The Effects of Microdecompression on Patients with Lumbar Degenerative Spinal Stenosis with or without Degenerative Spondylolisthesis.
To investigate the mid-term efficacy of bilateral decompression with a unilateral approach (BDUA) on symptoms and quality of life of in patients with lumbar spinal stenosis (LSS), with low grade (with percentage slip < 25%) degenerative spondylolisthesis or without spondylolisthesis. The study included patients who underwent BDUA due to one or two-level LSS related to degenerative spondylosis and/ or degenerative spondylolisthesis. Pre- and postoperative data of the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), and walking distance were compared. Evaluation was made up of a total of 53 patients, comprising 32 males and 21 females with a mean age of 60.6 ± 9.0 years. Compared with the preoperative data, VAS, ODI and walking distance improved significantly in all patients at the 3-year follow-up examination. Furthermore, a significant improvement was determined in the clinical parameters of patients with degenerative spondylolisthesis, with no worsening of slip and no requirement for instrumentation. Moreover, when patients were separated into two groups according to age, as elderly ( > 60 years) and adult ( < 60 years), similar improvements were seen in both groups. BDUA could be quite effective in reducing pain, improving quality of life and walking distance with no worsening of the grade or degree of slipping.


Optic neuritis in Singapore.
Optic neuritis (ON) is the commonest optic neuropathy encountered in the younger group of patients from the Singapore Neuro-Ophthalmology Study Group. Previous surveys in Asia and our study suggest that ON in Singapore differs from that in Western populations where the majority of cases are associated with multiple sclerosis (MS). Patients satisfying our entry criteria for ON seen between September 2002 and June 2004 were enrolled in the study. The data collected was recorded in a central database and analysed two years later. The majority (60 percent) of our patients had anterior ON with optic disc swelling (papillitis), were idiopathic in 49.1 percent, and associated with MS in only 25.5 percent. Bilateral cases comprised 16.4 percent of our series and were usually of the anterior variety and mostly idiopathic, although it is still essential to rule out secondary causes. Recurrent ON is indicative of an underlying disease process. The pattern of ON as seen in Singapore differs from that reported in Caucasian studies and from the seminal Optic Neuritis Treatment Trial. We found a higher incidence of optic disc swelling, i.e. anterior ON (papillitis), and a lesser association with MS; visual recovery is similarly good but our recurrence rate is lower.


Sex-based differences in movement and space use of the blacktip reef shark, Carcharhinus melanopterus.
Information on the spatial ecology of reef sharks is critical to understanding life-history patterns, yet gaps remain in our knowledge of how these species move and occupy space. Previous studies have focused on offshore reefs and atolls with little information available on the movement and space use of sharks utilising reef habitats closer to shore. Cross-shelf differences in physical and biological properties of reefs can alter regional ecosystem processes resulting in different movement patterns for resident sharks. Passive acoustic telemetry was used to examine residency, space use and depth use of 40 blacktip reef sharks, Carcharhinus melanopterus, on an inshore reef in Queensland, Australia, and assess temporal or biological influences. All sharks showed strong site-attachment to inshore reefs with residency highest among adult females. Sharks exhibited a sex-based, seasonal pattern in space use where males moved more, occupied more space and explored new areas during the reproductive season, while females utilised the same amount of space throughout the year, but shifted the location of the space used. A positive relationship was also observed between space use and size. There was evidence of seasonal site fidelity and long-distance movement with the coordinated, annual migration of two adult males to the study site during the mating season. Depth use was segregated with some small sharks occupying shallower depths than adults throughout the day and year, most likely as refuge from predation. Results highlight the importance of inshore reef habitats to blacktip reef sharks and provide evidence of connectivity with offshore reefs, at least for adult males.


How do the experiences and beliefs of adults and children with heterozygous familial hypercholesterolaemia influence their adherence to treatment? A systematic review of qualitative evidence protocol.
Heterozygous familial hypercholesterolaemia (FH) is a genetic disorder characterised by elevated levels of low density lipoprotein (LDL) cholesterol from birth, estimated to affect 1 in 250 of the UK population. Left untreated, FH substantially increases an individual's risk of premature coronary heart disease (CHD) and associated mortality. This risk can be minimised with timely diagnosis and successful treatment with medication and lifestyle changes, as advocated in national and international guidelines. Despite these recommendations, the limited research available suggests adherence to treatment may be sub-optimal. This review will identify and synthesise the available qualitative research regarding the experiences and beliefs of adults and children with FH in relation to their condition and its treatment, and the influence of these upon treatment adherence. The following electronic databases will be searched from their inception: Cochrane library, MEDLINE, Embase, PsycINFO (via OVID) and CINAHL. Studies available in English and reporting primary qualitative data will be included. Database searching will be supplemented with searches in relevant specialist websites. The references of identified papers will also be hand searched. Two reviewers will independently screen titles and abstracts of identified studies, with full texts of potentially relevant papers retrieved for review against pre-defined inclusion and exclusion criteria. The Critical Appraisal Skills Programme (CASP) Qualitative Research checklist will be used to assess quality of the included studies, and the results will be taken into consideration when reporting the findings. A data extraction tool will be created for use in this review to extract study findings relevant to the review questions. A thematic synthesis approach will be taken to analyse the results. Adherence to treatment recommendations is crucial for the successful management of FH and subsequent decrease in risk of CHD later in life. Common identified themes could provide an understanding of the beliefs and experiences which influence adherence to treatment recommendations and provide an insight into perceived barriers and facilitators. The findings are intended to be used in the development of future interventions or guidelines regarding treatment of children and adults with FH. PROSPERO registration number: CRD42018085946.


Response of cardiac endothelial nitric oxide synthase to plasma viscosity modulation in acute isovolemic hemodilution.
Endothelial nitric oxide synthase (eNOS) is generally expressed in endocardial cells, vascular endothelial cells and ventricular myocytes. However, there is no experimental study elucidating the relationship between cardiac eNOS expression and elevated plasma viscosity in low oxygen delivery pathological conditions such as hemorrhagic shock-resuscitation and hemodilution. This study tested the hypothesis that elevated plasma viscosity increases cardiac eNOS expression in a hemodilution model, leading to positive effects on cardiac performance. Two groups of golden Syrian hamster underwent an acute isovolemic hemodilution where 40% of blood volume was exchanged with 2% (low-viscogenic plasma expander [LVPE]) or 6% (high-viscogenic plasma expander [HVPE]) of dextran 2000 kDa. In control group, experiment was performed without hemodilution. All groups were performed in awake condition. Experimental parameters, i.e., mean arterial blood pressure (MAP), heart rate, hematocrit, blood gas content and viscosity, were measured. The eNOS expression was evaluated by eNOS Western blot analysis. After hemodilution, MAP decreased to 72% and 93% of baseline in the LVPE and HVPE, respectively. Furthermore, pO2 in the LVPE group increased highest among the groups. Plasma viscosity in the HVPE group was significantly higher than that in control and LVPE groups. The expression of eNOS in the HVPE group showed higher intensity compared to other groups, especially compared with the control group. Our results demonstrated that cardiac eNOS has responded to plasma viscosity modulation with HVPE and LVPE. This particularly supports the previous studies that revealed the positive effects on cardiac function in animals hemodiluted with HVPE.


[Symptomatic vasospasm. Clinical manifestations].
Symptomatic vasospasm in the setting of a subarachnoid hemorrhage is a complication of difficult diagnosis in some clinical situations. Objectives. Describe the clinical characteristics of cerebral vasospasm demonstrated by neurovascular studies in patients with ruptured saccular aneurysm. 19 consecutive patients with symptomatic vasospasm, evaluated with TCD and any variant of neurovascular study with contrast injection. All these cases were in degrees between 1 and 3 of the World Federation of Neurological Surgeons Scale. The cognitive and behavioral manifestations were the most frequent (53%), followed by neurological focal deficits (26%). Clinical vasospasm occurred most frequently between day 9 and 10. Vasospasm is predominant in the arteries of the anterior circulation. The high mortality (42%) and the antecedent of arterial hypertension characterized the group with symptomatic vasospasm. There was no statistical relationship between the result of the scale of Fisher and the symptomatic vasospasm. All the TCD parameters had statistical significance. The clinical manifestations more frequently associated with symptomatic vasospasm were cognitive and behavioral. This group of patients is characterized by a high mortality. The TCD is a test of great value to predict cerebral ischemia due to vasospasm.


Modified Julia Olefination on Anhydrides: Extension and Limitations. Application to the Synthesis of Maculalactone B.
The preparation of exo-enol esters from cyclic anhydrides is reported using a modified Julia olefination. The reaction is highly stereoselective. The Smiles rearrangement can be performed in a one-pot process, giving a straightforward access to exo-enol lactones. Furthermore, the reaction was extended to semistabilized sulfones, and this methodology was applied to the synthesis of maculalactone B.


α2δ3 is essential for normal structure and function of auditory nerve synapses and is a novel candidate for auditory processing disorders.
The auxiliary subunit α2δ3 modulates the expression and function of voltage-gated calcium channels. Here we show that α2δ3 mRNA is expressed in spiral ganglion neurons and auditory brainstem nuclei and that the protein is required for normal acoustic responses. Genetic deletion of α2δ3 led to impaired auditory processing, with reduced acoustic startle and distorted auditory brainstem responses. α2δ3(-/-) mice learned to discriminate pure tones, but they failed to discriminate temporally structured amplitude-modulated tones. Light and electron microscopy analyses revealed reduced levels of presynaptic Ca(2+) channels and smaller auditory nerve fiber terminals contacting cochlear nucleus bushy cells. Juxtacellular in vivo recordings of sound-evoked activity in α2δ3(-/-) mice demonstrated impaired transmission at these synapses. Together, our results identify a novel role for the α2δ3 auxiliary subunit in the structure and function of specific synapses in the mammalian auditory pathway and in auditory processing disorders.


[Combined hepatic-artery and portal-vein chemoembolization for colorectal cancer metastatic to the liver].
The purpose of the study was to evaluate the results of combined (hepatic artery and portal vein) oily chemoembolization (OCE) in patients with unresectable colorectal liver metastases. Courses of combined OCE were given to 45 patients (1990-2000). For arterial OCE (n = 150), 40-100 mg doxorubicin mixed with 10-15 ml iodized oil and gelatin sponge was used. OCE of the portal vein (n = 118) included injection of doxorubicin-in-oil without sponge. Response to treatment (partial tumor decrease or stabilization) was reported in 80%. Serious complications occurred in 3 patients (7%) but there was no mortality. The mean and median survival rates for those patients who died were 20.2 and 17 months, respectively. The 1-, 2-, and 3-year survival rates were 83, 40 and 14%, respectively. These results were significantly better than those for arterial OCE alone or hepatic arterial infusion. Combined (arterial and portal vein) OCE with doxorubicin appears the most effective locoregional treatment for unresectable colorectal liver metastases.


The safety and efficacy of intrathecal opioid analgesia for acute postoperative pain: seven years' experience with 5969 surgical patients at Indiana University Hospital.
To assess the efficacy of the analgesic technique and the incidence of complications, we prospectively evaluated patients who received intrathecal opioid analgesia (ITOA) to manage postsurgical pain. Daily quality assurance data were collected on the first postoperative day and tabulated for 5969 adult patients who had received ITOA for major urologic, orthopedic, general/ vascular, thoracic, and nonobstetrical gynecologic surgery. A scale of 1-10 was used to quantify each patient's satisfaction with analgesia. The incidence of side effects, complications, and naloxone usage was also recorded and tabulated. The mean satisfaction score using a 10-point numeric rating scale was 8.51, with a score of 1 connoting "complete dissatisfaction" and 10 connoting "complete satisfaction." Side effects were minor and easily managed. Pruritus was the most common (37%). Respiratory depression was the least common (3%), easily detected by nursing observation, never life-threatening, and always responsive to treatment with naloxone. There were no deaths, nerve injuries, central nervous system infections, or naloxone-related complications. Postdural puncture headaches were rare (0.54%), as was the need for epidural blood patch (0.37%). Over a 7-yr period, intrathecal opioid analgesia was used to control acute postoperative pain on nearly 6000 patients, resulting in a high degree of patient satisfaction and a low incidence of side effects and complications.


Clinical implications of inflammation for cardiovascular primary prevention.
While many questions remain unanswered in this challenging arena, the emerging status of biomarkers of inflammation provides an excellent illustration of how application of basic and clinical science of inflammation can lead to advances in clinical care. Yet we need to do better. We need to improve the number needed to treat. We should strive for further refinements in risk prediction to individualize interventions. Imaging and genetic biomarkers will likely find their place in clinical practice alongside traditional risk factors and biomarkers of inflammation in the years to come. We must aim to assure that individuals targeted for statin therapy do not lessen their adherence to a healthy lifestyle, believing that they enjoy pharmacological protection from unhealthy behaviours. At the other extreme, we need to counsel carefully certain patients to avoid creating a cohort of 'cardiac neurotics' with above median high-sensitivity C-reactive protein readings. We need to understand more about the mechanisms and clinical significance of unwanted actions of statins, including dysglycaemia. We need to devise measures to optimize lifestyle change at both a medical and societal level. For our individual patients, implementation of sustained lifestyle change has proved very challenging in practice, given the multiplicity of behaviours that require vigilance. The clinical use of biomarkers of inflammation may provide the practitioner with a tool to help gauge residual risk, and chart a course for its optimal management.


Examination of the mouse embryo by micro-CT.
Micro X-ray computed tomography (micro-CT) is widely used in preclinical studies of small animals. However, due to the low soft tissue contrast, segmentation of soft tissues in the micro-CT image is a challenging problem. To gain a better understanding of the macroscopic anatomy of the mouse embryo, 3 fixation methods and 3 metal stainings were examined for micro-CT using C57BL/6J mouse embryos in the present study. The examination demonstrated that 1% acetic acid/95% ethanol fixative together with zinc staining provided a high contrast micro-CT image, enabling the segmentation of soft tissues. Then, using this condition, the macroscopic embryo structure of the nude mouse was examined, revealing lack of a thymus. It appears that micro-CT with the fixation and staining condition devised in the present study could be a powerful tool in detecting the effects of various mutations at embryonic stages.


Profiling donepezil template into multipotent hybrids with antioxidant properties.
Alzheimer's disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer's disease.


TLR4 is required for macrophage efferocytosis during resolution of ventilator-induced lung injury.
Mechanical ventilation is a life-sustaining therapy for patients with respiratory failure but can cause further lung damage known as ventilator-induced lung injury (VILI). However, the intrinsic molecular mechanisms underlying recovery of VILI remain unknown. Phagocytosis of apoptotic cells (also known as efferocytosis) is a key mechanism orchestrating successful resolution of inflammation. Here we show the positive regulation of macrophage Toll-like receptor (TLR) 4 in efferocytosis and resolution of VILI. Mice were depleted of alveolar macrophages and then subjected to injurious ventilation (tidal volume, 20 mL/kg) for 4 h. On day 1 after mechanical ventilation, Tlr4+/+ or Tlr4-/- bone marrow-derived macrophages (BMDMs) were intratracheally administered to alveolar macrophage-depleted mice. We observed that mice depleted of alveolar macrophages exhibited defective resolution of neutrophilic inflammation, exuded protein, lung edema, and lung tissue injury after ventilation, whereas these delayed responses were reversed by administration of Tlr4+/+ BMDMs. Importantly, these proresolving effects by Tlr4+/+ BMDMs were abolished in mice receiving Tlr4-/- BMDMs. The number of macrophages containing apoptotic cells or bodies in bronchoalveolar lavage fluid was much less in mice receiving Tlr4-/- BMDMs than that in those receiving Tlr4+/+ BMDMs. Macrophage TLR4 deletion facilitated a disintegrin and metalloprotease 17 maturation and enhanced Mer cleavage in response to mechanical ventilation. Heat shock protein 70 dramatically increased Mer tyrosine kinase surface expression, phagocytosis of apoptotic neutrophils, and rescued the inflammatory phenotype in alveolar macrophage-depleted mice receiving Tlr4+/+ BMDMs, but not Tlr4-/- BMDMs. Our results suggest that macrophage TLR4 promotes resolution of VILI via modulation of Mer-mediated efferocytosis.


[Dynamics of the joint pains at night in rheumatoid arthritis and arthroses treated with Rengasil and piroxicam].
The effect of a novel nonsteroidal antiinflammatory drug Rengasil on pain at rest in rheumatoid arthritis and arthroses was studied in comparison with piroxicam and placebo. Intensity of nocturnal pains was estimated according to the "visual analogous scale". The relationship between the time of occurrence of a complete analgesic effect and severity of the pain syndrome before the beginning of monotherapy was established.


Seroprevalence of Toxoplasma gondii infection in Tibetan sheep in northwestern China.
The seroprevalence of Toxoplasma gondii infection in Tibetan sheep was surveyed in Qinghai Province, northwestern China, in May and June 2010. In total, 580 serum samples was collected from 6 counties, and antibodies to T. gondii were detected by indirect hemagglutination (IHA) test. Antibodies to T. gondii were found in 29.8% (173/580); regional differences showed the highest prevalences in Nangqian County (39.4%) and Zaduo County (48.7%). The results of the present study indicate that infection with T. gondii in sheep is widely spread in China, including Tibetan sheep in Qinghai Province, and is a potential public health concern.


Minimally invasive video-assisted thyroidectomy versus conventional thyroidectomy: A single-blinded, randomized controlled clinical trial.
We aimed to test the hypothesis that Minimally Invasive Video-assisted Thyroidectomy (MIVAT) affords comparable safety and efficacy as to the open conventional surgery, when dealing with patients with unilateral thyroid nodules or follicular lesions, in terms of cosmetic results, intraoperative and postoperative complications, postoperative pain and hospital stay. This was a single-blinded randomised controlled trial comparing the MIVAT with conventional thyroidectomy. The primary endpoints of the study were measurement of postoperative pain after 24 and 48 hours from operation and self-rated patient satisfaction with cosmetic outcome three months postoperatively. The secondary outcome measures were operative time, incidence of temporary and permanent recurrent laryngeal nerve injury, postoperative haematoma formation, length of incision, and duration of hospital stay. Operative time was significantly less with open thyroidectomy than with MIVAT, while MIVAT was associated with less pain 24 hours postoperatively. Blood loss did not reach significance between procedures. Comparisons between the two procedures with regard to pain scores after 24 and 48 hours, respectively, depicted statistically significant differences in favour of the MIVAT after 24 hours. MIVAT was associated with less scarring and more satisfactory cosmetic results. There were statistically no significant differences between both procedures for the presence of transient recurrent laryngeal nerve palsy and hypoparathyroidism. MIVAT is a safe procedure that produces outcomes, in view of short-term adverse events, similar to those of open thyroidectomy, and is superior in terms of immediate postoperative pain and cosmetic results.


Diversity of ubiquitin and ISG15 specificity among nairoviruses' viral ovarian tumor domain proteases.
Nairoviruses are responsible for numerous diseases that affect both humans and animal. Recent work has implicated the viral ovarian tumor domain (vOTU) as a possible nairovirus virulence factor due to its ability to edit ubiquitin (Ub) bound to cellular proteins and, at least in the case of Crimean-Congo hemorrhagic fever virus (CCHFV), to cleave the Ub-like protein interferon-stimulated gene 15 (ISG15), a protein involved in the regulation of host immunity. The prospective roles of vOTUs in immune evasion have generated several questions concerning whether vOTUs act through a preserved specificity for Ub- and ISG15-conjugated proteins and where that specificity may originate. To gain insight into the substrate specificity of vOTUs, enzymological studies were conducted on vOTUs from Dugbe, CCHFV, and Erve nairoviruses. These studies revealed that vOTUs originating from different nairoviruses display a significant divergence in their preference toward Ub and ISG15. In addition, a recently identified vOTU from turnip yellow mosaic tymovirus was evaluated to elucidate any possible similarities between vOTUs originating from different viral families. Although possessing a similar preference for certain polymeric Ub moieties, its activity toward Ub in general was significantly less then those of nairoviruses. Lastly, the X-ray crystallographic structure of the vOTU from the Dugbe nairovirus was obtained in complex with Ub to reveal structural commonalities of vOTUs originating from nairoviruses. The structure suggests that divergences between nairovirus vOTUs specificity originate at the primary structural level. Comparison of this structure to that originating from CCHFV identified key residues that infer the substrate specificity of vOTUs.


E101K and M123V alpha-cardiac actin gene mutations are not associated with cardiomyopathy in Iranian population.
Cardiomyopathies are myocardial disorders in which the heart muscle is structurally and functionally abnormal. Several mutations in sarcomere protein coding genes are responsible for different types of cardiomyopathies. ACTC1 is one of the main sarcomere components in heart muscle. Two mutations of E101K and M123V in this gene are shown to be associated with cardiomyopathies. In this case and control study, a sample of contains 30 hypertrophic cardiomyopathy and 100 dilated cardiomyopathy patients, as well as 130 healthy individuals were screened for two mutations of E101K and M123V. The genotypes of samples were determined in whole blood genomic DNA by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and mismatched-PCR-RLFP techniques. All patients and healthy peoples had wild type genotype for both locations and even no heterozygous was detected. Despite previous reports, no association was observed between both mutations with cardiomyopathy. Our results indicated that two mutations of E101K and M123V of ACTC1 gene may are not associated with cardiomyopathy in Iranian population.


Tungsten carbonyl σ-complexes with charge-compensated nido-carboranyl thioether ligands.
Charge-compensated nido-carboranyl thioether ligands [7-MeS-10-Me2S-7,8-C2B9H10] and [7,8-(MeS)2-10-Me2S-7,8-C2B9H9] were prepared and fully characterized. They readily react with labile tungsten carbonyls to give σ-complexes - mono-substituted (CO)5W[7-MeS-10-Me2S-7,8-C2B9H10-κ(1)-S(1)] and (CO)5W[7,8-(MeS)2-10-Me2S-7,8-C2B9H9-κ(1)-S(1)] and chelate (CO)4W[7,8-(MeS)2-10-Me2S-7,8-C2B9H9-κ(2)-S(1),S(2)]. The synthesized metallocomplexes were characterized by multinuclear NMR spectroscopy and single crystal X-ray diffraction. The donor ability of the 7-methylsulfide-nido-carborane ligand is not sensitive to introduction of the charge-compensating dimethylsulfonium group.


Instruments to Measure Betel Quid Dependency among Young and Adult Chewers - A Systematic Review with Meta-analysis.
Betel quid (BQ) consumption is prevalent globally, majorly consumed in South-Asia and South-East Asian countries. Among the other country studies done on BQ, the focus has been on its consumption prevalence, its physiological and psychological effects, and aids to discontinue this habit. Systematic literature research on suitability of different instruments (metric or scale) to measure BQ dependency is scarce, hence pointing to the need of more evidence-based studies in this domain. The aim of the article was to identify the instruments used in the published literature to measure BQ dependency among young and adult chewers and draw a comparison. The electronic retrieval systems and databases PubMed (Medline), Cochrane Library, Scopus, Web of Science, and Google Scholar were searched independently by two authors from January 2011 to September 2022 for the collection of desired data. Among 1271 articles, 337 were duplicates and removed, 866 did not meet selection criteria. Out of 68 articles, 57 were excluded due to the lack of relevant data. Finally, only 11 articles were included for the analysis in this systematic review. Due to a scarcity of researches in this direction, no scale can be assigned as the best Dependence Scale, thus necessitating more such systematic reviews and meta-analysis for better comprehension and usage of present dependence scales.


Endothelial injury and dysfunction in ischemic acute renal failure.
Ischemic acute renal failure is the most common cause of acute renal failure in hospitalized patients and has an average mortality rate of 50%. Although epithelial and vascular smooth muscle cell abnormalities have been clearly delineated in association with this condition, the extent of endothelial injury and dysfunction has been difficult to document, primarily for anatomic reasons. However, endothelial tight junction separation and endothelial cell detachment, blebbing, and necrosis have been observed after ischemia in other organs. In addition, adenosine triphosphate depletion studies in cultured endothelial cells have demonstrated that multiple actin-based alterations occur in a reversible and duration-dependent fashion. After an ischemic insult, total renal blood flow returns toward normal, but marked, regional alterations occur. Most affected is the outer medullary or corticomedullary junction region where blood flow remains approximately 10% of normal. In this area, the microvasculature becomes congested. Interstitial edema, red blood cell trapping, leukocyte adherence, and extravasation all contribute to this congestion. Increased expression of both P selectin and E selectin has been documented in renal endothelial cells after ischemic injury, and treatment with antibodies to either intercellular adhesion molecule-1, P selectins, or E selectins has been shown to minimize renal injury. During ischemia in vivo and adenosine triphosphate depletion in cell culture studies, F-actin destruction occurs, with polymerization leading to accumulation of intracellular actin aggregates. By using multiphoton microscopy, Voxx software, and the Tie-2 mouse with selective endothelial cell green fluorescent protein expression driven by the Tie-2 promoter, we have been able to identify macrovascular and microvascular endothelial cells in four dimensions (three dimensions plus time) intravitally. By using Texas red-labeled large molecular weight dextrans, we can document blood flow and vascular dysfunction. Intravital studies using multiphoton imaging techniques can now be conducted to identify and quantify endothelial cell injury and dysfunction in functioning organs.


Using the recurrence plots as indicators for the recognition of Parkinson's disease through phonemes assessment.
Parkinson's disease (PD) is considered to be the second most common neurodegenerative disease which affects the patients' life throughout the years. As a consequence, its early diagnosis is of major importance for the improvement of life quality, implying that the severe symptoms can be delayed through appropriate clinical intervention and treatment. Among the most important premature symptoms of PD are the voice impairments of articulation, phonation and prosody. The objective of this study is to investigate whether the voice's dynamic behavior can be used as possible indicator for PD. Thus in this work, we employ the recurrence plots (RPs) which derive from the analysis of the three modulated vowels /a/, /e/ and /o/, which belong to the PC-GITA dataset, and are fed as input images to a 3-channel Convolutional Neural Network-based (CNN) architecture, which, finally, differentiates the 50 PD patients from 50 healthy subjects. The experimental results obtained provide evidence that the RP-based approach is a promising tool for the recognition of PD patients through the analysis of voice recordings, with a classification accuracy achieved equal to 87%.


Regulation of lysine catabolism through lysine-ketoglutarate reductase and saccharopine dehydrogenase in Arabidopsis.
In plant and mammalian cells, excess lysine is catabolized by a pathway that is initiated by two enzymes, namely, lysine-ketoglutarate reductase and saccharopine dehydrogenase. In this study, we report the cloning of an Arabidopsis cDNA encoding a bifunctional polypeptide that contains both of these enzyme activities linked to each other. RNA gel blot analysis identified two mRNA bands-a large mRNA containing both lysine-ketoglutarate reductase and saccharopine dehydrogenase sequences and a smaller mRNA containing only the saccharopine dehydrogenase sequence. However, DNA gel blot hybridization using either the lysine-ketoglutarate reductase or the saccharopine dehydrogenase cDNA sequence as a probe suggested that the two mRNA populations apparently are encoded by the same gene. To test whether these two mRNAs are functional, protein extracts from Arabidopsis cells were fractionated by anion exchange chromatography. This fractionation revealed two separate peaks-one containing both coeluted lysine-ketoglutarate reductase and saccharopine dehydrogenase activities and the second containing only saccharopine dehydrogenase activity. RNA gel blot analysis and in situ hybridization showed that the gene encoding lysine-ketoglutarate reductase and saccharopine dehydrogenase is significantly upregulated in floral organs and in embryonic tissues of developing seeds. Our results suggest that lysine catabolism is subject to complex developmental and physiological regulation, which may operate at gene expression as well as post-translational levels.


The future of interventional and neurointerventional radiology: learning lessons from the past.
The rapid progression of medical imaging technology and the ability to leverage knowledge from non-invasive imaging means that Interventional Radiologists (IRs) and Interventional Neuroradiologists are optimally placed to incorporate minimally invasive interventional paradigms into clinical management to advance patient care. There is ample opportunity to radically change the management options for patients with a variety of diseases through the use of minimally invasive interventional procedures. However, this will need to be accompanied by an increased clinical role of IRs to become active partners in the clinical management of patients. Unfortunately, the development of IR clinical presence has lagged behind and is reflected by declining rates of IR involvement in certain areas of practice such as vascular interventions. Current and future IRs must be willing to take on clinical responsibilities; reviewing patients in clinic to determine suitability for a procedure and potential contraindications, rounding on hospital inpatients and be willing to manage procedure related complications, which are all important parts of a successful IR practice. Increasing our clinical presence has several advantages over the procedure-driven model including enhanced patient knowledge and informed consent for IR procedures, improved rapport with patients and other clinical colleagues through active participation and engagement in patient care, visibility as a means to facilitate referrals and consistency of follow-up with opportunities for further learning. Many of the solutions to these problems are already in progress and the use of IR as a "hired gun" or "technician" is a concept that should be relegated to the past, and replaced with recognition of IRs as clinicians and partners in delivering modern high quality multidisciplinary team-based patient care. The following article will review the history of IR, the challenges facing this rapidly evolving profession and discuss recent developments occurring globally that are essential in maintaining expertise, securing future growth and improving patient outcomes in the modern multidisciplinary practice of medicine.


Episodic simulation of future events is impaired in patients with major depressive disorder.
We examined future episodic simulation in patients with major depressive disorder (MDD) using a method that distinguishes between episodic and non-episodic details of events. Patients were impaired at generating specific episodic details concerning future events; non-episodic details were not affected. In addition, all participants generated more episodic details for positive than for negative stimulus words. These results suggest a deficit in autonoetic awareness among patients with MDD. Difficulties imagining future events may impact upon the success of therapeutic interventions aimed at altering biases in the prediction of positive and negative future happenings.


Analysis of context sequence surrounding translation initiation site from complete genome of model plants.
Regions flanking the translation initiation site (TIS) are thought to play a crucial role in translation efficiency of mRNAs, but their exact sequence and evolution in eukaryotes are still a matter of debate. We investigated the context sequences in 20 nucleotides around the TIS in multi-cellular eukaryotes, with a focus on two model plants and a comparison to human. We identified consensus sequences aaaaaaa(A/G)(A/C)aAUGGcgaataata and ggcggc(g/c)(A/G)(A/C)(G/C)AUGGCggcggcgg for Arabidopsis thaliana and Oryza sativa, respectively. We observe strongly conserved G at position +4 and A or C at position -2; however, the exact nucleotide frequencies vary between the three organisms even at these conserved positions. The frequency of pyrimidines, which are considered sub optimum at position -3, is higher in both plants than in human. Arabidopsis is GC-depleted (AU-enriched) compared to both rice and human, and the enrichment is slightly stronger upstream than downstream of AUG. While both plants are similar though not identical in their variation of nucleotide frequencies, rice and human are more similar to each other than Arabidopsis and human. All three organisms display clear periodicity in A + G and C + U content when analyzing normalized frequencies. These findings suggest that, besides few highly conserved positions, overall structure of the context sequence plays a larger role in TIS recognition than the actual nucleotide frequencies.


Nuclear envelope of the seminal-vesicle epithelium.
The nuclear envelope of seminal-vesicle epithelium was isolated by a procedure involving enzymic digestion with deoxyribonuclease I, sonication in the presence of 0.34 M-sodium citrate, and centrifugation through sucrose density gradients. The mass of envelope DNA was only 0.8% of that of envelope protein, and by transmission electron microscopy the envelope was 98-99% pure. We showed that the envelope possess a protein kinase activity which is uninfluenced by cyclic nucleotides. Both lysine-rich histone and dephosphophosvitin as substrates gave a greater specific activity than did envelope protein itself. Optimum requirements with respect to Na+, Mg2+, pH and ATP were established for each substrate, and the influence of other factors on enzyme activity was investigated. Data, obtained mainly with the use of lysine-rich histone, are presented which indicate that nuclear envelope from intact and 96 h-castrated guinea pigs may have equal protein kinase activities and, in separate experiments, equal phosphoprotein phosphatase activities. Clarification of these initial observations must await identification of the natural substrates or the envelope's phosphorylation-dephosphorylation reactions.


A metabolomic study of red and processed meat intake and acylcarnitine concentrations in human urine and blood.
Acylcarnitines (ACs) play a major role in fatty acid metabolism and are potential markers of metabolic dysfunction with higher blood concentrations reported in obese and diabetic individuals. Diet, and in particular red and processed meat intake, has been shown to influence AC concentrations but data on the effect of meat consumption on AC concentrations is limited. To investigate the effect of red and processed meat intake on AC concentrations in plasma and urine using a randomized controlled trial with replication in an observational cohort. In the randomized crossover trial, 12 volunteers successively consumed 2 different diets containing either pork or tofu for 3 d each. A panel of 44 ACs including several oxidized ACs was analyzed by LC-MS in plasma and urine samples collected after the 3-d period. ACs that were associated with pork intake were then measured in urine (n = 474) and serum samples (n = 451) from the European Prospective Investigation into Cancer and nutrition (EPIC) study and tested for associations with habitual red and processed meat intake derived from dietary questionnaires. In urine samples from the intervention study, pork intake was positively associated with concentrations of 18 short- and medium-chain ACs. Eleven of these were also positively associated with habitual red and processed meat intake in the EPIC cross-sectional study. In blood, C18:0 was positively associated with red meat intake in both the intervention study (q = 0.004, Student's t-test) and the cross-sectional study (q = 0.033, linear regression). AC concentrations in urine and blood were associated with red meat intake in both a highly controlled intervention study and in subjects of a cross-sectional study. Our data on the role of meat intake on this important pathway of fatty acid and energy metabolism may help understanding the role of red meat consumption in the etiology of some chronic diseases. This trial was registered at Clinicaltrials.gov as NCT03354130.


Designing effective governance for quality and safety in Canadian healthcare.
Governing boards of healthcare organizations in Canada are accountable for the performance of their organization and provide oversight on their decisions. Traditionally, many healthcare boards have focused on finances and community relations and have deferred responsibility for quality of care to the medical or professional staff. This deferral reflects not only recognition of the expertise of clinical leaders on these issues but also the historical separation of responsibilities between the administration and the medical staff, the former being responsible for financial and operational issues, and the latter for quality of care.


Chronic cerebellar stimulation in epilepsy. Clinical and anatomical studies.
Ten of 15 patients subjected to chronic cerebellar stimulation have had previously intractable seizures modified or inhibited up to periods of three years. Stimulation of anterior lobe appears to be more efficacious than stimulation of posterior lobe. Cerebellar biopsies, obtained in five patients at the time of stimulator placement, revealed in every instance a reduction in the molecular layer, decreased or absent Purkinje cells, and decreased stellate cells. One unimproved patient died during a seizure 17 months after stimulation was initiated. Histological examination of the brain did not reveal tissue damage attributable to the stimulator. There is no evidence of any adverse effect of chronic cerebellar stimulation in humans who have undergone stimulation for periods up to three years.


Biological assay of Cassia podocarpa: a plant related to senna.
Leaves of the plant, Cassia podocarpa, were collected from Opah village near Accra, and dried. A suspension of the powdered leaf was given by gavage to groups of ten mice. A record was kept of the number of wet faeces passed in 24 hours. There was a linear relationship between the log dose of leaf and the number of wet faeces. The effect was maximal between 6 and 24 hours of administration and was larger than has been noted with senna.


Contested Disability: Sickle Cell Disease.
The world's first "molecular disease," sickle cell disease (SCD) has captivated the medical community's attention as a multisystem blood disorder linked to abnormalities in one molecule: hemoglobin. While the molecular model of SCD has led to advances in medical management, its reductionism obfuscates the sociopolitical dimensions of the condition, affording little attention to the racialized, gendered, classed, and disabling disparities faced by people with SCD. Consequently, SCD is frequently contested as a disability-opportunities to support people with SCD in everyday challenges escape many healthcare providers. These trends speak to the legacy of anti-Black racism in the Global North, which deeply entwines disability with racialized boundaries of citizenship and broader debates about "deservingness" of welfare. To address these gaps, this article delineates the medical and social models of disability as well as anti-Black racism to explore how social workers can embed human rights for people with SCD in everyday practice. This article is contextualized in Ontario, Canada, a province that recently launched a quality standard, Sickle Cell Disease: Care for People of All Ages.


[Roundish crystal formations in the retina and vitreous body (calcium oxalate and scintillatio nivea)].
Crystals of calcium oxalate in the outer layers of the retina are usually found in blind eyes with long-standing retinal detachment. The crystals are strongly birefringent, mostly radially arranged, and round. In asteroid hyalosis - the scintillatio nivea of the vitreous - the crystals are always closely related to vitreous fibrils or the limiting membrane. The birefringent bodies are apparently formed and initially often covered by vitreous cells (hyalocytes). The birefringence corresponds to that of brushite (Ca HPO4 X 2 H2O).


Effectiveness in the implantation of law 155 of 2002 ordering the designation of spaces for breastfeeding in government agencies.
As part of an effort to promote and protect breastfeeding among working mothers in Puerto Rico, Public Law 427 was passed in December 2000. This law grants a paid breastfeeding daily break for milk extraction in the workplace. In support of this initiative Public Law 155 was passed in 2002 ordering Secretaries, Directors, Presidents and Public Administrators of the government of Puerto Rico to designate breastfeeding spaces in the workplaces. Describe the level of compliance with the dispositions of Law 155 in government agencies. A cross sectional descriptive study was carried out. A sample of 28 government agencies was randomly selected, representing 25% of the total number of agencies, and a structured telephone interview was administered using an instrument made up of 6 premises. RSEULTS: All (100%) of the agencies had knowledge about the existence of this law, but only 50% had set up and equipped the spaces. Of these, all had a table, a chair, and an electric outlet, 43% had available running water, and 71% provided a refrigerator for milk storage. Fifty three percent of the agencies reported having received followup communications to verify whether they were complying with the law, and 61% reported having a written public policy in support of breastfeeding for working mothers. Only 54% of the agencies stated they had offered some type of orientation to their women employees regarding their breastfeeding rights. In spite of over two years since the passing of Law 155, the majority of government agencies in Puerto Rico have not complied with its legal dispositions. It is necessary that the responsible entities watch for the satisfactory compliance with this law since working mothers need a secure and accesible place for milk extraction during the working day.


Malignant transformation of DMBA/TPA-induced papillomas and nevi in the skin of mice selectively lacking retinoid-X-receptor alpha in epidermal keratinocytes.
Retinoid-X-receptor alpha (RXRalpha), a member of the nuclear receptor (NR) superfamily, is a ligand-dependent transcriptional regulatory factor. It plays a crucial role in NR signalling through heterodimerization with some 15 NRs. We investigated the role of RXRalpha and its partners on mouse skin tumor formation and malignant progression upon topical DMBA/TPA treatment. In mutants selectively ablated for RXRalpha in keratinocytes, epidermal tumors increased in size and number, and frequently progressed to carcinomas. As keratinocyte-selective peroxisome proliferator-activated receptor gamma (PPARgamma) ablation had similar effects, RXRalpha/PPARgamma heterodimers most probably mediate epidermal tumor suppression. Keratinocyte-selective RXRalpha-null and vitamin-D-receptor null mice also exhibited more numerous dermal melanocytic growths (nevi) than control mice, but only nevi from RXRalpha mutant mice progressed to invasive human-melanoma-like tumors. Distinct RXRalpha-mediated molecular events appear therefore to be involved, in keratinocytes, in cell-autonomous suppression of epidermal tumorigenesis and malignant progression, and in non-cell-autonomous suppression of nevi formation and progression. Our study emphasizes the crucial role of keratinocytes in chemically induced epidermal and melanocytic tumorigenesis, and raises the possibility that they could play a similar role in UV-induced tumorigenesis, notably in nevi formation and progression to melanoma.


Role of hexose monophosphate shunt in parathyroid hormone secretion.
The metabolism of labeled glucose by collagenase-dispersed bovine parathyroid cells was examined. When the medium calcium ion concentration was increased to 2.0 mM, the rate of 14CO2 release from [1-14C]glucose was increased 169 +/- 45% compared with the rate of 0.5 mM calcium. There was no significant change in the rate of 14CO2 release from [6-14C]glucose by this maneuver. The greatest increase in 14CO2 release and decrease in parathyroid hormone secretion occurred between medium calcium ion concentrations of 0.5-1.5 mM. This difference in the metabolism of glucose represents a true increase in hexose shunt activity because the incorporation of label from either [1-14C]- or [6-14C]glucose into parathyroid tissue lipids was equal. This suggests equilibration of label at the level of triose-phosphates. The increase in hexose shunt activity was not due to a calcium-mediated increase in glucose uptake because calcium changes did not affect 2-[3H]deoxyglucose transport by the cells. Phenazine methosulfate added to cells incubated at 0.5 mM calcium selectively increased hexose shunt activity in a dose-dependent manner (91 +/- 33% overall) and concomitantly inhibited parathyroid hormone secretion 65% overall at 0.5 mM calcium. The compound 6-aminonicotinamide inhibited hexose shunt activity but could not overcome the inhibition of hormone secretion at 2.0 mM calcium. A decrease in protein biosynthesis cannot fully explain the inhibition of hormone secretion by calcium or phenazine methosulfate because [3H]-leucine incorporation into total cell protein was not as affected as secretion.(ABSTRACT TRUNCATED AT 250 WORDS)


Can an otorhinolaryngological visit induce the suspect of allergic rhinitis in children?
Allergic rhinitis (AR) is very frequent in childhood. AR is commonly associated with some co-morbidities and typical clinical features. This study aimed to test the hypothesis whether an otorhinolaryngological (ORL) visit could induce the suspect of AR. Globally, 1,002 children (550 males, mean age 5.77 years) were consecutively visited at an ORL clinic. Clinical visit, nasal endoscopy, and skin prick test were performed in all patients. In particular, history investigated atopic familiarity, birth, feeding type, passive smoking, comorbidities, including asthma, respiratory infections, otitis media, respiratory sleep disorder. Endoscopy assessed the tonsil and adenoid volume, turbinate contacts, mucosal color, and nasal discharge. Univariate and multivariate analysis were performed. The study showed that 547 (54.6%) children had AR. Some parameters were predicting factor for suspecting AR: middle turbinate contact (OR = 9.27), familial atopy (OR = 6.24), pale nasal mucosa (OR = 4.95), large adenoid volume (OR = 3.02 for score 4), and asthma co-morbidity (OR = 2.95). In conclusion this real-life study showed that during an ORL visit it is possible to suspect AR in children with turbinate hypertrophy, familial atopy, nasal pale mucosa, adenoid enlargement, and asthma comorbidity.


Efficacy of bronchial thermoplasty in patients with severe asthma.
Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in clinical practice in adults with severe, refractory asthma.Methods: Prospective, single-center, open, observational study comprising patients with uncontrolled asthma (asthma control questionnaire (ACQ) >1.5) and/or frequent exacerbations despite treatment with at least high dose inhaled corticosteroids plus a second controller. Efficacy outcomes was change from baseline 4, 8, 12 and 24 months in FEV1, FVC and FEV1/FVC ratio, asthma control questionnaire (ACQ) score and asthma quality of life score (mini-AQLQ). Results are presented as median with interquartile ranges (IQR). The following were recorded as adverse events: Un-scheduled health care contacts, rescue courses of oral corticosteroid (OCS) and/or antibiotics for exacerbation for exacerbations/respiratory tract infections (RTI).Results: Six-teen patients were enrolled (nine males, median age 50 years; 14 followed for 24 months). Compared to baseline, an improvement in FEV1, FVC, FEV1/FVC ratio, mini-AQLQ and ACQ was observed, i.e.FEV1 (IQR) 1.98 L (1.65-2.45) vs. 2.45 L (2.09-2.93) (p = 0.006), FVC (IQR) 3.23 L (2.76-4.05) vs. 3.75 L (3.22-4.36) (p = 0.041), FEV1/FVC 0.60 (IQR: 0.55-0.70) vs. 0.66 (IQR: 0.63-0.71) (p = 0.016), mini-AQLQ 4.0 (IQR: 3.2-4.9) vs. 5.6 (IQR 4.5-6.5) (p = 0.008, and ACQ 2.9 (IQR: 2.1-3.7) versus 1.5 (IQR 1.0-2.4) (p = 0.004). On the other hand, an increase was observed in unscheduled visits (p = 0.005), as well as use of OCS and antibiotics (p = 0.009 and p = 0.003, respectively).Conclusion: BT in adults with severe asthma improved ACQ, mini-AQLQ and lung function, but resulted in an increased frequency of unscheduled doctor-visits and rescue courses of OCS and antibiotics.


Laser pointer visual field screening.
Sensitivity of confrontation visual field (CVF) screening is low unless defects are significant. We compared the sensitivity of laser pointer visual field screening (LVF) with conventional CVF for identifying eyes with abnormal automated perimetry. Ninety consecutive patients presenting for HVF prospectively underwent a masked comparison of CVF and LVF testing (175 eyes) from April to May 2000. LVF was performed using a laser pointer target projected onto a tangent screen. Points were tested in random fashion on either side of the vertical and horizontal meridians, near central fixation, around the blind spot, and in each quadrant. Single and double simultaneous finger counting was used to test CVF. LVF demonstrated significantly greater sensitivity as compared with CVF (73% versus 31%, P = 0.001) in identifying field defects found on HVF. Specificities for LVF and CVF were 82% and 99%, respectively. The average testing times per eye were 0.5 minute for CVF, 1.5 minutes for LVF, and 8.0 minutes for HVF. In this cohort, laser visual field testing was significantly more sensitive than confrontation testing. It may represent an effective, time-efficient tool for visual field screening.


Optimizing stem cell culture.
Stem cells always balance between self-renewal and differentiation. Hence, stem cell culture parameters are critical and need to be continuously refined according to progress in our stem cell biology understanding and the latest technological developments. In the past few years, major efforts have been made to define more precisely the medium composition in which stem cells grow or differentiate. This led to the progressive replacement of ill-defined additives such as serum or feeder cell layers by recombinant cytokines or growth factors. Another example is the control of the oxygen pressure. For many years cell cultures have been done under atmospheric oxygen pressure which is much higher than the one experienced by stem cells in vivo. A consequence of cell metabolism is that cell culture conditions are constantly changing. Therefore, the development of high sensitive monitoring processes and control algorithms is required for ensuring cell culture medium homeostasis. Stem cells also sense the physical constraints of their microenvironment. Rigidity, stiffness, and geometry of the culture substrate influence stem cell fate. Hence, nanotopography is probably as important as medium formulation in the optimization of stem cell culture conditions. Recent advances include the development of synthetic bioinformative substrates designed at the micro- and nanoscale level. On going research in many different fields including stem cell biology, nanotechnology, and bioengineering suggest that our current way to culture cells in Petri dish or flasks will soon be outdated as flying across the Atlantic Ocean in the Lindbergh's plane.


[The operative cystoscope with joystick control mechanism of flexible tools inserted into the urinary bladder and the ureter].
The authors developed an operative cystoscope with joystick control mechanism of ureter catheters and other flexible tools. This construction allowed control of flexible tools inserted into the bladder and the ureter in various directions, thus providing a necessary observation of the operative field at endoscopic operations on the bladder and ureter. This was one of the factors, which determined the operation success.


Management of thyrotoxic crisis.
The thyrotoxic crisis is a medical emergency caused by an exacerbation of the hyperthyroid state characterized by decompensation of one or more organ systems. Early recognition and aggressive treatment are fundamental in limiting the morbidity and mortality associated with this condition. The crisis has an abrupt onset, and is evoked by a precipitating factor such as infectious diseases, ketoacidosis, acute trauma, thyroidal surgery, 131-I radio-metabolic treatment, administration of iodine-containing materials (amiodarone), parturition. The clinical picture is characterized by four main features: fever, tachycardia or supraventricular arrhythmias, central nervous system symptoms and finally gastrointestinal symptoms. The diagnosis of thyrotoxic crises is often made on the basis of clinical findings alone, since it is difficult in most emergency departments to obtain rapid confirmatory laboratory or nuclear medicine tests. The ultrasound thyroid scan, if available in the emergency room, may suggest an hyperthyroid state showing typical images of Basedow's disease or nodular goiter with their characteristic color-Doppler pattern of hyperactivity, easily distinguishable from a normal gland. The principles of thyroid storm treatments are: reduction of circulating TH's levels; inhibition of the peripheral effects of circulating thyroid hormones (TH); supportive care, in order to reverse systemic decompensation and treatment of the underlying precipitating event.


Neurodevelopmental sequelae in pneumococcal meningitis cases in Bangladesh: a comprehensive follow-up study.
Evaluation of the long-term impact of pneumococcal meningitis on surviving children and their families is critical to fully comprehending the burden of pneumococcal disease and to facilitating an evidence-based decision for the introduction of pneumococcal vaccine. This study was an investigation of the short- and long-term impacts of pneumococcal meningitis among Bangladeshi children. Case patients with pneumococcal meningitis who were hospitalized between January 2006 and March 2007 were subjected to short-term follow-up within 30-40 days of discharge. Case patients discharged prior to January 2005 were selected for long-term follow-up at 6-24 months after the date of discharge. Both cohorts were enrolled from Dhaka Shishu Hospital, a pediatric hospital in Bangladesh. Healthy children matched for age, sex, socioeconomic status, and area of residence were recruited from the community as control subjects. During follow-up visits, case patients and control subjects were assessed for their physical and neurodevelopmental status by use of a standardized protocol. The impact of pneumococcal meningitis on siblings and the family as a whole was assessed by means of qualitative interviews. Neurodevelopmental assessments of the short-term follow-up cohort (n=51) revealed hearing, vision, mental, and psychomotor deficits in 33%, 8%, 41%, and 49% of the case patients, respectively. These deficits were 18%, 4%, 41%, and 35% in the long-term follow-up cohort (n=51), respectively. Such deficits were seen in only 2% of the control subjects, none of whom had vision or hearing deficits. In addition to the risk of death, pneumococcal meningitis in children causes severe disabilities among survivors, as well as disruption of the life of other siblings and family members. This study demonstrated that high rates of sequelae are associated with pneumococcal meningitis. Neurodevelopmental assessment during follow-up of patients with meningitis is critical to our understanding of the burden of the adverse consequences of pneumococcal disease. These data, along with the fact of poor access to health care, provide a compelling argument in favor of the introduction of pneumococcal vaccine, specifically in a setting where access to health care is poor and disabled children remain incapacitated because of a lack of resources and facilities.


Neural dynamic optimization for control systems.III. Applications.
For pt.II. see ibid., p. 490-501. The paper presents neural dynamic optimization (NDO) as a method of optimal feedback control for nonlinear multi-input-multi-output (MIMO) systems. The main feature of NDO is that it enables neural networks to approximate the optimal feedback solution whose existence dynamic programming (DP) justifies, thereby reducing the complexities of computation and storage problems of the classical methods such as DP. This paper demonstrates NDO with several applications including control of autonomous vehicles and of a robot-arm, while the two other companion papers of this topic describes the background for the development of NDO and present the theory of the method, respectively.


[Effects of ursolic acid on liver injury and its possible mechanism in diabetes mellitus mice].
To study the effects of ursolic acid on liver injury in diabetic mice induced by high-fat diet combined with streptozotocin(STZ), and to explore its possible mechanisms. Diabetes mellitus was induced in twenty male ICR mice by a combination of high-fat diet for 6 weeks with low-dose streptozotocin (30 mg/kg, i. p.) for 5 consecutive days. After 9 days, fasting blood glucose levels were determined. Mice with fasting blood glucose levels exceeded 11. 1 mmol/L were diagnosed as diabetic mice and selected for further experiment. These mice were randomly divided into two groups(each group of 10):diabetic group, ursolic acid group (100 mg/kg, i. g.), and another 10 mice were set as control group. After continuous administration for 8 weeks, body weight (BW) were weighed, fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate transaminase (AST) in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver were measured. HE staining was used to observe pathological changes of liver tissue. Compared with the control group, the level of FBG, TC, TG, ALT, AST, MDA were dramatically increased (P<0. 05, P<0. 01) and SOD was markedly decreased (P<0.01) in the diabetic group; HE staining showed that parts of liver cells swelled and had a light fatty degeneration as well as lymphocyte infiltrated around the portal area in model group. Compared with the diabetic group, the level of FBG, TC, TG, ALT, AST, MDA were significantly declined (P<0.05, P<0.01) and SOD was considerably increased (P<0.01) in the ursolic acid group; HE staining showed that the liver cells relatively arranged in order, edema was not obvious and inflammatory cells infiltrated lightly in the ursolic acid group. Ursolic acid has a protective effect on liver injury in diabetic mice induced by high-fat diet combined with STZ by intraperitoneal ingector, and its mechanism may be associated with lowering blood glucose, regulating the lipid metabolism, reducing oxidative stress and enhancing the ability of anti-oxidation in liver.


Flexible black phosphorus ambipolar transistors, circuits and AM demodulator.
High-mobility two-dimensional (2D) semiconductors are desirable for high-performance mechanically flexible nanoelectronics. In this work, we report the first flexible black phosphorus (BP) field-effect transistors (FETs) with electron and hole mobilities superior to what has been previously achieved with other more studied flexible layered semiconducting transistors such as MoS2 and WSe2. Encapsulated bottom-gated BP ambipolar FETs on flexible polyimide afforded maximum carrier mobility of about 310 cm(2)/V·s with field-effect current modulation exceeding 3 orders of magnitude. The device ambipolar functionality and high-mobility were employed to realize essential circuits of electronic systems for flexible technology including ambipolar digital inverter, frequency doubler, and analog amplifiers featuring voltage gain higher than other reported layered semiconductor flexible amplifiers. In addition, we demonstrate the first flexible BP amplitude-modulated (AM) demodulator, an active stage useful for radio receivers, based on a single ambipolar BP transistor, which results in audible signals when connected to a loudspeaker or earphone. Moreover, the BP transistors feature mechanical robustness up to 2% uniaxial tensile strain and up to 5000 bending cycles.


Orbital wall fractures: evaluation and management.
Over a 49-month period, 121 orbital wall fractures were treated and 92 were followed for a median of 6.5 months (minimum, 3 months). Associated injuries included a 17% incidence of serious globe or optic nerve injuries and 13% incidence of lacrimal drainage disruption. Diplopia occurred in 23% and dystopia in 11%. Management was by observation alone in 14% and exploration in the remainder, with layered gelfilm for defects smaller than 4 cm2, alloplastic sheeting for defects to 6 cm2, and outer cortex of parietal bone for larger dehiscences. There were no decrements in vision from operation, dystopias were corrected to within 2 mm of normal, and diplopia persisted only in those with extraocular muscle paresis. There was no benefit to exploration of orbital wall defects smaller than 2.5 cm2 or with reduction of other midfacial fractures (e.g., malar) when neither dystopia nor entrapment was present, because defects not obturated in such cases had no sequelae.


Extended phage-typing scheme for Escherichia coli O157:H7.
In Canada, the number of human isolates of verotoxigenic (VT + ve) Escherichia coli O157:H7 from diarrhoeal cases and haemolytic uraemic syndrome and haemorrhagic colitis has increased from 25 in 1982 to 2384 in 1989. A total of 3273 VT + ve E. coli O157:H7 strains (3255 strains isolated in Canada and 18 isolates from other countries) were phage typed. The phage typing scheme has been extended from 14 to 62 phage types. Of these, five types occurred exclusively in other countries (type 47 in Japan; and types 49, 50, 51 and 52 in the U.K.). Thirty-five different phage types were identified in Canada; only nine of these (1, 2, 4, 8, 14, 21, 23, 31 and 32), each accounted for more than 1% of the cases from human sources. The same nine types were the only ones observed among the isolates from non-human sources (meat and slaughter houses) suggesting a food-borne transmission in most of the human cases. Phage types 1 (30.5%); 4 (21%); 8 (13.5%); 31 (8.9%) and 14 (8%) were encountered in varying frequencies in most of the provinces; infrequently occurring phage types also showed regional variation. Thirteen different phage types were identified among 151 outbreaks representing 556 isolates of E. coli O157:H7. More than one phage type were encountered in 12 outbreaks whereas in 141 outbreaks, all strains in each, had the same phage type.


Desmopressin orally disintegrating tablet effectively reduces nocturia: results of a randomized, double-blind, placebo-controlled trial.
The primary objective was to investigate the efficacy of desmopressin orally disintegrating tablet versus placebo in patients with nocturia. Pharmacodynamics, safety and patient-reported quality of life (QoL) outcomes were also evaluated. One of several benefits of the new formulation is increased bioavailability. Exploring lower doses allows for a better evaluation of therapeutic effect versus tolerability. This was a 4-week, randomized, double-blind study comparing 10, 25, 50, or 100 µg desmopressin versus placebo in adults with defined nocturia. The intent to treat population comprised 757 patients experiencing ∼3 voids/night and a high prevalence of nocturnal polyuria (∼90%). Increasing doses of desmopressin were associated with decreasing numbers of nocturnal voids and voided volume, greater proportions of subjects with >33% reduction in nocturnal voids, and increased duration of first sleep period. The lowest dose reaching statistical significance (P < 0.05 vs. placebo) varied by endpoint. Improvements were clinically meaningful, meaning that patients actually had fewer nightly voids. Post hoc analyses by gender suggested a lower minimum effective dose for women. Desmopressin was generally well tolerated. Reductions in serum sodium to <125 mmol/L in six women (taking >25 µg desmopressin) and two men (aged 67 and 82) taking 100 µg, support lower and gender-specific dosing to reduce the small but clinically significant risk of hyponatraemia. Each void reduced/hour of sleep gained was associated with significant improvements in QoL. Desmopressin orally disintegrating tablet is an effective and well-tolerated treatment for patients with nocturia. Further exploration of the lower dose range is warranted.


A cocrystal of L-ascorbic acid with picolinic acid: the role of O-H...O, N-H...O and C-H...O hydrogen bonds and L-ascorbic acid conformation in structure stabilization.
A new 1:1 cocrystal (L-Asc-Pic) of L-ascorbic acid (vitamin C) with picolinic acid was prepared as a powder and as single crystals. The crystal structure was solved and refined from single-crystal X-ray diffraction (SCXRD) data collected at 293 (2) and 100 (2) K. The samples of the L-Asc-Pic cocrystal were characterized by elemental (HCNS) analysis and titrimetric methods, TG/DTG/DSC, and IR and Raman spectroscopy. The asymmetric unit comprises a picolinic acid zwitterion and an L-ascorbic acid molecule. The stabilization energy of intermolecular interactions involving hydrogen bonds, the vibrational spectrum and the energies of the frontier molecular orbitals were calculated using the GAUSSIAN09 and the CrystalExplorer17 programs. The charge distribution on the atoms of the L-Asc-Pic cocrystal, L-ascorbic acid itself and its 12 known cocrystals (structures from Version 5.40 of the Cambridge Structural Database) were calculated by the methods of Mulliken, Voronoi and Hirshfeld charge analyses (ADF) at the bp86/TZ2P+ level of theory. The total effective charges and conformations of the L-ascorbic acid molecules in the new and previously reported cocrystals were compared with those of the two symmetry-independent molecules in the crystals of L-ascorbic acid. A correlation between molecular conformation and its effective charge is discussed.


[Current possibilities of the operative treatment of epilepsy].
Interest in surgical treatment for epileptic seizures has increased considerably over the last decades. Better understanding of the epileptic process itself and the advent of new functional diagnostic means have led to the recognition that 11%-50% of patients with partial seizures might benefit from surgery. The major aspects of this review article include a discussion of the criteria that must be met before considering surgery and the need to establish a proper diagnosis. Together with immaculate surgical techniques, these factors provide the basis for a successful outcome following operation. Surgical therapy has three objectives: (1) seizure control, (2) functional and behavioral improvement, and (3) interruption of an otherwise ongoing process. As the study of epileptogenesis and localization of the epileptic focus, besides information derived from the clinical pattern of the typical seizure itself, depends more on the techniques that reveal abnormalities of neuronal function, as opposed to structure, presurgical evaluation continues to depend largely on electrophysiological measurements. Special recording techniques and particularly long-term monitoring, using CCTV and stereotactically implanted depth electrodes (stereo EEG), are often mandatory. Other modern diagnostic means, such as single photon-emission computed tomography and positron computed tomography for functional abnormalities, as well as CT scan and NMR tomography for identification of structural abnormalities, add valuable information. The most common surgical resection performed today for epilepsy is anterior temporal lobectomy. About 60% of patients with partial epilepsy may become seizure-free after this procedure, with minimal side effects. Over 90% may achieve worthwhile benefit. Mesiobasal-limbic epilepsy can be successfully operated on by microsurgical "selective amygdalohippocampectomy".(ABSTRACT TRUNCATED AT 250 WORDS)


Chronic P7C3 treatment restores hippocampal neurogenesis in the Ts65Dn mouse model of Down Syndrome [Corrected].
Down syndrome (DS) is the most common genetic cause of intellectual disability and developmental delay. In addition to cognitive dysfunction, DS patients are marked by diminished neurogenesis, a neuropathological feature also found in the Ts65Dn mouse model of DS. Interestingly, manipulations that enhance neurogenesis - like environmental enrichment or pharmacological agents - improve cognition in Ts65Dn mice. P7C3 is a proneurogenic compound that enhances hippocampal neurogenesis, cell survival, and promotes cognition in aged animals. However, this compound has not been tested in the Ts65Dn mouse model of DS. We hypothesized that P7C3 treatment would reverse or ameliorate the neurogenic deficits in Ts65Dn mice. To test this, adult Ts65Dn and age-matched wild-type (WT) mice were administered vehicle or P7C3 twice daily for 3 months. After 3 months, brains were examined for indices of neurogenesis, including quantification of Ki67, DCX, activated caspase-3 (AC3), and surviving BrdU-immunoreactive(+) cells in the granule cell layer (GCL) of the hippocampal dentate gyrus. P7C3 had no effect on total Ki67+, DCX+, AC3+, or surviving BrdU+ cells in WT mice relative to vehicle. GCL volume was also not changed. In keeping with our hypothesis, however, P7C3-treated Ts65Dn mice had a significant increase in total Ki67+, DCX+, and surviving BrdU+ cells relative to vehicle. P7C3 treatment also decreased AC3+ cell number but had no effect on total GCL volume in Ts65Dn mice. Our findings show 3 months of P7C3 is sufficient to restore the neurogenic deficits observed in the Ts65Dn mouse model of DS.


Laparoscopic Nissen fundoplication for gastroesophageal reflux disease: clinical experience and outcome in first 100 patients.
Using retrospective chart review, the authors evaluated the results of laparoscopic Nissen fundoplication in their first 100 patients. All patients were diagnosed with gastroesophageal reflux disease. More than 90% of the patients in this series were symptomatically improved, and 92% of those studied endoscopically had healed esophagitis and intact fundoplication. No deaths, esophageal injuries, or splenic injuries occurred. Laparoscopic fundoplication can be performed safely and efficiently. Using a linear stapler enables rapid and safe fundi mobilization. Selective manometrics and ambulatory pH monitoring provide excellent results. Laparoscopic Nissen is safe and as effective as the open procedure. Research centers have noted some differences in postoperative function of the lower esophageal sphincter, but symptomatically patient satisfaction is comparable.


Evaluating the quality of care provided by graduates of international medical schools.
One-quarter of practicing physicians in the United States are graduates of international medical schools. The quality of care provided by doctors educated abroad has been the subject of ongoing concern. Our analysis of 244,153 hospitalizations in Pennsylvania found that patients of doctors who graduated from international medical schools and were not U.S. citizens at the time they entered medical school had significantly lower mortality rates than patients cared for by doctors who graduated from U.S. medical schools or who were U.S. citizens and received their degrees abroad. The patient population consisted of those with congestive heart failure or acute myocardial infarction. We found no significant mortality difference when comparing all international medical graduates with all U.S. medical school graduates.


Diagnosis and Management of Neonatal Herpes Simplex Infection in the Emergency Department.
Neonatal herpes simplex virus infection (HSV) is rare in neonates, with an estimated global incidence of 10 per 100,000 live births. Neonatal HSV is challenging to diagnose due to often vague signs and symptoms. Untreated, the mortality of some HSV subtypes exceeds 80%. Overtesting and overtreatment can result in prolonged hospitalizations and expose neonates to medication toxicity. In contrast, prompt evaluation and use of empiric antiviral therapy before the results of definitive testing can improve outcomes for infants with HSV. A wide degree of practice variation exists with respect to testing and treatment for neonatal HSV, and more research is required to safely risk-stratify this population. This review presents the epidemiology, risk factors, presenting features, and emergency department management of neonatal HSV infection.


Dilated perivascular spaces in the Basal Ganglia are a biomarker of small-vessel disease in a very elderly population with dementia.
Dilated perivascular spaces have been shown to be a specific biomarker of cerebral small-vessel disease in young patients with dementia. Our aim was to examine the discriminative power of dilated cerebral perivascular spaces as biomarkers of small-vessel disease in a very elderly population of patients with dementia. We studied healthy volunteers (n = 65; mean age, 78 ± 5.6 years) and subjects with vascular dementia (n = 39; mean age, 76.9 ± 7.7 years) and Alzheimer disease (n = 47; mean age, 74.1 ± 8.5 years). We compared white matter hyperintensity and 2 semiquantitative perivascular space scoring systems (perivascular space-1 and perivascular space-2). Intra- and interobserver agreement was assessed by using a weighted Cohen κ statistic. Multinomial regression modeling was used to assess the discriminative power of imaging features to distinguish clinical groups. White matter hyperintensity scores were higher in vascular dementia than in Alzheimer disease (P < .05) or healthy volunteers (P < .01). The perivascular space-1 score was higher in vascular dementia and Alzheimer disease than in healthy volunteers (P < .01). The perivascular space-2 score in the centrum semiovale showed no intergroup differences. However, perivascular space-2 in the basal ganglia was higher in vascular dementia than in Alzheimer disease (P < .05) or healthy volunteers (P < .001) and higher in Alzheimer disease than in healthy volunteers (P < .001). Modeling of dementia versus healthy volunteers, Alzheimer disease versus healthy volunteers, and vascular dementia against Alzheimer disease demonstrated perivascular space-2basal ganglia as the only imaging parameter with independent significant discriminative power (P < .01, P < .01, and P < .05) with areas under the receiver operating characteristic curve of 0.855, 0.774, and 0.71, respectively. Modeling of vascular dementia versus healthy volunteers showed that perivascular space-2basal ganglia (P < .01) and the modified Scheltens score (P < .05) contributed significant, independent discriminatory power, accounting for 34% and 13% of the variance in the model respectively. Dilated perivascular spaces remain a valuable biomarker of small-vessel disease in an elderly population.


Spontaneous Intracranial Hypotension in Pregnancy.
Spontaneous intracranial hypotension (SIH) is a debilitating disease typically featuring orthostatic headache and caused by a spinal CSF leak. This review will describe the characteristics of SIH in pregnant patients and the associated unique management and treatment considerations. Herein, a novel case is reported of a 41-year-old woman who presented with SIH pre-conception but saw marked improvement of symptoms after 5 weeks antepartum and symptom recurrence 2 months post-partum. A literature review of SIH in pregnancy revealed 14 reported patients across 10 studies since 2000. All the reported cases resulted in delivery of healthy infants and symptomatic improvement with conservative management or a variety of treatment modalities including non-targeted epidural blood patch (EBP). Clinical and imaging features of SIH in pregnancy are reviewed. We hypothesize an antenatal protective mechanism against SIH symptoms through cephalad redistribution of CSF volume from the spinal to intracranial compartments related to uterine growth and decreased CSF volume within the lumbar cistern. Treatment recommendations are discussed including duration of bed rest and decision for non-targeted multi-site EBPs. When required, non-invasive diagnostic spine MRI using fat-suppressed axial T2-weighted imaging may be helpful.


Event-Ready Bell Test Using Entangled Atoms Simultaneously Closing Detection and Locality Loopholes.
An experimental test of Bell's inequality allows ruling out any local-realistic description of nature by measuring correlations between distant systems. While such tests are conceptually simple, there are strict requirements concerning the detection efficiency of the involved measurements, as well as the enforcement of spacelike separation between the measurement events. Only very recently could both loopholes be closed simultaneously. Here we present a statistically significant, event-ready Bell test based on combining heralded entanglement of atoms separated by 398 m with fast and efficient measurements of the atomic spin states closing essential loopholes. We obtain a violation with S=2.221±0.033 (compared to the maximal value of 2 achievable with models based on local hidden variables) which allows us to refute the hypothesis of local realism with a significance level P<2.57×10^{-9}.


[The Ivory Cross: past, present and future. Promotion of oral health in the Netherlands by a national information organization].
In this article a description is given of the role of Dutch National Association for the Promotion of Oral Hygiene (Ivoren Kruis), the Dutch organisation of oral health education. In this review attention is paid to the past and to the recent working method of the association by which it tries to realise the improvement of the dental health on the population and individual level. Special attention is paid to the evaluation of all sort of activities and programmes on oral health education. The article concludes with a short view on the future of the organisation.


The role of the FOLFIRINOX regimen for advanced pancreatic cancer.
In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) emerged as a new option in patients with metastatic pancreatic cancer and a good performance status. However, at that time, some doubts were raised regarding safety issues. Similarly, no data on FOLFIRINOX were published in patients with unresectable/locally advanced or borderline resectable pancreatic cancer. This article presents the available experience with FOLFIRINOX outside clinical trials in metastatic and locally advanced pancreatic cancer patients. The safety of the regimen in patients with biliary stents and in previously treated patients is also described. FOLFIRINOX usage in clinical practice, including modification of the regimen (omission of bolus 5-fluorouracil; FOLFOXIRI regimen), is also presented. These data suggest that a phase III randomized study is warranted to further explore the role of FOLFIRINOX in locally advanced pancreatic cancer.


Testosterone decreases trust in socially naive humans.
Trust plays an important role in the formation and maintenance of human social relationships. But trusting others is associated with a cost, given the prevalence of cheaters and deceivers in human society. Recent research has shown that the peptide hormone oxytocin increases trust in humans. However, oxytocin also makes individuals susceptible to betrayal, because under influence of oxytocin, subjects perseverate in giving trust to others they know are untrustworthy. Testosterone, a steroid hormone associated with competition and dominance, is often viewed as an inhibitor of sociality, and may have antagonistic properties with oxytocin. The following experiment tests this possibility in a placebo-controlled, within-subjects design involving the administration of testosterone to 24 female subjects. We show that compared with the placebo, testosterone significantly decreases interpersonal trust, and, as further analyses established, this effect is determined by those who give trust easily. We suggest that testosterone adaptively increases social vigilance in these trusting individuals to better prepare them for competition over status and valued resources. In conclusion, our data provide unique insights into the hormonal regulation of human sociality by showing that testosterone downregulates interpersonal trust in an adaptive manner.


Commentary: the dynamic evolution of forensic psychiatry at Yale and the Zonanian sphere of influence.
Forensic psychiatry at Yale begins, develops, and endures through the life and work of Howard Zonana. But the developments at Yale are only a part of a more complex and global story of one man's extraordinary influence on the evolution of practice and thought in forensic psychiatry in legislation and case law, teaching and scholarship, professional organizational activity, and public policy. This article places Dr. Zonana's career and achievements in the historical context of the field of forensic psychiatry and traces several examples of his activism, scholarship, mentoring, and collegiality. It is a great pleasure to acknowledge our vast collective appreciation of Howard's influence in the lives of those who have had the privilege to know him and work with him and benefit from his many contributions to our field.


Peptide Hormone Insulin Regulates Function, Expression, and SUMOylation of Organic Anion Transporter 3.
Organic anion transporter 3 (OAT3) plays an important role in the disposition of various anionic drugs which impacts the pharmacokinetics and pharmacodynamics of the therapeutics, thus influencing the pharmacological effects and toxicity of the drugs. In this study, we investigated the effect of insulin on the regulation of OAT3 function, expression, and SUMOylation. We demonstrated that insulin induced an increase in OAT3 transport activity through a dose- and time-dependent manner in COS-7 cells. The insulin-induced elevation in OAT3 function was blocked by PKA inhibitor H89, which correlated well with OAT3 protein expression. Moreover, both PKA activator Bt2-cAMP-induced increase and insulin-induced increase in OAT3 function were blocked by PKB inhibitor AKTi1/2. To further investigate the involvement of SUMOylation, we treated OAT3-expressing cells with insulin in presence or absence of H89 or AKTi1/2 followed by examining OAT3 SUMOylation. We showed that insulin enhanced OAT3 SUMOylation, and such enhancement was abrogated by H89 and AKTi1/2. Lastly, insulin increased OAT3 function and SUMOylation in rat kidney slice. In conclusion, our investigations demonstrated that insulin regulated OAT3 function, expression, and SUMOylation through PKA/PKB signaling pathway. Graphical abstract.


Prevalence of acne and its impact on the quality of life in school-aged adolescents in Malaysia.
The objective of this study was to determine the prevalence of facial acne and its impact on the quality of life among adolescents attending secondary schools in Muar, Malaysia. A cross-sectional study was conducted where 409 samples were selected using stratified cluster random sampling from two secondary schools in Muar, involving Form 1 to Form 5 students. Students were diagnosed clinically and the severity of facial acne was assessed using Global Acne Grading System. A self-reported Cardiff Acne Disability Index was used to assess the quality of life among adolescents who had acne. The prevalence of facial acne among the adolescents was 67.5% (n = 276). Facial acne increased with increasing age (p = 0.001). It was more common among males (71.1%) than females (64.6%), p = 0.165. The males also had a higher prevalence of severe acne (p = 0.001). The quality of life was affected by the severity of acne. Students with severe acne had higher levels of Cardiff Acne Disability Index (rho = 0.521). Facial acne is a common disorder and appears to have a considerable impact on quality of life among adolescents. The above findings should alert health care professionals and the school authorities to actively identify, manage and educate adolescents with facial acne.


Transcriptional regulation of fruit ripening by tomato FRUITFULL homologs and associated MADS box proteins.
The tomato (Solanum lycopersicum) MADS box FRUITFULL homologs FUL1 and FUL2 act as key ripening regulators and interact with the master regulator MADS box protein RIPENING INHIBITOR (RIN). Here, we report the large-scale identification of direct targets of FUL1 and FUL2 by transcriptome analysis of FUL1/FUL2 suppressed fruits and chromatin immunoprecipitation coupled with microarray analysis (ChIP-chip) targeting tomato gene promoters. The ChIP-chip and transcriptome analysis identified FUL1/FUL2 target genes that contain at least one genomic region bound by FUL1 or FUL2 (regions that occur mainly in their promoters) and exhibit FUL1/FUL2-dependent expression during ripening. These analyses identified 860 direct FUL1 targets and 878 direct FUL2 targets; this set of genes includes both direct targets of RIN and nontargets of RIN. Functional classification of the FUL1/FUL2 targets revealed that these FUL homologs function in many biological processes via the regulation of ripening-related gene expression, both in cooperation with and independent of RIN. Our in vitro assay showed that the FUL homologs, RIN, and tomato AGAMOUS-LIKE1 form DNA binding complexes, suggesting that tetramer complexes of these MADS box proteins are mainly responsible for the regulation of ripening.


Ischaemia-reperfusion induced alterations of mitochondrial function in hypertrophied rat heart.
The impact of in vivo ischaemia and ischaemia-reperfusion (I-R) on mitochondrial respiratory function was investigated in hypertrophied (HP) hearts with aortic constriction compared with control hearts using an open-chest rat surgical model. Moreover, mitochondrial susceptibility to superoxide radicals (O2-.) in vitro was examined in HP and control hearts with or without I-R. With the site I substrates pyruvate-malate, mitochondrial state 4 (basal) respiration and the respiratory control index (RCI) were not affected by either ischaemia alone or I-R in both HP and control hearts. State 3 (ADP-stimulated) respiration was increased with I-R in control hearts, but showed a reduction after I-R in the HP hearts. Exposure of mitochondria to O2-. (20 nM hypoxanthine in the presence of 0.13 unit mL-1 xanthine oxidase) significantly increased state 4 respiration, whereas state 3 respiration and RCI were decreased in all treatment groups. I-R hearts in both HP and control showed greater increases in state 4 respiration with O2-. than either sham or ischaemic hearts. HP hearts exhibited a significantly lesser extent of inhibition in state 3 respiration and RCI by O2-. compared with control hearts. These changes in mitochondrial respiratory properties were not observed with the site II substrate succinate. Myocardial reduced vs. oxidized glutathione ratio was significantly decreased after I-R in both control and HP hearts. Malondialdehyde content showed an increase with I-R, but the increase was significant only in control hearts. These data indicate that short-term in vivo I-R does not impair heart mitochondrial respiratory function, but renders the organelles more vulnerable to imposed oxidative stress. Mitochondria from the HP hearts are more resistant to free radical damage under normal and ischaemic conditions; however, this advantage is severely compromised after reperfusion.


Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse.
The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. The fruit extract of TT ameliorates the MTZ-induced alterations in the testis.


Regulation of vitamin C homeostasis during deficiency.
Large cross-sectional population studies confirm that vitamin C deficiency is common in humans, affecting 5%-10% of adults in the industrialized world. Moreover, significant associations between poor vitamin C status and increased morbidity and mortality have consistently been observed. However, the absorption, distribution and elimination kinetics of vitamin C in vivo are highly complex, due to dose-dependent non-linearity, and the specific regulatory mechanisms are not fully understood. Particularly, little is known about how adaptive mechanisms during states of deficiency affect the overall regulation of vitamin C transport in the body. This review discusses mechanisms of vitamin C transport and potential means of regulation with special emphasis on capacity and functional properties, such as differences in the K(m) of vitamin C transporters in different target tissues, in some instances demonstrating a tissue-specific distribution.


Simultaneous measurement of intestinal crypt cell production rate and water absorption.
Intestinal cell proliferation and cell production is best quantified by measuring the rate of accumulation of vincristine arrested metaphases in microdissected intestinal crypts to determine the crypt cell production rate (CCPR). Studies of intestinal adaptation could be much more informative if a valid measure of intestinal function could also be included. One such method is the water absorption capacity. The CCPR of the jejunum and intestinal water absorption were measured in 19 groups of hypo and hyperproliferative rats which were in a 'steady state' of cell production and turnover. The minimum values were obtained after hypophysectomy and the maximum values were observed in lactation. Crypt cell production rate and absorption were significantly correlated (p less than 0.001) to each other. There was a significant (p less than 0.001) correlation between both CCPR and absorption and dry weight of the intestinal segment studies and food intake. Body weight was a poor predictor of either CCPR or absorption. The combined study of CCPR and water absorption is thus a practical and convenient approach to the study of intestinal cell proliferation and intestinal adaptation.


Analysis of antigenic determinants of retinal S-antigen with monoclonal antibodies.
Eight murine monoclonal antibodies to retinal S-antigen were found to recognize three antigenic clusters in competitive binding experiments. Variable patterns of immunohistochemical staining of retinal sections supported the competitive binding studies. Monoclonal antibodies to two of these three antigenic clusters on S-antigen reacted by Western immunoblotting with both intact S-antigen and two cyanogen bromide cleaved peptide fragments of bovine S-antigen. The binding of the monoclonal antibodies was localized to epitopes contained on two peptide fragments of 26,000 and 18,000 molecular weight. The same peptide fragments also react with polyclonal rat or rabbit antisera to bovine S-antigen. Monoclonal antibodies to the third antigenic cluster did not react with either intact or fragmented S-antigen in immunoblotting studies.