Sclerosing epithelioid fibrosarcoma of the bone: a case report of high resistance to chemotherapy and a survey of the literature.
Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue sarcoma mostly occurring in extraosseous sites. SEF represents a clinically challenging entity especially because no standardized treatment regimens are available. Intraosseous localization is an additional challenge with respect to the therapeutical approach. We report on a 16-year-old patient with SEF of the right proximal tibia. The patient underwent standardized neoadjuvant chemotherapy analogous to the EURAMOS-1 protocol for the treatment of osteosarcoma followed by tumor resection and endoprosthetic reconstruction. Histopathological analysis of the resected tumor showed >90% vital tumor cells suggesting no response to chemotherapy. Therefore, therapy was reassigned to the CWS 2002 High-Risk protocol for the treatment of soft tissue sarcoma. To date (22 months after diagnosis), there is no evidence of relapse or metastasis. Our data suggest that SEF may be resistant to a chemotherapy regimen containing Cisplatin, Doxorubicin, and Methotrexate, which should be considered in planning treatment for patients with SEF.


Keratinocyte growth factor improves repair in the injured tracheal epithelium.
Keratinocyte growth factor (KGF) is a critical growth factor in lung development and is a protective agent after lung injury, although the exact mechanisms of this protective effect have not yet been elucidated. Our laboratory has shown that circulating epithelial progenitor cells can traffic to the airway and that they appear to be derived from the bone marrow. On this basis, we hypothesized that KGF and its putative receptor (KGFR) would be important to these cells. We showed that the KGFR, which is found almost exclusively on epithelial cells, was present on cells in the bone marrow and circulation of mice that identified a subpopulation of cytokeratin 5+ circulating epithelial progenitor cells (CEPC). In addition, the KGFR co-localized with a population of cytokeratin 5+ basal cells in the repairing proximal airway. Systemic administration of KGF resulted in a significant increase in mobilization of cytokeratin 5+ CEPC at 6 h after injection. Administration of KGF to mouse recipients of heterotopic syngeneic tracheal transplants resulted in protection and more rapid repair of the tracheal epithelium, with an increase in the number of CEPC in the epithelium of the airway, and this effect was abrogated by blocking CEPC with anti-CXCL12 antibodies. KGF therefore appears to be an important growth factor for local resident progenitor epithelial cell repair and for mobilization and enhanced engraftment of CEPC to the injured proximal airway epithelium.


Critical Factors Favoring Outward Physician Migration from an Affluent Gulf Country.
Physician retention is essential to creating a strong and stable healthcare system worldwide. The density of physicians and nurses significantly impacts important population health outcomes. Globalization has enabled the mobility of physicians, but the recruitment and retention of quality physicians have not been without challenges. The purpose of this study was to identify the outward migration factors affecting expatriate physicians who have resided and worked in the United Arab Emirates (UAE) for at least 5 years, as compared with newly emigrated physicians. This physician population has likely adapted to the local environment and actively contributed to the advancement of medical care in the country; their attrition is a significant loss to the UAE healthcare system. A 23-point validated survey questionnaire, consisting of four domains, was electronically administered to the participants (n = 374), and responses were statistically analyzed, using descriptive statistics and the Chi-square test. Our results indicate that all physicians considered a ten-year visa to be factor contributing to retention, more so for the recent physician migrants to the UAE. Professional development opportunities, career-specific plans and income promoted only short-term retention of physicians in the UAE. Non-financial factors related to living and working conditions prevented migration of physicians who lived in the country for more than five years. Lifestyle-related factors are an important consideration in long-term retention of physicians in the UAE. Initiatives to promote career advancement and improve job satisfaction for mid- and late-career clinicians are necessary to set the foundation for a robust physician retention policy and to enhance the quality of the healthcare system. Long-term visas provide an additional factor for retention.


Comparative photobiology of growth responses to two UV-B wavebands and UV-C in dim-red-light- and white-light-grown cucumber (Cucumis sativus) seedlings: physiological evidence for photoreactivation.
We examined the influence of short-term exposures of different UV wavebands on the elongation and phototropic curvature of hypocotyls of cucumbers (Cucumis sativus L.) grown in white light (WL) and dim red light (DRL). We evaluated (1) whether different wavebands within the ultraviolet B (UV-B) region elicit different responses; (2) the hypocotyl elongation response elicited by ultraviolet C (UV-C); (3) whether irradiation with blue light-enriched white light (B/WL) given simultaneous with UV-B treatments reversed the effect of UV in a manner indicative of photoreactivation; and (4) whether responses in WL-grown plants were similar to those grown in DRL. Responses to brief (1-100 min) irradiations with three different UV wavebands all induced inhibition of elongation measured after 24 h. When WL-grown seedlings were irradiated with light containing proportionally greater short wavelength UV-B (37% of UV-B between 280 and 300 nm), inhibition of hypocotyl elongation was induced at a threshold of 0.5 kJ m(-2), whereas exposure to UV-B including only wavelengths longer than 290 nm (and only 8% of UV-B between 290 and 300 nm) induced inhibition of hypocotyl elongation at a threshold of 1.6 kJ m(-2). The UV-C treatment induced reduction in elongation at a threshold of <0.01 kJ m(-2) for DRL-grown plants and <0.03 kJ m(-2) for WL-grown plants. B/WL caused 50% reversal of the short-wavelength UV-B-induced inhibition of elongation in DRL-grown seedlings but did not reverse the effect of long-wavelength UV-B. B/WL caused 30% reversal of the UV-C-induced inhibition of elongation in WL-grown seedlings but did not affect the response to short-wavelength UV-B. Short-wavelength UV-B also induced positive phototropic curvature in both types of seedlings, and this was reversed 60% or completely in DRL-grown and WL-grown seedlings, respectively. The similarity of responses between the etiolated (DRL-grown) and de-etiolated (WL-grown) seedlings indicates that the short-wavelength specific response may be relevant to natural light environments, and the apparent photoreactivation implicates DNA damage as the sensory mechanism for the response.


Lychee pulp phenolics ameliorate hepatic lipid accumulation by reducing miR-33 and miR-122 expression in mice fed a high-fat diet.
Dietary phenolics exhibit hypolipidemic activity by changing lipid metabolism-related microRNA (miRNA) expression. Quercetin 3-O-rutinoside-7-O-α-l-rhamnosidase (quercetin 3-rut-7-rha), rutin and (-)-epicatechin are the main phenolics in lychee (Litchi chinensis Sonn.) pulp. A previous study reported that quercetin 3-rut-7-rha and rutin had hypolipidemic effects. To elucidate these effects and the underlying molecular mechanisms of lychee pulp phenolics (LPPs), the hepatic mRNA and protein expression of lipid metabolism-related genes and their associated miRNAs were measured after ten weeks of treatment with a high-fat diet (HFD) alone or in combination with LPPs. The administration of LPPs significantly reduced the HFD-induced increase in serum total cholesterol and triglyceride levels but increased the HDL-c content. The mRNA and protein expression levels of hepatic adenosine triphosphate-binding cassette transporter A1 (ABCA1) and carnitine palmitoyltransferase 1a (CPT1a) were upregulated, while fatty acid synthase (FAS) mRNA and the corresponding protein expression levels were downregulated by LPPs. Furthermore, the expression levels of miR-33, which directly modulates ABCA1 and CPT1a, and miR-122, which indirectly regulates FAS, were downregulated in mouse hepatocytes. The repression of miR-33 and miR-122 is a possible molecular mechanism of the hypolipidemic effects of LPPs in the liver. Our results suggest a novel hypolipidemic mechanism of LPPs.


Immunogenicity of xenogeneic cartilage matrix components in a rabbit model.
Purified xenogeneic cartilage matrix components, including proteoglycan subunits, chondroitin 4 sulfate, and chondroitin 6 sulfate, were inoculated into the knee joint of rabbits, and local as well as systemic responses were evaluated. proteoglycan was associated with synovial hyperplasia and infiltrates of eosinophils and lymphocytes and with rising titers of antiproteoglycan antibodies in a tanned sheep rbc hemagglutination assay over a six-week period of weekly intra-articular injections and observations. Chondroitin sulfates failed to evoke detectable changes in the joint or serum. Immunogenicity of cartilage matrix components may play a role in allogeneic and xenogeneic osteochondral grafts, and it is also possible that autogenous matrix immunogens exist and contribute to progression of degenerative joint disease. The immunogenicity of allogeneic and autogenous cartilage matrix components remains undefined.


Progress in clinical oncolytic virus-based therapy for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) carries a dismal prognosis, with advanced disease being resistant to both radiotherapy and conventional cytotoxic drugs, whilst anti-angiogenic drugs are marginally efficacious. Oncolytic viruses (OVs) offer the promise of selective cancer therapy through direct and immune-mediated mechanisms. The premise of OVs lies in their preferential genomic replication, protein expression and productive infection of malignant cells. Numerous OVs are being tested in preclinical models of HCC, with good evidence of direct and immune-mediated anti-tumour efficacy. Efforts to enhance the performance of these agents have concentrated on engineering OV cellular specificity, immune evasion, enhancing anti-tumour potency and improving delivery. The lead agent in HCC clinical trials, JX-594, a recombinant Wyeth strain vaccinia virus, has demonstrated evidence for significant benefit and earned orphan drug status. Thus, JX-594 appears to be transcending the barrier between novel laboratory science and credible clinical therapy. Relatively few other OVs have entered clinical testing, a hurdle that must be overcome if significant progress is to be made in this field. This review summarizes the preclinical and clinical experience of OV therapy in the difficult-to-treat area of HCC.


Lidocaine versus mepivacaine in sedated pediatric dental patients: randomized, prospective clinical study.
Dental anxiety is usually seen in the pediatric patients. specially in the case of minor oral surgical procedures and exodontia, cooperation of the patients and their families with the dentist will lead to superior treatment outcomes. Pain control is important in dentistry. The aim of this randomized prospective clinical study is to compare the local anaesthetic and haemodynamic effects of 2% lidocaine (Group 1) and 3% mepivacaine (Group 2) in sedated pediatric patients undergoing primary tooth extraction. 60 pediatric patients undergoing sedation for elective primary tooth extraction was prospectively included in the study in a randomized fashion. Inclusion and exclusion criteria were assigned. Patients were given premedication via oral route. Local anesthesia was achieved before extraction(s). There were no significant differences between the groups in patient demographics, number of teeth extracted, duration of the operation and time from the end of the procedure to discharge (p ≥ 0.05). FLACC pain scale scores were not statistically significant between the groups, except at 20 minutes post-operatively when the score is significantly lower in Group 2 (p=0.029). Prevention of pain during dental procedures can nurture the relationship of the patient and dentist. Tooth extraction under sedation in pediatric patients could be safe with both local anesthetics.


Transgenic overexpression of laminin alpha1 chain in laminin alpha2 chain-deficient mice rescues the disease throughout the lifespan.
Several approaches to treat laminin alpha2 chain-deficient congenital muscular dystrophy (MDC1A) in mouse models have been undertaken. Most have shown promising results in young animals. However, older animals have only been characterized to some extent. Herein we analyze the lifespan of laminin alpha2 chain-deficient mice with transgenic overexpression of laminin alpha1 chain. Further outcome measures included internalized myonuclei, heart fibrosis, grip strength, and serum creatine kinase activity. We show that laminin alpha2-chain-deficient animals that overexpress laminin alpha1 chain survive to up to 1.5-2 years of age. Furthermore, they displayed improved skeletal and heart muscle morphology, near-normal muscle strength, and normalized creatine kinase levels. Such an improvement of the dystrophic phenotype that persists to old age has not been previously demonstrated in mice. Our findings hold promise with regard to the efficient treatment of MDC1A patients in the future.


The influence of the relative timing of arterial and subarachnoid space pulse waves on spinal perivascular cerebrospinal fluid flow as a possible factor in syrinx development.
The mechanisms of syringomyelia have long puzzled neurosurgeons and researchers alike due to difficulties in identifying the driving forces behind fluid flow into a syrinx, apparently against a pressure gradient between the spinal cord and the subarachnoid space (SAS). Recently, the synchronization between CSF flow and the cardiac cycle has been postulated to affect fluid flow in the spinal cord. This study aims to determine the effect of changes in the timing of SAS pressure on perivascular flow into the spinal cord. This study uses a computational fluid dynamics model to investigate whether the relative timing of a spinal artery cardiovascular pulse wave and fluid pressure in the spinal SAS can influence CSF flow in the perivascular spaces. The results show that the mass flow rate of CSF through a model periarterial space is strongly influenced by the relative timing of the arterial pulse wave and the SAS pressure. These findings suggest that factors that might alter the timing of the pulse wave or the fluid flow in the SAS could potentially affect fluid flow into a syrinx.


A rare cause of back pain and radiculopathy - spinal tophi: a case report.
Gout is a monosodium urate deposition disease which is prevalent worldwide. The usual manifestations are crystal arthropathy and tophi deposition in the soft tissues. Spinal tophi may also occur and are rarely reported, resulting in various clinical manifestations such as back pain, spinal cord compression, radiculopathy, and even mimicking epidural abscess and spondylodiscitis. We report a case of a 42-year-old Chinese man with underlying gout who presented with back pain and radiculopathy. The diagnosis of spinal tophi was unsuspected and he was initially treated for epidural abscess and spondylodiscitis. He underwent a laminectomy and posterolateral fusion during which tophus material was discovered. He recovered and medications for gout were started. Spinal tophi are rare. The diagnosis is difficult and spinal tophi may be mistaken for epidural abscess, spondylodiscitis, or neoplasm.


Effects and complications of high efficiency dialysis.
Two and three Dow Cordis Hollow Fiber and Gambro Lundia artificial kidneys were used for high efficiency dialysis in large patients, intoxications, and for rapid ultrafiltration. BUN clearances of up to 240 ml/min were achieved. One episode of severe neuropathy occurred during high efficiency dialysis, and hypotensive episodes were more common. High efficiency dialysis has certain indications particularly in intoxication cases. However, because of possible side effects more experience is needed before its ultimate place in the treatment of uremia can be ascertained.


Incidence of delirium in the Canadian emergency department and its consequences on hospital length of stay: a prospective observational multicentre cohort study.
We aim to determine the incidence of delirium and describe its impacts on hospital length of stay (LOS) among non-delirious community-dwelling older adults with an 8-hour exposure to the emergency department (ED) environment. This is a prospective observational multicentre cohort study (March-July 2015). Patients were assessed two times per day during their entire ED stay and up to 24 hours on hospital ward. The study took place in four Canadian EDs. 338 included patients: (1) aged ≥65 years; (2) who had an ED stay ≥8 hours; (3) were admitted to hospital ward and (4) were independent/semi-independent. The primary outcomes of this study were incident delirium in the ED or within 24 hours of ward admission and ED and hospital LOS. Functional and cognitive status were assessed using validated Older Americans Resources and Services and the modified Telephone Interview for Cognitive Status tools. The Confusion Assessment Method was used to detect incident delirium. Univariate and multivariate analyses were conducted to evaluate outcomes. Mean age was 76.8 (±8.1), 17.7% were aged >85 years old and 48.8% were men. The mean incidence of delirium was 12.1% (n=41). Median IQR ED LOS was 32.4 (24.5-47.9) hours and hospital LOS was 146.6 (75.2-267.8) hours. Adjusted mean hospital LOS was increased by 105.4 hours (4.4 days) (95% CI 25.1 to 162.0, P<0.001) for patients who developed an episode of delirium compared with non-delirious patient. An incident delirium was observed in one of eight independent/semi-independent older adults after an 8-hour ED exposure. An episode of delirium increases hospital LOS by 4 days and therefore has important implications for patients and could contribute to ED overcrowding through a deleterious feedback loop.


Calcium antagonists and their mode of action: an historical overview.
The Ca2+ antagonists are a novel group of drugs useful in management of a variety of cardiac disorders. They differ from one another in terms of their chemistry, tissue specificity and selectivity. As a group, however, they share the common property of slowing Ca2+ entry through voltage-activated, ion-selective channels. Some of them exhibit other properties, including that of interfering with Na+ transport. At least one of them, diltiazem, has an intracellular action. Specific high and low affinity binding sites have been identified for two of the major groups of Ca2+-antagonists, with the binding sites for verapamil and its derivatives being distinct from those which can be occupied by the dihydropyridines. The number (Bmax) and affinity (KD) of these binding sites changes under certain pathological conditions--including a reduction in ischaemia and in spontaneous hypertension, an increase in the latter, at present, only demonstrated for the dihydropyridine binding sites. The sensitivity of a particular tissue to these drugs will depend upon a number of factors including the number of binding sites that are present, the contribution made by the Ca2+ entering through the voltage-activated channels to the functioning of the tissue, and properties which are peculiar to a particular type of Ca2+ antagonist, for example, whether, as in the case of verapamil, they exhibit use-dependence.


The effect of bevacizumab on colon anastomotic healing in rats.
The aim of the study was to investigate the effect of angiogenesis inhibition by bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF) antibody, on the healing process of colonic anastomoses in rats, assessing some specific involved factors. This new agent is used mainly in metastatic colorectal cancer. The angiogenesis plays an important role in both wound healing and metastatic invasion and spread of malignant cells. There has not been any evidence assessing the optimal time for its safe use in operated patients. Forty Wistar rats were randomly allocated into four equal groups. A colonic anastomosis was performed in all rats. Half of them received intraoperatively a single dose of bevacizumab 5 mg/body weight and the rest received placebo. The animals were sacrificed on the 7th (Avastin 7th, placebo 7th) and 14th (Avastin 14th, placebo 14th) postoperative day. The anastomosis was resected and sent for histological study and for tissue biochemical assays (VEGF, endothelin-1 (ET-1), C-reactive protein (CRP), pro-oxidant-antioxidant balance (PAB), carbonylated proteins, hydroxyproline) using specific enzyme-linked immunosorbent assay kits. For statistical analysis, the Mann-Whitney U test was used (of statistical significance when P < 0.05). No complication or anastomotic dehiscence was observed. Histology did not reveal statistically significant differences between groups concerning degree of inflammation, fibroblasts, collagen, and fibrosis. Likewise, hydroxyproline levels did not differ. However, some statistically significant differences were found in VEGF, CRP and carbonyl proteins (Avastin 7th vs placebo 7th, placebo 14th vs placebo 7th), ET-1, and PAB (Avastin 14th vs Avastin 7th), which did not finally affect the collagen synthesis marker hydroxyproline, nor did the anastomotic strength. Bevacizumab, when administered intraoperatively, has no significant effect on colon anastomotic healing in rats despite a transient mild ischemia.


Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke.
Leukocytes contribute to cerebral ischemia-reperfusion injury. However, few experimental models examine both in vivo behavior of leukocytes and microvascular rheology after stroke. The purpose of the present study was to characterize patterns of leukocyte accumulation in the cerebral microcirculation and to examine the relationship between leukocyte accumulation and microcirculatory hemodynamics after middle cerebral artery occlusion and reperfusion (MCAO-R). Male rats (250 to 350 g) were anesthetized and ventilated. Tail catheters were inserted for measurement of arterial blood gases and administration of drugs. Body temperature was maintained at 37 degrees C. Animals were subjected to 2 hours of MCAO by the filament method. A cranial-window preparation was performed, and the brain was superfused with warm, aerated artificial cerebrospinal fluid. Reperfusion was initiated by withdrawing the filament, and the pial microcirculation was observed by use of intravital fluorescence microscopy. Leukocyte accumulation in venules, arterioles, and capillaries; leukocyte rolling in venules; and leukocyte venular shear rate were assessed during 1 hour of reperfusion. We found significant leukocyte adhesion in cerebral venules during 1 hour of reperfusion after 2 hours of MCAO. Leukocyte trapping in capillaries and adhesion to arterioles after MCAO-R tended to increase compared with controls, but the increase was not significant. We also found that shear rate was significantly reduced in venules during early reperfusion after MCAO. A model using the filament method of stroke and fluorescence microscopy was used to examine white-cell behavior and hemodynamics in the cerebral microcirculation after MCAO-R. We observed a significant increase in leukocyte rolling and adhesion in venules and a significant decrease in blood shear rate in the microcirculation of the brain during early reperfusion. Leukocytes may activate and damage the blood vessels and surrounding brain cells, which contributes to an exaggerated inflammatory component to reperfusion. The model described can be used to examine precisely blood cell-endothelium interactions and hemodynamic changes in the microcirculation during postischemic reperfusion. Information from these and similar experiments may contribute to our understanding of the early inflammatory response in the brain during reperfusion after stroke.


A model to simulate pumping tests in wells with high loss and backflow.
Traditional methods of analyzing pumping tests in single wells fail when the well loss is very high due to a low transmissivity skin. Because of the restricted rate at which water can enter a high loss well from the aquifer, well casing storage becomes a significant factor. Additionally, if a slug of water enters the well from the pump column immediately after the pump is switched off, it has a long-lasting significant effect on the recovering water level in the well because it cannot be absorbed rapidly by the aquifer. A theoretical model is derived here that simulates the water level in a well in these circumstances. In the model, the continuously changing rate of water inflow from the aquifer to the well is approximated by a step function with a finite difference time step. It is demonstrated by a real example that the model can be applied easily to analyze pumping tests, including tests with a varying pumping rate. The analysis confirms suspected high well loss, calculates the unknown rate of backflow, and determines the aquifer's transmissivity.


Teucrium leucocladum: An Effective Tool for the Treatment of Hyperglycemia, Hyperlipidemia, and Oxidative Stress in Streptozotocin-Induced Diabetic Rats.
Teucrium leucocladum is among the most used traditional medicinal plants in Palestine, which is used for the treatment of hyperglycemia and colon spasms from ancient times. Therefore, the current investigation aimed for the first time to determine the hypoglycemic, hypolipidemic, and oxidative stress inhibitory effects of the aerial parts (stem and leaves) of T. leucocladum hydrophilic (water) extract in streptozotocin- (STZ-) induced diabetic rats (65 mg/kg), given intraperitoneally at a dose of 100 mg/kg for 21 days. The rats were divided into four groups as control (C), control + T. leucocladum extract (C + TL), diabetes (D), and diabetes + T. leucocladum extract (D + TL). The antioxidant activity was analyzed using in vitro 2,2-diphenyl-1-picrylhydrazyl and in vivo methods by measuring the plasma and tissue malondialdehyde (MDA) levels using a colorimetric assay. On the other hand, glutathione peroxidase (GSH-Px), erythrocyte superoxide dismutase (SOD) enzyme levels, serum paraoxonase (PON), and arylesterase (ARE) enzyme activities were assessed by utilizing standard biochemical kits. Besides, the blood glucose and serum insulin levels were assessed by a glucometer and Rat ELISA Kit, respectively. However, the autoanalyzer was used to evaluate the lipid profile. The diabetic rat group that administered T. leucocladum extract showed the best reduction in the tissue and plasma MDA levels and an increase of insulin-releasing potentials. Besides, the serum PON and ARE activities and erythrocyte superoxide dismutase and whole blood glutathione peroxidase enzyme levels were significantly increased in all animals treated with T. leucocladum extract. The current investigation demonstrated that T. leucocladum manifests antihyperglycemic and antihyperlipidemic effects and also increased the antioxidative defense system and reduced the lipid peroxidation process in experimental diabetic rats.


Pancreatic beta-cell-specific ablation of the multiple endocrine neoplasia type 1 (MEN1) gene causes full penetrance of insulinoma development in mice.
The function of the predisposition gene to multiple endocrine neoplasia type 1 (MEN1) syndrome remains largely unknown. Previous studies demonstrated that null mutation of the Men1 gene caused mid-gestation lethality in mice, whereas heterozygous Men1 knockout mice developed multiple endocrine tumors late in life. To seek direct evidence on the causal role of menin in suppressing tumor development, we generated mice in which the Men1 gene was disrupted specifically in pancreatic beta cells. These mice began to develop hyperplastic islets at as early as 2 months of age and insulinomas at 6 months of age. The islet lesions exhibited features of multistage tumor progression, including beta-cell dedifferentiation, angiogenesis, and altered expression of both E-cadherin and beta-catenin. Additionally, disturbance of blood insulin and glucose levels correlated with tumor development, mimicking human MEN1 symptoms. Our data indicate that this strain of mice provides a powerful tool for the study of the mechanisms of tumorigenesis related to MEN1 disease.


Leveraging public health's participation in a Health Information Exchange to improve communicable disease reporting.
Infectious diseases can appear and spread rapidly. Timely information about disease patterns and trends allows public health agencies to quickly investigate and efficiently contain those diseases. But disease case reporting to public health has traditionally been paper-based, resulting in somewhat slow, burdensome processes. Fortunately, the expanding use of electronic health records and health information exchanges has created opportunities for more rapid, complete, and easily managed case reporting and investigation. To assess how this new service might impact the efficiency and quality of a public health agency's case investigations, we compared the timeliness of usual case investigation to that of case investigations based on case report forms that were partially pre-populated with electronic data. Between September 2013-March 2014, chlamydia disease report forms for certain clinics in Indianapolis were electronically pre-populated with clinical, lab and patient data available through the Indiana Health Information Exchange, then provided to the patient's doctor. Doctors could then sign the form and deliver it to public health for investigation and population-level disease tracking. Methods: We utilized a novel matched case analysis of timeliness changes in receipt and processing of communicable disease report forms. Each Chlamydia cases reported with the pre-populated form were matched to cases reported in usual ways. We assessed the time from receipt of the case at the public health agency: 1) inclusion of the case into the public health surveillance system and 2) to close to case. A hierarchical random effects model was used to compare mean difference in each outcome between the target cases and the matched cases, with random intercepts for case. Twenty-one Chlamydia cases were reported to the public health agency using the pre-populated form. Sixteen of these pre-populated form cases were matched to at least one other case, with a mean of 23 matches per case. The mean Reporting Lag for the pre-populated form cases was 2.5 days, which was 2.7 days shorter than the mean Reporting Lag for the matched controls (p = <0.001). The mean time to close a pre-populated form case was 4.7 days, which was 0.2 days shorter than time to close for the matched controls (p = 0.792). Use of pre-populated forms significantly decreased the time it took for the local public health agency to begin documenting and closing chlamydia case investigations. Thoughtful use of electronic health data for case reporting may decrease the per-case workload of public health agencies, and improve the timeliness of information about the pattern and spread of disease.


Comprehensive assessment of executive functioning following childhood severe traumatic brain injury: clinical utility of the child executive functions battery.
To perform a detailed description of executive functioning following moderate-to-severe childhood traumatic brain injury (TBI), and to study demographic and severity factors influencing outcome. A convenience sample of children/adolescents aged 7-16 years, referred to a rehabilitation department after a TBI (n = 43), was compared to normative data using a newly developed neuropsychological test battery (Child Executive Functions Battery-CEF-B) and the BRIEF. Performance in the TBI group was significantly impaired in most of the CEF-B subtests, with moderate to large effect sizes. Regarding everyday life, patients were significantly impaired in most BRIEF clinical scales, either in parent or in teacher reports. Univariate correlations in the TBI group did not yield significant correlations between the CEF-B and socio-economic status, TBI severity, age at injury, or time since injury. Executive functioning is severely altered following moderate-to-severe childhood TBI and is best assessed using a combination of developmentally appropriate neuropsychological tests and behavioral ratings to provide a comprehensive understanding of children's executive functions.


A novel all-in-one intraoperative genotyping system for IDH1-mutant glioma.
IDH1 gene mutation has been demonstrated to be an oncogenic driver in a majority of lower-grade gliomas (LGGs). In contrast to other central nervous neoplasms and normal brain tissue without IDH1 mutation, almost 80% of LGGs exhibit IDH1 mutation. Therefore, expeditious detection of IDH1 mutation is useful, not only for intraoperative diagnosis of these gliomas but also for determination of the border between the tumor and normal brain tissue. In this study, we established a rapid genotyping assay with a simple DNA extraction method, involving only incubation of the tumor specimen with Tris-EDTA buffer, which can be easily performed in an operating room. In all 11 tested cases, we could identify the IDH1 status within 90-100 min intraoperatively. In a case of anaplastic astrocytoma, IDH-mutant, we could detect the tumor border by IDH1 profiling. In addition, with this assay, we could detect IDH1 mutation using cell-free tumor DNA derived from cerebrospinal fluid in a case of glioblastoma, IDH-mutant. Considering that clinical trials of mutated IDH1 inhibitors are ongoing, less-invasive intraoperative IDH1 gene profiling might be useful for decision making of the overall treatment strategy of LGGs. Our assay might be a useful tool for precision medicine and surgery of IDH1-mutant gliomas.


Factors Affecting Willingness to Use Hospice in Racially/Ethnically Diverse Older Men and Women.
Racial/ethnic minorities tend to underutilize hospice services. Guided by Andersen behavioral health model, the purpose of this study was to explore the predictors of the willingness to use hospice services in racially/ethnically diverse older men and women. Data were drawn from the Survey of Older Floridians: 504 non-Hispanic whites, 360 African Americans, 328 Cuban Americans, and 241 non-Cuban Hispanics. In each group, logistic regression models of the willingness to use hospice were estimated. A greater likelihood of willingness was observed among younger non-Hispanic whites and among African Americans with fewer functional disabilities. In non-Cuban Hispanics, English proficiency increased the willingness by 3.1 times. Findings of the study identified group-specific factors contributing to the willingness to use hospice services and hold implications for tailored intervention programs.


Activation of phonological codes during reading: evidence from errors detection and eye movements.
This experiment explored the role of phonology in the activation of word meanings when homophonic and nonhomophonic errors were embedded in meaningful texts. The resulting data supported the position that phonological codes are activated very early in eye fixation and are compatible with the verification model of Van Orden (1987).


Analysing microbiome intervention design studies: Comparison of alternative multivariate statistical methods.
The diet plays a major role in shaping gut microbiome composition and function in both humans and animals, and dietary intervention trials are often used to investigate and understand these effects. A plethora of statistical methods for analysing the differential abundance of microbial taxa exists, and new methods are constantly being developed, but there is a lack of benchmarking studies and clear consensus on the best multivariate statistical practices. This makes it hard for a biologist to decide which method to use. We compared the outcomes of generic multivariate ANOVA (ASCA and FFMANOVA) against statistical methods commonly used for community analyses (PERMANOVA and SIMPER) and methods designed for analysis of count data from high-throughput sequencing experiments (ALDEx2, ANCOM and DESeq2). The comparison is based on both simulated data and five published dietary intervention trials representing different subjects and study designs. We found that the methods testing differences at the community level were in agreement regarding both effect size and statistical significance. However, the methods that provided ranking and identification of differentially abundant operational taxonomic units (OTUs) gave incongruent results, implying that the choice of method is likely to influence the biological interpretations. The generic multivariate ANOVA tools have the flexibility needed for analysing multifactorial experiments and provide outputs at both the community and OTU levels; good performance in the simulation studies suggests that these statistical tools are also suitable for microbiome data sets.


Characterization of iron oxide thin films prepared by sol-gel processing.
Iron oxide thin films were prepared by spin-coating a gel solution of iron(III) nitrate dissolved in 2-methoxyethanol and acetylacetone on glass and quartz substrates. The film thickness was adjusted by changing the spinning rate of the spin coater. Annealing was carried out between 300 degrees C to 600 degrees C to investigate the phases present in the films. Viscosity of the main solution was found as 0.0035 Pa.s by viscosity measurement. TGA/DTA analyses showed that heat treatment should be done between 330 degrees C and 440 degrees C in order to produce maghemite thin films. SEM studies showed that single layer thickness of the films were between 65 and 80 nm. The structural characteristics were evaluated by changing the experimental parameters which are annealing temperature, annealing time and thickness of the films. From the X-ray diffraction analysis, maghemite formation was observed with decreasing annealing temperature, annealing time and film thickness. TEM results verified the presence of the maghemite phase by electron diffraction and selected area electron diffraction (SAED) methods. According to UV-Vis results transmittance of the films decreases with increasing annealing temperature.


Identification of the Rare Ala871Glu Mutation in the Androgen Receptor Gene Leading to Complete Androgen Insensitivity Syndrome in an Adolescent Girl with Primary Amenorrhea.
Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C>A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols.


Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study.
In a prospective, double-blind, intraindividual, cross-over, placebo-controlled multicenter study, clinical and biochemical effects of once daily postprandial dose regimens of 50, 100, and 200 mg spironolactone were investigated in 45 outpatients with primary hypertension, WHO (World Health Organization) Stage I-II. Each of the three active therapy periods, which were randomly allocated to patients, were of 2 months' duration, with intervening placebo periods, Clinical and biochemical parameters, including furosemide-stimulated plasma renin activity (PRA), were recorded at regular intervals. All three spironolactone doses resulted in statistically significant blood pressure (BP) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients. The 200 mg daily dose of spironolactone was found to be more effective than 50 but not 100 mg. When, correlating blood pressure response (delta MAP) to PRA, the profiling for positive spironolactone responders was characterized by high age and low PRA, irrespective of sex. Spironolactone therapy resulted in decreased serum sodium and magnesium values; potassium, creatinine, urate, and triglyceride levels were increased. However, all treatment values were within normal ranges. Side effects were infrequent and mainly of endocrine nature.


Successful transforaminal epidural blood patch in a patient with multilevel spinal fusion.
Epidural blood patch (EBP) is a vital tool in treating postdural puncture headache (PDPH). Traditional interlaminar epidural needle insertion into the epidural space, however, may be challenging due to anatomical variations. As an alternative method, we successfully performed an EBP via transforaminal approach. A mid-50-year-old male patient with multilevel spinal fusion developed PDPH after a failed spinal cord stimulator electrode placement. A transforaminal EBP was carried out by injecting a total of 8 mL of autologous blood into the neuroforamen at the L1-L2 level bilaterally. Our patient's positional headache resolved immediately after the procedure. To our knowledge, this is the first case reported of a transforaminal EBP in a patient with diffuse epidural adhesive fibrosis secondary to multilevel laminectomies and spinal fusion. This case report highlights potential risks and benefits of this novel technique and also discusses its therapeutic mechanism of action. We believe that a transforaminal EBP should be considered in patients who are poor candidates for the traditional interlaminar EBP.


Is the oxidative stress theory of aging dead?
Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates (e.g., C. elegans and Drosophila) and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules), direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited to a few studies with transgenic Drosophila that overexpress antioxidant enzymes. Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod1 gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice.


The factor validity of the Western Ontario Rotator Cuff Index.
The Western Ontario Rotator Cuff Index (WORC) is a self-report questionnaire developed specifically to evaluate disability in persons with pathology of the rotator cuff of the shoulder. The authors created items in 5 categories based on a model of quality of life, but never validated this structure. The purpose of this study was to examine the validity of the original 5-domain model of the WORC by performing factor analysis. Three hundred twenty nine subjects (age, mean: 52, SD: 12) were tested prior to undergoing surgery for rotator cuff pathologies. They completed the WORC, a self-report questionnaire, which has 21 items on the effect of the rotator cuff problem on symptoms, activities and emotions. Statistical calculations included correlations between items, Cronbach's alpha of the total scale and subscales, and principal component factor analysis with oblique rotation. Correlations ranged from .09 to .70 between all the items, from .29 to .70 between items within a subscale, and from .53 to .72 between subscale scores. Cronbach's alpha was .93 for the total scale, and .72 to .82 for the subscales. The factor analysis produced 3 factors that explained 57% of the variance. The first factor included symptoms and emotional items, the second included strength items and the third included daily activities. The results of this study did not support the 5-domain model of the WORC.


Hyaluronan esters drive Smad gene expression and signaling enhancing cardiogenesis in mouse embryonic and human mesenchymal stem cells.
Development of molecules chemically modifying the expression of crucial orchestrator(s) of stem cell commitment may have significant biomedical impact. We have recently developed hyaluronan mixed esters of butyric and retinoic acids (HBR), turning cardiovascular stem cell fate into a high-yield process. The HBR mechanism(s) remain still largely undefined. We show that in both mouse embryonic stem (ES) cells and human mesenchymal stem cells from fetal membranes of term placenta (FMhMSCs), HBR differentially affected the patterning of Smad proteins, one of the major conductors of stem cell cardiogenesis. Real-time RT-PCR and Western blot analyses revealed that in both cell types HBR enhanced gene and protein expression of Smad1,3, and 4, while down-regulating Smad7. HBR acted at the transcriptional level, as shown by nuclear run-off experiments in isolated nuclei. Immunofluorescence analysis indicated that HBR increased the fluorescent staining for Smad1,3, and 4, confirming that the transcriptional action of HBR encompassed the upregulation of the encoded Smad proteins. Chromatin immune precipitation and transcriptional analyses showed that HBR increased the transcription of the cardiogenic gene Nkx-2.5 through Smad4 binding to its own consensus Smad site. Treatment of mouse ES cells and FMhMSCs with HBR led to the concomitant overexpression of both Smad4 and α-sarcomeric actinin. Smad4 silencing by the aid of lentiviral-mediated Smad4 shRNA confirmed a dominant role of Smad4 in HBR-induced cardiogenesis. The use of HBR may pave the way to novel combinatorial strategies of molecular and stem cell therapy based on fine tuning of targeted Smad transciption and signaling leading to a high-throughput of cardiogenesis without the needs of gene transfer technologies.


Microplastics could be marginally more hazardous than natural suspended solids - A meta-analysis.
Microplastics (MP) are perceived as a threat to aquatic ecosystems but bear many similarities to suspended sediments which are often considered less harmful. It is, therefore pertinent to determine if and to what extent MP are different from other particles occurring in aquatic ecosystems in terms of their adverse effects. We applied meta-regressions to toxicity data extracted from the literature and harmonized the data to construct Species Sensitivity Distributions (SSDs) for both types of particles. The results were largely inconclusive due to high uncertainty but the central tendencies of our estimates still indicate that MP could be marginally more hazardous compared to suspended sediments. In part, the high uncertainty stems from the general lack of comparable experimental studies and dose-dependent point estimates. We therefore argue that until more comparable data is presented, risk assessors should act precautionary and treat MP in the 1-1000 µm size range as marginally more hazardous to aquatic organisms capable of ingesting such particles.


Lung cancer risk prediction: Prostate, Lung, Colorectal And Ovarian Cancer Screening Trial models and validation.
Identification of individuals at high risk for lung cancer should be of value to individuals, patients, clinicians, and researchers. Existing prediction models have only modest capabilities to classify persons at risk accurately. Prospective data from 70 962 control subjects in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) were used in models for the general population (model 1) and for a subcohort of ever-smokers (N = 38 254) (model 2). Both models included age, socioeconomic status (education), body mass index, family history of lung cancer, chronic obstructive pulmonary disease, recent chest x-ray, smoking status (never, former, or current), pack-years smoked, and smoking duration. Model 2 also included smoking quit-time (time in years since ever-smokers permanently quit smoking). External validation was performed with 44 223 PLCO intervention arm participants who completed a supplemental questionnaire and were subsequently followed. Known available risk factors were included in logistic regression models. Bootstrap optimism-corrected estimates of predictive performance were calculated (internal validation). Nonlinear relationships for age, pack-years smoked, smoking duration, and quit-time were modeled using restricted cubic splines. All reported P values are two-sided. During follow-up (median 9.2 years) of the control arm subjects, 1040 lung cancers occurred. During follow-up of the external validation sample (median 3.0 years), 213 lung cancers occurred. For models 1 and 2, bootstrap optimism-corrected receiver operator characteristic area under the curves were 0.857 and 0.805, and calibration slopes (model-predicted probabilities vs observed probabilities) were 0.987 and 0.979, respectively. In the external validation sample, models 1 and 2 had area under the curves of 0.841 and 0.784, respectively. These models had high discrimination in women, men, whites, and nonwhites. The PLCO lung cancer risk models demonstrate high discrimination and calibration.


Ultrasound screening of healthy infants for urinary tract abnormalities.
The purpose of the study was to determine the incidence of silent but significant urinary tract abnormalities that might be detected by screening renal ultrasound studies of apparently healthy infants. Of 437 babies studied, six were found to have uropathology severe enough to warrant surgery for an incidence of 1.37% or one of every 73 babies studied.


Statistical methods for unidirectional switch designs: Past, present, and future.
Clinical trials may apply or use a sequential introduction of a new treatment to determine its efficacy or effectiveness with respect to a control treatment. The reasons for choosing a particular switch design have different origins. For instance, they may be implemented for ethical or logistic reasons or for studying disease-modifying effects. Large-scale pragmatic trials with complex interventions often use stepped wedge designs (SWDs), where all participants start at the control group, and during the trial, the control treatment is switched to the new intervention at different moments. They typically use cross-sectional data and cluster randomization. On the other hand, new drugs for inhibition of cognitive decline in Alzheimer's or Parkinson's disease typically use delayed start designs (DSDs). Here, participants start in a parallel group design and at a certain moment in the trial, (part of) the control group switches to the new treatment. The studies are longitudinal in nature, and individuals are being randomized. Statistical methods for these unidirectional switch designs (USD) are quite complex and incomparable, and they have been developed by various authors under different terminologies, model specifications, and assumptions. This imposes unnecessary barriers for researchers to compare results or choose the most appropriate method for their own needs. This paper provides an overview of past and current statistical developments for the USDs (SWD and DSD). All designs are formulated in a unified framework of treatment patterns to make comparisons between switch designs easier. The focus is primarily on statistical models, methods of estimation, sample size calculation, and optimal designs for estimation of the treatment effect. Other relevant open issues are being discussed as well to provide suggestions for future research in USDs.


The efficiency of sonography in diagnosing volvulus in neonates with suspected intestinal malrotation.
This study is to prospectively evaluate the efficiency of sonography for volvulus diagnosis in neonates with clinically suspected intestinal malrotation.A total of 83 patients with suspected intestinal malrotation who underwent detailed abdominal sonography and upper gastrointestinal contrast study were included. Malrotation was characterized by inversion of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) in sonographic examination. The "whirlpool sign" of Color Doppler Sonography was recognized as a characteristic for malrotation with volvulus. The degrees of rotation of the SMV winding around SMA were also detected by sonography. Surgery was performed in patients with sonography diagnosed malrotation.A total of 39 patients were sonographically diagnosed as malrotation which was subsequently confirmed by surgery. The sensitivity and positive predictive value of the sonographic diagnosis were both 100% (39/39). The sensitivity, specificity and accuracy of "whirlpool sign" for the detection of midgut volvulus were 95.2% (20/21), 88.9% (16/18), and 92.3% (36/39), respectively. Greater degrees of rotation (equal or greater than 720°) showed higher risk (odds ratio, 5.0; P < .01) for intestinal necrosis occurrence.Sonography is more accurate in diagnosing suspected malrotation than upper gastrointestinal contrast study. Specific sonographic "whirlpool sign" related to volvulus may be used as a potential indicator for intestinal necrosis. In addition, sonography can exclude malrotation and may help the diagnosis of other diseases, such as annular pancreas and duodenal atresia.


Made by cells for cells - extracellular vesicles as next-generation mainstream medicines.
Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells. Since EVs not only mirror composition of their parent cells but also modify the recipient cells, they can be used in three key areas of medicine: regenerative medicine, disease detection and drug delivery. In this Review, we discuss the transformational and translational progress witnessed in EV-based medicine to date, focusing on two key elements: the mechanisms by which EVs aid tissue repair (for example, skin and bone tissue regeneration) and the potential of EVs to detect diseases at an early stage with high sensitivity and specificity (for example, detection of glioblastoma). Furthermore, we describe the progress and results of clinical trials of EVs and demonstrate the benefits of EVs when compared with traditional medicine, including cell therapy in regenerative medicine and solid biopsy in disease detection. Finally, we present the challenges, opportunities and regulatory framework confronting the clinical application of EV-based products.


Common Frame Dynamics for Conically-Constrained Spacecraft Attitude Control.
Attitude control subjected to pointing constraints is a requirement for most spacecraft missions carrying sensitive on-board equipment. Pointing constraints can be divided into two categories: exclusion zones that are defined for sensitive equipment such as telescopes or cameras that can be damaged from celestial objects, and inclusion zones that are defined for communication hardware and solar arrays. This work derives common frame dynamics that are fully derived for Modified Rodrigues Parameters and introduced to an existing novel technique for constrained spacecraft attitude control, which uses a kinematic steering law and servo sub-system. Lyapunov methods are used to redevelop the steering law and servo sub-system in the common frame for the tracking problem for both static and dynamic conic constraints. A numerical example and comparison between the original frame and the common frame for the static constrained tracking problem are presented under both unbounded and limited torque capabilities. Monte Carlo simulations are performed to validate the convergence of the constrained tracking problem for static conic constraints under small perturbations of the initial conditions. The performance of dynamic conic constraints in the tracking problem is addressed and a numerical example is presented. The result of using common frame dynamics in the constrained problem shows decreased control effort required to rotate the spacecraft.


Genome-scale identification of MLO domain-containing genes in soybean (Glycine max L. Merr.).
In plants, powdery-mildew-resistance locus o (Mlo) genes encode proteins that are calmodulin-binding proteins involved in a variety of cellular processes. However, systematic characterization of this gene family in soybean (Glycine max L. Merr.) has not been yet reported. In this study, we identified MLO domain-contained members in soybean and examined their expression under phytohormone treatment and abiotic stress conditions. A total of 20 soybean Mlo genes were identified (GmMlo1-20), which are distributed on 13 chromosomes, and display diverse exon-intron structures. Phylogenetic analysis indicated that the Mlo family can be classified into four subfamilies. Sequence comparison was used to reveal the conserved calmodulin-binding domain (CaMBD) in GmMLO proteins. The expression of GmMlo genes was influenced by various phytohormone treatments and abiotic stresses, suggesting that these Mlo genes have various roles in the response of soybean to environmental stimuli. Promoter sequence analysis revealed an overabundance of stress and/or phytohormone-related cis-elements in GmMlo genes. These data provide important clues for elucidating the functions of genes of the Mlo gene family.


Sympathetic neural effects on regional atrial recovery properties and cardiac rhythm.
The functional distribution of the cardiac sympathetic nerves to the atria and their arrhythmiogenic effects were determined in 16 open-chest pentobarbital-anesthetized dogs. Shortening of refractory periods at four right and two left atrial sites during stimulation of the nerves was taken as a criterion of their distribution. Stimulation of right stellate ganglion, craniovagal, and right stellate cardiac nerves produced localized shortening on the right atrium, particularly at the sinus node area, and invariably induced sinus tachycardia. The recurrent cardiac nerve produced little shortening at all sites and less arrhythmiogenic effect. The left stellate ganglion and ventrolateral cardiac nerve affected only left atrial sites and induced atrioventricular junctional rhythm. The ventromedial cardiac nerve affected all sites and had no consistent arrhythmiogenic effect. The innominate nerve had no substantial effect. We concluded that the functional distribution of the cardiac sympathetic nerves is localized, and that rate, rhythm, and refractory period changes induced by stimulation of these nerves are characteristic of the area of distribution.


Preparation and body distribution of freeze-dried powder of ursolic acid phospholipid nanoparticles.
Ursolic acid (UA) is a poor soluble natural triterpenoid. It has a wide variety of antitumor activities. We extracted it from Crataegus pinnatifida for the first time. To achieve a high bioavailability, targeting effect, stability, and an intravenous (i.v.) administration, the UA phospholipid nanopowders (UA-PL-NP) were prepared, characterized, and evaluated. With soybean phospholipid as the carrier and poloxamer 188 as emulsifier, the UA nanoparticle suspension was prepared by solvent emulsification-evaporation and ultrasonic dispersion. The UA-PL-NP was obtained by freeze drying. The body distribution in mice was studied after i.v. administration of UA-PL-NP and an UA control solution (UA-Sol). The entrapment efficiency (EE) and UA concentration in vitro and in vivo were analyzed by high-performance liquid chromatography (HPLC). The results showed that the UA-PL-NP had an average diameter of 273.8 nm with a zeta potential of -23.2 mV. The EE was up to 86.0%, and the drug loading (DL) was 12.8%. After i.v. administration of UA-PL-NP with low, middle and high doses, UA concentration in the livers of mice obviously increased during tested period and was highest in tested organs at 4 h. The AUC(0-12) ratio of UA-PL-NP in liver to that in plasma was much higher than that of UA-Sol, and the liver AUC(0-12) ratio of UA-PL-NP to UA-Sol was 8.6. These results indicate the UA-PL-NP have a good targeting to the liver after i.v. administration. Therefore, the UA-PL-NP is demonstrated to be available as an i.v. and liver targeting system for lipophilic antitumor triterpenoids.


MR contrast enhancement of the normal neonatal brain.
To determine the pattern of enhancement on contrast-enhanced MR studies of the brain in neonates. Contrast-enhanced brain MR studies of 16 neonates were reviewed retrospectively. All infants had normal neonatal courses, normal noncontrast MR findings, and normal neurologic examinations at age 12 months. All enhancing regions within the brain, dura, calvaria, and orbits were recorded. An enhancement factor, F = (Ic-Ip)/Ip, was calculated from region-of-interest intensity measurements in five regions of each hemisphere (basal ganglia, thalami, and three hemispheric locations), where Ic was signal intensity after contrast administration and Ip was the noncontrast signal intensity for each region. Enhancement was detected in the choroid plexus, pituitary infundibula, pineal glands, dura, veins and venous sinuses, cranial sutures, and irises of the orbital globes. No enhancement of the brain parenchyma was detected by visual inspection, although some change in signal intensity of the cerebral parenchyma was detected by the region-of-interest intensity measurements, with enhancement factors ranging from 0 to 0.08 (mean, 0.04). No consistent regional variation in enhancement was detected. Because the degree of enhancement was identical to that in the normal adult brain, the slight enhancement detected was attributed to contrast material in capillaries and small venules. In addition to the expected findings of enhancement of the pituitary stalk, the pineal gland, the choroid plexus, the dura, and the cerebral veins, we detected enhancement of the calvarial sutures and ocular irises. No evidence of enhancement of the cerebral parenchyma was detected, suggesting that the blood-brain barrier to gadolinium chelates is intact in the neonatal brain.


[Internist therapy of cholelithiasis].
Medical treatment of gallstones as an alternative to cholecystectomy has been established in recent years. Considering certain conditions--i.e. radiolucent cholesterol gallstones, functioning gallbladder, stone size, patients' cooperation--it is possible in up to 70% to dissolve gallstones completely or partially, using a therapeutic regimen of chenodeoxycholic or ursodeoxycholic acid at a dosage of 10 mg or 15 mg/kg body weight respectively. Side effects as diarrhoea or slight increase of serum transaminase levels are harmless and occur only with chenodeoxycholic acid. Therapeutic success may be controlled either by ultrasound or by cholecystography. Recurrence rate after dissolution is about 20%. Stones of the common bile duct can be treated easily by endoscopic papillotomy (EPT). In many cases the stone has to be removed with a basket; however, it may pass spontaneously. Certain indications for this procedure are obligatory. In the first place there is the patient over 50 years of age with the gallbladder already removed.


[The antibiotic galtamycin. The structure of galtamycinone].
The structure of galtamycinone, a chromophore moiety of galtamycin, a new antitumor antibiotic was determined by spectral analysis, i.e. UV, NMR and mass spectrometry. Galtamycinone was shown to be 1,4,6-trioxy-10 [4 (e), 5 (e)-dioxy-6 (e)-methyl-tetrahydropyran-2(e)-yl]-8-methyl tetracendion-5,12. It represents a new type of anthracycline chromophores containing a C-glycoside bond in its molecule.


Roux-en-Y Gastric Bypass Surgery in the Management of Familial Partial Lipodystrophy Type 1.
Familial partial lipodystrophy type 1 (FPLD1) is an extreme form of central adiposity, with peripheral lipodystrophy associated with severe manifestations of the metabolic syndrome, often poorly responsive to standard therapeutic approaches. Body mass index in FPLD1 varies but, in many cases, is below the level at which metabolic surgery is usually considered as a therapeutic option. We detailed the metabolic response to gastric bypass surgery of three patients with FPLD1, refractory to medical therapy. Roux-en-Y gastric bypass (RYGB) was associated with weight loss and substantial improvements in glycemic control and insulin sensitivity. All three patients were able to stop using insulin. Glucose tolerance testing in one patient demonstrated an increase in L-cell-derived gut hormone responses postoperatively. RYGB surgery substantially improved glycemic control in three patients with FPLD1, two of whom had body mass indices below 30 kg/m2. RYGB should be considered in patients with partial lipodystrophy and refractory metabolic disease.


RPP25 is developmentally regulated in prefrontal cortex and expressed at decreased levels in autism spectrum disorder.
Dysfunction of cerebral cortex in autism is thought to involve alterations in inhibitory neurotransmission. Here, we screened, in prefrontal cortex (PFC) of 15 subjects diagnosed with autism and 15 matched controls the expression of 44 transcripts that are either preferentially expressed in gamma-aminobutyric acidergic interneurons of the mature cortex or important for the development of inhibitory circuitry. Significant alterations in the autism cohort included decreased expression (-45%) of RPP25 (15q24.1), which is located within the autism susceptibility locus, 15q22-26. RPP25, which encodes the 25 kDa subunit of ribonuclease P involved in tRNA and pre-ribosomal RNA processing, was developmentally regulated in cerebral cortex with peak levels of expression during late fetal development (human) or around birth (mouse). In the PFC, RPP25 chromatin showed high levels of histone H3-lysine 4 trimethylation, an epigenetic mark associated with transcriptional regulation. Unexpectedly, and in contrast to peripheral tissues, levels of RPP25 protein remained undetectable in fetal and adult cerebral cortex. Taken together, these findings suggest a potential role for the RPP25 gene transcript in the neurobiology of developmental brain disorders.


The S-adenosyl-L-homocysteine hydrolase of Drosophila melanogaster: identification, deduced amino acid sequence and cytological localization of the structural gene.
S-adenosyl-L-homocysteine hydrolase (AdoHcyase, EC 188.8.131.52) catalyzes the hydrolysis of S-adeno-syl-L-homocysteine to adenosine and homocysteine and thus plays a crucial role in normal cellular metabolism. We have isolated the cDNA for Drosophila melanogaster AdoHcyase by screening a Drosophila ovarian expression library. The 1584-nucleotide cDNA encodes a protein of 431 amino acids, showing 80.5% identity with human AdoHcyase. Southern analysis of genomic DNA and in situ hybridization to salivary gland chromosomes indicate that a single gene encodes the D. melanogaster AdoHcyase. The gene resides in region 13C1-2 on the X chromosome. Transcript analysis shows a single AdoHcyase mRNA present in unfertilized eggs, and, at a more or less constant level of expression, in all developmental stages tested, ranging from early embryos to adults. The deduced amino acid sequence was compared to a putative AdoHcyase-like protein encoded by a cDNA mapping to the 89E region of the second chromosome and showing much lower similarity to known AdoHcyases. We discuss the hypothesis that a sequence that originated by duplication of an ancestral AdoHcyase gene has, in the course of evolution, been recruited to supply a different function.


Influence of question structure on the recall of self-reported drug use.
Epidemiological studies often rely on self-reported information as a source of drug exposure. Several studies have evaluated the accuracy of self-reported information on drug use. The influence of question structure on the accuracy of recall, however, has not been studied extensively in these studies. In this study we examined the recall accuracy of questionnaire information on drug use in a ongoing public health survey with special attention to the influence of question structure on sensitivity of recall. A sample of 372 hypertensive subjects for whom questionnaire information and pharmacy records were available was examined. Self-reported information on drug use was obtained through questions about medications used for a specific condition and one final open-ended question. This information was compared with the pharmacy medication history. About 71% of all drugs that were currently in use according to the pharmacy records were recalled through the self-administered questionnaire, and 94% of all drugs mentioned in the questionnaire could be traced in the pharmacy records. Recall sensitivity was higher for questions about medications used for a specific indication (88%) than for the open-ended question (41%). The type of drug that was used might have caused part of this difference in recall. We conclude that questionnaire structure might be of influence on the accuracy of recall of self-reported drug use, and more attention should be paid to the structure of questions on drug use.


Negative dielectrophoretic patterning with colloidal particles and encapsulation into a hydrogel.
Microparticle patterns have been fabricated on a nonconductive glass substrate and a conductive indium tin oxide (ITO) substrate using negative dielectrophoresis (n-DEP). The patterned microparticles on the substrate were immobilized by covalent bonding or embedded into polymer sheets or strings. The patterning device consisted of an ITO interdigitated microband array (IDA) electrode as the template, a glass or ITO substrate, and a polyester film (10-microm thickness) as the spacer. A suspension of 2-microm-diameter polystyrene particles was introduced into the device between the upper IDA and the bottom glass or ITO support. An ac electrical signal (typically 20 Vpp, 3 MHz) was then applied to the IDA, resulting in the formation of line patterns with low electric field gradient regions on the bottom support. When the glass substrate was used as the bottom support, the particles aligned under the microband electrodes of the IDA within 5 s because the aligned areas on the support were regions with the weakest electric field; however, for the ITO support, the particles were directed to the regions under the electrode gap and aligned on the support because these regions had the weakest electric field. The width of the particle lines could be roughly controlled by regulating the initial concentration of the suspended particles. The particles forming the line and grid patterns with single-particle widths were immobilized by using a cross-linking reaction between the amino groups on the aligned particles and N-hydroxysuccinimide-activated ester on the glass substrate activated by succinimidyl 4-(p-maleimidophenyl)-butyrate (SMPB). The patterned particles were also embedded in a photoreactive hydrogel polymer. A prepolymer solution of poly(ethylene glycol) diacrylate (PEG-DA) was used as the suspension medium to maintain the particle patterns in the polymerized hydrogel sheet and string following photopolymerization. The hydrogel sheets with particle patterns were fabricated by ultraviolet (UV) irradiation through the ITO-IDA template for 120 s. Hydrogel strings with the aligned particles were fabricated by using a conductive ITO support and a Pt-IDA template. Pt-IDA was used as a template as well as a photomask to block UV transmission. The present procedure affords extremely simple, rapid, and highly reproducible fabrication of particle arrays. The reusability of the template IDA electrode is also a substantial advantage over previous methods.


L-arginine supplementation in hyperdynamic endotoxemic pigs: effect on nitric oxide synthesis by the different organs.
Under septic conditions, the protective role of nitric oxide in the organs may become compromised at a time of increased demand as a result of decreased availability of L-arginine. It remains unknown whether supplementation with L-arginine, as a substrate, can modulate organ nitric oxide production. Controlled study with laboratory animals. University research laboratory. Female crossbred pigs. Pigs were challenged with Escherichia coli endotoxin (intravenously) and received intravenous fluid resuscitation for 24 hrs to reproduce a model of long-lasting hyperdynamic endotoxemia. Pigs were infused with either L-arginine or L-alanine intravenously during endotoxin and via the intragastric route after cessation of endotoxin infusion. The effects of L-arginine supplementation on nitric oxide synthesis and the relationships with arginine metabolism were determined with a stable isotope infusion protocol. Also, organ nitrite plus nitrate fluxes were measured. Implantation of multiple catheters enabled in vivo measurements across the hindquarter muscle, the portal-drained viscera, the liver, and the kidneys. The isotope conversion method showed that L-arginine intervention significantly increased nitric oxide production by the portal-drained viscera, liver, and kidneys, resulting in elevated whole-body nitric oxide synthesis under endotoxemic and postendotoxemic conditions. Organ nitrite plus nitrate fluxes only tended to increase because of high variance among data. In this endotoxemia model, supplemental use of L-arginine favored nitric oxide synthesis in various organs.


Bottom-Up Construction of Ni(II)-Incorporated Covalent Organic Framework for Metallaphotoredox Catalysis.
The construction of an all-in-one catalyst, in which the photosensitizer and the transition metal site are close to each other, is important for improving the efficiency of metallaphotoredox catalysis. However, the development of convenient synthetic strategies for the precise construction of an all-in-one catalyst remains a challenging task due to the requirement of precise installation of the catalytic sites. Herein, we have successfully established a facile bottom-up strategy for the direct synthesis of Ni(II)-incorporated covalent organic framework (COF), named LZU-713@Ni, as a versatile all-in-one metallaphotoredox catalyst. LZU-713@Ni showed excellent activity and recyclability in the photoredox/nickel-catalyzed C-O, C-S, and C-P cross-coupling reactions. Notably, this catalyst displayed a better catalytic activity than its homogeneous analogues, physically mixed dual catalyst system, and, especially, LZU-713/Ni which was prepared through post-synthetic modification. The improved catalytic efficiency of LZU-713@Ni should be attributed to the implementation of bottom-up strategy, which incorporated the fixed, ordered, and abundant catalytic sites into its framework. This work sheds new light on the exploration of concise and effective strategies for the construction of multifunctional COF-based photocatalysts.


Indicators of potential success among radiography students.
As the demand for qualified radiographers grows and the number of applicants to schools far exceeds the available capacity, program directors across the country face increasing difficulty in screening candidates for admission. This study sought to determine if there was a significant correlation between high school class rank, Scholastic Aptitude Test scores and the successful completion of a radiography curriculum as measured by a passing score on the American Registry of Radiologic Technologists examination.


Opportunistic Screening With Low-Dose Computed Tomography and Lung Cancer Mortality in China.
Despite the recommendations of lung cancer screening guidelines and the evidence supporting the effectiveness of population-based lung screening, a common barrier to effective lung cancer screening is that the participation rates of low-dose computed tomography (LDCT) screening among individuals with the highest risk are not large. There are limited data from clinical practice regarding whether opportunistic LDCT screening is associated with reduced lung-cancer mortality. To evaluate whether opportunistic LDCT screening is associated with improved prognosis among adults with lung cancer in mainland China. This cohort study included patients diagnosed with lung cancer at Weihai Municipal Hospital Healthcare Group, Weihai City, China, from 2016 to 2021. Data were analyzed from January 2022 to February 2023. Data collected included demographic indicators, tumor characteristics, comorbidities, blood indexes, and treatment information. Patients were classified into screened and nonscreened groups on the basis of whether or not their lung cancer diagnosis occurred through opportunistic screening. Follow-up outcome indicators included lung cancer-specific mortality and all-cause mortality. Propensity score matching (PSM) was adopted to account for potential imbalanced factors between groups. The associations between LDCT screening and outcomes were analyzed using Cox regression models based on the matched data. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis. A total of 5234 patients (mean [SD] baseline age, 61.8 [9.8] years; 2518 [48.1%] female) with complete opportunistic screening information were included in the analytical sample, with 2251 patients (42.91%) receiving their lung cancer diagnosis through opportunistic screening. After 1:1 PSM, 2788 patients (1394 in each group) were finally included. The baseline characteristics of the matched patients were balanced between groups. Opportunistic screening with LDCT was associated with a 49% lower risk of lung cancer death (HR, 0.51; 95% CI, 0.42-0.62) and 46% lower risk of all-cause death (HR, 0.54; 95% CI, 0.45-0.64). In this cohort study of patients with lung cancer, opportunistic lung cancer screening with LDCT was associated with lower lung cancer mortality and all-cause mortality. These findings suggest that opportunistic screening is an important supplement to population screening to improve prognosis of adults with lung cancer.


Efficient selection methods for black phosphorene nanoribbons.
Black phosphorene (BP) has shown anisotropic, electronic, mechanical, and thermal properties for various promising applications in recent years. To take full advantage of this unique anisotropy in its further functional design and application, it is of paramount importance to separate BP with well-defined chirality quickly and precisely. In this paper, we propose three efficient methods to separate BP ribbons with different chiralities by utilizing their strong chirality-dependent bending stiffness. Our results show that the bending stiffness in the zigzag direction is 4 times larger than that in the armchair direction. The mechanical anisotropy and bending-binding competition are used to realize chirality-dependent design. To fold, wrap or scroll the BP nanoribbons, it is necessary to overcome the bending stiffness by applying the binding energy between the BP nanoribbons and the contact surfaces. Due to the mechanical anisotropy, the BP nanoribbons could easily be folded, wrapped and scrolled along the armchair direction rather than the zigzag direction. Therefore, we introduce this characteristic in our chirality separation designs as, the self-folding model to fold up the armchair BP nanoribbons by nanoparticles, the suspension-bridge sieve model to pull down the armchair BP nanoribbons, and the nanorod-roller model to scroll up the armchair nanoribbons. Our separation methods in this research can be extended to other 2D materials with anisotropic mechanical properties. We hope our findings would offer a novel route for the manufacturing of BP-based electronic devices and self-assembly of nano-devices.


Sarcomatoid malignant mesothelioma presenting with intramedullary spinal cord metastasis: a case report and literature review.
Study Design Case report. Objective Malignant mesothelioma (MM) is an uncommon tumor of the pleural epithelium with a predilection for local spread into adjacent tissues. The sarcomatoid type accounts for ∼10% of MM cases and is associated with poorer survival than the epithelioid, desmoplastic, and biphasic types. MM commonly presents with involvement of the vertebral body or epidural space. However, intradural spinal extension of MM is extremely rare. Only eight cases of intradural spinal extension have been reported. We report this rare case and discuss the clinical manifestations of intradural spinal extension of MM with literature review. Methods This report describes the case of a 62-year-old man with Brown-Séquard syndrome and radiculopathy of the left C5 nerve root detected during treatment for pleural sarcomatoid MM. Magnetic resonance imaging (MRI) showed an intramedullary lesion at the C3 level and a small nodule at the left C5 nerve root with cervical canal stenosis. Results The patient underwent surgery, and intramedullary metastasis of sarcomatoid MM was diagnosed. Subsequently, radiotherapy was administered, resulting in temporary improvement of the patient's condition. Thereafter, his condition gradually deteriorated, and follow-up MRI showed a more extensive residual C3 intramedullary lesion. Thus, a second surgery was performed after chemotherapy, but the patient died 5 months after the initial diagnosis. Conclusion We present this rare case, and emphasize intramedullary spinal cord metastasis of MM as differential diagnosis in primary cord lesion.


Comparison of the antidromic sensory nerve action potentials obtained from all fingers on the same hand.
Supramaximal compound sensory nerve action potentials (CSNAPs) were recorded antidromically from five fingers of the same hand to electrical stimulation of the median, ulnar, and radial nerves in 17 normal subjects. The mean amplitudes of the median CSNAPs from the thumb, index, and middle fingers were similar in values. There was minimal radial sensory contribution to the thumb, with the mean radial CSNAP amplitude about one-fourth the size of the median CSNAPs. The mean median and ulnar CSNAP amplitudes from the ring finger were approximately half, and the mean ulnar CSNAP amplitude from the little finger was approximately 85%, of the median CSNAP amplitudes from the other fingers. The median, ulnar, and radial sensory nerve conduction velocities were close in values. There appears to be less variability in the population normative data when the size of the CSNAPs is expressed in terms of amplitude ratio rather than in absolute amplitude value.


Comparison of Amantadine, Modafinil, and Standard of Care in the Acute Treatment of Disorders of Consciousness After Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Many patients who experience severe TBI have persistent disorders of consciousness. Amantadine and modafinil are used for some neurological disorders; however, a comparison of the 2 medications in TBI has not been reported. This study compared the effectiveness of amantadine, modafinil, and standard of care (SOC) on disorders of consciousness after TBI. All adult TBI patients admitted between January 1, 2017, and September 31, 2020 who received amantadine, modafinil, or SOC treatments were screened. Data collection included: demographics, change in Glasgow Coma Scale (GCS), location of hemorrhage, medication duration, intensive care unit and hospital length of stay, adverse drug reactions, and concomitant sedative medications. Patients in the amantadine and modafinil groups were matched 1:2 with patients who received SOC therapies. The primary outcome was change in GCS ≥ 3 from baseline to discharge. A total of 142 patients met inclusion criteria. Medications were initiated a median of 8 days from admission. Patients in the SOC group experienced a greater improvement in GCS and shorter hospital length of stay compared with amantadine. A change in GCS ≥ 3 from medication initiation to hospital discharge occurred in 46.5% of amantadine patients and 53.8% of modafinil patients. In this study, TBI patients did not benefit from amantadine or modafinil compared with SOC therapies, and no differences were found between medication groups. Further studies are warranted to determine whether the addition of amantadine or modafinil in the weeks after TBI provides benefit.


[Cellular proliferation kinetics of Walker carcinosarcoma, Zajdela's ascitic hepatoma and their metastases to the lymph nodes].
The cell cycle of Walker carcinoma, Zajdela's hepatoma and their metastases into regional lymph nodes are studied. It is shown that cell cycle of metastases is shorter and the labeling index is higher than in primary tumours. The cell cycle shortening in Walker carcinosarcoma metastases is associated with a decrease in the duration of all its phases. The cell cycle of Zajdela's hepatoma metastases decreases with the S-phase length. The cell loss factor of primary tumours is less than that of their metastases. The results of the autoradiographic study correlate with the previously studied sensitivity of primary tumours and metastases to chemotherapy.


Campylobacter control measures in indoor broiler chicken: critical re-assessment of cost-utility and putative barriers to implementation.
As campylobacteriosis is one of the most important foodborne infections, a European Union (EU)-27 level cost-effectiveness model has been developed on the socio-economic costs and benefits of applying certain control measures for the reduction of Campylobacter in broiler meat. This is expected to be a gold standard for food safety policymakers in the EU; hence, the validity of its modelling assumptions is essential. The authors of the present paper conducted an independent review of model input parameters on health and economic burden and found that the model most probably overestimated the burden of human campylobacteriosis. A discounted, quality-adjusted life year (QALY)-based European estimate has been developed for human campylobacteriosis and resulted in 15.23 QALY loss per 1000 human gastroenteritis cases. Country-specific cost of illness estimates have been developed for various countries in the EU-27. Based on these model adaptations, a selected Campylobacter control strategy was re-assessed and its high cost-effectiveness was confirmed at the EU level, and also in all but three Member States. Bacteriocin treatment or vaccination of the animals, two alternative control measures were also re-evaluated, and these strategies seemed to be far less cost-effective than the investigated strategy. Putative barriers to the rapid implementation of the investigated Campylobacter control strategy are discussed, and potential solutions are proposed. Further research is required on stakeholder perspectives pertaining to the realistic barriers and implementation opportunities.


Effectiveness of a nurse educational oral feeding programme on feeding outcomes in neonates: protocol for an interrupted time series design.
Oral feeding is a complex physiological process. Several scales have been developed to assess the ability of the neonate to begin suck feedings and assist caregivers in determining feeding advancement. However, feeding premature neonates remains an ongoing challenge and depends above all on caregivers' feeding expertise. We will evaluate the effect of a nurse training programme on the achievement of full oral feeding with premature neonates. The study design will be an interrupted time series design with 3 phases: (1) A 6-month baseline period; (2) a 22-month intervention period and (3) a 6-month postintervention period. The intervention will consist of an educational programme, for nurses and assistant nurses, on feeding patterns in neonates. The training modules will be composed of a 2-day conference, 2 interactive multidisciplinary workshops, and routine practice nurse coaching. A total of 120 nurses and 12 assistant nurses, who work at the neonatal unit during the study period, will participate in the study. All premature neonates of <34 weeks postmenstrual age (PMA) will be included. The primary outcome will be the age of tube withdrawal PMA and chronological age are taken into account. The secondary outcomes will be the transition time, length of hospital stay, competent suckle feeding without cardiorespiratory compromise, rate of neonates presenting with feeding issues or feeding rejection signs, and current neonatal pathologies or deaths during hospital stay. A segmented regression analysis will be performed to assess the impact of the programme. Approval for the study was obtained from the Hospital Ethics Committee, and the Institutional Review Board, as well as the French Data Protection Agency. The findings from the study will be disseminated through peer-reviewed journals, national and international conference presentations and public events. NCT02404272 (https://clinicaltrials.gov).


[Chorio-amnionitis: clinical and biological aspects--medicolegal implications].
The authors present fetal and maternal risks in chorio-amnionitis diseases. Major fetal risk is the increase of the rate of cerebral palsy which is growing to five. The protocol of 2011 is presented for the prevention and treatment of chorio-amnionitis in premature rupture of the membranes in relation with gestational age. A French statistical survey, period 2001 to 2006, indicates maternal risks of chorio-amnionitis. Medicolegal implications of the chorio-amnionitis diseases emphasize the importance of placental investigations and bacteriological tests.


Reducing emissions from deforestation and forest degradation (REDD+): game changer or just another quick fix?
Reducing emissions from deforestation and forest degradation (REDD+) provides financial compensation to land owners who avoid converting standing forests to other land uses. In this paper, we review the main opportunities and challenges for REDD+ implementation, including expectations for REDD+ to deliver on multiple environmental and societal cobenefits. We also highlight a recent case study, the Norway-Indonesia REDD+ agreement and discuss how it might be a harbinger of outcomes in other forest-rich nations seeking REDD+ funds. Looking forward, we critically examine the fundamental assumptions of REDD+ as a solution for the atmospheric buildup of greenhouse gas emissions and tropical deforestation. We conclude that REDD+ is currently the most promising mechanism driving the conservation of tropical forests. Yet, to emerge as a true game changer, REDD+ must still demonstrate that it can access low transaction cost and high-volume carbon markets or funds, while also providing or complimenting a suite of nonmonetary incentives to encourage a developing nation's transition from forest losing to forest gaining, and align with, not undermine, a globally cohesive attempt to mitigate anthropogenic climate change.


Suggesting Missing Relations in Biomedical Ontologies Based on Lexical Regularities.
The number of biomedical ontologies has increased significantly in recent years. Many of such ontologies are the result of efforts of communities of domain experts and ontology engineers. The development and application of quality assurance (QA) methods should help these communities to develop useful ontologies for both humans and machines. According to previous studies, biomedical ontologies are rich in natural language content, but most of them are not so rich in axiomatic terms. Here, we are interested in studying the relation between content in natural language and content in axiomatic form. The analysis of the labels of the classes permits to identify lexical regularities (LRs), which are sets of words that are shared by labels of different classes. Our assumption is that the classes exhibiting an LR should be logically related through axioms, which is used to propose an algorithm to detect missing relations in the ontology. Here, we analyse a lexical regularity of SNOMED CT, congenital stenosis, which is reported as problematic by the SNOMED CT maintenance team.


Diverticular disease of the colon. The first of the Western diseases shown to be due to a deficiency of dietary fibre.
Diverticular disease of the colon is a new disease that appeared at the beginning of this century. It is now the commonest disease of the colon in the Western world, being found in 1 in 3 people of over 60 years of age. The pathogenesis of the disease involves excessive segmentation, but this does not explain its aetiology. The historical appearance of the disease on the clinical scene and its geographical distribution suggest that it is due to the removal of fibre from carbohydrates. The author treated 70 patients with symptomatic diverticular disease with a high-fibre diet. The results of this and the effects of bran are discussed.


Critical neuromorphic computing based on explosive synchronization.
Synchronous oscillations in neuronal ensembles have been proposed to provide a neural basis for the information processes in the brain. In this work, we present a neuromorphic computing algorithm based on oscillator synchronization in a critical regime. The algorithm uses the high-dimensional transient dynamics perturbed by an input and translates it into proper output stream. One of the benefits of adopting coupled phase oscillators as neuromorphic elements is that the synchrony among oscillators can be finely tuned at a critical state. Especially near a critical state, the marginally synchronized oscillators operate with high efficiency and maintain better computing performances. We also show that explosive synchronization that is induced from specific neuronal connectivity produces more improved and stable outputs. This work provides a systematic way to encode computing in a large size coupled oscillator, which may be useful in designing neuromorphic devices.


Highlights of Cardiovascular Disease Studies Presented at the 2021 American Heart Association Scientific Sessions.
This review highlights major studies across a broad array of topics presented at the virtual 2021 American Heart Association (AHA) Scientific Sessions. Assessed studies examine a remotely delivered hypertension and lipid program in 10,000 patients across a diverse healthcare network; a cluster-randomized trial of a village doctor-led intervention for hypertension control; empagliflozin in heart failure with preserved ejection fraction (EMPEROR-Preserved); efficacy and safety of empagliflozin in hospitalized heart failure patients (EMPULSE); icosapent ethyl versus placebo in outpatients with coronavirus disease 2019 (PREPARE-IT 2); clinical safety, pharmacokinetics, and low-density lipoprotein cholesterol-lowering efficacy of MK-0161, an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor; and effects of aspirin on dementia and cognitive impairment in the ASCEND trial. Research presented at the 2021 AHA Scientific Sessions emphasized the importance of interventions for cardiovascular disease prevention.


Prevalence and factors associated with poor sleep quality among secondary school teachers in a developing country.
This study aimed to determine the prevalence and factors associated with poor sleep quality among secondary school teachers in the state of Selangor, Malaysia. This was a cross sectional study, conducted in two phases. Phase I tested the reliability of the Pittsburgh Sleep Quality Index in the Malay language (M-PSQI), whereas Phase II determined the prevalence and factors associated with poor sleep quality where a total of 1,871 secondary school teachers were studied. Participants were recruited using multistage sampling. Self-administered questionnaire was used to collect data on socio-demographic and teaching characteristics, comorbidities and characteristics of sleep. The M-PSQI was used to measure sleep quality. The Depression Anxiety Stress Scale-21 was used to measure mental health status. Results showed that the M-PSQI had a good internal consistency and moderate reliability. The prevalence of poor sleep quality was 61 (95% CI: 54-67)%. Total teaching hours/day, depression and stress were significantly associated with poor sleep quality in the univariate analysis, while only stress (OR 1.04; 95% CI 1.02-1.05%) remained significant in the multivariate analyses. In conclusion, stress level of the secondary school teachers should be reduced to improve sleep quality.


Integrating financial modeling and patient care reengineering.
Healthcare organizations face significant pressure to decrease costs and increase quality. In response, many organizations are attempting to reengineer patient care processes through standardization, using critical paths and processes such as total quality management. Many of the organizational initiatives to analyze patient care, explore alternative processes, and establish standardized patient care have been managed primarily by clinical personnel who have not adequately incorporated financial analyses. A thorough understanding and documentation of the costs of providing standardized patient care have become essential parts of hospital management, particularly with regard to managed care contracting and financial planning under healthcare reform. This article presents a practical methodology to integrate financial analysis with the development of standardized clinical practices.