Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish.
Zebrafish intraspinal serotonergic neuron (ISN) morphology and distribution have been examined in detail at different ages; however, some aspects of the development of these cells remain unclear. Although antibodies to serotonin (5-HT) have detected ISNs in the ventral spinal cord of embryos, larvae, and adults, the only tryptophan hydroxylase (tph) transcript that has been described in the spinal cord is tph1a. Paradoxically, spinal tph1a is only expressed transiently in embryos, which brings the source of 5-HT in the ISNs of larvae and adults into question. Because the pet1 and tph2 promoters drive transgene expression in the spinal cord, we hypothesized that tph2 is expressed in spinal cords of zebrafish larvae. We confirmed this hypothesis through in situ hybridization. Next, we used 5-HT antibody labeling and transgenic markers of tph2-expressing neurons to identify a transient population of ISNs in embryos that was distinct from ISNs that appeared later in development. The existence of separate ISN populations may not have been recognized previously due to their shared location in the ventral spinal cord. Finally, we used transgenic markers and immunohistochemical labeling to identify the transient ISN population as GABAergic Kolmer-Agduhr double-prime (KA″) neurons. Altogether, this study revealed a novel developmental paradigm in which KA″ neurons are transiently serotonergic before the appearance of a stable population of tph2-expressing ISNs.


Motor activity and neurotransmitter release in the gastric fundus of streptozotocin-diabetic rats.
As deficiencies of the cholinergic and non-adrenergic non-cholinergic innervation of the gastrointestinal tract have been described in diabetic rats, we studied the simultaneous release of, and muscular response to, acetylcholine, vasoactive intestinal polypeptide and adenosine-5'-triphosphate in isolated preparations of gastric fundus from control and 8-week streptozotocin-treated diabetic rats. Muscular responses were measured in longitudinal muscle strips prepared from one half of the gastric fundus and release was studied in the other half. The contractile response to acetylcholine and electrical field stimulation was not different in control and diabetic rats. In the presence of atropine, and when tone was increased with prostaglandin F2 alpha, electrical field stimulation, vasoactive intestinal polypeptide and adenosine-5'-triphosphate induced relaxation with a similar response in control and diabetic rats. The basal release of acetylcholine, vasoactive intestinal polypeptide and adenosine-5'-triphosphate was not significantly different in control and diabetic rats. Electrical field stimulation significantly increased the release of the three substances and this increase was tetrodotoxin-sensitive. While the stimulation-induced increase of acetylcholine and vasoactive intestinal polypeptide was not different in control and in diabetic rats, the stimulation-induced release of adenosine-5'-triphosphate increased 3-fold in diabetic compared to control gastric fundus. Desensitization to alpha,beta-methylene adenosine-5'-triphosphate reduced the relaxant response to adenosine-5'-triphosphate and to electrical field stimulation, suggesting a role of adenosine-5'-triphosphate in non-adrenergic non-cholinergic neurotransmission of rat gastric fundus. The reduction of the non-adrenergic non-cholinergic relaxation by alpha,beta-methylene adenosine-5'-triphosphate was greater in diabetic tissues. This, with the increase in stimulation-induced adenosine-5'-triphosphate release, suggests that the purinergic component of the vagal non-adrenergic non-cholinergic response of the stomach may be increased in diabetics.


Discharge source coupled to a deceleration unit for anion beam generation: application to H2- photodetachment.
A cathode discharge source coupled to a deceleration unit for anion beam generation is described. The discharge source, made of stainless steel or duralumin electrodes and Macor insulators, is attached to the exit nozzle valve plate at one end, and to an Einzel lens to the other end. Subsequently, a cylindrical retardation unit is attached to the Einzel lens to decelerate the ions in order to optimize the laser beam interaction time required for spectroscopic investigations. The compact device is able to produce beam intensities of the order of 2 × 10(12) anions/cm(2) s and 20 μrad of angular divergence with kinetic energies ranging from 30 to 120 eV. Using distinct gas mixtures for the supersonic expansion together with a linear time-of-flight spectrometer, anions of great relevance in molecular astrophysics like, for example, H2(-), C3H(-), C2(-), C2H(-), HCN2(-), CO2(-), CO2H(-), C4(-), C4H(-), C5H4(-), C5H6(-), C7N(-), and C10N(-) were produced. Finally, in order to demonstrate the capability of the experimental technique the photodetachment cross-section of the metastable H2(-), predominantly in the (v = 0, J = 26) state, was measured following laser excitation at λexc = 565 nm obtaining a value of σph = 0.04 Ų [corrected]. To the best of our knowledge, it is the first time that this anion cross-section has been measured.


The relation of keratinization to bacterial colonization on the baboon tongue as demonstrated by scanning electron microscopy.
Scanning electron microscopic observations of the baboon tongue demonstrating specificity of microbial distribution as related to epithelial keratinization are presented. The number of bacteria inhabiting a surface was related to the degree of keratinization. Orthokeratotic dorsal tongue surfaces were most heavily colonized by bacteria. The parakeratotic and non-keratinized surfaces were less heavily populated, with non-keratinized areas showing the fewest numbers of bacteria.


A laboratory rill study of IMX-104 transport in overland flow.
The deposition of explosive contaminants in particulate form onto the soil surface during low-order detonations can lead to ground and surface water contamination. The vertical fate and transport of insensitive munitions formulation IMX-104 through soil has been thoroughly studied, however the lateral transport of explosive particles on the surface is less known. The objective of this research was to understand the impact of overland flow on the transport of IMX-104 constituent compounds 3-nitro-1,2,4-triazol-5-one (NTO), 2,4-dinitroanisole (DNAN), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). The effect of overland flow was examined in a rill flume using several flow rates (165-, 265-, and 300-mL min-1) and IMX-104 particle sizes (4.75-9.51 mm, 2.83-4.75 mm, 2-2.83 mm, and <2 mm). We found that the smaller particles were transported more in solution and with the sediment compared to the larger particles, which had a higher percent mass remaining on the surface. As flow rate increased, there was an increase in the percent mass found in solution and sediment and a decrease in the percent mass remaining on the surface. NTO fate was dominated by transport in solution, while DNAN, RDX and HMX were predominantly transported with the sediment. This research provides evidence of the role of overland flow in the fate of energetic compounds.


The width of lingual mandibular attached gingiva.
One hundred and twenty individuals in good oral health were divided into six groups according to age. Measurements were made on the depth of the gingival sulcus, and the distance from the margin of the free gingiva to the mucogingival junction on the lingual mandibular teeth. The mean, extreme, standard deviation and analysis of variance were computed. A distinct pattern of the width of healthy lingual attached gingiva was found. The largest width was found lingual to the first and second molars with a mean height of 4.7 mm. This was followed by the third molar [3mm] second bicuspid [2.5 mm] first bicuspid [2 mm], and cuspid, lateral and central [1.9mm]. Lingual attached gingiva showed that there was a variation in width with each tooth and between individuals. There was no variation in width of lingual attached gingiva between sexes. The extreme measuremtns ranged from less than 1 mm to 8 mm. The data from the study gives the dentist some indication of the mean and extreme ranges of lingual attached gingiva. This data can serve as a guide in diagnoiss and treatment planning and in selecting procedures to reestablish these zones of attached gingiva.


OsHDA710-Mediated Histone Deacetylation Regulates Callus Formation of Rice Mature Embryo.
Histone deacetylases (HDACs) play important roles in the regulation of eukaryotic gene expression. The role of HDACs in specialized transcriptional regulation and biological processes is poorly understood. In this study, we evaluated the global expression patterns of genes related to epigenetic modifications during callus initiation in rice. We found that the repression of HDAC activity by trichostatin A (TSA) or by OsHDA710 mutation (hda710) results in impaired callus formation of rice mature embryo and increased global histone H3 acetylation levels. The HDAC inhibition decreased auxin response and cell proliferation in callus formation. Meanwhile, the transcriptional repressors OsARF18 and OsARF22 were upregulated in the callus of hda710. The chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis demonstrated that the callus of hda710 exhibited enhanced histone H3 acetylation levels at the chromatin regions of OsARF18 and OsARF22. Furthermore, we found that OsARF18 and OsARF22 were regulated through OsHDA710 recruitment to their target loci. In addition, overexpression of OsARF18 decreased the transcription of downstream genes PLT1 and PLT2 and inhibited callus formation of the mature embryo. These results demonstrate that OsHDA710 regulates callus formation by suppressing repressive OsARFs via histone deacetylation during callus formation of rice mature embryo. This indicates that OsHDA710-mediated histone deacetylation is an epigenetic regulation pathway for maintaining auxin response during cell dedifferentiation.


Point-of-care ultrasound in the diagnosis of neonatal cerebral sinovenous thrombosis.
Cerebral sinovenous thrombosis (CSVT) mostly affects sick neonates in the neonatal intensive care unit (NICU) with predisposing or underlying conditions. The clinical presentation is nonspecific which often leads to a delayed or missed diagnosis. Point-of-care ultrasound (POCUS) use in the NICU is rapidly increasing. One of the main uses of neonatologist-performed POCUS is cranial ultrasound which permits diagnosis and monitoring of neurological disease at the bedside. We present the case of a neonate with a complex clinical situation where cranial POCUS permitted a prompt diagnosis and treatment of severe CSVT by imaging the transverse sinuses through the mastoid fontanelle.


The opioid industry document archive: New directions in research on corporate political strategy.
The opioid crisis in the United States has resulted in more than 500,000 deaths since 1999, and recent estimates suggest that attributable deaths could reach 842,000 by 2032. While heroin and synthetic products such as fentanyl now account for the majority of opioid overdoses, the prescription opioid crisis that emerged in the mid-1990s was the primary antecedent to the current situation. Recent settlements in litigation against opioid producers, suppliers and retailers has resulted in the release of almost 2.5 million previously confidential internal documents that have been made publicly accessible via the online Opioid Industry Documents Archive, a collaboration between the University of California, San Francisco and Johns Hopkins University. These corporate records provide critical insights into the operations and strategies of manufacturers and other actors in the opioid supply chain. This article describes the provenance of the opioid documents and their potential value as a research resource. It then outlines methodological approaches to their analysis, drawing on comparisons in conducting research using the Truth Tobacco Industry Documents. The Opioid Industry Documents Archive is a new and important addition to existing industry document collections that enable scrutiny and analysis of the role of corporate actors in determining health outcomes. Beyond their immediate application to researching the corporate and regulatory foundations of the current opioid crisis, the opioid document collections will contribute to a greater understanding of the commercial determinants of public health by providing means to better locate the causes of public health crises, identify politically acceptable solutions to their resolution, and inform strategies for preventing future corporate-driven epidemics.


Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies.
Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.


Review on optofluidic microreactors for artificial photosynthesis.
Artificial photosynthesis (APS) mimics natural photosynthesis (NPS) to store solar energy in chemical compounds for applications such as water splitting, CO2 fixation and coenzyme regeneration. NPS is naturally an optofluidic system since the cells (typical size 10 to 100 µm) of green plants, algae, and cyanobacteria enable light capture, biochemical and enzymatic reactions and the related material transport in a microscale, aqueous environment. The long history of evolution has equipped NPS with the remarkable merits of a large surface-area-to-volume ratio, fast small molecule diffusion and precise control of mass transfer. APS is expected to share many of the same advantages of NPS and could even provide more functionality if optofluidic technology is introduced. Recently, many studies have reported on optofluidic APS systems, but there is still a lack of an in-depth review. This article will start with a brief introduction of the physical mechanisms and will then review recent progresses in water splitting, CO2 fixation and coenzyme regeneration in optofluidic APS systems, followed by discussions on pending problems for real applications.


[High performance liquid chromatographic fingerprints of Baihe Zhimu Tang and its correlation to single herb].
The high performance liquid chromatographic (HPLC) fingerprints of Baihe Zhimu Tang were established for evaluating the effective substance basis and compatibility regulation of Baihe Zhimu Tang. An Agela Venusil XBP-C18 column (250 mm x 4.6 mm, 5 microm) was employed, and the gradient elution of acetonitrile and 0. 1% formic acid was used as mobile phase with a flow rate of 1 mL/min, the detection wavelength was set at 315 nm, and the column temperature was set at 25 degrees C. By taking mangiferin as the reference substance, the fingerprints of 10 batches of Baihe Zhimu Tang prepared by Bulbus Lilii and Rhizoma Anemarrhenae from different producing areas were analyzed under the same chromatographic conditions. The results showed that there were 16 common peaks contained in the tested samples. Five constituents were identified as 5-hydroxymethyl-2-furaldehyde (5-HMF), neomangiferin, mangiferin, isomangiferin and regaloside B by comparing the retention times and ultraviolet spectra of the peaks with those of the reference substances. The HPLC fingerprints of Baihe Zhimu Tang established with the above method show good characteristic and repeatability, and the method is stable and reliable, it can be used for the quality control of Baihe Zhimu Tang. The main chromatographic peaks of the HPLC fingerprints of Baihe Zhimu Tang were identified in the experiment and also 5-HMF was identified as the main constituent which changed significantly in decocting process.


Early-diagnosed silent sinus syndrome and cone-beam computed tomography in a pediatric patient: a case report.
Chronic maxillary atelectasis (CMA) is a progressive alteration in the volume of the maxillary sinuses that may result in facial asymmetry. CMA in asymptomatic patients is known as silent sinus syndrome (SSS) and is a rare entity, especially in pediatric patients. This study reports a case of SSS in a pediatric patient who received an early diagnosis through cone-beam computed tomography (CBCT). An asymptomatic 12-year-old female patient in orthodontic treatment presented with opacification of the left maxillary sinus on a panoramic radiograph. Clinically, the patient had discrete hypoglobus and enophthalmos. CBCT and nasal video-endoscopy revealed ostiomeatal obstruction with bone deformity, leading to diagnosis of SSS. Endonasal endoscopic maxillary sinusotomy was performed. Two years later, the patient remained asymptomatic, and a second CBCT exam confirmed a stable condition. This case highlights the role of optimal radiographic interpretation for early diagnosis of maxillofacial alterations in pediatric patients.


Risk factors for impaired fasting glucose or diabetes among HIV infected patients on ART in the Copperbelt Province of Zambia.
Africa has a high prevalence of both Human Immunodeficiency Virus and Non Communicable Diseases (NCDs) but in Zambia there are few data on co-morbid NCDs like Diabetes Mellitus (DM) among HIV-infected individuals. We aimed to identify risk factors for impaired fasting glucose or diabetes among HIV-infected Zambians on long-term Combined Antiretroviral Treatment (cART). This was a cross sectional study of adult HIV patients in five health facilities of Copperbelt Province in Zambia. HIV/AIDS patients aged 18 years and above, enrolled in care at those health facilities and had been on cART for more than 2 years were included. All patients known to have Diabetes mellitus were excluded from the study. Participants underwent assessment of random blood sugar levels at enrolment and returned the following morning for fasting glucose measured by glucometers. The primary outcome was proportion with impaired fasting glucose or DM. Multivariable logistic regression was used to examine if demographics, time on ART, type of ART regimen, body mass index and baseline CD4 count were predictors of impaired fasting glucose. Overall (n = 270) there were 186 females (69%) and 84 males (31%). The prevalence of impaired fasting blood sugar or diabetes after 8 h of fasting was 15% (95%CI: 11.1, 20.0). Ten percent (26/270) had impaired fasting glucose and 5 % (14/270) had diabetes. Impaired fasting glucose was higher in males than females [AOR = 3.26, (95% CI: 1.15-9.25; p-value = 0.03)]; as well as among patients on second line treatment than those on first line [AOR = 3.87 (95% CI 1.16-12.9); p-value = 0.03]. In contrast those with less likelihood of impaired fasting glucose included patients with a normal BMI (18.5-24.9) than overweight or obese patients [AOR = 0.09 (95% CI 0.03-0.31; p-value < 0.001)]; and participants who had less than 4 diabetes symptoms than those with more than 4 diabetes symptoms [AOR = 0.04 (95% CI 0.02-0.12); p-value < 0.001]. We have found high levels of impaired fasting glucose or diabetes among ART patients compared to what is reported in the general population suggesting missed care and support opportunities associated with metabolic imbalance management. There is thus a need to re-package HIV programming to include integration of diabetes screening as part of the overall care and support strategy.


High-Performance Mach-Zehnder Modulator Based on Thin-Film Lithium Niobate with Low Voltage-Length Product.
Electro-optic modulators (EOMs) based on a thin-film lithium niobate (TFLN) photonic integration platform play a crucial role in loading electrical signals onto optical signals. In this paper, we proposed on-chip EOMs operating at two commercially available wavelengths of 850 and 1550 nm and successfully demonstrated rather low voltage-length products (V π ·Ls) of 0.78 V·cm and 1.29 V·cm, respectively. Additionally, the EOM working at 1550 nm exhibits the capability of 3-dB electro-optic (E-O) bandwidth beyond 40 GHz due to the limitation of our test conditions. This study is quite helpful for understanding EOM structures in a TFLN platform, as well as the fabrication of high-performance and multifunctional EOM devices.


Retroperitoneal fibrosis and constrictive pericarditis-IgG4 related diseases: A case report.
Retroperitoneal fibrosis (RPF) is a rare disease characterized by infiltration of inflammatory cells and deposition of thickened fibrous tissues. The present study presents the case of a 53-year-old patient treated for generalized weakness and fatigue for 1 year prior to hospitalization. A cardiac ultrasound revealed pericardial effusion that required pericardiocentesis, during which 1,400 ml serous fluid with the characteristics of an exudate was aspirated. A pericardiectomy was performed due to persistent effusion and histological examination indicated pericardial fibrosis. A thoracic-abdominal computed tomography scan revealed the presence of retroperitoneal fibrosis. The patient was treated with corticosteroids and azathioprine. Follow-up examinations showed a significant reduction in the amount of abdominal fibrous tissue and no increase in pericardial effusion 1 year following the end of treatment. The patient continues to have regular follow-up control examinations with a cardiologist and nephrologist.


[Application of the polymerase chain reaction technique (PCR) to the molecular diagnosis of myotonic dystrophy].
We report the application of the PCR technique to study the CKMM polymorphisms in 39 Spanish Myotonic Dystrophy affected families. We have studied 255 subjects comprising 116 clinically affected DM patients. The molecular study was informative in 64% of the DM patients. For the 76 at risk individuals, the study was informative in 46 of them, confirming the non carrier status in 34 individuals and demonstrating the at risk haplotype in 12. In the remaining 30 subjects, it was not possible to establish a diagnose with this technique exclusively. The use of the CKMM probe in the DM genetic studies was extremely useful because of the close linkage with the gene (1 cM) and the high heterozygosity (PIC = 0.33). The allelic frequencies detected by the TaqI enzyme (allele I = 0.27; allele i = 0.73) and NcoI enzyme (allele J = 0.29; allele j = 0.71) are similar to the previously reported in other european populations.


Incidence of acute pancreatitis among patients with leptospirosis requiring extracorporeal membrane oxygenation (ECMO): a descriptive study.
Acute pancreatitis (AP) is an infrequently reported manifestation of leptospirosis. It is more commonly seen in patients with acute respiratory distress syndrome. Despite novel modalities such as extracorporeal membrane oxygenation (ECMO), the mortality rate remains high and whether this is associated with the lung injury caused by the inflammation in AP remains unclear. A descriptive study was conducted at a tertiary hospital in the Philippines. Primary outcome was defined as the presence or absence of AP. Secondary outcomes were defined as 28-day mortality rate, length of hospital stay, ECMO days, renal replacement therapy (RRT) days, days on mechanical ventilation, presence of local complications of AP and development of nosocomial infections. A total of 27 patients were included in the study, and 88.89% (n=24) were men. The mean age for all patients was 33.59±10.22 years. Out of the 27 patients, 19 (70.37%) were diagnosed with AP. Among these 19 patients, one (5.26%) had necrotising pancreatitis and two (10.52%) developed local complications of pancreatitis. Six patients (31.58%) died among those who developed AP, while one (12.50%) died among those who did not. The duration of hospital stay, ECMO, RRT, mechanical ventilation and development of nosocomial infections was also higher in the group who presented with AP. AP is an under-reported complication of leptospirosis. Our study demonstrated a higher mortality and morbidity in patients with leptospirosis who developed AP.


Characterization of monoclonal antibodies to human melanoma-associated antigens.
The hybridomas No. 165.28T, No. 473.54S, and No. 653.25N derived from the fusion of myeloma cells with splenocytes from mice immunized with cultured human melanoma cells secreted monoclonal antibodies recognizing antigenic determinants maximally expressed on cultured human melanoma cells and freshly explanted melanoma cells. Monoclonal antibody No. 376.74T reacted also with carcinoma cell lines but with a significantly lower titer. Rosette inhibition assay showed that these antigenic determinants were expressed on antigenic structures, which are not associated with beta 2 microglobulin and histocompatibility antigens. Two monoclonal antibodies recognized the same or closely associated antigenic determinants, and the remaining two monoclonal antibodies reacted with distinct antigenic determinants. All four monoclonal antibodies could mediate antibody-dependent cellular cytotoxicity of cultured melanoma cells, but none could mediate complement-dependent cytotoxicity.


The prevalence of hepatitis C among healthcare workers: a systematic review and meta-analysis.
The aim of this study was to estimate the prevalence of viral hepatitis C (HCV) infection among healthcare workers (HCWs) compared to the general population. A systematic search for the years 1989-2014 was conducted in the Medline, Embase and Cochrane databases. Studies on hepatitis C in HCWs were included if they incorporated either a control group or reference data for the general population. The study quality was classified as high, moderate or low. Pooled effect estimates were calculated to determine the odds of occupational infection. Heterogeneity between studies was analysed using the χ(2) test (p<0.10) and quantified using the I(2) test. 57 studies met our criteria for inclusion and 44 were included in the meta-analysis. Analysis of high and moderate quality studies showed a significantly increased OR for HCV infection in HCWs relative to control populations, with a value of 1.6 (95% CI 1.03 to 2.42). Stratification by study region gave an OR of 2.1 in low prevalence countries; while stratification by occupational groups gave an increased prevalence for medical (OR 2.2) and for laboratory staff (OR 2.2). The OR for professionals at high risk of blood contact was 2.7. The pooled analysis indicates that the prevalence of infection is significantly higher in HCWs than in the general population. The highest prevalence was observed among medical and laboratory staff. Prospective studies that focus on HCW-specific activity and personal risk factors for HCV infection are needed.


Effect of levodopa-carbidopa intestinal gel on resting tremors in patients with advanced Parkinson's disease.
Resting tremors occur in more than 70% of patients with advanced Parkinson's disease (PD). PD patients with resting tremors are typically treated with oral dopaminergic therapy or non-dopaminergic agents. However, treatment response with these medications is inconsistent and often unsatisfactory. Levodopa-carbidopa intestinal gel (LCIG, also known in the United States as carbidopa-levodopa enteral suspension (CLES)), administered continuously by a portable pump via a percutaneous endoscopic gastrojejunostomy (PEG-J) tube, significantly improves motor complications in patients with advanced PD. This was a post hoc analysis of a large phase 3, 12-month, open-label study evaluating long-term safety and efficacy of LCIG via PEG-J tube (NCT00335153). Unified Parkinson's Disease Rating Scale Part III Question 20 total scores at baseline, measuring resting tremors, were used to stratify patients into three subgroups (none, mild, or significant baseline resting tremors). Out of 354 enrolled patients, 286 had baseline and post-PEG-J assessments of resting tremors and were included in this analysis. At baseline the majority of patients (69%) had no resting tremors, whereas 13% had mild resting tremors, and 18% had significant resting tremors. A complete resolution in resting tremors after 12 months of LCIG treatment was reported for 78% and 70% of patients with mild and significant baseline resting tremors, respectively. Improvements in motor complications and quality of life occurred regardless of degree of baseline resting tremors. LCIG may provide more consistent and sustained improvements in resting tremors that were not well-controlled with optimized oral medication among patients with advanced PD.


Knowledge- and ambiguity-aware robot learning from corrective and evaluative feedback.
In order to deploy robots that could be adapted by non-expert users, interactive imitation learning (IIL) methods must be flexible regarding the interaction preferences of the teacher and avoid assumptions of perfect teachers (oracles), while considering they make mistakes influenced by diverse human factors. In this work, we propose an IIL method that improves the human-robot interaction for non-expert and imperfect teachers in two directions. First, uncertainty estimation is included to endow the agents with a lack of knowledge awareness (epistemic uncertainty) and demonstration ambiguity awareness (aleatoric uncertainty), such that the robot can request human input when it is deemed more necessary. Second, the proposed method enables the teachers to train with the flexibility of using corrective demonstrations, evaluative reinforcements, and implicit positive feedback. The experimental results show an improvement in learning convergence with respect to other learning methods when the agent learns from highly ambiguous teachers. Additionally, in a user study, it was found that the components of the proposed method improve the teaching experience and the data efficiency of the learning process.


Pharmacodynamic distinctions between ouabain, digoxin and digitoxin.
Current pharmacologic texts recognize no significant pharmacodynamic differences between the various cardiac glycosides. To reconsider this concept, a special recording device was constructed so that electrocardiograms and phonocardiograms could be obtained in small mammals without anesthesia or premedication, and a spectrum of cardiac glycosides was studied. Utilizing guinea-pigs, cardiac rate reduction of 20% was sought and achieved with 0.07 mg/kg ouabain, 0.34 mg/kg digoxin and 1.12 mg/kg digitoxin. With comparable rate reduction, digitoxin produced significantly greater shortening of electro-mechanical systole than did ouabain or digoxin (P less than 0.05). Other authors have shown that cardiac glycosides produce slowing of cardiac rate prior to onset of positive inotropic effect. Therefore it is probable that for a given amount of vagal effect (sinoatrial slowing) digitoxin possesses greater positive inotropic effect (abbreviation of electromechanical systole) in guinea-pigs than do ouabain or digoxin. A review of the literature suggests that the same holds true for humans.


Effects of Mindfulness on Diabetes Mellitus: Rationale and Overview.
Diabetes mellitus (DM) is an emerging global healthcare problem and its prevalence is increasing at an alarming rate. Despite improvements in both medical and pharmacological therapies, a complex medical condition may demand a diversified approach, such as: drug therapy, healthy diet and exercises, diabetes education programs, adherence to medical treatment and active participation of the patients in their lifestyle changes, such as stress management. The concept of mindfulness is here defined as the awareness that unfolds from the intention to attentively observe the current experience in a non-judgmental and non-evaluative way. This state of awareness can be enhanced through the use of mindfulness-based interventions (MBIs), which have been associated to many physical and psychological health indicators. The aim of this overview is to offer the rationale and potential benefits of mindfulness in the control of DM and its complications. a narrative review of the current and updated literature available on online database and which came up using the terms "mindfulness" and "diabetes mellitus". Mindfulness-based Interventions (MBIs) can be seen as preventive and complementary interventions in DM, particularly for the relief of symptoms related to depression and anxiety in diabetic patients and also in the management of other factors, including mindful eating, physical exercises and treatment adherence. Although many studies only present research protocols, mindfulness seems to have beneficial effects on all aspects of diabetes, including incidence, control and complications. Furthermore, longer term and more carefully controlled trials are necessary in order to draw consistent conclusions on the beneficial role of MBIs on DM.


Generic two-variable model of excitability.
We present a simple model that displays all classes of two-dimensional excitable regimes. One of the variables of the model displays the usual spikes observed in excitable systems. Since the model is written in terms of a "standard" vector field, it is always possible to fit it to experimental data displaying spikes in an algorithmic way. In fact, we use it to fit a series of membrane potential recordings obtained in the medicinal leech and time series generated with the FitzHugh-Nagumo equations and the excitability model of Eguía et al. [Phys. Rev. E 58, 2636 (1998)]. In each case, we determine the excitability class of the corresponding system.


Analysis of the unfolding process of green fluorescent protein by molecular dynamics simulation.
Molecular dynamics simulation of the enforced stretching of circularly permuted green fluorescent protein (cpGFP) was performed to observe the detailed process of unfolding of beta-sheets in cpGFP and to clarify the structural change arising from the force. The simulation using the generalized Born method with original force field parameters enabled us to observe the unfolding process of the entire region of the protein and to clarify atom motion of the individual domain during the stretching. The force required for the stretching of cpGFP was estimated from the differential of the computed potential energy. A prominent rise in force appeared three times during the stretching. The amplitude and the position of these three peaks were consistent with the observation in atomic force microscopy (AFM) experiments. Further, the movements of atoms involved in each peak were shown to be closely related to the dissociation of hydrogen bonds. Additional simulations for the unfolding process of titin and spectrin also gave satisfactory interpretation of the results of previous AFM experiments. The difference in the enforced stretching process between cpGFP and wild-type GFP was further discussed through the MD simulation.


Clinical presentation of pseudomyxoma peritonei.
We analysed the clinical symptoms and signs of pseudomyxoma peritonei (PMP), a rare syndrome affecting one to two persons per million annually. Presumably, patients with PMP would benefit from early diagnosis. This study was conducted to further characterise the manifestations of PMP. We performed a retrospective chart review of a consecutive series of 82 PMP cases at the Helsinki University Central Hospital from June 1984 to September 2009. We then analysed the patients' characteristics, clinical manifestations, indications for surgery and preoperative radiological investigations. The study involved 53 women (65%) and 29 men (35%). The preponderance of women was statistically significant (p = 0.008). Abdominal pain was the most common chief complaint in the initial evaluation with 23% of the cases. The subsequent more common chief complaints were acute abdomen with 21%, increased abdominal girth with 17%, coincidental diagnosis with 13%, other reasons with 13% and newly onset hernia with 12% of the cases. Suspected ovarian tumour was the most common cause for surgery overall, with 26 of 82 initial operations (32%). Of the 82 initial operations, 23 (28%) were performed with a suspicion or diagnosis of PMP. Computed tomography had a sensitivity of 51% in recognising PMP. While only 28% of patients underwent initial surgery for presumed PMP, the accuracy of preoperative diagnostics was modest. Diagnostics of PMP is challenging due to the mimicking nature of the disease. In case of indistinct intra-abdominal tumour, we recommend, careful patient examination prior to the initial surgery, when possible.


Translation and Psychometric Evaluation of the Arabic Version of the Breastfeeding Self-Efficacy Scale-Short Form Among Women in the United Arab Emirates.
Breastfeeding self-efficacy as a construct has been theoretically and empirically linked to exclusive breastfeeding in studies globally using the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF). However, its application in the Middle East and North Africa region is limited, as it has not been validated. To psychometrically validate the BSES-SF among a sample of mothers in the United Arab Emirates. We psychometrically evaluated the Arabic version of the BSES-SF using a sample of mothers (N = 457) residing in the United Arab Emirates. We used translation techniques, item-test and item-total correlations, confirmatory factor analysis, tests of reliability, and tests of validity. Item-test correlations of scale items ranged from 0.67 to 0.84, while item-total correlations ranged from 0.58 to 0.81. The confirmatory factor model assessed the 14-item scale to be unidimensional with satisfactory model fit indices. Our findings suggested the Arabic-language version of the BSES-SF was a reliable measure (α = 0.95) with strong construct and discriminant validity. BSES-SF scores significantly predicted exclusive breastfeeding (aOR = 1.04; 95% CI [1.02, 1.08]) and exclusive duration (β = .06; 95% CI [0.4, 0.08]), which suggested strong predictive, validity after adjusting for parity, maternal age, maternal education, and study site. We have provided rigorous evidence that the BSES-SF is a valid and reliable measure of breastfeeding self-efficacy among Arabic-speaking women in the UAE. Interventions designed specifically to increase breastfeeding self-efficacy among Arabic-speaking women may be a mechanism to increase the suboptimal rates of breastfeeding exclusivity occurring in much of the MENA region.


A review of the opioid analgesics fentanyl, alfentanil, and sufentanil.
Ultra-short-acting, potent, injectable narcotic agents are important drugs in general anesthetic regimens. These drugs are gaining popularity as both general anesthetic and intravenous sedation agents in oral and maxillofacial surgery. This paper will review the properties of fentanyl, alfentanil, and sufentanil.


Developmental expression of adenosine deaminase in placental tissues of the early postimplantation mouse embryo and uterine stroma.
In this study, we have investigated the distribution of adenosine deaminase (ADA) in embryonic, extra-embryonic, and decidual tissues of the developing mouse embryo. ADA catalyzes a key step in purine metabolism converting adenosine to inosine. ADA specific activity (nmol/min/micrograms protein) was present at low levels in the embryo-decidual unit during the first 2 days of postimplantation development but then increased starting late on Day 6 of gestation (Day 0 plug). By Day 9, ADA specific activity was 80-fold higher than on Day 6. A histochemical staining method for ADA activity was applied to cryostat sections of the implantation site. The developmental increase localized primarily to the trophoblast/antimesometrial decidua interface between Days 7 and 9 of gestation, and decidua basalis and the metrial gland by Day 11. Immunofluorescent staining with sheep anti-mouse ADA antiserum confirmed the presence of ADA antigenicity in tissues forming the maternal/fetal interface. ADA specific activity was 19-fold higher in homogenates of the Day 11 decidua/parietal yolk sac than in the thymus, a tissue generally thought of as ADA-rich. High levels of ADA activity and immunoreactivity were also detected in the embryonal plasma during organogenesis, but the embryo proper showed only low levels. These results indicate that ADA is tightly regulated within tissues forming the maternal/fetal interface during early postimplantation stages of development.


The Frequency of Vitamin D and Calcium Deficiencies Among Women of Reproductive Age in Wadi Etba, Southern Region of Libya.
Background Vitamin D (VD) is the sunshine vitamin. Its deficiency is widely spread worldwide and is implicated in various health problems that have serious financial, mental, and physical health burdens. In Libya, it also has a high incidence as many studies have been conducted on this issue, but the exact situation of VD deficiency in the southern region of Libya remains unclear. Aim The aim of this study is to investigate the frequency of VD deficiency and calcium status among females of reproductive age in Wadi Etba (located in the southern region of Libya). Material and methods This study included 622 females aged 20-40 years attending the Rural Hospital and Private Clinics in Wadi Etba for various health issues during the last five years. The study population was further subdivided into two age groups; 20-30 years and 31-40 years. VD and calcium were measured to determine the VD status among the study population. Results In general, 489 females had sub-optimal VD (<30 ng/mL), representing 78.6% of the total subjects. Normal VD levels were represented only by 133 subjects (21.4%). VD deficiency was represented by 354 subjects (57%) of the total subjects. A total of 232 (37%) subjects were VD-deficient females (18.3 ± 5.5 ng/ml), 122 subjects (20%) were considered poor (severe deficient, VD <10 ng/ml) represented with a mean serum VD of 8.2 ± 0.6. Furthermore, deficiency cases dominated the older age group. Regarding calcium (Ca+2) levels, 31% had lower than the normal range, 68% had normal range, and only 1% showed high Ca+2 levels. On the other hand, there was no correlation between serum levels of VD and Ca+2 levels. Conclusion VD deficiency has become a widespread condition in the southern region of Libya. Therefore, we recommended making lifestyle changes, including extending the exposure time to the sunlight radiation, fortifying foods and drinks with VD, and taking supplementary doses of VD to reduce the high incidence of VD deficiency.


Satisfaction with the initial police response and development of posttraumatic stress disorder symptoms in victims of domestic burglary.
The current study used a prospective design to investigate the association between early symptoms, satisfaction with the initial police response, and development of posttraumatic stress disorder (PTSD) symptomatology in victims of domestic burglary (n = 95). Early symptoms and satisfaction with the initial police response were assessed through telephone interviews conducted within the first month after the burglary and PTSD symptoms 4 to 6 weeks after baseline. Separate regression models were tested for satisfaction with performance and satisfaction with procedure. Results suggested that early symptoms were a risk factor for PTSD symptomatology (β = .50, p < .001 and β = .48, p < .001) above and beyond levels of peritraumatic distress (β = .21, p < .05 and β = .22, p < .05) and irrespective of level of satisfaction (β = -.02, ns and β = -.10, ns). Victims with high levels of early symptoms, however, were clearly at an increased risk of PTSD symptomatology if they scored low on satisfaction at baseline. Results were discussed in light of the framework of therapeutic jurisprudence.


Simian immunodeficiency virus integration preference is similar to that of human immunodeficiency virus type 1.
Simian immunodeficiency virus (SIV) is a useful model for studying human immunodeficiency virus (HIV) pathogenesis and vaccine efficacy. As with all other retroviruses, integration is a necessary step in the replication cycle of SIV. The location of the retrovirus integration site is known to impact on viral gene expression, establishment of viral latency, and other aspects of the replication cycle of a retrovirus. In this study, 148 SIV provirus integration sites were sequenced and mapped in the human genome. Our analysis showed that SIV integration, like that of HIV type 1 (HIV-1), exhibited a strong preference for actively transcribed regions in the genome (A. R. Schroder et al., Cell 110:521-529, 2002) and no preference for the CpG islands or transcription start sites, in contrast to observations for murine leukemia virus (X. Wu et al., Science 300:1749-1751, 2003). The parallel integration target site preferences of SIV and HIV-1 suggest that these lentiviruses may share similar mechanisms for target site selection and that SIV serves as an accurate model of HIV-1 with respect to integration.


The effect of volumetric breast density on the risk of screen-detected and interval breast cancers: a cohort study.
In the light of the breast density legislation in the USA, it is important to know a woman's breast cancer risk, but particularly her risk of a tumor that is not detected through mammographic screening (interval cancer). Therefore, we examined the associations of automatically measured volumetric breast density with screen-detected and interval cancer risk, separately. Volumetric breast measures were assessed automatically using Volpara version 1.5.0 (Matakina, New Zealand) for the first available digital mammography (DM) examination of 52,814 women (age 50 - 75 years) participating in the Dutch biennial breast cancer screening program between 2003 and 2011. Breast cancer information was obtained from the screening registration system and through linkage with the Netherlands Cancer Registry. We excluded all screen-detected breast cancers diagnosed as a result of the first digital screening examination. During a median follow-up period of 4.2 (IQR 2.0-6.2) years, 523 women were diagnosed with breast cancer of which 299 were screen-detected and 224 were interval breast cancers. The associations between volumetric breast measures and breast cancer risk were determined using Cox proportional hazards analyses. Percentage dense volume was found to be positively associated with both interval and screen-detected breast cancers (hazard ratio (HR) 8.37 (95% CI 4.34-16.17) and HR 1.39 (95% CI 0.82-2.36), respectively, for Volpara density grade category (VDG) 4 compared to VDG1 (p for heterogeneity < 0.001)). Dense volume (DV) was also found to be positively associated with both interval and screen-detected breast cancers (HR 4.92 (95% CI 2.98-8.12) and HR 2.30 (95% CI 1.39-3.80), respectively, for VDG-like category (C)4 compared to C1 (p for heterogeneity = 0.041)). The association between percentage dense volume categories and interval breast cancer risk (HR 8.37) was not significantly stronger than the association between absolute dense volume categories and interval breast cancer risk (HR 4.92). Our results suggest that both absolute dense volume and percentage dense volume are strong markers of breast cancer risk, but that they are even stronger markers for predicting the occurrence of tumors that are not detected during mammography breast cancer screening.


[Alcohol, drugs, medication and highway safety in Belgium. Belgian Toxicology and Trauma Study Research Group].
The BTTS study (Belgian Toxicology and Trauma Study) was performed in Belgium between January 15th 1995 and June 15th 1996. The purpose was to investigate how frequently the drivers involved in road accidents were driving under the influence of psychotropic drugs. Two thousand fifty-three blood tests were performed of which 207 in the Liège region. The results obtained at the national level are compared to those obtained at the level of the Liège region. In both cases, the BTTS study allows the conclusion that a considerable proportion of drivers involved in road accidents resulting in significant traumatic consequences were driving under the influence of substances with psychotropic properties.


Analysis of mass spectral serum profiles for biomarker selection.
Mass spectrometric profiles of peptides and proteins obtained by current technologies are characterized by complex spectra, high dimensionality and substantial noise. These characteristics generate challenges in the discovery of proteins and protein-profiles that distinguish disease states, e.g. cancer patients from healthy individuals. We present low-level methods for the processing of mass spectral data and a machine learning method that combines support vector machines, with particle swarm optimization for biomarker selection. The proposed method identified mass points that achieved high prediction accuracy in distinguishing liver cancer patients from healthy individuals in SELDI-QqTOF profiles of serum. MATLAB scripts to implement the methods described in this paper are available from the HWR's lab website http://lombardi.georgetown.edu/labpage


Differential gene expression revealed with RNA-Seq and parallel genotype selection of the ornithine decarboxylase gene in fish inhabiting polluted areas.
How organisms adapt to unfavorable environmental conditions by means of plasticity or selection of favorable genetic variants is a central issue in evolutionary biology. In the Maipo River basin, the fish Basilichthys microlepidotus inhabits polluted and non-polluted areas. Previous studies have suggested that directional selection drives genomic divergence between these areas in 4% of Amplified Fragment Length Polymorphism (AFLP) loci, but the underlying genes and functions remain unknown. We hypothesized that B. microlepidotus in this basin has plastic and/or genetic responses to these conditions. Using RNA-Seq, we identified differentially expressed genes in individuals from two polluted sites compared with fish inhabiting non-polluted sites. In one polluted site, the main upregulated genes were related to cellular proliferation as well as suppression and progression of tumors, while biological processes and molecular functions involved in apoptotic processes were overrepresented in the upregulated genes of the second polluted site. The ornithine decarboxylase gene (related to tumor promotion and progression), which was overexpressed in both polluted sites, was sequenced, and a parallel pattern of a heterozygote deficiency and increase of the same homozygote genotype in both polluted sites compared with fish inhabiting the non-polluted sites was detected. These results suggest the occurrence of both a plastic response in gene expression and an interplay between phenotypic change and genotypic selection in the face of anthropogenic pollution.


Linking Patient-Centered Outcomes to Neuropsychological Practice: A Conceptual Framework and Opportunities for Research.
In the current healthcare climate, reimbursement for services is increasingly linked to the ability to demonstrate beneficial patient outcomes. Neuropsychology faces some unique challenges in outcomes research, namely, that neuropsychologists often do not follow patients over time and the effect of neuropsychological services on patient outcomes may not be fully realized until under another provider's care. Yet there is an urgent need for empirical evidence linking neuropsychological practice to positive patient outcomes. To provide a framework for this research, we define a core set of patient-centered outcomes and neuropsychological processes that apply across practice settings and patient populations. Within each area, we review the available existing literature on neuropsychological outcomes, identifying substantial gaps in the literature for future research. This work will be critical for the field to demonstrate the benefit of neuropsychological services, to continue to advocate effectively for reimbursement, and to ensure high-quality patient care.


Differential effects of pancreatic polypeptide on luteinizing hormone release in female rats.
Observations that a pancreatic polypeptide-like substance is present in hypothalamus and may coexist with catecholamines prompted evaluation of its possible role in control of luteinizing hormone (LH) secretion. Intracerebroventricular administration of 0.5 or 2 micrograms of human pancreatic polypeptide to ovariectomized, hormonally untreated rats significantly decreased LH levels. However, when administered to ovariectomized rats pretreated with estradiol benzoate and progesterone, the neuropeptide significantly increased circulating LH in a dose-related manner. These results, which are similar to those reported for centrally administered norepinephrine, raise the possibility that pancreatic polypeptide, or a similar peptide, may participate in the physiologic regulation of LH release, either independently or perhaps as a neuromodulator or a cotransmitter with catecholamines.


Training efforts to reduce reports of workplace violence in a community health care facility.
The objective of this study was to measure reports of workplace violence (WPV) after an online training program on WPV for health care workers. Recognition of the prevalence of WPV (physical, emotional-verbal, and sexual) suggests a great need for employers to provide training to all health care workers as a first-line effort to reduce or prevent WPV. A 3-hour online training program for WPV was offered to 43 workers attending an informational session. Volunteers included 22 participants designated for training and 21 volunteers designated to serve as control subjects. Pretraining WPV work area assessments were completed by all participants and compared between training participants and control subjects. At 6 months, comparisons were made between 3 groups: Group A, those who completed the training; Group B, control subjects; and Group C, those who did not complete the training within the designated period. Group C was defined as a separate group because some participants within this group were workers from the same work areas as were Group A participants. Comparisons of preassessments and postassessments of WPV for Group A and assessments of WPV across the three groups were made. Participants reported 200 WPV events over a 6-month period before training. Pretraining reports of WPV were statistically different between training participants and control subjects for total and emotional-verbal WPV events. At 6 months after the training, a reduction in sample size and reports of all types of WPV was noted across the three groups (i.e., those who completed the training, those who did not complete it, and control subjects). Owing to the small number of reported physical and sexual WPV events, only total and emotional-verbal WPV events were examined. No difference was noted between the three groups for total events; however, emotional-verbal abuse was statistically significant between the groups. In addition, a statistically significant difference was noted among participants before and after the completion of the online training. Despite the reported prevalence of WPV, a significant number of health care workers did not make training a priority. Participants who were designated for training and who subsequently completed it reported the most number of events before and after training. Proportionately per number of participants after training, fewer total WPV events were reported; however, because of the attrition rate and group sample size, significance was not reached. Reports of emotional-verbal abuse remained high after training, which could suggest a heightened awareness of this type of WPV with a personal redefinition of WPV or a heightened staff and administration sensitivity to reporting. Although differences existed among training participants and control subjects before training, significance could not be achieved among the three groups owing to validity threats, including subject mortality, diffusion between groups, selection bias, and small sample size. However, the finding that training can make a difference is important and encourages replication of this study with a larger sample size and a larger setting. Finding high rates of emotional-verbal abuse across work areas and support for training benefits enhance the need for training programs with an increased focus on emotional-verbal WPV.


An Update on Nitric Oxide Production and Role Under Phosphorus Scarcity in Plants.
Phosphate (P) is characterized by its low availability and restricted mobility in soils, and also by a high redistribution capacity inside plants. In order to maintain P homeostasis in nutrient restricted conditions, plants have developed mechanisms which enable P acquisition from the soil solution, and an efficient reutilization of P already present in plant cells. Nitric oxide (NO) is a bioactive molecule with a plethora of functions in plants. Its endogenous synthesis depends on internal and environmental factors, and is closely tied with nitrogen (N) metabolism. Furthermore, there is evidence demonstrating that N supply affects P homeostasis and that P deficiency impacts on N assimilation. This review will provide an overview on how NO levels in planta are affected by P deficiency, the interrelationship with N metabolism, and a summary of the current understanding about the influence of this reactive N species over the processes triggered by P starvation, which could modify P use efficiency.


Biomechanical effects of a hard insert and air space in mouthguards on the shock absorption and protection against fractures of direct resin composite veneers from trauma.
Mouthguards (MTG) are used to prevent dental trauma. However, their protective effect on esthetic restorations and whether modified MTGs are beneficial is uncertain. The aim of this study was to evaluate the effect of hard inserts and air spaces in MTGs in protecting direct resin composite veneers during impact. Twenty resin composite veneers (1.0 mm) were prepared on upper right central incisors on printed maxilla models using polyether. The effect of the MTGs was evaluated in four groups (n = 5): Con-MTG, conventional custom-fit MTGs made with two layers of ethylene vinyl acetate (EVA); Air-MTG, MTGs with the insertion of 2.0 mm air space between the two layers of EVA and tooth surface; PETG-MTG, MTGs with 1.0 mm of polyethylene terephthalate glycol-modified (PETG) inserted between the EVA layers; and No-MTG, comprising resin composite veneers without MTG. The printed models were fixed in a pendulum device, and the impact was performed at 30°. The strain (μS) and shock absorption (%) of the MTG were recorded using strain gauges. Failure modes and cracks were evaluated using macro photography and transillumination and analyzed using the chi-square test. Strain and shock absorption data were analyzed using the one-way analysis of variance followed by Tukey's test (α = 0.05). Mouthguards reduced strain and enhanced shock absorption, regardless of the MTG type (p < .001). Con-MTG, Air-MTG, and PETG-MTG had shock absorption rates of 76.1%, 72.3%, and 33.4%, respectively (p < .001). The single No-MTG model had a root fracture, while all the others had superficial damage. None of the MTG models had cracks or fractures. Mouthguards protected the resin composite veneers. The Con-MTG and Air-MTG groups had lower strain and greater shock absorption than the PETG-MTG. Resin veneers had no cracks or damage following MTG use. However, 80% of the veneers had surface damage when no MTG was used.


Prevalence, predilection sites and pathological findings of Taenia multiceps coenuri in slaughtered goats from south-east Iran.
Coenurosis is a zoonotic disease in a variety of ruminants caused by the metacestode of Taenia multiceps. The coenuri in the brain and spinal cord of sheep and goats have been identified as Coenurus cerebralis whilst those reported in other tissues have been named Coenurus gaigeri. This study was conducted during the spring and summer of 2011. Out of 25 739 goats inspected in slaughterhouses, 23 carcasses (0.09%) revealed one or multiple visible swellings on the different muscles and visceral organs. The coenuri, of variable sizes, were found mainly in the muscles of the thigh, shoulder and neck, and were less common in the abdominal muscles and subcutaneous tissues. Coenuri were also found in the diaphragm, tongue, intercostal muscles, lung, parotid area and tunica adventitia of the aorta in a goat with severe infection. The brains of slaughtered goats that had coenuri in their skeletal muscles were examined and coenuri were found in two specimens (8.69%). The coenuri were located in the occipital lobe, the anterior part of the right cerebrum and the parietal lobe of the left cerebrum. Histopathologically, coenuri in the brain caused pressure atrophy and liquefactive necrosis in the surrounding tissues, hyperaemia, perivascular cuffing, neuronal degeneration, neuronophagia, satellitosis, diffuse microgliosis and astrocytosis. Coenuri in the skeletal muscles caused degenerative and necrotic changes, hyalinisation and myositis. In the lung, tissues around the coenurus revealed atelectasis and focal interstitial fibrosis. In the present study, concurrent occurrence of coenuri in the central nervous system and skeletal muscles supports the hypothesis that C. cerebralis and C. gaigeri are different names for the metacestodes of the same species of tapeworm.


[Early effectiveness of a new minimally invasive plate in treatment of varus-type ankle arthritis].
To evaluate the early effectiveness of a new minimally invasive plate in the treatment of varus-type ankle arthritis. A clinical data of 15 patients with varus-type ankle arthritis who met the selection criteria between March 2021 and October 2021 were retrospectively analyzed. All the patients were treated with medial open-wedge supramalleolar osteotomy and fibular osteotomy. The osteotomies were fixed with the new minimally invasive plate. There were 7 males and 8 females with an average age of 49.8 years (range, 16-71 years). The causes of ankle arthritis included post-fracture deformity in 1 case, sprain in 8 cases, and acquired clubfoot in 1 case; and 5 cases were without obvious factors. The disease duration ranged from 1 to 12 years, with an average of 4.1 years. Comparisons were made between pre-operation and the last follow-up in the Takakura staging, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, foot function index (FFI), visual analogue scale (VAS) score, tibial anterior surface angle (TAS), tibial lateral surface angle (TLS), and talar tilt (TT). All incisions healed by first intention. All patients were followed up 7-18 months (mean, 12.8 months). At last follow-up, the AOFAS ankle-hindfoot score, FFI, VAS score, and Takakura staging significantly improved when compared with the preoperative ones ( P<0.05). X-ray films showed that the osteotomy healed at 3 months after operation. At last follow-up, TAS significantly increased and TT decreased when compared with the preoperative ones ( P<0.05), and the difference in TLS between pre- and post-operation was not significant ( P>0.05). Complications included 1 case of intraoperative screw breakage and 2 cases of nerve injury of the affected foot. None of the patients complained of significant discomfort at the plate placement during follow-up, and no loosening of the internal fixator occurred. Eleven patients were very satisfied with the effeectiveness, while 4 were relatively satisfied. The new minimally invasive plate for the varus-type ankle arthritis has good early effectiveness in relieving ankle pain, correcting deformity, improving limb alignment and ankle function, and reducing the incidence of postoperative incisional complications.


Inferring mechanical properties of the SARS-CoV-2 virus particle with nano-indentation tests and numerical simulations.
The pandemic caused by the SARS-CoV-2 virus has claimed more than 6.5 million lives worldwide. This global challenge has led to accelerated development of highly effective vaccines tied to their ability to elicit a sustained immune response. While numerous studies have focused primarily on the spike (S) protein, less is known about the interior of the virus. Here we propose a methodology that combines several experimental and simulation techniques to elucidate the internal structure and mechanical properties of the SARS-CoV-2 virus. The mechanical response of the virus was analyzed by nanoindentation tests using a novel flat indenter and evaluated in comparison to a conventional sharp tip indentation. The elastic properties of the viral membrane were estimated by analytical solutions, molecular dynamics (MD) simulations on a membrane patch and by a 3D Finite Element (FE)-beam model of the virion's spike protein and membrane molecular structure. The FE-based inverse engineering approach provided a reasonable reproduction of the mechanical response of the virus from the sharp tip indentation and was successfully verified against the flat tip indentation results. The elastic modulus of the viral membrane was estimated in the range of 7-20 MPa. MD simulations showed that the presence of proteins significantly reduces the fracture strength of the membrane patch. However, FE simulations revealed an overall high fracture strength of the virus, with a mechanical behavior similar to the highly ductile behavior of engineering metallic materials. The failure mechanics of the membrane during sharp tip indentation includes progressive damage combined with localized collapse of the membrane due to severe bending. Furthermore, the results support the hypothesis of a close association of the long membrane proteins (M) with membrane-bound hexagonally packed ribonucleoproteins (RNPs). Beyond improved understanding of coronavirus structure, the present findings offer a knowledge base for the development of novel prevention and treatment methods that are independent of the immune system.


A Novel Relative Position Estimation Method for Capsule Robot Moving in Gastrointestinal Tract.
Recently, a variety of positioning and tracking methods have been proposed for capsule robots moving in the gastrointestinal (GI) tract to provide real-time unobstructed spatial pose results. However, the current absolute position-based result cannot match the GI structure due to its unstructured environment. To overcome this disadvantage and provide a proper position description method to match the GI tract, we here present a relative position estimation method for tracking the capsule robot, which uses the moving distance of the robot along the GI tract to indicate the position result. The procedure of the proposed method is as follows: firstly, the absolute position results of the capsule robot are obtained with the magnetic tracking method; then, the moving status of the robot along the GI tract is determined according to the moving direction; and finally, the movement trajectory of the capsule robot is fitted with the Bézier curve, where the moving distance can then be evaluated using the integral method. Compared to state-of-the-art capsule tracking methods, the proposed method can directly help to guide medical instruments by providing physicians the insertion distance in patients' bodies, which cannot be done based on absolute position results. Moreover, as relative distance information was used, no reference tracking objects needed to be mounted onto the human body. The experimental results prove that the proposed method achieves a good distance estimation of the capsule robot moving in the simulation platform.


The contribution of psychological factors to recovery after mild traumatic brain injury: is cluster analysis a useful approach?
Outcomes after mild traumatic brain injury (MTBI) vary, with slow or incomplete recovery for a significant minority. This study examines whether groups of cases with shared psychological factors but with different injury outcomes could be identified using cluster analysis. This is a prospective observational study following 147 adults presenting to a hospital-based emergency department or concussion services in Christchurch, New Zealand. This study examined associations between baseline demographic, clinical, psychological variables (distress, injury beliefs and symptom burden) and outcome 6 months later. A two-step approach to cluster analysis was applied (Ward's method to identify clusters, K-means to refine results). Three meaningful clusters emerged (high-adapters, medium-adapters, low-adapters). Baseline cluster-group membership was significantly associated with outcomes over time. High-adapters appeared recovered by 6-weeks and medium-adapters revealed improvements by 6-months. The low-adapters continued to endorse many symptoms, negative recovery expectations and distress, being significantly at risk for poor outcome more than 6-months after injury (OR (good outcome) = 0.12; CI = 0.03-0.53; p < 0.01). Cluster analysis supported the notion that groups could be identified early post-injury based on psychological factors, with group membership associated with differing outcomes over time. Implications for clinical care providers regarding therapy targets and cases that may benefit from different intensities of intervention are discussed.


Maternal responsiveness and toddler body mass index z-score: Prospective analysis of maternal and child mealtime interactions.
Responsive feeding, where parents are guided by children's hunger and satiation cues and provide appropriate structure and support for eating, is believed to promote healthier weight status. However, few studies have assessed prospective associations between observed parental feeding and toddler growth. We characterized toddler growth from 18 to 36 months and, in a subset of families, examined whether observed maternal responsiveness to toddler satiation cues and encouraging prompts to eat at 18 and 24 months were associated with toddler body mass index z-score (BMIz) from 18 to 36 months. Participants included 163 toddlers and their mothers with overweight/obesity who had participated in a lifestyle intervention during pregnancy. Anthropometrics were measured at 18, 24, and 36 months. In a subsample, mealtime interactions were recorded in families' homes at 18 (n = 77) and 24 (n = 75) months. On average, toddler BMIz remained stable from 18 to 36 months with 31.3% (n = 51) categorized with a healthy weight, 56.4% (n = 92) with at risk for overweight and 12.3% (n = 20) with overweight. Fewer maternal prompts to eat at 18 months was associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p = .002). Higher child weight status at 12 months was also associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p < .001). Neither 24-month maternal prompts nor 18 or 24 month responsiveness to satiation cues were associated with toddler BMIz. In this diverse sample, weight status was relatively stable from 18 to 36 months. Maternal prompts to eat measured earlier in toddlerhood and prior child weight status were associated with toddler BMIz.


[Experiences of family caregivers of patients with terminal cancer].
This study done to identify the experiences of families caring for patients with terminal cancer. The question was, "What is the caregiving experience of a family who has a member with terminal cancer?" Grounded Theory was applied and in-depth interviews were done with 11 family members. Interviews were recorded with the interviewees' consent and were transcribed and analyzed. Participants' relationships to patients were 6 spouses, 4 daughters, and 1 mother. The ages of the participants were between 32 and 62, with an average of 47.5. The study showed "enduring with bonds" as the main category and the main factor affecting this category was the "patients' diagnosis of terminal cancer." The caregiving experience was divided into four stages: shock, confusion, struggle, and acceptance. Mediating factors were relationship with the patient, intimacy with the patient, social support, communication, and trust. Conclusively, participants underwent internal maturity, and changes occurred in family and social and personal life. The families took care of the patients with responsibility and love. The study results should help with the understanding of a family with a member with terminal cancer and should be used to develop nursing, mediating, and consulting programs for these caregivers.


Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A.
In the canonical DNA double helix, Watson-Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated (∼0.02-0.4%) and short-lived (lifetimes ∼0.2-2.5 ms) Hoogsteen (HG) bps. To gain insights into transient HG bps, we used solution-state nuclear magnetic resonance spectroscopy, including measurements of residual dipolar couplings and molecular dynamics simulations, to examine how a single HG bp trapped using the N1-methylated adenine (m1A) lesion affects the structural and dynamic properties of two duplexes. The solution structure and dynamic ensembles of the duplexes reveals that in both cases, m1A forms a m1A•T HG bp, which is accompanied by local and global structural and dynamic perturbations in the double helix. These include a bias toward the BI backbone conformation; sugar repuckering, major-groove directed kinking (∼9°); and local melting of neighboring WC bps. These results provide atomic insights into WC/HG breathing dynamics in unmodified DNA duplexes as well as identify structural and dynamic signatures that could play roles in m1A recognition and repair.


Media for the enhancement of fluorescent pigment production by Pseudomonas species.
By a simple modification, common commercial dehydrated laboratory media can be used for the evaluation of fluorescent pigment excretion by Pseudomonas species. The addition of sufficient sterile egg white or of the iron-binding egg white protein, conalbumin, to bind all the iron in these media converted them to efficient diagnostic media. The amount of egg white found to be satisfactory was 10% of the final medium volume. Its conalbumin equivalent was 1.7 mg of conalbumin per ml of final medium. Such modified media are at least the equivalent of the medium recommended for the evaluation of this important characteristic.


Preoperative imaging of primary intra-abdominal gynaecological malignancies. Diagnostic accuracy of CT-scan and MRI. A Greek cohort study.
To determine the radiological modalities that provide at the initial workout the most accurate information regarding the operability and the type of operation for patients with primary cervical, endometrial, and ovarian carcinomas. The medical records of 611 patients with gynaecological cancer were reviewed. The preoperative radiological findings were compared with the intraoperative and pathological ones. The diagnostic accuracy of CT and MRI at various sites was evaluated for all three kinds of carcinoma in combination. MRI was more accurate than CT in determining cervical enlargement (82% vs 73%), parametrial invasion (91% vs 74%) and the only examination that could evaluate cervical tumour size as well as cervical stromal and myometrial infiltration. Regarding lymph node involvement their results were similar (86% vs 88%). Both methods were comparably accurate in evaluating ovarian tumours (82% vs 84%), ascites (82% vs 81%), omental (73% vs 77%) and mesenterial infiltration (88% vs 93%). They also proved to be highly accurate (100% vs 98%) in the evaluation of solid abdominal organs. Non-enchanced MRI should only be used for the preoperative evaluation of a patient with cervical carcinoma, while CT with intravenous and per os contrast media for one with ovarian cancer. Regarding patients with endometrial cancer, no high-resolution method is required for endometrioid grade I tumours, while contrast-enchanced MRI should be employed for all other cases.


When a Burr Can Not Penetrate the Calcified Lesion, Increasing Burr Size as Well as Decreasing Burr Size Can Be a Solution in Rotational Atherectomy.
In rotational atherectomy (RA), several burr sizes are available, such as 1.25 mm, 1.5 mm, 1.75 mm, or ≥ 2.0 mm. It is important to select an appropriate burr size for each lesion because rotational atherectomy has several unique complications regarding burrs such as entrapment or perforation. When a burr cannot penetrate the lesion, downsizing of the burr is generally recommended. Also, if the smallest burr (1.25 mm) cannot penetrate the lesion, a change to a more supportive or larger French guiding catheter has been recommended. We describe the case of a 68 year-old female who was referred to our department for percutaneous coronary intervention to the calcified stenosis in the middle of the left anterior descending coronary artery. We used the smallest burr (1.25 mm) and a supportive 7 Fr guiding catheter to penetrate the lesion. However, the smallest burr could not pass the lesion even after 14 sessions (total ablation time: 339 seconds). We intentionally increased the burr size from 1.25 mm to 1.5 mm. The 1.5 mm burr successfully passed the lesion without any perforation or burr entrapment. In this manuscript, we discuss why increasing the burr size was successful for this severely calcified lesion that was not penetrated by the smallest burr.


Impact of the localization of dendritic calcium persistent inward current on the input-output properties of spinal motoneuron pool: a computational study.
The goal of this study is to investigate how the dendritic Ca-PIC location influences nonlinear input-output properties and depends on the type of motoneurons across the motoneuron pool. A model motoneuron pool consisting of 10 motoneurons was constructed using a recently developed two-compartment modeling approach that reflected key cell type-associated properties experimentally identified. The dendritic excitability and firing output depended systematically on both the PIC location and the motoneuron type. The PIC onset and offset in the current-voltage (I-V) relationship tended to occur at more hyperpolarized voltages as the path length to the PIC channels from the soma increased and as the cell type shifted from high- to low-threshold motoneurons. At the same time, the firing acceleration and frequency hysteresis in the frequency-current (F-I) relationship became faster and larger, respectively. However, the PIC onset-offset hysteresis increased as the path length and the recruitment threshold increased. Furthermore, the gain of frequency-current function before full PIC activation was larger for PIC channels located over distal dendritic regions in low- compared with high-threshold motoneurons. When compared with previously published experimental observations, the modeling concurred when Ca-PIC channels were placed closer to the soma in high- than low-threshold motoneurons in the model motoneuron pool. All of these results suggest that the negative relationship of Ca-PIC location and cell recruitment threshold may underlie the systematic variation in I-V and F-I transformation across the motoneuron pool.NEW & NOTEWORTHY How does the dendritic location of calcium persistent inward current (Ca-PIC) influence dendritic excitability and firing behavior across the spinal motoneuron pool? This issue was investigated developing a model motoneuron pool that reflected key motoneuron type-specific properties experimentally identified. The simulation results point out the negative relationship between the distance of Ca-PIC source from the soma and cell recruitment threshold as a basis underlying the systematic variation in input-output properties of motoneurons over the motoneuron pool.


Identification of Metabolic risk phenotypes predisposing to Non-Alcoholic Fatty Liver Disease in a Pakistani Cohort.
Non-alcoholic fatty liver disease (NAFLD) has emerged in the last two decades with worldwide prevalence of 25.24%. Due to its increasing frequency in Pakistan, it was aimed to identify disease predisposing metabolic risks and their association with NAFLD. Anthropometric and biochemical investigations were collected from 1366 subjects with minor metabolic disturbances. Comparative analyses were performed to compute frequencies of common metabolic risk phenotypes while their associations with NAFLD were explored using regression analyses. The prevalence of NAFLD was also estimated in total, age, and gender-based population cohorts. Among metabolic risk phenotypes obesity, hyperglycemia, hypertension, and dyslipidemia significantly associated (p<0.001) with NAFLD risk irrespective of age, gender, and BMI. Prevalence of NAFLD in total study cohort was 14.8%, 16.1% in males, 13.4% in females, 19.9% in ≥40 years and 8.7% in ≤40 years respectively. General Pakistani populations experiencing common metabolic disturbances are at high risk of NAFLD development, especially male gender and advanced age. Based on these parameters the stratified NAFLD population could be treated accordingly.


A cDNA clone closely associated with non-A, non-B hepatitis.
A lambda gt11 cDNA library was constructed from RNA purified from hepatitis B viral surface antigen-negative human plasma with high alanine aminotransferase activity. A cDNA clone, designated as C8-2, was isolated by immunoscreening with mixed sera from non-A, non-B hepatitis (NANBH) carrier and convalescent chimpanzees. The recombinant protein produced by C8-2 reacted specifically with sera of patients in the chronic phase of NANBH. The sequence of C8-2, 269 bp, did not hybridized with any human or chimpanzee genomic DNA, and had no homology with those of primates and viruses. The existence of this sequence in RNA of possibly infectious plasma was shown by RNA blot hybridization and by Southern blot analysis of products amplified by the polymerase chain reaction. These results strongly suggest that C8-2 is derived from the agent of this viral hepatitis.


Bioactive Compounds Intake of the Brazilian Population According to Geographic Region.
Studies have been conducted in order to estimate bioactive compound consumption across populations, with substantial disparities according to the origin of the cohort examined. In this sense, Brazil is a continental country with marked differences in food plant availability across geographic regions. We aimed to estimate the bioactive compound intake according to Brazilian geographic region, as well as to determine the major contributors. Data were obtained from the National Dietary Survey 2017-2018, a cross-sectional population-based study including data on the individual food intake of 46,164 subjects aged ≥10 years. The consumption of polyphenols (total and classes) was significantly higher in the South compared with other regions (p = 0.0001). Total carotenoid intake was higher in the Midwest, followed by the Southeast (p = 0.0001). Tea was the main supplier of total polyphenol intake in the South, whereas coffee contributed the most to total polyphenol intake in other Brazilian regions. Açaí, caja juice, mango and corn were important suppliers of carotenoid intake in the North and Northeast. Bioactive compound intake presented variations according to Brazilian region, and individuals living in the South, Midwest and Southeast may experience higher bioactive-dense diets. We highlight the potential of many food plants for sustained explorations to the development of marketable products, possibly increasing the bioactive compound intake.


Localization of the synthesis of very-long-chain fatty acid in mitochondria from Saccharomyces cerevisiae.
The localization of the mitochondrial elongation activities ('elongases') from Saccharomyces cerevisiae has been investigated. It was shown, using carboxyatractyloside in the incubation mixture, that synthesis of very-long-chain fatty acids probably occurred outside the matrix and, by fractionation experiments, that elongases are membrane-bound enzymes. The solubilization of the outer membrane by digitonin showed that three elongating activities are correlated with a marker of the outer membrane and not with an inner membrane marker. A further partial purification of the outer membrane showed that elongases are present in the outer membrane of mitochondria.


Interactions of nitrifying bacteria and heterotrophs: identification of a Micavibrio-like putative predator of Nitrospira spp.
Chemolithoautotrophic nitrifying bacteria release soluble organic compounds, which can be substrates for heterotrophic microorganisms. The identities of these heterotrophs and the specificities of their interactions with nitrifiers are largely unknown. In this study, we incubated nitrifying activated sludge with (13)C-labeled bicarbonate and used stable isotope probing of 16S rRNA to monitor the flow of carbon from uncultured nitrifiers to heterotrophs. To facilitate the identification of heterotrophs, the abundant 16S rRNA molecules from nitrifiers were depleted by catalytic oligonucleotides containing locked nucleic acids (LNAzymes), which specifically cut the 16S rRNA of defined target organisms. Among the (13)C-labeled heterotrophs were organisms remotely related to Micavibrio, a microbial predator of Gram-negative bacteria. Fluorescence in situ hybridization revealed a close spatial association of these organisms with microcolonies of nitrite-oxidizing sublineage I Nitrospira in sludge flocs. The high specificity of this interaction was confirmed by confocal microscopy and a novel image analysis method to quantify the localization patterns of biofilm microorganisms in three-dimensional (3-D) space. Other isotope-labeled bacteria, which were affiliated with Thermomonas, colocalized less frequently with nitrifiers and thus were commensals or saprophytes rather than specific symbionts or predators. These results suggest that Nitrospira spp. are subject to bacterial predation, which may influence the abundance and diversity of these nitrite oxidizers and the stability of nitrification in engineered and natural ecosystems. In silico screening of published next-generation sequencing data sets revealed a broad environmental distribution of the uncultured Micavibrio-like lineage.


Discomfort and the cortical haemodynamic response to coloured gratings.
In five experiments we measured the amplitude of the haemodynamic response to visual patterns using near infrared spectroscopy of the visual cortex. The patterns were gratings with bars that differed in chromaticity but not in luminance. In all experiments, with a wide range of chromaticities of the grating bars, the amplitude of the haemodynamic response increased with the separation of the chromaticities in the CIE 1976 UCS diagram. The amplitude did not vary consistently with the cone activation, or with the signal in colour difference channels. In four further experiments, again with a wide range of chromaticities, the gratings were rated for visual comfort. Discomfort increased consistently with the separation of the chromaticities. Given that a large haemodynamic response to patterns is generally associated with headache, we suggest that the discomfort may be a homeostatic signal to reduce sustained metabolic load on the visual cortex.


Support vector regression for high-resolution beach surface moisture estimation from terrestrial LiDAR intensity data.
Beach Surface Moisture (BSM) is a key attribute in the coastal investigations of land-atmospheric water and energy fluxes, groundwater resource budgets and coastal beach/dune development. In this study, an attempt has been made for the first time to estimate BSM from terrestrial LiDAR intensity data based on the Support Vector Regression (SVR). A long-range static terrestrial LiDAR (Riegl VZ-2000) was adopted to collect point cloud data of high spatiotemporal resolution on the Ostend-Mariakerke beach, Belgium. Based on the field moisture samples, SVR models were developed to retrieve BSM, using the backscattered intensity, scanning ranges and incidence angles as input features. The impacts of the training samples' size and density on the predictive accuracy and generalization capability of the SVR models were fully investigated based on simulated BSM-intensity samples. Additionally, we compared the performance of the SVR models for BSM estimation with the traditional Stepwise Regression (SR) method and the Artificial Neural Network (ANN). Results show that SVR could accurately retrieve the BSM from the backscattered intensity with high reproducibility (average test RMSE of 0.71% ± 0.02% and R2 of 0.98% ± 0.002%). The Radial Basis Function (RBF) was the most suitable kernel for SVR model development in this study. The impacts of scanning geometry on the intensity could also be accurately corrected in the process of estimating BSM by the SVR models. However, compared to the SR method, the predictive accuracy and generalization performance of SVR models were significantly dependent on the training samples' coverage, size and distribution, suggesting the need for the training samples of uniform distribution and representativeness. The minimum size of training samples required for SVR model development was 54. Under this condition, SVR performed similarly to ANN with a test RMSE of 1.06%, but SVR still performed acceptably (with an RMSE of 1.83%) even using extremely few training samples (only 16 field samples of uniform distribution), far better than the ANN (with an RMSE of 4.02%).


Optic disc neovascularization in dominant exudative vitreoretinopathy.
Dominant exudative vitreoretinopathy (DEVR) is inherited retinal vascular disorder which is characterized by peripheral retinal neovascularization, tractional retinal detachment, subretinal, exudation, and vitreous fibrosis. A milder form of involvement characterized by capillary nonperfusion and straightening of the retinal vessels may be present in asymptomatic individuals. We describe a 15-year-old patient who presented with optic disc neovascularization, a finding not previously reported in association with DEVR. Angiographic evidence of DEVR in successive generations confirmed the diagnosis. The findings in mild and advanced DEVR are reviewed, and the pathogenesis of the capillary nonperfusion is discussed.


Production of hydrogen sulfide from d-cysteine and its therapeutic potential.
Accumulating evidence shows that H2S has physiological functions in various tissues and organs. It includes regulation of neuronal activity, vascular tension, a release of insulin, and protection of the heart, kidney, and brain from ischemic insult. H2S is produced by enzymes from l-cysteine; cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase. We recently discovered an additional pathway for the production of H2S from d-cysteine. d-Amino acid oxidase provides 3-mercaptopyruvate for 3MST to produce H2S. d-Cysteine protects cerebellar neurons from oxidative stress and attenuates ischemia-reperfusion injury caused in the kidney more effectively than l-cysteine. This review focuses on a novel pathway for the production of H2S and its therapeutic application especially to the renal diseases.


Bacterial DNA repair genes and their eukaryotic homologues: 4. The role of nucleotide excision DNA repair (NER) system in mammalian cells.
The eukaryotic cell encounters more than one million various kinds of DNA lesions per day. The nucleotide excision repair (NER) pathway is one of the most important repair mechanisms that removes a wide spectrum of different DNA lesions. NER operates through two sub pathways: global genome repair (GGR) and transcription-coupled repair (TCR). GGR repairs the DNA damage throughout the entire genome and is initiated by the HR23B/XPC complex, while the CSB protein-governed TCR process removes DNA lesions from the actively transcribed strand. The sequence of events and the role of particular NER proteins are currently being extensively discussed. NER proteins also participate in other cellular processes like replication, transcription, chromatin maintenance and protein turnover. Defects in NER underlay severe genetic disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD).


Post-Traumatic Epilepsy in Zebrafish Is Drug-Resistant and Impairs Cognitive Function.
Post-traumatic epilepsy (PTE) is acquired epilepsy after traumatic brain injury (TBI). Despite the availability of more than 20 antiseizure medications (ASMs), there is no way at present to prevent epileptogenesis in TBI survivors, and many cases of PTE become drug-resistant. Importantly, the adverse effects of ASMs can significantly affect patients' quality of life. Mammalian models are commonly used for studying refractory PTE, but are expensive and laborious. Zebrafish models have become popular for studying epilepsy, but most focus on larvae, and there have been no reports to date of pharmacological screening in an adult zebrafish model of acquired epilepsy. Valid animal models are critical for understanding PTE and for developing novel therapeutics. The aim of the present study was to characterize the cognitive impairments of a zebrafish model of TBI that leads to the development of PTE. Using combined behavioral and electrophysiological approaches, we also characterized the pharmacological effects of the most commonly used ASMs to manage PTE (valproate, carbamazepine, and phenytoin). Zebrafish with PTE exhibited impairments in learning and memory, difficulty in decision making, and reduced social preference. Valproate and carbamazepine had a limited protective effect against behavioral seizures, and all three drugs failed to significantly reduce electrographical seizures. The negative impacts of TBI and ASMs in zebrafish parallel those observed in other animals, making the zebrafish model of PTE a promising high-throughput model of refractory and drug-resistant epilepsy.


Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2.
In the mammalian central nervous system (CNS), the action of sodium dependent excitatory amino acid transporters (EAATs) is responsible for termination of glutamatergic neurotransmission by reuptake of ( S) -glutamate (Glu) from the synaptic cleft. Five EAAT subtypes have been identified, of which EAAT1-4 are present in the CNS, while EAAT5 is localized exclusively in the retina. In this study, we have used an enantioselective chemo-enzymatic strategy to synthesize 10 new Glu analogues 2a- k ( 2d is exempt) with different functionalities in the 4 R-position and characterized their pharmacological properties at the human EAAT1-3. In particular, one compound, 2k, displayed a significant preference as inhibitor of the EAAT2 subtype over EAAT1,3. The compound also displayed very low affinities toward ionotropic and metabotropic Glu receptors, making it the most selective EAAT2 inhibitor described so far.


Aberrant regulation of the integrin very late antigen-4 in systemic lupus erythematosus.
Integrin very late antigen-4 (VLA4) is induced during inflammation and can regulate monocyte migration. It has been implicated in atherogenesis, a significant concern in systemic lupus erythematosus (SLE). The aim of this study was to define VLA4 expression in SLE monocytes. Flow cytometry, reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry staining with confocal microscopy were used to evaluate VLA4 expression in SLE patients and controls. We found elevated expression of VLA4 in SLE patients with significantly increased VLA4 staining intracellularly compared to control. Exposure of control monocytes to SLE sera or immune complexes led to increased intracellular expression, and immune complexes were capable of driving redistribution of surface VLA4 to the cytoplasm. Therefore, VLA4 was found to be subject to complex regulation with SLE sera driving both RNA expression and redistribution of protein. Stimulation of SLE monocytes with a VLA4 ligand induced significant TNFα expression, confirming a functional effect. This behavior may contribute to increased atherosclerosis and monocyte infiltrates in end organs.


Gallstone Disease and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Observational Studies.
Gallstone disease shares certain risk factors with cardiovascular disease, particularly metabolic risk factors. Patients with gallstone disease may be at increased risk of cardiovascular disease. Several recent studies exploring the effect of gallstone disease on cardiovascular disease outcomes demonstrated inconsistent results. We conducted a systematic review and meta-analysis of cohort, case-control, and cross-sectional studies that compared the risk of developing cardiovascular disease events in patients with gallstone disease versus non-gallstone disease controls. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the pooled hazard ratio, odd ratio, and 95% confidence interval. Data were extracted from six studies involving 176,734 cases and 803,714 controls. The pooled hazard ratio of cardiovascular events in patients with gallstone disease was 1.28 (95% confidence interval: 1.23-1.33, I2 = 42%). The pooled odd ratio of cardiovascular events in patients with gallstone disease was 1.82 (95% confidence interval: 1.47-2.24, I2 = 68%). Our study demonstrated a statistically significant increase in the risk of cardiovascular disease among patients with gallstone disease.