 1.1–2.9]), hyperreactivity diagnosed by serum tests with food (OR = 5.3, [1.7–16.7]) or inhaled allergens (OR = 4.2, [95% CI = 2.1–8.5]), or furred animals (OR = 0.6, [95% CI = 0.5–0.9]). Conclusion These results suggest that there is no association between viral LRTI at < 5 years and the majority of categories of atopy studied during this work. These results, however, are not confirmed for the remaining categories of atopy and more particularly those diagnosed by serum tests. There is a real need to develop more accurate atopy diagnostic tools.
Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks: A Pooled Exposure-response Analysis of 14 Case-control Studies.

RATIONALE AND OBJECTIVES We expanded upon a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including 3 additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust, characterized by elemental carbon (EC) concentrations. METHODS We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios (ORs) and 95% confidence intervals (CI) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life-tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men. RESULTS Our study included 16,901 cases and 20,965 controls. In men, exposure-response between EC and lung cancer was observed: ORs ranged from 1.09 (95% CI 1.00, 1.18) to 1.41 (95% CI 1.30, 1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC-lung cancer exposure-response was observed in men regardless of smoking history, including among never smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m3 were 3.0%, 0.99%, and, 0.04%, respectively, for both sexes combined. CONCLUSION We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.
The short-term efficacy of mud therapy for knee osteoarthritis

Abstract The objective of this review is to systematically evaluate the short-term efficacy of mud therapy in the treatment of knee osteoarthritis (KOA). Randomized controlled trials, in which treatment of KOA is mud therapy, were included by systematically searching the PubMed, Embase, and the Cochrane Library databases. According to inclusion criteria and searching method, 11 articles, containing a total of 1106 patients, were included in the study. Our results showed significant differences in visual analog scale pain score and Western Ontario and McMaster Universities Osteoarthritis Index (pain, stiffness, function). In addition, the heterogeneity of study included is lower (I2 < 25%). According to the results of this meta-analysis, mud therapy can effectively alleviate the pain and improve joint function for KOA.
Association of hepatocellular carcinoma with thiazolidinediones use

Abstract The study aimed to investigate the association between the risk of hepatocellular carcinoma and thiazolidinediones use among type 2 diabetic patients who had risk factors for hepatocellular carcinoma. A population-based case-control study was performed using the database of the Taiwan National Health Insurance Program. The cases consisted of 23580 type 2 diabetic subjects aged 20 to 84 years with newly diagnosed hepatocellular carcinoma between 2000 and 2011. The sex- and age-matched controls consisted of 23580 randomly selected type 2 diabetic subjects without hepatocellular carcinoma between 2000 and 2011. Ever use of thiazolidinediones was defined as subjects who had at least 1 prescription of thiazolidinediones before the index date. Never use of thiazolidinediones was defined as subjects who did not have a prescription of thiazolidinediones before the index date. The odds ratio and 95% confidence interval for the association between hepatocellular carcinoma and cumulative duration of thiazolidinediones use was measured by a multivariable logistic regression model. Among subjects with any 1 of the comorbidities including alcohol-related disease, cirrhosis, hepatitis B infection, hepatitis C infection, and other chronic hepatitis, a multivariable logistic regression model demonstrated that there was a negative association between hepatocellular carcinoma and every 1-year increase of cumulative duration of thiazolidinediones use (adjusted odds ratio 0.94, 95% confidence interval 0.92–0.97). There was a negative association in a duration-dependent manner between the risk of hepatocellular carcinoma and thiazolidinediones use among type 2 diabetic patients who had risk factors for hepatocellular carcinoma.
Beneficial Effects of Melatonin on Apolipoprotein-E Knockout Mice by Morphological and 18F-FDG PET/CT Assessments

Atherosclerosis represents one of the main risk factors for the development of cardiovascular diseases. Their etiologies have been studied in recent years in order to better define therapeutic targets for intervention and to identify diagnostic methods. Two different subtypes of macrophages, M1 and M2, have been described in physiological conditions. They can also be found in the atherosclerotic process, where they both have opposite roles in disease progression. Perivascular brown adipose tissue is also involved in inflammation and endothelial damage. In this work, we provide insights into the protective role of melatonin in the atherosclerotic process by morphological and 18F-FDG-PET/CT analyses. In particular, we examined the effects of melatonin on pathways that are linked to atherosclerosis development. We showed that melatonin, by suppressing M1 activity, reduced inflammation and directed macrophage polarization toward the M2 macrophage subtype. Moreover, melatonin preserved the activity of perivascular brown adipose tissue. In addition, 18F-FDG uptake is very high in mice treated with melatonin, confirming that other factors may alter 18F-FDG distribution. In conclusion, we showed that melatonin affects inflammatory pathways that have been linked to atherosclerosis, assessed the relationships of the 18F-FDG PET/CT parameters with macrophage markers and the production of their cytokines, which that have been defined by morphological evaluations.