Development and validation of traditional & complementary medicine (TCM) scales for nurses: Using structural equation modelling (SEM).
This study aimed to develop and validate scales to assess attitudes towards patient' s use of TCM (APUTCM) and to measure a communicative competence in TCM (CCTCM) among nurses. The instrument development process was conducted from Sep 2013 to Jul 2014, using the following steps: 1) item development; 2) internal review and refinement; 3) face and content validation; 4) instrument administration to a development sample; and 5) evaluation of validity and reliability. A convenience sample was used to recruit registered and advanced practice nurses who worked in different regions throughout Taiwan. A total of 755 respondents completed the online questionnaire. Statistical analyses were performed using the software of SPSS Version 21.0 and Analysis of Moment Structures (AMOS) version 24.0. The scale-level indexes (S-CVI) of content validity for both scales were over 80%. The reliabilities for the 13-item APUTCM scale and for the five-item CCTCM scale were 0.88 and 0.84, respectively. The model suitability for both scales was assessed, and the findings revealed suitable parameters for all indicators: GFI = 0.954, AGFI = 0.932, CFI = 0.959, RMSEA = 0.62, and chi-square/df = 3.891 for APUTCM; and GFI = 0.992, AGFI = 0.969, CFI = 0.992, RMSEA = 0.63, and chi-square/df = 4.04 for CCTCM. The convergent and divergent validity of scores on both scales provided evidence in the expected direction. This scale development study provides preliminary evidence that suggests that the 13-item APUTCM and the five-item CCTCM are reliable and valid scales for assessing attitudes toward patient's TCM use and communicative competence in TCM.


Sleep debt and prevalence of proteinuria in subjects with short sleep duration on weekdays: a cross-sectional study.
Short sleep duration is a risk factor of chronic kidney disease, along with cardiovascular diseases and all-cause mortality. Several studies reported that many people sleep longer on weekends than on weekdays, suggesting that they should be compensated for their sleep debt on weekdays on the weekends. Few studies have reported the clinical impact of sleep debt on the kidney. This cross-sectional study included 5799 employees of Osaka University who visited its Health Care Center for their annual health examinations and answered ≤ 6 h of sleep duration on weekdays. The independent variable was the sleep debt index defined as a gap in self-reported sleep duration (≤ 5, 5-6, 6-7, 7-8, 8-9, and ≥ 9 h) between weekdays and weekends, which was categorized into ≤ 0, + 1, + 2, + 3 and ≥+4. An association between the sleep debt index and a prevalence of proteinuria defined as dipstick proteinuria of ≥ 1 + was assessed using logistic regression models adjusting for clinically relevant factors. More than four-fifths of the subjects had a positive sleep debt index (≤ 0, + 1, + 2, + 3, and ≥+4 recorded for 19%, 36%, 28%, 11%, and 6%, respectively). The multivariable-adjusted logistic regression models showed the sleep debt index ≥ 3 + was significantly associated with the prevalence of proteinuria (sleep debt index ≤ 0, adjusted odds ratio 1.13 [0.77, 1.65]; + 1, 1.00 [reference]; + 2, 1.29 [0.93, 1.79]; + 3, 1.54 [1.02, 2.33]; ≥ + 4, 1.87 [1.15, 3.05]). Sleep debt was associated with the prevalence of proteinuria in a dose-dependent manner.


Murine models of chronic graft-versus-host disease: insights and unresolved issues.
Chronic graft-versus-host-disease (cGVHD) is a major barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT), with highly variable clinical presentations. The pathophysiology of cGVHD remains relatively poorly understood. The utilization of murine models to study cGVHD encompasses experimental challenges distinct from those that have been successfully used to study acute GVHD (aGVHD). Nevertheless, despite these challenges, murine models of cGVHD have contributed to the understanding of cGVHD, and highlight its mechanistic complexity. In this article, insights into the pathophysiology of cGVHD obtained from murine studies are summarized in the context of their relevancy to clinical cGVHD. Despite experimental limitations, current and future models of murine cGVHD will continue to provide insights into the understanding of clinical cGVHD and provide information for new therapeutic interventions.


Global Spinal Realignment After Osteotomized Debridement in Active Lumbar Spinal Tuberculosis: Correlation with Patient-Reported Outcomes.
Osteotomized debridement (OD) has been proved to be highly effective in treating active thoracolumbar tuberculosis (TB); however, no research has investigated how OD affects spinal alignment. The goal of this study was to explore the global alignment compensatory mechanism after lumbar OD, as well as the correlation between spinopelvic parameters and patient-reported outcomes (PROs). Sixty-two patients with active lumbar spinal TB who underwent OD surgery were included. Spinopelvic parameters (C2-7 Cobb angle [C2-7 CA], sagittal vertical axis [SVA], proximal thoracic kyphosis, thoracic kyphosis, lumbar lordosis [LL], sacral slope [SS], pelvic tilt [PT], pelvic incidence [PI], spinosacral angle, and PI minus LL [PI-LL]) and PROs (Oswestry Disability Index [ODI] and Visual Analog Scale [VAS] score) were reviewed. The correlation between spinopelvic realignment and improved PROs was evaluated. Compared with preoperative measurements, C2-7 CA, proximal thoracic kyphosis, thoracic kyphosis, LL, SS, and spinosacral angle significantly increased after OD, whereas SVA, PT, and PI-LL significantly decreased. ODI and VAS score significantly improved postoperatively. The improvement of VAS was observed to be correlated with variations of C2-7 CA, SVA, LL, and PI-LL. The improvement of ODI was found to be correlated with variations of SVA, LL, and PI-LL. The multiple stepwise regression analysis showed that LL was an independent predictor for ODI and VAS score. The whole spine and pelvis are involved in realignment after lumbar spinal OD, which is closely related to PROs. More attention should be drawn to restoring an appropriate LL in lumbar TB surgery.


Antithrombotic activities of ferulic acid via intracellular cyclic nucleotide signaling.
Ferulic acid (FA) produces protective effects against cardiovascular dysfunctions. However, the mechanisms of FA is still not known. Here we examined the antithrombotic effects of FA and its potential mechanisms. Anticoagulation assays and platelet aggregation was evaluated in vitro and in vivo. Thromboxane B2 (TXB2), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate (cGMP) was determined using enzyme immunoassay kits. Nitric oxide (NO) production was measured using the Griess reaction. Protein expression was detected by Western blotting analysis. Oral administration of FA prevented death caused by pulmonary thrombosis and prolonged the tail bleeding and clotting time in mice,while, it did not alter the coagulation parameters, including the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). In addition, FA (50-200 µM) dose-dependently inhibited platelet aggregation induced by various platelet agonists, including adenosine diphosphate (ADP), thrombin, collagen, arachidonic acid (AA), and U46619. Further, FA attenuated intracellular Ca(2)(+) mobilization and TXB2 production induced by the platelet agonists. FA increased the levels of cAMP and cGMP and phosphorylated vasodilator-stimulated phosphoprotein (VASP) while decreased phospho-MAPK (mitogen-activated protein kinase) and phosphodiesterase (PDE) in washed rat platelets, VASP is a substrate of cyclic nucleotide and PDE is an enzyme family responsible for hydrolysis of cAMP/cGMP. These results suggest that antithrombotic activities of FA may be regulated by inhibition of platelet aggregation, rather than through inhibiting the release of thromboplastin or formation of thrombin. The mechanism of this action may involve activation of cAMP and cGMP signaling.


Psychotic-like experiences in the lonely predict conspiratorial beliefs and are associated with the diet during COVID-19.
The COVID-19 pandemic has increased the occurrence of conspiracy theories. It has been suggested that a greater endorsement of these theories may be associated with psychotic-like experiences (PLEs), as well as with social isolation. In this preregistered study, we investigated whether both PLEs and measures of social isolation (e.g., loneliness) can predict conspiratorial beliefs and, if so, which of these variables can mediate the association with conspiratorial beliefs. Furthermore, based on previous studies on schizophrenia, we explored whether the diet is associated with PLEs and conspiratorial beliefs. Participants (N = 142) completed online questionnaires measuring PLEs, social isolation, mental well-being, and conspiratorial beliefs. They also submitted their daily food intake for a week using a smartphone app. We found that loneliness predicted the endorsement of conspiracy theories during the COVID-19 lockdown. Strikingly, the proneness to experience subclinical psychotic symptoms played an underlying mediating role. In addition, these subclinical symptoms were associated with lower fruit, carbohydrate, and iron intakes, as well as with higher fat intake. Our results add insights into how conspiratorial beliefs can affect individuals' mental health and relationships. Moreover, these results open the avenue for potential novel intervention strategies to optimize food intake in individuals with PLEs.


CD40 ligand expressed in adenovirus can improve the immunogenicity of the GP3 and GP5 of porcine reproductive and respiratory syndrome virus in swine.
Porcine reproductive and respiratory syndrome virus (PRRSV) has recently caused heavy economic losses in swine industry worldwide. Current vaccination strategies only provide a limited protective efficacy, thus immune modulators are being considered to enhance the effectiveness of PRRSV vaccines. In this study, the recombinant adenoviruses expressing porcine CD40 ligand (CD40L) and GP3/GP5 of PRRSV were constructed and the immune responses were examined in pigs. The results showed that rAd-CD40L-GP35 (co-expressing CD40L and GP3-GP5) or rAd-GP35 (expressing GP3-GP5) plus rAd-CD40L (expressing CD40L) could provide significant higher specific anti-PRRSV ELISA antibody and neutralizing antibody. And the levels of proliferative responses of peripheral blood mononuclear cells (PBMC), IFN-γ and IL-4 were markedly increased in rAd-CD40L-GP35 and rAd-CD40L plus rAd-GP35 groups than those in rAd-GP35 group. Following homologous challenge with Chinese isolate of the North-American genotype of PRRSV, pigs inoculated with recombinant rAd-CD40L-GP35 and rAd-CD40L plus rAd-GP35 showed lighter clinical signs and lower viremia, as compared to those in rAd-GP35 group. It indicated that porcine CD40L could effectively increase humoral and cell-mediated immune responses of GP3 and GP5 of PRRSV. Porcine CD40L might be used as an attractive adjuvant or immunotargeting strategies to enhance the PRRSV subunit vaccine responses in swine.


Regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP).
To describe regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP). Retrospective cohort study of a large, US commercial managed care plan claims database with pharmacy coverage from 2008 to 2018. Singleton pregnancies with at least one prior spontaneous preterm birth (sPTB) were included. Regional and state-based differences in 17-OHP use were compared. Data were analyzed using t-tests and Fisher's exact tests. Of the 4,514 individuals with an indication for 17-OHP, 580 (12.8%) were prescribed 17-OHP. Regional and state-based differences in 17-OHP utilization were identified; Northeast 15.7%, Midwest 13.7%, South 12.0%, and West 10.4% (p=0.003). While significant regional differences in 17-OHP utilization were demonstrated, 17-OHP utilization remained low despite this cohort having insurance through a US commercial managed care plan. Suboptimal utilization demonstrates a disconnect between research and uptake in clinical practice. This underscores a need for implementation science in obstetrics to translate updated recommendations more effectively and efficiently into clinical practice.


Primary myxoid leiomyosarcoma of the ovary. A case report with review of the literature.
A case of primary myxoid leiomyosarcoma of the ovary in a 50-year-old Tunisian woman is presented. Bilateral salpingooophorectomy and hysterectomy were carried out without any adjuvant therapy. The tumour were investigated histologically and immunohistochemically. Smooth-muscle actin and progesterone receptors was strongly demonstrated in neoplastic cells, bcl-2 was weakly and diffusely demonstrated. Relevant literature is reviewed based on the histologic and immunohistochemical features with emphasis on diagnosis and therapeutic problems and prognosis indicators.


[The immunomodulating properties of the erythrocytes in an experimental staphylococcal infection].
Experiments on 130 mice of different strains have revealed that washed mouse erythrocytes taken on day 7 of experimental staphylococcal infection induce the pronounced increase of humoral immune response to sheep red blood cells in syngeneic recipients, while mouse erythrocytes taken on day 14 of this infection induce immunosuppression. Erythrocytes acquire immunosuppressive properties at the period of red blood regeneration.


Theoretical prediction of base sequence effects in DNA. Experimental reactivity of Z-DNA and B-Z transition enthalpies.
Molecular modeling is used to study the sequence dependence of conformation and stability within helically regular duplex Z-DNA. The variations of conformation that are found are sufficiently important to be classified as a new type of polymorphism within the Z family. It is also demonstrated that certain sequences can adopt more than one of these polymorphic forms. Comparison with experimental studies of chemical reactivity within a natural DNA fragment, forced into a left-handed conformation, suggests that the results of our modeling may be used to explain the chemical reactivity observed. Comparison of the Z results with similar studies of the B form allow enthalpies of transition to be calculated as a function of base sequence.


Clinical outcome of laparoscopic versus robot-assisted radical cystectomy for patients with bladder cancer: a retrospective study.
With the development of minimally invasive surgery technology, patients with bladder cancer are increasingly receiving laparoscopic radical cystectomy (LRC) or robotic-assisted radical cystectomy (RARC) treatment. The main purpose of this study was to compare the long-term outcomes of bladder cancer patients treated with LRC versus RARC. A retrospective study to identify patients with clinical stage Ta/T1/Tis to T3 bladder cancer who underwent RARC or LRC has been performed. The perioperative outcome, recurrence, and overall survival (OS) of the two surgical methods were compared. 218 patients were identified from March 2010 to December 2019 in our department, which including 82 (38%) patients who received LRC and 136 (62%) patients who received RARC. There was no significant difference between the two groups in terms of lymph node collection, lymph node positive rate, resection margin positive rate, and postoperative pathological staging. Compared with the LRC group, patients in the RARC group had a median estimated blood loss (180 vs. 250 ml; P = 0.02) and reduced complications at 90 days postoperatively (30.8% vs. 46.3%; P = 0.01). Recurrence, all-cause death, and cancer-specific death occurred in 77 (35%), 55 (25%), and 39 (18%) patients, respectively. The 5-year OS rate was 54.63% and 54.65% in the RARC and LRC group (P > 0.05). The 5-year cancer-specific survival (CSS) rate was 73.32% and 61.55% in RARC and LRC group (P > 0.05). There was no significant difference in OS [hazard ratio (HR) 1.083, 95% confidence interval (CI) 0.626-1.874; P = 0.78], and CSS (HR 0.789, 95%CI 0.411-1.515; P = 0.61) between two groups. Both RARC and LRC were safe and effective with a similar long-term clinical outcomes. Moreover, RARC had significantly lower median estimated blood loss and reduced postoperative complications.


Pharmacological study of Cymbopogon citratus leaves.
Cymbopogon citratus leaves are employed by the Cuban population as an antihypertensive and anti-inflammatory folk medicine. A 10% or 20% decoction of leaves was tested using arterial pressure in rats, urine production and carrageenan-induced edema in rats. The decoction showed some dose-related hypotensive effects given intravenously and some weak diuretic and anti-inflammatory effect when given orally.


1,2-dihydroisoquinolines as templates for cascade reactions to access isoquinoline alkaloid frameworks.
The synthesis of isoquinoline alkaloid frameworks has been achieved via a series of cascade reactions identified through reaction discovery utilizing 1,2-dihydroisoquinoline scaffolds.


Conventional medical attitudes to using a traditional medicine vodou-based model of pain management: survey of French dentists and the proposal of a pain model to facilitate integration.
The purposes of this study were to develop a pain management model using traditional medicine (TM) vodou healing methods; to survey a sample of French dentists to rate components of conventional and proposed TM vodou-based pain management model; and to assess the possibility of conventional, allopathic providers to integrate TM or complementary and alternative medicine concepts. From a set of 30 fact sheets collected from TM African healers (vodou healers), main clinical concepts and terminology were extracted. Twenty vodou-based pain management concepts were collected from an interview with a TM vodou practitioner. From this information, a 7-step vodou-based pain management model was created. A sample of 40 French dentists from Nantes, France, whose practices focused on the clinical treatment of dental pain, was surveyed to assess the importance of both TM (vodou) and conventional biomedical components. Seventy percent of the dentists sampled rated the rational components of the TM model as "very important" or "important" for pain treatment, whereas 2 other traditional concepts were considered to be "supernatural" or beyond understanding. This study showed that traditional healers used conventional concepts and conventional practitioners could use traditional concepts. This suggests that conventional allopathic medical providers have the capacity to integrate biomedical concepts and other therapeutic and explanatory models. This information may be helpful to understand and improve risk management by anticipating and preventing potential reasons for failure in TM integration strategies and to enhance communication between patients, healers, and physicians to optimize TM or complementary and alternative medicine integration.


Intravitreal aflibercept for diabetic macular edema in real-world clinical practice in Japan: 24-month outcomes.
To report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan. In this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency. In total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 μm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 μm (n = 140) at 24 months. Routine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice. ClinicalTrials.gov: NCT02425501.


Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery.
Postoperative progression and chemotherapy resistance is the major cause of treatment failure in patients with triple-negative breast cancer (TNBC). Currently, there is a lack of an ideal predictive model for the progression and drug sensitivity of postoperative TNBC patients. Diverse programmed cell death (PCD) patterns play an important role in tumor progression, which has the potential to be a prognostic and drug sensitivity indicator for TNBC after surgery. Twelve PCD patterns (apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, and oxeiptosis) were analyzed for model construction. Bulk transcriptome, single-cell transcriptome, genomics, and clinical information were collected from TCGA-BRCA, METABRIC, GSE58812, GSE21653, GSE176078, GSE75688, and KM-plotter cohorts to validate the model. The machine learning algorithm established a cell death index (CDI) with a 12-gene signature. Validated in five independent datasets, TNBC patients with high CDI had a worse prognosis after surgery. Two molecular subtypes of TNBC with distinct vital biological processes were identified by an unsupervised clustering model. A nomogram with high predictive performance was constructed by incorporating CDI with clinical features. Furthermore, CDI was associated with immune checkpoint genes and key tumor microenvironment components by integrated analysis of bulk and single-cell transcriptome. TNBC patients with high CDI are resistant to standard adjuvant chemotherapy regimens (docetaxel, oxaliplatin, etc.); however, they might be sensitive to palbociclib (an FDA-approved drug for luminal breast cancer). Generally, we established a novel CDI model by comprehensively analyzing diverse cell death patterns, which can accurately predict clinical prognosis and drug sensitivity of TNBC after surgery. A user-friendly website was created to facilitate the application of this prediction model (https://tnbc.shinyapps.io/CDI_Model/).


Surgical outcome of transconjunctival cryosurgical extraction of orbital cavernous hemangioma.
Transconjunctival cryosurgical extraction (TCE) is not an accepted method for the removal of most intraorbital tumors, and thus is not routinely performed. This study evaluates TCE for orbital cavernous hemangioma (OCH), which, due to its specific vascular structure, is suitable for this technique. In this retrospective case series, the medical charts of 12 consecutive patients with OCH who underwent TCE were reviewed. The operative complications and the surgical outcome were analyzed. Eleven tumors were intraconal and 1 was extraconal. No tumor involved the orbital apex. In 10 patients (83%), the operation was uneventful. One patient lost vision due to intraoperative cilioretinal arterial occlusion. In another patient, the tumor could not be identified and was subsequently removed via lateral orbitotomy. TCE, a relatively minor operation, is as safe as more extensive surgical procedures for the removal of OCH not located in the posterior third of the orbital space.


The impact of cultural and environmental changes on the epidemiology and control of human babesiosis.
The infection of humans with Babesia spp. has provided a well studied example of how cultural and environmental factors have contributed to the spread of an infection. Individuals developing babesiosis have been those engaging in life styles which put them at risk of tick bites. Farmers, hunters and other outdoor types are most frequently infected. The forms of human babesiosis which occur in the north-eastern United States are directly related to the spread of deer and the deer tick, which is the vector of the Babesia responsible for human infection. The spread of deer in the region was a direct result of cultural changes resulting in altered human behaviour which permitted deer to exist close to human settlement areas.


Stereospecificity of allergic contact dermatitis (ACD) to enantiomers. Part III. experimentally induced ACD to a natural sesquiterpene dialdehyde, polygodial in guinea pigs.
Guinea pigs were sensitized to polygodial 1, a natural sesquiterpene dialdehyde, using intradermal injections in Freund's complete adjuvant. Cross-reactions with a (+/-)-mixture of warburganal and (-)-warburganal 2 (a natural hydroxylated derivative of polygodial) showed a high specificity of the allergic response since the (-)-pseudoenantiomer (having the same configuration as the primary sensitizer) gave a stronger skin reaction than the racemic mixture.


The central light reflex of retinal arteries and veins in insulin-dependent diabetic subjects.
The width (Wr/Wo) and the intensity (Ir) of the central light reflex were studied on retinal arteries and veins in insulin-dependent diabetic patients. A diabetic group (n = 45) was compared to normal subjects (n = 57), and the groups were matched according to age and blood pressure levels. A computerized scanning microdensitometer was applied across various sites on vessels in fundus photographs. The Ir of the reflected light was significantly reduced in diabetic arteries and veins compared to the vessels in the control group (P less than 0.001). This may implicate abnormalities in blood rheology of the retinal circulation in diabetes. The Wr/Wo was found narrower in veins in diabetic patients (P less than 0.001). This probably indicates differences in haemodynamics of venous flow in diabetic and normal subjects. The intensity was correlated to the duration of diabetes (P less than 0.05), while neither the width nor the intensity were found related to sex, metabolic control, intraocular pressure or retinopathy.


Neuron-Derived Estrogen Is Critical for Astrocyte Activation and Neuroprotection of the Ischemic Brain.
17β-Estradiol (E2) is produced from androgens via the action of the enzyme aromatase. E2 is known to be made in neurons in the brain, but the functions of neuron-derived E2 in the ischemic brain are unclear. Here, we used a forebrain neuron-specific aromatase KO (FBN-ARO-KO) mouse model to deplete neuron-derived E2 in the forebrain and determine its roles after global cerebral ischemia. We demonstrated that ovariectomized female FBN-ARO-KO mice exhibited significantly attenuated astrocyte activation, astrocytic aromatization, and decreased hippocampal E2 levels compared with FLOX mice. Furthermore, FBN-ARO-KO mice had exacerbated neuronal damage and worse cognitive dysfunction after global cerebral ischemia. Similar results were observed in intact male mice. RNA-seq analysis revealed alterations in pathways and genes associated with astrocyte activation, neuroinflammation, and oxidative stress in FBN-ARO-KO mice. The compromised astrocyte activation in FBN-ARO-KO mice was associated with robust downregulation of the astrocyte-derived neurotrophic factors, BDNF and IGF-1, as well as the astrocytic glutamate transporter, GLT-1. Νeuronal FGF2, which acts in a paracrine manner to suppress astrocyte activation, was increased in FBN-ARO-KO neurons. Interestingly, blocking FGF2 signaling by central injection of FGFR3-neutralizing antibody was able to reverse the diminishment in neuroprotective astrocyte reactivity, and attenuate neuronal damage in FBN-ARO-KO mice. Moreover, in vivo E2 replacement suppressed FGF2 signaling and rescued the compromised reactive astrogliosis and cognitive deficits. Collectively, our data provide novel genetic evidence for a beneficial role of neuron-derived E2 in astrocyte activation, neuroprotection, and cognitive preservation following ischemic injury to the brain.SIGNIFICANCE STATEMENT Following cerebral ischemia, astrocytes become highly reactive and can exert neuroprotection through the release of neurotrophic factors and clearance of neurotoxic glutamate. The current study advances our understanding of this process by demonstrating that neuron-derived 17β-estradiol (E2) is neuroprotective and critical for induction of reactive astrocytes and their ability to produce astrocyte-derived neurotrophic factors, BDNF and IGF-1, and the glutamate transporter, GLT-1 after ischemic brain damage. These beneficial effects of neuron-derived E2 appear to be due, at least in part, to suppression of neuronal FGF2 signaling, which is a known suppressor of astrocyte activation. These findings suggest that neuron-derived E2 is neuroprotective after ischemic brain injury via a mechanism that involves suppression of neuronal FGF2 signaling, thereby facilitating astrocyte activation.


Oropharynx microbiota among alcoholics and non-alcoholics.
The oropharynx microbiota plays an important role in the origin of infections, especially among alcoholics whose airway defenses are impaired. To compare the normal oropharingeal flora in heavy alcohol drinker and non-alcoholics. 117 persons, 58 heavy alcohol drinkers and 59 non-alcoholics. Santa Casa de São Paulo Emergency Service. A blind prospective study. Prevalence of aerobic and anaerobic bacteria, and fungi. The study of the oropharynx microbiota among heavy alcohol drinkers demonstrated the presence of anaerobic microorganisms in 84.5% of them, including: Bacteroides sp, Prevotella melaninogenica, Fusobacterium sp, Veilonella sp, Peptostreptococcus sp, Propionibacterium sp, Bifidobacterium sp and Clostridium sp, versus 30.5% (p < 0.005) of non-alcoholics. Candida sp was present in 34.5% of heavy alcohol drinkers and 5.1% of non-alcoholics (p < 0.005). Enterobacteria predominated among heavy alcohol drinkers (25%) compared with non-alcoholics (5.5%) only in the age group 14 to 34 years (p < 0.05). Based upon these results, it was possible to conclude that the knowledge of the oropharynx microbiota among heavy drinkers and non-alcoholics has an important predictive value concerning probable etiologic agents of lower airway infections. Infections caused by anaerobic microorganisms and fungi should be taken into consideration during the choice of empirical therapy for heavy alcohol drinkers.


Bacteriocin production by Enterococcus faecium FAIR-E 198 in view of its application as adjunct starter in Greek Feta cheese making.
Bacteriocin production by Enterococcus faecium FAIR-E 198, isolated from Greek Feta cheese, was studied in batch fermentations, under conditions simulating Feta cheese preparation. Maximum enterocin activity and growth rate was obtained in de Man-Rogosa-Sharpe (MRS) broth at 37 degrees C with controlled pH 6.5. The enterocin was produced throughout the growth phase of the microorganism, showing primary metabolite kinetics with a peak activity during the mid-exponential phase. The use of skimmed milk as substrate revealed low enterocin activity. When fermentations were performed in skimmed milk in the presence of rennet, CaCl2, and a mixed starter culture, no enterocin activity was observed, although the examined strain grew well under the above conditions. Finally, when E. faecium FAIR-E 198 was applied as adjunct starter in Feta cheese making, no enterocin activity was detected throughout ripening. Results obtained underline the frequently underestimated finding that in vitro production by novel bacteriocinogenic starter or co-cultures is no guarantee for in situ efficiency. It was concluded that the complex food environment thoroughly interferes with bacteriocin production levels.


Pre-existing vascular disease in the radial artery and other coronary artery bypass conduits.
There is increasing interest in the radial artery (RA) as a coronary artery bypass graft (CABG). However, few studies have examined the prevalence of pre-existing disease in this vessel. Histological specimens from 177 RA were compared with 168 of internal mammary artery (IMA) and 86 of long saphenous vein (LSV) from the same patients undergoing CABG. The degree of stenosis, active atheroma, intimal thickening, and medial hyaline sclerosis was assessed. - 99% of IMAs, 98% of RAs and 100% of SVs had less than 30% stenosis. 91% of IMAs, 42% of RAs and 70% of SVs had less than 5% stenosis. Medial sclerosis was present in 10% of IMAs, 36% of LSVs and 46% of RAs. Medial calcification was present in 9% of RAs, 1% of LSVs and not in IMAs. The majority of conduits did not have evidence of severe disease. There is an increased prevalence of mild intimal thickening, medial sclerosis and medial calcification in RAs compared with IMAs and LSVs. The implications for longer-term graft patency are uncertain.


Insurance and education predict long-term survival after orthotopic heart transplantation in the United States.
Insurance status and education are known to affect health outcomes. However, their importance in orthotopic heart transplantation (OHT) is unknown. The United Network for Organ Sharing (UNOS) database provides a large cohort of OHT recipients in which to evaluate the effect of insurance and education on survival. UNOS data were retrospectively reviewed to identify adult primary OHT recipients (1997 to 2008). Patients were stratified by insurance at the time of transplantation (private/self-pay, Medicare, Medicaid, and other) and college education. All-cause mortality was examined using multivariable Cox proportional hazard regression incorporating 15 variables. Survival was modeled using the Kaplan-Meier method. Insurance for 20,676 patients was distributed as follows: private insurance/self-pay, 12,298 (59.5%); Medicare, 5,227 (25.3%); Medicaid, 2,320 (11.2%); and "other" insurance, 831 (4.0%). Educational levels were recorded for 15,735 patients (76.1% of cohort): 7,738 (49.2%) had a college degree. During 53 ± 41 months of follow-up, 6,125 patients (29.6%) died (6.7 deaths/100 patient-years). Survival differed by insurance and education. Medicare and Medicaid patients had 8.6% and 10.0% lower 10-year survival, respectively, than private/self-pay patients. College-educated patients had 7.0% higher 10-year survival. On multivariable analysis, college education decreased mortality risk by 11%. Medicare and Medicaid increased mortality risk by 18% and 33%, respectively (p ≤ 0.001). Our study examining insurance and education in a large cohort of OHT patients found that long-term mortality after OHT is higher in Medicare/Medicaid patients and in those without a college education. This study points to potential differences in the care of OHT patients based on education and insurance status.


2,3,9- and 2,3,11-trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands.
Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D2 dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D1 and D2 DR and establish the structure-activity relationship (SAR) as dopaminergic agents. In general, all the tested THPBs with protected phenolic hydroxyls showed a lower affinity for D1 and D2 DR than their corresponding homologues with free hydroxyl groups. In previous studies in which dopaminergic affinity of 1-benzyl-THIQs (BTHIQs) was evaluated, the presence of a Cl into the A-ring resulted in increased affinity and selectivity towards D2 DR. This is in contrast with the current study since the existence of a chlorine atom into the A-ring of the THPBs caused increased affinity for D1 DR but dramatically reduced the selectivity for D2 DR. An OH group in position 9 of the THPB (9f) resulted in a higher affinity for DR than its homologue with an OH group in position 11 (9e) (250 fold for D2 DR). None of the compounds showed any cytotoxicity in freshly isolated human neutrophils. A molecular modelling study of three representative THPBs was carried out. The combination of MD simulations with DFT calculations provided a clear picture of the ligand binding interactions from a structural and energetic point of view. Therefore, it is likely that compound 9d (2,3,9-trihydroxy-THPB) behave as D2 DR agonist since serine residues cluster are crucial for agonist binding and receptor activation.


Helix-loop-helix proteins are present and differentially expressed in different cell lines from the anterior pituitary.
The basic-helix-loop-helix (bHLH) class of transcriptional activators, important in the establishment of many different cell lineages, share two important properties: the ability to heterodimerize with other members of this family and to bind DNA containing the loose consensus sequence CANNTG. This study takes advantage of these shared characteristics to begin to address whether or not bHLH proteins are present in pituitary cells. Gel-shift and Southwestern assays using an oligonucleotide containing a bHLH binding consensus sequence demonstrate that pituitary-specific proteins are present in extracts from adult pituitary tissue and pituitary cell lines and bind specifically to this sequence. Pituitary extracts were also found to contain several factors which interact with Id protein, a negative regulator of bHLH activity, in Far-Western assays of protein-protein interactions. Finally, messenger RNA for Id is present in pituitary cell lines but is absent in adult pituitary tissue. Together, these studies indicate that bHLH proteins are present in pituitary cells and their levels are differentially regulated in the separate cell types.


Impact of SARS-CoV-2 RNA titer on the level of IgG antibodies in recovered patients with COVID-19 disease.
It is important to better understand the presence of neutralizing anti-SARS-CoV-2 antibodies in the population, as they potentially prevent (re)infection. To correlate the Cycle threshold (Ct value) of SARS-CoV-2 and its impact on specific Anti-SARS-CoV-2 IgG titer, to reveal the effect of age and disease severity on antibodies titer. A total of 153 infected participants laboratory-confirmed COVID-19 cases 4-11 months ago, aged 18-85 years old (mean = 43.58, SD ± 15.34) were enrolled in the study. They have not received any COVID-19 vaccine. A questionnaire was prepared including demographic data, age, gender, residence, and symptoms severity they suffered. Five mL of venous blood was taken from each participant to measure SARS-CoV-2 IgG antibodies against the receptor binding domain (RBD) by (VIDAS SARS-COV-2 IgG - Biomerieux kit). Ct values were measured by qRT-PCR (BIO-RAD-CFX96) kit which detected two virus genes, namely (RdRp-N genes). Lowest Ct values were detected significantly in age group 50-59 and 70-85 respectively. The highest mean of IgG was detected in age groups 70-85 and 50-59, and was found to be significantly correlated with disease severity. There is a direct relationship between Ct values and the titer of specific IgG, as increasing in viral load is associated with a higher level of antibodies. Antibodies were detected several months after infection with the highest mean after 10-11 months. Specific Anti-viral IgG are significantly associated with increasing age and disease severity, and the direct relation of IgG with viral load. Antibodies are detected several months post-infection but their protective efficacy is controversial.


Preparation, characterization and in vivo evaluation of curcumin self-nano phospholipid dispersion as an approach to enhance oral bioavailability.
The aim of this study was to examine the efficacy of self-nano phospholipid dispersions (SNPDs) based on Phosal(®) to improve the oral bioavailability of curcumin (CUR). SNPDs were prepared with Phosal(®) 53 and Miglyol 812 at different surfactant ratio. Formulations were evaluated for particle size, polydispersity index, zeta potential, and robustness toward dilution, TEM as well as in vitro drug release. The in vivo oral absorption of selected formulations in comparison to drug suspension was evaluated in rats. Moreover, formulations were assessed for in vitro characteristic changes before and after storage. The SNPDs were miscible with water in any ratio and did not show any phase separation or drug precipitation. All the formulas were monodisperse with nano range size from 158±2.6 nm to 610±6.24 nm. They passed the pharmacopeial tolerance for CUR dissolution. No change in dissolution profile and physicochemical characteristics was detected after storage. CUR-SNPDs are found to be more bioavailable compared with suspension during an in vivo study in rats and in vitro release studies failed to imitate the in vivo conditions. These formulations might be new alternative carriers that enhance the oral bioavailability of poorly water-soluble molecules, such as CUR.


Intraoperative high-dose calcium stimulation test in patients with sporadic medullary thyroid carcinoma is highly accurate in predicting lateral neck metastases.
Intraoperative measurement of calcitonin is not highly accurate in predicting the completeness of the operative resection after total thyroidectomy combined with central neck dissection (TT-CND) in patients with medullary thyroid carcinoma (MTC). We evaluated whether an intraoperative, high-dose calcium stimulation test (IO-CST) after TT-CND can predict lateral neck involvement. Eleven patients who underwent primary operation for sporadic MTC were included. High-dose (25 mg/kg) calcium gluconate was administered after TT-CND with calcitonin measured at 2, 5, and 10 minutes after the calcium gluconate infusion. There were 2 males and 9 females (mean age, 51 years; range, 18-88). Three patients showed lateral neck metastases. At a mean follow-up of 7.0 months (range, 2-10), 1 patient showed distant metastases and 1 a slightly increased calcitonin level. After IO-CST, serum calcitonin increased in all the 3 patients with lateral neck metastases, and it remained unchanged or decreased in the other patients without lateral neck metastases. Percent variation of serum calcitonin after IO-CST was 92% in patients with lateral neck metastases and -3.1 ± 4.9% in patients without lateral neck metastases. Calcitonin measurement after IO-CST in patients with sporadic MTC can be highly accurate in predicting lateral neck nodes involvement. These results could represent a stimulus toward the development of a quick calcitonin assay.


Split-face treatment of facial dyschromia: pulsed dye laser with a compression handpiece versus intense pulsed light.
Many visible light lasers and intense pulsed light (IPL) devices are available to treat photodamaged skin. The objective was to perform a multiple-treatment split-face comparison evaluating a pulsed dye laser (PDL) with a compression handpiece versus IPL for photorejuvenation. Ten subjects were treated three times at 3- to 4-week intervals. One side of the face was treated with the PDL with compression handpiece, and the other with IPL. One month after final treatment, blinded evaluation assessed for improvements in dyschromias and texture. Patients provided self-assessment of improvement in dyschromias and texture. Time to complete final treatments and pain during all treatments were recorded for each device. Improvement of the PDL was (mean) 86.5, 65, 85, 38, and 40% for dark lentigines, light lentigines, vessels <0.6 mm, vessels >0.6 mm, and texture, respectively, versus 82, 62.5, 78.5, 32.5, and 32%, respectively, for the IPL side. Patient-evaluated difference in improvement for vascular lesions significantly favored the PDL (p=.011). Mean third treatment times were 7.7 minutes for PDL versus 4.6 minutes for the IPL (p=.005). Mean pain ratings were 5.8 for the PDL and 3.1 for the IPL (p=.007). Purpura-free procedures depended on proper technical use of the compression handpiece when treating lentigines with the PDL. The PDL with compression handpiece and IPL are highly effective for photorejuvenation.


The effects of plyometric jump training on physical fitness attributes in basketball players: A meta-analysis.
There is a growing body of experimental evidence examining the effects of plyometric jump training (PJT) on physical fitness attributes in basketball players; however, this evidence has not yet been comprehensively and systematically aggregated. Therefore, our objective was to meta-analyze the effects of PJT on physical fitness attributes in basketball players, in comparison to a control condition. A systematic literature search was conducted in the databases PubMed, Web of Science, and Scopus, up to July 2020. Peer-reviewed controlled trials with baseline and follow-up measurements investigating the effects of PJT on physical fitness attributes (muscle power, i.e., jumping performance, linear sprint speed, change-of-direction speed, balance, and muscle strength) in basketball players, with no restrictions on their playing level, sex, or age. Hedge's g effect sizes (ES) were calculated for physical fitness variables. Using a random-effects model, potential sources of heterogeneity were selected, including subgroup analyses (age, sex, body mass, and height) and single training factor analysis (program duration, training frequency, and total number of training sessions). Computation of meta-regression was also performed. Thirty-two studies were included, involving 818 total basketball players. Significant (p < 0.05) small-to-large effects of PJT were evident on vertical jump power (ES = 0.45), countermovement jump height with (ES = 1.24) and without arm swing (ES = 0.88), squat jump height (ES = 0.80), drop jump height (ES = 0.53), horizontal jump distance (ES = 0.65), linear sprint time across distances ≤10 m (ES = 1.67) and >10 m (ES = 0.92), change-of-direction performance time across distances ≤40 m (ES = 1.15) and >40 m (ES = 1.02), dynamic (ES = 1.16) and static balance (ES = 1.48), and maximal strength (ES = 0.57). The meta-regression revealed that training duration, training frequency, and total number of sessions completed did not predict the effects of PJT on physical fitness attributes. Subgroup analysis indicated greater improvements in older compared to younger players in horizontal jump distance (>17.15 years, ES = 2.11; ≤17.15 years, ES = 0.10; p < 0.001), linear sprint time >10 m (>16.3 years, ES = 1.83; ≤16.3 years, ES = 0.36; p = 0.010), and change-of-direction performance time ≤40 m (>16.3 years, ES = 1.65; ≤16.3 years, ES = 0.75; p = 0.005). Greater increases in horizontal jump distance were apparent with >2 compared with ≤2 weekly PJT sessions (ES = 2.12 and ES = 0.39, respectively; p < 0.001). Data from 32 studies (28 of which demonstrate moderate-to-high methodological quality) indicate PJT improves muscle power, linear sprint speed, change-of-direction speed, balance, and muscle strength in basketball players independent of sex, age, or PJT program variables. However, the beneficial effects of PJT as measured by horizontal jump distance, linear sprint time >10 m, and change-of-direction performance time ≤40 m, appear to be more evident among older basketball players.


Determination of prognosis in patients with prostate cancer treated with radical prostatectomy: prognostic value of CD44v6 score.
A third of the patients treated with radical prostatectomy experience progression even when tumors are confined pathologically to the prostate. CD44 may be a promising prognostic marker for determining malignant potential. However, there has not been a standard scoring system because of its heterogeneous staining pattern. Thus, we developed an objective scoring system to evaluate reliably CD44v6 (Bender Medsystems, Vienna, Austria) as a prognostic marker for prostate cancer. A total of 22 patients with metastatic stage pT3bN0M0 or any pTN1M0 disease and 18 with nonmetastatic disease less than stage pT3bN0M0 were selected from a well examined group of 114 who underwent radical retropubic prostatectomy. Mean followup was 33 months (range 4 to 78). A combined CD44v6 score was determined by adding the scores of the primary and secondary areas. CD44v6 expression in terms of the CD44v6 score in primary and metastatic tissues was examined. The relationships of CD44v6 expression with pathological stage, progression and PSA-free survival were also evaluated. The prognostic value of the CD44v6 score for progression was analyzed by multivariate analysis. Progression in the metastatic group was significantly higher than in the nonmetastatic group (p <0.0001). CD44v6 expression of the primary tumors differed significantly in the 2 groups (p = 0.014). The CD44v6 score in primary tumor tissues inversely correlated with pathological stage (p = 0.004) and progression (p = 0.035), and positively correlated with PSA-free survival (p = 0.041). Furthermore, patients in the nonmetastatic group with a CD44v6 score of greater than 75 (cutoff value) had a significantly better prognosis (log rank test p = 0.0022), while those with a CD44v6 score of less than 75 had a prognosis similar to those in the metastatic group. On multivariate analysis pathological stage and surgical margin positivity were independent factors for progression but the CD44v6 score was not. According to our results the suggested CD44v6 score system is useful. A CD44v6 score of less than 75 may be a predictor of poor prognosis in the nonmetastatic group and this property may have potential application for planning adjuvant therapy.


Microsurgery and varicocele: state of the art.
Many surgical procedures have been proposed in the treatment of varicocele; however, the rate of recurrence and of postoperative complications, together with important correlation of this disease with male sterility, has played an important role in determining the success of microsurgery. In the present brief review, the indications for microsurgery and microsurgical dissection and/or anastomosis are described in comparison to traditional surgery.


Opioid agonists modulate release of neurotransmitters in bovine trachealis muscle.
Stimulation of opioid receptors in the airways can modulate cholinergic neurotransmission and thereby reduce bronchoconstriction. This protecting effect of opioids against bronchoconstriction may be of clinical interest. Inhalation of opioids as a method of analgesia is likely to result in an opioid concentration at airway receptors sufficient to protect against bronchoconstriction; the concentration may be insufficient when opioids are administered by conventional techniques. In addition, new selective opioids may be developed that could more selectively protect the airways against bronchoconstriction. The effect of three selective opioid agonists on the contractile response to electric field stimulation (EFS) was studied in isolated muscle strips from four regions of the bovine trachea (upper, or laryngeal; upper middle; lower middle; lower, or carinal). The selective kappa agonist trans-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl) cyclohexyl benzene acetamide (U-50488 H) and the selective mu-opioid agonist D-Ala2-N-MePhe4-Gly-ol5-enkephalin (DAMGO) reduced significantly (P < 0.001 and P < 0.001, respectively) the contractile response to EFS. The attenuation of the contractile response by U-50488 H was concentration-dependent (P < 0.0001) and tended to be larger at low stimulating frequencies (P = 0.055). The attenuation of the contractile response by DAMGO was frequency-dependent (P < 0.01). The selective delta-opioid agonist D-penicillamine2-D-penicillamine5-enkephalin had no significant effect on the contractile response to EFS (P = 0.71). There were no significant differences among the four regions of the trachea in their responses to the selective opioid agonists U-50488 H (P = 0.50) and DAMGO (P = 0.44). Neither U-50488 H nor DAMGO altered the contractile response to acetylcholine P > 0.11, P > 0.21, respectively), suggesting that the opioid agonists have a prejunctional effect. The attenuation of the contractile response to EFS by U-50488 H was partially but significantly antagonized by 10(-5) M naloxone (P < 0.01) and by 10(-5) and 10(-6) M of the selective kappa-opioid antagonist 2,2'-[1,1'-biphenyl] 4,4'-diyl- bis [2-hydroxy-4,4-dimethyl-morpholinium] (P < 0.05). Naloxone (10(-5) M) abolished the inhibitory effect of DAMGO, suggesting that opioid receptors are involved in the attenuation of the contractile response to EFS afforded by DAMGO and U-50488 H. We conclude that prejunctional kappa- and mu-opioid receptors attenuate the contractile response of isolated bovine trachealis muscle to EFS by inhibiting cholinergic neurotransmission. This effect is uniform throughout the trachealis muscle. delta-Opioid receptors are apparently not present in the bovine trachealis muscle. Caution must be used in extrapolating these results to the intact human. In this study little or no inhibitory effect of the opioids was observed at concentrations expected at airway receptor sites when administered by conventional techniques. However, the effect may be large enough to protect against bronchoconstriction when nebulized opioids are administered by inhalation.


Stability of arsenate-bearing Fe(III)/Al(III) co-precipitates in the presence of sulfide as reducing agent under anoxic conditions.
Currently, the co-precipitation of arsenate with ferric iron at molar ratios Fe(III)/As(V) ≥ 3 by lime neutralization produces tailings solids that are stable under oxic conditions. However not much is known about the stability of these hazardous co-precipitates under anoxic conditions. These can develop in tailings storage sites by the action of co-discharged reactive sulfides, organic reagent residuals or bacterial activity. The ferric matrix can then undergo reductive dissolution reactions, which could release arsenic into the pore water. Co-ions like aluminum could provide a redox-immune sink to scavenge any mobilized arsenic as a result of reduction of ferric. As such, in this work Fe(III)/As(V) = 4 and aluminum substituted Fe(III)/Al(III)/As(V) = 2/2/1 co-precipitates were produced in a mini continuous co-precipitation process circuit and subjected to excess sulfide addition under inert gas to evaluate their stability. It was found that the ferric-arsenate co-precipitate could retain up to 99% (30 mg/L in solution) of its arsenic content despite the high pH (10.5) and extremely reducing (Eh < -200 mV) environment. There was no significant reduction of arsenate and only 45% of ferric iron was reduced. Partial aluminum substitution was found to cut the amount of mobilized arsenic by 50% (down to 15 mg/L) hence mixed Fe(III)/Al(III)-arsenate co-precipitates may offer better resistance to reductive destabilization over the long term than all iron co-precipitates.


The Role of Preventive Ablation of Ventricular Tachycardia in the Patient with Coronary Artery Disease, Reduced Left Ventricular Function, and a New Implantable Cardioverter Defibrillator Implant.
Most patients referred for ventricular tachycardia (VT) ablation have already suffered multiple therapies for recurrent VT, typically in the form of implantable cardioverter defibrillator (ICD) shocks. Recent landmark trials have looked at these populations and suggest potential usefulness of early, preventive ablation of VT in patients with ischemic cardiomyopathy. In this review the potential role of early VT ablation in patients with ischemic cardiomyopathy, current controversies regarding VT ablation in this population, and ongoing and future research that may further inform clinical decision making regarding optimal timing of ablation in these patients are discussed.


Riceabetes: is the association of type 2 diabetes with rice intake due to a high carbohydrate intake or due to exposure to excess inorganic arsenic?
A high intake of rice is associated with a high incidence and prevalence of diabetes. While this may be partially due to the high glycemic index carbohydrate content, it may also be due to a high arsenic level found in rice. Arsenic increases insulin resistance and decreases beta-cell function through oxidative stress, high cytokine levels, activation of NF-kappa B and increased amyloid formation in the pancreatic beta cells.


Detection and Quantification of RNA Phosphorothioate Modifications Using Mass Spectrometry.
This article describes a protocol for detecting and quantifying RNA phosphorothioate modifications in cellular RNA samples. Starting from solid-phase synthesis of phosphorothioate RNA dinucleotides, followed by purification with reversed-phase HPLC, phosphorothioate RNA dinucleotide standards are prepared for UPLC-MS and LC-MS/MS methods. RNA samples are extracted from cells using TRIzol reagent, then digested with a nuclease mixture and analyzed by mass spectrometry. UPLC-MS is employed first to identify RNA phosphorothioate modifications. An optimized LC-MS/MS method is then employed to quantify the frequency of RNA phosphorothioate modifications in a series of model cells. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Synthesis, purification, and characterization of RNA phosphorothioate dinucleotides Basic Protocol 2: Digestion of RNA samples extracted from cells Basic Protocol 3: Detection and quantification of RNA phosphorothioate modifications by mass spectrometry.


A fluorescent probe for detection of Hg2+ ions constructed by tetramethyl cucurbit[6]uril and 1,2-bis(4-pyridyl)ethene.
In this paper, tetramethyl cucurbit[6]uril (TMeQ[6]) and 1,2-bis(4-pyridyl)ethene (G) were used to construct a supramolecular fluorescent probe G@TMeQ[6]. The host-guest interaction between TMeQ[6] and G was investigated using 1H NMR spectroscopy, single-crystal X-ray diffraction and various experimental techniques. The results show that TMeQ[6] and G form an inclusion complex with a host-guest ratio of 1:1 and the equilibrium association constant (Ka) was 2.494 × 104 M-1. The G@TMeQ[6] fluorescent probe can sensitively recognize Hg2+ ions by fluorescence enhancement. The linear range is 0.33 × 10-5-1.65 × 10-5 mol·L-1, R2 = 0.9926, and the limit of detection is 4.12 × 10-8 mol·L-1. The fluorescent probe can be used to detect the concentration of Hg2+ ions in aqueous solution, and provides a theoretical basis for the development of new fluorescent probes for detecting heavy metal ions.


Recidivism after orthopaedic trauma has diminished over time.
The purpose was to analyze our trauma population during two periods to assess for predictors of recidivism. Prior (2007-2011, n = 879) and recent (2014-2019, n = 954) orthopaedic trauma patients were reviewed. Recidivists were those returning with an unrelated injury. Recidivism rates were compared, and factors associated with recidivism were identified. Recidivism decreased: 18.7% to 14.3% (p = 0.01). Mean age and sex of the two cohorts were not different. Recent recidivists were more likely to sustain gunshot wound (GSW) injuries (22.1% vs 18.9%, p = 0.09), and mental illness was more common (56.6% vs 28.1%, p < 0.0001). The recent recidivist population was less often married (12.9% vs 23.8%, p = 0.03), and both recidivist groups were often underinsured (Medicaid or uninsured: (60.6% vs 67.0%)). Recidivism diminished, although more GSW and mental illness were seen. Recidivists are likely to be underinsured. The changing profile of recidivists may be attributed to socioeconomic trends and new programs to improve outcomes after trauma.


Oxalotrophic bacteria.
Oxalic acid and its salts are widespread in nature, as they are produced by many species of plants, algae and fungi. The bacteria, which are capable of using oxalate as a sole carbon and energy source, are described as being "oxalotrophic". Oxalotrophic bacteria do not constitute a homogeneous taxonomic group, but they do constitute a well-defined physiological group. A limited number of aerobic bacteria which are able to utilize oxalate as sole carbon and energy source have been completely described. Most of them are facultative methylotrophs and/or facultative hydrogen-oxidizing chemolithoautotrophs. In this review, the current status of the taxonomy and biodiversity of oxalotrophic bacteria in various environments, and aspects of their biotechnological potential, are briefly summarized.


A Case Series of Dacryoendoscopy in Childhood: A Diagnostic and Therapeutic Alternative for Complex Congenital Nasolacrimal Duct Obstruction Even in the First Year of Life.
Congenital nasolacrimal duct obstruction (CNLDO) is the most common cause of epiphora in infancy. Spontaneous resolution occurs in the majority of the cases by 1 year of age. Nevertheless, obstruction has a negative impact on the outcome of conservative or surgical therapy, especially in cases of complex CNLDO. When the condition persists beyond several months, early intervention with dacryoendoscopy (DE) around the age of 1 year could yield good results. The objective of the study is to analyze the success rate and effectiveness of early DE for complex CNLDO in the first year of life. A retrospective, non-comparative case series is presented. DE was performed under general anesthesia in patients between the age of 1 and 12 months with severe recurrent acute or chronic dacryocystitis. The medical histories, intraoperative and postoperative results after 3 months as well as via parents' interviews were analyzed to investigate the success rate. A total of 18 consecutive DE in 16 patients between the age of 1 and 12 months (mean 7.3 ± 3.4 months) were studied. Nine lacrimal ducts were diagnosed with persistent chronic dacryocystitis refractory to probing/syringing. The remaining 9 presented recurrent acute dacryocystitis. Diagnostic DE was performed in 18 cases. A therapeutic DE was conducted in 15 lacrimal ducts (83.3%) with simultaneous correction of the associated stenosiswith the tip of the endoscope. A visual controlled opening of the stenosis was impossible in 3 cases due to a too narrow presaccal anatomy (n = 1), an osseous duct stenosis (n = 1), and a bulging membrane of Hasner into the inferior nasal meatus (n = 1). Postoperative findings were classified into four categories: poor, fair, good and excellent. Good results were documented in 16.7% (n = 3) and excellent results in 77.7% (n = 14). The bony obstruction was treated with dacryocystorhinostomy. A minimum follow-up of 3 months was considered for final clinical analysis. Ten patients' parents (12 surgeries) were interviewed by telephone (mean follow-up 24.8 months). No recurrence of stenosis and no further postoperative complications were observed. DE is a diagnostic and therapeutic option for complex CNLDO in patients before the age of 1 year. The outcome of DE in the 3 months follow-up is highly indicative of positive final results in terms of patency of the lacrimal duct.


A Noonan-like pediatric patient with a de novo CBL pathogenic variant and an RNF213 polymorphism p.R4810K presenting with cardiopulmonary arrest due to left main coronary artery ostial atresia.
Left main coronary artery ostial atresia (LMCAOA) is an extremely rare condition. Here, we report the case of a 14-year-old boy with Noonan syndrome-like disorder in whom LMCAOA was detected following cardiopulmonary arrest. The patient had been diagnosed with Noonan syndrome-like disorder with a pathogenic splice site variant of CBL c.1228-2 A > G. He suddenly collapsed when he was running. After administering two electric shocks using an automated external defibrillator, the patient's heartbeat resumed. Cardiac catheterization confirmed the diagnosis of LMCAOA. Left main coronary artery angioplasty was performed. The patient was discharged without neurological sequelae. Brain magnetic resonance imaging revealed asymptomatic Moyamoya disease. In addition, RNF213 c.14429 G > A p.R4810K was identified. There are no reports on congenital coronary malformations of compound variations of RNF213 and CBL. In contrast, the RNF213 p.R4810K polymorphism has been established as a risk factor for angina pectoris and myocardial infarction in adults, and several congenital coronary malformations due to genetic abnormalities within the RAS/MAPK signaling pathway have been reported. This report aims to highlight the risk of sudden death in patients with RASopathy and RNF213 p.R4810K polymorphism and emphasize the significance of actively searching for coronary artery morphological abnormalities in these patients.


Hemorrhagic shock after contrast-enhanced ultrasound-guided liver biopsy: A case report of primary hepatic angiosarcoma.
Primary hepatic angiosarcoma (PHA) is a rare, highly aggressive malignancy. There is no specificity in clinical manifestations, laboratory examinations and imaging examinations. The definitive diagnosis of PHA depends on pathological analysis. The gold standard method to obtain specimens is percutaneous transhepatic biopsy under the guidance of contrast-enhanced ultrasound (CEUS). However, CEUS-guided biopsy for PHA is controversial. If a biopsy is necessary, a comprehensive preoperative evaluation is essential. In addition, CEUS has an auxiliary value in diagnosing PHA. In this case, we present an elderly woman who underwent CEUS-guided liver mass biopsy. The patient developed hemorrhagic shock after biopsy.


Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU).
Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. Non-systematic Review.


Evaluating the Regional Uptake of Minimally Invasive Colorectal Surgery: a Report from the Surgical Care Outcomes Assessment Program.
Minimally invasive surgery (MIS) for colorectal disease has well-known benefits, but many patients undergo open operations. When choosing an MIS approach, robotic technology may have benefits over traditional laparoscopy and is increasingly used. However, the broad adoption of MIS, and specifically robotics, across colorectal operations has not been well described. Our primary hypothesis is that rates of MIS in colorectal surgery are increasing, with different contributions of robotics to abdominal and pelvic colorectal operations. Rates of MIS colorectal operations are described using a prospective cohort of elective colorectal operations at hospitals in the Surgical Care Outcomes Assessment Program (SCOAP) from 2011 to 2018. The main outcome was proportion of cases approached using open, laparoscopic, and robotic surgery. Factors associated with increased use of MIS approaches were described. Across 21,423 elective colorectal operations, rates for MIS (laparoscopic or robotic surgery) increased from 44% in 2011 to 75% in 2018 (p < 0.001). Approaches for abdominal operations (n = 12,493) changed from 2 to 11% robotic, 43 to 63% laparoscopic, and 56 to 26% open (p < 0.001). Approaches for pelvic operations (n = 8930) changed from 3 to 33% robotic, 40 to 42% laparoscopic, and 57 to 24% open(p < 0.001). These trends were similar for high-(100 + operations/year) and low-volume hospitals and surgeons. At SCOAP hospitals, the majority of elective colorectal operations is now performed minimally invasively. The increase in the MIS approach is primarily driven by laparoscopy in abdominal procedures and robotics in pelvic procedures.


COVID-19 vaccine hesitancy among American Indian and Alaska native college students: the roles of discrimination, historical trauma, and healthcare system distrust.
For American Indians and Alaska Native (AIAN) and other communities of color, experiences with discrimination and historical trauma may contribute to healthcare system distrust and negatively affect health care decisions, including vaccination. A saturated path analysis was conducted to examine the direct and indirect associations of thoughts regarding historical losses (of culture, language, and traditional ways) and AIAN racial discrimination with historical loss associated distress, healthcare system distrust, and COVID-19 vaccine hesitancy among AIAN college students (N = 391). Historical loss thoughts and experiences with racial discrimination were strongly associated with each other, and both were uniquely associated with greater historical loss associated distress. In turn, historical loss associated distress was associated with greater healthcare system distrust, which in turn was associated with greater likelihood of being COVID-19 vaccine hesitant. While further research is needed, the findings suggest that to address health disparities for AIAN people it is necessary to consider how to best overcome healthcare system distrust and factors that contribute to it, including historical trauma and contemporary experiences with discrimination.


Adolescents' smoking behavior and its relationships with psychological constructs based on transtheoretical model: a cross-sectional survey.
Korean adolescents' smoking is currently being considered as a crucial factor determining the health status of adolescents and an important public health and social issue. The purpose of the study was to test the applicability of the Transtheoretical model to gain an understanding of smoking behavior change. A total of 706 adolescents who participated in the smoking cessation programs administered by the Korea Quit Smoking Association or Korean Association of Smoking & Health in 2003 were recruited. Four Korean-version questionnaires were used to identify the stages of smoking behavior and psychological attributes: Stage of Smoking Behavior Change Scale, Processes of Change Scale for Smoking, Decision Balance Scale for Smoking, and Self-efficacy Scale to avoid smoking. Korean adolescents' smoking behavior was differed according to gender. In addition, the findings revealed that behavioral and cognitive processes of change, self-efficacy, and positives differed across the stages of smoking behavior, and that psychological constructs of the transtheoretical model had a statistically significant impact on smoking behavior change. This research could spawn the development of theory-based and empirically supported smoking cessation intervention strategies and programs directed toward adolescents in the health care and nursing areas.


Effects of food intake and body weight on a serotonergic turnover index in rat hypothalamus.
Absolute levels and ratio of serotonergic compounds in food-related hypothalamic nuclei were determined with a chromatographic method comparing for control (C) versus lean (L) versus obese (O) rats. In all three groups, a second parameter, i.e., fasting (F) versus satiation (S) was superimposed on the body weight factor. Indoleamine levels failed to show statistical differences depending on the body weight and/or the nutritional status. A significant negative correlation between an index of the serotonin turnover, the 5-HIAA/5-HT ratio, and body weight was found for the paraventricular (PVN) nucleus in the C and L groups as well as for the lateral (LH) nucleus for the C and O groups. A positive correlation was found for the ventromedian (VMH) nucleus in the O group. These data suggest that the body weight factor is implicated in the central serotonergic regulation more than the feeding parameter.


The process of developing the professional identity of the Nurse Case Care Manager: A Grounded Theory Study.
The Nurse Case Care Manager (NCCM) is still an emerging figure in the Italian healthcare context. The knowledge of the dynamics inherent in the process of identity development shows how they can be decisive for the affirmation and recognition of this new role. The aim of the study was therefore to analyse the psychosocial processes of developing the identity of the NCCM for a better understanding of the variables that influence its development. A qualitative study with Grounded Theory method was conducted. From December 2018 to January 2019, 20 semi-structured interviews were given to the NCCM of the Emilia Romagna Region and the Lombardy Region. The analysis of the material has led to a structuring of the theoretical model on the processes of development of professional identity. Two main conditions have been identified: that of the "LOST CASE MANAGER" and that of the "CASE MANAGER DIRECTOR". This process requires time, perseverance, courage and personal skills. Two transversal background concepts have been identified, namely "available space" and "relationship with the family". The process of developing the NCCM's professional identity encounters several obstacles. Among these, in particular a lack of recognition by operators highlighting the need for greater organizational clarity in the context in which the professional operates, in order to facilitate the inclusion of the NCCM clarifying skills and effectiveness profile.


Ultra-fast recovery of cathode materials from spent LiFePO4 lithium-ion batteries by novel electromagnetic separation technology.
The separation of electrode materials from current collectors plays a significant role in determining the leaching efficiency of different metals from spent lithium-ion batteries (LIBs). In the presented research, a highly efficient, environmentally sustainable, and cost-effective cathode materials separation strategy was proposed for spent LiFePO4 batteries. Based on the difference in the thermal expansion coefficient of the binder and aluminum foil, the electromagnetic induction system was examined to harvest cathode materials for the first time, which could provide a high heating rate to erase the mechanical interlocking force between Al foil and coated material, and breaking the chemical bond or Van der Waals forces of the binder. The process avoids the usage of any chemicals such as acids and alkalis, thus eliminating the emission of wastewater. Our system shows ultra-fast separation (3 min) and achieves high-purity of recovered electrode materials and Al foils (99.6% and 99.2%). Furthermore, the morphology and crystalline structure of delaminated electrode materials remain almost the same compared with the pristine materials, which provides a previously unexplored technology to realize sustainable spent battery recycling.


Wound repair of the oral mucosa. Immunohistological and 3H-thymidine-autoradiographic observations.
The migratory and proliferative capacity of oral epithelium was studied after induction of subepithelial suction blisters in palatal rat mucosa. FITC-coupled lectins and their affinities to epithelial cells at the wound margin were analyzed by immunofluorescence microscopy. Immunocytochemical distribution of 67 K-keratin polypeptides in different epithelial layers were studied using specific antisera against keratin proteins. By means of 3H-thymidine-autoradiography the proliferation of epithelial basal cells and their migration at the wound edge was quantified by evaluation of the labelling index. Double labelling was performed, combining the autoradiographic and the keratin staining technique. It was found that the subepithelial suction blister showed rapid repair (epithelial regeneration after 3-4 days). Peanut Agglutinin (PNA) showed a selective affinity to the basal 2-3 layers of oral rat mucosa. No modifications of lectin affinities were found in epithelial wound repair. PNA-positive keratinocytes were demonstrated in the migratory epithelial tongue. The selective presence of 67 K-keratin (67 K) in the suprabasal epithelial cell layers was interpreted as an indication of the differentiation process in rat oral mucosa. The 3H-thymidine-labelling index of basal cells increased significantly, beginning at the wound edge after 24 h. The peak of the labelling index curve was located in the vicinity of the wound after 96 h. Double labelling technique revealed 67 K-negative and 3H-thymidine-positive basal cells as well as 67 K-positive and 3H-thymidine-negative cells at the migration front. These observations support findings that migrating epithelial cells in oral wound healing derive both from undifferentiated (str. basale) and from differentiated (inferior str. spinosum) cell compartments.


The impact of posttraumatic stress disorder on upper gastrointestinal investigations in Australian Defence Force veterans: a retrospective review.
Veterans with posttraumatic stress disorder (PTSD) commonly exhibit associated gastrointestinal (GI) symptoms. We compared upper GI endoscopy and abdominal ultrasound rates in veterans with and without PTSD. Veterans with PTSD were 77-81% more likely to undergo these procedures than those without PTSD. PTSD symptomatology influences GI investigation rate and more emphasis on clinician and patient education is recommended regarding stress-related gut symptoms.


Breaking down patient and physician barriers to optimize glycemic control in type 2 diabetes.
Approximately half of patients with type 2 diabetes (T2D) do not achieve globally recognized blood glucose targets, despite the availability of a wide range of effective glucose-lowering therapies. Failure to maintain good glycemic control increases the risk of diabetes-related complications and long-term health care costs. Patients must be brought under glycemic control to improve treatment outcomes, but existing barriers to optimizing glycemic control must first be overcome, including patient nonadherence to treatment, the failure of physicians to intensify therapy in a timely manner, and inadequacies in the health care system itself. The reasons for such barriers include treatment side effects, complex treatment regimens, needle anxiety, poor patient education, and the absence of an adequate patient care plan; however, newer therapies and devices, combined with comprehensive care plans involving adequate patient education, can help to minimize barriers and improve treatment outcomes.


A reliable technique of free vascularized sural nerve grafting and preliminary results of clinical applications.
A technique of harvesting a free vascularized sural nerve graft based on either the cutaneous branch of the peroneal artery or the muscular perforating branch of the posterior tibial artery is described. Anatomic dissections with dye injection studies confirmed the reliability of this blood supply to a 25 cm long segment of the sural nerve. The sural nerve can be sectioned into as many as four segments while safely maintaining each segment's vascularity through intact fascia. A skin monitor can be elevated with the nerve to monitor vascular patency. The free vascularized sural nerve was used to reconstruct 16 nerve defects in the upper extremity. All 13 skin monitors elevated have survived. Early follow-up (range, 2 to 31 months) has shown encouraging clinical recovery. Although our preliminary results are difficult to compare with other series, this technique appears promising in clinical circumstances when interfascicular nerve grafting is indicated but the recipient bed is heavily scarred and poorly vascularized.


BDNF acting in the hypothalamus induces acute pressor responses under permissive control of angiotensin II.
Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during hypertensive stimuli including stress and hyperosmolarity, but its role in PVN cardiovascular regulatory mechanisms is unclear. Chronic BDNF overexpression in the PVN has been shown to elevate sympathetic tone and blood pressure in part by modulating central angiotensin (Ang) II mechanisms. However, the cardiovascular effects of short-term increases in PVN levels of BDNF and the mechanisms governing them are unknown. Therefore, we investigated whether acute BDNF microinjections into the PVN of conscious and anesthetized Sprague-Dawley rats induce blood pressure elevations and whether Ang II signaling is involved in these hypertensive responses. In conscious rats, unilateral BDNF (12.5ng) microinjections into the PVN increased mean arterial pressure (MAP) by 27±1mmHg (P<0.001 vs vehicle), which was significantly attenuated by intracerebroventricular infusion of the Ang II-type-1 receptor (AT1R) antagonist losartan and by ganglionic blockade with intravenous hexamethonium infusion. In anesthetized rats, unilateral PVN microinjection of BDNF increased MAP by 31±4mmHg (P<0.001 vs vehicle), which was prevented by PVN microinjection pretreatments with the high-affinity BDNF receptor TrkB antagonist ANA-12, losartan, the angiotensin converting enzyme inhibitor lisinopril, or by intravenous hexamethonium. Additional experiments in hypothalamic samples including the PVN revealed that BDNF-induced TrkB receptor phosphorylation was prevented by ANA-12 and losartan pretreatments. Collectively, these data indicate that BDNF acting within the PVN acutely raises blood pressure under permissive control of Ang II-AT1R mechanisms and therefore may play an important role in mediating acute pressor responses to hypertensive stimuli.


Analysis of dynamic, bidirectional associations in older adult physical activity and sleep quality.
Sleep quality and physical activity (PA) appear to be interrelated; thus, by promoting one behaviour, it may be possible to improve the other in older adults. Examination of the within-person day-to-day variation in PA and sleep quality could potentially elucidate the directionality of the association of these behaviours. We measured sleep quality (i.e. fragmentation, efficiency, duration and latency) and moderate-to-vigorous PA using the MotionWatch8© over 14 consecutive days and nights in community-dwelling adults (n = 152; age range 53-101 years). Multilevel modelling estimated within-subject autoregressive and cross-lagged effects and between-subject associations between PA and sleep quality. On days when individuals engaged in a high amount of PA on one day (relative to their averages), they were more likely to engage in a high amount of PA on the next day (estimate, 0.19; 95% CI, 0.14, 0.24). Nights in which individuals had a long sleep latency were followed by nights in which they also had a long sleep latency (estimate, 0.09; 95% CI, 0.03, 0.14). In contrast, nights in which individuals slept for a long period of time were followed by nights in which they slept relatively less than their averages (estimate, -0.09; 95% CI, -0.13, -0.04). When individuals engaged in a large amount of PA during the day, they tended to sleep longer that following night (estimate, 0.01; 95% CI, 0.001, 0.02). All other associations between PA and sleep quality were not significant. Increasing PA therefore might increase sleep duration in older adults.


Precision grip responses to unexpected rotational perturbations scale with axis of rotation.
It has been established that rapid, pulse-like increases in precision grip forces ("catch-up responses") are elicited by unexpected translational perturbations and that response latency and strength scale according to the direction of linear slip relative to the hand as well as gravity. To determine if catch-up responses are elicited by unexpected rotational perturbations and are strength-, axis-, and/or direction-dependent, we imposed step torque loads about each of two axes which were defined relative to the subject's hand: the distal-proximal axis away from and towards the subject's palm, and the grip axis which connects the two fingertips. Precision grip responses were dominated initially by passive mechanics and then by active, unimodal catch-up responses. First dorsal interosseous activity, marking the start of the catch-up response, began 71-89 ms after the onset of perturbation. The onset latency, shape, and duration (217-231 ms) of the catch-up response were not affected by the axis, direction, or magnitude of the rotational perturbation, while strength was scaled by axis of rotation and slip conditions. Rotations about the grip axis that tilted the object away from the palm and induced rotational slip elicited stronger catch-up responses than rotations about the distal-proximal axis that twisted the object between the digits. To our knowledge, this study is the first to investigate grip responses to unexpected torque loads and to show characteristic, yet axis-dependent, catch-up responses for conditions other than pure linear slip.


Subclinical and Device-Detected Atrial Fibrillation: Pondering the Knowledge Gap: A Scientific Statement From the American Heart Association.
The widespread use of cardiac implantable electronic devices and wearable monitors has led to the detection of subclinical atrial fibrillation in a substantial proportion of patients. There is evidence that these asymptomatic arrhythmias are associated with increased risk of stroke. Thus, detection of subclinical atrial fibrillation may offer an opportunity to reduce stroke risk by initiating anticoagulation. However, it is unknown whether long-term anticoagulation is warranted and in what populations. This scientific statement explores the existing data on the prevalence, clinical significance, and management of subclinical atrial fibrillation and identifies current gaps in knowledge and areas of controversy and consensus.


Association between depression and death in people with CKD: a meta-analysis of cohort studies.
Depression occurs relatively commonly in people with chronic kidney disease (CKD), but it is uncertain whether depression is a risk factor for premature death in this population. Interventions to reduce mortality in CKD consistently have been ineffective and new strategies are needed. Systematic review and meta-analysis of cohort studies. Adults with CKD. Cohort studies identified in Ovid MEDLINE through week 3 December 2012 without language restriction. Depression status as determined by physician diagnosis, clinical coding, or self-reported scales. All-cause and cardiovascular mortality. Outcomes were summarized as relative risks (RRs) with 95% CIs using random-effects meta-analysis. 22 studies (83,381 participants) comprising 12,063 cases of depression (mean prevalence, 27.4%; 95% CI, 20.0%-36.3%) with a follow-up of 3 months to 6.5 years were included. Methodological quality generally was good or fair. Depression consistently increased the risk of death from any cause (RR, 1.59; 95% CI, 1.35-1.87), but had less certain effects on cardiovascular mortality (RR, 1.88; 95% CI, 0.84-4.19). Associations for mortality were similar regardless of the diagnostic method used for depression, but were weaker in analyses controlled for preexisting cardiovascular disease (RR, 1.36; 95% CI, 1.23-1.50). Meta-analyses adjusting for antidepressant medication use were not possible, and data for kidney transplant recipients and individuals with earlier stages of CKD not treated with dialysis were limited. Depression is associated with a substantially increased risk of death in people with CKD. Effective treatment for depression in people with CKD may reduce mortality.


CD133+CD34+ and CD133+CD38+ blood progenitor cells as predictors of platelet engraftment in patients undergoing autologous peripheral blood stem cell transplantation.
Hematopoietic stem cells (HSC) have been characterized by CD34+ expression and an adequate dose of CD34+ cells is associated with a complete engraftment. CD133 is a more specific marker of HSC. We studied the relationship between graft content of CD34+, CD133+, and CD38+ cells and trilineage engraftment after autologous stem cell transplantation in patients with different hematological disorders. Blood samples were obtained before and after mobilization with recombinant granulocyte-colony stimulating factor (G-CSF, 16 μg/kg), from apheresis collections, and after transplantation. Cell subsets were quantified by flow cytometry, and the dose of each population infused was correlated with success of engraftment. G-CSF induced mobilization of CD133+CD38+ cells (12.6-fold) and CD133+CD34+ cells (14.7-fold). A correlation was observed between the infused dose of CD133+CD34+ and CD133+CD38+ cells and platelet engraftment. CD133+CD34+ and CD133+CD38+ cells were mobilized with G-CSF and these cell subsets were correlated with platelet engraftment.


Regression of tumors by IFN-alpha electroporation gene therapy and analysis of the responsible genes by cDNA array.
The key to success with nonviral gene therapy as a treatment for cancer is to discover effective therapeutic genes and gene delivery methods and to understand how tumors are eradicated. We discovered that electroporation of IFN-alpha DNA into tumors in the SCCVII tumor-bearing mice led to tumor eradication in 50% of the mice and a more than two-fold increase in survival time when compared with controls (P = 0.0012). Analyses using cDNA array and Northern blot indicated that the genes responsible for the therapeutic effect of electro-IFN-alpha gene therapy included IRF-7, Granzyme A, Granzyme C, Gjb2, Krt14, Mig, IP-10 and MCP3. Because most of these genes have been known to either inhibit angiogenesis (Mig, IP-10), inhibit tumor growth (Gjb2, MCP3), kill tumor cells (Granzyme A and C), or induce expression of antitumor gene (IRF-7), they may become promising therapeutic gene candidates for a combination gene therapy approach to cancer treatment.


rd1 Mouse retina shows an imbalance in the activity of cysteine protease cathepsins and their endogenous inhibitor cystatin C.
To compare in vivo levels, spatial localization, and in vitro secretion of cysteine protease cathepsins and cystatin C (cysC) in the retinal degeneration 1 (rd1) mouse model of retinitis pigmentosa and control (wt) mouse retinas. The spatial localization, protein contents, cysC levels and cathepsin-B, -S, and -L activities in wt and rd1 retinas at postnatal (PN) days 2, 7, 14, 21, and 28 were analyzed by immunostaining, spectrophotometry, ELISA, and fluorescence spectrophotometry. The in vitro secretion of cysC and cysteine proteases by PN7 retinal explants into the conditioned medium (RCM) was quantified. The pigment epithelium, photoreceptors, and inner retinal and ganglion cell layers of both wt and rd1 retinas showed cysC and cathepsin-B labeling. CysC immunostaining was extensive in the optic nerve head fibers. The rd1 explants secreted higher amounts of cysteine protease into the RCM. The protein content in wt and rd1 retinal extracts increased up to PN14, then decreased in rd1 but not in wt. In rd1 extracts at PN14 to -28, cathepsin activity was higher and increased with age, but the cysC level was higher and constant. The ratios of cathepsin activity to cysC (cathepsin-L at PN2 and total, -B, and -L at PN14 to -28) were higher in rd1 extracts. Similar localization of both cathepsin-B and cysC in wt and rd1 retinas along with lower proteins and higher cathepsin activity in rd1 retinal extracts and RCM are consistent with their localization in extracellular matrix and a role in physiopathologic remodeling in wt and rd1 retinas.


[Age-related characteristics of lipid peroxidation in the blood in alloxan diabetes].
The experiments on male rats aged 5-6 and 24-26 months have shown that alloxan diabetes is characterized by an increase in the content of blood glucose, total lipids and malonic dialdehyde. The time-course of these parameters reveals clear age dependence; the glucose and total lipid content is higher in young rats and that of lipid peroxidation products in old animals. The antioxidant effect of insulin, which is estimated by the malonic, dialdehyde content in the blood, decreases with age.


Vasography: experimental study.
Vasography may cause stricture of the vas deferens. The probable causes of this obstruction are traumatic lesion at the puncture site and the radiological contrast material used. Because of this problem we performed an experimental study using Wistar rats, which were divided into four groups: Group A - Control, Group B - injection of a saline solution, Group C - hypaque injection, Group D - hypaque plus saline solution. According to the results obtained it was concluded that the needle puncture is not responsible for stricture of the vas deferens. Hypaque is responsible for 5% of strictures and the use of a saline solution to wash the vas did not show any benefit.


Room-Temperature Organocatalytic Cycloaddition of Azides with β-Keto Sulfones: Toward Sulfonyl-1,2,3-triazoles.
Organocatalytic enamine-azide [3 + 2] cycloadditions between β-keto sulfones and aryl azides can be performed at room temperature in good to excellent yields of products in the presence of catalytic amounts of pyrrolidine (5 mol %). The proposed organocatalytic methodology was found to be applicable to β-keto arylsulfones containing a range of substituents. A wide variety of aryl azides also work. Basically, this constitutes a remarkably efficient protocol for the synthesis of novel 1,2,3-triazole compounds.


PTSD and surgical residents: Everybody hurts… sometimes.
We aim to evaluate the prevalence of PTSD, its association with physician burnout, and risk factors for PTSD among surgical residents. A cross-sectional national survey of surgical residents was conducted screening for PTSD. Causative traumatic stressors were queried, and thirty-one potential risk factors for PTSD were evaluated. A positive PTSD screen (PTSD+) was found in 22% of 582 surgical residents, and an additional 35% were "at risk" for PTSD. Traumatic experiences occurred most commonly as a PGY1, and the most common stressor was bullying. An increase in average hours of work per week (p < 0.001), a high-risk screen for PBO (p < 0.001), and feeling unhealthy (p = 0.001) were associated with an increasing prevalence of screening PTSD+. The prevalence of screening PTSD+ among surgical residents (22%) was more than three times the general population. Increased work-hours, a high-risk PBO screen, and reduced resident wellness were associated with screening PTSD+.


18-year follow-up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I.
Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase and characterized by a progressive course with multisystem involvement. Clinically, MPS I is divided into two forms: (1) severe (Hurler syndrome), which presents in infancy and is characterized by rapid progressive neurological involvement; (2) attenuated (Hurler/Scheie and Scheie syndromes), which displays a slower progression and absent to mild nervous system involvement. The specific treatment for attenuated MPS I consists of enzyme-replacement therapy with laronidase (human recombinant α-L-iduronidase, Aldurazyme). We present updated data after 18 years of laronidase treatment in two siblings affected by the attenuated form of MPS I who started therapy at 5 months and 5 years of age, respectively. Clinical and laboratory data of the siblings show that long-term enzyme replacement therapy may improve/stabilize many symptoms already present at the time of the diagnosis and reduce the disease progression. This study confirms that early diagnosis and early initiation of enzyme-replacement therapy are essential to modify positively the natural history of the attenuated form of MPS I.


Antioxidant phenylpropanoid glycosides from Smilax bracteata.
From the ethanolic extract of Smilax bracteata, six phenylpropanoid glycosides, smilasides G-L (1-6), along with four known phenylpropanoid compounds, helonioside A, helonioside B, smilaside E, and (1-p-O-coumaroyl-6-O-feruroyl)-beta-d-fructofuranosyl-alpha-d-glucopyranoside, and fourteen known phenolic compounds were isolated. Their structures were elucidated on the basis of spectroscopic analyses. Moreover, 1-6 exhibited moderate scavenging activities against DPPH radicals.


Management of a Rare Lymphoepithelial Carcinoma of the Submandibular Gland in Elderly.
Lymphoepithelial carcinoma (LEC) of salivary glands is a rare malignant salivary gland tumour and demonstrates genetic and regional distribution. It commonly occurs in major salivary gland especially parotid gland. We report a case of LEC of submandibular gland occurring in a 70 year-old lady.