Radiation induces osteogenesis in human aortic valve interstitial cells.
Irradiation of the chest or chest wall has been shown to cause calcific aortic stenosis. However, the mechanisms are unknown. Aortic valve interstitial cells have been implicated in the pathogenesis of aortic stenosis; they have been shown to change from the phenotype of a myofibroblast to an osteoblastlike cell. We therefore hypothesized that irradiation of human aortic valve interstitial cells induces an osteogenic phenotype. In isolated human aortic valve interstitial cells, our purpose was to determine the effect of irradiation on the production of osteogenic factors: (1) bone morphogenetic protein 2, (2) osteopontin, (3) alkaline phosphatase, and (4) the transcription factor Runx2. Human aortic valve interstitial cells were isolated from normal aortic valves obtained from explanted hearts of patients undergoing cardiac transplantation (n = 4) and were grown in culture. The cells were grown to confluence, irradiated with 10 Gy using a cesium-137 irradiator, and then lysed 24 hours after irradiation. Cell lysates were analyzed via immunoblot and densitometry for bone morphogenetic protein 2, osteopontin, alkaline phosphatase, and Runx2. Statistical analysis was performed using analysis of variance, with P < .05 indicating significance. Irradiation induced an osteogenic phenotype in human aortic valve interstitial cells. Irradiation induced a 2-fold increase in bone morphogenetic protein 2, a 7-fold increase in osteopontin, a 3-fold increase in alkaline phosphatase, and a 2-fold increase in Runx2. Radiation induces an osteogenic phenotype in human aortic valve interstitial cells. The irradiated cells had a significantly increased expression of the osteogenic factors bone morphogenetic protein 2, osteopontin, alkaline phosphatase, and Runx2. These data offer mechanistic insight into the pathogenesis of radiation-induced valvular heart disease.


Axillary failure in patients treated with MammoSite accelerated partial breast irradiation.
The risk of axillary failure (AF) after accelerated partial breast irradiation (APBI) using MammoSite brachytherapy is unknown and has been source of concern as the axillary region is not treated with this technique. We aimed to determine the rate of AF in patients treated with APBI and identify factors associated with its occurrence. Data from the American Society of Breast Surgeons MammoSite Registry Trial were reviewed and patients with AF were identified. Clinical, pathologic and treatment-related variables were analyzed to determine which factors were associated with AF. A total of 1440 patients underwent MammoSite APBI. A total of 1449 cases were treated (9 patients received bilateral treatment), 1255 cases (87%) of invasive breast cancer and 194 cases (13%) of ductal carcinoma in situ (DCIS). The median length of follow-up was 59 months. There were 10 patients who had an AF. Of these, 9 patients had an initial diagnosis of invasive cancer and 1 had an initial diagnosis of DCIS. The 5-year actuarial rate of AF was 0.79%. The only independent risk factor for AF identified by multivariate analysis was the presence of high-grade disease (P=.008). The 5-year overall survival rate in patients with an AF was 77.8% (there was 1 death related to breast cancer). The rate of AF after MammoSite APBI is low and appears to be similar to that achieved with whole-breast irradiation.


[A study on the regulatory mechanism of hypothalamo-hypophyseo-ovarian system in estrous cycles of rats: Changes in responsiveness of the anterior pituitary gland to synthetic LH-RH (author's transl)].
It is generally accepted that the sexual cycle in mammals is accomplished by the systematic coupling of components of the hypothalamo-hypophyseo-gonadal system. However, how these components are related to each other to develop the sexual cyclicity has not yet been clearly established. A gonadotropin releasing factor (GnRF), which has been extracted and purified from porcine hypothalamus and whose molecular structure was determined in 1971, has been synthesized in many laboratories. The synthetic GnRF, named LRF or LH-RH, has gonadotropin releasing activity for many species of mammals, including humans. The debut of the synthetic LRF has given us a pure material and a direct means of stimulating, relatively easily, the gonadotroph cells in the anterior pituitary glands. In the present study, variations in the gonadotropin releasing activity of the pituitary gland in relation to synthetic LRF was investigated throughout the sexual cycle of rats. The relationship between pituitary sensitivity and levels of steroid hormones in the blood is discussed.


Candida lusitaniae as an unusual cause of recurrent vaginitis and its successful treatment with intravaginal boric acid.
Increasing use of short-course antifungal therapies in patients with recurrent vulvovaginitis may enable the emergence of less-common, more resistant yeast strains as vaginal pathogens. We report the case of a patient with chronically symptomatic and repeatedly treated vaginal candidiasis whose infection was attributable to Candida lusitaniae, a previously unreported cause of candidal vaginitis.


Medicinal plants used to treat malaria in Madagascar.
Two-hundred thirty-nine Madagascan medicinal plants have been either retrieved from computerized ethnobotany information or identified in our own ethnomedicine work as having antimalarial properties. Such a high rate percent of plants compared to those used empirically to treat other diseases reflects the importance and the complication of this major tropical disease in Madagascar.


Technical features, perioperative and anatomical outcomes of a standardized suturing pattern for robotic sacrocolpopexy.
Several technical alternatives to repair mesh using laparoscopic sacrocolpopexy exist. We aim to describe the outcomes and surgical technique of robotic-assisted colpo-/cervicosacropexy using a standardized suturing scheme to repair the mesh. We retrospectively reported data of 60 consecutive cases of robotic-assisted colpo-/cervicosacropexy for advanced multicompartmental prolapse using a standardized suturing design. We placed three non-absorbable stitches on the cervix or three absorbable stitches on the apex of the vaginal vault, six long-term absorbable stitches on the anterior vaginal wall deep to the basis of the vesical trigone, six similar posterior stitches with the deeper row of sutures down to the levator ani plane and three non-absorbable stitches on the sacral promontory as the cranial support for Y-shaped polypropylene mesh. Median operative time was 188 ± 43 min. All the procedures were successfully performed using a Da Vinci Si platform in a three-arm configuration, and no conversion to open or traditional laparoscopic surgery was needed. The length of hospital stay was 1.2 ± 1.7 days, and no readmission within 30 postoperative days was reported. At a follow-up of 12 and 24 months, no case of extrusion or exposure of the mesh occurred, and the retreatment rate was 6.7%. Our suturing technique is safe and effective, with negligible risk of complications and good medium-term results. It is plausible that robotic systems may facilitate precise, accurate and reproducible placement of the stitches, thereby favoring wider diffusion of minimally invasive treatment of advanced prolapse.


Validation of a Computerized Adaptive Test Suicide Scale (CAT-SS) among United States Military Veterans.
To validate the Computerized Adaptive Test Suicide Scale (CAT-SS), Veterans completed measures at baseline (n = 305), and 6- (n = 249), and 12-months (n = 185), including the CAT-SS (median items 11, duration of administration 107 seconds) and the Columbia-Suicide Severity Rating Scale (C-SSRS). Logistic regression was used to relate CAT-SS scores (baseline) to C-SSRS assessed outcomes (active ideation with plan and intent; attempt; interrupted, aborted or self-interrupted attempt, or preparatory acts or behaviors; all outcomes combined). A mixed-effects logistic regression model was used to evaluate the relationship between the lagged CAT-SS scores and outcomes (6- and 12-months). The baseline CAT-SS demonstrated predictive accuracy for all outcomes at 6-months, and similar results were found for baseline and all outcomes at and through 12-months. Longitudinal analysis revealed for every 10-point change in the CAT-SS there was a 50-77% increase in the likelihood of suicide-related outcomes. The CAT-SS demonstrated added value when compared to current suicide risk prediction practices.


Is Telerehabilitation a Viable Option for People With Low Back Pain? Associations Between Telerehabilitation and Outcomes During the COVID-19 Pandemic.
The aims of this study were to examine associations between frequency of telerehabilitation (TR) and outcomes of functional status (FS), number of visits, and patient satisfaction during COVID-19 and to compare FS outcomes by TR delivery mode for individuals with low back pain. Propensity score matching was used to match episodes of care with or without TR exposure by the probability of receiving TR. FS, visits, and satisfaction were compared for individuals without TR and those who received care by TR for "any," "few," "most," or "all" frequencies (4 matched samples), and FS was compared for individuals receiving synchronous, asynchronous, and mixed TR modes (3 matched samples). Standardized differences were used to compare samples before and after matching. Outcomes between matched samples were compared using z tests with 95% CI. The sample consisted of 91,117 episodes of care from 1398 clinics located in 46 states (58% women; mean age = 55 [SD = 18]). Of those, only 5013 episodes (5.5%) involved any amount of TR. All standardized differences between matched samples were <0.1. There was no significant difference in FS points (range = 0-100, with higher representing better FS) between matched samples, except for episodes that had ``few'' (-1.7) and ``all'' (+2.0) TR frequencies or that involved the asynchronous (-2.6) TR mode. These point differences suggest limited clinical importance. Episodes with any TR frequency involved significantly fewer visits (0.7-1.3) than episodes with no TR, except that those with the "most" TR frequency had non-significantly fewer visits (0.6). A smaller proportion of individuals with TR (-4.0% to -5.0%) than of individuals with no telerehabilitation reported being very satisfied with treatment results, except for those with the "all" TR frequency. A positive association between TR and rehabilitation outcomes was observed, with a trend for better FS outcomes and fewer visits when all care was delivered through TR. Satisfaction tended to be lower with TR use. Overall, this observational study showed that for people with low back pain, physical therapy delivered through TR was equally effective as and more efficient than in-person care, with a trend of higher effectiveness when used for all visits during the episode of care. No differences in FS outcomes were observed between care delivered with synchronous and mixed TR delivery modes and care delivered with no TR. However, the asynchronous mode of TR was associated with worse functional outcomes than no TR. Although the majority of people were very satisfied with their treatment results with and without TR, very high satisfaction rates were reported by a slightly smaller proportion of individuals with TR versus those without TR. Our results suggest that TR is a viable option for rehabilitation care for individuals with low back pain and should also be considered in the post-COVID-19 era.


Dominant negative insulin-like growth factor-1 receptor inhibits neointimal formation through suppression of vascular smooth muscle cell migration and proliferation, and induction of apoptosis.
Blocking of the IGF-1 signaling pathway targeting the IGF-1 receptor (IGF-1R) provides a potential treatment strategy for restenosis. In this study, we have examined the effects of a dominant negative IGF-1R (IGF-1Rt) on primary rat VSMCs in vitro and on injured rat carotid artery in vivo. Ad/IGF-1Rt infection inhibited VSMC migration and proliferation, and it also induced apoptosis by inhibiting phosphorylation of Akt and phosphorylation of ERK1/2. Consistent with the anti-proliferative and apoptotic effects in vitro, the Ad/IGF-1Rt infection markedly reduced neointimal formation in carotid injury model. Ad/IGF-1Rt treated carotid arteries exhibited a suppressed proliferation index, PCNA expression, and also were stained positive for TUNEL assay. These results indicate that a dominant negative IGF-1R has the potential to reduce neointimal formation of injured rats' carotid arteries. The delivery of dominant negative IGF-1R by adenoviral or other vectors may provide a useful strategy for inhibiting restenosis after angioplasty.


The restriction endonuclease cleavage map of rat liver mitochondrial DNA.
Mitochondrial DNA from rat liver contains six sites for cleavage by the restriction endonucleases Hind III and EcoRI. A large stretch of DNA, comprising about 40% of the mitochondrial genome is not cleaved by either of the enzymes; eight cleavage sites are located on a DNA stretch of 35% of the genome length suggestive of an unequal distribution of the A - T baspairs over the molecule. The number of Hind III and Eco R I fragments is much higher than reported for other mammalian mitochondrial DNAs up to now.


Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic ESCO2 variations.
Roberts syndrome (RBS), also known as Roberts-SC phocomelia syndrome, is a rare autosomal recessive developmental disorder caused by mutations in the ESCO2 gene. Cardinal clinical manifestations are pre- and postnatal growth retardation and craniofacial and limb malformations. Here, we report RBS in a Chinese adolescent with novel biallelic ESCO2 variations and complex cerebrovascular diseases. Medical history, neurological examinations, neuroimaging, and pathology were collected in the proband and the family. Whole exome sequencing (WES) with copy number variation analysis was performed to screen for genetic variations. The clinical features of the proband were craniofacial and limb malformations together with complex cerebrovascular diseases. She suffered ischemic stroke at 6 years old and died of cerebellar hemorrhage secondary to an aneurysm at 13 years old. Besides, neuroimaging showed the triad of leukoencephalopathy, calcifications, and cysts. Brain histopathology revealed angiomatous changes and perivascular cysts suggesting chronic small cerebral vasculopathy. Whole exome sequencing (WES) identified novel biallelic variations in the ESCO2 gene (c.1220A>T, p.H407L and c.1562delC, p.A521fs). We describe complex cerebrovascular diseases in Roberts syndrome caused by novel ESCO2 biallelic variations. This case expands not only the cerebral involvement in Roberts syndrome but also the disease spectrum of the neuroimaging triad with leukoencephalopathy, calcifications, and cysts.


Band Gap of 3D Metal Oxides and Quasi-2D Materials from Hybrid Density Functional Theory: Are Dielectric-Dependent Functionals Superior?
Reproduction of the band gaps of semiconductors and insulators represents a well-known problem for standard DFT approaches based on semilocal functionals. The problem can be partly solved using hybrid functionals, in which a given portion of exact exchange is mixed with the DFT exchange. Recently, a new class of dielectric-dependent functionals has been introduced in which the amount of exact exchange is derived from the static dielectric function of a given compound. In this study we considered in a systematic way on an equal footing a set of 24 nonmagnetic three-dimensional (3D) bulk metal oxides and 24 quasi-two-dimensional (quasi-2D) semiconductors (oxides, hydroxides, chlorides, oxyhalides, nitrides, and transition metal dichalcogenides) and computed the corresponding Kohn-Sham band gaps with three global hybrid functionals and four range-separated hybrid functionals. These in turn were divided into standard (PBE0, B3LYP, HSE06, SC-BLYP) and dielectric-dependent (DD-B3LYP, DD-SC-BLYP, DD-CAM-B3LYP) functionals. We also performed a statistical analysis of the DFT data set along with structural parameters of these 2D and 3D materials. The surprising result is that overall there is no real improvement with the use of dielectric-dependent functionals compared to PBE0, HSE06, and B3LYP. Short-range DD-SC-BLYP gives a minor improvement in the band gaps for bulk metal oxides compared with standard SC-BLYP, but the mean absolute error is still 0.12 eV higher than with B3LYP. The use of dielectric-dependent standard or short-range functionals such as DD-B3LYP or DD-HSE06 worsens the situation. However, the dielectric-dependent version of the long-range-separated functional implemented with the Coulomb attenuating method (CAM), DD-CAM-B3LYP, leads to a clear improvement for band gaps of quasi-2D materials. On the basis of this analysis, the conclusion is that the use of a standard hybrid functional such as B3LYP or HSE06 is recommended for nonmagnetic bulk 3D metal oxides. On the other hand, the treatment of layered materials such as MoO3 or V2O5 benefits from the use of dielectric-dependent range-separated functionals.


What we need to know about PPE associated with the COVID-19 pandemic in the marine environment.
Since the COVID-19 outbreak was declared as a global health emergency, the use of multiple types of plastic-based PPEs as a measure to reduce the infection increased tremendously. Recent evidence suggests that the overuse of PPEs during the COVID-19 pandemic is worsening plastic pollution in the marine environment. In this short focus, we discussed the potential sources, fate, and effects of PPE plastic to the marine environment and proposed five key research needs, involving (1) the occurrence and abundance of PPEs, (2) the sources, fate, and drivers of PPEs, (3) PPEs as a source of microplastics, (4) PPEs as a vector of invasive species and pathogens, and (5) PPEs as a source and vector of chemical pollutants in the marine environment. We suggest that addressing these knowledge gaps will lay the groundwork for improved COVID-19-associated waste management and legislation to prevent marine plastic pollution to continue exacerbating.


Impact of model resolution on the representation of the wind field along Nares Strait.
Nares Strait is a major pathway along which multi-year sea ice leaves the Arctic, an ice class that has seen a recent dramatic reduction in extent. The winds that blow along the strait play an important role in modulating this ice export as well as in establishing the Arctic's largest and most productive polynya, the North Water, that forms at its southern terminus. However, its remote location has limited our knowledge of the winds along the strait. Here we use automatic weather station data from Hans Island, in the middle of the strait, to assess the ability of a set of atmospheric renalyses and analyses with a common lineage but with varying horizontal resolution to represent the variability in the wind field. We find that the flow is highly bidirectional, consistent with topographic channeling, with the highest wind speeds from the north and that a model resolution of ~ 9 km is required to capture the observed variability. The wind field at Hans Island is also found to be representative of variability in the flow along much of Nares Strait.


Attenuating effect of melatonin on pyridoxal-stimulated release of adrenomedullary catecholamines in the rat.
To investigate the ability of melatonin (MEL) to suppress adrenomedullary catecholamine (CAT) release in the rat, with pyridoxal (PL) being used as an adrenomedullary stimulus and liver and gastrocnemius muscle glycogenolysis acting as indices of CAT release. MEL (1-4 mg/kg, i.p.) and PL (300 mg/kg, i.p.) were administered separately or together to male Sprague-Dawley rats (275-300 g), and blood samples for the assay of plasma glucose and CATs were periodically collected for up to 3 h after PL. Immediately thereafter, the liver and gastrocnemius muscle were surgically removed and used for the assay of glycogen. The role of adrenoceptors in PL-induced glycogenolysis was examined by parallel experiments in which idazoxan (IDX, 1 mg/kg), propranolol (PRO, 2 mg/kg) or metoprolol (MET, 2 mg/kg) were administered alongside MEL. In addition, MEL (4 mg/kg) was co-administered with taurine (TAU, 2.4 mmol/kg), a known adrenomedullary membrane stabilizer. MEL attenuated the release of adrenomedullary CATs and accompanying liver and gastrocnemius muscle glycogenolysis due to PL in a dose-dependent manner. A co-treatment with MEL and an adrenoceptor blocker had a greater attenuating effect on PL-induced glycogenolysis and hyperglycemia than MEL but without impinging on the CAT levels seen with MEL alone. Evidence of maximal inhibitory action by MEL on PL-induced plasma CAT elevation was suggested by the about equal levels of plasma CATs after treatments with MEL and with MEL plus TAU. The present study demonstrates the modulatory effect of MEL of exogenous origin on adrenomedullary CAT secretion when present in supraphysiological concentrations.


Tranylcypromine induced hypertension is not mediated by the inhibition of prostacyclin synthesis.
Tranylcypromine (TCP) is a monoamine oxidase inhibitor used extensively in the treatment of patients with reactive depression. Hypertensive crisis can complicate drug therapy, but the mechanism through which TCP causes high blood pressure is unknown. The present study was undertaken because recent investigations have shown that TCP can inhibit production of a potent vasodilator hormone, prostacyclin (PGI2), by blood vessels, possibly explaining the mechanism of pressor effects by the drug. Heart rate, left atrial, pulmonary artery and aortic pressures were monitored in dogs under control conditions and continuously following the IV infusion of TCP at the rate of 1 mg/kg over a period of one minute. Right femoral and the left internal mammary arteries were obtained during the control period and the left femoral and right internal mammary arteries resected between 6 and 30 minutes following drug infusion for PGI2 studies. Concentrations of the drug that caused significant elevation of the mean systemic pressure to 203 +/- 8 mmHg had no inhibitory effect on PGI2 production. Therefore, the influence of TCP on the hemodynamic parameters does not appear to be mediated through the inhibition of vascular PGI2 synthesis.


Coping Through Religiosity, Spirituality and Social Support Among Muslim Chronic Hepatitis Patients.
Academics acknowledge religiosity, spirituality and social support as socio-behavioral factors that influence patients' ability to deal with chronic illness. This study has attempted to describe empirical reality of how these factors influence patients. The sample of this study was 500 chronically ill hepatitis patients and was selected through the multistage sampling techniques. Through structured interview schedule, data were collected during the period of September 2016 to March 2017 from five most populated cities of Punjab (Pakistan). Data were analyzed through descriptive (frequency and percentage) and inferential statistics (Cronbach's alpha, Pearson correlation, and structural equation modeling). The study suggests some recommendations and suggestions to policy makers regarding the significance of religiosity, spirituality and social support as coping strategies during chronic illness. The findings illustrate that social support has more association with coping than religiosity and spirituality of the patients.


Unhealthy food advertising. A position paper by the AEP Committee on Nutrition and Breastfeeding.
Some important factors influencing and maintaining unhealthy habits are food advertising and products accessibility. In order to develop and support recommendations, an analysis of the available evidence on the impact of food advertising on the health of children and adolescents has been carried out. Literature review of systematic reviews and meta-analyses published up to January 2022 for the term "food advertising" that analyzed the impact of food advertising on weight, body mass index (BMI), adiposity, dietary intake, behavior toward the advertised product, its purchase or consumption in children and adolescents. Twenty-one systematic reviews fulfilled the inclusion criteria, including a total of 490 primary studies, 5 of which also contained a meta-analysis. The vast majority of the primary studies evaluate intermediate effects, related to the behavior of children and adolescents in relation to advertised products and their consumption. There is great variety in terms of the type of advertising and effects studied. Most of the studies agree that there is an association between food advertising and effect analyzed, being more evident in children under 12 years of age and in obese children. Most recent systematic reviews are focused on online advertising, noticing the negative effects especially in adolescents. Children and adolescents are a particularly vulnerable population to food advertising strategies. Despite the difficulty to demonstrate an independent effect, there is evidence of an association between food advertising and childhood and adolescents' behavior respect to the announced products, and the increase of consumption at short-term. In Spain unhealthy product advertising are still very common in the media and in the children and adolescent's online environment. The Nutrition and Breastfeeding Committee of the Spanish Association of Pediatrics supports the need for regulation and limitation of unhealthy food advertising, covering all media and marketing strategies.


Generalized granuloma annulare in a patient with temporal arteritis--are these conditions associated?
A case of generalized granuloma annulare associated with temporal arteritis is described. The patient, a 79-year-old man, noticed numerous asymptomatic lesions on his trunk and extremities for 3 months. Four months later, he suffered from headache and loss of vision. Both were successfully treated by oral administration of prednisolone.


Silicon spintronics.
Worldwide efforts are underway to integrate semiconductors and magnetic materials, aiming to create a revolutionary and energy-efficient information technology in which digital data are encoded in the spin of electrons. Implementing spin functionality in silicon, the mainstream semiconductor, is vital to establish a spin-based electronics with potential to change information technology beyond imagination. Can silicon spintronics live up to the expectation? Remarkable advances in the creation and control of spin polarization in silicon suggest so. Here, I review the key developments and achievements, and describe the building blocks of silicon spintronics. Unexpected and puzzling results are discussed, and open issues and challenges identified. More surprises lie ahead as silicon spintronics comes of age.


Pregnane X Receptor Not Nuclear Factor-kappa B Up-regulates P-glycoprotein Expression in the Brain of Chronic Epileptic Rats Induced by Kainic Acid.
Drug-resistance epilepsy (DRE) is attributed to the brain P-glycoprotein (P-gp) overexpression. We previously reported that nuclear factor-kappa B (NF-κB) played a critical role in regulating P-gp expression at the brain of the acute seizure rats. This study was extended further to investigate the interaction effect of NF-κB and pregnane X receptor (PXR) on P-gp expression at the brain of chronic epileptic rats treated with carbamazepine (CBZ). The chronic epileptic models were induced by the micro-injection of kainic acid (KA) into rats' hippocampus. Subsequently, the successful models were treated with different intervention agents of CBZ; PMA(a non-specific PXR activity inhibitor) or PDTC(a specific NF-κB activity inhibitor) respectively. The expression levels of P-gp and its encoded gene mdr1a/b were significantly up-regulated on the brain of KA-induced chronic epilepsy rats or the epilepsy rats treated with CBZ for 1 week, meanwhile with a high expression of PXR. The treatment of PMA dramatically reduced both PXR and P-gp expressions at the protein and mRNA levels in the chronic epilepsy brain. By compared to the epilepsy model group, the P-gp expression was not markedly attenuated by the inhibition of NF-κB activity with PDTC treatment, nevertheless with a decrease of NF-κB expression in this intervention group. Higher levels of proinflammatory cytokines(IL-1β, IL-6, TNF-α) were found both in the brain tissue and the serum in the epilepsy rats of each group. There was a declined trend of the pro-inflammatory cytokines expression of the PDTC treatment group but with no statistical significance. This study demonstrates for the first time that P-gp up-regulation is due to increase PXR expression in the chronic phase of epilepsy, differently from that NF-κB signaling may induce the P-gp expression in the acute seizure phase. Our results offer insights into the mechanism underlying the development of DRE using or not using CBZ treatment.


Effects of Aramchol in patients with nonalcoholic fatty liver disease (NAFLD). A systematic review and meta-analysis.
Nonalcoholic fatty liver disease (NAFLD) comprises a wide range of related liver disorders affecting mainly people who drink no or very little alcohol. Aramchol is a new synthetic molecule that has been shown to reduce liver fat content. There is little evidence supporting its efficacy in humans. To evaluate the efficacy of Aramchol in patients with NAFLD according to different randomized clinical trials. We searched PubMed, SCOPUS, Web of Science, and Cochrane Library for relevant clinical trials assessing the use of Aramchol in patients with NAFLD. Risk of bias assessment was performed using Cochrane's risk of bias tool. We included the following outcomes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), glycated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), HOMA-IR, and insulin level. We included 3 clinical trials. We found that the Aramchol group did not show any significant difference from the control group regarding ALT (MD = 3.92 (-21.20, 29.04), p = 0.76), AP (MD = -0.59 (-8.85, 7.67), p = 0.89), HbA1c (MD = -0.11 (-0.32, 0.10), p = 0.29), TC (MD = 14.25 (-626, 34.77), p = 0.17), TG (MD = 2.29 (-39.30, 43.87), p = 0.91), HOMA-IR (MD = -0.11 (-1.58, 1.37), p = 0.89), and insulin levels (MD = -0.88 (-5.82, 4.06), p = 0.73). AST levels were significantly higher in the Aramchol group (MD =11.04 (4.91, 17.16), p = 0.04). Aramchol was a safe and tolerable drug to be used in patients with NAFLD. However, it was not superior to placebo in reducing the biochemical liver markers.


Erratum: X-ray Beam Induced Current Measurements for Multi-Modal X-ray Microscopy of Solar Cells.
An erratum was issued for: X-ray Beam Induced Current Measurements for Multi-Modal X-ray Microscopy of Solar Cells. An equation was updated. Equation 9 was updated from: to.


Intraoperative fluoroscopic dose assessment in prostate brachytherapy patients.
To evaluate a fluoroscopy-based intraoperative dosimetry system to guide placement of additional sources to underdosed areas, and perform computed tomography (CT) verification. Twenty-six patients with prostate carcinoma treated with either I-125 or Pd-103 brachytherapy at the Puget Sound VA using intraoperative postimplant dosimetry were analyzed. Implants were performed by standard techniques. After completion of the initial planned brachytherapy procedure, the initial fluoroscopic intraoperative dose reconstruction analysis (I-FL) was performed with three fluoroscopic images acquired at 0 (AP), +15, and -15 degrees. Automatic seed identification was performed and the three-dimensional (3D) seed coordinates were computed and imported into VariSeed for dose visualization. Based on a 3D assessment of the isodose patterns additional seeds were implanted, and the final fluoroscopic intraoperative dose reconstruction was performed (FL). A postimplant computed tomography (CT) scan was obtained after the procedure and dosimetric parameters and isodose patterns were analyzed and compared. An average of 4.7 additional seeds were implanted after intraoperative analysis of the dose coverage (I-FL), and a median of 5 seeds. After implantation of additional seeds the mean V100 increased from 89% (I-FL) to 92% (FL) (p < 0.001). In I-125 patients an improvement from 91% to 94% (p = 0.01), and 87% to 93% (p = 0.001) was seen for Pd-103. The D90 increased from 105% (I-FL) to 122% (FL) (p < 0.001) for I-125, and 92% (I-FL) to 102% (FL) (p = 0.008) for Pd-103. A minimal change occurred in the R100 from a mean of 0.32 mL (I-FL) to 0.6 mL (FL) (p = 0.19). No statistical difference was noted in the R100 (rectal volume receiving 100% of the prescribed dose) between the two techniques. The rate of adverse isodose patterns decreased between I-FL and FL from 42% to 8%, respectively. The I-125 patients demonstrated a complete resolution of adverse isodose patterns after the initial isodose reconstruction (I-FL). The Pd-103 patients demonstrated a final rate of 8% gaps, 0% islands, and 0% holes on corrected isodose reconstruction. The use of intraoperative fluoroscopy-based dose assessment can accurately guide in the implantation of additional sources to supplement inadequately dosed areas within the prostate gland. Additionally, guided implantation of additional source, can significantly improve V100s and D90s, without significantly increasing rectal doses.


Transgenic alfalfa plants co-expressing glutathione S-transferase (GST) and human CYP2E1 show enhanced resistance to mixed contaminates of heavy metals and organic pollutants.
Transgenic alfalfa plants simultaneously expressing human CYP2E1 and glutathione S-transferase (GST) were generated from hypocotyl segments by the use of an Agrobacterium transformation system for the phytoremediation of the mixed contaminated soil with heavy metals and organic pollutants. The transgenic alfalfa plants were screened by a combination of kanamycin resistance, PCR, GST and CYP2E1 activity and Western blot analysis. The capabilities of mixed contaminants (heavy metals-organic compounds) resistance of pKHCG transgenic alfalfa plants became markedly increased compared with the transgenic alfalfa plants expressing single gene (GST or CYP2E1) and the non-transgenic control plants. The pKHCG alfalfa plants exhibited strong resistance towards the mixtures of cadmium (Cd) and trichloroethylene (TCE) that were metabolized by the introduced GST and CYP2E1 in combination. Our results show that the pKHCG transgenic alfalfa plants have good potential for phytoremediation because they have cross-tolerance towards the complex contaminants of heavy metals and organic pollutants. Therefore, these transgenic alfalfa plants co-expressing GST and human P450 CDNAs may have a great potential for phytoremediation of mixed environmental contaminants.


Correction: CO2 free production of ethylene oxide via liquid phase epoxidation of ethylene using niobium oxide incorporated mesoporous silica material as the catalyst.
[This corrects the article DOI: 10.1039/D2RA07240H.].


Abnormalities of the local immune system in intestinal neoplasia: a morphological study.
In colonic adenocarcinomata abnormalities have been noted in all morphological aspects of the local immune system of the bowel; thus, in such tumours there is a defective production of secretory IgA, a diminished content of secretory component (SC) and a marked decrease in intraepithelial lymphocytes. By contrast, no such abnormalities were noted in the non-neoplastic areas of the bowel, either immediately adjacent to, or some distance from, the carcinoma. These findings suggest that there is not usually any generalised morphological abnormality of the local immune systems in intestinal neoplasia and that the immunological abnormalities noted within the tumour are a result of the changed nature of the epithelium, thus altering, or interfering with, the normal interactions between epithelial and lymphoid tissue in the gut.


Use of the Clock Drawing Test and the Rey-Osterrieth Complex Figure Test-copy with convolutional neural networks to predict cognitive impairment.
The Clock Drawing Test (CDT) and Rey-Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool. The CDT and RCFT-copy data were obtained from patients aged 60-80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform ( www.colab. google.com ) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI). The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them. The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.


Nanoporous gold film encapsulating cytochrome c for the fabrication of a H2O2 biosensor.
A layer-by-layer route to prepare nanoporous Au film materials on transparent ITO substrates is reported by alternatively assembling Au and Ag nanoparticles through 1,5-pentanedithiol as a cross-linker, followed by that Ag nanoparticles are dissolved at room temperature in HAuCl4 solution. Electron transfer of cytochrome c (cyt. c) - an excellent model for investigation of biomolecules, is greatly facilitated at the nanoporous Au film with electron transfer rate constant (ks) of 3.9s(-1). Meanwhile, cyt. c adsorped onto the nanoporous Au film still maintain its enzymatic activity toward H2O2. On the basis of these experimental results, the cyt. c-nanoporous Au film is exploited to an amperometric biosensor for H2O2 with high selectivity, broad linear range, low detection limit, and long stability.


Evolutionary Relationship of the Scale-Bearing Kraken (incertae sedis, Monadofilosa, Cercozoa, Rhizaria): Combining Ultrastructure Data and a Two-Gene Phylogeny.
The genus Kraken represents a distinct lineage of filose amoebae within the Cercozoa. Currently a single species, Kraken carinae, has been described. SSU rDNA phylogeny showed an affiliation to the Cercomonadida, branching with weak support at its base, close to Paracercomonas, Metabolomonas, and Brevimastigomonas. Light microscopical analyses showed several unique features of the genus Kraken, but ultrastructure data were lacking. In this study, K. carinae has been studied by electron microscopy, these data conjoined with a two-gene phylogeny were used to give more insight into the evolutionary relationship of the genus Kraken within Cercozoa. The data confirmed the absence of flagella, but also showed novel characteristics, such as the presence of extrusomes, osmiophilic bodies, and mitochondria with flat cristae. Surprising was the presence of single-tier scales which are carried by cell outgrowths, much of what is expected of the last common ancestor of the class Imbricatea. The phylogenetic analyses however confirmed previous results, indicating Kraken as a sister group to Paracercomonas in Sarcomonadea with an increased but still low support of 0.98 PP/63 BP. Based on the unique features of Kraken we establish the Krakenidae fam. nov. that we, due to contradictory results in morphology and phylogeny, assign incertae sedis, Monadofilosa.


Will We Ever Again Conduct in-Person Psychotherapy Sessions? Factors Associated with the Decision to Provide in-Person Therapy in the Age of COVID-19.
The COVID-19 pandemic has forced a new reality on the delivery of psychotherapeutic services. Therapists have had to rapidly adapt to telehealth therapy using various video conferencing technologies while working from spaces that were not necessarily designed for delivering therapy sessions. While COVID-19 continues to be present in therapists' lives and shapes how they provide services, answering the question of whether to meet with clients in person again is a decision laden with complexity and ambivalence. In this mixed-method study, surveys with 169 therapists and interviews with 17 therapists were used to determine the factors that currently influence their attitudes toward resuming traditional in-person psychotherapy in light of COVID-19. We focused on the therapists' personal and professional characteristics to assess their plans to continue with telepsychotherapy or return to a traditional psychotherapy setting. Our findings suggest that positive attitudes toward telepsychotherapy, the lack of an effective vaccine, clients' satisfaction with telepsychotherapy, insurance reimbursement for telepsychotherapy, and negative attitudes toward wearing masks during sessions influenced therapists' decisions on whether or not to return to traditional in-person psychotherapy in the age of COVID-19.


[Development of the Q-PEX standard for quality certification of pharmaceutical care for outpatients of Pharmacy services].
The objective of this study is to describe the process of creation and development of the quality certification standard for pharmaceutical care for outpatients of the Pharmacy services. The methodology was carried out by a group of experts from the Spanish Society of Hospital Pharmacy (SEFH) and consisted of three phases: situation analysis, development of the standard and definition of the self-assessment tool and, finally, piloting in several hospitals, determining its feasibility, carrying out a new revision and readaptation. A standard was defined with 118 items distributed in ten areas. Of these, 19 were considered compulsory, 36 basic, 40 medium and 23 advanced. Three levels of certification were established, as well as the definition and percentages of compliance with the requirements. The certification process was divided into two stages, the one of previous preparation and the audit itself, where the initial certification would be covered, with four phases - first three led by the certification Company, and the last one by SEFH and the subsequent follow-up and re-certification audits. Two hospitals piloted the process carried out the piloting of the whole process, both obtaining a basic level after the adoption of measures and corrective actions, after which the final definition of the external evaluation of the standard and the name of the standard was agreed upon «Q-PEX», as well as, the registration of the intellectual property of said standard in July-2020. The standard for certification of the quality of pharmaceutical care for outpatients developed aims to help the continuous advancement of Hospital Pharmacy services.


The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in cardiovascular and malignant diseases.
Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active eicosanoids. The primary epoxidation products are four regioisomers of cis-epoxyeicosatrienoic acid (EET): 5,6-, 8,9-, 11,12-, and 14,15-EET. CYP2J2, CYP2C8, and CYP2C9 are the predominant epoxygenase isoforms involved in EET formation. CYP2J and CYP2C gene families in humans are abundantly expressed in the endothelium, myocardium, and kidney. The cardiovascular effects of CYP epoxygenases and EETs range from vasodilation, anti-hypertension, pro-angiogenesis, anti-atherosclerosis, and anti-inflammation to anti-injury caused by ischemia-reperfusion. Using transgenic animals for in vivo analyses of CYP epoxygenases revealed comprehensive and marked cardiovascular protective effects. In contrast, CYP epoxygenases and their metabolites, EETs, are upregulated in human tumors and promote tumor progression and metastasis. These biological effects result from the anti-apoptosis, pro-mitogenesis, and anti-migration roles of CYP epoxygenases and EETs at the cellular level. Importantly, soluble epoxide hydrolase (sEH) inhibitors are anti-hypertensive and anti-inflammatory and, therefore, protect the heart from damage, whereas the terfenadine-related, specific inhibitors of CYP2J2 exhibit strong anti-tumor activity in vitro and in vivo. Thus, CYP2J2 and arachidonic acid-derived metabolites likely play important roles in regulating cardiovascular functions and malignancy under physiological and/or pathological conditions. Moreover, although challenges remain to improving the drug-like properties of sEH inhibitors and identifying efficient ways to deliver sEH inhibitors, sEH will likely become an important therapeutic target for cardiovascular diseases. In addition, CYP2J2 may be a therapeutic target for treating human cancers and leukemia.


Ovine pulmonary transit of tetracycline and minocycline.
Following cannulation of the right external jugular vein and the efferent duct of the right caudal mediastinal lymph node (the caudal end of this node was ligated to cut off the inflow of systemic lymph, i.e., 90%-95% of the efferent lymph was of pulmonary origin), sheep were given either tetracycline or minocycline as single doses of 5 mg/kg body weight infused intravenously over 30 min. Venous blood plasma and pulmonary lymph collected contemporaneously before infusion and from 5 min to 24 hr postinfusion were assayed by a well-agar diffusion method using Bacillus cereus. Peak concentrations of both drugs were observed in both plasma and lymph at 5 min postinfusion. Tetracycline penetrated into the lymph better than minocycline (percent penetration 67.3% of cf. 38.2%). The concentration of tetracycline was significantly higher in lymph during and 5 min postinfusion (p less than 0.01), a factor that may be of importance when selecting a tetracycline for the treatment of a pulmonary infection.


Repeat revision TKR for failed management of peri-prosthetic infection has long-term success but often require multiple operations: a case control study.
Prosthetic joint infection (PJI) is associated with poor outcomes and catastrophic complications. The aim of this study was to present the outcomes of re-revision surgery for PJI of the knee following previous failed two-stage exchange arthroplasty. A retrospective analysis was performed of 32 patients who underwent re-revision knee arthroplasty, having already undergone at least one previous two-stage exchange for PJI with a minimum follow-up of two-years for alive patients. Outcomes were compared to a matched control of two-stage revisions for PJI of a primary knee replacement also containing 32 patients. Outcomes investigated were eradication of infection, re-operation, mortality and limb-salvage rate. Successful eradication of infection was achieved in 50% of patients following re-revision surgery, compared with 91% following two-stage exchange of primary knee replacement for PJI (p < 0.001). Fourteen (44%) patients required further re-operation compared with three (9%) patients in the primary group (p = 0.006). Amputation was performed in one case (3%) with thirteen patients (92%) who had infection controlled by debridement, antibiotics and implant retention (DAIR), further revision surgery or arthrodesis. Two patients died with infection (6%) and the long-term rate for infection control was 91%. The mean number of procedures following surgery for the re-revision group was 2.8 (0-9) compared with 0.13 (0-1) for the primary two-stage group (p < 0.001). Five-year patient survival was 90.6% (95% CI 77.1-100). The limb-salvage rate for the re-revision cohort was 97%. Outcomes for re-revision knee arthroplasty for PJI have higher re-operation and failure rates, but no worse mortality than in revisions of primary knee replacements. Failures can successfully be managed by further operation.


Study on antibacterial and fluoride-releasing properties of a novel composite resin with fluorine-doped nano-zirconia fillers.
A novel composite resin (CR) with fluorine-doped nano-zirconia (F-ZrO2) fillers was developed as an antibacterial restorative material. This article described the synthesis and investigated the fluoride release, antibacterial property and cytotoxicity of the novel CR. F-ZrO2 powders with different fluorine contents (0% F-ZrO2, 5% F-ZrO2, 10% F-ZrO2 or 20% F-ZrO2) were synthesized by chemical precipitation method and characterized by XRD, SEM and TEM-EDS. The content and release of fluoride were also determined. 20% F-ZrO2 powers were selected to develop the novel CRs (FZ-25, FZ-50, and FZ-75). The fluoride release from the novel CRs during 28 days was recorded. The antibacterial property of the novel CRs was investigated with direct contact test (DCT) and metabolic activity test (CCK8). The cytotoxicity of the CRs was also evaluated here. F-ZrO2 powders with different fluorine contents were obtained. The fluoride release increased with increasing of the fluoride content. Through the antibacterial performance evaluation, 20% F-ZrO2 powders, which exhibiting the best antibacterial property, were selected as the fillers for preparing the novel CR. The novel CR with F-ZrO2 fillers exhibited an effective antibacterial effect. Compared with the control group, the antibacterial rates of FZ-25, FZ-50 and FZ-75 were 51.65%, 54.14% and 66.80% (p<0.05), respectively. No obvious cytotoxicity of the novel CR was detected in this study. The novel CR with continuous fluoride release and proper antibacterial property is expected to be used as an antibacterial material to reduce secondary caries.


Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes.
Narcolepsy-cataplexy, a neurological disorder associated with the absence of hypothalamic orexin (hypocretin) neuropeptides, consists of two underlying problems: inability to maintain wakefulness and intrusion of rapid eye movement (REM) sleep into wakefulness. Here we document, using behavioral, electrophysiological, and pharmacological criteria, two distinct classes of behavioral arrests exhibited by mice deficient in orexin-mediated signaling. Both OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal attacks of non-REM sleep ("sleep attacks") and show similar degrees of disrupted wakefulness. In contrast, OX2R(-/-) mice are only mildly affected with cataplexy-like attacks of REM sleep, whereas orexin(-/-) mice are severely affected. Absence of OX2Rs eliminates orexin-evoked excitation of histaminergic neurons in the hypothalamus, which gate non-REM sleep onset. While normal regulation of wake/non-REM sleep transitions depends critically upon OX2R activation, the profound dysregulation of REM sleep control unique to the narcolepsy-cataplexy syndrome emerges from loss of signaling through both OX2R-dependent and OX2R-independent pathways.


The value and limitations of short-term genotoxicity assays and the inadequacy of current criteria for selecting chemicals for cancer bioassays.
The Salmonella gene mutation assay is established as the primary in vitro test for genotoxicity. It does not, however, detect all known genotoxic carcinogens, and several mammalian cell genotoxicity assays are now used to complement the Salmonella test--the most usual being cytogenetic analysis in vitro. Use of these two tests provides an adequate screen for genotoxins, but leaves undetected a variety of weak, DNA-unreactive animal carcinogens such as DDT, saccharin and diethylhexyl phthalate. A reappraisal of the present confused situation examines the underlying problems and options for action. It is suggested that the most effective way of focussing resources on the detection of possible new human carcinogens involves in vitro evaluation of genotoxicity, followed where appropriate by further evaluation in vivo, with urgent attention being paid to the methods currently used to select chemicals for cancer bioassays and to the resolution of the current debate on the validity of some recent classifications of carcinogenicity.


Colo-anal sleeve anastomosis in the treatment of diffuse cavernous haemangioma involving the rectum.
An operative technique, involving a colo-anal sleeve anastomosis, is described for the treatment of cavernous haemangioma of the rectum. All the patients with this condition treated since 1930 at St Mark's Hospital are reviewed, and the presentation and results of treatment in the last 5 patients who have had a resection and colo-anal sleeve anastomosis are discussed.


Evaluating the potential of engineered Trichoderma atroviride and its laccase-mediated system for the efficient bioconversion of 5-hydroxymethylfufural.
5-Hydroxymethylfurfural (HMF) is a fermentation inhibitor which is formed during acid-based thermochemical pre-treatment of biomass. The present study involves two approaches for HMF conversion; the first includes screening and identification of fungal strains which produce oxidoreductases for HMF bioconversion, and thereafter evaluating their roles in HMF conversion. Out of the ten fungal strains screened, genetically engineered Trichoderma atroviride (Lac+) showed maximum HMF bioconversion and the activities of ligninolytic enzymes produced were noted. Maximum HMF conversion of 99% was achieved at pH 5.0 and 30 °C when 72 h old 10% inoculum of T. atroviride (Lac+) was utilized for 6 days. Based on the fungal bioconversion of HMF to 2, 5 diformylfuran with 58% yield, laccase was observed to influence the conversion process. Thus, a comparative study was established on HMF conversion by 100 U/mL of commercial laccases and partially purified laccase from T. atroviride (Lac+). In the presence of TEMPO, T. atroviride laccase showed comparable HMF conversion to commercial laccases, which establishes the efficiency of fungi and ligninolytic enzymes in bioconversion of HMF to value-added products.


Structural aspects of multi-domain RING/Ubox E3 ligases in DNA repair.
Ubiquitin conjugation plays critical roles in virtually all DNA repair pathways. This review provides an overview of the known multi-domain RING/Ubox E3 ligases and their domain structures. An analysis of known RING/Ubox X-ray and NMR structures leads to a discussion of the effects of dimerization. Structural and mechanistic data relating to the E3 ligase preferences for E2 interaction and chain-type specificity are reviewed and the role of the E3 ligases in regulation of the repair pathways is discussed.


Effect of glucose-insulin-potassium infusion on plasma free fatty acid concentrations in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction.
To determine the effect of glucose-insulin-potassium infusion on circulating levels of free fatty acids in the setting of contemporary management of ST-elevation myocardial infarction, we randomly assigned 20 patients who were undergoing primary angioplasty to glucose-insulin-potassium infusion or to standard care. Treatment with glucose-insulin-potassium was associated with significantly lower levels of free fatty acid after 24 hours compared with standard care.


Coexistence of low levels of HBsAg and high levels of anti-HBs may increase risk of hepatocellular carcinoma in chronic hepatitis B patients with high HBV load.
The clinical significance of coexistence of HBsAg/anti-HBs in chronic hepatitis B (CHB) patients remains controversial. This study was aimed to assess the association of this serological pattern with hepatocellular carcinoma (HCC) in patients with CHB. In this cross-section study, 206 CHB patients with coexistence of HBsAg/anti-HBs and 206 CHB patients with HBsAg alone were included to evaluate the risk of HCC development by logistic regression analysis. In addition, a retrospective cohort of 260 patients with CHB was recruited to estimate the cumulative incidence of HCC by Kaplan-Meier analysis. The serological pattern of coexistence of HBsAg/anti-HBs, with high levels of ("High") HBsAg/low levels of ("Low") anti-HBs, were considered as independent risk factors for HCC. In particular, patients with "High" HBsAg/"High" anti-HBs [odds ratio (OR), 4.295; 95% confidence interval (CI), 1.104-16.699; p = 0.035] and "Low" HBsAg/ "High" anti-HBs (OR, 3.207; 95%CI, 1.299-7.919; p = 0.012) exhibited significantly higher risk for HCC development. However, only "Low" HBsAg /"High" anti-HBs might increase risk of HCC in CHB patients with high HBV load (logrank p < 0.001) in our cohort study. The coexistence of "Low" HBsAg /"High" anti-HBs might increase the risk of HCC development in CHB patients with high HBV load, which reflected that the long-term interaction between immune response and virus might lead to the development of HCC. The identification of the patients with poor prognosis will help clinicians to refine the therapeutic decisions and individualize follow-up strategies.


Consumption of alcoholic beverages in Brazil: estimation of prevalence ratios - 2013 and 2019.
To estimate the prevalence of weekly, monthly and abusive alcohol consumption in Brazil in 2013 and 2019, compare the period estimates, and verify the magnitude of the differences. Analysis of data on alcohol consumption in the adult population (18 years or older) from the National Health Survey (PNS), 2013 and 2019. The number of interviewees in 2013 was 60,202 and 88,531 in 2019. The samples were characterized according to demographic, socioeconomic, health, and alcohol consumption variables and differences in proportions in the period were compared using Pearson's c2 test, with Rao-Scott approximation and a 5% significance level. Multivariate Poisson regression models were estimated for the outcome variables of monthly, weekly and abusive consumption of alcoholic beverages, in order to estimate the magnitude of the differences between the 2013 and 2019 PNS estimates, using the prevalence ratio (PR). Models were adjusted per sex and age group and stratified per sex and demographic region. There was a difference in the distribution of the population according to race, occupation, income, age group, marital status, and education. There was an increase in alcohol consumption for all outcome variables, with the exception of weekly consumption in males. The PR of weekly consumption was 1.02 (95%CI 1.014-1.026), and in females the PR was 1.05 (95%CI 1.04-1.06). The highest PRs in the general population and per sex occur for abusive consumption. The increase in weekly consumption per region occurred in the South, Southeast, and Central-West regions. Males are the main alcohol consumers in Brazil; the PRs for both males and females show that there was an increase in monthly, weekly and abusive consumption in the research period; it is noteworthy that females have increased their consumption pattern with greater intensity than males.


Fatty acyl derivatives of glucosamine 1-phosphate in Escherichia coli and their relation to lipid A. Complete structure of A diacyl GlcN-1-P found in a phosphatidylglycerol-deficient mutant.
We have determined the complete structure of a glycolipid (designated lipid X) previously found to accumulate in certain Escherichia coli mutants defective in phosphatidylglycerol synthesis (Nishijima, M., and Raetz, C.R.H. (1979) J. Biol. Chem. 254, 7837-7844). Based on fast atom bombardment mass spectrometry and proton nuclear magnetic resonance studies, this substance is an acylated metabolite of glucosamine 1-phosphate. Lipid X of E. coli has a Mr = 711.87 as the free acid (C34H66NO12P) and contains two beta-hydroxymyristate moieties, one attached as an amide at the 2 position and the other as an ester at the 3 position of the sugar. It has free hydroxyl groups at the 4 and 6 positions, and the anomeric configuration is alpha. The structure of lipid X from E. coli closely resembles the reducing end subunit of lipid A, and it might represent a very early precursor in the biosynthesis of lipid A. To our knowledge, fatty acyl derivatives of glucosamine 1-phosphate have not been reported previously.


Heart Rate Variability: A Personal Journey.
Heart rate variabfility (HRV) has been a focal point throughout my academic history. To put into perspective, I have published studies spanning seven decades focusing on HRV (1969-2022). My interest in HRV started early in graduate school and continues to be an important portal informing my theoretical perspective. The current paper tracks some of this history, which started as an empirical observation and moved through several scientific stages including development of quantitative methods and investigations of neural mechanisms. Along this journey a variety of hypotheses were tested including the relative sensitivity of HRV metrics to neural mechanisms, psychological processes, and medical diagnoses. In addition, the research led to the identification of portal of intervention that have become strategies to optimize mental and physical health. These apparent disparate programs of inquiry have been tightly merged as the Polyvagal Theory evolved. In the sections below, I have shared my personal journey through these stages of scientific inquiry and my attempts to integrate the new knowledge in an expansive theoretical model.


Differentiation of nitrous oxide emission factors for agricultural soils.
Nitrous oxide (N(2)O) direct soil emissions from agriculture are often estimated using the default IPCC emission factor (EF) of 1%. However, a large variation in EFs exists due to differences in environment, crops and management. We developed an approach to determine N(2)O EFs that depend on N-input sources and environmental factors. The starting point of the method was a monitoring study in which an EF of 1% was found. The conditions of this experiment were set as the reference from which the effects of 16 sources of N input, three soil types, two land-use types and annual precipitation on the N(2)O EF were estimated. The derived EF inference scheme performed on average better than the default IPCC EF. The use of differentiated EFs, including different regional conditions, allows accounting for the effects of more mitigation measures and offers European countries a possibility to use a Tier 2 approach.


[Changes in the ocular muscles in progressive scleroderma (author's transl)].
One patient out of 13 with generalized scleroderma displayed related changes of ocular motility. Histologic examination of the external ocular muscles of one of our patients who had died, revealed a massive increase of the interstitial collagen, and various stages of muscular degeneration. These changes correspond closely with the histopathological findings in the myocardium.


Chronic obstructive pulmonary disease and lung cancer: access to palliative care, emergency room visits and hospital deaths.
Despite the severe symptoms experienced by dying COPD patients, specialized palliative care (SPC) services focus mainly on cancer patients. We aimed to study the access to SPC that COPD and lung cancer (LC) patients receive and how that access affects the need for acute hospital care. A descriptive regional registry study using data acquired through VAL, the Stockholm Regional Council's central data warehouse, which covers nearly all healthcare use in the county of Stockholm. All the patients who died of COPD or LC from 2015 to 2019 were included. T-tests, chi-2 tests, and univariable and multivariable logistic regression analyses were performed on the accumulated data. In total, 6479 patients, (2917 with COPD and 3562 with LC) were studied. The patients with LC had more access to SPC during the last three months of life than did those with COPD (77% vs. 18%, respectively; p < .0001), whereas patients with COPD were more likely to be residents of nursing homes than those with LC (32% vs. 9%, respectively; p < .0001). Higher socioeconomic status (SES) (p < .01) and patient age < 80 years (p < .001) were associated with increased access to SPC for LC patients. Access to SPC correlated with fewer emergency room visits (p < .0001 for both COPD and LC patients) and fewer admissions to acute hospitals during the last month of life (p < .0001 for both groups). More COPD patients died in acute hospitals than lung cancer patients, (39% vs. 20%; χ2 = 287, p < .0001), with significantly lower figures for those who had access to SPC (p < .0001). Compared to dying COPD patients, LC patients have more access to SPC. Access to SPC reduces the need for emergency room visits and admissions to acute hospitals.


Completely endoscopic removal of a dislocated Amplatzer atrial septal defect closure device.
Surgical treatment of residual shunts after transcatheter occlusion of atrial septal defect or patent foramen ovale is reported in approximately one to two percent of these percutaneous interventions. Minimally invasive surgery on the atrial septum is getting more and more common but little data is available on Amplatzer device explantation through limited access. No completely endoscopic device removal has been described previously. We report a case of a 57-year-old woman in whom an Amplatzer device was removed in a robotic totally endoscopic fashion through ports only using the daVinci telemanipulation system.


Investigating Effects of Interactive Virtual Reality Games and Gender on Immersion, Empathy and Behavior Into Environmental Education.
Environmental concerns are obstacles that all humans should confront. Accordingly, Taiwan has incorporated environmental education into its curriculum guidelines; however, difficulties have been encountered in its implementation because Taiwanese society clings to the concept of credentialism, students cannot focus in class, and course content is too abstract. Virtual reality (VR) techniques have been incorporated into the field of education for years; because they can increase the interestingness of learning and also concretely present matters through gamification, the present study applied VR techniques to resolve the aforementioned difficulties. VR can build environments and situations that would be impossible to visit in the real world, e.g., travel inside a human body, or the physically impossible-the surface of Mars. The aim was to increase students' immersion in class would generate empathy toward the natural environment and perform actual behaviors to protect it. In terms of the experimental design, gender and teaching methods were defined as independent variables, and observation and questionnaires were conducted and applied to examine students' immersion, empathy, and behaviors after learning. Participants in the experimental group watched a 3D video through a semi-immersive VR device, whereas those in the control group watched an ordinary video accompanied by an explanation from the teacher. The numbers of male and female students were equally allocated, and the learning outcomes of the two groups were further examined. A two-way multivariate analysis of variance test was conducted to examine the influences of 2(genders) × 2(teaching methods) on students' immersion, empathy, and actual behaviors and also mainly to inspect whether the differences between genders and teaching methods resulted in a direct influence or interaction. The experimental results revealed that the effectiveness of the application of VR techniques is affected by gender; female students presented more favorable performance in both empathy and actual behaviors. In brief, VR techniques can generally enhance students' learning outcomes; however, limitations such as the cost of VR devices and material designs should also be considered.


Pre-treatment with Tandospirone attenuates fentanyl-induced respiratory depression without affecting the analgesic effects of fentanyl in rodents.
Opioid analgesics are widely used to treat acute, postoperative, and chronic pain. However, opioid receptor activation can result in severe respiratory depression. In this study, we demonstrated that Tandospirone (TS), a selective serotonin-1A receptor partial agonist, is effective against opioid-induced respiratory depression. Fentanyl was used to establish a respiratory depression model in rodents. We observed the effects of TS on respiratory depression in rats by using plethysmographic recordings and arterial oxygen saturation. In addition, we evaluated the effects of TS on fentanyl-induced sedation and analgesia by using the loss of righting reflex (LORR) and hot-plate tests, respectively. Rats (n = 5) were treated with TS or saline 5 min prior to fentanyl administration. TS [2 mg/kg, intravenous (i.v.)] dose-dependently attenuated fentanyl-induced respiratory depression versus saline + fentanyl group. Furthermore, pre-treatment with TS (2 mg/kg, i.v.) increased arterial oxygen saturation to 76.5 ± 2.0% at 5 min after fentanyl injection, compared with 35.9 ± 2.5% in saline pre-treated rats (P < 0.001), whereas the time to induction of LORR (P > 0.99) and duration of LORR (P = 0.95) did not differ between the "TS + fentanyl" and "saline + fentanyl" group. The antinociceptive effect of fentanyl was not affected by the administration of TS (P = 0.99) in mice (n = 10). In conclusion, we found that TS, a novel non-benzodiazepine anxiolytic/antidepressant drug, could attenuate severe fentanyl-induced respiratory depression and did not affect the analgesic/sedative effect of fentanyl. The clinical application of TS could significantly improve pain management.


Percutaneous coronary intervention with off-site cardiac surgery backup for acute myocardial infarction as a strategy to reduce door-to-balloon time.
We investigated whether primary percutaneous coronary intervention (PCI) for patients admitted with an acute ST-segment elevation myocardial infarction could be performed more rapidly and with comparable outcomes in a community hospital versus a tertiary center with cardiac surgery. We started the first PCI with an off-site surgery program in The Netherlands in 2002 and report the results of 439 consecutive patients. In the safety phase, 199 patients presenting with ST-segment elevation myocardial infarction were randomly assigned to treatment at our off-site center versus a more distant cardiac surgery center. In the confirmation phase, 240 consecutive patients were treated in the off-site hospital. Safety and efficacy end points were the rate of an angiographically successful PCI procedure (diameter stenosis <50% and Thrombolysis In Myocardial Infarction grade 3 flow) in the absence of major adverse cardiac and cerebrovascular events at 30 days. The randomization phase showed a 37-minute decrease in door-to-balloon time (p <0.001) with comparable procedural and clinical successes (91% Thrombolysis In Myocardial Infarction grade 3 flow in the 2 groups). In the confirmation phase, the 30-day rate without major adverse cardiac and cerebrovascular events was 95%. None of the 439 patients in the study required emergency surgery for failed primary PCI. In conclusion, time to treatment with primary PCI can be significantly shortened when treating patients in a community hospital setting with off-site cardiac surgery backup compared with transport for PCI to a referral center with on-site surgery. PCI at hospitals with off-site cardiac surgery backup can be considered a needed strategy to improve access to primary PCI for a larger segment of the population and can be delivered with a very favorable safety profile.


Regioselective reductive openings of 4,6-benzylidene acetals: synthetic and mechanistic aspects.
The use of benzylidene acetals as protecting groups in carbohydrate chemistry is utterly important. The main advantage of benzylidene acetal is the ability for regioselective openings. 4,6-benzylidene acetal can be opened selectively under reductive conditions to yield either free 4-OH or 6-OH. There are a plethora of methods available for regioselective openings, but only a few of these are widely used. In recent years, the mechanism has been investigated for borane mediated openings and it seems likely that the regioselectivity is determined by borane, rather than Lewis acid. When borane is activated by Lewis acids, borane is the most electrophilic species that consequently coordinates to the most nucleophilic oxygen of the acetals, usually O-6. This results in the formation of 6-O-benzyl ethers. If borane is not activated, Lewis acid is the most electrophilic species that thus adds to O-6 and hence generates the 4-O-benzyl ether.


First-principles study of the liquid and amorphous phases of Sb2Te phase change memory material.
We have investigated the local structure of liquid and amorphous phases of Sb2Te phase change memory material by the means of density functional theory-molecular dynamics simulations. The models of liquid and amorphous states were generated by quenching from the melt. The results show that the local environment of liquid Sb2Te is a mixed bonding geometry, where the average coordination numbers (CNs) of Sb and Te atoms are 4.93 and 4.23, respectively. Compared with crystalline state, there are more Sb-Sb bonds (∼53%) and less Sb-Te bonds (∼42%) with the presence of Te-Te bonds (∼5%) in liquid Sb2Te. Therefore, the formation of homopolar bonds and the breaking of heteropolar bonds are important structural transformations in melt process. For amorphous Sb2Te, the average CNs of Sb and Te atoms are 4.54 and 3.57, respectively. They are mostly in an octahedral environment, similar to the case in crystalline phase. The fractions of Sb-Sb, Te-Te, and Sb-Te bonds are ∼52%, ∼2%, and ∼46%, respectively. Thus, the increase in the fraction of octahedron accompanied with the decrease in average CN is the major structural changes in quenching process. Furthermore, the octahedral geometry in both the crystalline and amorphous Sb2Te increases the local structural similarity, facilitating the rapid low-energy crystallization.


Diet-derived male sex pheromone compounds affect female choice in a noctuid moth.
Sexual signals often function in species recognition and may also guide mate choice within a species. In noctuid moths, both males and females may exercise mate choice. Females of the tobacco budworm Chloridea virescens prefer to mate with larger males, but the signal(s) underlying female choice remain unknown. Male hairpencil volatiles are emitted during close range courtship displays. However, previously identified male hairpencil volatiles, namely acetate esters, aldehydes, alcohols, and fatty acids, are not associated with female choice. Recently, two new hairpencil compounds were identified that elicit strong electrophysiological responses in female antennae: methyl salicylate (MeSA) and δ-decalactone. In this study, we investigated the effect of larval diet and adult feeding on MeSA and δ-decalactone content in hairpencils and determined whether these compounds are involved in female choice. We found that larval diet affected MeSA content in hairpencils, but not δ-decalactone. Conversely, adult feeding affected the level of δ-decalactone, but not MeSA: sugar-water feeding increased δ-decalactone content compared to plain water. In two-choice assays, females mated more with males that had higher amounts of δ-decalactone, and less with males with higher amounts of MeSA.


Head and Neck CTA Utilization: Analysis of Ordering Frequency and Nonroutine Results Communication, With Focus on the 50 Most Common Emergency Department Clinical Presentations.
BACKGROUND. Utilization of head and neck CTA in the emergency department (ED) has grown disproportionately to other neuroimaging examinations. OBJECTIVE. The purpose of this article was to characterize utilization of head and neck CTA in the ED, comparing utilization and frequency of nonroutine results communication among patients' chief concerns. METHODS. All adult ED visits for a single health care system from January 2014 to December 2017 were retrospectively reviewed. Variables recorded included chief concerns, whether head and neck CTA was performed, and, if so, whether the report documented nonroutine results communication. The 50 chief concerns resulting in the highest number of head and neck CTA examinations were identified. Frequencies of head and neck CTA ordering and of nonroutine results communication were calculated. A subset of reports documenting nonroutine communication were manually reviewed. RESULTS. Head and neck CTA was ordered in 2.5% (17,903) of 708,145 ED visits in 236,476 patients (mean age, 49.8 ± 20.5 [SD] years; 110,952 men, 125,521 women, 3 unknown sex). Head and neck CTA was ordered for 833 distinct chief concerns. Nonroutine results communication was documented for 17.6% (3155/17,903) of examinations. Among the 50 chief concerns associated with the highest number of examinations, frequency of ordering head and neck CTA ranged from less than 0.5% (five concerns) to 55.2% (stroke code), and frequency of nonroutine communication ranged from 5.6% (transient ischemic attack) to 67.5% (unresponsive). Chief concerns not among the 50 most common accounted for 50.0% (8956/17,903) of examinations; these exhibited a collective frequency of nonroutine communication of 4.8% (429/8956). Manual review of 11.1% (350/3155) of reports with a nonroutine communication indicated an acute finding related to the indication in 51.1%, nonemergent but potentially explanatory finding in 14.0%, incidental finding in 28.0%, and communication of negative results in 6.9%. CONCLUSION. Head and neck CTA is ordered in 2.5% of ED visits for a wide range of chief concerns. Frequencies of ordering and of nonroutine results communication are highly variable among chief concerns. Acute indication-related findings account for half of nonroutine radiologist communications. CLINICAL IMPACT. Insight into patterns regarding head and neck CTA ordering and nonroutine results may help optimize patient selection and radiologist communications in the ED setting.


[Intraoperative use of an image intensifier in coral calculus operations (author's transl)].
The applicability of the image converter in kidneys stone operations, and particularly in coral calculus operations, is discussed. A comparison is made with other X-ray methods and the advantages of an extended area of use of the image converter is presented.


Optogenetically-induced multimerization of the dopamine transporter increases uptake and trafficking to the plasma membrane.
The dopamine transporter (DAT) is essential for the reuptake of the released neurotransmitter dopamine (DA) in the brain. Psychostimulants, methamphetamine and cocaine, have been reported to induce the formation of DAT multimeric complexes in vivo and in vitro. The interpretation of DAT multimer function has been primarily in the context of compounds that induce structural and functional modifications of the DAT, complicating the understanding of the significance of DAT multimers. To examine multimerization in the absence of DAT ligands as well as in their presence, we developed a novel, optogenetic fusion chimera of cryptochrome 2 and DAT with an mCherry fluorescent reporter (Cry2-DAT). Using blue light to induce Cry2-DAT multimeric protein complex formation, we were able to simultaneously test the functional contributions of DAT multimerization in the absence or presence of substrates or inhibitors with high spatiotemporal precision. We found that blue light-stimulated Cry2-DAT multimers significantly increased IDT307 uptake and MFZ 9-18 binding in the absence of ligands as well as after methamphetamine and nomifensine treatment. Blue light-induced Cry2-DAT multimerization increased colocalization with recycling endosomal marker Rab11 and had decreased presence in Rab5-positive early endosomes and Rab7-positive late endosomes. Our data suggest that the increased uptake and binding results from induced and rapid trafficking of DAT multimers to the plasma membrane. Our data suggest that DAT multimers may function to help maintain DA homeostasis.


COVID-19 Global Humanitarian Response Plan: An optimal distribution model for high-priority countries.
The 2019 novel coronavirus disease (COVID-19) has spread rapidly worldwide, and the outbreak of the disease was designated a global pandemic by the World Health Organization. Such outbreaks would certainly be catastrophic for some of the best-ranked health systems and would be more catastrophic in countries with more fragile health systems. Accordingly, the World Health Organization and other organizations have been appealing to donor countries to support a rapid response plan. The primary objectives of this response plan are to appeal for funds from donors and to distribute these funds to the most affected countries based on the requirements. In this study, we developed a mathematical model to provide initial insights into the efficient and equitable distribution of urgent funds to high-priority countries. Three phases were proposed for the construction of this mathematical model. In the first phase, the final epidemic sizes in all the target countries were predicted by using three epidemiological models. In the second phase, the urgent requirements for each country were estimated in parallel with the estimates issued by the humanitarian response plan, based on the size of the epidemic and several other factors. In the third and final phase, a multi-objective optimization model was proposed. The first objective was to maximize the funds from donors to cover all the requirements. The second objective was to minimize the unmet demands by ensuring a fair distribution of the urgent funds based on the requirements of the target countries. Predictions of the basic reproduction numbers and the final epidemic sizes were calculated for all target countries. The urgent requirements were estimated, and the requirements issued by the humanitarian response plan for all target countries were also considered. Moreover, a proposed response plan for the distribution network was demonstrated. Donors must provide urgent funds exceeding US$ 2,608,084,209 to cover at least 40 % of each target country's requirements. Overall, results demonstrate the importance of an urgent and fair distribution of funds to the target countries to overcome the outbreak of COVID-19. Rapid responses by donor countries to humanitarian appeals will facilitate the immediate and fair distribution of relief supplies to the poorest countries. This distribution may help to support health systems, restrain the spread of COVID-19, and prevent an unlimited catastrophe.


Normalisation of metabolite images in 1H NMR spectroscopic imaging.
Single slice proton magnetic resonance spectroscopic images were taken from a volume of interest (VOI), which was localised using the point resolved spectroscopy (PRESS) sequence. Non-uniformities in the excitation profile of the VOI within the image plane were accounted for using a uniformity correction image. Metabolite images were divided on a voxel-by-voxel basis with a water image obtained from a VOI of the same spatial dimensions from a phantom acquisition. Normalisation procedures carried out on phantom metabolite images were needed to account for the spatial shift in the excitation profile of the VOI, which varies linearly with the chemical shift of the metabolite. Patient metabolite images were then normalised using a VOI water image from a phantom acquisition, which was spatially shifted according to the metabolite chemical shift. In a study of 14 stroke patients, metabolite maps of the distribution of choline, creatine and N-acetyl aspartate (NAA) were constructed. The spectral signal intensities from these metabolites in the infarcted and in the contralateral region were calculated using the raw maps and secondly with the same maps after the B1 normalisation process. In the initial analysis only the metabolite NAA showed a significant decrease, whilst all three metabolites showed a significant reduction in the normalised analysis. These results confirm that normalisation of PRESS localised images does have a significant bearing upon any quantitative measurements made using such images.


Microbiome diversity from sponges biogeographically distributed between South America and Antarctica.
Sponges from South America and Antarctica are evolutionarily closely related. Specific symbiont signatures that could differentiate these two geographic regions are unknown. This study aimed to investigate the microbiome diversity of sponges from South America and Antarctica. In total 71 sponge specimens were analyzed (Antarctica: N = 59, 13 different species; South America: N = 12, 6 different species). Illumina 16S rRNA sequences were generated (2.88 million sequences; 40K ± 29K/sample). The most abundant symbionts were heterotrophic (94.8 %) and belonged mainly to Proteobacteria and Bacteroidota. EC94 was the most abundant symbiont and dominated the microbiome of some species (70-87 %), comprising at least 10 phylogroups. Each of the EC94 phylogroups was specific to one genus or species of sponge. Furthermore, South America sponges had higher abundance of photosynthetic microorganisms (2.3 %) and sponges from Antarctica, the highest abundance of chemosynthetic (5.5 %). Sponge symbionts may contribute to the function of their hosts. The unique features from each of these two regions (e.g., light, temperature, and nutrients) possibly stimulate distinct microbiome diversity from sponges biogeographically distributed across continents.


Rectal toxicity profile after transperineal interstitial permanent prostate brachytherapy: use of a comprehensive toxicity scoring system and identification of rectal dosimetric toxicity predictors.
To better understand rectal toxicity after prostate brachytherapy, we employed the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0), a comprehensive system with distinct and separately reported gastrointestinal adverse event items (unlike Radiation Therapy Oncology Group morbidity scoring), to evaluate item-specific postimplant rectal toxicities. We analyzed 135 patients treated with brachytherapy +/- hormonal therapy, using CTCAE v3.0 to score acute/late rectal toxicities (median follow-up, 41 months). Dosimetric parameters were evaluated for ability to predict toxicities. Use of CTCAE yielded a novel rectal toxicity profile consisting of diarrhea, incontinence, urgency, proctitis, pain, spasms, and hemorrhage event rates. No item had a < 5% Grade 1-2 acute toxicity rate (except spasms). Rectal dosimetry predicted late toxicities: for diarrhea, 5% Grade 1 toxicity rate for %V25 (percent of rectal volume receiving 25% of prescribed prostate dose) < or = 25% vs. 60% for %V25 > 25% (p < 0.001); for maximum toxicity, 10% Grade 1 toxicity rate for %V10 < or = 40% vs. 44% for %V10 > 40% (p = 0.007). A comprehensive understanding of item-specific postimplant rectal toxicities was obtained using CTCAE. Rectal %V25 > 25% and %V10 > 40% predicted worse late diarrhea and maximum toxicity, respectively.


Pathways to and factors associated with rape stigma experienced by rape survivors in South Africa: Analysis of baseline data from a rape cohort.
Rape stigma, both external and self-stigmatization (self-blame), is associated with adverse health outcomes. Understanding its origins and resilience factors is critical for reducing and preventing it. We describe the prevalence of rape stigma, the characteristics of women experiencing it and the pathways to experiencing greater stigma. The Rape Impact Cohort Evaluation study enrolled 852 women aged 16-40 years who had been raped from post-rape care centres in Durban, South Africa. We present a descriptive analysis of the baseline data, a multinomial logistic regression model of factors associated with different levels of stigma and a structural equation model (SEM). Most women reported stigmatizing thoughts or experiences, with self-stigmatizing thoughts being more prevalent than external stigmatization. The multinomial model showed that experiences of childhood or other trauma, emotional intimate partner violence (IPV), having less gender equitable attitudes and food insecurity were significantly associated with medium or high versus low levels of stigma. Internal and external stigma were significantly associated with each other. Women who had been previously raped reported less stigma. The SEM showed a direct path between food insecurity and rape stigma, with poorer women experiencing more stigma. Indirect paths were mediated by more traditional gender attitudes and childhood trauma experience and other trauma exposure. Our findings confirm the intersectionality of rape stigma, with its structural drivers of food insecurity and gender inequality, as well as its strong association with prior trauma exposure. Rape survivors may benefit from gender-empowering psychological support that addresses blame and shame.


Response to Immunosuppressive Therapy in Acquired Aplastic Anaemia: Experience of a Tertiary Care Centre from Eastern India.
The current study was conducted to assess response to immunosuppressive therapy (IST) in acquired aplastic anaemia (AA). It was a retrospective and prospective observational study. Patients were diagnosed as per standard international guidelines and IST was started as per standard protocol. Patients were followed up at 3 months and 6 months for assessment of response as per published standard guidelines. Total 76 cases were included in the study. The median age of the study population was 36 years with a range of 6-66 years with a male to female ratio of 2.04:1. Most common clinical presentation was pallor followed by bleeding. Commonest type of disease in the study group was severe AA. Among total 76 patients, 32 patients received Atgam and 44 patients received Thymogam. Within 3 months of ATG administration, 4 patients died and 1 patient was lost to follow up. At 3 months, 2 (2.63%) patients were on complete response (CR), 32 (42.10%) patients were in partial response (PR) and 37 (48.68%) patients were on no response (NR). Overall response (OR) at 3 months was 44.73%. At 6 months 5 (6.57%) patients were in CR, 43 (56.57%) patients in PR and 23 (30.26%) patients in NR; the OR was 63.14%. Overall response at 3 months was 44.73% and overall response at 6 months was 63.14%. The study revealed better overall survival for patients with ATGAM treatment than THYMOGAM treatment arm.


Idioventricular parasystolic rhythms.
A description is given of the electrocardiograms of three subjects with artificial demand pacemakers in whom no inhibition of the idioventricular rhythms occurs, thus causing unusual relationships between the artificial and the spontaneous rhythms. The latter are protected and therefore appear to be parasystolic. In the first two cases, interpolated artificial beats are inscribed in the spontaneous rhythm. In the third case, the spontaneous parasystole is intermittent and alternates with concealed extrasystolic beats originating in the same focus.


Endocarditis-TR: Diagnosis, treatment, and prognosis of the infective endocarditis patients admitting tertiary centres of Turkey.
Infective endocarditis (IE) is still a significant cause of morbidity and mortality among cardiovascular diseases. ENDOCARDITIS-TR study aims to evaluate the compliance of the diagnostic and therapeutic methods being used in Turkey with current guidelines. The ENDOCARDITIS-TR trial is a multicentre, prospective, observational study consisting of patients admitted to tertiary centres with a definite diagnose of IE. In addition to the demographic, clinical, microbiological, and echocardiographic findings of the patients, adverse events, indications for surgery, and in-hospital mortality were recorded during a 2-year time interval. A total of 208 IE patients from 7 tertiary centres in Turkey were enrolled in the study. The study population included 125 (60.1%) native valve IE (NVE), 65 (31.3%) prosthetic IE (PVIE), and 18 (8.7%) intracardiac device-related IE (CDRIE). One hundred thirty-five patients (64.9%) were culture positive, and the most frequent pathogenic agent was methicillin-susceptible Staphylococcus aureus (MSSA) (18.3%). Among 155 (74.5%) patients with an indication for surgery, only 87 (56.1%) patients underwent surgery. The all-cause mortality rate was 29.3% in-hospital follow-up. Multivariable Cox regression analysis revealed that absence of surgery when indicated (HR: 3.29 95% CI: 0.93-11.64 p = 0.05), albumin level at admission (HR: 0.46 95% CI: 0.29-0.73 P < 0.01), abscess formation (HR: 2.11 95% CI: 1.01-4.38 p = 0.04) and systemic embolism (HR: 1.78 95% CI: 1.05-3.02 p = 0.03) were ascertained independent predictors of in-hospital all-cause mortality. The short-term results of the ENDOCARDITIS-TR trial showed the high frequency of staphylococcal IE, relatively high in-hospital mortality rates, shortage of surgical treatment despite guideline-based surgical indications and low usage of novel imaging techniques. The results of this study will provide a better insight to physicians in respect to their adherence to clinical practice guidelines.


Comparison of myocardial deformation and velocity dyssynchrony for identification of responders to cardiac resynchronization therapy.
It is unclear whether myocardial velocity or deformation indices of dyssynchrony are better at predicting response to cardiac resynchronization therapy (CRT). Therefore, two indices of left ventricular (LV) dyssynchrony based on myocardial velocity and deformation were compared to predict success of CRT. Sixty patients with dilated cardiomyopathy, New York Heart Association class III-IV, LV ejection fraction (EF) < or =35%, QRS >120 ms underwent CRT. The standard deviation of the averaged time-to-peak longitudinal negative strain (Tepsilon-SD) and positive systolic velocity (Tv-SD) of 12 LV segments were calculated before and after 6 months of CRT. Responders were defined at month 6 by > or =20% EF increase and/or > or =15% end-systolic volume (ESV) decrease with respect to baseline. On univariable analysis, baseline Tepsilon-SD and Tv-SD were both significantly associated with CRT response; however, the area under the receiver operating characteristic curve was better for Tepsilon-SD. On bivariable analysis, only Tepsilon-SD retained an independent prognostic value for CRT response. Results of the analysis did not change when the logistic models were adjusted for aetiology. Baseline dyssynchrony of longitudinal myocardial peak deformation (Tepsilon-SD) appears to be better than dyssynchrony of longitudinal myocardial peak systolic velocities (Tv-SD) for the identification of CRT responders.


Different recombinant murine leukemia viruses use different cell surface receptors.
Retroviruses can be grouped by viral interference measurements into classes which use common cell surface receptors. We previously tested a large number of isolates of mink cell focus-inducing (MCF) murine leukemia viruses (MuLVs), and reported that all of them share a distinct receptor on NIH/3T3 cells (A. Rein, Virology 120, 251, 1982). We now extend this generalization to several additional recombinant isolates, including two (SL3-2 and GPA-V2) which would not be considered MCFs on the basis of host-range data. We note the superiority of interference tests, based on positive, unambiguous data, over host-range tests for virus classification. We also show that in contrast to the MCFs, which are all derived from ecotropic MuLVs, a recombinant derived from wild mouse amphotropic MuLV (S. Rasheed et al., Int. J. Cancer 29, 345, 1982) uses a unique receptor on NIH/3T3 cells. This suggests that (a) mouse cells contain more than one type of endogenous env sequence; and (b) there is some specificity in the generation of recombinants, since ecotropic MuLVs appear to give rise only to MCFs, while amphotropic MuLV has generated a distinct type of recombinant. It also represents a second case (in addition to the MCFs) in which an env gene recombinant is more pathogenic than its exogenous parent. We also show that xenotropic MuLV does not interfere with MCFs in NZB mouse cells; thus, despite the close homology between MCF and xenotropic env sequences, the gp70 of xenotropic MuLV appears to have no detectable affinity for the MCF receptor.


Plastic pollution and fungal, protozoan, and helminth pathogens - A neglected environmental and public health issue?
Plastic waste is ubiquitous in the environment and can become colonised by distinct microbial biofilm communities, known collectively as the 'plastisphere.' The plastisphere can facilitate the increased survival and dissemination of human pathogenic prokaryotes (e.g., bacteria); however, our understanding of the potential for plastics to harbour and disseminate eukaryotic pathogens is lacking. Eukaryotic microorganisms are abundant in natural environments and represent some of the most important disease-causing agents, collectively responsible for tens of millions of infections, and millions of deaths worldwide. While prokaryotic plastisphere communities in terrestrial, freshwater, and marine environments are relatively well characterised, such biofilms will also contain eukaryotic species. Here, we critically review the potential for fungal, protozoan, and helminth pathogens to associate with the plastisphere, and consider the regulation and mechanisms of this interaction. As the volume of plastics in the environment continues to rise there is an urgent need to understand the role of the plastisphere for the survival, virulence, dissemination, and transfer of eukaryotic pathogens, and the effect this can have on environmental and human health.