Considerations of traditional Chinese medicine as adjunct therapy in the management of ulcerative colitis.
Ulcerative colitis (UC) has been treated with traditional Chinese medicine (TCM) for literally thousands of years. This paper gives an overview of TCM in the management of UC, provides an account of the state of the evidence, identifies gaps in the research base, and makes recommendations for future research. TCM is based on patterns and this influences the selection of the type of herbal medication or manipulation technique used for treatment. The majority of clinical studies on the efficacy of Chinese herbal medicine and acupuncture in the treatment of UC have methodological shortcomings. The extent of heterogeneity in many of these clinical trials, poor design quality of past studies prevent meaningful systematic reviews (SRs) or meta-analysis, although there are positive signs that TCM may be useful in relieving abdominal pain and reducing inflammation. Many unknowns still exist, including the active ingredients within Chinese herbal medicine and the potential for interaction with other drugs or western medications. While there may be a potential role for utilizing TCM in the treatment of UC patients relying on both traditional concepts and modern developments, it should be recognized that there are no studies that irrefutably support the use of TCM in the treatment of UC. Further basic or translational research must be done to elucidate mechanisms of action of these agents, and well-designed and well-conducted clinical studies must also be done to determine efficacy and safety of these agents.


Effect of spermine on mitochondrial matrix calcium in relation to its enhancement of mitochondrial calcium uptake.
The mechanism of spermine-induced enhancement of mitochondrial Ca2+ uptake was explored using the fluorescent Ca2+ indicator Fluo-3/AM to measure the free matrix Ca2+ concentration. Simultaneously, the extramitochondrial Ca2+ concentration was registered by a Ca(2+)-ion selective electrode. Spermine lowered the extramitochondrial steady state Ca2+ concentration and at the same time induced a decrease of the intramitochondrial Ca2+ concentration. However, there is a concentration-dependent reversal of the stimulatory action of spermine, which may be explained by the existence of a second, low-affinity binding site for spermine which mediates an inhibition of uptake in spite of the existence of an inwardly directed Ca2+ gradient.


Return to motor activity after anterior cruciate ligament reconstruction--pilot study.
Background. Reconstruction surgery is the most frequent treatment for patients with anterior cruciate ligament (ACL) lesions. The goal of the study was to present patients' subjective evaluation of their return to motor activity after ACL reconstruction and investigate whether and what demographic or clinical factors determine the recovery of physical function of ACL reconstruction patients. Material and methods. The study involved a group of fifty (50) patients who underwent ACL reconstruction. The mean age of patients was 32 years. A questionnaire was used to collect data from the patients. The first part of the questionnaire was concerned with personal and clinical data, while the second part was the KOOS form. Results. The incidence of unfavourable, post-operative symptoms was lower in elderly patients, as well as in those with longer periods between injury and reconstruction. The patients in whom the patellar ligament was used for the reconstruction demonstrated better outcomes as regards returning to sports and recreational activity than those in whom flexor tendons were used. The patients who returned to practising a sport reported more pain episodes and problems with daily and sports activities. Their quality of life was inferior to those who did not return to unrestricted sports activity. Conclusions. 1. Neither sex nor BMI has any statistically significant effect on the recovery of mobility after ACL reconstruction. 2. ACL reconstruction with a graft harvested from the central band of the patellar ligament appears to be more appropriate for patients willing to return to full sports and recreational activity. 3. It is better to carry our ACL reconstruction when normal knee joint function has been regained and injury-related symptoms have subsided.


Barriers and opportunities to restricting marketing of unhealthy foods and beverages to children in Nepal: a policy analysis.
Marketing of foods and non-alcoholic beverages high in saturated fats, trans-fatty acids, free sugars, or salt ("unhealthy foods") to children is contributing to increasing child obesity. However, many countries have not implemented WHO recommendations to restrict marketing of unhealthy foods to children. We sought to understand the absence of marketing restrictions and identify potential strategic actions to develop and implement such restrictions in Nepal. Eighteen semi-structured interviews were conducted. Thematic analysis was based on Baker et al.'s 18 factor-framework for understanding what drives political commitment to nutrition, organised by five categories: Actors; Institutions; Political and societal contexts; Knowledge, evidence and framing; Capacities and resources. All factors in Baker et al.'s framework were reported to be acting largely as barriers to Nepal developing and implementing marketing restrictions. Six factors were identified by the highest number of respondents: the threat of private sector interference in policy-making; lack of international actor support; absence of well-designed and enacted policies and legislation; lack of political commitment to regulate; insufficient mobilisation of existing evidence to spur action and lack of national evidence to guide regulatory design; and weak implementation capacity. Opportunities for progress were identified as Nepal's ability to combat private sector interference - as previously demonstrated in tobacco control. This is the first study conducted in Nepal examining the lack of restrictions on marketing unhealthy foods to children. Our findings reflect the manifestation of power in the policy process. The absence of civil society and a multi-stakeholder coalition demanding change on marketing of unhealthy food to children, the threat of private sector interference in introducing marketing restrictions, the promotion of norms and narratives around modernity, consumption and the primary role of the individual in regulating diet - all have helped create a policy vacuum on marketing restrictions. We propose that stakeholders focus on five strategic actions, including: developing a multi-stakeholder coalition to put and keep marketing restrictions on the health agenda; framing the need for marketing restrictions as critical to protect child rights and government regulation as the solution; and increasing support, particularly through developing more robust global policy guidance.


ISOLATION AND PUNRIFICATION OF PSORALEN AND BERGAPTEN FROM FICUS CARICA L LEAVES BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY.
High-speed countercurrent chromatography was successfully applied for the first time for the separation of psoralen and bergapten from Ficus carica L leaves. The crudeextract obtained by light petroleum (b.p.: 60°C-90°C) from the dried leaves of Ficus carica L. was separated with a two-phase solvent system of n-Hexane-ethyl acetate-methanol-water (1:1:1:1, v/v). Each peak fraction was analyzed by high-performance liquid chromatography. The method yielded 4.4 mg of psoralen at 99.1% purity and 2.1 mg of bergapten at 98.2% purity from 400 mg of the crude extract in a single run. The two compounds were identified by (1)H-NMR, (13)C-NMR and MS.


Prevalence of Elevated NT-proBNP and its Prognostic Value by Blood Pressure Treatment and Control.
The prognostic utility of NT-proBNP in the setting of hypertension has not been well-characterized in the general US adult population. We measured NT-proBNP in stored blood samples collected from participants 1 year or older who participated in the 1999-2004 National Health and Nutrition Examination Survey. In adults 20 years or older without a history of cardiovascular disease, we assessed the prevalence of elevated NT-pro-BNP by blood pressure (BP) treatment and control categories. We examined the extent to which NT-proBNP identifies participants at higher risk for mortality across BP treatment and control categories. Among US adults without CVD, the prevalence of elevated NT-proBNP (≥125 pg/ml) was 27.2% among those with untreated hypertension, 24.9% among those with treated controlled hypertension, and 43.3% among those with treated uncontrolled hypertension. Over a median follow-up of 17.3 years and after adjusting for demographic and clinical risk factors, US adults with treated controlled hypertension and elevated NT-proBNP had increased risk of all-cause mortality (HR 2.29, 95% CI 1.79, 2.95) and cardiovascular mortality (HR 3.83, 95% CI 2.34, 6.29), compared to adults without hypertension and with low levels of NT-proBNP (<125 pg/ml). Across all levels of SBP and irrespective of antihypertensive medication use, elevated NT-proBNP was associated with an increased risk of mortality, compared to low levels of NT-proBNP. Among a general population of adults free of CVD, NT-proBNP can provide additional prognostic information within and across categories of BP. Measurement of NT-proBNP may have potential for clinical use to optimize hypertension treatment.


Challenging rigidity in Anorexia (treatment, training and supervision): questioning manual adherence in the face of complexity.
Anorexia Nervosa is a debilitating illness. While there have been many advancements to treatment protocols and outcomes for people with eating disorders, the field acknowledges there remains considerable room for improvement. This timely Special Edition of the Journal of Eating Disorders has invited those of us in the field to consider a range of topics in aid of this task, including potential modifications and implementation of evidence-based practice, specific and common psychotherapy factors, treatment manuals, adherence and individualising treatment approaches for individuals and families. BODY: In this paper, we briefly outline the key manualised treatments currently available to treat children, adolescents and adults with Anorexia Nervosa, considering the benefits, potential reasons for adaptations and limitations. We then review the current evidence for training strict adherence to treatment manuals which is often a key focus in training and supervision, questioning the association of increased treatment adherence with improved therapeutic outcome. We then summarise some key evidence behind other therapeutic factors which have been demonstrated to affect outcome regardless of which manual is implemented, such as readiness to change and therapeutic alliance. The paper concludes with implications and considerations for future research, clinical guidelines, training and supervision, highlighting the need to consider the therapeutic relationship and processes alongside manual content to conduct best evidence-informed practice.


Determination of testosterone production rates in men and women using stable isotope/dilution and mass spectrometry.
Production rates of testosterone were determined in healthy men and women during the follicular phase of their menstrual cycle using the stable isotope dilution technique and analysis by gas chromatography/mass spectrometry. In an initial series of experiments, 0.07 mg/h (men) or 0.01 mg/h (women) 1,2-d-testosterone was infused for 36 h. After an equilibration period of 12 h, blood samples were obtained at 20-min intervals throughout 24 h. In men, no diurnal rhythmicity of testosterone production was observed, whereas in women, testosterone production rates were largest from 0400-1200 h. In a second series of experiments, the infused dose of 1,2-d-testosterone was reduced to 0.015 mg/h (men) and 0.0001 mg/h (women), respectively. Blood samples were obtained at 20-min intervals during the last 12 h (0800-2000 h) of the observation period. In accordance with results obtained by others using radioactive tracers, estimated production rates were 147 +/- 31 microg/h (3.7 +/- 2.2 mg/day in men) and 1.8 +/- 0.6 microg/h (0.04 +/- 0.01 [corrected] mg/day in women). To reduce both the duration of the experiment and the number of samples to be processed, we subsequently demonstrated that similar production rates may be obtained when the equilibration period before blood sampling is reduced to 6 h and the period of blood sampling is reduced to 4 h. This protocol is suitable for clinical use in a routine setting to obtain analytically correct estimates of testosterone production in vivo.


Transcriptomic analysis of oyster Crassostrea gigas larvae illustrates the response patterns regulated by catecholaminergic system upon acute heat and bacterial stress.
Bacterial infection and heat stress, as two major environmental threats of marine molluscs, could affect larval development and dramatically promote mortality of oysters. In the present study, next-generation sequencing, together with determinations of mRNA expression and measurements of enzyme activities, were employed to understand the response patterns of oyster larvae under acute heat and bacterial stress. After RNA-seq, a total of 9472 differentially expressed genes including 4895 significantly up-regulated ones and 4577 significantly down-regulated ones were obtained from 12 transcriptome libraries. GO overrepresentation analysis of the up-regulated genes revealed that the neuroendocrine immunomodulation pathway was activated after acute heat and bacterial stimulation, in which the catecholaminergic regulation played an important role. GO overrepresentation analysis of the down-regulated genes suggested that the immune capacity of Crassostrea gigas larvae was suppressed under stress, which was further validated since superoxide dismutase (SOD) and phenoloxidase (PO) activities in the total protein extract of larvae decreased dramatically after stress. Moreover, the shell formation of trochophore was inhibited and severe mortality was caused after acute heat and bacterial stress. These results collectively indicated that acute heat and bacterial stress could significantly inhibit larval development and suppress immune response of oyster C. gigas larvae. And the neuroendocrine immunomodulation, especially the catecholaminergic regulation, played an indispensable role in the stress response of molluscan larvae.


Shikonin stimulates MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smad5 signal transduction pathway.
Shikonin, the predominant naphthoquinone pigment isolated from the Chinese plant Lithospermum erythrorhizon, is anti‑inflammatory, antiviral and exerts anticancer effects, amongst other biological activities. However, it is unknown whether shikonin affects bone formation. In the present study, the role of shikonin on cell proliferation was assessed via MTT assay, and shikonin was identified to markedly promote cell growth in a time‑ and dose‑dependent manner in the MC3T3‑E1 cell line. In addition, flow cytometric analysis was performed to evaluate the effect of shikonin on the cell cycle, and it was observed that shikonin markedly increased the percentage of S‑phase MC3T3‑E1 cells to accelerate the G1/S transition. To investigate the potential molecular mechanism by which shikonin enhances bone formation, the changes in bone morphogenic protein‑2 (BMP‑2), SMAD family member 5 (Smad5), runt related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC) expression levels induced by shikonin were investigated using western blot analysis and quantitative polymerase chain reaction. The results indicated that shikonin increased the BMP‑2 and Smad5 mRNA levels, and upregulated Smad5 and Runx2 protein expression levels to promote osteoblast differentiation. Furthermore, ALP staining was performed, and revealed that shikonin enhanced ALP activity. These results indicate that shikonin promotes cell proliferation and differentiation of MC3T3-E1 cells via the BMP-2/Smad5 signaling pathway.


New bone formation by orthodontic tooth movement for implant placement.
Bone defects at the anterior regions of the jaws often cause esthetic problems such as gingival disharmonies and longer crowns than neighboring teeth. Variety of procedures can be used in this region for achieving sufficient bone volume with or without different bone graft materials. All of these procedures has their own advantages and disadventages. New bone formation was defined with orthodontic tooth movement in different regions. In this case we present the use of orthodontic tooth movement, for achieving sufficient bone volume, in anterior maxillary region, for esthetic and functional results.


DNA origami frame filled with two types of single-stranded tiles.
DNA origami and DNA single-stranded tiles (SSTs) are two basic motifs that are widely used in fabricating DNA nanostructures. Typically, DNA origami is self-folded via a long single phage strand (scaffold strand) and this process is aided by a myriad of short oligonucleotides (staple strand). Unlike DNA origami, SSTs construct nanostructures using many unique strands connected with each other to obtain specific shapes. These motifs are material- and labour-consuming, and require multiple different synthetic oligonucleotides, and DNA SSTs tend to remain kinetically trapped in the form of tubes. In this study, we present a new strategy that combines DNA origami with DNA SSTs to construct a DNA nanostructure with a predesigned shape. A rectangular DNA origami frame with ten dozen helper strands was filled with two types of SSTs assembled repeatedly, which avoided the kinetic trap and used fewer synthetic oligonucleotides. The assembly results were identified using atomic force microscopy. The experimental analysis demonstrated the stability and feasibility of the strategy.


Resorption of the undersurface of the distal clavicle in rheumatoid arthritis.
An elongated erosion on the undersurface of the distal clavicle, adjacent to the coracoid process, may be seen in the shoulder of a patient with rheumatoid arthritis. This finding is apparently related to inflammatory changes in the coracoclavicular ligament. Such an erosion may occur with or without additional radiographic alterations and, although not entirely specific, suggests rheumatoid arthritis.


Maintaining a cautious state of mind during a recognition test: a large-scale fMRI study.
Decision criterion is an important factor in recognition memory, determining the amount of evidence required to judge an item as previously encountered. For a typical recognition memory test involving the prior study of a set of items, a conservative criterion establishes a higher standard of evidence for recognition and designates fewer items as previously studied. In contrast, a liberal criterion establishes a lower standard of evidence and designates more items as previously studied. Therefore, the hit rate and the correct rejection rate on a recognition memory test can be affected by both the memory strength of the studied items and the criterion used to make that judgment. Yet most neuroimaging studies of the successful retrieval effect (a contrast between hits and correct rejections) fail to measure or consider decision criterion. The goal of the current fMRI study with ninety-five participants was to directly manipulate decision criteria on two tests of recognition memory by varying the likelihood of an item's prior occurrence. Our results indicate that regions of the lateral prefrontal and parietal cortex associated with successful retrieval are significantly more active when using conservative criteria than liberal criteria. Furthermore, our results reveal that activity in these regions associated with successful retrieval can be accounted for by individual differences in the conservativeness of the decision criterion above and beyond any differences in memory strength. These results expound on the role of cognitive control in recognition memory and the neural mechanisms that mediate this processing.


Hennekam Syndrome: A Case Report.
Hennekam syndrome is a rare autosomal recessive disorder resulting from malformation of the lymphatic system. The characteristic signs of Hennekam syndrome are lymphangiectasia, lymph edema, facial anomalies, and mental retardation. This is a case in which a patient presented with left-arm lymphedema, facial-feature anomalies, and multiple organ lymphangiectasia consistent with symptoms of Hennekam syndrome. There is no curative therapy at this time, but rehabilitative treatments including complete decongestive therapy for edema control appeared to be beneficial.


Jurassic sandstone from the tropical atlantic.
The oldest sediment yet sampled from the abyssal margins of South America, late Jurassic (or possibly very early Cretaceous) shallow-water, coarse-grained, calcareous sandstone containing palynomorphs and mollusk prisms, was recovered from a depth of 4400 meters on the seaward scarp of the Demerara Plateau. The sandstone was deposited in a shallow, late Jurassic epicontinental sea after the initial stages of rifting when the newly created Atlantic began to founder.


An analysis of postoperative epidural analgesia failure by computed tomography epidurography.
In this prospective study involving 125 patients, we analyzed epidural analgesia failure after major abdominal surgery using computed tomography (CT) epidurographies to compare the incidence of dislodgement of epidural catheters and leakage of solution from the epidural space between two groups of patients: patients with successful or failed epidural analgesia. Our hypothesis was that the incidence of dislodgement and leakage should be low when epidural analgesia is successful. A thoracic epidural catheter was inserted before general anesthesia and secured by subcutaneous tunneling. Bupivacaine (0.25%) was administered during surgery followed by continuous epidural analgesia with 0.125% bupivacaine (10 mL/h) and morphine (0.25 mg/h) for 48 h. Failure was defined as a visual analog scale pain score at rest more than 30 mm and/or interruption of epidural analgesia before 48 h for any reason. When failure was not due to unintentionally withdrawn, kinked catheters or adverse events (n = 11), a CT scan with contrast injection was performed. Control CT scans were also performed in patients with adequate analgesia (i.e., the success group). The incidence of failure was 24.8% (n = 31). CT scans in the failure group (n = 20) showed seven patients with catheters outside the epidural space, nine with normal distribution, one with unilateral spread, and three with leakage of solution outside the epidural space. In the success group, CT scans (n = 19) showed 11 patients with normal distribution, five with unilateral spread, and three with leakage. We conclude that the major cause of epidural analgesia failure was dislodgment of the catheter. CT scans were mostly useful for detecting leakage of injectate, which may be the early phase of dislodgment.


Endogenous carbon monoxide production: a rare and detrimental complication of extracorporeal membrane oxygenation.
Extracorporeal membrane oxygenation (ECMO) is a technique that can support gas-exchange and cardiac function in patients with acute respiratory or cardiac failure that is not responsive to conservative treatment. ECMO is a high-risk procedure in critically ill patients and both technical and patient-related complications frequently occur. We report on a patient with end-stage pulmonary fibrosis (histiocytosis x), in whom ECMO was used as bridge to urgent lung transplantation. Respiratory insufficiency necessitating ECMO therapy was due to spontaneous pneumothorax with bronchopleural fistula. Access was initially made by femoral veno-venous canulation. Due to right heart failure, access was switched to veno-arterial using the two existing canulae as efferent system and implanting a third canula on the femoral artery using a graft. Despite marked hemodynamic improvement after this intervention, high flow rates creating high premembrane pressures were required to ensure oxygenation. High levels of carboxyhemoglobin (COHb) occurred, most likely due to massive mechanical hemolysis in the ECMO circuit. This may have had detrimental effects by further complicating tissue oxygenation. We recommend that COHb should routinely be checked in ECMO patients.


The influence of peri-implant keratinized mucosa on brushing discomfort and peri-implant tissue health.
The aim of this study was to compare the level of brushing discomfort (BD) during oral hygiene and peri-implant clinical variables between patients presenting implant sites with a band ≥2 mm and <2 mm of keratinized mucosa (KM). Participating patients were recruited during routine maintenance follow-up visits from January to October 2013. Based on the presence of KM, patients were allocated into two groups: implant sites with ≥2 mm of KM (Wide Group); and implant sites with <2 mm of KM (Narrow Group). Patients were clinically assessed, and plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BoP) data were collected from three sites at the buccal aspect of each implant. Subsequently, patients received standardized oral hygiene instructions and cleaning devices and were asked to clean around the experimental implant sites. All patients reported on the level of BD using the visual analog scale (VAS). Non-paired Student's t-test, Wilcoxon's signed-rank test, and chi-square tests were performed to analyze the outcome variables (P < 0.05). Eighty patients with a total of 270 implant sites were included. Implant sites in the Narrow Group exhibited higher levels of BD (P < 0.001), PI (P = 0.0021), and BoP (P = 0.017) than implant sites in the Wide Group. Implant sites with a band of <2 mm of KM were shown to be more prone to brushing discomfort, plaque accumulation, and peri-implant soft tissue inflammation when compared to implant sites with ≥2 mm of KM.


Beyond ISN/RPS Lupus Nephritis Classification: Adding Chronicity Index to Clinical Variables Predicts Kidney Survival.
A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health activity and chronicity indices have been proposed to classify LN lesions, but they should be validated by future studies. The aims of this study were (1) to detect the histologic features associated with the development of kidney function impairment (KFI), and (2) to identify the best clinical-histologic model to predict KFI at time of kidney biopsy. Patients with LN who had more than ten glomeruli per kidney biopsy specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards models were used to investigate whether activity and chronicity indices could predict KFI development. Among 203 participants with LN followed for 14 years, correlations were found between the activity index, and its components, and clinical-laboratory signs of active LN at baseline. The chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indices. In the multivariate analysis, glomerulosclerosis (OR, 3.05; 95% CI, 1.17 to 7.91; P=0.02) and fibrous crescents (OR, 6.84; 95% CI, 3.22 to 14.52; P<0.001) associated with either moderate/severe tubular atrophy (OR, 3.17; 95% CI, 1.04 to 9.64; P=0.04), or with interstitial fibrosis (OR, 2.36; 95% CI, 1.05 to 5.32; P=0.04), predicted KFI. Considering both clinical and histologic features, serum creatinine (OR, 1.68; 95% CI, 1.31 to 2.15; P<0.001), arterial hypertension (OR, 4.64; 95% CI, 1.90 to 11.32; P<0.001), glomerulosclerosis (OR, 2.12; 95% CI, 1.00 to 4.50; P=0.05), and fibrous crescents (OR, 5.18; 95% CI, 2.43 to 11.04; P<0.001) independently predicted KFI. Older age (P<0.001) and longer delay between clinical onset of LN and kidney biopsy (P<0.001) were significantly correlated with baseline chronicity index. The chronicity index and its components, but not the activity index, were significantly associated with an impairment of kidney function. The Cox model showed that serum creatinine, arterial hypertension, chronic glomerular lesions, and delay in kidney biopsy predicted KFI. These data reinforce the importance of timely kidney biopsy in LN.


Enhanced susceptibility of triple transgenic Alzheimer's disease (3xTg-AD) mice to acute infection.
Infection is a recognised risk factor for Alzheimer's disease (AD) and can worsen symptoms in established disease. AD patients have higher rates of infection and are more likely to require hospital admissions due to infections than individuals without dementia. Infections have also been found to increase the risk of those over 84 years of age being diagnosed with dementia. However, few studies have investigated immune responses to infection in AD. Here, we investigated the immune responses of the triple transgenic Alzheimer's disease (3xTg-AD) mouse model of AD to infection with the parasites Toxoplasma gondii and Trichuris muris. Cytometric bead array, histology, immunohistochemistry and immunofluorescence were used to evaluate immune responses and the effects on the brain of acute infection. 3xTg-AD mice, despite having comparable parasite loads, were more susceptible to infection with more severe morbidity. A worsened outcome to infection can be linked to an exaggerated immune response. 3xTg-AD mice had an increased pro-inflammatory response characterised by the production of pro-inflammatory mediators such as tumour necrosis TNF-α, IL-6, CCL5 and CXCL-1, as well as an increase in immune cell infiltration to the sites of infection. T cell responses to parasite antigen also showed elevated production of the pro-inflammatory cytokines TNF-α (10 fold) and IL-6 (twofold). We investigated whether 3xTg-AD mice had a propensity for a more Th1-dominated response using the T. muris worm infection and showed that akin to T. gondii, there was an enhanced pro-inflammatory response which was associated with retention of worms in the gut and associated pathology. Irrespective of whether the infection was one that could infect the brain or cause a local gut inflammation, 3xTg-AD mice had increased numbers of activated microglia during infection in both the cortex and the hippocampus. Our findings suggest that in AD, responses to infection are exaggerated outside of the CNS. Additionally, the results presented here indicate that both systemic and localised inflammation caused by an infection exacerbate neuroinflammation in AD.


A Digitally Dynamic Power Supply Technique for 16-Channel 12 V-Tolerant Stimulator Realized in a 0.18- μm 1.8-V/3.3-V Low-Voltage CMOS Process.
A new digitally dynamic power supply technique for 16-channel 12-V-tolerant stimulator is proposed and realized in a 0.18-μm 1.8-V/3.3-V CMOS process. The proposed stimulator uses four stacked transistors as the pull-down switch and pull-up switch to withstand 4 times the nominal supply voltage (4 × V DD). With the dc input voltage of 3.3 V, the regulated three-stage charge pump, which is capable of providing 11.3-V voltage at 3-mA loading current, achieves dc conversion efficiency of up to 69% with 400-pF integrated capacitance. Power consumption is reduced by implementing the regulated charge pump to provide a dynamic dc output voltage with a 0.5-V step. The proposed digitally dynamic power supply technique, which is implemented by using a p-type metal oxide semiconductor (PMOS) inverter with pull-down current source and digital controller, greatly improves the power efficiency of a system. The silicon area of the stimulator is approximately 3.5 mm2 for a 16-channel implementation. The functionalities of the proposed stimulator have been successfully verified through animal test.


Effect of Prestroke Glycemic Variability Estimated Glycated Albumin on Stroke Severity and Infarct Volume in Diabetic Patients Presenting With Acute Ischemic Stroke.
Background: We investigated whether prestroke glycemic variability, represented by glycated albumin (GA), affects the initial stroke severity and infarct volume in diabetic patients presenting with acute ischemic stroke. Methods: We evaluated a total of 296 acute ischemic stroke patients with diabetes mellitus who were hospitalized within 48 h of stroke onset. GA was measured in all acute ischemic stroke patients consecutively during the study period. The primary outcome was the initial National Institute Health Stroke Scale (NIHSS) score. The secondary outcome was infarct volume on diffusion-weighted imaging, which was performed within 24 h of stroke onset. Higher GA (≥16.0%) was determined to reflect glycemic fluctuation prior to ischemic stroke. Results: The number of patients with higher GA was 217 (73.3%). The prevalence of a severe initial NIHSS score (>14) was higher in patients with higher GA than in those with lower GA (3.8% vs. 15.7%, p = 0.01). The proportion of participants in the highest quartile of infarct volume was higher in the higher GA group (11.4% vs. 36.4%, p < 0.001). A multivariable analysis showed that higher GA was significantly associated with a severe NIHSS score (odds ratio, [95% confidence interval], 7.99 [1.75-36.45]) and large infarct volume (3.76 [1.05-13.45]). Conclusions: Prestroke glucose variability estimated by GA was associated with an increased risk of severe initial stroke severity and large infarct volume in acute ischemic stroke patients with diabetes mellitus.


An unusual cause of collapse and neck pain.
Following a collapse at home, a previously well 24-year-old Ukrainian man living in Ireland was brought to the emergency department. He complained of neck pain and cervical spine radiographs revealed loss of lordosis, scalloping of the posterior vertebral bodies and widening of the neural exit foramina at C7. In view of these unusual radiological findings, further examination of the patient demonstrated multiple flat uniformly hyperpigmented brown macules with multiple subcutaneous well-circumscribed lesions along the distribution of the peripheral nerves. An MRI scan of the neck revealed multiple neurofibromas in the vertebral canal with cord compression at C7-T1. A diagnosis of neurofibromatosis type 1 was made. Other investigations to determine the aetiology of the collapse were normal and the patient was discharged with follow-up at specialist neurology and neurosurgical clinics. In recent years there have been increased numbers of economic migrants presenting to the emergency department in the UK and Ireland from European Union accession states. This case highlights the need for increased awareness among emergency physicians to previously undiagnosed genetic and congenital conditions.


Bleeding in patients with activated partial thromboplastin time inhibitors.
We present a case in which an activated partial thromboplastin time (aPTT) inhibitor may have significantly contributed to prolonged bleeding in a patient and review five similar cases. The possibility of an aPTT inhibitor should be considered in the evaluation of patients with unexplained prolongation of PTT and PT. Such patients may develop significant bleeding even in the absence of other hematologic abnormalities.


NIH funding in family medicine: an analysis of 2003 awards.
We wanted to analyze National Institutes of Health (NIH) awards to departments of family medicine. We obtained the list of NIH awards to departments of family medicine in 2003, and collected additional information from the Internet regarding each principal investigator (PI), including whether he or she worked primarily in a core (central) organizational component within a family medicine department. One hundred forty-nine NIH awards were granted to 45 departments of family medicine, for a total of 60,085,000 dollars. Of 146 awards with a designated PI, approximately two thirds of awards (89, 61%) and awarded dollars (39,850,000 dollars, 70%) went to PIs who were either not full-time family medicine faculty primarily working in family medicine departments, or they were not working in core family medicine organizational components. Few awards to physician PIs in these non-core areas were to family physicians (4 of 37, 11%), whereas most awards to physician PIs in core family medicine areas went to family physicians (40 of 45, 89%). In contrast, most K awards (research career programs) went to PIs in core areas (19 of 23, 83%), and most to family physicians (17 of 23, 74%). Nationally, only 17 R01 awards (research project, traditional) went to family physicians. Most NIH awards to family medicine departments went to PIs in noncore organizational components, where most physician PIs were not family physicians. Family medicine departments interested in increasing NIH funding may want to consider 4 models that appear to exist: individual faculty in core departmental components, K awards, core faculty also working in university-wide organizational components that provide research infrastructure, and integrating noncore administrative components into the department.


Novel use of a continuous PECS II block for mastitis pain treatment.
Nipple trauma and mastitis (an inflammatory condition of the breast) are common causes of intense pain during breast feeding. Although such pain normally results in early weaning, which has negative impacts on both maternal and child health, little is understood about the treatment of pain experienced during breast feeding. Here, we describe our experience with a woman who presented at 26 days post partum with a 15-day history of deep nipple wounds that caused bilateral mastitis and excruciating pain that radiated dorsally. Antibiotic, antifungal and non-pharmacological therapies were unsuccessful, and she wished to suspend breast feeding. We performed a bilateral pectoralis nerve block type II and inserted intrafascial catheters between the pectoralis minor and serratus muscles for continuous analgesia. Following block completion, the pain in her torso resolved immediately. The local anesthetic infusion continued for 40 hours and the patient had sustained analgesia with rapid healing of nipple lesions and her breast feeding commencing at 36 hours after block placement.


Non-sentinel node metastasis prediction during surgery in breast cancer patients with one to three positive sentinel node(s) following neoadjuvant chemotherapy.
Our aim was to develop a tool to accurately predict the possibility of non-sentinel lymph node metastasis (NSLNM) during surgery so that a surgeon might decide the extent of further axillary lymph node dissection intraoperatively for patients with 1-3 positive sentinel lymph node(s) (SLN) after neoadjuvant chemotherapy. After retrospective analysis of Asan Medical Center (AMC) database, we included 558 patients' records who were treated between 2005 and 2019. 13 factors were assessed for their utility to predict NSLNM with chi-square and logistic regression with a bootstrapped, backward elimination method. Based on the result of the univariate analysis for statistical significance, number of positive SLN(s), number of frozen nodes, Progesterone Receptor (PR) positivity, clinical N stage were selected for the multivariate analysis and were utilized to generate a nomogram for prediction of residual nodal disease. The resulting nomogram was tested for validation by using a patient group of more recent, different time window at AMC. We designed a nomogram to be predictive of the NSLNM which consisted of 4 components: number of SLN(s), number of frozen nodes, PR positivity, and clinical N stage before neoadjuvant chemotherapy. The Area under the receiver operating characteristics curve (AUC) value of this formula was 0.709 (95% CI, 0.658-0.761) for development set and 0.715 (95% CI, 0.634-0.796) for validation set, respectively. This newly created AMC nomogram may provide a useful information to a surgeon for intraoperative guidance to decide the extent of further axillary surgery.


Detection of myocarditis during the first year after discovery of a dilated cardiomyopathy by endomyocardial biopsy and gallium-67 myocardial scintigraphy: prospective multicentre French study of 91 patients.
The purpose of this study was to assess the frequency of inflammatory lesions in the myocardium of subjects with dilated cardiomyopathy and to determine if there was any correlation between the results of two methods of evaluation, one (endomyocardial biopsy) invasive and the other (gallium-67 scintigraphy) noninvasive. Of 115 subjects recruited in seven centres, 91 met the inclusion criteria (left ventricular dilatation greater than or equal to 100 ml m-2 and ejection fraction less than 55% with normal coronary arteriography) and had endomyocardial biopsy (mean five specimens) and Ga-67 myocardial scintigraphy after several days. Scanning was considered doubtful 19 times and positive 13 times. The histologic count of mononuclear cells in the myocardial interstitium in 20 fields was greater than 5 cells field-1 in only four cases. No correlation was found between the two methods. Subjectivity in the choice of the criterion of positivity of Ga-67 scintigraphy and difficulties in identifying lymphocytes upon pathological examination were the major problems encountered. Despite limitations, both techniques suggest that cellular infiltrates are minimal and quite infrequent in dilated cardiomyopathy.


Toll-Like Receptors 2 and 4 Predict New-Onset Atrial Fibrillation in Acute Myocardial Infarction Patients.
Myocardial infarction (MI) can cause new-onset atrial fibrillation (AF) due to cardiac remodeling. As a recent study has shown, inflammatory factors are closely tied to cell death and survival in myocardial ischemia injury. Toll-like receptors (TLRs) have been shown to participate in the process of myocardial infarction as innate immune factors.The subjects were divided into 3 groups: healthy controls (n = 82), MI patients (n = 84), and AFMI (new-onset atrial fibrillation after myocardial infarction) patients (n = 85). Peripheral blood mononuclear cell (PBMC) TLR mRNA expression was detected by rt-PCR. Western blot was used to analyze PBMC TLRs and their downstream signal protein expression. PBMCs were presented as TLR2 expression or TLR4 expression using flow cytometry.From mRNA to protein detection, PBMC TLR2 and TLR4 were significantly higher in the AFMI group than in the control group and MI group. A similar tendency was also observed in the expression of downstream signaling proteins. When further analyzed with TLR2 and TLR4 antibodies by flow cytometry, PBMC levels also appeared to be higher in AFMI patients than those in MI patients and the healthy control group.In our study, PBMC TLRs and their downstream signaling proteins were significantly higher in the acute myocardial infarction patients with new-onset atrial fibrillation compared with healthy people and acute myocardial infarction patients without new-onset atrial fibrillation. They have the potential to be novel biomarkers for new-onset atrial fibrillation after acute myocardial infarction.


Evaluation of ultrasound measurements of abdominal fat for the prediction of gestational diabetes in the first and second trimesters of pregnancy.
To evaluate whether ultrasound abdominal fat measurements in the first and second trimesters can predict adverse gestational outcomes, particularly gestational diabetes mellitus (GDM), and identify early patients at higher risk for complications. A prospective cohort study of 126 pregnant women at 11-14 and 20-24 weeks of gestation with normal fasting glucose levels during early pregnancy. From 126 participants with complete data, 13.5% were diagnosed with GDM, based on the cutoffs established for the peripherical blood glucose. Subcutaneous, visceral, and maximum preperitoneal abdominal fat were measured using ultrasound techniques. GDM status was determined by oral glucose tolerance test (OGTT) with 75 g glucose overload, and the following values were considered abnormal: fasting glucose ≥92 mg/dl and/or 1 h after overload ≥180 mg/dl and/or 2 h after overload ≥153 mg/dl. The receiver operator characteristic (ROC) curve was used to determine the optimal threshold to predict GDM. Maximum preperitoneal fat measurement was predictive of GDM, and subcutaneous and visceral abdominal fat measurements did not show significant differences in the prediction of GDM. According to the ROC curve, a threshold of 45.25 mm of preperitoneal fat was identified as the optimal cutoff point, with 87% sensitivity and 41% specificity to predict GDM. The raw and adjusted odds ratios for age and pre-pregnancy body mass index were 0.730 (95% confidence interval [CI], 0.561-0.900) and 0.777 (95% CI, 0.623-0.931), respectively. The use of a 45.25 mm threshold for maximum preperitoneal fat, measured by ultrasound to predict the risk of GDM, appears to be a feasible, inexpensive, and practical alternative to incorporate into clinical practice during the first trimester of pregnancy.


Major benefits of guarding behavior in subsocial bees: implications for social evolution.
Parental care is a behavior that increases the growth and survival of offspring, often at a cost to the parents' own survival and/or future reproduction. In this study, we focused on nest guarding, which is one of the most important types of extended parental care; we studied this behavior in two solitary bee species of the genus Ceratina with social ancestors. We performed the experiment of removing the laying female, who usually guards the nest after completing its provisioning, to test the effects of nest guarding on the offspring survival and nest fate. By dissecting natural nests, we found that Ceratina cucurbitina females always guarded their offspring until the offspring reached adulthood. In addition, the females of this species were able to crawl across the nest partitions and inspect the offspring in the brood cells. In contrast, several Ceratina chalybea females guarded their nests until the offspring reached adulthood, but others closed the nest entrance with a plug and deserted the nest. Nests with a low number of provisioned cells were more likely to be plugged and abandoned than nests with a higher number of cells. The female removal experiment had a significantly negative effect on offspring survival in both species. These nests frequently failed due to the attacks of natural enemies (e.g., ants, chalcidoid wasps, and other competing Ceratina bees). Increased offspring survival is the most important benefit of the guarding strategy. The abandonment of a potentially unsuccessful brood might constitute a benefit of the nest plugging behavior. The facultative nest desertion strategy is a derived behavior in the studied bees and constitutes an example of an evolutionary reduction in the extent of parental care.


Light penetration of normal and photokeratitis induced rabbit cornea.
The passage of light through photokeratitic and normal corneas was investigated using a grating monochromator. The energy output was measured at each selected central wavelength from 280 to 700 nm. The absorption by epithelial and stromal suspensions was continuously registered over the total light spectrum in a recording spectrophotometer. The penetrating quantity of the physiologically effective middle wave ultraviolet (UVB) rays varies according to wavelengths from about 11% at 290 nm up to 50% at 320 nm. Photokeratitis did not alter the transmission characteristics at wavelengths below 310 nm. At longer wavelengths transmission was significantly decreased in photokeratitic corneas compared to normal. No difference was found between the light absorption of the supernatants of photokeratitic and normal corneas.


Strategies for closing the posterior rectus sheath during enhanced view totally extraperitoneal Rives-Stoppa repair.
The popularity of endolaparoscopic extraperitoneal repairs has been on the rise due to advantages such as sublay mesh placement and early return to daily activities. However, the procedure requires overcoming a learning curve, and with increased adoption, new complications have emerged. One significant complication is the rupture of the posterior rectus sheath (PRS). In this article, we present our modifications of the technique to reduce tension during PRS closure. The study included 105 patients who underwent endolaparoscopic extraperitoneal repairs for ventral hernias using two different techniques. Group A (n = 68) underwent the original technique, whereas Group B (n = 37) underwent the modified technique. The modifications in Group B included preserving the peritoneal bridge between the two PRS and the hernia sac, conducting a complete dissection of the space of Bogros and adopting a transverse or oblique closure of PRS along the lines of least tension. To assess the efficacy of these modifications in preventing PRS rupture, we compared the results of both groups. Our findings indicate that following all the technical steps of the modified technique resulted in a reduced need for transversus abdominis release for PRS closure and a lower incidence of PRS rupture in the postoperative period. However, to further validate the effectiveness of these modifications, a larger follow-up period and a bigger sample size are required. The adoption of the modified technique can help achieve a tension-free PRS closure.


Solubilization and refolding of bacterial inclusion body proteins.
Inclusion bodies produced in Escherichia coli are composed of densely packed denatured protein molecules in the form of particles. Refolding of inclusion body proteins into bioactive forms is cumbersome, results in poor recovery and accounts for the major cost in production of recombinant proteins from E. coli. With new information available on the structure and function of protein aggregates in bacterial inclusion bodies, it has been possible to develop improved solubilization and refolding procedures for higher recovery of bioactive protein. Inclusion bodies are formed from partially folded protein intermediates and are composed of aggregates of mostly single types of polypeptide. This helps to isolate and purify the protein aggregates to homogeneity before solubilization and refolding. Proteins inside inclusion body aggregates have native-like secondary structures. It is assumed that restoration of this native-like secondary structure using mild solubilization conditions will help in improved recovery of bioactive protein in comparison to solubilization using a high concentration of chaotropic agent. Analysis of the dominant forces causing aggregation during inclusion body formation provides information to develop suitable mild solubilization procedures for inclusion body proteins. Refolding from such solubilized protein will be very high due to restoration of native-like secondary structure. Human growth hormone inclusion bodies were purified to homogeneity from E. coli cells before solubilization and refolding. Pure inclusion bodies were solubilized at alkaline pH in the presence of 2 M urea solution. The solubilized proteins were refolded using a pulsatile renaturation process and subsequently purified using chromatographic procedures. More than 40% of the inclusion body proteins could be refolded back to the bioactive native conformation. Mild solubilization is thus the key for high recovery of bioactive protein from inclusion bodies.


Retirement is no excuse for physical inactivity or isolation.
At all age levels and especially in the elderly population, a sedentary lifestyle and low fitness levels are independent risk factors for all causes of mortality, including cardiovascular mortality. Exercise improves cardiovascular outcomes by increasing vagal activity and attenuating sympathetic hyperactivity. The risk of diabetes mellitus type 2 developing is reduced by 40% in men of normal weight and 60% in overweight men when on a regular exercise program. Physical activity in the elderly sustains cerebral perfusion, maintaining cognitive function. Isolation, which is not uncommon among the elderly, fosters cognitive decline. Stimulating mental activity can protect against dementia.


Diabetes Update: Primary Care of Patients With Type 1 Diabetes.
The incidence and prevalence of type 1 diabetes (T1D) are increasing among white, black, Hispanic, and Asian individuals in the United States. Children often present with acute symptoms, including severe polyuria, polydipsia, weight loss, and ketonemia; adults may develop more gradual symptoms that initially appear similar to those of type 2 diabetes (T2D). Latent autoimmune diabetes of adults and maturity-onset diabetes of the young are conditions that may be confused with T1D, although they are actually more closely related to T2D. Insulin analogues, continuous blood glucose level monitoring, and insulin pumps provide increased flexibility in T1D management. Noninsulin therapies also are being studied for management of T1D and T2D. The tailoring care of plans to the developmental age of each patient is critical to provide necessary screening and prevent common complications.


Observing crystal nucleation in four dimensions using atomic electron tomography.
Nucleation plays a critical role in many physical and biological phenomena that range from crystallization, melting and evaporation to the formation of clouds and the initiation of neurodegenerative diseases1-3. However, nucleation is a challenging process to study experimentally, especially in its early stages, when several atoms or molecules start to form a new phase from a parent phase. A number of experimental and computational methods have been used to investigate nucleation processes4-17, but experimental determination of the three-dimensional atomic structure and the dynamics of early-stage nuclei has been unachievable. Here we use atomic electron tomography to study early-stage nucleation in four dimensions (that is, including time) at atomic resolution. Using FePt nanoparticles as a model system, we find that early-stage nuclei are irregularly shaped, each has a core of one to a few atoms with the maximum order parameter, and the order parameter gradient points from the core to the boundary of the nucleus. We capture the structure and dynamics of the same nuclei undergoing growth, fluctuation, dissolution, merging and/or division, which are regulated by the order parameter distribution and its gradient. These experimental observations are corroborated by molecular dynamics simulations of heterogeneous and homogeneous nucleation in liquid-solid phase transitions of Pt. Our experimental and molecular dynamics results indicate that a theory beyond classical nucleation theory1,2,18 is needed to describe early-stage nucleation at the atomic scale. We anticipate that the reported approach will open the door to the study of many fundamental problems in materials science, nanoscience, condensed matter physics and chemistry, such as phase transition, atomic diffusion, grain boundary dynamics, interface motion, defect dynamics and surface reconstruction with four-dimensional atomic resolution.


Mistletoe viscotoxins increase natural killer cell-mediated cytotoxicity.
Mistletoe extracts have immunomodulatory activity. We show that nontoxic concentrations of Viscum album extracts increase natural killer (NK) cell-mediated killing of tumor cells but spare nontarget cells from NK lysis. The compounds responsible for this bioactivity were isolated from mistletoe and characterized. They have low molecular mass and are thermostable and protease-resistant. After complete purification by HPLC, they were identified by tandem MS as viscotoxins A1, A2 and A3 (VTA1, VTA2 and VTA3, respectively). Whereas micromolar concentrations of these viscotoxins are cytotoxic to the targets, the bioactivity with respect to NK lysis is within the nanomolar range and differs between viscotoxin isoforms: VTA1 (85 nm), VTA2 (18 nm) and VTA3 (8 nm). Microphysiometry and assays of cell killing indicate that, within such nontoxic concentrations, viscotoxins do not activate NK cells, but act on cell conjugates to increase the resulting lysis.


Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats.
Depression, a psychiatric and dysthymic disorder, severely affects the learning, work and life quality. The main pathogenesis of depression is associated with central nervous system (CNS) dysfunction. Taurine has been demonstrated to exert protective effects on the brain development and can improve learning ability and memory. Our study investigated the antidepressant-like effects of taurine pre-treatment by examining the changes in depression-like behavior, hormones, neurotransmitters, inflammatory factors and neurotrophic factors in the hippocampus of a chronic unpredictable mild stress (CUMS)-induced depressive rat model. Taurine was found to inhibit the decrease of sucrose consumption and prevent the deficiency of spatial memory and anxiety in rats exposed to CUMS, suggesting a preventive effect of taurine on depression-like behavior. Furthermore, the decreased levels of 5-hydroxytryptamine, dopamine, noradrenaline; the increased levels of glutamate, corticosterone; and the decreased expressions of fibroblast growth factor-2, vascular endothelial growth factor and brain derived neurotrophic factor in depressive rats were hindered by taurine pre-administration. However, tumor necrosis factor-α and interleukin-1β levels were not significantly changed by taurine. The results demonstrated that the anti-depressive effect of taurine may be involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and the promotion of neurogenesis, neuronal survival and growth in the hippocampus.


Cryopreservation of human embryonic stem cells by vitrification.
The efficiency of traditional cryopreservation of human embryonic stem (ES) cells is low, and there have been few attempts to prove new cryopreservation methods effective. This study was designed to evaluate the efficiency of cryopreservation of human ES cells using vitrification method. Human ES cells clumped from an identical cell line were randomly allocated to be cryopreserved by vitrification or by slow freezing. The recovery rates, the growth and differentiation potential of thawed human ES cells were compared between these two groups. The pluripotency of human ES cells after thawing was identified. Eighty-one point nine percent (59/72) of human ES cell clumps were recovered after vitrification, while only 22.8% (16/70) were recovered after slow freezing (P < 0.01). The colonies after vitrification manifested have not only faster growth but also a lower level of differentiation when compared to colonies subjected to the slow freezing protocol. However, the rates of growth and differentiation in undifferentiated colonies from both groups were identical to the rates in those of non-cryopreserved stem cells after a prolonged culture period. Passage 6 of vitrified human ES cells retained the properties of pluripotent cells, a normal karyotype and expressed the transcription factor OCT-4, stage specific expressed antigen-4 (SSEA-4) and SSEA-3. Teratoma growth of these cells demonstrated the ability to develop into all three germ layers. Vitrification is effective in cryopreserving human ES cells. During a prolonged culture, human ES cells retain their pluripotency after cryopreservation.


The role of inflammatory mediators in the pathogenesis of periodontal disease.
The role of bacteria in the initiation of periodontitis is well-documented and the end result, destruction of the alveolar bone and periodontal connective tissue, is readily observed; but the events occurring between these two points in time remain obscure and are the focus of this paper. Bacteria induce tissue destruction indirectly by activating host defense cells, which in turn produce and release mediators that stimulate the effectors of connective tissue breakdown. Components of microbial plaque have the capacity to induce the initial infiltrate of inflammatory cells including lymphocytes, macrophages, and PMNs. Microbial components, especially lipopolysaccharide (LPS), have the capacity to activate macrophages to synthesize and secrete a wide array of molecules including the cytokines interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-alpha), prostaglandins, especially PGE2, and hydrolytic enzymes. Likewise, bacterial substances activate T lymphocytes and they produce IL-1 and lymphotoxin (LT), a molecule having properties very similar to TNF-alpha. These cytokines manifest potent proinflammatory and catabolic activities, and play key roles in periodontal tissue breakdown. They induce fibroblasts and macrophages to produce neutral metalloproteinases such as procollagenase and prostromelysin, the serine proteinase urokinase-type plasminogen activator (u-PA), tissue inhibitor of metalloproteinase (TIMP), and prostaglandins, u-PA converts plasminogen into plasmin, which can activate neutral metalloproteinase proenzymes, and these enzymes degrade the extracellular matrix components. TIMP inactivates the active enzymes and thereby blocks further tissue degradation. Several amplification and suppression mechanisms are involved in the process. While LPS activates macrophages to produce IL-1, IL-1 is autostimulatory and can therefore amplify and perpetuate its own production. Interferon-gamma (INF-gamma) suppresses autostimulation, but it enhances LPS-induced IL-1 production. PGE2 exerts a control over the whole process by suppressing production of both IL-1 and TNF-alpha. Furthermore, the activated cells produce an IL-1 receptor antagonist that binds to the IL-1 receptor but does not induce the biologic consequences of IL-1 binding. Other cytokines such as transforming growth factor-beta (TGF-beta) suppress production of metalloproteinases and u-PA. Thus the progression and extent of tissue degradation is likely to be determined in major part by relative concentrations and half-life of IL-1, TNF-alpha, and related cytokines, competing molecules such as the IL-1 receptor antagonist, and suppressive molecules such as TGF-beta and PGE2. These molecules control levels of latent and active metalloproteinase and u-PA, and the availability and concentration of TIMP determines the extent and duration of degradative activity.


The levels of nitric oxide in megaloblastic anemia.
The purpose of this study was to investigate the relationship between nitric oxide degradation products (nitrate and nitrite) levels and megaloblastic anemia which is treated with cyalocobalamin. A total of 30 patients with megaloblastic anemia (16 Male, 14 Female) were included in the study. Cyanocobalamin was administered (1.000 µg/day intramuscularly) until the reticulocyte crisis occurred to the normal range. The control group consisted of 30 healthy subjects (15 Male, 15 Female). Nitric oxide levels were measured before treatment and compared with the values obtained during peak reticulocyte count. Plasma direct nitrite, total nitrite and nitrate levels were 24,86±3,87, 60.56±7,01 and 36,02±5,24 in before treatment versus 15,48±3,05, 38,92±6,44 and 22,77±6,04 μmol/dl in after treatment, respectively. Plasma direct nitrite, total nitrite and nitrate levels were significantly lower in after treatment compared with the before treatment (p<0.001). Nitric oxide levels are seen to increase in megaloblastic anemia. This study suggested that abnormalities in the nitric oxide levels in megaloblastic anemia are restored by vitamin B12 replacement therapy.


Proteomic Findings in Melanoma.
Although the emergence of proteomics as an independent branch of science is fairly recent, within a short period of time it has contributed substantially in various disciplines. The tool of mass spectrometry has become indispensable in the analysis of complex biological samples. Clinical applications of proteomics include detection of predictive and diagnostic markers, understanding mechanism of action of drugs as well as resistance mechanisms against them and assessment of therapeutic efficacy and toxicity of drugs in patients. Here, we have summarized the major contributions of proteomics towards the study of melanoma, which is a deadly variety of skin cancer with a high mortality rate.


Dietary sodium stimulates ouabainlike activity in adrenalectomized spontaneously hypertensive rats.
Both the adrenal glands and the hypothalamus have been proposed to produce compound(s) with ouabainlike activity (OLA). To evaluate the contribution of the adrenal glands, 4-wk-old spontaneously hypertensive rats (SHR) were sham operated or adrenalectomized. The adrenalectomized SHR were given daily injections of corticosterone and aldosterone. Subsequently, rats were randomized to control or high (8%) dietary Na+, and after 2.5 wk, blood pressure and OLA in plasma, hypothalamus, and pituitary were evaluated. Hypertension developed somewhat less in adrenalectomized vs. sham-operated SHR. On control Na+ intake, adrenalectomy caused only minor decreases in circulating and central OLA. Adrenalectomy did not prevent the 50-90% increases in plasma, hypothalamus, and pituitary OLA caused by high Na+ intake for 2.5 wk. These findings are consistent with the concept that, at least in SHR, the central nervous system may represent the major source of both central and peripheral OLA.


Ampelopsis japonica Makino Extract Inhibits the Inflammatory Reaction Induced by Pathogen-Associated Molecular Patterns in Epidermal Keratinocytes.
Keratinocytes are the major cells in epidermis, providing barrier components such as cornified cells through the sophisticated differentiation process. In addition, keratinocytes exerts their role as the defense cells via activation of innate immunity. It has been known that pathogen-associated molecular patterns (PAMPs) including double-strand RNA and nucleotides can provoke inflammatory reaction in keratinocytes. The aim of this study is to evaluate the effect of Ampelopsis japonica Makino extract (AE) on PAMPs-induced inflammatory reaction of keratinocytes. The effects of AE were determined using poly (I:C)-induced inflammation and imiquimod-induced psoriasiform dermatitis models. In cultured keratinocytes, AE significantly inhibited poly(I:C)-induced expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α. AE significantly inhibited poly(I:C)-induced release of caspase-1 active form (p20), and down-regulated nuclear factor-κB signaling pathway. In imiquimod-induced psoriasiform dermatitis model, topical application of AE resulted in significant reduction of epidermal hyperplasia. These results suggest that AE may be a potential candidate for the treatment of skin inflammation.


Computer-Based Case Simulations for Assessment in Health Care: A Literature Review of Validity Evidence.
Simulation for education and training in health-care professions has been widely applied. However, its value as an assessment tool for competence is not fully known. Logistical barriers of simulation-based assessments have led some health-care organizations to utilize computer-based case simulations (CCSs) for assessment. This article provides a review of the literature on the identification of psychometrically sound, CCS instruments designed to measure decision-making competence in health-care professionals. CINAHL, MEDLINE, and Ovid databases identified 84 potentially relevant articles published between January 2000 and May 2017. A total of 12 articles met criteria for inclusion in this review. Findings of these 12 articles indicate that summative assessment in health care using CCSs in the form of clinical scenarios is utilized to assess higher order performance aspects of competence in the form of decision-making. Psychometric strength was validated in eight articles and supported by four replication studies. Two of the eight articles reported evidence of construct validity and support the need for evidence based on a theoretical framework. This literature review offers implications for further research on the use of CCS tools as a method for assessment of competence in health-care professionals and the need for psychometric evidence to support it.


Susceptibility of anaerobic bacteria from several French hospitals to three major antibiotics.
The in vitro activity of cefoxitin was compared with those of metronidazole and clindamycin against 322 strains of anaerobic bacteria collected from several hospitals during 1982 and tested by an agar dilution method. Metronidazole and cefoxitin inhibited at least 89% of strains tested, whereas clindamycin was less active.


[New treatments of atopic dermatitis].
Topical steroids are still used suboptimally, but remain the mainstay of atopic dermatitis treatment. Topical steroid phobia is rampant in many countries, a real advantage for the entry on the market of topical immunomodulators (TIMs), which inhibit both antigen specific and non-specific T cell activation in the skin, by blockade of gene transcription of proinflammatory cytokines such as IL2 and TNF alpha. Topical tacrolimus and pimecrolimus have the most advanced clinical development. Tacrolimus, already used orally in transplantation medicine, is already available in France since 2003 as a 0.03% ointment for children (Protopic, Fujisawa). Its introduction on the market has substantially changed prescription habits in atopic dermatitis. Recalcitrant adolescent and adult head and neck lesions are the major target, but the drug is is also widely used in children, with a good safety profile. The risk of herpes virus superinfections did not increase significantly in clinical trials but needs further monitoring. Long-term prescription will need a closer look at a still much debated increased skin cancer risk. The marked efficacy on thin skin sites and absence of atrophogenic properties of the drug balance its side effects at the first applications on inflamed skin (pruritus, burning sensation). Clinical studies using pimecrolimus (Elidel, Novartis), marketed as a 1% cream, show a satisfactorily efficacy profile in adults and children including infants. The drug is better tolerated and is already widely introduced on the international market since 2002 with a pediatric positioning, but is nor available yet in 2004 in France. Besides phototherapy, systemic immunosuppressants remain useful drugs in severe disease especially in older children and adolescents, cyclosporin remaining the leading drug. Preventive immunomodulation modifying the intestinal microflora is very promising approach which deserves a large-scale assessment.


Learning and Remembering with Others: The Key Role of Retrieval in Shaping Group Recall and Collective Memory.
People frequently collaborate to learn and remember information, and this may help groups create a shared representation of the world (i.e., collective memories). However, contrary to intuitions, collaboration also lowers group recall levels. Such impairment occurs regardless of whether people collaborate when first experiencing, or encoding, an event (the collaborative encoding deficit), or when retrieving, or remembering, the event (the collaborative inhibition effect). In understanding how collaboration impairs group recall and enhances collective or shared memories it remains unknown as to where collaboration exerts the greatest influence - at encoding or at retrieval - to shape these distinct phenomena. The current study simultaneously compared collaboration at these two stages and revealed the power of collaborative retrieval. Collaboration impaired the group recall product at both time points, but especially so at retrieval. Furthermore, only collaborative retrieval played a significant role in the formation of collective memories.


Hexane extracts from fruit of two varieties of Capsicum chinense Jacq.: their volatile constituents and antiacetylcholinesterase, antileishmanial and antiproliferative activities.
This article aims to investigate volatile constituents and antiacetylcholinesterase, antileishmanial and antiproliferative activities of hexane extracts from Capsicum chinense fruit (unripe bode pepper 'HE-UB' and ripe little beak pepper 'HE-RB'). HE-UB and HE-RB were screened by the microplate assay method to determine their antiacetylcholinesterase activity. Both exhibited inhibitory potential, i. e., IC50 = 41.5 and 20.3 µg/mL, respectively. HE-UB (IC50 = 67.19 µg/mL) and HE-RB (IC50 = 38.16 µg/mL) exhibited antileishmanial activity against promastigote forms of Leishmania (Leishmania) amazonensis. In addition, HE-UB and HE-RB demonstrated cytotoxic activity against different human tumor cell lines with IC50 ranging from 325.40 to 425.0 µg/mL. Both GC-FID and GC-MS analyses revealed that the major component in both extracts was E-caryophyllene. In short, HE-RB was more satisfactory than HE-UB in all in vitro activities under evaluation. These findings may be used as initial data for further studies of Capsicum species.


Step-Wise Velocity of an Air Bubble Rising in a Vertical Tube Filled with a Liquid Dispersion of Nanoparticles.
The motion of air bubbles in tubes filled with aqueous suspensions of nanoparticles (nanofluids) is of practical interest for bubble jets, lab-on-a-chip, and transporting media. Therefore, the focus of this study is the dynamics of air bubbles rising in a tube in a nanofluid. Many authors experimentally and analytically proposed that the velocity of rising air bubbles is constant for long air bubbles suspended in a vertical tube in common liquids (e.g. an aqueous glycerol solution) when the capillary number is larger than 10-4. For the first time, we report here a systematic study of an air bubble rising in a vertical tube in a nanofluid (e.g. an aqueous silica dioxide nanoparticle suspension, nominal particle size, 19 nm). We varied the bubble length scaled by the diameter of the tubes (L/D), the concentration of the nanofluid (10 and 12.5 v %), and the tube diameter (0.45, 0.47, and 0.50 cm). The presence of the nanoparticles creates a significant change in the bubble velocity compared with the bubble rising in the common liquid with the same bulk viscosity. We observed a novel phenomenon of a step-wise increase in the air bubble rising velocity versus bubble length for small capillary numbers less than 10-7. This step-wise velocity increase versus the bubble length was not observed in a common fluid. The step-wise velocity increase is attributed to the nanoparticle self-layering phenomenon in the film adjacent to the tube wall. To elucidate the role of the nanoparticle film self-layering on the bubble rising velocity, the effect of the capillary number, the tube diameter (e.g. the capillary pressure), and nanofilm viscosity are investigated. We propose a model that takes into consideration the nanoparticle layering in the film confinement to explain the step-wise velocity phenomenon versus the length of the bubble. The oscillatory film interaction energy isotherm is calculated and the Frenkel approach is used to estimate the film viscosity.


Thermodynamics of pyridine coordination in 1,4-phenylene bridged bimetallic (Pd, Pt) complexes containing two N,C,N' motifs, 1,4-M2-[C6(CH2NR2)4-2,3,5,6].
The thermodynamics of pyridine coordination in 1,4-phenylene-bridged binuclear palladium and platinum organometallic complexes [1,4-(MOTf)2-&{C6(CH2NR2)4-2,3,5,6}] (11, M =Pd, Pt; R =CH3, C2H5, R2 = -(CH2)5-) are measured by 1H NMR in DMSO-d6. The coordination of substituted pyridines by bimetallic complexes 11 or 12 in DMSO is found to proceed via two effectively independent metalligand binding events, and the association constants for pyridine coordination and rate constants for pyridine exchange are nearly identical to those measured previously on monometallic analogs. A linear free energy relationship between the association constant for pyridine coordination and the inductive Hammett constant of the pyridine substituent is observed, and the sensitivity (rho = -1.7 to -2.1) in DMSO depends only slightly on metal (Pd vs Pt) and spectator ligand (pincer dialkylamine vs triarylphosphine). The association constant for a particular pyridine ligand, however, varies by roughly 3 orders of magnitude across the series of metal complexes. The effective independence of the two coordination sites and the range of available thermodynamic and kinetic behaviors of the coordination guide the use of these versatile building blocks in metallosupramolecular applications.


Regional macular light sensitivity changes in myopic Chinese adults: an MP1 study.
To investigate the variation of macular light sensitivity (MLS) in myopic Chinese adults by using microperimetry. MLS was recorded with the MP1 microperimeter (Nidek Technologies, Padova, Italy) in eyes affected by various degrees of myopia. Subjects were divided into group A (18-30 years) and group B (31-60 years). Subjects in both age groups were further divided based on refractive status: (1) high myopia (spherical equivalent, SE<-6.00 D); (2) low to moderate myopia (-6.00 D<or=SE<or=-1.00 D); and (3) no myopia (-1.00 D<SE<or=+0.50). All patients had corrected visual acuity greater than 20/20. The macular area covered by the MP1 grid contains nine areas. MLS was quantified in each part and correlated with the refractive data. MLS correlated significantly with SE or axial length (AL). Average MLS of the outer ring, total macula, and superior quadrant significantly decreased in the high and the low to moderate myopia eyes (both P<0.05) in both age groups. MLS in the temporal, inferior, and nasal quadrants decreased in the high myopia eyes, but not in the low to moderate myopia eyes, except in the temporal quadrant in group A and in the nasal quadrant in group B. Axial myopia was associated with reduced total and quadrant-specific MLS, particularly in the superior quadrant. These findings emphasize functional differences in the macula between high, low to moderate, and no myopia. Any evaluation of MLS by MP1 microperimetry in the macula should be interpreted in the context of the degree of refractive error and the region of measurement.


Protecting and Improving the Lives of Older Adults in the COVID-19 Era.
The COVID-19 pandemic has impacted the lives of people throughout the world, either directly, due to exposure to the virus, or indirectly, due to measures taken to mitigate the virus' effects. Older adults have been particularly hard hit, dying in disproportionately higher numbers, especially in long-term care facilities. Local, regional, and national government actions taken to mitigate the spread of COVID-19 have thus served, in part, to shield older adults from the virus, though not without adverse side effects, including increased social isolation, enhanced economic risk, revealed ageism, delayed medical treatment, and challenges getting basic needs met. This special issue of the Journal of Aging & Social Policy explores the myriad ways in which the COVID-19 pandemic has affected older adults and their families, caregivers, and communities. It proposes policies and strategies for protecting and improving the lives of older people during the pandemic. It draws lessons for aging policy and practice more generally, given underlying challenges brought to the fore by government, provider, community, and individual responses to the pandemic.


Cardiology in a Digital Age: Opportunities and Challenges for e-Health: A Literature Review.
To date, mortality rates associated with heart diseases are dangerously increasing, making them the leading cause of death globally. From this point of view, digital technologies can provide health systems with the necessary support to increase prevention and monitoring, and improve care delivery. The present study proposes a review of the literature to understand the state of the art and the outcomes of international experiences. A reference framework is defined to develop reflections to optimize the use of resources and technologies, favoring the development of new organizational models and intervention strategies. Findings highlight the potential significance of e-health and telemedicine in supporting novel solutions and organizational models for cardiac illnesses as a response to the requirements and restrictions of patients and health systems. While privacy concerns and technology-acceptance-related issues arise, new avenues for research and clinical practice emerge, with the need to study ad hoc managerial models according to the type of patient and disease.


Historical pesticide exposure in California using pesticide use reports and land-use surveys: an assessment of misclassification error and bias.
We used California's Pesticide Use Report (PUR) and land-use survey data to conduct a simulation study evaluating the potential consequences of misclassifying residential exposure from proximity to agricultural pesticide application in health effect studies. We developed a geographic model linking the PUR with crop location data from land-use surveys to assess the impact of exposure misclassification from simpler exposure models based solely on PUR or land-use data. We simulated the random selection of population controls recruited into a hypothetical case-control study within an agricultural region. Using residential parcel data, we derived annual exposure prevalences, sensitivity, and specificity for five pesticides and relied on the PUR plus land-use model as the "gold standard." Based on these estimates, we calculated the attenuation of prespecified true odds ratios (ORs), assuming nondifferential exposure misclassification. True ORs were severely attenuated a) when residential exposure status was based on a larger geographic area yielding higher sensitivity but low specificity for exposure, in contrast to relying on a smaller area and increasing specificity; b) for less frequently applied pesticides; and c) with increasing mobility of residents among the study population. Considerable effect estimate attenuation also occurred when we used residential distance to crops as a proxy for pesticide exposure. Finally, exposure classifications based on annual instead of seasonal summaries of PUR resulted in highly attenuated ORs, especially during seasons when applications of specific pesticides were unlikely to occur. These results underscore the importance of increasing the spatiotemporal resolution of pesticide exposure models to minimize misclassification.


Oligomerization-Enhanced Receptor-Ligand Binding Revealed by Dual-Color Simultaneous Tracking on Living Cell Membranes.
GPCR oligomerization plays a critical role in cellular signaling, yet the stoichiometry of the interactions between oligomers and binding ligands in living cells remains a longstanding challenge. Here, by developing a dual-color simultaneous tracking system based on a total internal reflection fluorescence microscope (TIRFM), the CCR5-CCL5 interactions are visualized and quantitatively assessed in real time. Results show that each oligomeric state of CCR5 could bind with CCL5 but with different binding affinities; CCR5 dimers have a 3.5-fold higher binding affinity than the monomers. The dimerization may cause an asymmetric conformational change which makes the first binding pocket have a 3.5-fold higher binding affinity and the second have only a half compared with the monomeric CCR5. This study is the first example to directly scrutinize the CCR5-CCL5 interactions at the single-molecule level on living cell membranes and will offer great potential for the interaction stoichiometry study of diverse surface proteins.


Recurrent respiratory papillomatosis with pulmonary cystic disease in a child, following maternal genital warts.
Human papillomavirus (HPV) infection of the genital tract is associated with the development of genital warts. A causal link between maternal HPV infection and development of laryngeal papillomatosis in the offspring has been proposed. We report a case of pulmonary cystic disease, a rare but serious complication of laryngeal papillomatosis in a child, following maternal genital warts.


Newborn Screening for Duchenne Muscular Dystrophy: First Year Results of a Population-Based Pilot.
Advancements in therapies for Duchenne muscular dystrophy (DMD) have made diagnosis within the newborn period a high priority. We undertook a consortia approach to advance DMD newborn screening in the United States. This manuscript describes the formation of the Duchenne Newborn Screening Consortium, the development of the pilot protocols, data collection tools including parent surveys, and findings from the first year of a two-year pilot. The DMD pilot design is population-based recruitment of infants born in New York State. Data tools were developed to document the analytical and clinical validity of DMD NBS, capture parental attitudes, and collect longitudinal health information for diagnosed newborns. Data visualizations were updated monthly to inform the consortium on enrollment. After 12 months, 15,754 newborns were screened for DMD by the New York State Newborn Screening (NYS NBS) Program. One hundred and forty screened infants had borderline screening results, and sixteen infants were referred for molecular testing. Three male infants were diagnosed with dystrophinopathy. Data from the first year of a two-year NBS pilot for DMD demonstrate the feasibility of NBS for DMD. The consortia approach was found to be a useful model, and the Newborn Screening Translational Research Network's data tools played a key role in describing the NBS pilot findings and engaging stakeholders.


Relations of perceived ethnic disparity to involvement in ethnic and host cultures.
Among 124 single foreign students residing in the USA, this study examined the relations between perceived ethnic disparity, consisting of physical, cultural. and linguistic dimensions, and ethnic and host culture involvement. The Ethnic Disparity Perception Inventory, a 44-item Likert scale devised to measure perceived ethnic disparity, showed perceived physical disparity (r = .60) and cultural disparity (r = .51) were positively related to ethnic involvement. Perceived cultural disparity (r = -.22) and linguistic disparity (r = -.27) were negatively associated with involvement in the host culture. Multiple regression analysis indicated that, although the findings held for non-White respondents, for White respondents (n = 39) perceived physical disparity (beta = .54), not cultural disparity, was a significant predictor of ethnic involvement (Adjusted R2 = .268) and perceived cultural disparity (beta = -.37), not linguistic disparity, was a significant (negative) indicator of host culture involvement (Adjusted R2 = .110).


Hypotensive resuscitation in a head-injured multi-trauma patient.
The concept of permissive hypotension is a controversial topic in trauma care. While driving blood pressure to "normal" levels with large volume crystalloid infusions is not appropriate, definitive data on the target blood pressure for hypotensive resuscitation are lacking. Indeed, the concept of systolic blood pressure as a marker for resuscitation is arguable. In this case presentation, a panel of experts in trauma resuscitation discusses the merits and limitations of hypotensive resuscitation in the context of a patient who has sustained multiple injuries, including a head injury. The controversies highlighted herein call attention to the role of the intensivist in managing a continuing resuscitation while coordinating the care of other physicians whose therapies can run at cross-purposes to one another. The challenges of the practice of critical care in the 21st century are no more apparent than in the care of a complex trauma patient.


The Sickle Cell Disease Ontology: recent development and expansion of the universal sickle cell knowledge representation.
The Sickle Cell Disease (SCD) Ontology (SCDO, https://scdontology.h3abionet.org/) provides a comprehensive knowledge base of SCD management, systems and standardized human and machine-readable resources that unambiguously describe terminology and concepts about SCD for researchers, patients and clinicians. The SCDO was launched in 2016 and is continuously updated in quantity, as well as in quality, to effectively support the curation of SCD research, patient databasing and clinical informatics applications. SCD knowledge from the scientific literature is used to update existing SCDO terms and create new terms where necessary. Here, we report major updates to the SCDO, from December 2019 until April 2021, for promoting interoperability and facilitating SCD data harmonization, sharing and integration across different studies and for retrospective multi-site research collaborations. SCDO developers continue to collaborate with the SCD community, clinicians and researchers to improve specific ontology areas and expand standardized descriptions to conditions influencing SCD phenotypic expressions and clinical manifestations of the sickling process, e.g. thalassemias. Database URL: https://scdontology.h3abionet.org/.


Hypothalamic regulation of sleep and arousal.
Normal waking is associated with neuronal activity in several chemically defined ascending arousal systems. These include monoaminergic neurons in the brainstem and posterior hypothalamus, cholinergic neurons in the brainstem and basal forebrain, and hypocretin (orexin) neurons in the lateral hypothalamus. Collectively, these systems impart tonic activation to their neuronal targets in the diencephalon and neocortex that is reflected in the low-voltage fast-frequency electroencephalogram patterns of wakefulness. Neuronal discharge in these arousal systems declines rapidly at sleep onset. Transitions from waking to sleep, therefore, involve coordinated inhibition of multiple arousal systems. An important source of sleep-related inhibition of arousal arises from neurons located in the preoptic hypothalamus. These preoptic neurons are strongly activated during sleep, exhibiting sleep/waking state-dependent discharge patterns that are the reciprocal of that observed in the arousal systems. The majority of preoptic sleep regulatory neurons synthesize the inhibitory neurotransmitter GABA. Anatomical and functional evidence supports the hypothesis that GABAergic neurons in the median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) exert inhibitory control over the monoaminergic systems and the hypocretin system during sleep. Recent findings indicate that MnPN and VLPO neurons integrate homeostatic aspects of sleep regulation and are important targets for endogenous sleep factors, such as adenosine and growth hormone releasing hormone.


Therapeutic considerations in congenital absence of the right pulmonary artery. Use of internal mammary artery as a preparatory shunt.
Congenital unilateral absence of a pulmonary artery is rare. When present, it is usually associated with other cardiac malformations. In this communication an infant with coarctation of the aorta, ventricular septal defect and absent right pulmonary artery is reported. After correction of the first two defects, due to persistent respiratory difficulty, the infant had exploration of the right pulmonary hilum in hopes of finding a pulmonary artery remnant and re-establishing blood flow to that lung. A small hilar vessel supplying all three lobes of the right lung was found and as a first stage, to enhance pulmonary arterial growth, a palliative systemic to pulmonary artery shunt was performed utilizing a large internal mammary artery. This is the first report of a case in which the internal mammary artery is used in an infant to establish systemic to pulmonary arterial flow in congenital unilateral absence of a pulmonary artery.


Obstetric vesicovaginal fistula as an international public-health problem.
Vesicovaginal fistula is a devastating injury in which an abnormal opening forms between a woman's bladder and vagina, resulting in urinary incontinence. This condition is rare in developed countries, but in developing countries it is a common complication of childbirth resulting from prolonged obstructed labour. Estimates suggest that at least 3 million women in poor countries have unrepaired vesicovaginal fistulas, and that 30 000-130 000 new cases develop each year in Africa alone. The general public and the world medical community remain largely unaware of this problem. In this article I review the pathophysiology of vesicovaginal fistula in obstructed labour and describe the effect of this condition on the lives of women in developing countries. Policy recommendations to combat this problem include enhancing public awareness, raising the priority of women's reproductive health for developing countries and aid agencies, expanding access to emergency obstetric services, and creation of fistula repair centres.


Site-specific generation of excited state wavepackets with high-intensity attosecond x rays.
High-intensity attosecond x rays can produce coherent superpositions of valence-excited states through two-photon Raman transitions. The broad-bandwidth, high-field nature of the pulses results in a multitude of accessible excited states. Multiconfigurational quantum chemistry with the time-dependent Schrödinger equation is used to examine population transfer dynamics in stimulated x-ray Raman scattering of the nitric oxide oxygen and nitrogen K-edges. Two pulse schemes initiate wavepackets of different characters and demonstrate how chemical differences between core-excitation pathways affect the dynamics. The population transfer to valence-excited states is found to be sensitive to the electronic structure and pulse conditions, highlighting complexities attributed to the Rabi frequency. The orthogonally polarized two-color-pulse setup has increased selectivity while facilitating longer, less intense pulses than the one-pulse setup. Population transfer in the 1s → Rydberg region is more effective but less selective at the nitrogen K-edge; the selectivity is reduced by double core-excited states. Result interpretation is aided by resonant inelastic x-ray scattering maps.


Endovascular versus open repair of ruptured abdominal aortic aneurysms.
Although major improvement has occurred to make elective repair of abdominal aortic aneurysms a safe procedure, the incidence of ruptured abdominal aortic aneurysms and mortality rates are still disappointing. Endovascular abdominal aortic aneurysm repair has produced quantum changes in aneurysm treatment. The successful application of the endovascular approach for the treatment of abdominal aortic aneurysms in the elective setting has prompted a strong interest regarding its possible use in dealing with the long-standing challenge of a ruptured abdominal aortic aneurysm. Since the first report, several centers have reported results and a wide spectrum of opinion regarding its application, with special consideration to logistical and practical barriers for appropriate utilization. The purpose of this article is to review all the available literature on the endovascular repair of ruptured abdominal aortic aneurysms and to analyze the most recent trends in their management, with special consideration given to comparing results of conventional and endovascular approaches.


A Novel Antibiotic Spacer for Significant Proximal Femoral Loss - Surgical Technique.
Infections of proximal femora with prosthetic implants in situ have long been a major concern in orthopedic surgery. The gold standard in the management of infected proximal femurs in the presence of prosthetic implants has traditionally been a two-stage revision. However, this is challenging in the setting of extensive bone loss. A 3 case series of such infections leading to extensive loss of the proximal femur is presented. We specifically describe our technique of debriding the infected segments as well as utilization of a trochanteric slide osteotomy to resect the femur.We also demonstrate preparation of the "pseudoacetabulum" and femoral component with an antibiotic spacer. The high cost of such a procedure is offset by reduction in time spent in hospital. The spacer also helps to allow mobilization by partial weight bearing on a stable femoral component and provide pain control which improves quality of life as compared to prolonged intravenous antimicrobial therapy.


A developmental study of specific spelling disability.
Previous studies have identified a group of individuals with specific problems in spelling, and compared them to a group with problems in reading and spelling. Those who are poor at reading and spelling are thought to have more severe underlying language problems. This study compared the cognitive abilities of three groups of children: one specifically spelling disabled, one spelling and reading disabled, and one control group without reading or spelling problems. The groups were identified at age 14. A five-year retrospective analysis of their performance revealed that both of the disabled groups had been significantly poorer than the controls, not only in spelling but also in reading. Both the disabled groups showed other signs often associated with dyslexia such as poor WISC-R Coding and Digit Span. Analyses of their spelling errors did not reveal the superior phonetic abilities which some other studies have found to differentiate specifically spelling disabled from reading + spelling disabled groups. The specific spelling disabled group did show some evidence of superiority in Verbal IQ subtests. These results are consistent with the idea that specific spelling disability is a residual problem of individuals who, possibly by means of underlying verbal strengths, have managed to compensate for earlier reading difficulties.


Monoclonal antibodies to ricin: in vitro inhibition of toxicity and utility as diagnostic reagents.
Monoclonal antibodies (MAbs) against ricin toxin (RT) and its subunits were produced in mice. The MAbs were initially selected based upon the ability to either bind ricin or the individual subunits in a solid-phase enzyme-linked immunosorbent assay (ELISA). Several candidates were selected for further evaluation, including their ability to inhibit ricin intoxication in vitro and their utility as immunodiagnostic reagents. Although their ability to capture antigen when bound to the solid phase was poor, some MAbs demonstrated potential utility as detection reagents in solid-phase immunoassays. Several MAbs were also able to inhibit ricin-mediated eukaryotic cell cytotoxicity in vitro. These MAbs may prove useful for preventing and/or treating ricin intoxication.