Diabetes Mellitus Is an Independent Risk Factor for a Stiff Left Atrial Physiology After Catheter Ablation for Atrial Fibrillation.
Scar tissue formation after catheter ablation for atrial fibrillation (AF) may adversely affect the diastolic properties of the left atrium (LA), which can result in a stiff LA physiology in a small proportion of patients. In this study, we aimed to explore the relationship between diabetes mellitus and a stiff LA physiology after AF catheter ablation (AFCA). A total of 1,326 patients who underwent de novo AFCA, and baseline and 1-year follow-up echocardiographies were enrolled. After 1:3 propensity score (PS) matching for age, sex, and AF type, we compared 211 patients with DM with 633 patients without DM. A stiff LA physiology was defined as estimated pulmonary arterial pressure increase of >10 mmHg and a right ventricular systolic pressure of >35 mmHg at 1-year follow-up echocardiography. Pulmonary vascular resistance (PVR) was estimated using echocardiographic parameters. Among the 844 PS-matched patients, a stiff LA physiology was observed in 32 patients (4.1%). The patients with DM showed a higher peak LA pressure (p < 0.001) and greater LA wall stress (p = 0.001) than did those without. A stiff LA physiology was independently associated with DM [Odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.02-5.59, p = 0.045], empirical extra-pulmonary vein LA ablation (OR = 3.14, 95% CI 1.07-9.3, p = 0.038) and the ΔPVR (OR = 1.78, 95% CI 1.37-2.31, p < 0.001). The ΔPVR was independently associated with DM (β = 0.37, 95% CI 0.06-0.67, p = 0.020) and a stiff LA physiology (β = 1.40, 95% CI 0.70-2.10, p < 0.001). During the 38.8 ± 29.3months follow-up, the incidence of the clinical recurrence of AF was significantly higher in the patients with a stiff LA physiology than in those without (log rank p = 0.032). A stiff LA physiology was independently associated with DM because of the relatively small decrease in the PVR after AFCA in this population. The patients with a stiff LA physiology had worse rhythm outcomes after AFCA than those without.


Risk factors associated with coronary artery calcification in midlife women: a population-based study.
The aim of this study was to investigate the association between individual risk factors and coronary artery calcification (CAC), as a marker of subclinical cardiovascular disease, in a population-based nested cross-sectional study of midlife women. Anthropometric and metabolic data from 295 women from the South of Brazil were analyzed. Habitual physical activity was assessed by pedometer. CAC was assessed by a multi-detector computed tomography system. Average Agatston score was used to stratify participants as CAC > 0 and CAC = 0. Women with CAC > 0 (34.7%) were older (58.7 ± 5.4 vs. 56.3 ± 5.2 years, p < .001) and had higher prevalence of central adiposity (71 vs. 59%, p = .04) and hypertension (71 vs. 52%, p = .002) than women in the CAC = 0 group. Hormone therapy (HT) was more prevalent in the group with CAC = 0 (19.7 vs. 9.8%, p = .029). The prevalence ratios for CAC > 0 were 0.545 (95%CI:0.309-0.962, p = .036) for HT and 1.752 (95%CI:1.207-2.541, p = .003) for hypertension, after adjustment for age, educational level, smoking, alcohol intake, and physical activity. The present data in a population-based sample of midlife women indicate that hypertension and age were positively associated with higher risk for CAC > 0 and HT was related with CAC = 0.


Microsurgical reconstruction of the smile--contemporary trends.
The treatment of facial palsy is a complex and challenging area of plastic surgery. Microsurgical innovation has introduced the modern age of dynamic reconstruction for facial palsy. This review will focus on microsurgical reconstruction for smile restoration in patients with long-standing facial palsy. The most common donor muscles and nerves will be presented. The advantages and disadvantages of single-stage versus multi-stage reconstruction will be discussed. Contemporary trends will be highlighted and the authors' preferred practice outlined.


A computational study of the interaction noise from a small axial-flow fan.
Small axial-flow fans used for computer cooling and many other appliances feature a rotor driven by a downstream motor held by several cylindrical struts. This study focuses on the aerodynamic mechanism of rotor-strut interaction for an isolated fan. The three-dimensional, unsteady flow field is calculated using FLUENT, and the sound radiation predicted by acoustic analogy is compared with measurement data. Striking differences are found between the pressure oscillations in various parts of the structural surfaces during an interaction event. The suction surface of the blade experiences a sudden increase in pressure when the blade trailing edge sweeps past a strut, while the process of pressure decrease on the pressure side of the blade is rather gradual during the interaction. The contribution of the latter towards the total thrust force on the structure is cancelled out significantly by that on the strut. In terms of the acoustic contributions from the rotor and strut, the upstream rotor dominates and this feature differs from the usual rotor-stator interaction acoustics in which the downstream part is responsible for most of the noise. It is therefore argued that the dominant interaction mechanism is potential flow in nature.


Increased adrenal sensitivity to angiotensin II in idiopathic hyperaldosteronism.
Plasma aldosterone increases briskly during upright posture in patients with idiopathic hyperaldosteronism, despite only small increases in PRA and presumably small increases in angiotensin II. To examine the postulate that small increments in angiotensin II mediate these brisk increases in aldosterone, we infused graded doses of angiotensin II into normal subjects and patients with idiopathic hyperaldosteronism and compared the changes in levels of plasma aldosterone in the two groups. Supplemental sodium and dexamethasone were given before the infusion to minimize the influence of endogenous angiotensin II and ACTH. In response to the infusion of angiotensin II, increases in the levels of plasma aldosterone of patients with idiopathic hyperaldosteronism were significantly greater than those of normal subjects. In addition, levels of plasma aldosterone increased at a lower rate of infusion of angiotensin II in patients than in normal subjects. It is concluded that patients with idiopathic hyperaldosteronism have increased adrenal sensitivity to angiotensin II. This increased sensitivity may explain the brisk increases in aldosterone that occur during upright posture in these patients.


Cytokine production from peripheral blood mononuclear cells and polymorphonuclear leukocytes in patients studied for suspected obstructive sleep apnea.
The relationship between obstructive sleep apnea (OSA) and atherosclerosis-related inflammation has been poorly investigated, particularly focusing on functional responses of immune cells playing a key role in atherogenesis and in comparison with control groups with similar cardiovascular risk factors which are known to be themselves associated with inflammation. We sought to determine cellular tumor necrosis factor-alpha (TNF-α) production from peripheral blood mononuclear cells (PBMCs) and interleukin (IL)-8 release from neutrophils (PMNs) in patients studied for suspected OSA. Thirty-six consecutive patients who underwent a nocturnal complete cardiorespiratory evaluation for suspected OSA were initially evaluated. Serum, PBMCs, and PMNs were isolated (at baseline and after 12 weeks) from patients with apnea-ipopnea index (AHI) >20 (OSA group, n = 16) and from control patients with AHI <5 (nonOSA group, n = 11). All patients continued the same pharmacological therapy for 12 weeks; the OSA group was additionally treated with nocturnal continuous positive-airway-pressure ventilation (cPAP). The two groups had similar clinical characteristics (prevalence of hypertension, dyslipidemia, diabetes, and cardio-metabolic therapies) except for obesity. Resting and stimulated TNF-α production from PBMCs and IL-8 release from PMNs were similar in the two groups. Serum cytokines resulted within the normal range. In the OSA group, cPAP was not associated with changes in cellular responses. In patients showing similar prevalence of major cardiovascular risk factors and cardio-metabolic therapies, differing for the presence or absence of OSA, cytokine productions from PBMC and PMN were similar and were not modified during cPAP therapy. Studies designed to investigate OSA-associated inflammation should carefully match the control group subjects.


Translation of the Debriefing Assessment for Simulation in Healthcare in Portuguese and cross-cultural adaptation for Portugal and Brazil.
Debriefing Assessment for Simulation in Healthcare (DASH©) is an instrument to assist in developing and evaluating debriefing skills. The objectives of this study were to translate the DASH from English to Portuguese and to conduct a cross-cultural adaptation of this translated instrument for Portugal and Brazil. A forward translation of the DASH score sheets and Rater's Handbook was accomplished and reviewed by authors from both Portuguese-speaking countries to reach the consensus harmonized version. A backward translation was reviewed by the original authors and discussed with the authors to produce the approved harmonized translation. This was then tested through a questionnaire to assess clarity, comprehensiveness, appropriateness, and cultural relevance among 10 simulation specialists from Portugal and Brazil. During the forward translation, 19 discrepancies were detected in the Portuguese DASH. After backward translation, 7 discrepancies were discussed and harmonized. All 10 simulation specialists from both countries reviewed the harmonized translation and made 70 suggestions, 64 of which were incorporated in the instrument after discussion among authors. The translated DASH has undergone translation to Portuguese and a cross-cultural adaptation across Portugal and Brazil. It may be used to assess debriefings in healthcare settings in these countries.


Quality of Regulatory Decision-Making Practices: Issues Facing Companies and Agencies.
The science of decision making is well established, although in reality it is a mixture of science and art. What is currently lacking is research into decision making in medicines research and development. The aims of this study were to determine the current decision-making practices and methodologies for measuring the quality of the decision making and the barriers and solutions for making quality decisions within pharmaceutical companies and regulatory agencies. Two analogous questionnaires were developed for use in this study. Fourteen agencies and 25 companies were asked to complete the questionnaire, assessing their decision making for submitting or approving a new drug application. The 68% and 71% response rate from companies and agencies, respectively, suggests interest in this topic, but the area is largely unexplored within the pharmaceutical environment. Moreover, all companies and 90% of the agencies believed that decision making at their organizations could be improved. Although both stakeholders have, to some extent, already implemented frameworks and various methodologies, these are often informal and unsystematic. Challenges remain and there is a need to change the organizational culture by increasing the awareness of the quality aspect in decision making. The findings of this study support the need to further characterize and assess the practices and behaviors of individuals and organizations. Furthermore, the barriers, mainly relating to the influence of biases, should be addressed by developing the general principles of a formal quality decision framework and identifying quality decision-making practices in order to ensure that structured decisions are made throughout the life cycle of medicines.


Next-Generation and Single-Cell Sequencing Approaches to Study Atherosclerosis and Vascular Inflammation Pathophysiology: A Systematic Review.
Atherosclerosis is a chronic inflammatory disease that remains the leading cause of morbidity and mortality worldwide. Despite decades of research into the development and progression of this disease, current management and treatment approaches remain unsatisfactory and further studies are required to understand the exact pathophysiology. This review aims to provide a comprehensive assessment of currently published data utilizing single-cell and next-generation sequencing techniques to identify key cellular and molecular contributions to atherosclerosis and vascular inflammation. Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were undertaken from inception until February 2022. A narrative synthesis of all included studies was performed for all included studies. Quality assessment and risk of bias analysis was evaluated using the ARRIVE and SYRCLE checklist tools. Thirty-four studies were eligible for narrative synthesis, with 16 articles utilizing single-cell exclusively, 10 utilizing next-generation sequencing and 8 using a combination of these approaches. Studies investigated numerous targets, ranging from exploratory tissue and plaque analysis, cell phenotype investigation and physiological/hemodynamic contributions to disease progression at both the single-cell and whole genome level. A significant area of focus was placed on smooth muscle cell, macrophage, and stem/progenitor contributions to disease, with little focus placed on contributions of other cell types including lymphocytes and endothelial cells. A significant level of heterogeneity exists in the outcomes from single-cell sequencing of similar samples, leading to inter-sample and inter-study variation. Single-cell and next-generation sequencing methodologies offer novel means of elucidating atherosclerosis with significantly higher resolution than previous methodologies. These approaches also show significant potential for translatability into other vascular disease states, by facilitating cell-specific gene expression profiles between disease states. Implementation of these technologies may offer novel approaches to understanding the disease pathophysiology and improving disease prevention, management, and treatment.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021229960, identifier: CRD42021229960.


99mTc-WBC scintigraphy with SPECT/CT in the evaluation of arterial graft infection.
The goals of our study were to retrospectively review our experience in using Tc-white blood cell (WBC) single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in the evaluation of possible arterial graft infection and to attempt to establish objective criteria for assessment. Eleven Tc-WBC SPECT/CT studies performed for the evaluation of clinically suspected arterial graft infection were retrospectively reviewed and compared with reference outcomes. In an attempt to define objective criteria for interpretation, comparison was also made with background liver and bone marrow activity. When compared with reference outcomes, the subjective scan interpretations showed 6 of 11 true positives (TP), 4 of 11 true negatives (TN), and 1 of 11 false positive (FP). Using the liver as a comparator resulted in 4 of 10 TP, 5 of 10 TN, and 1 of 10 FN. Using the bone marrow as a comparator resulted in 3 of 10 TP, 5 of 10 TN, and 2 of 10 FN. In one patient neither the liver nor the bone marrow was in the field of view. These findings suggest a high accuracy for Tc-WBC SPECT/CT in assessing clinically suspected arterial graft infection. Furthermore, the liver may be the best objective comparator for standardized interpretation.


[Prevention of meningococcal meningitis].
In Germany, the incidence of meningococcal disease is approximately 1/100,000 and has not risen during recent years. Transmission occurs by direct contact with respiratory droplets, mostly from asymptomatic carriers and less frequently from patients with meningococal disease. The incubation period can vary from 2-10 days but usually is 3-4 days. Incidence is highest in children and decreases with age. The mortality from meningococcal disease is approximately 10%. In case meningococcal meningitis is clinically suspected antibiotic treatment (in Germany with penicillin G or a cephalosporin) should not be delayed. Patients must be isolated for at least 24 hours after the institution of antibiotic therapy. For early detection of local outbreaks, public health authorities should be quickly informed of suspected cases. Persons in close contact should be treated with antimicrobial chemoprophylaxis. In addition to rifampin, ciprofloxacin or ceftriaxone can be used for chemoprophylaxis. For control of local outbreaks of serogroup C meningococcal disease, the meningococcal vaccine can be used.


Treating acid reflux disease in patients with Down syndrome: pharmacological and physiological approaches.
Down syndrome (DS) is often accompanied by gastrointestinal disease, occurring mainly in early infancy and frequently requiring therapy. Among motility disorders, the most frequent is gastroesophageal reflux disease (GERD), which may often be misdiagnosed because of its atypical manifestations. Early diagnosis of esophageal functional disorders is essential to prevent respiratory problems, growth retardation in children, weight loss in adults, and to establish the correct type of surgery if needed. Furthermore, the involvement of the enteric nervous system in the pathophysiology of GERD in DS is not yet completely understood but seems supported by much evidence. In fact DS is often associated with motor disorders and this evidence must be considered in the choice of therapy: in particular all options available to improve motility seem to be effective in these patients. The effectiveness of therapy is strictly related to the rate of mental impairment, so that modulating therapy is essential, especially in view of the severity of the neurological status.


Regenerative potential of allopregnanolone.
The neuroendocrine status of the brain has been linked to the quality of the aging process, to the risk of Alzheimer's disease and to progression of neurodegenerative pathology. Data from multiple levels of analysis ranging from in vitro cellular models to in vivo animal models to clinical investigations indicate that the decline of neurosteroids play a key role in successful aging and prevention of neurodegenerative disease Alzheimer's. Among the neurosteroids in decline during aging is allopregnanolone (APalpha, a metabolite of progesterone, which is reduced in the serum, plasma and brain of aged vs. young subjects. Further, Alzheimer's disease (AD) victims exhibit an even greater reduction in plasma and brain levels of APalpha relative to age-matched neurologically normal controls. Our earlier work has shown that APalpha is a neurogenic agent for rodent hippocampal neural progenitors and for human neural progenitor cells derived from the cerebral cortex. Our ongoing research seeks to determine the neurogenic potential of APalpha in the triple transgenic mouse model of Alzheimer's disease (3 x TgAD) as AD related pathology progresses from imperceptible to mild to severe. Initial analyses suggest that APalpha may maintain the regenerative ability of the brain, modify progression of AD related pathology and reverse learning and memory deficits in 3 x TgAD mice. This review summarizes current APalpha research in different animal models, neural progenitor regeneration within a degenerative milieu and the challenge for developing neuroregenerative therapeutics.


Resolution of a proteinuric nephropathy associated with Babesia gibsoni infection in a dog.
A 4 yr old male castrated Labrador retriever was evaluated for a short history of inappetance, lethargy, small-bowel diarrhea, polyuria, and polydipsia. Clinicopathologic abnormalities were consistent with protein-losing nephropathy and renal azotemia. Expansive infectious disease testing implicated Babesia gibsoni via whole blood polymerase chain reaction. Renal histopathology results were consistent with membranoproliferative glomerulonephritis and immune complex deposition. The dog was treated with azithromycin, atovaquone, and one dose of corticosteroids/cyclophosphamide. Three months after therapy was completed, the dog was clinically healthy, and all clinicopathologic abnormalities (including Babesia species polymerase chain reaction) had resolved. Atypical presentations of Babesia gibsoni should be considered with proteinuric nephropathy.


Identification of the External Branch of the Superior Laryngeal Nerve during Thyroid Surgery.
To compare the level of intra-operative identification of external branch of the superior laryngeal nerve (EBSLN) through classical conventional clinical methods of prevention against those applying intraoperative neuromonitoring (IONM). The study included 102 patients with interventions on the thyroid gland performed in the surgical clinics of St George University Hospital and the Department of Special Surgery of Plovdiv Medical University. All operative procedures were performed by the standard technique of capsular dissection and IONM. Of all 102 thyroid procedures 87 (85.3%) patients underwent total thyroidectomy and 15 (14.7%) had unilateral thyroid lobectomy. One hundred fifty-five (82.01%) out of 189 expected EBSLN were identified and investigated intraoperatively when trying to identify visually EBSLN by the so called classical (conventional) methods of prevention. With the use of IONM, 181 (96.76%) EBSLN were correctly identified. Compared to the preliminary results of visual identification - 155/189 (82.01%) EBSLN, the degree of identification of EBSLN through IONM reached 96.76% which is a statistically significant difference (P <0.05) Conclusion: The use of IONM during thyroid resection significantly improves the degree of identification of EBSLN compared to conventional means of prevention. Routine use of IONM in surgical interventions on the thyroid gland will be beneficial for more secure identification and prevention of EBSLN.


Cerebellar vasoreactivity in stroke patients with crossed cerebellar diaschisis assessed by acetazolamide and 99mTc-HMPAO SPECT.
Crossed cerebellar diaschisis (CCD) tends to persist or even worsen after supratentorial infarction. Several studies have shown impairment of cerebral vasomotor responsiveness in the hemispheric area of diaschisis in patients with hemispheric infarction. This finding has led to the concern that the lack of CCD reversibility might be associated with chronic circulatory abnormalities. We therefore assessed the vasoreactivity in the cerebellar hemisphere in which diaschisis is manifested using acetazolamide (ACZ) and SPECT. Eight stroke patients with CCD (5 with unilateral hemispheric infarcts and 3 with unilateral intracerebral hemorrhage) had 99mTc-HMPAO SPECT scanning at rest and 20 min after intravenous injection of 1.0 g ACZ. The time interval after stroke ranged from 25 to 904 d. From the total counts obtained from each cerebellar hemisphere, the asymmetry index (AI) was calculated as (unaffected - affected cerebellar hemisphere)/unaffected cerebellar hemisphere x100. After ACZ, the mean AI (8.7+/-6.6) was significantly decreased (P<0.05) compared with that at rest (17.7+/-5.8). Seven of the 8 patients showed decrease in the AI after ACZ. In 1 patient, the direction of the asymmetry was reversed after ACZ so that the AI was negative. The ACZ-induced change in the AI did not show a significant correlation with the time interval after stroke, whether calculated in absolute terms or as a percentage change. This study shows that normal vascular supply is maintained in the CCD-affected cerebellar hemisphere over long periods of time after a stroke. Thus, the lack of CCD reversibility may not be attributed to a chronic circulatory insufficiency. The results lend support to the concept of functional deactivation and subsequent transneuronal degeneration as a likely explanation for CCD. It is unclear whether decreased AI after ACZ indicates a higher vascular response of the affected cerebellar hemisphere than that of the normal side.


Medulloblastoma: conventional radiation therapy in comparison to chemo radiation therapy in the post-operative treatment of high-risk patients.
The aim of this study is to assess treatment results of 48 pediatric high-risk medulloblastoma cases that were treated by surgery, radiotherapy with or without chemotherapy. The impact of adjuvant combination chemotherapy on treatment results will be assessed. Forty-eight cases of pediatric high-risk medulloblastoma treated from July 2001 to July 2004 were randomized into two groups. The first (group I) included 21 patients who received postoperative craniospinal radiation therapy (36Gy+boost 20Gy to the posterior fossa). The second (group II) included 27 cases who received postoperative combination cranio-spinal radiation therapy (with the same dose as the first group) and chemotherapy (vincristine, etoposide, cisplatin). Both groups were compared as regards overall survival (OS), disease free survival (DFS), response rate and treatment toxicity. In-group I, complete remission (CR) was achieved in 71.4% of the cases; partial remission (PR) in 14.3% of the patients; stationary disease (SD) in 14.3% and none of the cases suffered from progressive disease. The three-year OS was 69.5% and the three-year DFS was 61.3%. In-group II, CR was achieved in 59.3% of the cases; PR in 3.7%; SD in 3.7% and PD in 37.3% of the cases. The three-year OS was 48.4% and the 3-year DFS was 48.9%. Regarding acute treatment toxicity in group I, nine patients (31.5%) developed grade I myelo-suppression and seven cases (24.5%) developed grade II myelo-suppression with three to five days treatment interruption. Whereas in group II, 13 patients (45.5%) developed grade I myelosuppression and seven cases (24.5%) developed grade II myelo-suppression requiring interruption of treatment for a period ranging from five to seven days with spontaneous recovery. In group I no other acute toxicity was recognized, whereas in group II other toxicities related to chemotherapy were noticed. For example, three patients (11%) developed peripheral neuritis during the course of treatment and two patients (7%) developed renal impairment, which responded to medical treatment. Late treatment toxicity, manifested as reduction in intelligence quotient (IQ), was noticed, which makes conventional treatment of medulloblastoma unsatisfactory. In group I; 13 patients (62%) suffered a reduction of 8-20% in IQ in comparison to their normal siblings, whereas in Group II; 13 patients (48%) developed a reduction in IQ ranging from 12-21%. The current treatment of medulloblasotma has a detrimental effect on long-term survivors. Whereas acute toxicity is considered mild and tolerable, late toxicity regarding diminution in IQ makes current treatment unsatisfactory because of the long-term mental disability of the cured patients. We believe that, the poorer outcome in the chemo-radiation group was due to the treatment interruption during radiation therapy caused by myelosuppression since the incidence of myelosuppression was higher in the chemo-radiation group and the recovery time was longer.


Debunking the essential effect of temperature and voltage on the current curve and the nanotube morphology.
The formation mechanism of anodic TiO2 nanotubes remains to be unclear till now. Many researchers study the influence of temperatures above 0 °C instead of below 0 °C. Few papers before have explained the relationship between the current-time curve and the morphology of the nanotubes. In this study, the innovative 'oxygen bubble model' and the ionic current and electronic current theories were introduced to explain the growth of nanotubes below 0 °C. The length of anodic TiO2 nanotubes at 15 °C, 0 °C, -10 °C were 1.28 μm, 0.93 μm and 0.21 μm, respectively, but the diameter of anodic TiO2 nanotubes was almost the same, at about 164 nm. When the temperature was low, the magnitude of electronic current and the ionic current was small, the mold effect was weak and nanotubes could not be formed. At the same time, this study shows that the dissolution reaction of the field-assisted solution theory has no electron gain or loss, and it has nothing to do with the current, which negates the field-assisted dissolution theory. A novel two-step anodization was used to verify the conclusion. It was found that nanotubes could be obtained when the anodizing current was decreasing or increasing. Also, ginseng-shaped nanotubes are formed at a particular voltage sequence. Based on the 'oxygen bubble model' and the ionic current and electronic current theories, the formation process of nanotubes of two-step anodization is explained clearly.


Electron density investigation of a push-pull ethylene (C14H24N2O2.H2O) by X-ray diffraction at T = 21 K.
The electron charge distribution in a strongly twisted push-pull ethylene [PPE, 3-(1,3-diisopropyl-2-imidazolidinylidene)-2,4-pentanedione] has been determined by low temperature (T = 21 K) single-crystal X-ray diffraction analysis. The derived electronic properties are consistent with a zwitterionic molecule, as indicated by a charge transfer of 0.82(16) e from the push to the pull moieties and a charge polarization of 0.29(7) e on the olefinic bond. A dipole moment of 12(3) D has been determined, which compares well with ab initio theoretical results in terms of both modulus and orientation. The second moments, which have also been obtained with good precision, characterize PPE as a highly quadrupolar molecule. The special electronic features of the molecule confer particular topological properties to the electron density distribution, as evidenced by comparison with "standard" organic molecules. The crystallographic asymmetric unit of the present system includes one water molecule, which is hydrogen bonded to PPE. Its topological properties have also been investigated, together with an analysis of the hydrogen bonds involved.


Xiaoaiping injection combined with chemotherapy for advanced gastric cancer: An updated systematic review and meta-analysis.
Aim: To evaluate the clinical efficacy and safety of Xiaoaiping injection combined with chemotherapy in the treatment of advanced gastric cancer by meta-analysis. Methods: Seven databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, Cochrane Library, PubMed, Embase, and Web of Science, were searched by computer for randomized controlled clinical trials of Xiaoaiping injection combined with chemotherapy in the treatment of gastric cancer. Risk of bias assessment and meta-analysis were performed by Review Manager 5.3 software. Results: There were 16 articles that met the inclusion criteria, with a total of 1,236 patients, 617 in the observation group and 619 in the control group. The results of meta-analysis showed that the observation group was better than chemotherapy alone control group in RR [OR = 1.86, p < 0.00001]; disease control rate (DCR) [OR = 2.45, p < 0.00001]; Karnofsky performance status (KPS) score [OR = 3.21, p < 0.00001] or [MD = 7.73, p = 0.001]. In terms of biochemical indicators, Xiaoaiping significantly reduced inflammation factors level, including tumor necrosis factor alpha (TNF-α) [MD = -15.00, p < 0.00001]; interleukin-6 (IL-6) [MD = -13.00, p < 0.00001]; C-reaction protein (CRP) [MD = -5.80, p < 0.00001]. Xiaoaiping could enhance immune function, significantly reducing myeloid-derived suppressor cells (MDSCs) [MD = -6.20, p < 0.00001] and Treg [MD = -1.70, p < 0.00001]. Xiaoaiping injection combined with chemotherapy could significantly decrease tumor markers, including carcinoembryonic antigen (CEA) [MD = -11.64, p < 0.00001]; CA199 [MD = -33.57, p = 0.02]; CA242 [MD = -20.66, p < 0.00001]; CA125 [MD = -12.50, p = 0.0005]. In the comparison of adverse reactions, the incidence rate of Xiaoaiping injection group was significantly lower than that of control group. The funnel plot showed that the left and right sides are basically symmetrical, and it can be considered that there is no obvious publication bias. Conclusion: Xiaoaiping injection combined with chemotherapy has better curative effect and less adverse reactions in the treatment of gastric cancer. However, limited by the quality of the included studies, more high-quality studies are still needed to be verified. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022353842], identifier [CRD42022353842].


Radiological evaluation of the pancreas in malnutrition-related (phasic insulin dependent) diabetes mellitus.
This study was undertaken to investigate pancreatic changes associated with phasic insulin dependent diabetes mellitus (PIDDM). Twelve PIDDM patients were studied. They were compared with groups of patients, 10 insulin dependent (IDDM), 10 non-insulin dependent (NIDDM), and 10 normal controls. Each group was matched for age, sex, and body mass index. For the study, the mean age was 56.7 +/- 2.5 years, mean body mass index 24.0 +/- 0.8, and mean duration of diabetes 14.2 +/- 2.2 years. Flat abdominal radiograph and ultrasonography were performed on each participant. The results suggest an increased echogenicity of the pancreas in the phasic insulin dependent group of patients.


Why Tenure Responsive Land-Use Planning Matters: Insights for Land Use Consolidation for Food Security in Rwanda.
Land use consolidation aims to address food insecurity challenges in Rwanda. However, there is contradictory evidence on whether this tool has met food security objectives or not. This study addresses two questions: How has the land use consolidation improved (or not improved) food security at the local level? How can food security challenges be addressed using a renewed approach to land use consolidation that adopts a tenure responsive land use planning procedure? We investigate these questions in Nyange Sector (in the Musanze District) of Rwanda using mixed research methods. The study generates theoretical and policy relevant outcomes. Theoretically, it links the concept of tenure responsive land-use planning to food security improvements. Policy wise, it provides an operational framework for implementing land use consolidation to make it more responsive to food security (based on tenure responsive land-use planning measures) in Rwanda.


Absolute configuration of 2-sec-butyl-4,5-dihydrothiazole in male mouse urine.
The absolute configuration of 2-sec-butyl-4,5-dihydrothiazole (DHT) in urine of adult male mice was determined through chiral trifluoroacetyl derivative capillary chromatography by comparing the retention time with synthetic standards. (S)-DHT was extracted from fresh urine, while neither (R)-DHT nor the racemization of (S)-DHT were detected. We can conclude that DHT in urine possesses the S configuration, although we cannot exclude a minor component in the R configuration. (S)-DHT was then characterized for binding to the complex of major urinary proteins of male mouse urine (MUP) and for a behavioral response, the competitive scent marking behavior (countermarking). The binding constant of (S)-DHT to MUP (determined by competitive displacement) was 8.2 +/- 0.6 microM (mean +/- SD) and was 10.5 +/- 0.6 microM for R-DHT, thus excluding a relevant difference in binding. (S)-DHT modified countermarking in a peculiar way. Male mice were slow in countermarking urinary spots streaked 2 days earlier and on top of which (S)-DHT was added shortly before the test. This response was not seen when adding (S)-DHT to freshly streaked urinary spots or to clean paper. Unlike (S)-DHT, (R)-DHT prompted countermarking rather than delaying it. We can further conclude that (S)-DHT in male mouse urine is an aversive chemosignal for countermarking.


Neurohormonal regulation of cardiac ion channels in chronic heart failure.
Alteration of neurohormonal homeostasis is a hallmark of the pathophysiology of chronic heart failure (CHF). In particular, overactivation of the renin-angiotensin-aldosterone system and the sympathetic catecholaminergic system is consistently observed. Chronic overactivation of these hormonal pathways leads to a detrimental arrhythmogenic remodeling of cardiac tissue due to dysregulation of cardiac ion channels. Sudden cardiac death resulting from ventricular arrhythmias is a major cause of mortality in patients with CHF. All the drug classes known to reduce mortality in patients with CHF are neurohormonal blockers. The aim of this review was to provide an overview of how cardiac ion channels are regulated by hormones known to play a central role in the pathogenesis of CHF.


Frailty and Acute Postoperative Urinary Retention in Older Women Undergoing Pelvic Organ Prolapse Surgery.
Acute postoperative urinary retention (POUR) is common after pelvic reconstructive surgery, occurring in 15-45% of women. There is a paucity of data on the relationship between frailty and POUR after prolapse surgery. This study aimed to examine the association between frailty and POUR in older women who underwent pelvic organ prolapse surgery. This secondary analysis of a prospective study of postoperative delirium enrolled women 60 years and older undergoing prolapse surgery. The Fried Frailty Index was used to assess frailty before surgery. Acute POUR was defined as failure to pass a retrograde voiding trial at hospital discharge with postvoid residual volume of greater than 100 mL. Analyses included 165 women, with a mean ± SD age of 72.5 ± 6.1 years and a body mass index of 28.0 ± 4.4 kg/m2. There were 49 laparoscopic/robotic apical suspension procedures (29.7%), 60 vaginal obliterative procedures (36.4%), 47 vaginal apical suspension procedures (28.5%), and 9 isolated anterior and/or posterior colporrhaphies (5.5%), of which 9 had a concomitant incontinence procedure. Seventy-eight women (47.3%) experienced acute POUR. Thirty-one (18.8%) met the criteria for "not frail," 115 (88.5%) were "prefrail," and 19 (11.5%) were "frail." Neither frailty status nor score was associated with POUR. In an analysis of individual Fried Frailty Index components, self-reported unintentional weight loss was significantly associated with POUR (odds ratio, 4.6; 95% confidence interval, 1.23-17.15). This remained significant on multivariable logistic regression (adjusted odds ratio, 4.06; 95% confidence interval, 1.01-16.39). Frailty was not associated with POUR in older women undergoing prolapse surgery. The observed association between POUR and unintended weight loss before surgery warrants further investigation.


Iscom (immunostimulating complex) vaccines containing mono- or polyvalent pili of enterotoxigenic E. coli; immune response of rabbit and swine.
Iscom (immunostimulating complex) vaccines were prepared to contain K88ab, K88ac, K99 and 987P pili (fimbriae) of enterotoxigenic E. coli bacteria as monovalent or quadrivalent preparations. The iscoms injected into rabbits and into pigs elicited similar or higher immune response in both animal species than the oil adjuvanted vaccine containing about 5 times more of the same pilus protein. It is concluded that inclusion of pili into iscoms results in immunogenic preparations likely worth pursuing for vaccine production against enterotoxic colibacillosis of newborn pigs. The iscoms did not induce local reaction at the injection sites in contrast to the oil adjuvanted vaccines.


Influence of pixel size on quantification of airway wall thickness in computed tomography.
The purpose of this study was to determine the point where a further decrease in voxel size does not result in better automatic quantification of the bronchial wall thickness by using 2 different assessment techniques. The results from the commonly used full-width-at-half-maximum (FWHM) principle and a new technique (integral-based method [IBM]) were compared for thin-section multidetector computed tomography (MDCT) data sets from an airway phantom containing 10 different tubular airway phantoms and in a human subsegmental bronchus in vivo. Correlation with the actual wall thickness and comparison of the wall thicknesses assessed for different voxel sizes were performed, and the image resolutions were also compared subjectively. The relative error ranged from 0% (biggest phantom) to 330% (smallest phantom, biggest field of view, smaller matrix, and FWHM). Using IBM, the maximum relative error was 10% in the same setting. For FWHM, the improvement was marginal for most settings with a pixel spacing less than 0.195 x 0.195 x 0.8 mm; however, it still decreases the relative error from 290% to 273.6% for a wall thickness of 0.3 mm and a pixel spacing of 0.076 x 0.076 x 0.8 mm. (1) Using a special technique such as IBM to account for computed tomography's blurring effect in assessing airway wall thickness had the greatest impact on correct quantification. (2) The visual impression and the automatic quantification using the FWHM technique improved marginally by decreasing the voxel size to less than 0.195 x 0.195 x 0.8 mm. (3) The FWHM technique as a model for visual quantification is not reliable for airway wall thicknesses less than 1.5 mm.


Biorational control programme for the German cockroach (Blattaria: Blattellidae) in selected urban communities.
This study assessed the effectiveness of a biorational control approach using 2% hydramethylnon gel bait on German cockroaches, Blattella germanica (L.) in some residential and hospital buildings in South Western Iran. In total, three buildings consisting of 150 apartment units and 101 hospital units were monitored weekly via sticky trap for German cockroach infestations over a period of eight months. These infested units were randomly subjected to intervention and control treatments. Pamphlets and posters were provided and lectures were given to support the educational programmes as a tactic of the biorational system. Survey on cockroach index for intervention units showed 67-94% recovery to achieve clean level of infestation for intervention units of the residential buildings and 83% for the hospital. Mean percentage reductions for treatment groups throughout the 15-week treatment period were 76.8% for the residential buildings and 88.1% for the hospital, showing significant differences compared to the control groups. Linear regression of infestation rates were recorded weekly after treatment and their negative slope for treatment groups substantiated significant reductions for interventions. The results of this study showed that biorational control method, using gel bait, educational programmes and sanitation, is an effective way to manage German cockroach infestation.


Maternal morbidity associated with early-onset and late-onset preeclampsia.
To examine temporal trends in early-onset compared with late-onset preeclampsia and associated severe maternal morbidity. The study included all singleton deliveries in Washington State between 2000 and 2008 (N=670,120). Preeclampsia onset was determined using hospital records linked to birth certificates. Severe maternal morbidity was defined as any potentially life-threatening condition. Logistic regression was used to obtain adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). The preeclampsia rate was 3.0 per 100 singleton births, and increased slightly from 2.9 to 3.1 between 2000 and 2008. Rates of early-onset and late-onset disease were 0.3% and 2.7%, respectively. The temporal increase was significant only for early-onset disease (4.5%/year; 95% CI 2.3-5.8%) after adjustment for changes in maternal characteristics. Maternal death rates were higher among women with early-onset (42.1/100,000 deliveries) and late-onset preeclampsia (11.2/100,000) compared with women without preeclampsia (4.2/100,000). The rate of severe maternal morbidity (excluding obstetric trauma) was 12.2 per 100 deliveries in the early-onset group (aOR 3.7, 95% CI 3.2-4.3), 5.5 per 100 deliveries in the late-onset group (aOR 1.7, 95% CI 1.6-1.9), and approximately 3 per 100 in women without preeclampsia. Early-onset preeclampsia conferred a substantially higher risk of cardiovascular, respiratory, central nervous system, renal, hepatic, and other morbidity. However, rates of obstetric trauma were significantly lower among women with preeclampsia. Women with early-onset and late-onset preeclampsia have significantly higher rates of specific maternal morbidity compared with women without early-onset and late-onset disease. : II.


Framework for Evaluating and Developing Sustainable Telehealth Programs.
During the COVID-19 pandemic and public health emergency, telehealth programs vastly expanded with strong support from various federal and state agencies. However, the uncertainty regarding future reimbursement policies for telehealth services has resulted in concerns about long-term sustainability of innovative health service delivery models beyond the financial support. Given the limited literature on creating telehealth programs with long-term sustainability in consideration, we have developed a framework for gathering appropriate data during various stages of program implementation to evaluate clinical effectiveness and economic sustainability that is applicable across various settings, with additional attention to health equity. Recognizing the difficulty of sustaining telehealth programs solely through a fee-for-service payment model, we encourage all telehealth stakeholders, especially payers and policymakers, to consider cost-effectiveness of telehealth programs and support alternate payment models for ensuring long-term sustainability.


A Systematic Review of Care Needs for Surgical Patients with Chronic Opioid Use.
An understudied aspect of the opioid crisis with implications for nursing is care of hospitalized surgical patients with chronic opioid use. Care needs of these patients are not well understood. This systematic review identified salient care needs and explored the role of nursing in meeting these needs.


Global Changes in Secondary Atmospheric Pollutants During the 2020 COVID-19 Pandemic.
We use the global Community Earth System Model to investigate the response of secondary pollutants (ozone O3, secondary organic aerosols SOA) in different parts of the world in response to modified emissions of primary pollutants during the COVID-19 pandemic. We quantify the respective effects of the reductions in NOx and in volatile organic carbon (VOC) emissions, which, in most cases, affect oxidants in opposite ways. Using model simulations, we show that the level of NOx has been reduced by typically 40% in China during February 2020 and by similar amounts in many areas of Europe and North America in mid-March to mid-April 2020, in good agreement with space and surface observations. We show that, relative to a situation in which the emission reductions are ignored and despite the calculated increase in hydroxyl and peroxy radicals, the ozone concentration increased only in a few NOx-saturated regions (northern China, northern Europe, and the US) during the winter months of the pandemic when the titration of this molecule by NOx was reduced. In other regions, where ozone is NOx-controlled, the concentration of ozone decreased. SOA concentrations decrease in response to the concurrent reduction in the NOx and VOC emissions. The model also shows that atmospheric meteorological anomalies produced substantial variations in the concentrations of chemical species during the pandemic. In Europe, for example, a large fraction of the ozone increase in February 2020 was associated with meteorological anomalies, while in the North China Plain, enhanced ozone concentrations resulted primarily from reduced emissions of primary pollutants.


Circumstantial evidence in support of bivelocity hydrodynamic theory for mixtures.
Based upon findings with respect to the viability of the expression j(v)=-rhoD(v)nablav hypothesized to represent the constitutive equation for the diffusive volume flux in ideal binary mixtures (rho=mass density, v=1/rho=specific volume, and D(v)=volume diffusion coefficient), implicit evidence is offered in support of the recently developed theory of bivelocity continuum hydrodynamics for mixtures. Present findings for the case of mixtures add to existing evidence already available for the single-component case, thus supporting the viability of bivelocity hydrodynamic theory in general.


Intensive Periodontal Treatment Does Not Affect the Lipid Profile and Endothelial Function of Patients with Type 2 Diabetes: A Randomized Clinical Trial.
Background: Local eradication of periodontal infection could potentially have a much broader impact on the diabetic condition by also contributing to the modification of the lipid profile, which is directly compromised in the alteration of endothelium-dependent vasodilation. The aim of this trial was to assess the benefits of intensive periodontal treatment (IPT) on the lipid profile and endothelial function of diabetic patients. Methods: This was a 6-month, randomized controlled trial involving diabetic patients with generalized periodontitis. The study group comprised 290 individuals who were randomly assigned to receive Intensive Periodontal Treatment (IPT, Intervention Group) or conventional adult prophylaxis (Control Periodontal Treatment, CPT, Control Group). Outcomes encompassed lipid profile involving serum total cholesterol, serum triglyceride, low-density lipoprotein cholesterol, high-density lipo-protein cholesterol, and flow-mediated vasodilation (FMD) as an index of endothelium-dependent vasodilation (primary outcomes); periodontal indices and high-sensitive C-reactive protein were evaluated at baseline, 3 and 6 months after periodontal treatment. Results: An increase in endothelium-dependent flow-mediated dilatation (FMD) was observed in the Intensive Periodontal Treatment group in comparison with Control (p < 0.001), but results are not statistically different. There were no differences in lipid profile in individuals of both groups. Conclusions: An intensive periodontal treatment might improve endothelial function, suggesting a direct beneficial effect on the vasculature, possibly mediated by systemic inflammatory reduction. However, no statistically significant differences between groups were observed, and no benefits were proved on lipid profile.


Views of health professionals on discussing sexual issues with patients.
This survey was carried out to study the views of multidisciplinary health professionals about discussing sexual issues with patients. A questionnaire was sent to professionals (nurses, doctors, physiotherapists and occupational therapists) to return by post. A duplicate questionnaire was sent 4 weeks later to a random sample of respondents. A total of 813 replies were analysed (61% response rate). Mean age+(SD) of respondents was 37+10. Most were female (85%). Test-retest reliability of the questions showed moderate to very good agreement. Most respondents (90%) agreed that addressing sexual issues ought to be part of the holistic care of patients. However, most staff (86%) were found to be poorly trained and most (94%) were unlikely to discuss sexual issues with their patients. The gender and age of respondents was not significantly related to their participation in such discussion. Therapists had less training, lower comfort level, and less willingness to discuss sexual issues than doctors and nurses while doctors discussed sexual issues significantly often more than others (p< or =0.001). Respondents from rehabilitation wards were equivalent to those from medical or surgical wards in their training and comfort. However, they participated in discussing sexuality with patients less often than those from medical wards. Health professionals agreed that patients' sexual issues needed to be addressed and discussed in health services. However, they were poorly trained, ill prepared and rarely participated in such discussion. This suggests that training in sexuality and sexual issues should be implemented as part of the training of health care professionals.


Effect of Nystatin on the Metabolism of Xylitol and Xylose by Pachysolen tannophilus.
Ethanol production from xylitol by resting cells of Pachysolen tannophilus was increased 40-fold in the presence of nystatin, amphotericin B, and filipin, a group of antifungal agents that alter the permeability of the plasma membrane. Furthermore, these agents had little or no effect on ethanol formation from xylitol or xylose by the cell extract. During xylose metabolism, nystatin caused the intracellular xylitol to leak out into the medium at a 23-fold-faster rate but did not affect overall xylose utilization and CO(2) evolution. These observations explain the rate of xylitol utilization by cell extract being higher than that by whole cells (J. Xu and K. B. Taylor, Appl. Environ. Microbiol. 59:231-235, 1993) as well as the relative inability of P. tannophilus to utilize xylitol to support significant ethanol production and cell growth.


Pemphigus erythematosus and cutaneous epitheliotropic lymphoma in a Labrador Retriever dog.
Paraneoplastic pemphigus is an autoimmune blistering skin disease associated with concurrent neoplasia that is rarely observed in veterinary medicine. This case report presents a ten-year-old female Labrador Retriever dog with generalized seborrhea and alopecic, crusting and ulcerative lesions in the periocular and perioral regions, the lips and the groins. Hematology analysis showed a marked increase in the number of lymphocytes, while the rest of the values were normal. Skin biopsies were collected and the histological findings were consistent with pemphigus in association with an epitheliotropic lymphoma. Immunohistochemical analysis was performed. There was deposition of immunoglobulin G (IgG) in the basement membrane and in the intercellular space that corresponded with an immunostaining pattern characteristic of pemphigus erythematosus (PE). The lymphoma was positive to CD3 cells and was classified as a T-cell epitheliotropic lymphoma. To our knowledge, this is the first case of PE and cutaneous lymphoma coexisting in a dog, expanding the list of associations between immune-mediated diseases and cancer in dogs, and providing support to the eventual connection between autoimmunity and neoplasia in this species.


[Effect of ultrasound-guided serratus plane block combined with pectoral nerve block I on postoperative analgesia after radical mastectomy].
Objective: To study the effect of ultrasonic-guided serratus plane block combined with pectoral nerve block Ⅰ on postoperative analgesia after radical mastectomy. Methods: A total of 30 patients, all female, aged [M (Q1, Q3)] 53 (43, 62) years old, who underwent radical mastectomy in Beijing Tongren Hospital from May to August 2021 were selected. The patients were divided into two groups (n=15 in each group) using a random number table: general anesthesia alone+patient controlled intravenous analgesia (PCIA) group (control group) and serratus plane block combined with pectoral nerve block Ⅰ before general anesthesia+PCIA group (combined group). Numerical rating scale (NRS) at rest in both groups were detected in the post anesthesia care unit (PACU) and 4, 8, 12, 24, 36 and 48 h after operation. The time of first pain, the time of first pressing of the automatic analgesic device after the operation, the dosage of remifentanil during operation, cumulative dosages of sufentanil at 24 h and 48 h postoperatively, and the incidence of adverse effects were all recorded. Results: The NRS scores in combined group in the PACU and 4, 8, 12 and 24 h after surgery were (2.1±1.7), (1.7±1.5), (1.5±1.4), (1.5±1.3) and (1.7±1.3), respectively, while the NRS scores in control group at each time points were (4.5±2.0), (3.2±1.4), (2.7±0.9), (2.8±0.9) and (2.4±0.8), respectively, and the NRS scores in combined group were significantly lower than those in control group (all P<0.05). The NRS scores in combined group at 36 and 48 h after surgery were (1.8±1.6) and (1.6±1.2), while the NRS scores in control group were (2.2±0.9) and (2.1±0.8), and the differences between the two groups were not statistically significant (both P>0.05). The time of first pain and the time of the first pressing of the automatic analgesic device in combined group were (573±174) min and (962±313) min, which were significantly longer than those of control group [(13±6) min and (135±41) min] (both P<0.05). The dosage of remifentanil during operation and cumulative dosage of sufentanil at 24 h postoperatively in combined group were (410±129) μg and (14±4) μg, which were lower than those in control group [(580±225) μg and (21±11) μg] (both P<0.05). Cumulative dosage of sufentanil at 48 h postoperatively in combined group was (29±11) μg, while in control group was (36±14) μg, and the difference between the two groups was not statistically significant (P=0.131). The incidence of postoperative dizziness in combined group was 6.7% (1/15), which was lower than that of control group [40.0% (6/15)] (P=0.031). The incidence of nausea and pruritus was 6.7% (1/15) and 0 in combined group, while 20.0% (3/15) and 6.7% (1/15) in control group, with no statistical significance (both P>0.05). Conclusion: Serratus plane block combined with pectoral nerve block Ⅰ can effectively relieve postoperative pain, decrease the need for opioids, and reduce the incidence of adverse effects.


Functional measurements based on feature tracking of cine magnetic resonance images identify left ventricular segments with myocardial scar.
The aim of the study was to perform a feature tracking analysis on cine magnetic resonance (MR) images to elucidate if functional measurements of the motion of the left ventricular wall may detect scar defined with gadolinium enhanced MR.Myocardial contraction can be measured in terms of the velocity, displacement and local deformation (strain) of a particular myocardial segment. Contraction of the myocardial wall will be reduced in the presence of scar and as a consequence of reduced myocardial blood flow. Thirty patients (3 women and 27 men) were selected based on the presence or absence of extensive scar in the anteroseptal area of the left ventricle. The patients were investigated in stable clinical condition, 4-8 weeks post ST-elevation myocardial infarction treated with percutaneous coronary intervention. Seventeen had a scar area >75% in at least one anteroseptal segment (scar) and thirteen had scar area <1% (non-scar). Velocity, displacement and strain were calculated in the longitudinal direction, tangential to the endocardial outline, and in the radial direction, perpendicular to the tangent. In the scar patients, segments with scar showed lower functional measurements than remote segments. Radial measurements of velocity, displacement and strain performed better in terms of receiver-operator-characteristic curves (ROC) than the corresponding longitudinal measurements. The best area-under-curve was for radial strain, 0.89, where a cut-off value of 38.8% had 80% sensitivity and 86% specificity for the detection of a segment with scar area >50%. As a percentage of the mean, intraobserver variability was 16-14-26% for radial measurements of displacement-velocity-strain and corresponding interobserver variability was 13-12-18%. Feature tracking analysis of cine-MR displays velocity, displacement and strain in the radial and longitudinal direction and may be used for the detection of transmural scar. The accuracy and repeatability of the radial functional measurements is satisfactory and global measures agree.


MHC class I TCR engineered anti-tumor CD4 T cells: implications for cancer immunotherapy.
T cell immunity is critical for a protective immune response against cancers. Traditionally, this function has been ascribed to CD8 T lymphocytes with cytotoxic activity, which are restricted by MHC class I molecules. The lack of direct cytolytic effector function on part of CD4 T cells, which are MHC class II restricted, coupled with the MHC class II negative nature of most human cancers have been the main reasons for CD8 centered cancer immunotherapy approaches, so far. However, recent findings showing that CD4 T cells play an essential role towards the generation of a productive CD8 response and that the CD4 T cells can also play a direct role in anti-tumor immunity have resulted in growing enthusiasm towards engaging CD4 T cells in cancer immunotherapy. We here discuss the current approaches used for immune based cancer therapy, role of natural MHC class II-restricted CD4 T cells in tumor immunity, factors limiting the engagement of natural CD4 T cells in cancer immunotherapy protocols alongside CD8 T cells, and recent advances in TCR engineering approach to address these limitations. We will also discuss the significance of the MHC class I directed anti-tumor CD4 T cells in tumor immunity.


2,3-Bis(phenylsulfonyl)-1,3-butadiene as a reagent for the synthesis of the azatricyclic core of (+/-)-halichlorine.
An efficient stereocontrolled route to the azatricyclic core of an advanced halichlorine intermediate is described. Reaction of the oxime derived from 2-(oxo-cyclopentyl)acetic acid ethyl ester with 2,3-bis(phenylsulfonyl)-1,3-butadiene gives rise to a 7-oxa-1-azanorbornane cycloadduct in high yield. The formation of the bicyclic isoxazolidine arises from conjugate addition of the oxime onto the diene to afford a transient nitrone that then undergoes an intramolecular dipolar cycloaddition. Treatment of the cycloadduct with 5% Na/Hg results in reductive nitrogen-oxygen bond cleavage to furnish a spirocyclic piperidinone, which was further elaborated to an advanced intermediate employed in an earlier synthesis of halichlorine.


A human tetraploid pachytene spermatocyte as the possible origin of diploid sperm: a case report.
Diploid spermatozoa represent 0.2-0.3% of all spermatozoa in the normal population and cause 8.3% of diandric triploids. Errors in meiosis I and II are the most common mechanisms by which diploid spermatozoa are produced. Endoreduplication before meiosis has been suggested as a possible origin for tetraploid meiocytes, which might, in turn, produce diploid sperm. Synaptonemal complex (SC) spreads of a fertile man were immunolabelled (SCP3, MLH1 and CENP) and hybridized with subtelomere-specific multiplex fluorescent in situ hybridization (stM-FISH) assay for SCs identification. The unexpected finding of a tetraploid pachytene cell and the identification of all of its SCs demonstrate that synapsis and crossover events can occur in human tetraploid cells. Moreover, it indicates that diploid sperm may also originate from mitotic errors (endoreduplication) occurring before meiosis.


Anti-Colitic Effect of Purple Carrot on Dextran Sulfate Sodium (DSS)-Induced Colitis in C57BL/6J Mice.
The anti-colitic effect of purple carrot (PC) on 2% dextran sulfate sodium (DSS)-induced colitis in C57BL6/J mice was compared with those of yellow carrot (YC), beet (BT), and red cabbage (RC). Component analysis showed that PC contained cyanidin-3-xyloglucoside, cyanidin-3-xylosyl(sinapoly-glucosyl)galactoside, cyanidin-3-xylosyl(feruloylglucosyl) galactoside, and cyanidin-3-O-(6-O-glycosyl-2-O-xylosylgalactoside). PC diet (5% in AIN 93G diet) strongly reduced DSS-induced colon shortening and inflammatory cell infiltration in mice, followed by RC, BT, and YC diets. Treatment with PC reduced serum levels of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 as well as reduced mRNA expression in colon tissue of colitis mice in comparison with other treatments. In addition, PC treatment inhibited colonic mRNA expression of inflammatory factors such as inducible nitric oxide synthase and cyclooxygenase-2 in mice. These results suggest that PC can attenuate the inflammatory reaction in mice with DSS-induced colitis, probably due to the anthocyanins in PC.


High incidence of metastatic disease in primary high grade and large extremity soft tissue sarcomas treated without chemotherapy.
The risk of metastasis and the survival in patients with primary extremity soft tissue sarcomas is worse when tumour size is large and the grade of malignancy is high. Such tumours may receive chemotherapy and/or radiation therapy (RTX) for optimising local control. Irradiation can either be applied preoperatively or after tumour resection. The question arises if the kind of RTX in the absence of chemotherapy influences the outcome concerning local control, metastatic disease, survival and complications. We retrospectively reviewed the clinical outcome of 233 patients with a primary extremity soft tissue sarcoma treated between 1990 - 2000 with a mean follow-up of 35.8 (4-120) months in our institute. 41 patients had high grade, deep and large tumours (>8 cm), an AJCC stage III (no evidence of metastasis prior to treatment) and were treated with limb salvage surgery and irradiation but stayed without additional chemotherapy. Two groups of patients were compared: the first group received postoperative RTX after tumour resection (n = 33); the second group was treated with preoperative RTX (n = 8). Both groups did not differ concerning clinical parameters. We analysed primary and secondary outcomes. 56% (23/41) of the population developed metastatic disease, 24% (10/41) local recurrence. The risk of metastasis was higher in the group with preoperative irradiation (p = 0.046). The overall (p = 0.0248) and relapse free survival (p = 0.104) were worse in this group. The delay to tumour resection amounted 8 weeks on average in the preoperative group. Local control was not different (p = 0.38) in both study groups. Wound infections and other combined therapy related complications were equally distributed (p = 0.22). Without chemotherapy there remains a high risk of metastasis in AJCC grade 3 patients. In high risk patients treated without chemotherapy the elapsed time to tumour resection after preoperative radiation might contribute to the development of metastasis. This outcome may support the thesis that a combination of RTX and offensive multimodal treatment protocols is advantageous in such a subset of patients.


Magnetite-loaded carrier erythrocytes as contrast agents for magnetic resonance imaging.
Superparamagnetic iron oxide nanoparticles (SPIONs) are commonly used in magnetic resonance imaging (MRI), but their fast phagocytosis makes them less than ideal for this application. To circumvent the lymphocyte-macrophage system, we encapsulated SPIONs into red blood cells (RBCs). For loading, the RBC's membrane was opened by swelling under hypoosmotic conditions and subsequently resealed. In this work, we demonstrate that SPIONs can be loaded into RBCs in a concentration sufficient to obtain strong contrast enhancement in MRI.


Differential beta-arrestin binding of AT1 and AT2 angiotensin receptors.
Agonist stimulation of G protein-coupled receptors causes receptor activation, phosphorylation, beta-arrestin binding and receptor internalization. Angiotensin II (AngII) causes rapid internalization of the AT1 receptors, whereas AngII-bound AT2 receptors do not internalize. Although the activation of the rat AT1A receptor with AngII causes translocation of beta-arrestin2 to the receptor, no association of this molecule with the AT2 receptor can be detected after AngII treatment with confocal microscopy or bioluminescence resonance energy transfer. These data demonstrate that the two subtypes of angiotensin receptors have different mechanisms of regulation.


Bioequivalence assessment of metformin hydrochloride using a limited sampling strategy.
The aim of this study was to develop a limited sampling strategy (LSS) that can be used to assess the bioequivalence of two metformin hydrochloride preparations. Healthy subjects (n = 20) enrolled in the bioequivalence study received a single oral tablet of 1,000 mg metformin reference formulation or test formulation. The plasma concentration of metformin was determined using a validated HPLC method. A multiple linear regression analysis of the observed metformin Cmax and AUC0-24 versus the concentration of reference formulation was performed to develop LSS models for estimating these parameters. The models were internally validated by the Jackknife method. The best models were employed to assess the bioequivalence of the two metformin formulations. The linear relationship between pharmacokinetic parameters and a single concentration point was poor. Several models for the estimation of these parameters met the predefined criteria (r2 > 0.9). The Jackknife validation procedure revealed that LSS models based on two sampling times - C1.5 and C2 for Cmax; C4.0 and C10.0 for AUC0-24 - were accurate predictor of Cmax and AUC0-24. Prediction errors (PE) were less than 2%, and absolute prediction errors (AE) were less than 10%. PEs beyond 15% occurred in less than 5% of total samples. The bioequivalence assessment of the two metformin formulations, based on the best LSS models, provided results similar to those obtained using all the observed concentration-time data points, and indicated that the two metformin formulations were bioequivalent. A LSS method for assessing the bioequivalence of metformin formulations was established and proved to be applicable and accurate. This LSS method could be considered appropriate for a metformin bioequivalence study, providing an inexpensive cost of sampling acquisition and analysis.


Quality of different chondroitin sulfate preparations in relation to their therapeutic activity.
Chondroitin sulfate is currently recommended by the European League Against Rheumatism (EULAR) as a SYSADOA (symptomatic slow acting drug for osteoarthritis) in Europe in the treatment of knee and hand osteoarthritis based on research evidence and meta-analysis of numerous clinical studies. Furthermore, recent clinical trials demonstrated its possible structure-modifying effects. Chondroitin sulfate, alone or in combination with glucosamine or other ingredients, is also utilized as a nutraceutical in dietary supplements in Europe and the USA. However, it is derived from animal sources by extraction and purification processes. As a consequence, source material, manufacturing processes, the presence of contaminants and many other factors contribute to the overall biological and pharmacological actions of these agents. We aim to review the quality control of chondroitin sulfate in pharmaceutical-grade preparations and nutraceuticals. Pharmaceutical-grade formulations of chondroitin sulfate are of high and standardized quality, purity and properties, due to the stricter regulations to which this drug is subjected by local national health institutes as regards production and characteristics. On the contrary, as several published studies available in literature indicate, the chondroitin sulfate quality of several nutraceuticals is poor. Additionally, there are no definite regulations governing the origin of the ingredients in these nutraceuticals and the origin of the ingredients in natural products is the most important factor ensuring quality, and thus safety and efficacy, in particular for chondroitin sulfate, due to its extraction from different sources. Due to the poor chondroitin sulfate quality of some nutraceuticals, we conclude that stricter regulations regarding their quality control should be introduced to guarantee the manufacture of high quality products for nutraceutical utilization and to protect customers from low-quality, ineffective and potentially dangerous products. There is a need for specific and accurate analytical procedures, which should be enforced to confirm purity and label claims both for raw materials and finished chondroitin sulfate products, and also to govern the origin of ingredients. Until these stricter regulations are in place, then it is strongly recommended that pharmaceutical-grade chondroitin sulfate is used rather than food supplements.


Rho kinase inhibition enhances axonal regeneration in the injured CNS.
Myelin-associated inhibitors limit axonal regeneration in the injured brain and spinal cord. A common target of many neurite outgrowth inhibitors is the Rho family of small GTPases. Activation of Rho and a downstream effector of Rho, p160ROCK, inhibits neurite outgrowth. Here, we demonstrate that Rho is directly activated by the myelin-associated inhibitor Nogo-66. Using a binding assay to measure Rho activity, we detected increased levels of GTP Rho in PC12 and dorsal root ganglion (DRG) cell lysates after Nogo-66 stimulation. Rho activity levels were not affected by Amino-Nogo stimulation. Rho inactivation with C3 transferase promotes neurite outgrowth of chick DRG neurons in vitro, but with the delivery method used here, it fails to promote neurite outgrowth after corticospinal tract (CST) lesions in the adult rat. Inhibition of p160ROCK with Y-27632 also promotes neurite outgrowth on myelin-associated inhibitors in vitro. Furthermore, Y-27632 enhances sprouting of CST fibers in vivo and accelerates locomotor recovery after CST lesions in adult rats.


Factors Influencing the Consumption of Seaweed amongst Young Adults.
Seaweed has been traditionally consumed in Asian and Pacific cultures, yet aside from sushi, is still not commonly eaten in Western societies. Edible seaweeds offer distinct nutritional benefits to terrestrial crops, particularly with respect to mineral and fibre content. Understanding the motivations that drive young Australians to eat seaweed is necessary for food product development and consumer marketing strategies, as well as informing future sustainable production through seaweed aquaculture and wild-harvest practices. An observational cross-sectional online survey with n = 1403 young (19-30 years) Australian seaweed consumers was conducted. The 19-item survey included closed-ended, open-ended, and Likert scale responses. Most respondents were female (89.0%), with tertiary level education or above (57.7%). Seaweed was eaten mostly as a snack (87.7%) and in home-prepared meals (30.7%). The key advantages to consumption were flavour (89.1%), nutrient content (49.1%), and health benefits (44.6%), whilst the key barriers were poor accessibility (59.5%), unaffordable pricing (46.5%), and undesirable packaging (19.0%). The consumers reported wanting more promotion to improve their knowledge about seaweed, in addition to environmentally sustainable packaging and sourcing. Pathways to overcome barriers and encourage greater seaweed consumption are discussed. Most critically, improving the promotion and environmental sustainability of seaweed products will improve intake amongst current and future consumers.


Potency measurements of the complement system facilitated by antibodies targeting the zymogen form of complement factor D (Adipsin).
The serine protease complement factor D is fundamental in the activation of the complement system. In addition, it was the first adipokine described (named Adipsin) and shown to improve beta cell function in diabetes. As part of an amplification loop of complement activation, factor D is a rate-limiting enzyme, and its accessibility contributes to the potency of complement activation. The dogma has been that conversion of the zymogen form, profactor D, to mature factor D occurred during secretion by adipocytes by uncharacterized proteases. However, recent findings demonstrated that the serine protease MASP-3 of the lectin pathway of the complement system mediated this conversion, suggesting that pattern recognition of pathogen/danger-associated molecular patterns could be a prior requirement for all complement activation. To facilitate studies addressing this hypothesis, we have developed monoclonal antibodies specific for human profactor D without binding to mature factor D. We demonstrate their applications in accessing the conversion of profactor D into mature factor D and in measuring levels of profactor D.


Heterozygous hypobetalipoproteinemia with fasting chylomicronemia.
We describe a disorder in which low-density lipoprotein (LDL)-cholesterol and apolipoprotein B are in low concentration (0.47 mmol/L and 0.28 g/L, respectively) and chylomicrons are still present in plasma after an 18-h fast. The d less than 1.006 fraction was isolated by flotation ultracentrifugation and the apolipoproteins were analyzed by electrophoresis, immunoblotting with anti-apolipoprotein B-100 antiserum, and isoelectric focusing. In the d less than 1.006 fraction of the fasting serum, we found an apolipoprotein B form with the same apparent molecular mass as apolipoprotein B-48 and similar in amount to apolipoprotein B-100 (respective percentages, 46% and 54%). The monosialylated form of the apolipoprotein C-III was severely decreased. After an oral fat load, the repartition of the two species of apolipoprotein B did not change greatly (respective percentages, 60% and 40%), and the concentration of serum triglyceride increased only from 1.20 to 1.65 mmol/L.


LR White sections as slot grid support films for transmission electron microscopy.
The utility of LR White sections as slot grid support films for the examination of thin resin-embedded tissue sections by transmission electron microscopy was investigated and compared with traditional formvar-carbon films. Throughout a variety of staining procedures, which involved the use of organic solvent, oxidizing agents, strong acid and prolonged incubation, LR White support films remained intact and the attached tissue sections remained adherent. By contrast, complete loss of formvar-carbon support films occurred in 25% of preparations during routine staining with aqueous reagents. This loss increased to 62% following staining with either alcoholic or oxidizing and acidic stains, and to 66% following prolonged (immunohistochemical) staining. Tissue contrast, ultrastructural detail and immunohistochemical staining intensity were comparable between sections on the two types of support film. The use of LR White sections as support films for slot grids represents a quick, cheap, simple and robust alternative to traditional support films and, furthermore, requires no carbon coating.


The role of excitatory amino acids in neuropsychiatric illness.
Over the past several years, research has demonstrated that the excitatory amino acids serve as the major excitatory neurotransmitters in cerebral cortex and hippocampus. Neurons that contain excitatory amino acids play crucial roles in neuropsychological functioning, learning, and memory. In addition, these neurons exert descending control over subcortical structures that is behaviorally antagonistic to the effects mediated by the ascending dopaminergic system. Disturbances of excitatory amino acid systems may contribute to the pathogenesis of schizophrenia and to other neuropsychiatric syndromes associated with delirium or dementia.


Predictors of 1-year outcomes of major depressive disorder among individuals with a lifetime diagnosis: a population-based study.
Examining predictors of the outcomes of major depressive disorder (MDD) is important for clinical practice and population health. There are few population-based longitudinal studies on this topic. The objectives of this study were to (1) estimate the proportions of persistent and recurrent MDD among those with MDD over 1 year, and (2) identify demographic, socio-economic, workplace psychosocial and clinical factors associated with the outcomes. From a population-based longitudinal study of the working population, participants with a lifetime diagnosis of MDD were selected (n=834). They were classified into two groups: those with and those without current MDD. The proportions of 1-year persistence and recurrence of MDD were estimated. MDD was assessed by the World Health Organization (WHO) Composite International Diagnostic Interview, CIDI-Auto 2.1, by telephone. The proportions of persistent and recurrent MDD in 1 year were 38.5% [95% confidence interval (CI) 31.1-46.5] and 13.3% (95% CI 10.2-17.1) respectively. Long working hours, negative thinking and having co-morbid social phobia were predictive of persistence of MDD. Perceived work-family conflict, the severity of a major depressive episode and symptoms of depressed mood were significantly associated with the recurrence of MDD. Clinical and psychosocial factors are important in the prognosis of MDD. The factors associated with persistence and recurrence of MDD may be different. More large longitudinal studies on this topic are needed so that clinicians may predict potential outcomes based on the clinical profile and provide interventions accordingly. They may also take clinical action to change relevant psychosocial factors to minimize the chance of persistence and/or recurrence of MDD.


Probiotic fermentation of plant based products: possibilities and opportunities.
Functional foods are claimed to have several health-specific advantages. In addition to their basic nutritive value, they contain a proper balance of ingredients which help in the prevention and treatment of illnesses and diseases. Within this category, products containing lactic acid bacteria or probiotics are increasingly gaining importance. The recognition of the beneficial effects of dairy products containing probiotics has been well established. The allergy to dairy products, lactose intolerance, and cholesterol content are the major drawbacks related to the use of fermented dairy products for a large percentage of consumers. Modern consumers are increasingly interested in their personal health, and expect the food that they eat to be healthy or even capable of preventing illness. Because of this, probiotic food products made out of fermentation of cereals and fruits and vegetables is receiving attention from the scientific world as well as consumers and constitutes the major part of this review. The use of mathematical models for the probiotic fermentation will help in reducing the time and effort involved in the optimization of the probiotic fermentation process. We have tried to summarize the developments in the use of mathematical models for probiotic fermentation. Future technological prospects exist in innovations which represent solutions for the stability and viability problems of probiotics in new food environments. Current research on novel probiotic formulations and microencapsulation technologies exploiting biological carrier and barrier materials has also been discussed.


[Effect of glucocorticoids and adrenaline on insulin receptors in plasma membranes and nuclear envelopes of the rat liver].
To elucidate the course of regulation of insulin receptors in nuclear envelope and its relationship with insulin receptors in the plasma membrane a comparative study of these receptors in both subcellular fractions was conducted under the influence of the involved cell surface receptor factor. It is found that under adrenalectomy the number of nuclear envelope receptors and degree of their affinity did not increase as this occurs in plasma membrane receptors. Hydrocortisone replacement therapy in these animals lowers the receptor number in the both fractions. Hydrocortisone-induced hypercorticism does not change 125I-insulin binding by nuclear envelope but decreases its binding (accounted for the number of receptors and affinity) by the plasma membrane. Under hyperadrenalinemia the number of receptors decreases in the both subcellular fractions. The results suggest no independent regulation of insulin receptors on the surfaces of nuclei and cells.


Fewer Basins Will Follow Their Budyko Curves Under Global Warming and Fossil-Fueled Development.
The Budyko framework consists of a curvilinear relationship between the evaporative ratio (i.e., actual evaporation over precipitation) and the aridity index (i.e., potential evaporation over precipitation) and defines evaporation's water and energy limits. A basin's movement within the Budyko space illustrates its hydroclimatic change and helps identify the main drivers of change. On the one hand, long-term aridity changes drive evaporative ratio changes, moving basins along their Budyko curves. On the other hand, historical human development can cause river basins to deviate from their curves. The question is if basins will deviate or follow their Budyko curves under the future effects of global warming and related human developments. To answer this, we quantify the movement in the Budyko space of 405 river basins from 1901-1950 to 2051-2100 based on the outputs of seven models from the Coupled Model Intercomparison Project - Phase 6 (CMIP6). We account for the implications of using different potential evaporation models and study low- and high-emissions scenarios. We find considerable differences of movement in Budyko space regarding direction and intensity when using the two estimates of potential evaporation. However, regardless of the potential evaporation estimate and the scenario used, most river basins will not follow their reference Budyko curves (>72%). Furthermore, the number of basins not following their curves increases under high greenhouse gas emissions and fossil-fueled development SP585 and across dry and wet basin groups. We elaborate on the possible explanations for a large number of basins not following their Budyko curves.


[Sample selection in epidemiologic studies].
Problems with sample selection in epidemiological studies starts with the definition of representativeness of the sample. The definition of representativeness as a "miniature of the population" is impractical, especially for very rare disease, and not suitable for certain types of epidemiological studies. More plausible are operational definitions, which refer to certain statistical features of the sample or to the sampling method suitable for the study design. The article reviews different meanings of representativeness used directly or implicitly in epidemiological and statistical studies and gives examples of certain methods of sample selection for the specific purposes including matching in design. Some important sources of selection bias and methods of avoiding it are also addressed in this article.


Mobility of multiwalled carbon nanotubes in porous media.
Engineered multiwalled carbon nanotubes (MWCNTs) are the subject of intense research and are expected to gain widespread usage in a broad variety of commercial products. However, concerns have been raised regarding potential environmental and human health risks. The mobility of MWCNTs in porous media is examined in this study using one-dimensional flow-through column experiments under conditions representative of subsurface and drinking water treatment systems. Results demonstrate that pore water velocity strongly influenced MWCNT transport, with high MWCNT mobility at pore water velocities greater than 4.0 m/d. A numerical simulator, which incorporated a newly developed theoretical collector efficiency relationship for MWCNTs in spherical porous media, was developed to model observed column results. The model, which incorporated traditional colloid filtration theory in conjunction with a site-blocking term, yielded good agreement with observed results in quartz sand-packed column experiments. Experiments were also conducted in glass bead-packed columns with the same mean grain size as the quartz sand-packed columns. MWCNTs were more mobile in the glass bead-packed columns.


The effects of occupant age on patterns of rib fractures to belt-restrained drivers and front passengers in frontal crashes in Japan.
The injuries sustained by elderly car occupants in traffic accidents are usually more severe than those of younger occupants. Accident statistics data show that injuries to elderly occupants frequently occur in the chest. Belted drivers and front seat passengers in cars involved in frontal collisions were investigated using detailed data on traffic accidents in Japan. From a total of 246 vehicle occupants, the total number of injuries among the 167 occupants listed as injured was 462. Most of the injuries to the chest were minor ones such as skin abrasions or contusions. However, 21 occupants sustained rib fractures and 7 persons even sustained internal organ injuries. Younger occupants appeared not to sustain rib fractures even in higher impact collisions. Conversely, elderly occupants frequently experienced rib fractures near the seat belt line even under lower impact severity. It was also typically observed that rib fractures in case of airbag deployment were more often found in the lower part of chest compared with those cases of seat belt restraint alone. Symptoms of these differences in injury are described in detail in consideration of the gender and age of occupants, airbag deployments, and accident severity. In addition, regression analysis was carried out to evaluate the influence of age on rib fractures. Results show that rib fractures in elderly occupants occur at a delta V 30 km/h lower than that of younger occupants.


Di (2-ethylhexyl) Phthalate Exposure Impairs Growth of Antral Follicle in Mice.
Di (2-ethylhexyl) phthalate (DEHP) is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 μg/kg DEHP every 5 days from postnatal day 0 (0 dpp) to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative) related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and γH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox-sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre-pubertal stage in mice.


Bioavailability of glycitein relatively to other soy isoflavones in healthy young Caucasian men.
Glycitein is a Selective Estradiol Receptor Modulator (SERM) from soy. The study reports plasma bioavailability and urine excretion of glycitein compared to other soy isoflavones after a unique intake of food supplement based on soy germ containing 55.24mg isoflavones. Eighteen plasma and urinary sampling profiles collected over 48h from healthy young Caucasian men were analysed using specific ELISAs. Eight profiles contained equol. Glycitein T(max), C(max), AUC(0→24h) and T(½) in plasma were calculated. Urine T(max), % of excretion at 24h and clearance were assessed. Glycitein is one of the best absorbed flavonoids. Plasma steady-state level can be achieved by several intakes a day. Glycitein bioavailability is similar to that of daidzein and its urinary excretion is significantly higher than that of genistein. Equol does not affect glycitein bioavailability. Knowing glycitein bioavailability in man is essential for the development of soy-germ-based food supplements for health applications.


Prenatal detection of chromosomal abnormalities and copy number variants in fetuses with corpus callosum agenesis.
The corpus callosum is the main pathway that connects interhemispheric communication. Agenesis of corpus callosum (ACC) have not consistently detected replicate genetic risk factors, potentially due to Etiological heterogeneity of this trait. This study aimed to retrospectively analyze the molecular basis for the ACC and the potential genotyping-phenotyping association and provide the basis for genetic counselling. Karyotyping and chromosomal microarray analysis were performed for copy number variants. Three cases had 1p36 deletions, two cases had 2q31.2 and 2p16.3 microdeletions, one case had microdeletion of Xq26.3q27.1, five cases involved derived chromosomes due to unbalanced translocations. These cases had variable deletions and duplications with partial overlapping. Phenotypically, besides agenesis of corpus callosum and other brain morphological abnormalities as well as heart abnormalities. ACC may occur alone or be related to other abnormal clinical phenotypes, and its genetic mechanism is very complicated. These results revealed ACC is associated with a variety of chromosomal abnormalities. The findings of the present study expand the genotypes associated with ACC, and further delineation of the genotype-phenotype correlations for ACC. With current applications of chromosome microarray analysis, congenital submicroscopic copy-number variations in fetuses can be detected more effectively.


Optimization of asymmetric catalysts using achiral ligands: metal geometry-induced ligand asymmetry.
[reaction: see text] Traditionally, asymmetric catalysts have been optimized by modification of resolved chiral ligands. In this Letter, we optimize the asymmetric addition of diethylzinc to aldehydes by modification of achiral methylene bis(phenol) ligands. Upon coordination of the substrate, the achiral ligand becomes asymmetric, a concept termed Metal Geometry-Induced Ligand Asymmetry. The enantioselectivity of the catalyst formed from a single resolved ligand and several achiral ligands ranged from 9% (R) to 83% (S).


Older Adults' Perceived Barriers to Participation in a Falls Prevention Strategy.
There is a need to increase older adults' access and adherence to falls prevention strategies. This study aims to explore older adults' perceived barriers to participation in a fall prevention strategy. A qualitative descriptive approach was used. Semi-structured interviews were conducted with 18 older adult users of a Day Care Unit from a Private Institution of Social Solidarity in the region of Lisbon and Tagus Valley in Portugal. The recruitment was made in September 2019. The interviews were recorded transcribed verbatim and analysed thematically using the method of constant comparisons. The barriers to participation in a fall prevention strategy are healthcare system gaps, social context, economic context, health status, psychological capability, and lack of knowledge to demystify myths and misconceptions about falls. There are different barriers to participate in a fall prevention strategy. It is urgent to eliminate or reduce the effect of these barriers to increase older adults' participation in fall prevention strategies.


Triceps Tendon Repair.
Although triceps tendon ruptures can result from a traumatic incident, chronic overuse causing degenerative changes to the insertion and leading to a complete or partial rupture is more common. In our practice, we have found that anabolic steroid abuse by weightlifters is the most common predisposing factor. The initial diagnosis is often missed. A thorough clinical examination is imperative to avoid missing a partial or complete rupture. Ultrasound or magnetic resonance imaging can confirm the diagnosis. Early diagnosis increases the chance of a direct repair. Operative treatment with direct repair is usually indicated for full-thickness or large partial-thickness tears. Direct repair may be possible for selected chronic tears. Triceps tendon repair is performed with the following steps.Step 1: The patient is placed in lateral decubitus.Step 2: The stump is debrided, and retraction of the tendon is evaluated.Step 3: Two crossed bone tunnels are drilled, and an anchor is placed centrally in the olecranon.Step 4: The elbow is extended, and the tendon is reduced and sutured centrally to the anchor and medially and laterally with use of the sutures from the bone tunnels.Step 5: The elbow is flexed to evaluate tension. If gapping occurs, the repair should be reinforced with extra sutures. Tension-free range of motion will guide postoperative rehabilitation.Step 6: A posterior splint is applied in the operating room with the elbow extended.Step 7: A dynamic brace is applied on the first postoperative day. Extension is free but flexion is blocked at the tension-free range; 30° of extra flexion is permitted every 2 weeks. Full flexion is always allowed after 6 weeks. Strengthening starts at 3 months. Pitfalls of the procedure include difficulty in differentiating between tendon and scar in subacute and chronic ruptures. It may not be possible to directly repair the triceps back to bone, and a graft may be needed to reconstruct the tendon. It is important to know where the ulnar nerve is and to release it if needed. It is important not to debride past the cortical surface of the olecranon if an anchor is used because, if this is done, fixation may be insufficient. The anchor should be predrilled as the cortical bone of the tip of the olecranon is very dense. Reruptures occur in up to 21% of cases. A functional range of motion is usually achieved with an average loss of extension of 10° and average flexion to 136°. At 1 year, one can expect a peak strength of approximately 80% of that on the uninjured side and endurance strength of 99%1.