Disparities in access to high-volume parathyroid surgeons in the United States: A call to action.
Parathyroidectomy by a high-volume surgeon is associated with a reduced risk of perioperative complications and of failure to cure primary and secondary hyperparathyroidism. There are limited data on disparities in access to high-volume parathyroid surgeons in the United States. We used publicly available 2019 Medicare Provider Utilization and Payment data to identify all surgeons who performed >10 parathyroidectomies for Medicare fee-for-service beneficiaries, anticipating that fee-for-service beneficiaries likely represent only a subset of their high-volume practices. High-volume parathyroid surgeon characteristics and geographic distribution were evaluated. Inequality in the distribution of surgeons was measured by the Gini coefficient. The association between neighborhood disadvantage, based on the Area Deprivation Index, and proximity to high-volume parathyroid surgeons was evaluated using a one-way analysis of variance with Bonferroni-corrected pairwise comparisons. A sensitivity analysis was performed restricting to high-volume parathyroid surgeons within each hospital referral region, evidence-based regional markets for tertiary medical care. We identified 445 high-volume parathyroid surgeons who met inclusion criteria with >10 parathyroidectomies for Medicare fee-for-service beneficiaries. High-volume parathyroid surgeons were 71% male sex, and 59.8% were general surgeons. High-volume parathyroid surgeons were more likely to practice in a Metropolitan Statistical Area with a population >1 million than in less populous metropolitan or rural areas. The number of high-volume parathyroid surgeons per 100,000 fee-for-service Medicare beneficiaries in the 53 most populous Metropolitan Statistical Areas ranged from 0 to 4.94, with the highest density identified in Salt Lake City, Utah. In 2019, 50% of parathyroidectomies performed by high-volume parathyroid surgeons were performed by 20% of surgeons in this group, suggesting unequal distribution of surgical care (Gini coefficient 0.41). Patients in disadvantaged neighborhoods were farther from high-volume parathyroid surgeons than those in advantaged neighborhoods (median distance: disadvantaged 27.8 miles, partially disadvantaged 20.7 miles, partially advantaged 12.1 miles, advantaged 8.4 miles; P < .001). This association was also shown in the analysis of distance to high-volume parathyroid surgeons within the hospital referral region (P < .001). Older adults living in disadvantaged neighborhoods have less access to high-volume parathyroid surgeons, which may adversely affect treatment and outcomes for patients with primary and secondary hyperparathyroidism. This disparity highlights the need for actionable strategies to provide equitable access to care, including improved regionalization of high-volume parathyroid surgeon services and easing travel-related burdens for underserved patients.


Treatment-Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance.
Objective: To describe the clinical characteristics of adolescents with antidepressant treatment-resistant major depressive disorder (MDD) and to examine the utility of the Antidepressant Treatment Record (ATR) in categorizing treatment resistance in this population. Methods: Adolescents with treatment-resistant MDD enrolled in an interventional study underwent a baseline evaluation with the ATR, Children's Depression Rating Scale-Revised (CDRS-R), and Clinical Global Impressions-Severity (CGI-S) scales. Demographic and clinical characteristics were examined with regard to ATR-defined level of resistance (level 1 to ≥3) using analysis of variance and χ2 tests. Results: In adolescents with treatment-resistant MDD (N = 97), aged 12-21 years, most were female (65%), white (89%), and had recurrent illness (78%). Patients were severely ill (median CGI-S score of 5), had a mean CDRS-R score of 63 ± 10, and 17.5% had been hospitalized for depression-related symptoms. Fifty-two patients were classified as ATR 1, whereas 32 were classified as ATR level 2 and 13 patients as ≥3, respectively. For increasing ATR-defined levels, illness duration increased from 12.0 (range: 1.5-31.9) to 14.8 (range: 1.8-31.7) to 19.5 (range: 2.5-36.2) months and the likelihood of treatment with serotonin norepinephrine reuptake inhibitors (SNRIs) and dopamine norepinephrine reuptake inhibitors (DNRIs) similarly increased (p = 0.006 for both SNRIs and DNRIs) as did the likelihood of treatment with mixed dopamine serotonin receptor antagonists (χ2 = 17, p < 0.001). Conclusions: This study underscores the morbidity and chronicity of treatment-resistant MDD in adolescents. The present characterization of related clinical features describes the use of nonselective serotonin reuptake inhibitors in adolescents with treatment-resistant depression and raises the possibility that those with the greatest medication treatment resistance are less likely to have had recurrent episodes. The study also demonstrates the utility of the ATR in categorizing treatment resistance in adolescents with MDD.


Dynamical regimes and stability of circular granular ratchets.
Ratchets are simple mechanical devices which combine spatial asymmetry and nonequilibrium to produce counterintuitive transport of particles. The operation and properties of linear ratchets have already been extensively explored. However, very little is known about circular granular ratchets, startling devices able to convert vertical vibrations into rotations of the device. Here, we report results of systematic numerical investigations of the operational characteristics of circular granular ratchets. Several distinct behaviors are identified and explained in terms of the inner flow fields of the ratchet. All dynamical regimes found are robust and should not be difficult to observe in laboratory experiments.


A feasibility study for megavoltage cone beam CT using a commercial EPID.
This study used a standard commercial electronic portal imaging device (EPID) area detector attached to an isocentric linear accelerator and the Feldkamp algorithm to produce cone beam tomographic reconstructions. The EPID has a active area of 32.5 x 32.5 cm2, and can record 12-bit images using two monitor units (MU), with a resolution of 2.1 x 2.0 mm2 FWHM. Since the EPID was not large enough to record the full patient projection at about 1.5 geometric magnification, it was necessary to offset the detector to collect half-cone projections. Corrections are required to convert pixel values into units of exit dose and to realign the projections to overcome the +/- 4 mm support arm sag. With a geometric magnification of 1.5 the sensitive volume is a cylinder of radius 21 cm and length 17 cm. Unfortunately, the patient couch contains metal bed support rails that lie just outside this cylinder, and produce streak artefacts in the reconstruction. Using 90 views the system delivers a central dose of 90 cGy, and has a density resolution of 4%.


New SmCG phases in a hydrogen-bonded bent-core liquid crystal featuring a branched siloxane terminal group.
In this study, we synthesized three analogous bent-core molecules, a hydrogen-bonded complex and a covalent-bonded compound with branched siloxane units (H-SiO and C-SiO, respectively) and a hydrogen-bonded complex with an alkyl unit (H-Alk), and investigated the effects of the hydrogen bonding and branched siloxane terminal units on their mesomorphic properties. The covalent-bonded compound C-SiO and the hydrogen-bonded complex H-Alk exhibited typical SmCP phases; in contrast, the hydrogen-bonded complex H-SiO exhibited a series of general tilt smectic (SmCG) phases with highly ordered layer structures (i.e., SmC̃G(2)P(F)-USmCG(2)P(A)-SmCG(2)P(F)-SmCGP(F) upon cooling). During the SmCG-type phase transition process, a 2D-modulated ribbon structure transferred into highly ordered layers via undulated layers, as the hydrogen-bonding strength increased with reduced temperatures. As the SmCG domains were aligned under dc electric fields, a gradual decrease in the leaning angle from ca. 60° to 50° (while the tilt angle kept at ca. 31°) could be determined by in situ wide-angle X-ray scattering (WAXS). Combined with Fourier transform infrared and Raman spectroscopic data, our results suggest that the change in the leaning angle was governed by the competition of the hydrogen bonds and microsegregation of siloxane units within the bilayer structure of the hydrogen-bonded complex H-SiO. In addition, the ferroelectric-(antiferroelectric)-ferroelectric transitions proven by the switching current responses in the SmCG-type phases of H-SiO reveal that the polar switching occurred through collective rotations around the long axis of H-SiO. Therefore, novel SmCG phases with a series of highly ordered 2D-structures were induced by the effects of the hydrogen bonding and branched terminal siloxane unit in the bent-core hydrogen-bonded LC complex H-SiO.


Geographical information system and environmental epidemiology: a cross-sectional spatial analysis of the effects of traffic-related air pollution on population respiratory health.
Traffic-related air pollution is a potential risk factor for human respiratory health. A Geographical Information System (GIS) approach was used to examine whether distance from a main road (the Tosco-Romagnola road) affected respiratory health status. We used data collected during an epidemiological survey performed in the Pisa-Cascina area (central Italy) in the period 1991-93. A total of 2841 subjects participated in the survey and filled out a standardized questionnaire on health status, socio-demographic information, and personal habits. A variable proportion of subjects performed lung function and allergy tests. Highly exposed subjects were defined as those living within 100 m of the main road, moderately exposed as those living between 100 and 250 m from the road, and unexposed as those living between 250 and 800 m from the road. Statistical analyses were conducted to compare the risks for respiratory symptoms and diseases between exposed and unexposed. All analyses were stratified by gender. The study comprised 2062 subjects: mean age was 45.9 years for men and 48.9 years for women. Compared to subjects living between 250 m and 800 m from the main road, subjects living within 100 m of the main road had increased adjusted risks for persistent wheeze (OR = 1.76, 95% CI = 1.08-2.87), COPD diagnosis (OR = 1.80, 95% CI = 1.03-3.08), and reduced FEV1/FVC ratio (OR = 2.07, 95% CI = 1.11-3.87) among males, and for dyspnea (OR = 1.61, 95% CI = 1.13-2.27), positivity to skin prick test (OR = 1.83, 95% CI = 1.11-3.00), asthma diagnosis (OR = 1.68, 95% CI = 0.97-2.88) and attacks of shortness of breath with wheeze (OR = 1.67, 95% CI = 0.98-2.84) among females. This study points out the potential effects of traffic-related air pollution on respiratory health status, including lung function impairment. It also highlights the added value of GIS in environmental health research.


Ex Vivo Expanded Human NK Cells Survive and Proliferate in Humanized Mice with Autologous Human Immune Cells.
Adoptive immune cell therapy is emerging as a promising immunotherapy for cancer. Particularly, the adoptive transfer of NK cells has garnered attention due to their natural cytotoxicity against tumor cells and safety upon adoptive transfer to patients. Although strategies exist to efficiently generate large quantities of expanded NK cells ex vivo, it remains unknown whether these expanded NK cells can persist and/or proliferate in vivo in the absence of exogenous human cytokines. Here, we have examined the adoptive transfer of ex vivo expanded human cord blood-derived NK cells into humanized mice reconstituted with autologous human cord blood immune cells. We report that ex vivo expanded NK cells are able to survive and possibly proliferate in vivo in humanized mice without exogenous cytokine administration, but not in control mice that lack human immune cells. These findings demonstrate that the presence of autologous human immune cells supports the in vivo survival of ex vivo expanded human NK cells. These results support the application of ex vivo expanded NK cells in cancer immunotherapy and provide a translational humanized mouse model to test the lifespan, safety, and functionality of adoptively transferred cells in the presence of autologous human immune cells prior to clinical use.


Involvement of yeast carboxy-terminal domain kinase I (CTDK-I) in transcription elongation in vivo.
Yeast cells lacking transcription elongation factor genes such as PPR2 (TFIIS) and ELP (Elongator) are viable and show deleterious phenotypes only when transcription is rendered less effective by RNA polymerase mutations or by decreasing nucleotide pools. Here we demonstrate that deletion of the CTK1 gene, encoding the kinase subunit of RNA polymerase II carboxy-terminal domain kinase I (CTDK-I), is synthetically lethal when combined with deletion of PPR2 or ELP genes. The inviability of ctk1 elp3 double mutants can be rescued by expression of an Elp3 mutant that has retained its ability to form the Elongator complex but has severely diminished histone acetyltransferase activity, suggesting that the functional overlap between CTDK-I and Elongator is in assembly of RNA polymerase II elongation complexes. Our results suggest that CTDK-I plays an important role in transcriptional elongation in vivo, possibly by creating a form of RNA polymerase that is less prone to transcriptional arrest.


Satellite measurements of sea surface temperature through clouds
Measurements of sea surface temperature (SST) can be made by satellite microwave radiometry in all weather conditions except rain. Microwaves penetrate clouds with little attenuation, giving an uninterrupted view of the ocean surface. This is a distinct advantage over infrared measurements of SST, which are obstructed by clouds. Comparisons with ocean buoys show a root mean square difference of about 0.6 degrees C, which is partly due to the satellite-buoy spatial-temporal sampling mismatch and the difference between the ocean skin temperature and bulk temperature. Microwave SST retrievals provide insights in a number of areas, including tropical instability waves, marine boundary layer dynamics, and the prediction of hurricane intensity.


Professional football players at risk for non-acute groin injuries during the first half of the season: A prospective cohort study in The Netherlands.
To study the incidence, diagnostics, treatment, anatomical region and return to play of non-acute groin injuries among professional footballers in the Netherlands. Prospective cohort study. Medical staff members of all Dutch professional football clubs, recording prospectively injury occurrence of all professional footballers in their clubs, were asked to fill in an injury form about time-loss (⩾ 8 days) non-acute groin injury over the 2012-2013 season. A cohort of 410 players from 12 professional football clubs were included (response rate = 44%). The season incidence of non-acute groin injuries was nearly 7% (29 non-acute groin injuries). In 82% of all cases, the player suffered from non-acute groin injury in the first half of the season. The average time to return to play was 35 days, ranging from 8 to 84 days. The adductors were the most affected anatomical regions (82%), with the most frequent diagnosis being overuse of the adductors (36%), followed by adductor tendinopathy (18%). In addition to medical history and physical examination, ultrasound (50%) and MRI (32%) were the diagnostic methods most frequently mentioned. As well as physical therapy, treatment consisted mostly of manual therapy (96%) and dry needling (61%). A professional club with a squad of 25 players can expect on average two non-acute groin injuries per season with an average time-loss of 35 days. Players are more at risk in the first half of the season. In Dutch professional football, ultrasound is commonly used to diagnose non-acute groin injury, while manual therapy is the most commonly applied treatment.


[Safety and efficacy of bevacizumab combined with taxanes in the first-line treatment of metastatic breast cancer: ATHENA study-France].
The efficacy of the combination bevacizumab-chemotherapy in the first-line treatment of metastatic breast cancer (mBC) was demonstrated in several randomized clinical trials. However, limited safety data is available in daily medical practice. ATHENA is an international phase-IIIb study conducted in 2,251 patients with locally advanced or mBC, treated in first-line with bevacizumab combined with taxanes-based chemotherapy. The primary objective is safety assessment. In France, 365 patients were included. Their median age was 56 years (24-93 years) and ECOG performance status was 0 or 1 in 93.9% of patients. Bevacizumab was essentially combined with a taxanes monotherapy: docetaxel (37.3%) or paclitaxel (28.8%) or taxanes-based combination therapy (9.4%). The most frequent grade superior or equal to 3 adverse event (AE) was neutropenia (34.5%). Grade superior or equal to 3 AEs of special interest related to bevacizumab were arterial and venous thromboembolism (5.1%), high blood pressure (4.2%), proteinuria (2.3%) and hemorrhage (2%). Median time to progression was 9.5 months (95% CI: 8.8-10.4). The safety profile and the efficacy of the combination bevacizumab-taxanes in a population more representative of daily oncology practice in France are comparable to those reported in clinical trials in mBC.


Arc-support Line Segments Revisited: An Efficient High-quality Ellipse Detection.
Over the years many ellipse detection algorithms spring up and are studied broadly, while the critical issue of detecting ellipses accurately and efficiently in real-world images remains a challenge. In this paper, we propose a valuable industry-oriented ellipse detector by arc-support line segments, which simultaneously reaches high detection accuracy and efficiency. To simplify the complicated curves in an image while retaining the general properties including convexity and polarity, the arc-support line segments are extracted, which grounds the successful detection of ellipses. The arc-support groups are formed by iteratively and robustly linking the arc-support line segments that latently belong to a common ellipse. Afterward, two complementary approaches, namely, locally selecting the arc-support group with higher saliency and globally searching all the valid paired groups, are adopted to fit the initial ellipses in a fast way. Then, the ellipse candidate set can be formulated by hierarchical clustering of 5D parameter space of initial ellipses. Finally, the salient ellipse candidates are selected and refined as detections subject to the stringent and effective verification. Extensive experiments on three public datasets are implemented and our method achieves the best F-measure scores compared to the state-of-the-art methods. The source code is available at https://github.com/AlanLuSun/High-quality-ellipse-detection.


Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometrium.
Pro-protein convertases (PCs) are a family of serine proteases (furin, PC1/3, PC2, PACE4, PC4, PC5/6, PC7/8) responsible for post-translational processing and activation of inactive precursors of many regulatory proteins. Endometrial PC6 is critical for implantation in mice and for decidualization of human endometrial stromal cells (ESCs). This study investigated the endometrial expression of other PCs during the menstrual cycle and early pregnancy to elucidate potential redundancies. Furin, PC4, PACE4, and PC7 along with PC6 transcripts were detected in total endometrial RNA, whereas PC1 and PC2 transcription levels were negligible. Quantitative RT-PCR demonstrated highest levels of furin mRNA during menstruation and lowest levels during the proliferative phase. Furin protein was immunolocalized in endometrial luminal and glandular epithelia, stromal fibroblasts, endothelia, and leukocytes. PACE4 and PC7 proteins were also immunodetected in endometrial stroma and glands. Total furin, PC7, and PACE4 proteins were constitutive in both stromal and glandular compartments throughout the cycle and during first trimester pregnancy. Furthermore, Furin and PC7 transcription was unaltered during decidualization of ESCs in vitro in contrast to PC6 which is significantly up-regulated during decidualization. Thus, whereas PC6 is tightly regulated during endometrial preparation for implantation, furin, PACE4, and PC7 are constitutively expressed in human endometrium, but must be considered if PC6 is to be targeted for manipulation of fertility.


Treatment with Anlotinib After Chemotherapy and EGFR-TKI Resistance in Lung Adenosquamous Carcinoma with Concurrent EGFR and PIK3CA Mutations: A Case Report and Literature Review.
Concurrent mutations of epidermal growth factor receptor (EGFR) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in non-small cell lung cancer (NSCLC) are rare, and the presence of concurrent mutations may complicate treatment. Herein, we report a case of primary lung adenosquamous carcinoma with concurrent EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations, and the results of a literature review to help management and treatment. A 49-year-old female was admitted our department for coughing and excessive sputum production for more than 1 month. Computed tomography (CT) of the chest identified a lesion, and a CT-guided needle biopsy was performed. Pathological examination and immunohistochemistry (IHC) staining confirmed a diagnosis of primary lung adenosquamous carcinoma. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) gene sequencing demonstrated mutations in both EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations in adenocarcinoma (AC) component. She was treated with pemetrexed plus platinum-based chemotherapy and an EGFR-tyrosine kinase inhibitor (TKI). Disease progression occurred with gefitinib or osimertinib as maintenance therapy. A repeat CT-guided needle biopsy was performed, and generation sequencing (NGS) revealed EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations. Anlotinib monotherapy was then administered as the third-line treatment, and there was a PR. The patient is currently still receiving treatment and follow-up. To our knowledge, there is little evidence that anlotinib is beneficial when there are concurrent EGFR and PIK3CA mutations. PIK3CA mutations are associated with poor therapeutic effects and short survival time. Concurrent EGFR and PIK3CA mutations do not respond to EGFR-TKI treatment. Chemotherapy should be given in combination with a TKI and can prolong the progression-free survival (PFS) and overall survival (OS) of patients with lung cancer.


The influence of ascorbic acid on survival of mice following whole body X-irradiation.
Two strains of mice (Swiss and CF1), male and female, were used in this study. The mice drank either distilled water or 0.1% ascorbic acid in distilled water for one week prior to and during the experiments. Mice were irradiated in groups of 10; they received total body X-irradiation in a single exposure ranging from 200 R to 750 R. Time of death was recorded daily while weight changes and volume of water consumed were recorded every other day. At the low exposure levels, our results indicated that: a) mice drinking ascorbic acid in distilled water died about one week earlier than those drinking distilled water only, and b) the LD 50/30 was higher in mice drinking only distilled water. The differences between both groups were noticeable at exposures up to 550 R; at higher exposures, there was no difference. This study showed that high levels of ascorbic acid potentiated the effect of X-ray whole body irradiation.


Thoughts on the prevention of urologic liability claims.
We have approached the problems of increasing urological liability claims with a superficial study of their causes and some suggested solutions. We believe that this approach is important because it is one that the urological community can take immediately rather than waiting for changes in state and federal laws that may be of benefit in decreasing the impact of these suits. It seems to be the common disease and the simple operation that lead to the lodging of a claim.


The mycotoxin patulin alters the barrier function of the intestinal epithelium: mechanism of action of the toxin and protective effects of glutathione.
Patulin is a mycotoxin mainly found in apple and apple products. In addition to being toxic for animals, mutagenic, carcinogenic and teratogenic, patulin induces intestinal injuries, including epithelial cell degeneration, inflammation, ulceration, and hemorrhages. In a study of the cellular mechanisms associated with the intestinal toxicity of patulin, two human epithelial intestinal cell lines (HT-29-D4 and Caco-2-14) were exposed to the mycotoxin. Micromolar concentrations of patulin were found to induce a rapid and dramatic decrease of transepithelial resistance (TER) in both cell lines without major signs of toxicity as assessed by the LDH release assay. Since TER reflects the organization of tight junctions, these data indicate that patulin affected the barrier function of the intestinal epithelium. The inhibitory effect of patulin on TER was closely associated with its reactivity for SH groups: (i) cysteine and glutathione prevented the cells from patulin injury; (ii) patulin toxicity was potentiated by buthionine sulfoximine, a specific glutathione-depleting agent; (iii) treatment of the cells with N-ethylmaleimide, a compound known to react with SH groups, resulted in a marked decrease of TER. Moreover, the inhibitory effect of patulin on TER was mimicked and potentiated by phenylarsine oxide, a specific inhibitor of protein tyrosine phosphatase (PTP). This cellular enzyme is a key regulator of intestinal epithelial barrier function. The active site of PTP contains a cysteine residue (Cys215) that is essential for phosphatase activity. Sulfhydryl-reacting compounds such as acetaldehyde decrease TER through covalent modification of Cys215 of PTP. We propose that the toxicity of patulin for intestinal cells involves, among other potential mechanisms, an inactivation of the active site of PTP.


Pubertal changes in net renal tubular secretion of digoxin.
To evaluate the effect of puberty on the net renal tubular secretion of digoxin, we measured the ratio of digoxin clearance to creatinine clearance in 23 patients aged 4 to 21 yr and correlated this ratio with both sexual maturity (Tanner stage) and chronologic age. All subjects were at steady-state levels for digoxin treatment; all had normal serum creatinine values for age as well as normal serum potassium levels. Mean ratio for immature children (n = 14, Tanner 1 through 3.5) was 1.45 +/- 0.66. Mean ratio for mature adolescents (n = 9, Tanner 4 through 5) was 0.95 +/- 0.28. The difference between the two groups was significant (P less than 0.05). When patients were regrouped by age using either 13 or 15 yr as a cutoff, the difference in ratios was no longer statistically significant. Based on 45 subjects (new and from our previous study) aged 2 mo to 80 yr, there was a significant decrease in the clearance ratio with increasing age, but when the 23 subjects aged 4 to 21 yr were analyzed separately, the correlation between ratio and age was not significant. It appears that the decrease in net renal tubular secretion of digoxin from childhood to adulthood correlates better with full sexual maturation at puberty (Tanner 4 through 5) than with chronologic age. This observation may represent a developmental change in pharmacokinetics with broader significance than for digoxin disposition alone.


Molecular cloning of Echis ocellatus disintegrins reveals non-venom-secreted proteins and a pathway for the evolution of ocellatusin.
We report the cloning and sequence analysis of Echis ocellatus cDNAs coding for dimeric disintegrin subunits and for the short disintegrin ocellatusin. All the dimeric disintegrin subunit messengers belong to the short-coding class, indicating that short messengers may be more widely distributed than previously thought. Mass spectrometric analysis of the HPLC-separated venom proteins was performed to characterize the dimeric disintegrins expressed in the venom proteome. In addition to previously reported EO4 and EO5 heterodimers, a novel dimeric disintegrin containing RGD- and KGD-bearing subunits was identified. However, a WGD-containing polypeptide encoded by clone Eo1-1 was not detected in the venom, suggesting the occurrence of larger genomic than proteomic diversity, which could represent part of a non-venom-secreted reservoir of disintegrin that may eventually acquire physiological relevance for the snake upon changes of ecological niches and prey habits. On the other hand, the realization of the existence of two distinct messengers coding for the short disintegrin ocellatusin reveals key events of the evolutionary emergence of the short disintegrin ocellatusin from a short-coding dimeric disintegrin precursor by two nucleotide mutations.


Association of body weight and body condition with survival in dogs with heart failure.
Obesity is a risk factor for cardiovascular disease in people, but overweight and obese human heart failure patients have improved survival compared with normal--or underweight controls--the obesity paradox. The purpose of this study was to determine if there is an association of body weight and body condition with survival in dogs with heart failure. That body condition and changes in body weight are predictors of survival in dogs with heart failure. One hundred and eight dogs with heart failure (International Small Animal Cardiac Health Council stages 2, 3a, or 3b) secondary to dilated cardiomyopathy or chronic valvular disease. Medical records were reviewed, and data regarding initial body weight and body condition score (BCS), subsequent changes in body weight, and treatment were collected. Survival times were determined for dogs that were discharged from the hospital and lived >24 hours. Survival was significantly different between dogs that gained, lost, or maintained body weight over the course of their disease (P= .04), with dogs that gained weight surviving the longest. BCS and medications were not significantly associated with survival time; however, n-3 fatty acid intake was associated with longer survival time (P= .009). These results suggest that changes in body weight might be an important consideration in the survival of dogs with heart failure.


Spectral theory of the turbulent mean-velocity profile.
It has long been surmised that the mean-velocity profile (MVP) of pipe flows is closely related to the spectrum of turbulent energy. Here we perform a spectral analysis to identify the eddies that dominate the production of shear stress via momentum transfer. This analysis allows us to express the MVP as a functional of the spectrum. Each part of the MVP relates to a specific spectral range: the buffer layer to the dissipative range, the log layer to the inertial range, and the wake to the energetic range. The parameters of the spectrum set the thickness of the viscous layer, the amplitude of the buffer layer, and the amplitude of the wake.


A perspective on communicating with the female patient.
Most doctors' medical school training does not differentiate history taking between men and women. As a result, many physicians communicate with both sexes exactly the same. However, there are unique aspects of care, making it important to understand the differences between men and women and to take these differences into consideration when taking a medical history from a woman. This article will review those unique differences and provide you with suggestions for enhancing your communication with women.


Uruburuella testudinis sp. nov., isolated from tortoise (Testudo).
A polyphasic taxonomic analysis was carried out on 11 uncommon Gram-stain-negative, non-motile, catalase- and oxidase-positive, but indole-negative, bacterial strains isolated from tortoises. Phenotypically and genetically they represented a homogeneous group of organisms most closely related to, but distinct from, Uruburuella suis. In a reconstructed 16S rRNA gene tree they clustered on a monophyletic branch next to U. suis with gene similarities between strains of 99.5-100%, and of up to 98.2% with U. suis . DNA-DNA hybridization indicated the organisms represented a novel species with only 40% DNA-DNA similarity with U. suis . Partial sequencing of rpoB resulted in two subclusters confirming the 16S rRNA gene phylogeny; both genes allowed clear separation and identification of the novel species. Furthermore, they could be unambiguously identified by matrix-assisted laser desorption ionization time-of-flight MS, where, again, they formed a highly homogeneous cluster separate from U. suis and other members of the family Neisseriaceae . The major fatty acids were C(16 : 0) and summed feature C(16 : 1)ω7c/iso-C(15 : 0) 2-OH. The DNA G+C content was 54.4 mol%. Based on phenotypic and genetic data we propose classifying these organisms as representatives of a novel species named Uruburuella testudinis sp. nov. The type strain is 07_OD624(T) ( = DSM 26510(T) = CCUG 63373(T)).


The effect of cold therapy on the postoperative course of total hip and knee arthroplasty patients.
Fifty total hip arthroplasty (THA) patients and 24 total knee arthroplasty (TKA) patients were randomized in a controlled study to examine the effects of cold therapy (via thermal blankets) in the postoperative period. The postoperative hospital stay was significantly shorter for the cold-therapy (50 degrees F) compared with control (70 degrees F) groups (by 1.4 days, P = 0.03) for THA patients. There was a similar but nonsignificant trend observed in the TKA groups (1.5 days shorter, P = 0.19). Total knee arthroplasty patients using cold therapy achieved independent ambulation an average of 1 day sooner than TKA control patients, but this difference did not reach statistical significance (P = 0.08). There were no statistically significant differences between the control groups or the test groups for both THA and TKA patients in narcotic usage, postoperative range-of-motion (ROM), or rate of progression of ROM.


Blood flow velocity waveforms in human fetal intracranial arteries.
Blood flow velocity waveforms were recorded by pulsed Doppler examination from fetal intracranial arteries in 83 normal and 84 high-risk pregnancies. The normal cases showed a decreasing resistance index of the waveform toward the end of pregnancy, and a continuous forward flow that was always present in these arteries. A low resistance index predicted the birth of a small-for-dates newborn and/or the appearance of subsequent cardiotocographic abnormality, with 57% sensitivity and 94% specificity. Two hydrocephalic fetuses had abnormally high resistance index values. An abnormal fetal intracranial arterial velocity waveform can be seen as a sign of increased perinatal risk.


Charge Transfer, Intersystem Crossing, and Electron Spin Dynamics in a Compact Perylenemonoimide-Phenoxazine Electron Donor-Acceptor Dyad.
With phenoxazine (PXZ) as the electron donor and perylene-3,4-dicarboximide (PMI) as the electron acceptor, we prepared a compact, orthogonal electron donor-acceptor dyad (PMI-PXZ) to study the spin-orbit charge transfer-induced intersystem crossing (SOCT-ISC). A weak charge transfer (CT) absorption band, due to S0 → 1CT transition, was observed (ε = 2840 M-1 cm-1 at 554 nm, FWHM: 2850 cm-1), which is different from that of the previously reported analogue dyad with phenothiazine as the electron donor (PMI-PTZ), for which no CT absorption band was observed. A long-lived triplet state was observed (lifetime τT = 182 μs) with nanosecond transient absorption spectroscopy, and the singlet oxygen quantum yield (ΦΔ = 76%) is higher than that of the previously reported analogue dyad PMI-PTZ (ΦΔ = 57%). Ultrafast charge separation (ca. 0.14 ps) and slow charge recombination (1.4 ns) were observed with femtosecond transient absorption spectroscopy. With time-resolved electron paramagnetic resonance spectroscopy (TREPR), we confirmed the SOCT-ISC mechanism, and the electron spin polarization phase pattern of the triplet-state TREPR spectrum is (e, e, a, e, a, a), which is dramatically different from that of PMI-PTZ (a, e, a, e, a, e), indicating that the triplet-state TREPR spectrum of a specific chromophore in the electron donor-acceptor dyads is not only dependent on the geometry of the dyads but also dependent on the structure of the electron donor (or acceptor). Even one-atom variation in the donor structure may cause significant influence on the electron spin selectivity of the ISC of the electron donor-acceptor dyads.


Tumour necrosis as assessed with 18F-FDG PET is a potential prognostic marker in diffuse large B cell lymphoma independent of MYC rearrangements.
MYC gene rearrangements in diffuse large B cell lymphomas (DLBCLs) result in high proliferation rates and are associated with a poor prognosis. Strong proliferation is associated with high metabolic demand and tumour necrosis. The aim of this study was to investigate differences in the presence of necrosis and semiquantitative 18F-FDG PET metrics between DLBCL cases with or without a MYC rearrangement. The prognostic impact of necrosis and semiquantitative 18F-FDG PET parameters was investigated in an explorative survival analysis. Fluorescence in situ hybridisation analysis for MYC rearrangements, visual assesment, semiquantitative analysis of 18F-FDG PET scans and patient survival analysis were performed in 61 DLBCL patients, treated at a single referral hospital between 2008 and 2015. Of 61 tumours, 21 (34%) had a MYC rearrangement (MYC+). MYC status was neither associated with the presence of necrosis on 18F-FDG PET scans (necrosisPET; p = 1.0) nor associated with the investigated semiquantitative parameters maximum standard uptake value (SUVmax; p = 0.43), single highest SUVmax (p = 0.49), metabolic active tumour volume (MATV; p = 0.68) or total lesion glycolysis (TLG; p = 0.62). A multivariate patient survival analysis of the entire cohort showed necrosisPET as an independent prognostic marker for disease-specific survival (DSS) (HR = 13.9; 95% CI 3.0-65; p = 0.001). MYC rearrangements in DLBCL have no influence on the visual parameter necrosisPET or the semi-quantiative parameters SUVmax, MATV and TLG. Irrespective of MYC rearrangements, necrosisPET is an independent, adverse prognostic factor for DSS. • Retrospective analysis indicates that MYC rearrangement is not associated with necrosis on 18 F-FDG PET (necrosis PET ) scans or semiquantitative 18 F-FDG PET parameters. • Necrosis PET is a potential independent adverse prognostic factor for disease-specific survival in patients with DLBCL and is not influenced by the presence of MYC rearrangements.


[Psychopedagogic counseling for twins and twin families (author's transl)].
In 1973 the Mendel Institute, within the specialized services it offers to Italian twins, instituted psychopedagogic counseling for twins and their families. This service is carried out in the intermediate field between neuropsychiatry and social work. Cases involving family and social maladjustment were referring for counseling. During the academic year 1973-1974, the service examined 96 cases, of which 58 involved problems of school retardation and 38 involved family maladjustment because of changed parent-twin relationships. The counseling service aimed at achieving improved family and school relationships by means of various therapeutic interventions. The psychopedagogic counseling, besides the immediate therapy, has permitted deeper study of maladjustment by means of analyses of the twins' condition as a possible additional cause of the maladjustment itself. Analysis of the cases in this limited sample would seem to indicate an indirect incidence of the twin situation per se (couple effect), somewhat emphasized by the family and social environment.


Rare presentation of thrombosis with bleeding in Behcet's disease.
Behcet's disease (BD) is a rare autoimmune and autoinflammatory disease characterised by recurrent oral and genital aphthous ulcers as well as gastrointestinal, ocular, neurological, articular and vascular inflammation. Patients are at risk for both thrombotic events and bleeding, so providers are often challenged in deciding whether to start patients on anticoagulation. We report a rare, complex case of a patient with BD who presented with massive gastrointestinal bleeding. This case report highlights the management of recurrent thrombosis due to protein C and S deficiency in a patient with BD who also presents with acute gastrointestinal bleeding.


Specificity of action of Ca++ entry blockers. A comparison of their actions in rat arteries and in human coronary arteries.
Among the large number of compounds which inhibit the contraction evoked by calcium in depolarized smooth muscle, calcium entry blockers are those that specifically block calcium entry during muscle activation. They affect neither Ca++ efflux nor intracellular Ca++ release. A comparative study of the diphenylpiperazines, cinnarizine and flunarizine, with the dihydropyridine, nifedipine, allows conclusions to be drawn as to their specificity of action. We have also examined the action of calcium entry blockers, considering tissue and stimulus selectivity. The inhibition of smooth muscle contraction can be quantitatively related to blockade of Ca++ influx. In rat aorta and mesenteric arteries, the potency of Ca++ entry blockers depends on the stimulus in the following order of sensitivity: K depolarization greater norepinephrine greater than PGF2 alpha. As far as flunarizine, but not nifedipine, is concerned, the activity is higher in mesenteric arteries than in aorta. This raises the possibility that calcium channels have receptor and organ specificity, a hypothesis which is supported by the observation that the order of potency of several calcium entry blockers is different in various vessels including human coronary arteries, and that the action of the blockers increases with the age of the patient.


Searching for disability in electronic databases of published literature.
As researchers in disability and health conduct systematic reviews with greater frequency, the definition of disability used in these reviews gains importance. Translating a comprehensive conceptual definition of "disability" into an operational definition that utilizes electronic databases in the health sciences is a difficult step necessary for performing systematic literature reviews in the field. Consistency of definition across studies will help build a body of evidence that is comparable and amenable to synthesis. To illustrate a process for operationalizing the World Health Organization's International Classification of Disability, Functioning, and Health concept of disability for MEDLINE, PsycINFO, and CINAHL databases. We created an electronic search strategy in conjunction with a reference librarian and an expert panel. Quality control steps included comparison of search results to results of a search for a specific disabling condition and to articles nominated by the expert panel. The complete search strategy is presented. Results of the quality control steps indicated that our strategy was sufficiently sensitive and specific. Our search strategy will be valuable to researchers conducting literature reviews on broad populations with disabilities.


Theory of mind in the early course of schizophrenia: stability, symptom and neurocognitive correlates, and relationship with functioning.
Numerous studies have reported links between theory of mind (ToM) deficits, neurocognition and negative symptoms with functional outcome in chronic schizophrenia patients. Although the ToM deficit has been observed in first-episode patients, fewer studies have addressed ToM as a possible trait marker, neurocognitive and symptom correlations longitudinally, and associations with later functioning. Recent-onset schizophrenia patients (n = 77) were assessed at baseline after reaching medication stabilization, and again at 6 months (n = 48). Healthy controls (n = 21) were screened, and demographically comparable with the patients. ToM was assessed with a Social Animations Task (SAT), in which the participants' descriptions of scenes depicting abstract visual stimuli 'interacting' in three conditions (ToM, goal directed and random) were rated for degree of intentionality attributed to the figures and for appropriateness. Neurocognition, symptoms and role functioning were also assessed. On the SAT, patients had lower scores than controls for both intentionality (p < 0.01) and appropriateness (p < 0.01) during the ToM condition, at baseline and 6 months. The ToM deficit was stable and present even in remitted patients. Analyses at baseline and 6 months indicated that for patients, ToM intentionality and appropriateness were significantly correlated with neurocognition, negative symptoms and role functioning. The relationship between ToM and role functioning was mediated by negative symptoms. The ToM deficit was found in recent-onset schizophrenia patients and appears to be moderately trait-like. ToM is also moderately correlated with neurocognition, negative and positive symptoms, and role functioning. ToM appears to influence negative symptoms which in turn makes an impact on role functioning.


Assessment of antioxidant enzyme activities in erythrocytes of pre-hypertensive and hypertensive women.
Few studies that have investigated hypertension have considered a state of oxidative stress that can contribute to the development of atherosclerosis and other hypertension induced organ damage. The aim of this study was to investigate whether pre-hypertension and hypertension status is associated with activities of erythrocyte antioxidant enzymes in a random sample of cardiovascular disease-free women. In this case-control study, 53 pre-hypertensive women, 32 hypertensive women and 75 healthy controls were included. General information was gathered using questionnaires and face-to-face interviews. Blood pressure and anthropometric measurements were measured for each subject. Venous blood samples were drawn from subjects and plasma was separated. Activities of erythrocyte antioxidant enzymes were also evaluated by measuring activities of copper zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT) in selected subjects. Fifty-three (33.1%) and 32 (20%) participants were pre-hypertensive and hypertensive, respectively. The hypertensive and pre-hypertensive women had lower CuZn-SOD (p < 0.001) and GPX (p < 0.01) activities compared to normotensives. Furthermore, hypertensive women had lower CAT activity compared to pre-hypertensive and normotensive women (p < 0.001). Moreover, significant differences were also observed between hypertensive and pre-hypertensive women in erythrocyte CAT activity (p < 0.01). The present findings show that activities of erythrocyte antioxidant enzymes decrease in pre-hypertensive and hypertensive women, which may eventually lead to atherosclerosis and other high blood pressure related health problems.


Repression of BET activity sensitizes homologous recombination-proficient cancers to PARP inhibition.
Strategies to enhance response to poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) in primary and acquired homologous recombination (HR)-proficient tumors would be a major advance in cancer care. We used a drug synergy screen that combined a PARPi, olaparib, with 20 well-characterized epigenetic drugs and identified bromodomain and extraterminal domain inhibitors (BETis; JQ1, I-BET762, and OTX015) as drugs that acted synergistically with olaparib in HR-proficient cancer cells. Functional assays demonstrated that repressed BET activity reduces HR and thus enhances PARPi-induced DNA damage in cancer cells. We also found that inhibition or depletion of BET proteins impairs transcription of BRCA1 and RAD51, two genes essential for HR. Moreover, BETi treatment sensitized tumors to PARP inhibition in preclinical animal models of HR-proficient breast and ovarian cancers. Finally, we showed that the BRD4 gene was focally amplified across 20 types of common cancers. Combination with BETi could greatly expand the utility of PARP inhibition to patients with HR-proficient cancer.


Self-supervised representation learning using feature pyramid siamese networks for colorectal polyp detection.
Colorectal cancer is a leading cause of cancer-related deaths globally. In recent years, the use of convolutional neural networks in computer-aided diagnosis (CAD) has facilitated simpler detection of early lesions like polyps during real-time colonoscopy. However, the majority of existing techniques require a large training dataset annotated by experienced experts. To alleviate the laborious task of image annotation and utilize the vast amounts of readily available unlabeled colonoscopy data to further improve the polyp detection ability, this study proposed a novel self-supervised representation learning method called feature pyramid siamese networks (FPSiam). First, a feature pyramid encoder module was proposed to effectively extract and fuse both local and global feature representations among colonoscopic images, which is important for dense prediction tasks like polyp detection. Next, a self-supervised visual feature representation containing the general feature of colonoscopic images is learned by the siamese networks. Finally, the feature representation will be transferred to the downstream colorectal polyp detection task. A total of 103 videos (861,400 frames), 100 videos (24,789 frames), and 60 videos (15,397 frames) in the LDPolypVideo dataset are used to pre-train, train, and test the performance of the proposed FPSiam and its counterparts, respectively. The experimental results have illustrated that our FPSiam approach obtains the optimal capability, which is better than that of other state-of-the-art self-supervised learning methods and is also higher than the method based on transfer learning by 2.3 mAP and 3.6 mAP for two typical detectors. In conclusion, FPSiam provides a cost-efficient solution for developing colorectal polyp detection systems, especially in conditions where only a small fraction of the dataset is labeled while the majority remains unlabeled. Besides, it also brings fresh perspectives into other endoscopic image analysis tasks.


A Call-In for Allyship and Anti-Ableism in Intellectual Disability Research.
Provoked by decades of grassroots activism, anti-ableist work is underway to advance disability rights. Intellectual disability (ID) researchers can integrate these social changes into their work by interrogating and transforming the beliefs and practices that underpin ID research. We share actionable ideas to foster anti-ableism and allyship in ID research. These include: (1) Learn from and nurture long-term, mutual relationships with people with ID; (2) Amplify the voices of people with ID in institutional structures that influence research; (3) Infuse anti-ableist frameworks into our own research; and (4) Embody a career-long commitment to disability rights, reflexive practice, and growth.


Effect of prednisolone on the glycosaminoglycan components of the regenerating articular cartilage.
Investigations were performed on the effect of prednisolone (0.5 mg/kg) on the regenerating femoral articular cartilage of the knee joint in dogs that had been subjected to semiarthroplasty. After 70 days of prednisolone treatment the dogs were killed and the regenerating articular cartilage was removed, minced, and dried with acetone. The acetone-dried material was used for the determination of galactosamine, glucosamine, uronic acid, sulphate, sialic acid and hydroxyproline. Prednisolone treatment elicited a quantitative increase in galactosamine (30.2%), uronic acid (76.2%), and sulphate (9.1%), while no difference was observed in sialic acid content between the treated and untreated groups. From the molar ratio of the measured components it appears that prednisolone produced an increase in chondroitin sulphate and hyaluronic acid, and a decrease in the keratosulphate content of cartilage. By comparing the values measured in the regenerating articular cartilage of control and prednisolone-treated dogs with the values obtained in the mature articular cartilage, we may conclude that prednisolone--at least as regards the glycosaminoglycans of the ground substance--exerts an accelerating effect on cartilage regeneration.


Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults.
Merozoite surface protein 1(42) (MSP1(42)) is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP1(42) were mixed (MSP1(42)-C1). To improve the level of antibody response, MSP1(42)-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909. A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP1(42)-C1/Alhydrogel +/- CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 microg protein adsorbed to Alhydrogel +/- 560 microg CPG 7909 at 0, 1 and 2 months. Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema) and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP1(42) antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP1(42)-C1/Alhydrogel alone (p<0.0001). After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range -2 to 10%) in the non CPG groups versus 14% (3 to 32%) in the CPG groups. The favorable safety profile and high antibody responses induced with MSP1(42)-C1/Alhydrogel + CPG 7909 are encouraging. MSP1(42)-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909. ClinicalTrials.gov Identifier: NCT00320658.


Cholesterol effectively blocks entry of flavivirus.
Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2) are enveloped flaviviruses that enter cells through receptor-mediated endocytosis and low pH-triggered membrane fusion and then replicate in intracellular membrane structures. Lipid rafts, cholesterol-enriched lipid-ordered membrane domains, are platforms for a variety of cellular functions. In this study, we found that disruption of lipid raft formation by cholesterol depletion with methyl-beta-cyclodextrin or cholesterol chelation with filipin III reduces JEV and DEN-2 infection, mainly at the intracellular replication steps and, to a lesser extent, at viral entry. Using a membrane flotation assay, we found that several flaviviral nonstructural proteins are associated with detergent-resistant membrane structures, indicating that the replication complex of JEV and DEN-2 localizes to the membranes that possess the lipid raft property. Interestingly, we also found that addition of cholesterol readily blocks flaviviral infection, a result that contrasts with previous reports of other viruses, such as Sindbis virus, whose infectivity is enhanced by cholesterol. Cholesterol mainly affected the early step of the flavivirus life cycle, because the presence of cholesterol during viral adsorption greatly blocked JEV and DEN-2 infectivity. Flavirial entry, probably at fusion and RNA uncoating steps, was hindered by cholesterol. Our results thus suggest a stringent requirement for membrane components, especially with respect to the amount of cholesterol, in various steps of the flavivirus life cycle.


Internal defenses of the snail Biomphalaria glabrata.
The three populations of hemocytes and the fixed phagocytes of Biomphalaria glabrata show different affinities for the following injected foreign materials: ferritin, horseradish peroxidase, zymosan particles, latex beads, and live bacteria. Ferritin and horseradish peroxidase, which are internalized by micropinocytosis, induce a moderate activation of hemocytes. Particles trigger a strong activation that consists of mobilization of the cytoskeleton, with formation of pseudopodia and filopodia and modifications of the plasma membrane that enable hemocytes to adhere together, as in encapsulations. Phagocytosis of zymosan and live bacteria induces alterations in mitochondria that may reflect changes in the respiratory activity. Phagocytosis of particles follows different processes: fixed phagocytes ingest latex beads of two different sizes according to the "zipper model", which implies sequential binding between phagocyte receptors and opsonized ligands; zymosan particles are ingested by medium-size hemocytes by a variant of the zipper model in which a limited close contact between cell and particle resembles focal contacts in cell spreading; bacteria or large latex beads are ingested by large hemocytes without apparent close contact following a "trigger model" which resembles macropinocytosis.


[Effects of bezafibrate in the diet of hypertensive patients with dyslipidemia and hyperfibrinogenemia].
To evaluate the fibrinogen and lipids response to diet plus bezafibrate in insulin-resistant patients with arterial hypertension and mixed hyperlipidemia. A randomized double blind parallel design was used during a 90 days treatment period. Fibrinogen, lipids, insulin and peptide C assays as well as a glucose tolerance test were done at the start and end of treatment. The 28 patients received a hypolipemic diet low in refined sugars with bezafibrate added (400 mg/day) in 15 and a placebo in 13. The groups were similar in age, blood pressure and BMI. At the end of treatment, fibrinogen, cholesterol, triglycerides and LDL-C were lower in both groups as compared to the initial values, but only in the bezafibrate group there were: a) significant decrease in triglycerides (64 mg/dL, p 0.01); and b) marginal changes in fibrinogen (decreased 35 mg/dL, p = 0.09), total cholesterol (decreased 26 mg/dL, p = 0.10) and glucose/insulin ratio (increased from 4.4 to 5.2, p = 0.09). Bezafibrate lowered slightly the insulin level but did not affect peptide C. A correlation of changes in fibrinogen levels and the 60 min insulin concentration in the glucose tolerance test was higher in the bezafibrate group (r = 0.61) than in the placebo group (r = 0.23). In insulin resistant patients with high cardiovascular risk, bezafibrate and a placebo added to a hypolipemic diet decreased plasma fibrinogen. Bezafibrate lowered significantly the levels of triglycerides in these patients.


Higher gamma-glutamyl transferase levels are associated with an increased risk of incident systemic sclerosis: a nationwide population-based study.
Gamma-glutamyl transferase (GGT) is known to promote oxidative stress. As oxidative stress is a key component in the pathogenesis of systemic sclerosis (SSc), we investigated whether GGT levels are associated with the risk of incident SSc. A cohort of individuals without SSc who underwent national health examination in 2009 were extracted from the Korean National Health Insurance Service database. The incidence rate of SSc during the observation period, between 2009 and 2019, was estimated. GGT levels measured in 2009 were categorized into quartiles (Q1 [lowest], Q2, Q3, and Q4 [highest]). Multivariable Cox proportional hazard models were used to estimate the risk of incident SSc according to the quartiles of GGT, using Q1 as the reference. A total of 6,091,788 individuals were included. Incidence rate of SSc was 1.16 per 100,000 person-years over a mean observation period of 9.2 years. After adjusting for age, sex, body mass index, economic income, smoking status, alcohol consumption, physical activity, hypertension, type 2 diabetes, dyslipidemia, and chronic kidney disease, higher quartiles of GGT levels were significantly associated with a higher risk of incident SSc (Q4: adjusted hazard ratio [aHR] 1.807, 95% confidence interval CI 1.446-2.259; Q3: aHR 1.221, 95% CI 0.971-1.536; and Q2: aHR 1.034, 95% CI 0.807-1.324; p for trend < 0.001). Higher GGT levels were associated with a higher risk of incident SSc. These findings could lead to a closer monitoring for high risk individuals and an earlier diagnosis and treatment.


Radioimmunoassay and enzyme immunoassay compared for determination of digoxin.
Patients' sera were analyzed for digoxin by using two different radioimmunoassays and an enzyme immunoassay. Quantitative results obtained by enzyme immunoassay (I) were compared to results obtained on aliquots of the same sample by the radioimmunoassays (II and III). The correlation coefficients were: I vs. II 0.90, n=108; I vs. III 0.94, n=102; and II vs. III 0.95, n=158. Day-to-day precision (10 days) on a low control (1.3 mug/liter) and a high control 3.0 mg/liter), expressed as coefficients of variation, were: I, 13% and 7.8%, II, 4.0% and 4.7%; and III, 8.9% and 4.2%. Ten digoxin-supplemented samples (0-8 mug/liter) were analyzed by the three methods. Correlation coefficients were: supplemented sample vs. I, O.99; supplemented sample vs. II, 0.97; supplemented sample vs. III, 0.98.


Comparative effects of gamma and microwave irradiation on the quality of black pepper.
Powdered black pepper from Egyptian markets, was irradiated with different recommended doses of gamma rays (5.0 and 10.0 kGy) and with microwaves for different periods (20, 40 and 75 s) to improve its hygienic quality. The most common bacterial isolates were of three genera Bacillus, Clostridium and Micrococcus (7.5 x 10(6)), whereas the predominant fungi (7.8 x 10(4)) were Aspergillus species, A. glaucus, A. flavus, A. niger and A. ochraceus. Doses of gamma irradiation used (5.0 and 10 kGy) were sufficient to decrease spore-forming bacteria (SFB) and to inhibit the fungal flora and coliforms which contaminated the black pepper powder. Microwave treatments for 40 s and 75 s were of the same effectiveness whereas treatment for 20 s was less so. GLC analysis proved the presence of 31 peaks, only 19 compounds were identified as monoterpene hydrocarbons (56.21%), the major one being beta-phellandrene and limonene. Sesquiterpenes were also present, mainly beta-caryollphyllene (3.69%) as well as oxygenated compounds such as terpenol, geraniol, Me-chavicol, eugenol and anisol. Gamma irradiation at 5 kGy and 10 kGy respectively decreased the numbers of identified compounds from 21 (86.58% concentration) in untreated pepper to 16 (59.22% concentration), 15 (54.06% concentration). In comparison, microwave treatments, particularly for 40 s and 75 s, increased the concentration of the same compounds. The results obtained indicate that microwave treatment, under these conditions, is a safe and suitable technique for decontamination of black pepper which does not result in a great loss of flavour compounds, as compared with recommended doses of gamma irradiation.


Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T/+ tf/tf has severely reduced hippocampal commissure and absent corpus callosum.
A morphometric survey of brain size and forebrain commissures of 21 inbred mouse strains from the Jackson Laboratory was done with animals tested in two laboratories as part of the Mouse Phenome Project. Strain BTBR T/+ tf/tf was found to have 100% total absence of the corpus callosum as well as severe reduction of the hippocampal commissure in almost every animal, the most severe commissure defect observed to date in any commercially available mouse strain. The strain 129S1/SvImJ had a milder defect with incomplete penetrance. Crosses of BTBR mice with inbred strains BALB/cWah1, 129P1/ReJ, and the recombinant strain 9XCA/Wah having a severe commissure defect supported a two-locus model of the genetic defect in these strains. Brain size varied greatly among strains but for any one strain was almost identical in mice housed for 5 weeks in the two laboratories. Sex differences in brain weight and forebrain commissure sizes were not statistically significant.


Adaptive versus maladaptive coping and beliefs and their relation to chronic pain adjustment.
Coping and beliefs are cornerstones to our understanding of adjustment to chronic pain. This study sought to test the hypothesis that maladaptive pain-related coping and beliefs are more strongly related to measures of patient adjustment than are adaptive coping and beliefs. A sample of 106 veterans with mixed chronic pain diagnoses in a multidisciplinary pain treatment program were administered measures of pain beliefs and pain coping, and composite scores were computed to reflect adaptive and maladaptive responses. Correlations between the composite scores and outcomes (pain intensity, pain interference, depression) were examined. Hierarchical multiple regressions were also conducted to estimate the independent contributions of adaptive and maladaptive responses. The maladaptive response composite score was found to be significantly related to pain interference and depression, whereas both adaptive and maladaptive response composite scores were found to be significantly related to pain intensity. The maladaptive response composite showed stronger independent associations with pain interference and depression after controlling for demographic variables, pain intensity, and adaptive responses. Contrary to expectations, only the adaptive response composite showed an independent association with pain intensity. The findings suggest that the relative importance of adaptive versus maladaptive beliefs and coping may differ as a function of the outcome domain in question. The findings support current cognitive-behavioral interventions that focus on reducing the frequency of maladaptive coping responses and beliefs as a way to improve patient functioning.


Regulation of glucose uptake in differentiated cells.
Glucose uptake into the cell is mediated by a family of glycosylated membrane proteins, called glucose transporters (GTs) that are able to facilitate passive hexose transfer across the lipid plasma membrane. The tissue-specific transporter isoforms generally differ in their affinity to the natural substrate D-glucose according to the specific functions of the respective organ. The mechanisms by which external and internal signals regulate glucose uptake into the cells belong to one of the most extensively studied fields of cell physiology. However, in spite of significant progress in identifying the involved molecular components and signaling pathways, the final cellular mechanism responsible for the short-term regulation of glucose uptake is still a matter of intense debate. The widely accepted translocation hypothesis, which explains transport regulation by exo- and endocytic modulation of the number of GTs in the plasma membrane, insufficiently accounts for the whole insulin-induced transport stimulation and is insufficient to integrate the wide variety of different transport-modulating signals in differentiated tissue cells into a common mechanistic concept. Some time ago, a novel type of glucose transport regulation has been proposed prevailing in differentiated tissue cells. This mechanism depends on the presence of glucose transporters on microvilli of differentiated cells. The basic framework for this theory was provided by a recently presented novel concept of ion channel regulation via microvillar structures [Lange, K. (1999): Microvillar Ca++ signaling: A new view on an old problem. J. Cell. Physiol. 180, 19-35; Lange, K. (2000): Regulation of cell volume via microvillar ion channels. J. Cell. Physiol. 185, 21-35; Lange, K. (2000): Microvillar ion channels - Cytoskeletal regulation of ion fluxes. J. Theor. Biol. 206, 561-584], earlier studies on glucose transport regulation and a number actual biochemical findings. Here, a survey on both concepts is given and the ability of the novel mechanism of microvillar transport regulation to integrate a large body of experimental data into the common concept of cellular regulation via microvillar pathways is discussed.


Fourier analysis and systems identification of the p53 feedback loop.
A key circuit in the response of cells to damage is the p53-mdm2 feedback loop. This circuit shows sustained, noisy oscillations in individual human cells following DNA breaks. Here, we apply an engineering approach known as systems identification to quantify the in vivo interactions in the circuit on the basis of accurate measurements of its power spectrum. We obtained oscillation time courses of p53 and Mdm2 protein levels from several hundred cells and analyzed their Fourier spectra. We find characteristic spectra with distinct low-frequency components that are well-described by a third-order linear model with white noise. The model identifies the sign and strength of the known interactions, including a negative feedback loop between p53 and its upstream regulator. It also implies that noise can trigger and maintain the oscillations. The model also captures the power spectra of p53 dynamics without DNA damage. Parameters such as noise amplitudes and protein lifetimes are estimated. This approach employs natural biological noise as a diagnostic that stimulates the system at many frequencies at once. It seems to be a useful way to find the in vivo design of circuits and may be applied to other systems by monitoring their power spectrum in individual cells.


Cigarette smoke exposure combined with lipopolysaccharides induced pulmonary fibrosis in mice.
Cigarette smoke (CS) is a risk factor for pulmonary fibrosis and lipopolysaccharides (LPS) are associated with human occupational lung diseases; however, their combined role in pulmonary fibrosis remains unknown. Therefore, we investigated whether CS combined with LPS induces pulmonary fibrosis in mice. C57BL/6 mice were exposed to CS or normal air for 21 or 35 days, followed by LPS or saline instillation on day 14, 21, and 28. Lung function was tested, and lung tissues were harvested for histological and molecular analyses. Compared to the control, CS and LPS groups, the CS + LPS group showed reduced body weight and survival rate, increased respiratory resistance, decreased lung compliance, marked alveolar structure destruction, and fibrotic lesion formation. Lung tissues showed a considerable increase in IL-6, TNF-α, IL-1β, α-SMA, and TGF-β levels and collagen content. Our results indicate that cigarette smoke exposure followed by LPS in mice induces pulmonary fibrosis with pathophysiology consistent with that of human pulmonary fibrosis.


[Substantiation and effectiveness of various methods of detoxification in burns].
On the basis of comparison of the intoxication manifestations at the cellular level, findings of blood toxicometry, and as well study of the factors of antitoxic resistance of an organism in 217 patients who suffered from burns, the indications for performance of basic transfusion therapy, extracorporeal detoxication of the blood, and also postsorptive transfusion therapy have been established.


[Determining the thyroid hormones T3 and T4 in the urine: an unreliable test for hypothyroidism].
A 24-year-old woman complained of tiredness, sensitivity to cold, and feelings of depression. A diagnosis of hypothyroidism based on decreased 24 h urinary T3 and T4 excretion was made, and she was treated with levothyroxin. No blood tests were done. She was referred with the question if she had other endocrine disorders. Her periods were regular, and on physical examination no abnormalities except slight acne were found. Similarly, hypothyroidism was diagnosed by decreased thyroid hormone excretion in 24 h urine, again without blood tests, in a 68-year-old woman whose mother had a goitre, and who had already been prescribed liothyronine. She had no complaints, and physical examination was unremarkable. The thyroid gland was not palpable. Thyroid peroxidase antibodies were absent in both patients. After discontinuation of medication with thyroid hormones they both remained euthyroid. It is concluded that thyroid disease did not exist in those 2 patients. Measurement of 24 h urinary T3 and T4 excretion is not an accurate diagnostic test for hypothyroidism.


General and sports nutrition knowledge among Jordanian adult coaches and athletes: A cross-sectional survey.
Nutrition knowledge (NK) is a modifiable determinant of diet intake and can positively influence athletic performance. This study aimed to (1) adapt and translate a validated general and sports NK questionnaire into Arabic (2) assess the NK of Jordanian sportspeople, and (3) evaluate the relationship between NK and various sociodemographic factors. The Abridged Nutrition for Sport Knowledge Questionnaire (ANSKQ) was translated into Arabic using forward-backward translation and underwent pilot testing and psychometric validation (internal consistency, test-retest reliability, inter-rater agreement) using a convenience sample of 30 individuals. Following ANSKQ validation, athletes a from 50 sport institutes in Jordan were invited (via email) to complete the Arabic ANSKQ online. Differences in NK based on demographics were analysed using t-test or ANOVA for continuous variables and chi-square tests for categorical variables. The ability of demographic factors to predict NK score-category (poor/good/average/excellent) was assessed using multivariate logistic regression. The Arabic ANSKQ had excellent internal consistency (Cronbach's alpha = 0.92), test-retest reliability (Pearson r = 0.926) and inter-rater agreement (Cohen's k statistic = 0.89). A total of 3636 eligible participants completed the Arabic ANSKQ. Participants were mostly athletes (91.4%), female (68.0%), had normal BMI (50.6%), and played high-intensity sports (59.6%). 88.3% of participants had poor NK (<50%). There were statistically significant differences in NK score based on participant role (athlete vs coach), age, gender, BMI, nationality, smoking, years playing sport, sport frequency, sport intensity, and nutrition training. Multivariate modelling showed participant role, BMI, education level, sport frequency and nutrition training were predictors of NK category. In conclusion, Jordanian sportspeople have poor NK and may benefit from increased nutrition training.


Sibling sex ratio and sexual orientation in men and women: new tests in two national probability samples.
One line of research on the etiology of sexual orientation has examined sibling sex ratio, the ratio of brothers to sisters collectively reported by a group of individuals, but this research has only used clinical and/or convenience samples. In the present study, homosexual men and women's sibling sex ratio was examined in two national probability samples. Results indicated that homosexual men had a sex ratio of 129.54 male live births to 100 female live births. This ratio was within the range of elevated sex ratios found in some previous studies of homosexual men, although it was only marginally significant (p = .09) relative to the known human sex ratio with regard to live births. Additional analyses indicated that this effect was likely the result of a high fraternal birth order (i.e., an elevated number of older brothers) in homosexual men. The sibling sex ratio for lesbians was 122.58 male live births to 100 female live births, which did not significantly differ from the known human sex ratio with regard to live births. The results for lesbians, however, should be interpreted with caution because the sample size (and resulting power) was low. The results in men add to research suggesting that homosexual men, unselected for gender identity or gender role behavior, do not have elevated sibling sex ratios. These results also suggest that research should concentrate on finding the cause(s) of the fraternal birth order effect, the consistent finding that homosexual men have an elevated number of older brothers.


Impact of copper ligand mutations on a cupredoxin with a green copper center.
Mononuclear cupredoxins contain a type 1 copper center with a trigonal or tetragonal geometry usually maintained by four ligands, a cystein, two histidines and a methionine. The recent discovery of new members of this family with unusual properties demonstrates, however, the versatility of this class of proteins. Changes in their ligand set lead to drastic variation in their metal site geometry and in the resulting spectroscopic and redox features. In our work, we report the identification of the copper ligands in the recently discovered cupredoxin AcoP. We show that even though AcoP possesses a classical copper ligand set, it has a highly perturbed copper center. In depth studies of mutant's properties suggest a high degree of constraint existing in the copper center of the wild type protein and even the addition of exogenous ligands does not lead to the reconstitution of the initial copper center. Not only the chemical nature of the axial ligand but also constraints brought by its covalent binding to the protein backbone might be critical to maintain a green copper site with high redox potential. This work illustrates the importance of experimentally dissecting the molecular diversity of cupredoxins to determine the molecular determinants responsible for their copper center geometry and redox potential.


Continuous Infusion Low-Dose Unfractionated Heparin for the Management of Hypercoagulability Associated With COVID-19.
The Coronavirus Disease 2019 (COVID-19) is associated with severe hypercoagulability. There is currently limited evidence supporting the routine use of therapeutic anticoagulation in the setting of COVID-19. The primary objective was to compare the incidence of thromboembolic events in adult patients with COVID-19 treated with an unfractionated heparin (UFH) infusion versus prophylactic dose anticoagulation. Secondary objectives included exploration of the efficacy and safety of an UFH infusion through the evaluation of organ function and incidence of minor and major bleeding. Retrospective observational cohort study with propensity score matching of COVID-19 patients who received an UFH infusion targeting an aPTT between 40 and 60 seconds. Fifty-six patients were included in this study. There was no difference in the composite of thromboembolic events comprised of venous thromboembolism, arterial thrombosis, and catheter-related thrombosis between the UFH and control group (17.9% vs. 3.6%, P = 0.19). There was a significant increase in median D-dimer concentrations from day 1 to day 7 in the control group (475 ng/mL [291-999] vs. 10820 ng/mL [606-21033], P = 0.04). Patients treated with UFH had a higher incidence of minor bleeding (35.7% vs. 0%, P < 0.005) and required more units of packed red blood cell transfusion (0.8 units ± 1.6 vs. 0 units, P = 0.01). Continuous infusion of UFH for patients with COVID-19 infection did not decrease the overall incidence of thromboembolic complications. UFH was associated with stabilization of D-dimer concentrations and increased rates of minor bleeding and transfusions.


Tumors of the sublingual gland: a national clinicopathologic study of 29 cases.
Tumors of the salivary glands are a heterogeneous group of diseases most often originating in the major salivary glands. Only a minor proportion of mainly malignant tumors arise in the sublingual gland. Due to the rarity of sublingual gland tumors (SGTs), little is known about the clinicopathologic characteristics, prognostic factors, and clinical course. We present a large national series of histopathologically revised SGTs from the past 35 years in Denmark with clinicopathologic correlation. Twenty nine cases were identified, of which 96.6 % were malignant and 16/28 (57.1 %) were adenoid cystic carcinomas (ACC). Patient demography was similar to salivary gland tumors in other locations. All fine needle aspiration cytologies (FNACs) interpreted as benign were from ACCs. Metastatic disease was found in 12.5 % of ACCs at diagnosis with one third of all ACC patients having metastases at the end of follow-up. Stage >II and T-stage >2 were significantly associated with shortened disease-specific survival (DSS) (p = 0.005 and <0.001, respectively), whereas perineural invasion and involved margins was not. No parameters were associated with disease-free survival. In conclusion, the majority of SGTs are malignant, most frequently ACC with a high rate of metastatic spread. The diagnostic value of FNAC in SGTs seems inferior to what is found for other major salivary glands. DSS is determined by stage and T-stage and not by histopathological parameters. International collaboration is warranted to confirm and elaborate these findings in larger materials.


Investigation of pathogenic germline variants in gastric cancer and development of "GasCanBase" database.
Gastric cancer, which is also known as stomach cancer, can be influenced by both germline and somatic mutations. Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in germline have long been reported to play a pivotal role in cancer progression. The aim of this study is to examine the nsSNP in GC-associated genes. The study also aims to develop a database with extensive information regarding the nsSNPs in the GC-associated genes and their impacts. A total of 34,588 nsSNPs from 1,493,460 SNPs of the 40 genes were extracted from the available SNP database. Drug binding and energy minimization were examined by molecular docking and YASARA. To validate the existence of the germline CDH1 gene mutation (rs34466743) in the isolated blood DNA of gastric cancer (GC) patients, polymerase chain reaction (PCR) and DNA sequencing were performed. According to the results of the gene network analysis, 17 genes may interact with other types of cancer. A total of 11,363 nsSNPs were detected within the 40 GC genes. Among these, 474 nsSNPs were predicted to be damaging and 40 to be the most damaging. The SNPs in domain regions were thought to be strong candidates that alter protein functions. Our findings proposed that most of the selected nsSNPs were within the domains or motif regions. Free Energy Deviation calculation of protein structure pointed toward noteworthy changes in the structure of each protein that can demolish its natural function. Subsequently, drug binding confirmed the structural variation and the ineffectiveness of the drug against the mutant model in individuals with these germline variants. Furthermore, in vitro analysis of the rs34466743 germline variant from the CDH1 gene confirmed the strength and robustness of the pipeline that could expand the somatic alteration for causing cancer. In addition, a comprehensive gastric cancer polymorphism database named "GasCanBase" was developed to make data available to researchers. The findings of this study and the "GasCanBase" database may greatly contribute to our understanding of molecular epidemiology and the development of precise therapeutics for gastric cancer. GasCanBase is available at: https://www.gascanbase.com/.


A roadmap for caGrid, an enterprise Grid architecture for biomedical research.
caGrid is a middleware system which combines the Grid computing, the service oriented architecture, and the model driven architecture paradigms to support development of interoperable data and analytical resources and federation of such resources in a Grid environment. The functionality provided by caGrid is an essential and integral component of the cancer Biomedical Informatics Grid (caBIG) program. This program is established by the National Cancer Institute as a nationwide effort to develop enabling informatics technologies for collaborative, multi-institutional biomedical research with the overarching goal of accelerating translational cancer research. Although the main application domain for caGrid is cancer research, the infrastructure provides a generic framework that can be employed in other biomedical research and healthcare domains. The development of caGrid is an ongoing effort, adding new functionality and improvements based on feedback and use cases from the community. This paper provides an overview of potential future architecture and tooling directions and areas of improvement for caGrid and caGrid-like systems. This summary is based on discussions at a roadmap workshop held in February with participants from biomedical research, Grid computing, and high performance computing communities.


Bovine IFNGR2, IL12RB1, IL12RB2, and IL23R polymorphisms and MAP infection status.
Mycobacterium avium ssp. paratuberculosis (MAP) infection causes a chronic granulomatous inflammatory condition of the bovine gut that is characterized by diarrhea, progressive weight loss, and emaciation, and ultimately leads to loss in productivity and profitability of dairy operations. The host cytokine machinery is known to play an important role in protecting against MAP infection. Therefore, the goal of the present study was to assess whether polymorphisms in candidate genes encoding important cytokines and cytokine receptors are associated with MAP infection status of dairy cattle. MAP infection status was evaluated based on serum and milk enzyme-linked immunosorbent assays (ELISAs) for MAP-specific antibodies. Twenty previously reported polymorphisms in genes encoding bovine interferon gamma (IFNG), IFNGR1, IFNGR2, IL22, IL22RA1, IL12RB1, IL12RB2, and IL23R were genotyped in a resource population of 446 dairy Holsteins with known MAP infection status, and logistic regression was used to assess the statistical association with a binomial MAP infection status phenotype. Four SNPs in IFNGR2, IL12RB1, IL12RB2, and IL23R were found to be associated with the MAP infection status of the resource population. These results underscore the importance of cytokines and their receptors in conferring protection against MAP infection and warrant further functional characterization of these associations.


DGC/Zeta as A New Strategy to Improve Clinical Outcome in Male Factor Infertility Patients following Intracytoplasmic Sperm Injection: A Randomized, Single-Blind, Clinical Trial.
The aim of this blind randomised clinical trial study was to assess the clinical efficiency of combined density gradient centrifugation/Zeta (DGC/Zeta) sperm selection procedure compared to conventional DGC in infertile men candidates for intracytoplasmic sperm injection (ICSI). The literature shows that DGC/Zeta is more effective compared to DGC alone in selection of sperms with normal chromatin and improves the clinical outcome of the ICSI procedure. Therefore, this study re-evaluates the efficiency of DGC/Zeta in improving the clinical outcomes of ICSI in an independent clinical setting. In this randomized, single-blind, clinical trial, a total of 240 couples with male factor infertility and at least one abnormal sperm parameter were informed regarding the study and 220 participated. Based on inclusion and exclusion criteria, 103 and 102 couples were randomly allocated into the DGC/Zeta and DGC groups, respectively. ICSI outcomes were followed and compared between the two groups. Although there was no significant difference in fertilization rate (P=0.67) between the DGC/Zeta and DGC groups, mean percentage of good embryo quality (P=0.04), good blastocysts quality (P=0.049), expanded blastocysts (P=0.007), chemical pregnancies (P=0.005) and clinical pregnancies (P=0.007) were significantly higher in the DGC/ Zeta group compared to DGC. In addition, implantation rate was insignificantly higher in DGC/Zeta compared to DGC (P=0.17). This is the second independent study showing combined DGC/Zeta procedure improves ICSI outcomes, especially the pregnancy rate, compared to the classical DGC procedure and this is likely related to the improved quality of sperm selected by the DGC/Zeta procedure (Registration number: IRCT20180628040270N1).


Prescription drug safe storage practices in Arizona tribal communities.
This paper provides an overview of an opioid poisoning prevention pilot project conducted in several American Indian/Alaskan Native communities using an applied public health approach. The intent of the project was to identify a prescription medication safeguarding option for use in the home environment. The authors engaged the target population to obtain their buy-in to select an intervention that was acceptable and appropriate for their needs. Focus groups and key informant interviews conducted in several tribal communities resulted in the selection of a heavy-duty, lockable storage box as the intervention. Through community-based partnerships, 55 boxes were installed in participating households. Along with the box, participants also received education on safe medication storage and disposal. At baseline, only 1% of the participants reported storing their medication securely. During a 60-day follow-up visit, 95% of the observed boxes were being used to store medications. Also at baseline, 31% of the participants reported a history of lost or stolen medications. There were no reported lost or stolen medications during the 60-day project period among the participants. During the follow-up visits, project staff also found the boxes being used to store other items valuable to the participants. Reportedly, having their medication and other valuables secured in one location provided a heightened feeling of security. Since the completion of this pilot project, several organisations and entities have replicated it in their communities.


Nuclear depletion of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is an indicator of energy disruption in neurons.
Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is a multifunctional protein critical for cellular survival. Its involvement in adaptive survival responses includes key roles in redox sensing, transcriptional regulation, and repair of DNA damage via the base excision repair (BER) pathway. Ape1 is abundant in most cell types and central in integrating the first BER step catalyzed by different DNA glycosylases. BER is the main process for removal of oxidative DNA lesions in postmitotic brain cells, and after ischemic brain injury preservation of Ape1 coincides with neuronal survival, while its loss has been associated with neuronal death. Here, we report that in cultured primary neurons, diminution of cellular ATP by either oligomycin or H(2)O(2) is accompanied by depletion of nuclear Ape1, while other BER proteins are unaffected and retain their nuclear localization under these conditions. Importantly, while H(2)O(2) induces γH2AX phosphorylation, indicative of chromatin rearrangements in response to DNA damage, oligomycin does not. Furthermore, despite comparable diminution of ATP content, H(2)O(2) and oligomycin differentially affect critical parameters of mitochondrial respiration that ultimately determine cellular ATP content. Taken together, our findings demonstrate that in neurons, nuclear compartmentalization of Ape1 depends on ATP and loss of nuclear Ape1 reflects disruption of neuronal energy homeostasis. Energy crisis is a hallmark of stroke and other ischemic/hypoxic brain injuries. In vivo studies have shown that Ape1 deficit precedes neuronal loss in injured brain regions. Thus, our findings bring to light the possibility that energy failure-induced Ape1 depletion triggers neuronal death in ischemic brain injuries.


[Benefit of adjuvant 5-fluorouracil based chemotherapy for colon cancer: a retrospective cohort study].
Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94). Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.


Maternal diet and insulin secretion in islets of lactating, nonlactating, and young rats.
The effects of dietary phosphorus (P) on insulin secretion by pancreatic islets of rats at peak lactation (14 days after parturition) and by islets of nonlactating previously pregnant rats have been determined. In addition, the effects of changed dietary P in the maternal diet on insulin secretion by islets of the 1- and 14-day-old offspring were studied. Lactating rats had increased food intake relative to nonlactating rats and correspondingly increased P intake on the 0.4 and 0.7% P diets. Serum P levels were elevated in lactating rats consuming the 0.7% P feed relative to those on the 0.4% P feed and also relative to the nonlactating rats on the 0.7% P feed. Lactating rats had decreased bone calcium compared with the nonlactating rats. Islets from lactating rats on the 0.7% P feed secreted more insulin in response to glucose or to 3-isobutyl-1-methylxanthine (IBMX) than lactating rats on the 0.4% P feed. Additionally, lactating rats on the 0.7% P feed secreted more insulin in response to glucose than nonlactating rats on the same 0.7% P feed. The maternal diet had no influence on the endocrine pancreatic responses of the 1- and 14-day-old offspring in response to glucose or IBMX.


Design of minimally strained nucleic Acid nanotubes.
A practical theoretical framework is presented for designing and classifying minimally strained nucleic acid nanotubes. The structures are based on the double crossover motif where each double-helical domain is connected to each of its neighbors via two or more Holliday-junction-like reciprocal exchanges, such that each domain is parallel to the main tube axis. Modeling is based on a five-parameter characterization of the segmented double-helical structure. Once the constraint equations have been derived, the primary design problem for a minimally strained N-domain structure is reduced to solving three simultaneous equations in 2N+2 variables. Symmetry analysis and tube merging then allow for the design of a wide variety of tubes, which can be tailored to satisfy requirements such as specific inner and outer radii, or multiple lobed structures. The general form of the equations allows similar techniques to be applied to various nucleic acid helices: B-DNA, A-DNA, RNA, DNA-PNA, or others. Possible applications for such tubes include nanoscale scaffolding as well as custom-shaped enclosures for other nano-objects.


Update of application of olfactory ensheathing cells and stem cells/exosomes in the treatment of retinal disorders.
Age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa and other retinal disorders are the main causes of visual impairment worldwide. In the past, these retinal diseases, especially dry age-related macular degeneration, proliferative diabetic retinopathy and retinitis pigmentosa, were treated with traditional surgery and drugs. However, the effect was moderate. In recent years, researchers have used embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, olfactory ensheathing cells and other stem cells to conduct experiments and found that stem cells can inhibit inflammation, regulate immune response, secrete neurotrophic factors, and differentiate into retinal cells to replace and promote restoration of the damaged parts. These stem cells have the potential to treat retinal diseases. Whether it is in animal experiments or clinical trials, the increase in the number of retinal cells, maintenance of function and improvement of visual function all reflect the advanced of stem cells to treat retinal diseases, but its risk preserves the donor's hidden pathogenic genes, immune rejection and tumorigenicity. With the development of exosomes study, researchers have discovered that exosomes come from a wide range of sources and can be secreted by almost all types of cells. Using exosomes with stem cell to treat retinal diseases is more effective than using stem cells alone. This review article summarizes the recent advances in the application of olfactory ensheathing cells and stem cells/exosomes in the treatment of retinal disorders.