Introduction: Atrial pacing can unmask or aggravate a preexisting interatrial block (IAB). Our study aimed to determine whether atrial pacing is associated with the development of atrial high-rate episodes (AHRE) during follow-up. Methods and Results: Patients with dual-chamber cardiac implantable electronic devices (CIED), no previous documented atrial fibrillation, and with a 6-month minimum follow-up were included. In all patients, sinus and paced P-wave duration was measured. AHRE was defined as an episode of atrial rate ≥ 225 bpm with a minimum duration of 5 min, excluding those documented during the first three months after implantation. Two hundred twenty patients were included (75 ± 10 years, 61% male). After a mean follow-up of 59±25 months, 46% of patients presented AHRE. Mean paced P-wave duration was significantly longer than the sinus P-wave duration (154±27 vs 115±18 ms; p < 0.001). Sinus and paced P-waves were significantly longer in those who developed AHRE (sinus: 119±20 vs 112±16; p = 0.006; paced: 161±29 vs 148±23; p < 0.001). A paced P-wave ≥160 ms was the best predictor of AHRE, especially those lasting >24 h (OR 4.2 (95% CI) [1.6-11.4]; p = 0.004). Conclusion: Atrial pacing significantly prolongs P-wave duration and is associated with further development of AHRE. A paced P-wave ≥160 ms is a strong predictor of AHRE and should be taken into consideration as a new definition of IAB in the presence of atrial pacing.

We report a case of cutaneous lymphangioma secondary to breast cancer radiotherapy after mastectomy.

L’industria alimentare è tra i settori che cresce sempre di più dal punto di vista economico, ciò vuol dire che all’aumento del prodotto ne consegue un aumento della domanda di risorse, in particolare di acqua. La maggior parte degli stabilimenti lattiero-caseari utilizza una propria fonte d’acqua, la quale dovrebbe soddisfare i requisiti, dunque, è obbligatorio il suo trattamento. In questo articolo viene approfondita la gestione delle risorse e la qualità dell’acqua di due stabilimenti lattiero-caseari situati in Polonia. Quindi, si evidenzia il processo tecnico, la qualità dell’acqua e il suo consumo. Ciò, porterà alla riduzione del consumo di acqua e soprattutto al recupero e riutilizzo della stessa senza compromettere la qualità, l’igiene e la sicurezza dei prodotti, ragion per cui, si ha  un miglioramento dal punto di vista della gestione sia della risorsa che del refluo. 

Our case indicates that when bronchorrhea and mucinous pleural effusion with pancreatic cancer are observed, bronchorrhea due to malignant disease should be taken into consideration and, bronchorrhea derived from not bronchial asthma but lung metastasis of pancreatic cancer could lead to be refractory.

Background: Interval compression (IC), defined as 2 week-long cycles of alternating vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide, improves survival for localized Ewing sarcoma. The outcomes of patients with metastatic disease treated with IC are uncertain. Methods: We retrospectively reviewed the charts of pediatric patients with metastatic Ewing sarcoma treated with IC at our center between January-2013 and March-2020. We calculated event-free survival and overall survival and used log rank tests for univariate comparisons. Results: We identified 34 patients aged 2.7–17.1 years (median,11.6 years). Twenty-six patients (76%) had pulmonary metastases, and 14 (41%) had extra-pulmonary metastases in the bone (n = 11), lymph nodes (n = 2), and intraspinal tissue (n = 1). All patients received local control therapy: surgery only (n = 7, 21%), radiotherapy only (n = 18, 53%), or both (n = 9, 26%). The estimated 3-year OS and EFS were 62%±9% and 39%±9%, respectively. Patients with pulmonary only metastasis had a 3-year OS of 88%±8% in comparison to those with extra-pulmonary metastasis of 27%±13% (P=0.0074). Survival did not differ according to age group (> vs < 12 years), metastasis site, or primary tumor site, but 3-year event-free survival significantly differed according to local control therapy (surgery only, 83% ± 15%; combined surgery and radiation, 30% ± 18%; radiation only, 15% ± 10%; P = .048). Conclusion: IC yielded similar outcomes for patients with metastatic Ewing sarcoma to that reported in the literature using other regimens. We suggest including this approach to other blocks of therapy

Glycoside hydrolase enzymes are important for hydrolyzing the β-1,4 glycosidic bond in polysaccharides for deconstruction of carbohydrates. The two-step retaining reaction mechanism was explored with different sized QM-cluster models built by the Residue Interaction Network ResidUe Selector (RINRUS) software using both the wild-type protein and its E217Q mutant. The first step is the glycosylation, in which the acidic residue 217 donates a proton to the glycosidic oxygen leading to bond cleavage. In the subsequent deglycosylation step, one water molecule migrates into the active site and attacks the anomeric carbon. Residue interaction-based QM-cluster models lead to reliable structural and energetic results for proposed glycoside hydrolase mechanisms. The free energies of activation for glycosylation in the largest QM-cluster models were predicted to be 19.5 and 31.4 kcal mol -1 for the wild-type protein and its E217Q mutant, which agree with experimental trends that mutation of the acidic residue Glu217 to Gln will slow down the reaction, and are higher in free energy than the deglycosylation transition states (13.8 and 25.5 kcal mol -1 for the wild-type protein and its mutant, respectively). For the mutated protein, glycosylation led to a low-energy product. This thermodynamic sink may correspond to the intermediate state which was isolated in the X-ray crystal structure. Hence, the glycosylation is validated to be the rate-limiting step in both the wild-type and mutated enzyme. The E217Q mutation led to a higher glycosylation activation free energy that also agrees with experimental observation that mutation of E217 will slow down the reaction, but not deactivate catalysis.

Objective. Clinicians and regulators are receiving reports of changes to menstrual periods following COVID-19 vaccination. However, it is unclear if the two are biologically linked. If they are, people using hormonal contraception are predicted to be less likely to report a change and spontaneously cycling people vaccinated prior to ovulation more likely. The objective was to test these hypotheses. Design. Retrospective cohort study. Setting. UK. Population. 1273 people who had received at least one dose of a COVID-19 vaccination, have periods or withdrawal bleeds and keep a record of the dates of these. Methods. Participants reported whether they use any hormonal contraception and, for each dose of the vaccine, on which day of their menstrual cycle they were vaccinated and details of how the timing and flow of their next period compared to their normal experience. Main outcome measures. Association between 1. the use of hormonal contraception and reported changes to timing or flow of the next menstrual period, and 2. the timing of vaccination within the menstrual cycle and reported changes to timing or flow of the next menstrual period. Results. The data from this cohort did not support the pre-specified hypotheses that people using hormonal contraception would be less likely to report a change, or that spontaneously cycling people vaccinated prior to ovulation would be more likely to report a change. Conclusions. This study did not detect strong signals supporting the idea that COVID-19 vaccination is linked to menstrual changes in most people. Funding. No specific funding.

Objective: To determine stress-sensitivity and neurodevelopmental outcome in 8- to 9-year-old children following antenatal exposure to glucocorticoid (GC) prophylaxis for neonatal respiratory distress syndrome. Design: Clinical cohort study. Setting: University-based obstetric clinic in Central Germany. Population: 31 term or near-term born children whose mothers received single or multiple courses of betamethasone (BM) to induce fetal lung maturation in threatened preterm birth compared to 39 non-exposed children. Methods: Multi-system assessment of the individual stress response together with an analysis of cognitive, behavioral and electrocortical functioning. Main Outcome Measures: Activity of the hypothalamus-pituitary-adrenal axis (HPAA, primary outcome domain) and the autonomic nervous system (ANS, secondary outcome domain) including markers of heart rate variability (HRV). Additional endpoints were the cognitive performance (IQ) and attention-deficit/hyperactivity disorder (ADHD) core symptoms. Results: HPAA activity was not affected by antenatal GC-exposure. ANS activity in GC-exposed children shifted towards a higher parasympathetic tone reflected by a higher overall high-frequency band power of HRV (1313 vs. 762 msec2/Hz, p=0.03). BM-exposed children had lower cognitive performance (IQ 96.9 vs. 108.0, p<0.01) and a marginally higher ADHD score (FBB-ADHD scale 5.5 vs. 4.6 points, p=0.04). A monotonic dose-response relationship between GC-exposure and stress-induced activity of the ANS and IQ was estimated post-hoc. Conclusions: Antenatal exposure to supraphysiological concentrations of BM in the context of threatened preterm birth was associated with multidimensional changes in stress-sensitivity and neurodevelopment in later life. As these changes may be dose-dependent, antenatal GC prophylaxis should be used at the minimum effective dose after a careful risk-benefit assessment.

Objectives: Newer generations of stented pericardial valves may offer hemodynamic benefit in patients with small aortic annulus. The aim of this study was to determine the effectiveness of isolated aortic valve replacement with one such valve, the Trifecta valve, when compared to Aortic root enlargement surgery in reducing postoperative gradients and the severity of PPM in patients with small aortic annulus. Patients and methods: A prospective observational study of 100 patients with SAA who underwent AVR from March 2020 to October 2021 in Cairo university hospitals and other centers. The cohort was divided into two groups based on surgical technique: Isolated AVR using Trifecta valve or ARE and mechanical valve placement. Preoperative characteristics, intraoperative times and postoperative outcomes were recorded and compared in all patients, including a pre-discharge echocardiography. Results: Increased operative times, increased ICU stay and need for blood products were observed in the ARE group and operative time was determined as an independent risk factor. Higher rate of complications such as need for permanent pacemaker as well increased postoperative drainage was also recorded in ARE group, with no difference between groups in in-hospital mortality. Higher incidence of PPM was recorded in the Trifecta group (24%) compared to the ARE group (8%). but, the severity of PPM within the Trifecta group was reduced compared to the ARE group, and no degree of PPM was observed in Trifecta valves sized 21. Conclusion The Trifecta valve offers excellent postoperative hemodynamics and significant reduction in severity of PPM in patients with SAA undergoing AVR, with gradients and iEOA almost comparable to larger sized valves implanted after ARE, making the increased surgical burden of ARE unnecessary in most patients.

The aim of the study was to clarify the effect of melatonin on neuropathic pain by N-type calcium channel (Cav2.2) inhibition in dorsal root ganglion (DRG) neurons after spared nerve injury (SNI) surgery. Immunofluorescence was used to identify the co-expression of Cav2.2 and the MT2 receptor and detect the changes in Cav2.2 expression in DRG neurons. Western-blot was also performed to detect the expression of Cav2.2 in DRG neurons. The action potential and current of Cav2.2 channels in DRG neurons were detected using whole-cell patch clamp analysis. Behavioral studies were conducted using thermal stimulation and acetone after melatonin was injected intraperitoneally. The results revealed that Cav2.2 and the MT2 receptor were co-expressed in medium and small sized DRG neurons, and the intensity of Cav2.2 increased after SNI. Injection of melatonin activated the MT2 receptor and relieved nociceptive pain through decreased the Cav2.2 expression and current in DRG neurons. Melatonin can significantly decrease the increase in Cav2.2 current density and excitability after SNI. In addition, the Cav2.2 activation curve shifted to the left after SNI, but there was no change in inactivation. 10 μM melatonin significantly inhibited the excitability of DRG neurons and Cav2.2 current, the inactivation curve of Cav2.2 current shifted significantly to the left. However, the MT2 receptor antagonist 4-P-PDOT reversed the inhibition of melatonin on Cav2.2 current. We conclude that melatonin inhibits the increased Cav2.2 expression and current; on the other hand, it reduces the excitability of DRG neurons after SNI surgery via the MT2 receptor pathway.

Aim: We have studied population genetic change through time in the Northern dragonhead, Dracocephalum ruyschiana (Lamiaceae); a plant species that has experienced a drastic population decline and habitat loss in Europe. We aimed at adding a historic level to the monitoring of dragonhead by testing a microfluidic SNP array approach on herbarium specimens up to 200 years old and comparing the genomic results with that of modern populations in Norway. We also aimed to gain a more holistic species knowledge to guide monitoring efforts by combining herbarium genomics with ecological niche modelling (ENM). Location: Europe (mainly Norway) Methods: We have applied a microfluidic array consisting of 96 SNP markers on 130 herbarium specimens collected from 1820 to 2008. Obtained genotype data were compared with SNP data from modern samples using various population genetic analyses. We used sample metadata and observational records to model the species’ environmental niche. Results: The SNP array successfully genotyped all included herbarium specimens but was less capable of capturing diversity outside of Norway, which was genetically highly divergent from the Norwegian dragonheads. The historic-modern comparison revealed similar genetic structure in space and limited change through time in Norway. The ENM suggests that dragonhead has not fully achieved its potential distribution in Norway, which is anchored in warmer and drier regions, including areas where it does not occur today. Main conclusions: With the appropriate design procedures, the SNP array technology is promising for genotyping old herbarium specimens; an invaluable source of information from the past. We found no signs of the severe reduction in population size in our temporal genomic data of Norwegian dragonhead. Regardless, the regional populations in Norway are genetically divergent, both from each other and more so from populations outside of Norway, rendering continued protection of all existing populations of the species relevant.

Objective: To evaluate whether elective induction of labour (eIOL) influences the rate of caesarean birth in uncomplicated pregnant women at term, compared to expectant management. Design: Retrospective cohort study. Setting: Births in Victoria between 2010 and 2018. Population: Term, singleton, vertex births from low-moderate risk pregnancies (n=396,164). Methods: Preliminary analyses compared eIOL at 37 weeks with expectant management both beyond that gestational age (preliminary analysis I) and at that gestational age and beyond (preliminary analysis II). Similar comparisons were made for eIOL at 38, 39, 40 and 41 weeks’ gestation and expectant management. The primary analysis repeated these comparisons, limiting the population to nulliparous women whose recorded indication for induction did not include one of a specified list of conditions. Chi-square tests and multivariable logistic regression were used. Adjusted odds ratios and 99% confidence intervals were reported. P<0.01 denoted statistical significance. Main Outcome Measures: Unplanned caesarean birth, perinatal mortality Results: The proportion of nulliparous, low-moderate risk women who underwent IOL ≥37 weeks’ gestation in Victoria increased from 24.6% in 2010 to 30.0% in 2018 (p-value <0.001). eIOL in nulliparous women was associated with an increased odds of caesarean birth when performed at 38 (aOR 1.23((1.13-1.32)), 39 (aOR 1.31((1.23-1.40)), 40 (aOR 1.42((1.35-1.50)), and 41 weeks’ gestation (aOR 1.43((1.35-1.51)). Perinatal mortality was rare in both groups and non-significantly lower in the induced group at most gestations. Conclusions: eIOL was associated with an increased odds of caesarean birth from 38 weeks’ gestation and a decrease in the odds of perinatal mortality.

A document by Shaun Pritchard -Personal. Click on the document to view its contents.

The kappa opioid receptor (KOPr) has exceptional potential as an analgesic target, seemingly devoid of the many peripheral side-effects of Mu receptors. Kappa-selective, small molecule pharmaceutical agents have been developed, but centrally mediated side effects have the limited their clinical translation. Here, we modify an active endogenous Dynorphin peptide with the aim of improving drug-likeness and developing safer KOPr agonists for clinical use. Using rational, iterative design and modern peptide chemistry, we developed a series of potent, selective and metabolically stable peptides from Dynorphin 1-7. Peptides were assessed for cAMP-modulation against Kappa, Mu and Delta opioid receptors, metabolic stability, KOPr specificity and binding, and interrogated for in vitro desensitisation and pERK signalling capability. Finally, lead peptides were evaluated for efficacy in Freund’s complete adjuvant rat model of inflammatory nociception. A library of 70 peptides was synthesised and assessed for pharmacological and metabolic stability factors. At least 10 peptide candidates showed low nanomolar activity (˂50 nM) in a cAMP assay, specificity for KORr, and plasma half-life >60 min, with 6 candidates also stable in trypsin. None of the selected peptides showed pERK activity, with a bias towards cAMP signalling. In vivo, KA305 and KA311 showed anti-nociception opioid receptor-specific activity comparable to morphine and U50 844. These highly potent and metabolically stable peptides are promising opioid analgesic leads for clinical translation. Since they are biased peptide KOPr agonists, it is plausible they lack many of the most significant side effects, such as tolerance, addiction, sedation and euphoria/dysphoria, common to opioid analgesics.

In this case of medication overuse headache in a patient with myasthenia gravis, an acupuncturist identified the use of an over-the-counter analgesic that was not revealed to the attending physician. This case highlights the potential role of an acupuncturist as part of the medical care team involved in headache management.

Massive myocardial calcification is a very rare finding. Accurate identification and characterization may help the clinicians to determine the etiology and clinical significance. In this case, the diagnostic pathway excluded previous myocardial infarction, myocarditis and calcium-phosphate disorders. A possible dystrophic etiology was considered. There are no standardized imaging features available to classify specific subtypes of intramyocardial calcifications. The relative merits of cardiac computed tomography and magnetic resonance in providing complimentary diagnostic information for calcific myocardial lesions is shown. Knowledge of the potential etiology and their imaging patterns are important to provide a concise and accurate differential diagnosis.

Little is known on how disasters interact in their impacts on patient care. We experienced a breast cancer patient whose initial presentation was delayed for two years due to the COVID-19 pandemic and Typhoon Hagibis. Increasing awareness is needed on the combined impacts of disasters on breast cancer management.

Hypophysitis is a rare inflammatory condition that may present both clinically and radiologically as a neoplastic lesion. Xanthogranulomas are rare intracranial lesions with controversial etiology. Here, we report a clinical case of histologically confirmed xanthogranuloma in a young female with type I diabetes mellitus and hypothyroidism.

Despite a growing literature-base devoted to documenting biodiversity patterns in cities, little is known about the processes that influence these patterns, and whether they are consistent over time. In particular, numerous studies have identified the capacity of cities to host a rich diversity of plant species. This trend, however, is driven primarily by introduced species, which comprise a large proportion of the urban species pool relative to natives. Using an experimental common garden study, we assessed the relative influence of local assembly processes (i.e., soil environmental filtering and competition from spontaneous urban species) on the taxonomic and functional diversity of native plant communities sampled over four seasons in 2016-2018. Taxonomic and functional diversity exhibited different responses to local processes, supporting the general conclusion that species- and trait-based measures of biodiversity offer distinct insights into community assembly dynamics. Additionally, we found that neither soil nor competition from spontaneous urban species influenced taxonomic or functional composition of native species. Functional composition, however, did shift strongly over time and was driven by community-weighted mean differences in both measured traits (maximum height, Hmax; specific leaf area, SLA; leaf chlorophyll a fluorescence, chl a) and the relative proportions of different functional groups (legumes, annual and biennial-perennial species, C4 grasses, and forbs). In contrast, taxonomic composition only diverged between early and late seasons. Overall, our results indicate that native species are not only capable of establishing and persisting in vacant urban habitats, they can functionally respond to local filtering pressures over time. This suggests that regional dispersal limitation may be a primary factor limiting native species in urban environments. Thus, future regreening and management plans should focus on enhancing the dispersal potential of native plant species in urban environments, in order to achieve set goals for increasing native species diversity and associated ecosystem services in cities.

Figure S1. a) The memristive synaptic behavior with an ideally symmetric and linear weight update ability (constant ΔG for identical pulses) but limited conductance levels (N =20). b) Test accuracy for 10,000 images in the MNIST dataset obtained during the training of memristive DBN as a function of the training epoch (CDth=64).

Introduction: Cavernous hemangioma accounts for 0.6% of bladder tumors. We present a rare case Case Presentation: A 3-year-old girl presented with intravaginal swelling, dysuria, and hematuria. She received 26 cycles of VAC for embryonal rhabdomyosarcoma. Histopathology confirmed CH. Conclusion: CH should be considered in the differentials of childhood genitourinary masses.

Background: Trisomy 17 is a rare chromosomal disorder with limited existing literature that mostly refer to mosaic Trisomy 17 cases. Our report summarizes the clinical course of a neonate with a Trisomy 17 karyotype der (14;17) (q10; p10), + 17 pat. Key words: Trisomy 17, Unbalanced translocation, Paternal origin

An 81-year-old man presented to our hospital with a 6-month history of weight loss and lymphadenopathy. On examination, he had high fever and right axillary lymphadenopathy. A right axillary lymph-node excisional biopsy showed findings of mixed cellularity Hodgkin's lymphoma. However, he died before the results of the biopsy were obtained.

Water inside plants forms a continuous chain from water in soils to the water evaporating from leaf surfaces. Failures in this chain result in reduced transpiration and photosynthesis and these failures are caused by soil drying and/or cavitation-induced xylem embolism. Xylem embolism and plant hydraulic failure share a number of analogies to “catastrophe theory” in dynamical systems. These catastrophes are often represented in the physiological and ecological literature as tipping points or alternative stable states when control variables exogenous (e.g. soil water potential) or endogenous (e.g. leaf water potential) to the plant are allowed to slowly vary. Here, plant hydraulics viewed from the perspective of catastrophes at multiple spatial scales is considered with attention to bubble expansion (i.e. cavitation), organ-scale vulnerability to embolism, and whole-plant biomass as a proxy for transpiration and hydraulic function. The hydraulic safety-efficiency tradeoff, hydraulic segmentation and maximum plant transpiration are examined using this framework. Underlying mechanisms for hydraulic failure at very fine scales such as pit membranes, intermediate scales such as xylem network properties and at larger scales such as soil-tree hydraulic pathways are discussed. Lacunarity areas in plant hydraulics are also flagged where progress is urgently needed.