Elevation of alkaline phosphatase (ALP) is reported to be an abnormal feature in TAFRO syndrome. However, the cause is unknown. Herein, we report a case of TAFRO syndrome showing intrahepatic cholangitis on autopsy, which may be the cause of ALP elevation in TAFRO syndrome.

This study focuses on a 10-m2 plot within a granitic hillslope in Cevennes mountainous area in France, in order to study infiltration and subsurface hydrological processes during heavy rainfalls and flash floods. The monitoring device included water content at several depths (0-70cm for the shallow soil water; 0-10m for the deep water) during both intense artificial and natural rainfall events, chemical and physical tracers, time-lapse electrical resistivity tomography. During the most intense events, the infiltrated water was estimated to be some hundreds of millimeters, which largely exceeds the topsoil capacity (≤40 cm deep in most of the cases). The weathered/fractured rock area below the soil clearly has an active role in the water storage and sub-surface flow dynamics. Vertical flow was dominant in the first 0-10m, and lateral flow was effective at 8-10 m depth, at the top of the saturated area. The speed of the vertical flow was estimated between 1 and 10 m/h, whereas it was estimated between 0.1 and 1 m/h for the lateral flow. The interpretation of the experiments led to a local pattern of the 2D-hydrological processes and profile properties. It suggests that fast triggering of floods at the catchment scale cannot be explained by a mass transfer within the hillslope, but should be due to a pressure wave propagation through the bedrock fractures, which allows exfiltration of the water downstream the hillslope.

Tree functional traits together with processes such as forest regeneration, growth, and mortality affect forest and tree structure. Forest management inherently impacts these processes. Moreover, forest structure, biodiversity, resilience, and carbon uptake can be sustained and enhanced with forest management activities. To assess structural complexity of individual trees, comprehensive and quantitative measures are needed, and they are often lacking for current forest management practices. Here, we utilized 3D information from individual Scots pine (Pinus sylvestris L.) trees obtained with terrestrial laser scanning (TLS) to first, assess effects of forest management on structural complexity of individual trees, and second, understand relationship between several tree attributes and structural complexity. We studied structural complexity of individual trees represented by a single scale independent metric called “box dimension”. This study aimed at identifying drivers affecting structural complexity of individual Scots pine trees in boreal forest conditions. The results showed that thinning increased structural complexity of individual Scots pine trees. Furthermore, we found a relationship between structural complexity and stem and crown size and shape as well as tree growth. Thus, it can be concluded that forest management affected structural complexity of individual Scots pine trees in managed boreal forests, and stem, crown, and growth attributes were identified as drivers of it.

Injury to epicardial coronary arteries following mitral valve replacement surgery, albeit rare, could have fatal complications. In this case, we suggest conservative medical treatment as a safe approach in patients who are not suitable to undergo revascularization.

This study presents a rare case of postoperative amyloidosis of the tongue base and provides a summary of the known literature of tongue amyloidosis. The diagnosis was by physical examination, radiological findings, and histopathological Congo red stain. Bone marrow biopsy the revealed “Plasma cell myeloma” as a cause.

In this paper, we investigate the existence and uniqueness of solutions and Ulam's type stabilities including the well-known Ulam-Hyers stability and the newly extended Ulam-Hyers' conformable exponential stability for two classes of fractional differential equations with the conformable fractional derivative and the time delay. The Banach contraction principle, the technique of Picard operator, the Gronwall integral inequalities and generalized iterated integral inequality in the sense of conformable fractional integral are the main tools for deriving our main results. Finally, several illustrative examples will be presented to demonstrate our work.

Aim: We aimed to evaluate the association of premature ejaculation with OSAS and to assess the effects of continuous positive airway pressure (CPAP) therapy on premature ejaculation. Methods: Sexually active men between the ages of 20-50 who were newly diagnosed with PE, and diagnosed with OSAS were included in the study. Arabic Premature Ejaculation Index (AIPE) and Intravaginal Ejection Delay Time (IELT) were questioned for the diagnosis of PE. Patients with OSAS who accepted to participate in the study were given one year CPAP treatment, and AIPE and IELT were questioned again, after the treatment. Results: Epworth score was significantly lower in the control group compared with the OSAS groups. In the beginning, IELT and AIPE scores were significantly higher in the control group compared with the OSAS groups. At the end of the treatment, in both OSAS groups, both sores improved. Conclusion: For the first time in literature we determined that the presence of OSAS was associated with significantly worse IELT and AIPE scores in males with PE, and the treatment of OSAS was related to the significant improvement in both scores, in the absence of any specific treatments for PE. -What’s already known? -The pathology of OSAS depends on repeated episodes of hypoxia during sleep that may result in cyclic changes in arterial oxygen saturation and increased production of reactive oxygen species. Higher prevalence of sexual dysfunction and erectile dysfunction was reported in OSAS patients. -What does this article add? -To the best of our knowledge first time in the literature we determined that the presence of OSAS was associated with significantly worse IELT and AIPE scores in males with PE, and the treatment of OSAS was related to the significant improvement in both scores, in the absence of any specific treatments for PE

The diploid Poropuntius huangchuchieni in the cyprinid family, which is widely distributed in the Mekong and Red River basins, is one of the most closely related diploid progenitor-like species of allotetraploid common carp, which was generated by merging of two diploid genomes during evolution. Therefore, the P. huangchuchieni genome is essential for polyploidy evolution studies in Cyprinidae. Here, we report a high-quality chromosome-level genome assembly of P. huangchuchieni by integrating Oxford Nanopore and Hi-C technology. The assembled genome size was 1021.38 Mb, 895.66 Mb of which was anchored onto 25 chromosomes with a N50 of 32.93 Mb. The genome contained 486.28 Mb repetitive elements and 24,099 protein-coding genes. Approximately 95.9% of the complete BUSCOs were detected, suggesting a high completeness of the genome. Evolutionary analysis revealed that P. huangchuchieni diverged from Cyprinus carpio at approximately 12 Mya. Genome comparison between P. huangchuchieni and the B subgenome of C. carpio provided insights into chromosomal rearrangements during the allotetraploid speciation. With the complete gene set, 17,474 orthologous genes were identified between P. huangchuchieni and C. carpio, providing a broad view of the gene component in the allotetraploid genome, which is critical for future genetic analyses. The high-quality genomic dataset created for P. huangchuchieni provides a diploid progenitor-like reference for the evolution and adaptation of allotetraploid carps.

IImmunodeficiency and hyperinflammation characterize COVID-19 associated states; thus, repurposing of multiple cytokine and/or anti-cytokine drugs currently being used in other therapeutic areas has been suggested as a potential therapeutic strategy in COVID-19 patients. Clinical trials involving these drugs target the most frequent and life-threatening peripheral consequences of the disease, mainly focusing on lung, heart, and coagulation functions; however, a growing number of reports describe a wide range of COVID-associated neurological manifestations (altogether defined as neuro-COVID) including anosmia, seizures, confusion, stroke, encephalopathy, and paralysis. Notably, the underlying pathophysiological mechanisms for neuro-COVID may also include dysregulation of cytokines/chemokines, deficiencies in the innate immune response, and autoimmunity. This suggests that therapeutic attempts with drugs targeting cytokine-mediated inflammation in peripheral organs could also positively affect neuro-COVID manifestations. As a matter of fact, some of these drugs have also been scrutinized for their potential efficacy in treating neuroinflammatory diseases such as optic neuromyelitis, epilepsy, stroke, and traumatic brain injury, among others. On the other hand, anti-cytokine drugs, by impairing relevant physiological activities exerted by these mediators in the CNS, may also be endowed with significant neurological risk. Therefore, the primary aim of the present manuscript is to review the available preclinical and clinical data regarding the neurological effects of the drugs targeting cytokine-mediated inflammation, in order to raise awareness about their potentially beneficial or detrimental neurological consequences when used to treat COVID-19 patients.

We present prolonged viral shedding in an immunocompromised HIV patient with a literature review of risk factors for prolonged viral shedding and its implications for isolation strategies. We explore the role of PCR-CT-value (cycle threshold) as an instrument for guiding isolation policies and the impact of HIV on Covid-19.

A man aged 60’s suffered nephrotic syndrome with IgM nephropathy seven years earlier. Four years later, immune-checkpoint inhibitors (ICPIs) were administered against metastasizing pulmonary adenocarcinoma. Sixty-two weeks after 21 ICPIs injections, the cancer vanished but nephrotic syndrome relapsed. Acute pancreatitis followed and usual interstitial pneumonia exacerbated, as late-onset immune-related adverse-events.

We present a case of Systemic capillary leak syndrome in a patient who underwent surgery for colon cancer perforating peritonitis. We treated the patient with plasma filtration with dialysis.

1.Ectomycorrhizal (ECM) roots are evolutionary strategies of plants for effective nutrient uptake under varying abiotic conditions. Formation and morphological differentiations of ECM roots are important strategies in foraging environments. However, little is known on how such strategies mediate the nutrients of the below- and aboveground tissues and the balances among nutrient elements across environmental gradients. 2.We studied the function of ECM symbiosis in Abies faxoniana across its distributional range in Southwest China. The effects of differential ECM strategies, i.e. the contact exploration type, the short-distance exploration type, and the medium-distance exploration type, and root tips functional traits, etc., on root and foliar N and P and N:P ratio were examined across natural environmental gradients. 3.The ECM symbionts preferentially facilitated P uptake in A. faxoniana under both N and P limitations. The uptakes of N and P were primarily promoted by the effectiveness of ECM roots, e.g. ECM root tips per unit biomass, superficial area of ECM root tips, the ratio of living and dead root tips, but negatively related to the ECM proliferations and morphological differentiations. Generally, plant N and P nutrients were always promoted by the contact exploration type, while negatively affected by the short-distance exploration type in A. faxoniana. Root and foliar N and P nutrients were expected to be affected by the medium-distance exploration type in dynamics. Especially, root P limitation could be relieved when the frequency of medium-distance exploration type up to c.15%, whilst root N limitation was strengthen when the frequency of medium-distance exploration type over 20%. 4.We suggest that both below- and above-ground nutritional traits of host tree species could be strongly affected by ECM symbiosis in natural environments. The ECM strategies responding to environmental conditions significantly affect the plant nutrient uptakes and trade-offs. ECM soil exploration types are the great supplementary mechanisms for plant nutrient uptake.

The sinoatrial node in medication-resistant inappropriate sinus tachycardia: to modify or to ablate?Khalil El Gharib1*1Hôtel-Dieu de France, Beirut, Lebanon*Author for correspondence: [email protected]: IST, sinus node modification, sinus node ablation, radiofrequency ablation, surgical ablationNo conflict of interest to discloseFunding: noneInappropriate sinus tachycardia (IST) is defined as a resting heart rate >100 beats per minute (with a mean heart rate >90 beats per minute over 24 hours) associated with highly symptomatic palpitations(1). The syndrome is associated neither with structural heart disease nor with any secondary cause of sinus tachycardia(2) and evidence suggests that enhanced intrinsic automaticity of the sinoatrial node, which can be due to anti-β-adrenergic antibodies, is behind its genesis(3). However, it is benign in terms of clinical outcomes and echocardiographic evidence of ventricular dysfunction(4), being rarely associated with tachycardia-induced cardiomyopathy(3).Patients with IST are essentially treated with ß-blockers to alleviate their symptoms(5). Ivabradine, a drug that inhibits funny calcium channels, particularly abundant in the SA node, showed modest benefit, receiving class IIa recommen­dation in the treatment of IST(4). But, the duration of medical therapy might be indefinite, and, a considerable number of patients would respond inadequately, or have no response, even after prolonged therapy(5). Historically, such patients would have subtotal right atrial excision, atrioventricular junctional ablation with permanent pacemaker implantation, or chemical occlusion of the sinus node artery(6). These options are considered today unacceptable in this setting, and other therapeutic approaches should be unveiled when resistance to medical treatment appears.Electrophysiological study was initially purely diagnostic, but recent advances in technology have allowed us to intervene(7); patients with ventricular and supraventricular tachyarrhythmias are successfully treated with percutaneous catheter procedures. Of these, SA node ablation/ modification has been proposed as alternative approaches in IST that is not responding to medical treatment; trials reported auspicious results, highlighted here.Electrophysiologic mapping to the site of the earliest endocardial activation during either spontaneous sinus tachycardia or isoproterenol-induced sinus tachycardia has rendered these procedures feasible(8). Additionally, combination with intracardiac echocardiography permitted a more accurate electrophysiologic and anatomic localization of the sinoatrial node(9).Sinus node modification is not a focal ablation, but requires complete abolition of the cranial portion of the SA node complex, the one that exhibits the most of the autonomic activity(9). It is defined as successful when the heart rate decreases by 30 beats per minute (bpm) during isoproterenol infusion(8). Short-term success was also defined by other investigators when there was a reduction of the baseline sinus rate to less than 90 bpm and the sinus rate during isoproterenol infusion by more than 20% or by 25%(8). The acute success rate for modification has been varying between 76 and 100 % across trials, while long-term clinical outcomes are modest at best, with reported freedom from IST ranging from 23 to 85%(10).Complications specific to SA node modification include superior vena cava (SVC) syndrome, diaphragmatic paralysis, and sinus node dysfunction(10). And while modification with conventional methods has its setbacks, modification using laser energy can be considered in the setting of IST. This modality creates clear-cut homogenous transmural lesions of the myocardium that comprises the scattered “functional” SA node(11). The burnt myocardium will then heal into a dense fibrous scar, decreasing potential amplitudes. And when adapting laser energy settings to the thickness of the myocardial wall, collateral dam­ages such as esophageal fistulae, lung burns, and phrenic nerve palsy will be avoided(11); thus, this technique may prove itself as a new intriguing alternative for the safe and effective treatment of IST.SA node modification is apt in achieving acute reductions in postprocedural heart rate. However, and as aforementioned, success rates are suboptimal in terms of symptomatic control with a significant recurrence rate(12). Catheter ablation aiming at either total exclusion and obliteration of the SA node has been described and performed, success being defined as a slowing of >50% from the baseline rate of tachycardia along with a junctional escape rhythm(12). With radiofrequency (RF) applications, the earliest local atrial activation time would shift from a cranial location to a more caudal one, usually at the mid-lateral right atrium(5). Reviews have reported that acute success rates were consistently to be as high as 88.9%, with an overall frequency of recurrence of 19.6%, the latter occurring within a wide range of post-ablation intervals, anywhere from a few weeks to several months after the procedure(12). Additionally, Takemoto and colleagues documented a significant drop in B-type natriuretic peptide levels, 6 to 12 months after ablation, suggesting fewer stretching shears on cardiac muscle.Two types of response of the sinus tachycardia to RFA were observed across studies, whether a step-wise reduction in sinus rate accompanying migration of the site of earliest atrial activation in a cranial-caudal direction along the lateral right atrial wall, or an abrupt drop in heart rate in response to RFA at a focal site of earliest atrial activation(13).However, RFA of inappropriate sinus tachycardia requires a large number of applications of radiofrequency energy and is, as in SA node modification, associated with a high recurrence rate(13). Complete remission is achieved only in approximately 50% of patients in some studies(14); longer history of IST and those reporting near syncope/syncope having a higher probability of recurrence(15).While other studies have shown that RF ablation of the SA node can achieve even longer-term reductions in the sinus rate and relief of symptoms in two-thirds of patients with drug-refractory, inappropriate sinus tachycardia(13), aiming specific sites related to the SA node should be elaborated, for better and optimal outcomes Killu and colleagues created a lesion in the arcuate ridge resulting in complete abolition of the tachycardia, since arrhythmias arising in this region may exhibit both electrocardiographic and clinical similarities to IST(16). This has led to consider ablation of the arcuate ridge as a treatment of refractory IST, necessitating larger trials to confirm its potential role.Phrenic nerve injury is a severe and dreaded complication of SN ablation(12). Pericarditis, right diaphragmatic paralysis, and SVC syndrome are other undesirable side effects of the procedures, variously reported in studies. but a common complication was observed in them all, atrial tachyarrhythmias(12). It has been hypothesized that myocardial pathology, such as inflammation and fibrosis, considered iatrogenic due to the ablation procedures, may be promoting arrhythmias both in the region of the SA node, as well as in remote locations(12). Through multivariable analysis, higher resting heart rates post-ablation and smaller cranial-to-caudal shifts have been defined as predictors of atrial arrhythmias(15). In conclusion, catheter ablation could be considered an effective treatment for highly symptomatic, drug-refractory patients, even for those who did not respond to SA node modification(5).The sinus node is located close to the epicardial surface and catheter-based ablations do not always make full-thickness lesions across the atrial muscle, leading to failure of the ablation(17), besides the numerous trabeculae and the widely variable anatomy.Surgical ablation is not a first-line or routine management strategy for IST, but it has been proposed when IST resists or recurs after SN modification/ endocardial ablation(17). Effectively, in several studies, epicardial lesions, through a single small incision in one of the intercostal spaces, successfully slowed heart rate and shifted activation to a more caudal location, and surprisingly, subsequent endocardial lesions led to an even greater drop in heart rate and more caudal site of earliest activation(18). These outcomes were again replicated when using minimally invasive thoracoscopic ablation of the epicardial site of the SA node, concluding of the promising efficacy and the safety of this approach, since it preserves the phrenic nerve(17), although continued follow-up after surgery is required.Medication-resistant IST remains a medical challenge for physicians and cardiologists; and in the era of great advances in interventional cardiology, its treatment remains debatable. Sinus node modification/ ablation is not recommended as first-line therapy in IST, this procedure should be considered only in drug-refractory patients who have severe symptoms(13). Although the number of patients in the available studies is generally small, both procedures have documented an encouraging success rate in the short-term, while being less impressive in the long-term. It has been hypothesized that this discrepancy is due to the relatively large potential area of atrial pacemaker cells(18); modification or ablation may fail to ablate or isolate all the pathways that comprise the functional SA node because they often target the anatomic part and the area of earliest atrial activation(19). Others have explained that the long-term slowing in rhythm fails because these procedures inconsistently produce transmural lesions in the right atrium. Surgical treatment of IST has proposed a solution to the latter conflict when isolating the SA node with a wide cuff of surrounding atrial muscle(19). And with the advent of bipolar RF clamps and minimally invasive cardiac surgical techniques with thoracoscopic guidance, this approach appears more appealing than before, especially when combined with endocardial ablation(19). But again, current data specifies employing these techniques in highly selected cases.

Objective: This study aimed to evaluate the long-term outcome of patients with PDA associated with UAPA. Methods: Patients diagnosed with PDA associated with UAPA were retrospectively enrolled from January 2005 to June 2019. Clinical data, treatment and follow-up information were evaluated. Results: 11 patients (5 males and 6 females) were diagnosed with PDA associated with UAPA. Percutaneous closure was conducted in 9 patients successfully. The median age was 37 months. The mean diameter of the PDA and occluders were 5.3±1.8mm (range 2-8.1 mm), 11.5±3.9 mm (4-16 mm) respectively. The median in 5 patients with the pulmonary: systemic flow ratio (Qp:Qs) was 1.41(1.28-8.7) and total lung resistance was 12 wood (1.8-13.6) . The mean systolic pulmonary artery pressure was 68.3±19.1mmHg（42-105mmHg). In 5 patients with pre- and post-procedure catheter data, the systolic pulmonary arterial pressure decreased significantly after closure 77.0±20.2 v 58.8±17.5 mmHg (p = 0.024), and so was the mean pulmonary arterial pressure 58.2±14.6 v 39.0±14.1 mmHg (p = 0.18). The pulmonary artery pressure and heart size gradually decreased to normal in 8 patients, and the quality of life was significantly improved. The ratio of lung to systemic circulation pressure in all these patients was less than 0.75. Conclusions: In appropriate patients with PDA associated with UAPA, transcatheter closure of PDA has the potential to improve the pulmonary artery hypertension. The ratio of lung to systemic circulation pressure less than 0.75 may be important reference index for predicting whether the pulmonary artery pressure could be reduced to normal after occlusion.

Objectives. We aimed to validate a Spanish version of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (SRBD-PSQ) in children living in a high-altitude Colombian city. Methods. In a prospective cohort validation study, patients aged between 2 and 18 years who attended the Ear, Nose, and Throat pediatric department of our institution for symptoms related to sleep-related breathing disorders had a baseline visit at enrollment, a second visit the day scheduled for the surgical intervention, and a follow-up visit at least three months after the surgical intervention. In these three visits, we gathered the necessary data for assessing the criterion validity, construct validity, test–retest reliability, internal consistency, and sensitivity to change of the Spanish version of the SRBD-PSQ. Results. In total, 121 patients were included in the analyses. The exploratory factor analysis (generalized least squares method, varimax rotation) yielded a four-factor structure, explaining 65.93% of the cumulative variance. The intraclass correlation coefficient (ICC) of the measurements was 0.887 (95% CI: 0.809–0.934), and the Lin concordance correlation coefficient was 0.882 (95% CI, 0.821-0.943). SRBD-PSQ scores at baseline were significantly higher than those obtained after adeno-tonsillectomy surgery (median [IQR] 11.0 [9.0- 14.0] vs. 4.00 [1.50- 7.0]; p<0.0001). Cronbach’s α was 0.7055 for the questionnaire as a whole. Conclusions. The Spanish version of the SRBD-PSQ has acceptable construct validity, excellent test-retest reliability and sensitivity to change, and adequate internal consistency-reliability when used in pediatric patients living at high altitude with symptoms related to sleep-related breathing disorders.

Aims: The symptoms of menopause in postmenopausal women adversely affect the quality of life. Menopausal symptoms are more severe with comorbid disorders such as depression; it may be lighter in physically active people. The present study aimed to evaluate the relationship between menopausal symptoms and physical activity and depressive mood. Material and Method: 190 women under 65 years of age who were at least one year passed since their last menstrual period participated in the study. Sociodemographic data form, Menopause Symptom Rating Scale, International Physical Activity Questionnaire - Short Form and Beck’s Depression Inventory were applied to the participants. Results: It was seen that 51.6% (98 subjects) of the women who participated in the study had severe menopausal symptoms. 52.6% (100 subjects) of the participants were physically inactive, and their menopausal symptoms increased as the physical activity scale score decreased (p=0.001). Menopausal symptoms increased as the Beck’s Depression Inventory score increased (p<0.001). It was observed that depression inventory scores decreased as the level of physical activity increased (p<0.001). Conclusion: Adoption of regular physical activity habits by postmenopausal women and providing treatment to those with depression will contribute to alleviating the severity of menopausal symptoms.

Many organisms show signs of deterioration with age, both in terms of survival and reproduction. Theory suggests that variation in such senescence patterns can be driven by resource availability or reproductive history. Here, we test this theory by manipulating nutritional stress and age at first reproduction and measuring age-dependent reproductive output in tsetse (Glossina morsitans morsitans), a viviparous fly with high maternal allocation. Across all treatments, offspring wet weight followed a bell-shaped curve with maternal age. Nutritionally stressed females had higher probability of abortion, produced smaller offspring with lower starvation tolerance. Despite this, there was no strong evidence of differences between treatments in the pattern of abortion probability, offspring wet weight or offspring starvation tolerance with age. Therefore, although we found strong evidence of general reproductive senescence in tsetse, variation in the onset and rate of senescence was not explained by resource allocation trade-offs or the costs of reproduction.