Reflections from the Book of the Dead: Weighing the Impact of Epicardial Fat on Atrial Fibrillation Vulnerability T. Jared Bunch MDDepartment of Medicine, School of Medicine, University of Utah, Salt Lake City, UtahAddress for correspondence: T. Jared Bunch, M.D.University of Utah School of Medicine Department of Internal Medicine Division of Cardiovascular Medicine 30 North 1900 East, Room 4A100 Salt Lake City, UT 84132 Phone: 801-213-2387 E-mail: jared.bunch@hsc.utah.edu

BACKGROUND Although low voltage zones (LVZs) in the left atrium (LA) are seen as arrhythmogenic substrate in some patients with atrial fibrillation (AF), pathophysiologic factors responsible for LVZ formation remain unclear. OBJECTIVE To elucidate the anatomical relation between the LA and ascending aorta responsible for remodeling of the anterior LA wall. METHODS We assessed the relation between existence of LVZs on the anterior LA wall and measurements taken on 3-dimensional computed tomography images obtained from 102 patients who underwent AF ablation. RESULTS Twenty-nine patients (28%) had LVZs >1.0 cm2 on the LA wall at the LA-ascending aorta contact area (LVZ Group); no LVZs were seen in the other 73 patients (No LVZ Group). In the LVZ Group (vs. No LVZ Group), the aorta-LA angle was smaller (21.0±7.7° vs. 24.9±7.1°, P = 0.015), the aorta-left ventricle (LV) angle was greater (131.3±8.8° vs. 126.0±7.9°; P = 0.005), non-coronary cusp (NCC) diameter was greater (20.4±2.2 mm vs. 19.3±2.5 mm; P = 0.036), and the NCC was closer to the anterior LA wall (2.29±0.68 mm vs. 2.76±0.79 mm; P = 0.006). The aorta-LA angle correlated positively with patients’ body mass index (BMI) and negatively with body weight and BMI. CONCLUSION Deviation of the ascending aorta course and distention of the NCC appear to be related to the development of LA anterior wall LVZs at the LA-ascending aorta contact area. Mechanical pressure exerted by extracardiac structures on the LA along with limited thoracic space may contribute to the development of LVZs associated with AF.

Title: Making the Cut for Generator ReplacementsAuthors: Venkatesh Ravi, MD1; Jeremiah Wasserlauf, MD, MS1;1: Section of electrophysiology, Division of Cardiology, Department of Medicine, Rush University Medical Center, Chicago, USACorresponding author:Jeremiah Wasserlauf, MD, MSAssistant Professor of Medicine,Cardiac Electrophysiology, Department of Internal Medicine/Division of Cardiology,Rush University Medical Center.1717 W. Congress Parkway, Suite 345, Chicago, IL 60612Email: Jeremiah_wasserlauf@rush.eduFunding: NoneDisclosure: Dr. Jeremiah Wasserlauf has received consulting fees from Stryker. No other conflicts of interest to disclose.EditorialCardiac implantable electronic devices (CIED) have become a common treatment modality for cardiac arrhythmia with over 300,000 new implants every year in the United States. A growing number of patients will require device replacement procedures throughout their lifetime.1 In a registry of 1744 patients undergoing CIED replacement procedures, lead damage or dislodgement requiring revision was found to occur in 1% of patients without previously planned addition of leads.2 The resulting lead addition and extraction procedures give rise to added procedural time, risk of complications, prolonged hospitalization, and increased health care costs.2 Polyurethane and copolymer insulation materials are more susceptible to thermal damage when compared to silicone.3,4 Avoidance of lead damage during CIED replacement procedures has been a topic of increasing investigation, with studies evaluating differences between electrosurgical modes, power settings, blade orientation, and equipment manufacturers. Operators have the option to choose between standard electrocautery with non-insulated blades, and cautery with insulated blades (PEAK PlasmaBlade, Medtronic Inc., Minneapolis, MN, or Photonblade, Stryker, Kalamazoo, MI).Electrocautery operates by generating a high current density which results in resistive heating and thereby cuts or coagulates tissue. PlasmaBlade uses a proprietary power output waveform to deliver energy along the exposed edge of a thin, insulated electrode powered by a proprietary electrosurgical generator. Photonblade is an alternative insulated electrocautery blade that is compatible with a standard electrosurgical generator. In a retrospective study by Kypta et al, PlasmaBlade was associated with a lesser risk of lead damage and shorter procedure duration and hospital stay when compared with electrocautery and scissors.3 In an ex vivo animal tissue model using Photonblade, coagulation mode during cautery was associated with more damage than cut, and this effect was greatest when contact occurred using the active edge as opposed to the insulated flat side of the cautery blade, and when the lead insulation consisted of polyurethane or copolymer. Visible lead damage was found to be more common with PlasmaBlade when compared to Photonblade. 4In this edition of the Journal of Cardiovascular Electrophysiology , Ananwattanasuk et al performed a retrospective analysis of traditional electrocautery vs PlasmaBlade on lead parameters and complications following CIED generator replacement procedures.5 The study included 410 consecutive patients (840 leads) who underwent CIED replacement using conventional electrocautery (EC group) and 410 patients (824 leads) who underwent CIED replacement using PlasmaBlade (PK group). The power settings for the PK group were 6 in CUT mode and 8 in COAG mode. In the EC group, power output was set to 40 Watts for both CUT and COAG mode. CUT mode was used for tissue dissection and COAG was only used for hemostasis. The two groups had similar device systems and baseline characteristics. In comparison to the PK group, the EC group had a slightly lower proportion of silicone leads (78% vs 83%, p < 0.01) and a slightly higher proportion of polyurethane leads (19% vs 13%, p < 0.01). The study found no statistically significant difference in lead damage requiring lead revision between the EC group and PK group (0.6% vs 0.4%, p=0.5). There was no difference in procedural complications between the two groups (2.2% vs 1.2%, p = 0.28). There was no difference in lead sensing. There was a higher number of patients with a decrease in lead impedance in the PK group compared to the EC group (61.5% vs 52.1%, p < 0.01), and perhaps unexpectedly, more patients with an increase in lead impedance in the EC group compared to the PK group (46.8% vs 34.2%, p<0.01).On average, the change in pacing impedance changed less than 10% in both groups. A majority of leads in both groups were comprised of silicone which may have been a primary contributor to the low rate of lead damage observed. These findings contrast with the older retrospective study that found a lower risk of lead damage with PlasmaBlade compared to a historical control group where titanium scissors were used with conventional electrocautery for hemostasis. The difference observed in the prior study between groups, and the overall higher rates of lead damage in that study may have been related to the use of scissors or perhaps a greater proportion of leads with non-silicone insulation (lead insulation material was not reported). The present study by Ananwattanasuk et al contributes to the literature with a larger cohort of patients and contemporary operative technique.It is never too late to scrutinize the benefit of tools that have added costs as our procedural techniques evolve. The authors should be commended for rigorously collecting not only clinical outcomes but also electrical device parameters to assess for subclinical lead damage. Although generator replacements are short and less complex when compared to other EP procedures, the total cost of generator replacement procedures is estimated at several billion dollars yearly in the US alone.6 Leadless pacemakers and the evolution of modular systems are attractive and may solve some problems related to lead damage during generator replacements, or perhaps one day eliminate generator replacements altogether. However, with the current number of CIEDs in operation and the aging population, a growing number of patients will continue to require generator replacement procedures over the next several decades. The overall safety of generator replacement procedures has improved though advances such as avoidance of routine capsulectomy, antibiotic-impregnated pouches for appropriate candidates, and prolonged replacement intervals due to improved battery longevity. Through an unremitting focus on safety and cost-effectiveness, we will stay on the cutting edge of straightforward and complex procedures in the EP lab.References1. Greenspon AJ, Patel JD, Lau E, et al. 16-year trends in the infection burden for pacemakers and implantable cardioverter-defibrillators in the United States 1993 to 2008. J Am Coll Cardiol. 2011;58:1001-1006.2. Poole JE, Gleva MJ, Mela T, et al. Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures: results from the REPLACE registry.Circulation. 2010;122:1553-1561.3. Kypta A, Blessberger H, Saleh K, et al. An electrical plasma surgery tool for device replacement–retrospective evaluation of complications and economic evaluation of costs and resource use. Pacing Clin Electrophysiol. 2015;38:28-34.4. Wasserlauf J, Esheim T, Jarett NM, et al. Avoiding damage to transvenous leads-A comparison of electrocautery techniques and two insulated electrocautery blades. Pacing Clin Electrophysiol.2018;41:1593-1599.5. Ananwattanasuk T, Jame S, Bogun F, et al. Journal of Cardiovascular Electrophysiology. 2021.6. Hauser RG. The growing mismatch between patient longevity and the service life of implantable cardioverter-defibrillators. J Am Coll Cardiol. 2005;45:2022-2025.

Letter to the Editor, BJOG Exchange

William K. Reid, M.D.Hematology & Oncology 613 Greenwood Rd. Chapel Hill, N.C. 27514 Cellular: (615)405-5162 Email: wkrmd2017@gmail.comMonday, January 25, 2021Hypothesis: Mycotoxins Causing Amyotrophic Lateral SclerosisReviewer’s questions:1. Pattern of Cascade through the Neuroaxis in ALS2. Biomarkers for ALS & for MycotoxinsI. ALS Cascade Upper & Lower Motor Neurons :It is intriguing to relate the available data on neurotoxic mycotoxins with the clinical findings in ALS. ALS is a motor neuron disease with insidious, progressive weakness and muscle wasting. One of the essential clues to the diagnosis of ALS is the involvement of both upper and lower motor neuron disease. The diagnostic strategy presented by Statland et al 20151 defines upper motor neuron deficits with spasticity and hyperreflexia and lower motor neuron disease with muscle wasting, weakness, fasciculations, fibrillations and positive sharp waves. In ALS there is a mixture of both upper and lower motor neuron deficits. The pathology of the neurotoxic mycotoxins, especially the trichothecenes(Dai, C. et al 20192), closely mimics the pathology of ALS with oxidative stress, mitochondrial dysfunction and respiratory chain damage.Intranasal Pathways Bypass of Blood Brain Barrier & CSF :The trichothecenes, T-2 Toxin and Deoxynivalenol, are major contaminants of the world food supply. If the opportunistic fungi responsible for these secondary metabolites develop a niche in the body by colonization or infection, these potent, lipophilic mycotoxins are able to cross barriers, especially the blood brain barrier and accumulate in the brain and spinal cord. Marcesca, M. 20133 reports on of transport of food-associated trichothecenes from the gut to the brain.There is a more intriguing possibility if there is a focus of a fungal infection in the upper airway, especially the upper sinus cavity. There is a growing body of research documenting intranasal delivery of compounds and drugs to the brain and spinal cord. Thorne, R.G. et al 2004 4report on transport of IGF-1 in the nose of rats. Thorne, R.G. et al 20085 report on transfer of interferon-beta in a monkey’s nose to brain. There are extensive studies documenting intranasal absorption of insulin in the objective of replacing injection requirements. Lochhead, J.J. et al 20196 found insulin had neuroprotective effects traveling along the trigeminal nerve. Avgerinos, K.L. et al 20187 found intranasal insulin in 293 patients improved memory in patients with Alzheimer’s or mild cognitive deficits. Intranasal glucagon was effective in adults with type 1 diabetes and insulin-induced hypoglycemia (Rickels, M.R. et al 20168). What these studies discovered are pathways bypassing the blood brain barrier as well as the CSF.Pardridge, W.M. in 20119 and 201210UCLA pointed out misconceptions surrounding drug and compound levels in the CSF, blood and brain. His studies showed that CSF drug levels were the same as systemic blood levels and were not equivalent to brain or spinal cord levels. Over the past 10 years the literature has defined two intranasal pathways that bypass both the CSF and the blood brain barrier.The upper sinus cavity is lined by olfactory mucosa that has direct passage of olfactory nerve endings exposed to the external environment. There is a second lining of respiratory mucosa fed by the ophthalmic and maxillary branches trigeminal nerve. Djupesland, P.G. et al 201411 describes the delivery of drugs from the nasal cavity directly into the brain. Passage is rapid in 5 minutes to 60 minutes passing by convective or bulk flow. Drugs bypass the blood brain barrier and the CSF.The olfactory pathway passes compounds of significant size into the olfactory bulb. The drugs move outside of the neurons with movement by pulsatile flow extracellular pathways. The trigeminal pathways from nasal cavity to brain moves to the midbrain, pons and the lower motor neurons of the spinal cord. The olfactory pathway feeds into the limbic system and forebrain.If there is an infection of the upper nasal cavity involving opportunistic fungi, such as Fusarium species that release lipophilic, neurotoxic mycotoxins, it could poison the brain and spinal cord in an insidious fashion. The pathway from the olfactory bulb to the upper brain would involve the upper motor neurons. The pathway from the trigeminal nerve branches would transport drugs to the brainstem and lower motor neurons (Djupesland, P.G. et al 201411, Lochhead, J.J. et al 201512, Ganger, S. & Schindowski, J. 201813). There are studies of giving chemotherapy intranasally for glioblastoma multiforme (Bruinsmann, F.A. et al 201914, van Woensel, M. et al 201315).Pseudobulbar Affect :Intranasal passage of neurotoxins into the brain and spinal cord would explain the dual injury to upper and lower motor neurons. The olfactory intranasal pathway leads to the olfactory bulb and limbic system. This pathway could help to explain pseudobulbar affect. Thakore, N.J. & Pioro, E.P. 201716 in Cleveland reported on pseudobulbar affect found in 209 out of 735 ALS patients. They found an association with bulbar onset and dysfunction with predominantly upper motor neuron disease. The ALS patients with pseudobulbar affect were younger in age with a shorter duration of disease. They found an association with worse bulbar findings, dysarthria and dysphagia. There was an association with the use of Baclofen, a surrogate for upper motor neuron dysfunction.Misconceptions of Blood Brain Barrier & CSF :Pardridge 20119 and 201210, report on the literature before 2011 with the misconceptions about CSF drug and metabolite levels. The intranasal passage of drugs and metabolites to the brain did not feed into the CSF. This leads to misconceptions when studies assume CSF levels are equivalent to brain and spinal cord levels. In order to get accurate brain levels requires Intracerebral Microdialysis, PET scans or functional MRI (Chefer, V.I. et al 200917, Lasley, S.M. 201918).

Background: The sustainability of the results of mitraclip procedures is a source of concern. Aims: To investigate risk factors of severe mitral regurgitation (MR) recurrence after Mitraclip in primary MR. Methods and results: Eighty-three patients undergoing successful Mitraclip procedures were retrospectively included. Valve anatomy and Mitraclips placement were comprehensively analyzed by post-processing 3D echocardiographic acquisition. The primary composite endpoint was the recurrence of severe MR. Mean age was 83±7 years-old, 37 (44%) were female. Median follow-up was 381 days (IQR 195-717) and 17 (20%) patients reached the primary endpoint. Main causes of recurrence of severe MR were relapse of a prolapse (64%) and single leaflet detachment (23%). Posterior coaptation line length (HR 1.06 95%CI 1.01-1.12 p=0.02), poor imaging quality (HR 3.84, 95%CI1.12-13.19; p=0.03), and inter-clip distance (HR 1.60, 95%CI 1.27-2.02; p<0.01) were associated with the occurrence of the primary endpoint. Conclusions: Recurrence of severe MR after a MitraClip procedure for primary MR is common and results from a complex interplay between anatomical (tissue excess) and procedural criteria (quality of ultrasound guidance and MitraClips spacing).

We study the asymptotic behaviors of the semigroup generated by the linearized Landau operator in the case of the very soft potentials and Coulomb potential. Compared with the hard potentials, Maxwellian molecules and moderately soft potentials, there is no spectral gap for the linearized Landau operator with the very soft and Coulomb potentials. By introducing a new decomposition of the linear Landau collision operator $L$ including an accretive operator and a relatively compact operator, we establish the complete spectrum structure for the linearized Landau operator with the very soft and Coulomb potentials and furthermore derive the time decay estimates of the corresponding semigroup in a weighted velocity space.

Background: lymphomas arising in cardiac myxomas represent a particularly rare pathology, with only few cases reported in the literature. Case presentation: we report a completely exeresis of malignant lymphoma arising in a cardiac myxoma in a 44 years-old female patient. The myxoma presented like a floating mass within the left atrium with a maximum diameter of 3.5 cm. The clinical post-operative period was uneventful and the patient was dismissed on sixth post-operative day. Conclusions: This case reinforces the concept of a radical exeresis of cardiac neoplasms

Comparisons of microsatellite and single-nucleotide polymorphisms (SNPs) have found that SNPs outperform microsatellites in population genetic analyses, calling into the question the continued utility of microsatellites in population and landscape genetics. Yet highly polymorphic markers may be of value in species that have reduced genetic variation. This study repeated analyses previously done using microsatellites with SNPs developed from ddRAD sequencing in the black-capped vireo source-sink system. SNPs provided greater resolution of genetic diversity, population differentiation, and migrant detection but could not reconstruct parentage relationships due to insufficient heterozygosities. The biological inferences made by both sets of markers were similar: asymmetrical gene flow from source populations to the remaining sink populations. With the landscape genetic analyses, we found different results between the two molecular markers, but associations of the top environmental features (riparian, open habitat, agriculture, and human development) with dispersal estimates were shared between marker types. Despite the higher precision of SNPs, we find that microsatellites effectively uncover population processes and patterns and are superior for parentage analyses in this species with reduced genetic diversity. This study illustrates the continued applicability and relevance of microsatellites in population genetic research.

The first-order relativistic corrections to the non-relativistic energies of hydrogen-like atom embedded in plasma screening environments are calculated in the framework of direct perturbation theory by using the generalized pseudospectral method. The standard Debye-Hückel potential, exponential cosine screened Coulomb potential, and Hulthén potential are employed to model different screening conditions and their effects on the eigenenergies of hydrogen-like atoms are investigated. The relativistic corrections which include the relativistic mass correction, Darwin term, and the spin-orbit coupling term for both the ground and excited states are reported as functions of screening parameters. Comparison with previous theoretical predictions shows that both the relativistic mass correction and spin-orbit coupling obtained in this work are in good agreement with previous estimations, while significant discrepancy and even opposite trend is found for the Darwin term. The overall relativistic-corrected system energies predicted in this work, however, are in good agreement with the fully relativistic calculations available in the literature. We finally present the scaling law of the first-order relativistic corrections and discuss the validity of the direct perturbation theory with respect to both the nuclear charge and the screening parameter.

1. IntroductionTropical mountainous ecosystems are recognized as providers of valuable ecological and hydrological services (Viviroli et al, 2007). In Central America, the Páramo, a high‐elevation tropical grassland ecosystem, extends over ~ 200 km2 in Costa Rica and Panama, with ~50% of this area located within the Chirripó National Park between 3,100 and 3,820 m asl (-83.49°, 9.46°). Vegetation mostly consists of 0.5 to 2.5 m tall bamboo dominated (Chusquea subtessellata ) grasslands, covering up to 60% of the total Páramo area in Costa Rica (Fig.1a). The climate is controlled by the northeast trade winds, the latitudinal migration of the Intertropical Convergence Zone (ITCZ), cold continental outbreaks (i.e., northerly winds), and the seasonal influence of Caribbean cyclones. These circulation patterns produce two rainfall maxima on the Pacific slope, one in June and one in September, which are interrupted by a relative minimum between July-August, known as the Mid-Summer Drought, due to intensification of trade winds over the Caribbean Sea (Magaña et al., 1999; Waylen, 1996). The wettest season extends from May to November (contributing up to 89% of the annual precipitation), whereas the driest season is from December to April (Fig. 2a; Esquivel-Hernández et al., 2018). The surface water system of Chirripó is characterized by a lake district which comprises approximately 30 lakes of glacial origin and streams flowing down the Caribbean and Pacific slopes (Fig 1b). Lake catchments are characterized by steep slopes that promote rapid hydrological responses such as fast water‐level changes. Input of water to these glacial lakes is mostly controlled by the seasonal inputs of rainfall, which mix up with stream and subsurface waters. In April 2015, the Chirripó Hydrological Research Site (CHRS) was installed with the goal of advancing the understanding of the hydrological functioning in the Central American Páramo using environmental tracers (i.e., water stable isotopes) in combination with hydrometric data. A detailed map of CHRS is available in Esquivel-Hernández et al. (2019).

Background Hypothyroxinemia, i.e. Low free T4 with normal TSH level, which overlaps, to a great extent, with the laboratory criteria of central hypothyroidism, could be easily neglected, if attention is paid only to patients with elevated TSH. We aimed to assess the association between mirtazapine use and hypothyroxinemia in patients affected by major depressive disorder. Methods We conducted a retrospective cohort study in the Second Affiliated Hospital of Xinxiang Medical University between January 2016 and December 2018. Patients affected by major depression disorder and admitted to the hospital for treatment during the study period and had thyroid tests at admission and after treatment were included. Patients with abnormal thyroid function at baseline or received mood stabilizers or quetiapine during hospitalization were excluded. Mirtazapine use was the exposure measure, and hypothyroxinemia was as the primary outcome of this study. Log-binomial model was used to estimate the association between mirtazapine use and hypothyroxinemia, after adjusting for potential confounding factors. Results A total of 220 eligible patients were included in the final analysis. Of them, 88 used mirtazapine. The incidence of hypothyroxinemia in patients who used mirtazapine was higher (37.5%) than those patients who did not use (19.7%). The relative risk of developing hypothyroxinemia was 1.64 (95% confidence interval: 1.31-1.78) for mirtazapine use, after adjusting for confounding factors. Conclusion Mirtazapine use was associated with the risk of developing hypothyroxinemia. Clinicians should be aware that hypothyroxinemia may be neglected in patients treated by mirtazapine due to attention paid only to those with elevated TSH.

Adaptive radiations offer an excellent opportunity to understand the eco-evolutionary dynamics of gut microbiota and host niche specialization. In a laboratory common garden, we compared the gut microbiota of two novel trophic specialists, a scale-eater and a molluscivore, to a set of four outgroup generalist populations from which this adaptive radiation originated. We predicted an adaptive and highly divergent microbiome composition in the specialists matching their rapid rates of craniofacial diversification in the past 10 kya. We measured gut lengths and sequenced 16S rRNA amplicons of gut microbiomes from lab-reared fish fed the same high protein diet for one month. In contrast to our predictions, gut microbiota largely reflected 5 Mya phylogenetic divergence times among generalist populations in support of phylosymbiosis. However, we did find significant enrichment of Burkholderiaceae bacteria in both lab-reared scale-eater populations. These bacteria sometimes digest collagen, the major component of fish scales, supporting an adaptive shift. We also found some enrichment of Rhodobacteraceae and Planctomycetacia in lab-reared molluscivore populations, but these bacteria target cellulose. Minor shifts in gut microbiota appear adaptive for scale-eating in this radiation, whereas overall microbiome composition was phylogenetically conserved. This contrasts with predictions of adaptive radiation theory and observations of rapid diversification in all other trophic traits in these hosts, including craniofacial morphology, foraging behavior, aggression, and gene expression, suggesting that microbiome divergence proceeds as a nonadaptive radiation.

Purpose Mammary Paget disease of the breast is rare form of breast cancer. Recent trends in the management have changed from mastectomy to breast conserving surgery, its safety is still controversial. The study aimed to predict the patients prone to local recurrence, and to find out the answer to the question of who should be a candidate for breast conserving surgery. Methods Between January 2007 and December 2017, 69 patients who underwent surgery and pathology report diagnosed as Paget’s disease, were analyzed retrospectively. As factors that may affect local recurrence; age, presence of nipple symptoms, mass detection in radiological imaging, type of the surgery, stage, pathological findings of the tumor (histological type, multicentricity, ER, PR, HER2, Ki 67 proliferative index, molecular subtype) were evaluated. Results Among 69 patients, 26 patients had ductal carcinoma in situ and others had invasive ductal carcinoma. Number of the patients underwent breast conserving surgery and mastectomy was 15 and 54 respectively. Patients were followed-up for a median time of 45 months. Recurrence was developed in 12 patients, half of them with local recurrence. Type of the surgery was the unique factor influencing local recurrence (p=0.001). Subgroup analysis was performed among patients undergoing breast conserving surgery, only Ki 67 proliferative index above 30 (p=0.002) was found to affect local recurrence. Conclusion Although the number of patients is small, it should be kept in mind that local recurrence may be high when BCS is performed in patients with the tumor’s Ki 67 proliferative index is above 30.

Objective: The aim of the present study is to study the correlation between urinary cortisol and melatonin metabolites and prostate cancer. Method: Patients with a histologically confirmed new prostate carcinoma with no previous malignancies have been included in the study as “cases.” Healthy individuals who applied to check-up and sleep disorder polyclinics were included as the healthy control group. Serum prostate-specific antigen (PSA), urinary melatonin sulfate, and cortisol levels in the first-morning spot urine samples were measured during the admission and diagnosis for all participants. Results: A total of 180 patients with a proven pathology of prostate adenocarcinoma and 240 healthy males participated in the study as the control group. When compared with the control group, significantly lower urinary melatonin sulfate levels (49.85±46.58) ng/mg vs. (64.25±66.75) ng/mg, p = 0.003) and significantly lower melatonin sulfate/cortisol (M/C) ratios (2.38 ± 3.20 vs. 5.28 ± 15.32, p <0.001) (respectively) levels were found in the patients. Subjects who had high M/C ratios and urinary melatonin-sulfate were less exposed to risk of prostate cancer at a statistically significant rate than those with lower urinary melatonin-sulfate or M/C ratios. We also discovered that subjects with a low M/C ratio and preoperative PSA levels above 10 ng/mL were 3.58 times more likely (95% CI = 1.58–8.12) to develop prostate cancer than those with a high M/C ratio and preoperative low PSA (<10 ng/mL). Conclusion: We concluded that there was association between lower morning melatonin sulfate levels or M/C ratio and the risk of prostate cancer. Moreover, patients who had both low PSA levels and M/C ratios higher than 10 ng/mL were much more exposed to advanced (end-stage) disease and prostate cancer.

Background: It’s known that prisoners have worse physical and mental health conditions. Objective: This study aims to determine the prevalence of DM in the selected Turkish prisons. Methods: In this cross-sectional study, 722 volunteer from a total of 4000 prisoners in Ankara Sincan Prison Campus between March and June 2013, were enrolled. Results: Mean FBG level of whole study population was 101±28mg/dL. The mean age and BMI of the prisoners with DM was significantly higher when compared to the non-diabetics. We found the prevalence of DM as 3.8%. Despite the presence of 252 (FBG≥100 mg/dL) prisoners with impaired FBG, we could perform OGTT only in 12 prisoners. Three of them were diagnosed with impaired glucose tolerance, and one was diagnosed with overt diabetes. Conclusions: It may be estimated that there must be 4990 (3.8%) diabetic patients including 525 (0.4%) newly diagnosed ones among in all Turkish prisons. In our study, the most important handicap for determining DM prevalence in prisons is the tendency of the prisoners to hide their disease.

Mask mandates have been a globally used epidemiologic intervention during the ongoing COVID-19 (coronavirus disease 2019) pandemic. Although there is extensive supporting literature on the use of facemask to reduce infection rates, its effect on the individual and course of disease has remained controversial. The purpose of this study was to find if mandatory masking influences the case fatality rate. This study used data on case updates, mask mandates, and demographic status related to the Kansas state, USA. The data were analyzed using a parallelization approach based on county-level data.The results showed that in Kansas during the summer of 2020, the counties with mask mandate had significantly higher case fatality rates compared to counties without mask mandate, with a risk ratio of 1.85 [1.51-2.10] for death with COVID-19.Even after adjusting for the number of ‘protected persons’, i.e., the number of persons who were not infected in the mask-mandated group compared to the no-mask group, the risk ratio remained significantly high at 1.52 [1.24-1.72]. By analyzing the excess mortality in Kansas, this study determines that over 95% of this effect can solely be attributed to COVID-19. The cause of this trend and the possible connection between long-term effects associated with SARS-CoV-2 and facemasks are explained in the theory herein by the 'foegen effect'; i.e., deep reinhalation of pure virions caught in the facemasks as droplets can worsen the prognosis. This finding suggests that the use of facemasks in COVID-19 pandemic did contribute to an increase in the death toll counterintuitive of its purpose, making mask mandates a highly debatable epidemiologic intervention.

A 61-year-old female with 50000 ventricular premature contractions and reduced left ventricular ejection fraction of 35% referred to our center. Although the origin was considered to be originated from the junction between the left and right coronary cusp, a single radiofrequency application above the aortic sinus cusp could eliminate it.

Introduction: Studies about the reference values of the conventional and tissue Doppler echocardiography in African populations are limited. Objectives: The aim of this study is to evaluate the effect of aging and gender in left ventricular diastolic function assessed by conventional and tissue Doppler echocardiography in healthy Angolans. Methods: Cross-sectional study performed involving healthy participants aged between 18 and 85 years, attending in a diagnostic center in Luanda, Angola. Two-dimensional transthoracic echocardiography and Doppler study were performed according to the Guidelines of the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Results: A total of 103 men (47.5%) (mean age: 39,5±10,8) and 114 women (52,5%) (mean age: 43,0±12,5 years) were included. Compared to men, women were older (p=0,025) and showed significantly smaller body surface area (p<0,001). Mitral E velocity, and E/e’ ratio were significantly higher in women compared to men. While, DT of mitral E velocity was longer in men compared to women (p=0,041), E wave velocity and E/A ratio show a negative significant correlation with increasing age (r -0,33; P ≤ 0.001 and r -0,48; P ≤ 0.001, respectively). Conversely, A wave velocity shows a significant positive correlation with age (r 0,47; P < 0.001). Average e′ wave velocity shows a significant negative correlation with aging (r -0,40; P ≤ 0.0001). Conclusions: In healthy Angolan adult population, the parameters of left ventricular diastolic function deteriorated with age reflecting a normal aging process. This must be taken into account when assessing diastolic function at different age’s categories.

Catalytic CO2 reduction mediated by Ru-PNP pincer complexes has been studied using density functional theory (DFT). Calculations clearly reveal that modification of the PNP pincer framework by introducing planar conjugation in the backbone improves the catalytic efficiency. Activation strain model reveals that reduction of strain in the transition states with modified PNP framework associated with the insertion of CO2 molecule is responsible for lowering the activation barrier. Calculations also reveal that electron withdrawing substituents at the PNP ligand improves the catalytic performance.

Efforts to protect and restore tropical wetlands impacted by feral pigs (Sus scrofa) in northern Australia have more recently included exclusion fences, an abatement response proposing fences improve wetland condition by protecting habitat for fish production and water quality. Here we tested: 1) whether the fish assemblage are similar in wetlands with and without fences; and 2) whether specific environmental processes influence fish composition differently between fenced and unfenced wetlands. Twenty-one floodplain and riverine wetlands in the Archer River catchment (Queensland) were surveyed during post-wet (June-August) and late-dry season (November-December) in 2016, 2017 and 2018, using a fyke soaked overnight (~14-15hrs). A total of 6,353 fish representing twenty-six species from 15 families were captured. There were no multivariate differences in fish assemblages between seasons, years and for fenced and unfenced wetlands (PERMANOVA, Pseudo-F <0.58, P<0.68). Late-dry season fish were considerably smaller compared to post-wet season: a strategy presumably to maximise rapid disposal following rain. At each wetland a calibrated Hydrolab was deployed (between 2-4 days, with 20min logging) in the epilimnion (0.2m), and revealed distinct diel water quality cycling of temperature, dissolved oxygen and pH (conductivity represented freshwater wetlands) which was more obvious in the late-dry season survey, because of extreme summer conditions. Water quality varied among wetlands, in terms of the daily amplitude, and extent of daily photosynthesis recovery, which highlights the need to consider local site conditions rather than applying general assumptions around water quality conditions for these types of wetlands examined here. Though many fish access (fenced and unfenced) wetlands during wet season connection, the seasonal effect of reduced water level conditions seems to be more over-improvised compared to whether fences are installed or not, as wetlands supported few, juvenile, or no fish species because they had dried completed regardless of whether fences were present or not.

Aims: To optimize the dosing regimen in patients with severe renal impairment based on population pharmacokinetic/pharmacodynamic (PPK/PD) analysis. Methods: The pharmacokinetics and safety of nemonoxacin was evaluated in a single-dose, open-label, nonrandomized, parallel-group study after single oral dose of 0.5 g nemonoxacin capsule in 10 patients with severe renal impairment and 10 healthy controls. Both blood and urine samples were collected within 48 hours after admission and determined the concentrations. A PPK model was built using nonlinear mixed effects modelling. The probability of target attainment (PTA) and the cumulative fraction of response (CFR) against S. Pneumoniae and S. aureus was calculated by Monte Carlo simulation. Results: The data best fitted to a two-compartment model, from which the PPK parameters were estimated, including clearance (8.55 L/h), central compartment volume (80.8 L), and peripheral compartment volume (50.6 L). The accumulative urinary excretion was 23.4±6.5% in severe renal impairment patients and 66.1±16.8% in healthy controls. PPK/PD modeling and simulation of 4 dosage regimens found that nemonoxacin 0.5 g q48h was the optimal dosing regimen in severe renal impairment patients, evidenced by higher PTA (92.7%) and CFR (>99%) at nemonoxacin MIC ≤ 1 mg/L against S. pneumoniae and S. aureus. The alternative regimens (0.25 g q24h; loading dose 0.5 g on Day 1 followed by 0.25 g q24h) were insufficient to cover the pathogens even if MIC ≤ 0.5 mg/L. Conclusion: An extended dosing interval (0.5 g q48h) may be appropriate for optimal efficacy of nemonoxacin in case of severe renal impairment.

Background: Air pollution can be a risk factor for respiratory viral transmission and infection. The COVID-19 outbreak in 2020 may have affected ambient air pollution levels. Therefore, this study aimed to investigate air pollution levels and respiratory virus infection rates before and after the COVID-19 pandemic as well as determine relationships between these factors. Methods: The daily mean temperature and concentrations of air pollutants (PM2.5, PM10, O3, NO2, CO, and SO2) in five metropolitan cities in South Korea were collected for the months of February to May from 2015 to 2020. Results of 14 respiratory viruses isolated using polymerase chain reaction in children with upper or lower respiratory tract infections were gathered during the same period. Trends of respiratory virus infection, temperature, and air pollutant level from February to May for six years were evaluated and possible relationships between respiratory virus infections and ambient air pollutant levels were assessed. Results: Most air pollutants exhibited significantly decreasing trends in 2020 compared to the years before COVID-19. There were no differences in temperature. Adenovirus, bocavirus, metapneumovirus, parainfluenza virus 3, and rhinovirus were the most frequently detected viruses from February to May from 2015 to 2019, and infection rates dropped significantly in 2020. The concentration of ambient O3 was associated with rhinovirus infection in hospitalized children (aOR [95% CI], 1.028 [1.002, 1.055]). Conclusions: After the COVID-19 outbreak, ambient air pollution levels and respiratory virus transmission decreased in the pediatric population of South Korea.

Purpose: The aim of this study to investigate the effect of bromelain-arnica gel combination on periorbital edema and ecchymosis seen after open septorhinoplasty. Methods: Sixty patients who performed open septorhinoplasty with osteotomies were included to the study. These patients were allocated into two groups: in group 1, 30 patients as control and in group 2, 30 patients as study group who were treated with topical bromelain-arnica gel after surgery. Scoring of eyelid edema and peroirbital ecchymosis were evaluated on the first, third and seventh postoperative days using scale of 0 to 4 used by observers. Results: We observed that the administration of topical bromelain-arnica gel after surgery was effective clinically and statistically in decreasing the score of both edema and ecchymosis in open septorhinoplasty with ostetomies. In group 2 patients, periorbital edema and ecchymosis scores were significantly lower compared to control group (p < 0.05). Conclusions: Our results support that topical administration of bromelain and arnica gel combination provided both clinically and statistically significant reduction in periorbital edema and ecchymosis following septorhinoplasty.