The Role of Diet in Pediatric Inflammatory Bowel Disease.
The pathogenesis of inflammatory bowel disease (IBD) involves a complex interaction between genetics, immune response, and the environment. Epidemiologic associations between diet and development of IBD plus the ability of diet to modify the microbiota and modulate immune function have led to the hypothesis that diet can prevent and/or treat IBD. It is well established that the induction of remission and healing of the mucosa in Crohn's disease can be accomplished with exclusive enteral nutrition. Whole food-based alternatives such as the Crohn's disease exclusion diet have shown promising results.


Clinical and molecular epidemiology of healthcare-associated infections due to extended-spectrum beta-lactamase (ESBL)-producing strains of Escherichia coli and Klebsiella pneumoniae that harbor multiple ESBL genes.
To characterize healthcare-associated infections due to extended-spectrum beta-lactamase (ESBL)-producing strains of Escherichia coli and Klebsiella pneumoniae that harbor multiple ESBL genes, as opposed to a single ESBL gene. All patients with a confirmed healthcare-associated infection due to an ESBL-producing strain of E. coli or K. pneumoniae were enrolled in the study. Molecular typing of isolates was performed, and the comparative risks and outcomes of patients were analyzed. Among 71 patients with healthcare-associated infection due to an ESBL-producing strain of E. coli or K. pneumoniae, the gene for CTX-M, with or without other ESBL genes, was identified in all 51 (100%) of the patients infected with an E. coli strain and in 18 (90%) of the 20 patients infected with a K. pneumoniae strain. Of these 71 patients, 17 (24%) met the definition of healthcare-associated infection due to an ESBL-producing strain that harbored multiple genes; in multivariate analysis, previous exposure to 3 or more classes of antibiotics (adjusted odds ratio, 4.5 [95% confidence interval, 1.7-75.2]) was the sole risk factor for healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes. Isolates recovered from patients with healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes were more resistant to various antibiotic classes, and, compared with patients with healthcare-associated infection due to an ESBL-producing strain that harbored a single ESBL gene, they were more likely to have ineffective initial empirical antimicrobial therapy (52% vs 94%; odds ratio, 5.1 [95% confidence interval, 1.04-14.5]). CTX-M ESBL is highly prevalent in Thailand. Patients with healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes were more likely to have had ineffective initial empirical antimicrobial therapy, and, given that antibiotic selection pressure was the only associated risk, we suggest focused antimicrobial stewardship programs to limit the emergence and spread of healthcare-associated infection due to ESBL-producing strains in this middle-income country.


Senescent-induced dysregulation of cAMP/CREB signaling and correlations with cognitive decline.
It is well known that alongside senescence there is a gradual decline in cognitive ability, most noticeably certain kinds of memory such as working, episodic, spatial, and long term memory. However, until recently, not much has been known regarding the specific mechanisms responsible for the decline in cognitive ability with age. Over the past decades, researchers have become more interested in cAMP signaling, and its downstream transcription factor cAMP response element binding protein (CREB) in the context of senescence. However, there is still a lack of understanding on what ultimately causes the cognitive deficits observed with senescence. This review will focus on the changes in intracellular signaling in the brain, more specifically, alterations in cAMP/CREB signaling in aging. In addition, the downstream effects of altered cAMP signaling on cognitive ability with age will be further discussed. Overall, understanding the senescent-related changes that occur in cAMP/CREB signaling could be important for the development of novel drug targets for both healthy aging, and pathological aging such as Alzheimer's disease.


Coherent stochastic resonance in the case of two absorbing boundaries.
The coherent stochastic resonance is observed and studied with a multistep periodic signal in a continuous medium having two absorbing boundaries. The general features of this process are exhibited. The universal features at the resonance point are demonstrated. The kinetic behaviors around the resonance point are also presented.


Disaster reconnaissance framework for sustainable post-disaster materials management.
A first foundational assessment is provided for disaster debris reconnaissance that includes identifying tools and techniques for reconnaissance activities, identifying challenges in field reconnaissance, and identifying and developing preliminary guidelines and standards based on advancements from a workshop held in 2022. In this workshop, reconnaissance activities were analyzed in twofold: in relation to post-disaster debris and waste materials and in relation to waste management infrastructure. A four-phase timeline was included to capture the full lifecycle of management activities ranging from collection to temporary storage to final management route: pre-disaster or pre-reconnaissance, post-disaster response (days/weeks), short-term recovery (weeks/months), and long-term recovery (months/years). For successful reconnaissance, objectives of field activities and data collection needs; data types and metrics; and measurement and determination methods need to be identified. A reconnaissance framework, represented using a 3x2x2x4 matrix, is proposed to incorporate data attributes (tools, challenges, guides), reconnaissance attributes (debris, infrastructure; factors, actions), and time attributes (pre-event, response, short-term, long-term). This framework supports field reconnaissance missions and protocols that are longitudinally based and focused on post-disaster waste material and infrastructure metrics that advance sustainable materials management practices. To properly frame and develop effective reconnaissance activities, actions for all data attributes (tools, challenges, guides) are proposed to integrate sustainability and resilience considerations. While existing metrics, tools, methods, standards, and protocols can be adapted for sustainable post-disaster materials management reconnaissance, development of new approaches are needed for addressing unique aspects of disaster debris management.


[Physiological and Pathological Development of calcaneal apophysis in Children].
The apophysis of the calcaneal bone forms an insertional region for the strong plantarflexors with the Achillis tendon and serves as an origin for the plantar aponeurosis and the short intrinsic foot muscles. Both components create a tendinous sling whithin which the apophysis acts as a pivot, which functions when it runs a straight course and its tension is adequate. This mechanism results in combined tractional and compressional forces which work together with the ground reaction forces during gait as molding elements of the calcaneous bone. Every longer lasting change in the magnitude and distribution of these forces can be followed by structural adaptations especially during the growth period. Furthermore the calcaneal apophysis functions as a connecting link between the ankle and thigh bones on one side and the mid- and forefoot region on the other side. When studying the causal relationships which influence the apophyseal growth and shape intrinsic and extrinsic components must be distinguished. Every analysis of calcaneal pathologies should use clinical and instrumented diagnostics. Any classification must separate between bony and soft tissue elements and consider structural and functional influences in three planes. If an exact classification can be established an individual hypothesis must be formulated out of which therapeutic measures can be developed. Treatment must focus on the pathologic changes of shape as well as on functional aspects. A thorough knowledge of the normal development and function of the calcaneal apophysis serves as a basis for further understanding and treating pathologic changes of this hitherto only sparsely investigated functional region.


New guidelines for management of concussion in sport: special concern for youth.
The incidence of sports related concussion appears to be increasing, raising alarm over long-term consequences of these head injuries on cognitive function in youth. The American Academy of Neurology (AAN) has recently revised its position statement on concussion in sports, reflecting the burgeoning scientific evidence on its epidemiology, neurophysiology and prognosis. The AAN, along with other scientific organizations addressing concussion policy, has abandoned the use of algorithms for assigning a grade to concussions and instead stresses an individualized approach to concussion management. Recent evidence suggests that children and adolescents may be more susceptible to concussions from head blows, and may take longer to recover, than adults. Young women in certain sports also appear to be more susceptible to concussion than young men. The AAN recommends a more conservative approach to management of sports concussion in children and adolescents. Under no circumstances should a young athlete be allowed to participate in sport while still symptomatic. The use of standardized assessment tools is recommended to aid the healthcare provider in assessing the young athlete's recovery.


Short and long-term outcomes from a multisession diabetes education program targeting low-income minority patients: a six-month follow up.
A diabetes self-management education (DSME) program was offered to patients at a primary care clinic serving low-income people. The purpose of the analyses presented here was to understand the feasibility of the program and effectiveness of the intervention. The program was facilitated by a nurse and licensed dietician. Data were collected at baseline, after each class, and after 6 months. Patients were interviewed to identify diabetes self-care behaviors before the first class, after the fourth class, and at 6 months. Knowledge related to content areas was measured before and after each class. Glycosylated hemoglobin (HbA(1c)), blood pressure, weight, and body mass index (BMI) were collected at baseline and after 6 months. Medical records were reviewed for LDL levels, co-morbidity, and diabetes management. Frequencies, χ(2) and t tests, and repeated measures t tests were used to analyze data. Patients were mostly non-Hispanic black or Hispanic (93.1%); mean BMI was 34.89 kg/m(2). About one-half (41.95%) completed the program. Significant improvements were observed for knowledge related to each of the 4 content areas: diet (P < 0.001), diabetes management (P = 0.003), monitoring blood glucose (P < 0.001), and preventing complications (P = 0.001). Among long-term outcomes, mean HbA(1c) was significantly reduced (0.82%), from 8.60% to 7.78% (P = 0.007), with 26.67% of patients reducing HbA(1c) from ≥7.0% at baseline to <7% at follow up (P < 0.001). Patients demonstrated a significant improvement in readiness to improve dietary behaviors (P = 0.016). Outcomes suggested that minority patients with a high risk for poor diabetes outcomes might be retained in a multisession DSME program and benefit from increasing knowledge of diabetes content. Further evaluation is necessary to determine the cost-effectiveness of this intervention.


High-yield synthesis of multi-branched gold nanoparticles and their surface-enhanced Raman scattering properties.
Multi-branched gold nanoparticles were synthesized in high-yield through the reduction of HAuCl(4) by using hydrazine as a reducing agent. Practically 100% of the particles have numerous branches. The high reduction capability of hydrazine is found to be crucial for the formation of these branched gold nanoparticles. Their size can be controlled from 20 to 130 nm by varying the amounts of hydrazine. The prepared nanoparticles exhibit efficient surface-enhanced Raman scattering (SERS) properties and the SERS activity of the particles depends on the aspect ratio of their branches, which are most likely related to a great increase in the localized electromagnetic field enhancement from their unique sharp surface features arising from the branches.


Intra versus interspecific interactions of ladybeetles (Coleoptera: Coccinellidae) attacking aphids.
The nature and relative strengths of intra versus interspecific interactions among foraging ladybeetle larvae were studied experimentally by measuring short-term growth rates of predators and reductions in population sizes of prey in laboratory microcosms. In these microcosms, ladybeetle larvae foraged singly or as conspecific or heterospecific pairs, for pea aphids on bean plants over a two-day period. Similarly sized third instar larvae ofHippodamia convergens andH. tredecimpunctata, H. convergens andH. sinuata, andH. convergens andCoccinella septempunctata, were tested in experiments designed to ensure that paired larvae experienced moderate competition. Interspecific competition in these experiments did not differ significantly from intraspecific competition, in that an individual's weight gain did not depend on whether its competitor was heterospecific or conspecific. Furthermore, aphid populations were reduced equally by heterospecific and conspecific pairs. These results suggest that there is little or no difference between intra and interspecific interactions among larvae of these ladybeetles when two similarly sized individuals co-occur on a host plant. Thus, the species diversityper se of assemblages of ladybeetle larvae may have little influence over the short term on the reduction of aphid populations by ladybeetle predation.


Photoaffinity labeling with [3H]RU 28362: a powerful tool for the study of rat brain glucocorticoid receptors.
In order to study the receptor system for adrenocortical steroids in rat brain the synthetic glucocorticoid RU 28362 (11 beta, 17 beta-dihydroxy-6-methyl-17 alpha-(1-propynyl) androsta-1,4,6-trien-3-one) has been used for photoaffinity labeling. Competition and dissociation studies revealed a single class of binding sites for RU 28362 in rat brain cytosol. Photoaffinity labeling was performed by u.v.-irradiation for 2 min with a coupling efficiency of about 25%. The high efficiency permitted investigation of crude cytosolic preparations under denaturating conditions. Sodium dodecyl sulfate (SDS) and high resolution two-dimensional gel electrophoresis confirmed the high specificity of the photoaffinity labeling. The molecular weight (93 kD) as well as the isoelectric point (5.6) evaluated by these methods corresponded well to data reported for the classical glucocorticoid receptor in rat liver.


Nanoparticles of perfluorocarbon emulsion contribute to the reduction of methemoglobin to oxyhemoglobin.
Here we show that methemoglobin is converted to oxyhemoglobin in the presence of perfluorocarbon (PFС) emulsion. Methemoglobin in blood at the level of above 30% can cause severe complications and lethal outcome. Some pharm chemicals in blood in vivo and in vitro can lead to oxidation of iron, Fe(2+)→Fe(3+), and to increased level of methemoglobin. The oxidized heme is not able to carry oxygen, hypoxia arises and irreversible changes are developing in vital organs. We added NaNO2 solution in different concentrations to blood in vitro in order to yield methemoglobin. Then the suspension of PFC nanoparticles was added. As methemoglobin interacted with PFC nanoparticles the optical density of peaks typical for oxyhemoglobin increased and spectral peak of methemoglobin decreased. The greater the concentration of PFC and the more was the incubation time, the more efficient was the process of reduction of methemoglobin to oxyhemoglobin. We proved experimentally that with an initial concentration of methemoglobin in average 95% the addition of nanoparticles of PFC decreases its concentration to 9% in average. At the same time the concentration of oxyhemoglobin increased in average from 5% to 81%.


Applicability and safety of recombinant activated factor VII to control non-haemophilic haemorrhage: investigational experience in 265 children.
Experience of recombinant activated factor VII (rFVIIa, NovoSeven; Novo Nordisk A/S, Bagsvaerd, Denmark) to control haemorrhage in non-haemophilic children is limited. The object of this study was to examine the applicability and safety of rFVIIa amongst a group of non-haemophilic paediatric subjects. Details of all non-haemophilic children < or =16 years receiving rFVIIa whose data were recorded in the investigational, internet-based registry, haemostasis.com were analysed. A total of 265 children (mean age 7.7 years) were treated with rFVIIa; the median dose administered was 78.4 microg kg(-1) body weight (range 9.0-393.4) and the median total dose received 100.0 microg kg(-1) body weight (range 10.9-1341.2). Therapeutic areas included surgery (34.5%), coagulopathy (including thrombocytopenia; 29.0%), spontaneous bleeding (17.2%), trauma (8.4%) and intracranial haemorrhage (4.5%). Two patients experienced thromboembolic events following administration of rFVIIa. Thirty-nine patients died on account of haemorrhage or complications relating to their underlying condition; neither the thromboembolic events nor the deaths were related to rFVIIa administration. Bleeding stopped in 118/237 (49.8%), markedly decreased in 54/237 (22.8%), decreased in 51/237 (21.5%), remained unchanged in 13/237 (5.5%) and increased in 1/237 (0.4%) patients. These results suggest that rFVIIa is safe and widely applicable in children to control non-haemophilic haemorrhage.


Impact of particle sizes on health risks and source-specific health risks for heavy metals in road dust.
To analyze the impact of particle sizes on sources and related health risks for heavy metals, road dust samples in Beijing were collected and sifted into five particle sizes. The positive matrix factorization (PMF), human health risk assessment model (HHRA), and Monte Carlo simulation were used in the health risk assessment and source apportionment. Results showed that mass of particles < 74 μm occupied about 50% of the total particles, while only 8.48% of the particles were > 500 μm. Mass distribution and concentrations of heavy metals in each particle size changed in temporal. Over 85.00% of carcinogenic risks (CR) were from particles <74 μm, whereas CR from particles >250 μm were ignorable. Sources for health risks in each particle size were traffic exhaust, fuel combustion, construction, and use of pesticides and fertilizers. Proportions of sources to CR differed among particle sizes. Traffic exhaust and fuel combustion contributed over 90% to CR in particles <74 μm, whereas construction contributed the highest (31.68-54.14%) among all sources in particles 74-250 μm. Furthermore, the difference between health risks based on sifted road dust and that based on unsifted road dust was quantitatively analyzed. Source-specific health risk apportionment based on unsifted road dust was not presentative to all particle sizes, and true value of health risks could be over 2.5 times of the estimated value based on unsifted road dust, emphasized the importance of sifting of road dust.


Effect of mometasone furoate on early and late phase inflammation in patients with seasonal allergic rhinitis.
Mometasone furoate is a potent glucocorticoid that can markedly inhibit proinflammatory Th2 cytokines in vitro. An aqueous nasal spray formulation has been shown to be clinically active in reducing the symptoms of perennial and seasonal allergic rhinitis. To determine whether pretreatment with mometasone furoate 200 microg once daily decreases specific indices of early and late phase nasal inflammation compared with placebo. A randomized, double-blind, placebo-controlled crossover study was conducted using nasal provocation with ragweed antigen in 21 patients with ragweed-induced allergic rhinitis out of the ragweed season; the treatment period was 2 weeks. Symptom scores, rhinoprobe cytology, and nasal lavage fluid were collected during early and late phase periods for nasal cytokines (interleukin, 1, 4, 5, 6, and 8) and leukotriene B4 determinations using ELISA and RIA. Mean nasal symptom scores and sneezing frequency were consistently lower with mometasone furoate compared with placebo. Treatment was associated with a statistically significant early phase (30-minute time point) reduction in nasal lavage histamine levels compared with placebo (14.3 versus 20.2 ng/mL, P = .02). Within-treatment comparisons suggested that mometasone furoate reduced the antigen-induced late-phase response for IL-6, IL-8, and eosinophils compared with pretreatment. There were similar, but smaller, changes seen in the placebo group for these measurements. There were no statistically significant changes following antigen challenge in IL-1, IL-4, IL-5, LTB4, or in other nasal cytology parameters. These results suggest that the clinical activity of mometasone furoate nasal spray in seasonal allergic rhinitis is likely due, in part, to a reduction in the levels of histamine in nasal secretions related to the early phase response, and reductions in IL-6, IL-8, and eosinophils during the late phase response.


Clinical considerations for sarcopenia in older Colombian Afro-descendant and mestizo women.
To identify the frequencies of clinical suspicion of sarcopenia (CSS) and probable sarcopenia (PS) and their association with ethnic groups. This cross-sectional study categorized 700 women into Afro-descendant and mestizo ethnic groups. Calf circumference, muscle strength, and gait speed were measured. CSS was assessed using a sarcopenia risk scale and the measurement of calf circumference; the muscle strength of the dominant hand was used to establish PS. Unadjusted logistic regressions assessed associations between CSS/PS and ethnicity. Two adjusted logistic regression models included relevant covariates. CSS and PS were identified in 10.4% to 20.7% and 7.8% to 14.1% of study participants, respectively. Compared with mestizos, Afro-descendants had a more favorable sarcopenia risk score, greater calf circumference, and greater muscle strength and were associated with a lower risk for CSS (odds ratio [OR]: 0.13, 95% confidence interval [CI]: 0.06-0.28 and OR: 0.12, 95% CI: 0.07-0.21) and PS (OR: 0.12, 95% CI: 0.05-0.30 and OR: 0.11, 95% CI: 0.06-0.21). Compared with mestizos, CSS and PS were less frequent among Afro-descendants, who had 87% to 88% lower probability of CSS and 88% to 89% lower probability of PS.


Medical reliability of advanced prehospital cardiac life support.
Records of 263 consecutive patients receiving prehospital advanced cardiac life support for dysrhythmias associated with clinical cardiac arrest were reviewed to determine 1) accuracy of diagnosis of presenting rhythm by the paramedic in the field and the medical control physician at the telemetry base station; and 2) whether the treatment rendered was appropriate. The initial rhythm was misinterpreted by the paramedic in 41 patients (16%) and by the medical control physician in 22 patients (11%). In 16 patients (8%) both paramedic and physician misinterpreted the initial rhythm. Treatment errors occurred in 120 patients (46%). Forty-seven errors (18%) resulted from failure to establish an intravenous line, 17 (6%) resulted from failure to secure a controlled airway, and 38 (14%) were medication errors from failure to adhere to protocol. We conclude that errors in management of prehospital cardiac arrest victims in our emergency medical services system result most often from mistakes in specific therapy rather than from failure to identify the precipitating dysrhythmia.


Hypertriglyceridemic pancreatitis managed with heparin and insulin: a case report.
Alcohol and gall stones are common causes of pancreatitis. Other causes of pancreatitis include hypertriglyceridemia, trauma, congenital anomalies, and medications. Hypertriglyceridemic pancreatitis is distinguished, as it is more severe and complicated. The management of hypertriglyceridemic pancreatitis, other than the basic care given to other pancreatitis patients, is to decrease the serum triglyceride level to less than 500 mg/dl as soon as possible. Plasmapheresis, hemofiltration, and other modalities have been proven effective therapies, but, are expensive and not easily accessible. Insulin and heparin which are cheaper alternatives for treatment, have been reported in case reports along with one randomized controlled trial. The number of patients in these reports was small, so, the therapy is not well established. For most African countries like ours, the only option for management is heparin and insulin. Despite this fact, there has not been any publication regarding this issue on our continent. We report the case of a 24 years old Ethiopian male who presented with severe central abdominal pain, easy fatiguability, and vomiting of one-day duration. He was tachycardic and tachypneic with diffuse abdominal tenderness, and had tendon xanthomas. His plasma was lactescent with a serum triglyceride level of 4775 mg/dl. His abdominal CT scan showed diffuse pancreatic swelling with a peripancreatic fluid collection, and his serum lipase was elevated. With a diagnosis of hypertriglyceridemic pancreatitis, he was managed with intravenous insulin infusion along with subcutaneous heparin. His random blood sugar was checked hourly with three episodes of hypoglycemia during therapy. His serum triglyceride level dropped to less than 500 mg/dl in three days, and he was discharged with no complications. Since our findings are consistent with a prior randomized controlled trial and compilation of case reports, it would strengthen the evidence for safety and efficacy of insulin and heparin therapy. This therapy, which is the only available therapy in most countries of our continent, would decrease most of the complications of hypertriglyceridemic pancreatitis that we face. We believe, our report would be a wake-up call for researchers and clinicians in our continent to change their practice and strengthen the evidence for the treatment.


Differential role of reactive oxygen species in the activation of mitogen-activated protein kinases and Akt by key receptors on B-lymphocytes: CD40, the B cell antigen receptor, and CXCR4.
Antibodies produced by B-lymphocytes play a key role in the host defense against infection. The development, survival, and activation of B cell is regulated by multiple receptors including the B cell antigen receptor (BCR), which detects the presence of pathogens, CD40, which binds co-stimulatory molecules on activated T cells, and chemokines such as SDF-1 (CXCL12) that play key roles in B cell development and trafficking. Signaling by many receptors results in the generation of reactive oxygen species (ROS) that function as second messengers by regulating the activity of redox-sensitive kinases and phosphatases. We investigated the role of ROS in signaling by the BCR, CD40, and CXCR4, the receptor for SDF-1. We focused on activation of ERK, JNK, p38, and Akt, kinases that regulate multiple processes including cell survival, proliferation, and migration. Using the anti-oxidants N-acetyl L-cysteine (NAC) and ebselen to deplete intracellular ROS, we identified a differential requirement for ROS in the activation of ERK, JNK, p38, and Akt by these receptors. We found that CD40 activated JNK, p38, and Akt via redox-dependent pathways that were sensitive to ROS depletion by NAC and ebselen. In contrast, BCR-induced activation of ERK, JNK, p38, and Akt was not affected by ROS depletion. We also found that CXCR4-induced Akt activation was ROS-dependent even though activation of the ERK, JNK, and p38 MAP kinases by CXCR4 occurred via ROS-independent pathways. The differential requirement for ROS in the activation of ERK, JNK, p38, and Akt by the BCR, CD40, and CXCR4 likely reflects the multiplicity of upstream activators for each of these kinases, only some of which may be regulated in a redox-dependent manner. These findings support the idea that ROS are important second messengers in B cells and suggest that oxidants or anti-oxidants could be used to modulate B cell activation.


Observed behaviors during clinical interviews predict improvement in depression.
A considerable percentage of depressed patients does not respond to antidepressive treatment. Early indicators of prognosis are needed. The aims of this study are to examine a) whether the interpersonal behavior of patients and psychiatrist, as assessed by means of direct observation of behavior during a baseline clinical interview, might have predictive value with respect to therapeutic outcome, and b) which predictive potency might have measures of psychomotor activation. The relational behaviors (i.e. looking, yes-nodding, gesturing) occur less in patients who will improve, whereas the non-relational behaviors (i.e. intensive body touching, head movements) occur more in these patients. Global clinical assessment of psychomotor activation could not be related to outcome.


Recurrence of pericardial effusion after different procedure modalities in patients with non-small-cell lung cancer.
Lung cancer with related pericardial effusion is not rare. Intervention is a crucial step for symptomatic effusion. It is unknown, however, whether the different invasive interventions for pericardial effusion result in different survival outcomes. This study analyzed the clinical characteristics and prognostic factors for patients with non-small-cell lung cancer (NSCLC) who have undergone different procedures. From January 2006 to June 2018, we collected data from patients with NSCLC who have received invasive intervention for pericardial effusions. The patients were divided into three categories: simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy. Kaplan-Meier curve and log-rank test were used to analyze the pericardial effusion recurrence-free survival (RFS) and overall survival (OS). A total of 244 patients were enrolled. Adenocarcinoma (83.6%) was the major NSCLC subtype. Invasive intervention, including simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy, had been carried out on 52, 170, and 22 patients, respectively. The 1-year RFS rates in simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy were 19.2%, 31.2%, and 31.8%, respectively (P = 0.128), and the median RFS was 1.67, 5.03, and 8.32 months, respectively (P = 0.008). There was no significant difference in OS, however, with the median OS at 1.67, 6.43, and 8.32 months, respectively (P = 0.064). According to the multivariable analysis, the gravity in pericardial fluid analysis, receiving systemic therapy after pericardial effusion, and the time period from stage IV lung cancer to the presence of pericardial effusion were independent prognostic factors for pericardial effusion RFS and OS. Patients who have undergone simple pericardiocentesis alone for the management of NSCLC-related pericardial effusion have lower 1-year RFS rates than those who have undergone balloon pericardiotomy and surgical pericardiectomy. Therefore, balloon pericardiotomy and surgical pericardiectomy should be carried out for patients with NSCLC-related pericardial effusion if tolerable.


High-dose nitroglycerin infusion description of safety and efficacy in sympathetic crashing acute pulmonary edema: The HI-DOSE SCAPE study.
Sympathetic crashing acute pulmonary edema (SCAPE) is a medical emergency in which severe, acute elevation in blood pressure results in acute heart failure and fluid accumulation in the lungs. Without prompt recognition and treatment, the condition often progresses rapidly to respiratory failure necessitating intubation and intensive care unit (ICU) admission. In addition to non-invasive positive pressure ventilation (NIPPV), high-dose nitroglycerin (HDN) has become a mainstay of treatment; however, an optimal dosing strategy has not been established. The purpose of this study was to describe the characteristics and outcomes of patients who received an HDN infusion (≥ 100 μg/min) for the management of SCAPE in the Emergency Department (ED) of a large urban academic medical center. Outcomes were also analyzed to determine predictors of safety and efficacy including use of adjunct medication therapies. There were 67 adult patients who received HDN infusion for SCAPE from January 1, 2018 to December 31, 2018. The median (IQR) systolic blood pressure (SBP) on initiation of HDN infusion was 211 (192-233) mmHg. Patients were 63% male, 84% black, 51% had a history of heart failure (HF), and 36% had end-stage renal disease (ESRD). IV nitroglycerin (NTG) was initiated at a median (IQR) dose of 100 (100-200) mcg/min with median (IQR) peak rate in the first hour of 200 (127.5-200) mcg/min and an absolute maximum observed rate of 400 μg/min overall. 73% of patients received NIPPV, 48% sublingual (SL) or IV bolus nitroglycerin before HDN infusion, 58% loop diuretic, and 34% angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Rates of ICU admission, intubation, acute kidney injury (AKI) at 48 h, and hypotension were 37%, 21%, 13%, and 4% respectively. This is the largest to date study describing the use of an HDN infusion (≥100 μg/min) strategy for the management of SCAPE. HDN infusion may be a safe alternative strategy to intermittent bolus HDN.


Postkeratoplasty crystalline deposits mimicking bacterial infectious crystalline keratopathy.
Three corneal transplant patients developed white, crystalline, anterior stromal lesions in their grafts while receiving long-term topical corticosteroid therapy. A presumed diagnosis of infectious crystalline keratopathy was made in each case. However, histologic examination of the lesions failed to show gram-positive cocci. A fungal infiltrate was present in the first two patients, and calcium deposits produced the lesion in the third patient.


Metabolic alterations in focally activated primary somatosensory cortex of alpha-chloralose-anesthetized rats measured by 1H MRS at 11.7 T.
Previously, magnetic resonance spectroscopy studies of alterations in cerebral metabolite concentration during functional activation have been focused on phosphocreatine using 31P MRS and lactate using 1H MRS with controversial results. Recently, significant improvements on the spectral resolution and sensitivity of in vivo spectroscopy have been made at ultrahigh magnetic field strength. Using highly resolved localized short-TE 1H MRS at 11.7 T, we report metabolic responses of rat somatosensory cortex to forepaw stimulation in alpha-chloralose-anesthetized rats. The phosphocreatine/creatine ratio was found to be significantly decreased by 15.1 +/- 4.6% (mean +/- SEM, P < 0.01). Lactate remained very low (approximately <0.3 micromol/g w/w) with no statistically significant changes observed during forepaw stimulation at a temporal resolution of 10.7 min. An increase in glutamine and a decrease in glutamate and myo-inositol were also detected in the stimulated state. Our results suggest that, under the experimental conditions used in this study, increased energy consumption due to focal activation causes a shift in the creatine kinase reaction towards the direction of adenosine triphosphate production. At the same time, metabolic matching prevails during increased energy consumption with no significant increase in the glycolytic product lactate in the focally activated primary somatosensory cortex of alpha-chloralose-anesthetized rats.


Copper oxide nanoparticles: In vitro and in vivo toxicity, mechanisms of action and factors influencing their toxicology.
Copper oxide nanoparticles (CuO NPs) have received increasing interest due to their distinctive properties, including small particle size, high surface area, and reactivity. Due to these properties, their applications have been expanded rapidly in various areas such as biomedical properties, industrial catalysts, gas sensors, electronic materials, and environmental remediation. However, because of these widespread uses, there is now an increased risk of human exposure, which could lead to short- and long-term toxicity. This review addresses the underlying toxicity mechanisms of CuO NPs in cells which include reactive oxygen species generation, leaching of Cu ion, coordination effects, non-homeostasis effect, autophagy, and inflammation. In addition, different key factors responsible for toxicity, characterization, surface modification, dissolution, NPs dose, exposure pathways and environment are discussed to understand the toxicological impact of CuO NPs. In vitro and in vivo studies have shown that CuO NPs cause oxidative stress, cytotoxicity, genotoxicity, immunotoxicity, neurotoxicity, and inflammation in bacterial, algal, fish, rodents, and human cell lines. Therefore, to make CuO NPs a more suitable candidate for various applications, it is essential to address their potential toxic effects, and hence, more studies should be done on the long-term and chronic impacts of CuO NPs at different concentrations to assure the safe usage of CuO NPs.


The use of a biodegradable collagen/vicryl composite membrane to repair partial nephrectomy in rabbits.
A composite membrane produced from collagen and vicryl mesh has been used to cover the kidney surface following partial nephrectomy in rabbits. The membrane readily held sutures, gave satisfactory haemostasis, and prevented leakage of urine. The experiments showed that the prosthesis biodegraded in less than twenty weeks. The only observed long-term effect of the material was thickening of the renal capsule. The results indicate that this membrane may be a suitable reparative material for use in traumatised kidneys in humans.


Effects of concomitant surgeries during midurethral slings (MUS) on postoperative complications, voiding dysfunction, continence outcomes, and urodynamic variables.
To determine whether concomitant surgeries affected outcomes in a randomized trial comparing retropubic midurethral sling (MUS) vs transobturator MUS. Subjects (n = 597) were stratified into 4 groups based on type of concomitant surgeries: group I had anterior/apical with or without posterior repairs (n = 79, 13%); group II had posterior repairs or perineorrhaphy only (n = 38, 6%); group III had nonprolapse procedures (n = 34, 6%); and group IV had no concomitant surgeries (n = 446, 75%). Complication rates, voiding dysfunction, objective and subjective surgical failure rates, and changes in urodynamic values (postop minus preop) were assessed and compared in these 4 groups. There were no differences in complications, voiding dysfunction, and subjective failure outcomes between these 4 groups. Group I had lower odds ratio of objective surgical failure compared with group IV (OR 0.38, 95% CI 0.18-0.81, P = .05). The OR of failure of all patients undergoing concomitant surgeries (groups I-III) was lower than group IV (OR 0.57, 95% CI 0.35-0.95, P = .03). The change in Pdet@Qmax (from pressure-flow) was significantly higher in group III vs IV (P = .01). The change in Q(max.) (from uroflowmetry) was significantly less in groups I and II vs group IV (P = .046 and .04, respectively). Concomitant surgeries did not increase complications. Subjects who underwent certain concomitant surgeries had lower failure rates than those undergoing slings only. These data support safety and efficacy of performing concomitant surgery at the time of MUS.


The potential use of dual frequency bioimpedance in predicting the distribution of total body water in health and disease.
The distribution of water between extracellular fluid (ECF; measured by the inulin dilution technique) and intracellular fluid (ICF; calculated as the difference between total body water, which was measured by the deuterium dilution technique, and ECF) was measured in 12 healthy subjects. The results were compared with predictions made by anthropometry and whole body impedance obtained at 1kHz (Z(1)) and 50 kHz (Z(50)). Z(1) and Z(50) were also measured in 82 health subjects and 27 patients without clinically detectable oedema, and in 10 patients with oedema. Anthropometry and height(2)/Z(1) showed similar correlations with inulin space (r = 0.64, SEE = 1.74 L and r = 0.65, SEE = 1.75 L respectively). The ratios of Z (1)Z (50) in oedematous patients (1.03 +/- 0.02), which were universally lower than those obtained in normal subjects (1.18 +/- 0.04), overlapped with those obtained in patients without oedema (1.11 +/- 0.05). The study suggests that in this group of normal subjects low frequency bioimpedance measurements are not superior to anthropometric estimates of ECF. They also suggest a limitation in the use of the dual frequency bioimpedance meter to distiguish between patients with and without oedema.


Mammalian sperm hyperactivation regulates navigation via physical boundaries and promotes pseudo-chemotaxis.
Mammalian sperm migration within the complex and dynamic environment of the female reproductive tract toward the fertilization site requires navigational mechanisms, through which sperm respond to the tract environment and maintain the appropriate swimming behavior. In the oviduct (fallopian tube), sperm undergo a process called "hyperactivation," which involves switching from a nearly symmetrical, low-amplitude, and flagellar beating pattern to an asymmetrical, high-amplitude beating pattern that is required for fertilization in vivo. Here, exploring bovine sperm motion in high-aspect ratio microfluidic reservoirs as well as theoretical and computational modeling, we demonstrate that sperm hyperactivation, in response to pharmacological agonists, modulates sperm-sidewall interactions and thus navigation via physical boundaries. Prior to hyperactivation, sperm remained swimming along the sidewalls of the reservoirs; however, once hyperactivation caused the intrinsic curvature of sperm to exceed a critical value, swimming along the sidewalls was reduced. We further studied the effect of noise in the intrinsic curvature near the critical value and found that these nonthermal fluctuations yielded an interesting "Run-Stop" motion on the sidewall. Finally, we observed that hyperactivation produced a "pseudo-chemotaxis" behavior, in that sperm stayed longer within microfluidic chambers containing higher concentrations of hyperactivation agonists.


Post-exercise dynamics of serum amyloid A blood concentration in thoroughbred horses classified as injured and non-injured after the race.
The aim of this study was to evaluate serum amyloid A (SAA) concentration in horses with orthopedic injuries acquired during racing and in healthy ones after completing the race. Injuries of bone and tendon did not cause radical increase in SAA concentration observed in other inflammatory conditions. SAA concentration correlated positively with white blood cell count (WBC) on the 3rd-4th days after race being significantly higher in the injured horses than in the control group in that time. It was suggested that racing effort may cause increase in SAA level, more pronounced in horses manifesting clinical signs of orthopedic injury after the race.


Long-term surgical results of trabeculectomy for secondary glaucoma in Val30Met hereditary transthyretin amyloidosis.
This study reports the long-term results of trabeculectomy (LEC) for secondary glaucoma in hereditary transthyretin (ATTRv) amyloidosis patients and its correlation with prior vitrectomy. A retrospective case series was conducted involving 31 consecutive eyes of 20 ATTRv amyloidosis patients who underwent LEC between 2007 and 2020. The mean follow-up period was 73.2 ± 37.0 months (range: 20-181 months). Postoperative intraocular pressures (IOPs) were evaluated based on the following criteria: (a) IOP between 6 and 21 mmHg without additional glaucoma surgeries, except for laser suture lysis, (b) IOP between 6 and 15 mmHg without additional glaucoma surgeries, except for laser suture lysis, and (c) IOP between 6 and 21 mmHg without additional glaucoma surgeries, except for needling and laser suture lysis. Kaplan-Meier analysis revealed survival rates after LEC of 0.52 at 36 months, 0.42 at 60 months, and 0.25 at 84 months under criterion (a); 0.49 at 36 months, 0.27 at 60 months, and 0.11 at 84 months under criterion (b); and 0.76 at 36 months, 0.71 at 60 months, and 0.65 at 84 months under criterion (c). Eyes with a history of small gauge transconjunctival vitrectomy (SGTV) exhibited a tendency towards lower survival rates, although no statistically significant difference was observed (log-rank test; p = 0.193 under criterion (a) and p = 0.0553 under criterion (b)). Our findings suggest that LEC and additional needling procedures can provide some control over IOP; however, the overall postoperative outcomes of LEC for ATTRv amyloidosis remain unsatisfactory, even in the era of SGTV with reduced conjunctival scarring.


[Projections to the inferior olive of the cat. I. Comparisons of input from the dorsal column nuclei, the lateral cervical nucleus, the spino-olivary pathways, the cerebral cortex and the cerebellum].
The present experiments compare the projections from the dorsal column nuclei (DCN), the lateral cervical nucleus (LCN), the spino-olivary pathways (SO), the motor cortex (Ms1) and the cerebellum (CB) to the inferior olive of the cat. A differential labeling strategy was used for these comparisons. It was found that projections from the contralateral DCN and LCN and the ipsilateral SO overlap extensively with each other in the dorsal accessory division of the inferior olive and the caudal half of the medial accessory olive. Projections from the contralateral motor cortex partially overlap these somato-sensory projections but they also extend into the principal division and into the rostral half of the medial accessory olive where other authors have found input from other "motor" sources such as the red n., the globus pallidus and the caudate n. The contralateral cerebellum projects heavily to most of the inferior olive except for a few regions in the caudal portions of the two accessory nuclei. These results show that there is a partial segregation between somatosensory and motor inputs within the inferior olive and that the cerebellar feedback fibers appear to avoid at least parts of those regions where the somatosensory input is heavy. Some of this segregation, particularly within the medial accessory olive and the principal n., correlates with differences in both the olivo-cerebellar connectivity and the cytoarchitecture of these regions. Although the somatosensory and motor inputs are partially segregated, there are also several regions where these inputs overlap. These regions are: (1) an area in the medial half of the rostral portions of the dorsal accessory olive, and (2) a small oval zone in the middle of the caudal half of the medial accessory olive. This overlap provides an anatomical basis for electrophysiological evidence which demonstrates the existence of cells in some of these regions that respond to activation of both the cerebral cortex and the spinal cord (e.g., Crill and Kennedy, '67).


Prosopis glandulosa and the nitrogen balance of rangelands: extent and occurrence of nodulation.
We report the recovery of root nodules from P. glandulosa var. glandulosa in the eastern portion of its range, where the species reaches its greatest vegetational development. Single cores 4.7 cm in diameter and up to 250 cm deep yielded from 0 to over 250 nodules. Nodules were found at all depths below 10 cm, with the highest concentration often around 100 cm. Detailed studies of three trees revealed relatively small volume densities of about 0.02 nodules cm-3, high surface area densities of 2-4 nodules cm-2, and high nodule biomass of 8-23 g m-2, when compared to cultivated legumes. Nodules are small, weakly attached to roots that are seldom over 0.5 mm in diameter, and not easily observed under field conditions. No nodules were recovered from cores from the more arid western portion of P.glandulosa's range, although seedlings nodulated readily in these soils in the glasshouse as well as in most unamended soils from throughout mesquite's geographical range. Local differences in nodulating potential of soils included a negative association with mesquite canopies and a positive association with depth. These results suggest a significant role for biological fixation in the nitrogen regime and vegetation dynamics of Prosopis-dominated ecosystems.


Effects of VasoCare therapy on the initiation and progression of atherosclerosis.
VasoCare therapy, which involves the administration of autologous blood following the ex vivo exposure to physico-chemical stressors, has been shown to modulate immune responses. Since immune mechanisms have been recognized to be pivotal in the pathogenesis of atherosclerosis, we hypothesized that VasoCare treatment would inhibit atherosclerosis in LDL-R (-/-) mice. Three groups of LDL-R (-/-) mice were studied: a control group that was fed normal chow (Group I) and no other treatment; a control group that received a high cholesterol (HC) diet for 8 weeks (group II) with sham saline injections; and a third group (III) that received HC diet for 8 weeks and VasoCare treatment initiated after four weeks of HC feeding. Atherosclerotic area (AA), relative to total aortic area (TA), was assessed after 8 weeks of HC feeding by oil red O staining, and cross sectional plaque area at the level of the aortic valve leaflets was determined by quantitative morphometry. HC mice exhibited substantial aortic lipid deposition which was profoundly reduced in the VasoCare treated animals (AA/TA ratios in group II: 0.32+/-0.15 vs. group III: 0.17+/-0.06; P<0.05). This was associated with a significant decrease in cross sectional area of plaque in the aortic sinuses. VasoCare therapy also reduced the xanthoma formation and limb swelling characteristic of this animal model. However, cholesterol levels, measured by an enzymatic assay, showed similar marked increases in total serum cholesterol (CHO) in the animals receiving HC diet alone and those receiving the HC diet and VasoCare treatment [group I: 5.4+/-0.8 mM, group II: 46.7+/-3.6 mM, and group III: 44.7+/-2.8 mM (P<0.01 vs. group I)]. We conclude that VasoCare treatment inhibits progression of atherosclerotic lesions in a murine model of human familial hypercholesterolemia by a mechanism independent of cholesterol lowering.


Age-related radiographic parameters difference between the degenerative lumbar spinal stenosis patients and healthy people and correlation analysis.
To identify age-related radiographic risk factors for degenerative lumbar spinal stenosis (DLSS) and analyze correlations among them. A total of 180 cases were enrolled in this study, and lumbar magnetic resonance was performed. Among them, 93 cases suffered DLSS and lumbar dynamic X-ray was examined. And following parameters were measured and evaluated: intervertebral disk height (IDH), the ratio of IDH(IDHL4-5/L3-4), initial IDH of L4-5(iIDHL4-5) in the DLSS group, disk degeneration (DD), cartilaginous endplate failure (CEF), Modic changes, the thickness of ligamentum flavum (LF), range of intervertebral motion (ROM), facet joint opening (FJO), facet joint angle (FJA), the standard cross-sectional area (SCSA) of the multifidus, erector spinae, and psoas major muscles. The data of two groups were compared, and the possible risk factors of DLSS were analyzed. Compared with the control group, the DLSS group had higher IDH except for L4-5 and larger iIDHL4-5 (P < 0.05). Significant differences were shown in CEF and the thickness of LF at L1-S1 and DD at L4-5 (P < 0.05). The DLSS group had smaller SCSA of multifidus, erector spinae, and psoas major muscles but greater FJA, FJO (P < 0.05). And the risk of DLSS increased when iIDHL4-5 ≥ 10.73 mm, FJA ≥ 52.03° , or FJO ≥ 3.75 mm. IDH positively correlated with SCSA of multifidus and psoas major muscles and ROM at L1-S1 (P < 0.05). DD showed negative linear relations with SCSA of multifidus and psoas muscle and positive linear relation with CEF at L1-2, L2-3, and L5-S1 (P < 0.05). Larger initial disk height and excessive CEF may induce DLSS by increasing intervertebral mobility to promote DD, and atrophied paravertebral muscles by weakening the stability of lumbar spine.


Grimontia marina sp. nov., a marine bacterium isolated from the Yellow Sea.
A novel species belonging to the genus Grimontia is described in this study. A Gram-negative, chemoheterotrophic, obligately aerobic, catalase- and oxidase-positive, motile by a single polar flagellum, and rod-shaped bacterium, designated IMCC5001(T), was isolated from surface seawater of the Yellow Sea. Strain IMCC5001(T) grew optimally at 30°C in the presence of 3.5% NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate was related most closely to Grimontia hollisae with a sequence similarity of 95.8%, and formed a robust phyletic lineage with Grimontia hollisae. Differential physiological characteristics between the new strain and Grimontia hollisae KCCM 41680(T) and chemotaxonomic characterization including determination of DNA G+C content, fatty acid methyl esters, quinone composition, and polar lipid profiles justified the assignment of strain IMCC5001(T) to the genus Grimontia as a novel species. In conclusion, strain IMCC5001(T) represents a new species, for which the name Grimontia marina sp. nov. is proposed, with the type strain IMCC5001(T) (=KCTC 22666(T) =NBRC 105794(T)).


Bronchodilator reversibility testing in chronic obstructive pulmonary disease.
A limited or absent bronchodilator response is used to classify chronic obstructive pulmonary disease (COPD) and can determine the treatment offered. The reliability of the recommended response criteria and their relationship to disease progression has not been established. 660 patients meeting European Respiratory Society (ERS) diagnostic criteria for irreversible COPD were studied. Spirometric parameters were measured on three occasions before and after salbutamol and ipratropium bromide sequentially or in combination over 2 months. Responses were classified using the American Thoracic Society/GOLD (ATS) and ERS criteria. Patients were followed for 3 years with post-bronchodilator FEV(1) and exacerbation history recorded 3 monthly and health status 6 monthly. FEV(1) increased significantly with each bronchodilator, a response that was normally distributed. Mean post-bronchodilator FEV(1) was reproducible between visits (intraclass correlation 0.93). The absolute change in FEV(1) was independent of the pre-bronchodilator value but the percentage change correlated with pre-bronchodilator FEV(1) (r=-0.44; p<0.0001). Using ATS criteria, 52.1% of patients changed responder status between visits compared with 38.2% using ERS criteria. Smoking status, atopy, and withdrawing inhaled corticosteroids were unrelated to bronchodilator response, as was the rate of decline in FEV(1), decline in health status, and exacerbation rate. In moderate to severe COPD bronchodilator responsiveness is a continuous variable. Classifying patients as "responders" and "non-responders" can be misleading and does not predict disease progression.


Role of foreign direct investment and fiscal decentralization on urban haze pollution in China.
Government management is the main tool to solve environmental pollution. Considering the unique fiscal decentralization institution in China, this paper investigates the effect of foreign direct investment (FDI) on urban haze pollution in China from the perspective of spatial econometrics. The Generalized Spatial Two Stage Least Squares (GS2SLS) method is employed to treat the spatial correlation of air pollution. Based on a panel dataset comprising 276 Chinese cities during 2004-2018, we find a positive effect of FDI on urban haze pollution. For one standard deviation increase in FDI, the average annual PM2.5 concentration increase by 1.5%, ceteris paribus. Evidence also suggests that this effect varies across regions with different levels of fiscal decentralization. Through the test of the moderating effect and the threshold effect, we found that the higher of the fiscal decentralization, the weaker of the impact of FDI on haze pollution. This study proposes a new solution for sustainable development: increasing the financial autonomy of local governments to restrain the attraction of non-cleaner investment.


The immunologic composition of neonatal milk: cellular components.
The cellular content of neonatal mammary gland secretions from 12 full-term infants less than 2 weeks postdelivery was studied. The predominant cell types observed were lymphocytes and macrophages with greater than 90% viability in each. The concentration of lymphocytes was significantly (P less than 0.001) correlated with the concentration of macrophages. The immunoglobulin content of this fluid was predominantly IgG with minimal concentrations of IgA, and no IgM detected. These data suggest both the presence of regulatory mechanisms for the cellular composition of neonatal breast secretions and that neonatal milk may bear a significant connection with the developing mucosal immune system.


Bilateral internal carotid absence: a case report of a rare congenital anomaly.
Bilateral internal carotid artery agenesis (ICAA) is a rare developmental anomaly of unknown etiology that is often associated with disruption of adequate perfusion to the central nervous system. Nevertheless, some patients remain asymptomatic due to collateral circulation involving the communicating arteries of the Circle of Willis. Secondary to the hemodynamical stress through the collateral circulation, affected patients are at an increased risk of developing subarachnoid hemorrhage and intracranial aneurysms. We report an unusual case of a 62-year-old man with bilateral ICAA who expired following two asystolic events during minor surgery. This case emphasizes the plasticity of the cerebral collateral circulation during development, to the point of normal cerebral perfusion throughout life with no ischemic complications.


Molecular typing of Mycobacterium tuberculosis by mycobacterial interspersed repetitive unit-variable-number tandem repeat analysis, a more accurate method for identifying epidemiological links between patients with tuberculosis.
IS6110 fingerprinting of Mycobacterium tuberculosis is the standard identification method in studies on transmission of tuberculosis. However, intensive epidemiological investigation may fail to confirm transmission links between patients clustered by IS6110-restriction fragment length polymorphism (RFLP) typing. We applied typing based on variable numbers of tandem repeats (VNTRs) of mycobacterial interspersed repetitive units (MIRUs) to isolates from 125 patients in 42 IS6110 clusters, for which thorough epidemiological data were available, to investigate the potential of this method in distinguishing epidemiologically linked from nonlinked patients. Of seven IS6110 clusters without epidemiological links, five were split by MIRU-VNTR typing, while nearly all IS6110 clusters with proven or likely links displayed conserved MIRU-VNTR types. These results provide molecular evidence that not all clusters determined on the basis of multibanded IS6110 RFLP patterns necessarily reflect transmission of tuberculosis. They support the use of MIRU-VNTR typing as a more reliable and faster method for transmission analysis.


The effects of joint stress on sticklebacks.
The effects on the three-spined stickleback, (Gasterosteus aculeatus L.), of various combinations of stresses due to parasitism by Schistocephalus solidus, dietary restriction, and exposure to cadmium (0.032 mg 1-1) were investigated. Sticklebacks exposed to a combination of all three stressors died first with a median period of survival significantly shorter than that for fish subjected to fewer stressors. Compared with fish on a restricted diet alone, parasitism plus dietary restriction also reduced survival; however, the combination of cadmium exposure and restricted diet did not. A possible explanation for this finding is proposed.


The cell cycle regulator protein 14-3-3σ is essential for hair follicle integrity and epidermal homeostasis.
The 14-3-3σ (Stratifin; Sfn) is a cell cycle regulator intimately involved in the program of epithelial keratinization. 14-3-3σ is unique in that it is expressed primarily in epithelial cells and is frequently silenced in epithelial cancers. Despite its well-documented role as a cell cycle regulator and as a tumor suppressor, the function of 14-3-3σ in the intricate balance of proliferation and differentiation in epithelial development is poorly understood. A mutation in 14-3-3σ was found to be responsible for the repeated epilation (Er) phenotype. It has previously been shown that Sfn(+/Er) mice are characterized by repeated hair loss and regrowth, whereas Sfn(Er/Er) mice die at birth displaying severe oral fusions and limb abnormalities as a result of defects in keratinizing epithelia. Here we show that mice heterozygous for the 14-3-3σ mutation have severe defects in hair shaft differentiation, resulting in destruction of the hair shaft during morphogenesis. Furthermore, we report that the interfollicular epidermis and sebaceous glands are hyperproliferative, coincident with expanded nuclear Yap1 (Yes-associated protein 1)--a critical modulator of epidermal stem cell proliferation. We also report that hair follicle stem cells in the bulge cycle abnormally, raising important questions as to the role of 14-3-3σ in the bulge.


Students' expectations on the surgery clerkship exceed those of residents and faculty.
The perceptions and expectations of students on the surgery clerkship were evaluated and compared with those of surgical residents and faculty. A voluntary and anonymous survey was distributed to third year medical students, general surgery residents, and surgery faculty. Statistical analysis was performed using the χ(2) and Cochran-Mantel-Haenszel tests (P value <0.05 was significant). Medical students, surgery residents and faculty largely agreed on student responsibilities during morning rounds. However, more students (96.9%) than residents (86.2%) and faculty (77.3%) believed they should be writing progress notes, and fewer students (85%) than residents (100%) and faculty (95.5%) thought they should be taught during morning rounds (P < 0.01 and P = 0.04, respectively). The expected and actual educational experience on the surgical clerkship was similar. The amount of instruction provided each week by residents and faculty was similar to the amount expected by students; each group believed that surgical residents were good educators. Students, residents, and faculty agreed on many essential skills for a student to learn by the clerkship's end; however, more students (85.8%) than residents (58.6%) and faculty (68.2%) viewed identifying surgical complications as an essential skill (P < 0.01). Overall, the expectations of the medical students, surgical residents, and surgical faculty on the surgery clerkship were well matched. However, there were some instances where the students thought they should be more involved in patient care than did the residents and the faculty. It is important for surgical educators to be aware of these discrepancies to fully maximize the educational experience of medical students.


Systemic therapy for pulmonary carcinoids.
Between 25 and 33% of neuroendocrine tumours arise in the lung as low-grade typical pulmonary carcinoids (TPC), intermediate-grade atypical pulmonary carcinoids (APC), and high-grade large cell neuroendocrine or small cell carcinomas. The relatively uncommon incidence and prevalence of PCs are progressively increasing. However, data regarding systemic treatment for PCs are limited, controversial and based on old reports with few randomized or placebo-controlled trials, small sample sizes, or including tumours with very different behaviours. Moreover, conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids, treatment arms are not well defined or mix different therapies, and the indolent nature of some PCs is not adequately considered in designing control arms. Here, we reviewed and discuss current recommendations regarding systemic treatments for PCs.


Principles of human chemoprevention.
Preventive strategy has decreased the morbidity and mortality from many diseases, but so far similar progress against cancer using chemoprevention as a strategy has not been achieved in a useful way. This article discusses the biology of cancer as it relates to chemoprevention, and the process and principles that the development of candidate chemopreventive agents should follow.


Vascular endothelial growth factor stimulates endothelial differentiation from mesenchymal stem cells via Rho/myocardin-related transcription factor--a signaling pathway.
Mesenchymal stem cells (MSCs) are pluripotent progenitors that can differentiate into a variety of cell types. Vascular endothelial growth factor (VEGF) is one of the major factors of initiating and regulating angiogenesis. It has been reported that VEGF can induce MSCs differentiated into endothelial cells (ECs). However, the mechanism that VEGF-induced MSC differentiation is not completely understood. Here, we showed that VEGF induced human and rat bone marrow-derived MSCs differentiation to ECs. Rho family plays an important role in VEGF-induced endothelial cell migration and angiogenesis. Our results indicated that in MSCs, VEGF activated Rho/ROCK signaling pathway and promoted nuclear translocation of myocardin-related transcription factor-A (MRTF-A), which is controlled by Rho/ROCK signaling. In addition, Rho inhibitor C3 transferase, ROCK inhibitor Y27632 or depletion of endogenous MRTF-A abolished the VEGF-induced differentiation of MSCs into ECs. Furthermore, VEGF also enhanced the expression levels of CYR61/CCN1, as a regulator of vascular development and angiogenesis, and knockdown of endogenous MRTF-A reduced VEGF-induced the upregulation of CYR61/CCN1. Report assays with site-direct mutation analysis of CYR61/CCN1 promoter demonstrated that MRTF-A transactivated CYR61/CCN1 promoter mainly depending on CArG box. In this study, we identify the Rho/MRTF-A signaling pathway as a main actor in controlling VEGF-induced differentiation of human and rat bone marrow-derived MSCs into endothelial cells.


Apoptosis and p53 expression in human gliomas.
Twenty-five human gliomas of different histological grade and type were studied for p53 expression by immunohistochemistry and for apoptosis using ApopTag method. p53 expression (percentage of positive cells) was highest in anaplastic astrocytomas, followed by low grade astrocytomas and surprisingly in glioblastomas. Granular cytoplasmic p53 positivity appeared in 4/5 low grade oligodendroglioma and in 2/5 low grade mixed oligoastrocytomas. The means of apoptosis index in the different tumor types ranged between 0.8 and 11.5 with the highest values in anaplastic astrocytoma and glioblastomas. Although the number of cases per group were relatively low and the individual vales showed differences it seems that p53 expression is related to the biological aggressiveness of gliomas. It is also suggested that high level of apoptosis in malignant glioma could represent a p53 independent pathway.


The role of endoscopic ultrasound in the diagnosis and management of Barrett's esophagus.
Although initial studies suggest a limited role for EUS in the detection of BE and the diagnosis and staging of dysplasia, a defined role in several specific situations is emerging. EUS is useful in selecting appropriate candidates for nonoperative therapies by excluding patients with submucosal cancers and those with malignant lymph nodes. EUS may also help in the selection of patients for EMR, either alone or in combination with ablative therapies.


14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma.
Deletions of the long arm of chromosome 14 [del(14q)] are rare but recurrently observed in mature B-cell neoplasms, particularly in chronic lymphocytic leukemia (CLL). To further characterize this aberration, we studied 81 cases with del(14q): 54 of CLL and 27 of small lymphocytic lymphoma (SLL), the largest reported series to date. Using karyotype and fluorescence in situ hybridization (FISH), the most frequent additional abnormality was trisomy 12 (tri12), observed in 28/79 (35%) cases, followed by del13q14 (12/79, 15%), delTP53 (11/80, 14%) delATM (5/79, 6%), and del6q21 (3/76, 4%). IGHV genes were unmutated in 41/53 (77%) patients, with a high frequency of IGHV1-69 (21/52, 40%). NOTCH1 gene was mutated in 14/45 (31%) patients. There was no significant difference in cytogenetic and molecular abnormalities between CLL and SLL. Investigations using FISH and SNP-array demonstrated the heterogeneous size of the 14q deletions. However, a group with the same del(14)(q24.1q32.33) was identified in 48% of cases. In this group, tri12 (P = 0.004) and NOTCH1 mutations (P = 0.02) were significantly more frequent than in the other patients. In CLL patients with del(14q), median treatment-free survival (TFS) was 27 months. In conclusion, del(14q) is associated with tri12 and with pejorative prognostic factors: unmutated IGHV genes (with over-representation of the IGHV1-69 repertoire), NOTCH1 mutations, and a short TFS.


Searching for Correlations Between the Development of Neurodegenerative Hallmarks: Targeting Huntingtin as a Contributing Factor.
This paper aims to study four general hallmarks of neurodegeneration and the correlations between them, with emphasis on the huntingtin (htt) interactions contributing to their prevention or promotion in its wild-type and mutated forms. Most of the neurodegenerative diseases share same or similar cell dysfunctions and huntingtin seems to associate in an polyglutamine-length dependent manner with components of the mechanisms that can go impaired. Therefore, the protein is proposed as contributing factor to the development of selective neurodegeneration.


Digoxin enhances the pressor response to aldosterone administration in conscious sheep.
1. This study examined the hypothesis that inhibition of Na,K ATPase with digoxin would enhance the pressor response to aldosterone infusion in conscious sheep. 2. While intravenous infusion of digoxin (10 micrograms/kg per day for 5 days) had no effect on blood pressure and aldosterone infusion (6 micrograms/kg per day for 5 days) increased blood pressure by 7 mmHg, combined infusion of digoxin and aldosterone increased blood pressure by 17 mmHg. 3. The metabolic effects of the combined digoxin and aldosterone infusion were similar to those for aldosterone alone, suggesting that digoxin did not enhance the mineralocorticoid action of aldosterone. 4. The results of this study suggest that changes in Na influx (aldosterone-dependent) and efflux (digoxin-dependent) are important in the genesis of aldosterone-induced hypertension.


Intensive care unit tracheostomy: a snapshot of UK practice.
Tracheostomy is a common procedure in intensive care patient management. The aim of this study was to capture the practice of tracheostomy in Intensive Care Units in the United Kingdom. A postal survey was sent to the lead clinicians of 228 general intensive care units (ICUs) throughout the United Kingdom excluding specialist units. We aimed to identify the current practice of tracheostomy, including timing of insertion, equipment used and post-operative care and follow-up. A response rate of 86.84% was achieved. Percutaneous tracheostomy continues to be favoured over surgical tracheostomy with less than 8% of ICUs opting for surgical tracheostomies > 50% of the time. 89% of units required only 2 operators to perform the technique and single stage dilatation is the technique of choice in 83% of units. The Ciaglia technique, which was strongly favoured less than a decade ago, is currently practiced in less than 5% of ICUs. Bronchoscopic guidance is an important adjunct to the technique of percutaneous tracheostomy with 80% of units using it routinely. Follow-up care of patients remains poor with 59% of ICUs not having routine follow-up once the patient has left the unit. The practice of percutaneous tracheostomy remains the preferred technique within the UK. There seems to be a growing preference for single stage dilatational techniques. Timing of tracheostomy remains variable despite evidence to suggest benefit from an earlier procedure. Follow-up of tracheostomised patients after discharge from ICU is still low, which may mean significant morbidity from the procedure is being missed.


Adenosine uptake, transport, and metabolism in human erythrocytes.
Using rapid kinetic techniques, we have determined the kinetics of zero-trans influx and equilibrium exchange of adenosine, and its uptake and in situ phosphorylation at 25 degrees C in human erythrocytes which were pretreated with 2'-deoxycoformycin to inhibit deamination of adenosine. Both the Km and Vmax for adenosine transport were about 300 times higher than those for the in situ phosphorylation of adenosine (Km about 0.2 microM), so that the first order rate constants for both processes were about the same. In contrast, the first order rate constant for adenosine deamination by untreated, intact cells was about 20% of that of adenosine transport or phosphorylation. These kinetic properties of the various steps, in combination with substrate inhibition of adenosine phosphorylation above 1 microM adenosine, assure that, at extracellular concentrations of physiological relevance (less than 1 microM), adenosine is very rapidly and efficiently salvaged by the erythrocytes and converted to ATP, whereas at extracellular concentrations of 10 microM or higher, practically all adenosine transported into the cells is deaminated. When the concentration of adenosine was 0.1 microM, a 10% (v/v) suspension of erythrocytes depleted the extracellular fluid of adenosine within 1 min of incubation at 25 degrees C.


LysM-containing proteins function in the resistance of Litopenaeus vannamei against Vibrio parahaemolyticus infection.
Lysin motif (LysM) is a functional domain that can bind to peptidoglycans, chitin and their derivatives. The LysM-containing proteins participate in multiple biological processes, such as the hydrolysis of bacterial cell walls and the perception of PAMPs in plants and high animals. In the present study, two genes encoding LysM-containing proteins, designated as LvLysM1 and LvLysM2, were identified in the Pacific white shrimp, Litopenaeus vannamei, and their functions during Vibrio infection were analyzed. The open-reading frame (ORF) of LvLysM1 was 795 bp, only encoding a LysM domain at the N-terminal region. The ORF of LvLysM2 was 834 bp, encoding a LysM domain at the central region and a transmembrane region at the C-terminal region. Both LvLysM1 and LvLysM2 were widely transcribed in all tested shrimp tissues. Enzyme-linked immunosorbent assay (ELISA) showed that the recombinant protein of LvLysM2 could bind to different bacterial polysaccharides, while LvLysM1 showed no direct binding activity. The transcripts of LvLysMs in gills increased significantly after infection with Vibrio parahaemolyticus. When LvLysM1 or LvLysM2 was knocked down by dsRNA, the mortality of shrimp was significantly increased after infection with Vibrio parahaemolyticus. Interestingly, some SNPs existed in these two genes were apparently correlated with the VpAHPND resistance of shrimp. These results suggested that LvLysM1 and LvLysM2 might contribute to the disease resistance of shrimp. The data provide new knowledge about the function of LysM-containing proteins in shrimp and potential genetic markers for disease resistance breeding.


Effect of radical amplified photopolymerization (RAP) in resin-based composites.
The objective of this study was to evaluate the effect of irradiation time and specimens thickness on the polymerization kinetic and variation in micro-mechanical properties of two commercial resin-based composites (RBCs) based on radical amplified photopolymerization (RAP) technology™, and to compare them with four camphorquinone (CQ)/amine-based RBCs. The materials were analysed by assessing the polymerization kinetic and the degree of cure (DC) at 0.1 mm and 2 mm depth during 5 minutes after photoinitiation, after curing for 10 s, 20 s and 40 s (Elipar Freelight2). The variation in micro-mechanical properties (Vickers hardness (HV), indentation modulus (E), and depth of cure (DOC)) was assessed in 100 μm steps on 6-mm-high specimens irradiated as above and stored in the water for 24 h at 37 °C. The results were statistically compared using one-way ANOVA with Tukey HSD post hoc test (α = 0.05) and a general linear model. The parameter material exerted the strongest effect on DC (partial eta-squared η p (2) = 0.83), followed by irradiation time (η p (2) = 0.27), and depth (η p (2) = 0.09). The polymerization kinetic, well described by an exponential sum function, showed in all materials a faster decrease in carbon-carbon double bonds at 0.1 mm than at 2 mm depth. The materials based on RAP achieved the highest DC values and a faster polymerization at both depths. The irradiation time exerted the strongest effect on the mechanical properties (DOC, η p (2) = 0.96; HV, η p (2) = 0.89; E, η p (2) = 0.86), followed by depth (HV, η p (2) = 0.63; E, η p (2) = 0.54) and material (HV, η p (2) = 0.40; E, η p (2) = 0.67). At the most favorable curing conditions (40 s, surface), the mechanical properties of the analyzed materials varied between 11.38 (0.80) GPa in Estelite® Sigma Quick and 20.80 (1.42) GPa in Estelite® Posterior for E, and between 74.33 (3.56) N/mm(2) in Tetric EvoCeram® and 120.71 (6.24) N/mm(2) in Estelite® Posterior for HV. RAP-initiated material demonstrated a higher increase in DOC with prolonged irradiation time than the analyzed CQ/amine based materials. An irradiation time of 20 s is also recommended for RAP-initiated RBCs.


Standardized healthcare pathway in intrauterine growth restriction and minimum evidence-based care.
Fetal growth restricted fetuses are less likely to receive evidence-based care; a previous work demonstrated an improvement in neonatal prognosis when fetuses with intrauterine growth restriction (IUGR) received minimum evidence based-care. The objective of the study was to evaluate the impact of a standardized healthcare pathway on the implementation of the recommended clinical practice in the antenatal management of IUGR fetuses, in comparison to a traditional pathway. The quality of the implementation of practice has been defined whether or not minimum evidence-based care (MEC), defined according to the recommendations of the French college of gynecologists and obstetricians (CNGOF), has been implemented. From a historical cohort of 31,052 children, born at the Femme Mère Enfant Hospital (Lyon, France) between January 1st, 2011 and December 31st, 2017, we selected the population of IUGR fetuses. We compared the rate of MEC between the IUGR fetuses followed-up in the traditional healthcare pathway versus the IUGR fetuses followed-up in a standardized healthcare pathway between 2015 and 2017. A total of 245 IUGR were tracked between 2015 and 2017. Over this period, 120 fetuses were followed within the traditional pathway and 125 within the IUGR pathway. The standardized pathway resulted in a higher rate of MEC (86,4%) when compared to IUGR fetuses followed-up in the traditional pathway (27,5% (OR* 20 (95 % CI 10.0-39.7). Among early-onset IUGR: 31 % received MEC in the traditional pathway versus 83 % in the standardized pathway (p<0.001). Among late-onset IUGR: 22 % received MEC in the traditional pathway versus 92 % in the standardized pathway (p<0.001). The provided care in the standardized pathway resulted in an increase of complete antenatal corticosteroid therapy (92,8 %) when compared to the traditional pathway (50.0 %; p<0.001) and a reduction of the rate of caesarean sections before labor for non-reassuring fetal heart rate (15 %) when compared to the traditional pathway (41.3 % p=0.007). The standardized pathway improves the implementation of the local recommendations in the management of early- and late-onset IUGR. This study is the first to suggest a standardized care pathway in prenatal medicine. A medico-economic study could estimate the health care savings that such a pathway would provide by allowing a medical management in accordance with the recommendations.


Recovery of cortical acetylcholine output after ganglioside treatment in rats with lesion of the nucleus basalis.
The changes in acetylcholine release from the cerebral cortex induced by a unilateral electrolytic lesion of the nucleus basalis and by a treatment with GM1 monosialoganglioside (30 mg/kg i.p. for 20 days) were investigated. Acetylcholine release was measured using the cortical cup technique in rats transected at midpontine level. In the lesioned rats treated with saline an ipsilateral 38% decrease in acetylcholine release was observed. GM1 treatment prevented the decrease and brought about a 30% contralateral increase. These results indicate that GM1 induces a functional recovery of the cholinergic neurons ascending to the cortex.


Nicotine promotes rooting in leaf explants of in vitro raised seedlings of tomato, Lycopersicon esculentum Miller var. Pusa Ruby.
Nicotine promotes rooting in leaf explants of tomato (Lycopersicon esculentum Miller var. Pusa Ruby). Nicotine at 10(-9) to 10(-3) M concentrations was added to the MS basal medium. The optimum response (three-fold increase in rooting) was obtained at 10(-7) M nicotine-enriched MS medium. At the same level i.e. 10(-7) M Nicotine induced dramatic increase (11-fold) in the number of secondary roots per root. We have shown earlier that exogenous acetylcholine induces a similar response in tomato leaves. Since nicotine is an agonist of one of the two acetylcholine receptors in animals, its ability to simulate ACh action in a plant system suggests the presence of the same molecular mechanism operative in both, animal and plant cells.


Intellectual disability: dendritic anomalies and emerging genetic perspectives.
Intellectual disability (ID) corresponds to several neurodevelopmental disorders of heterogeneous origin in which cognitive deficits are commonly associated with abnormalities of dendrites and dendritic spines. These histological changes in the brain serve as a proxy for underlying deficits in neuronal network connectivity, mostly a result of genetic factors. Historically, chromosomal abnormalities have been reported by conventional karyotyping, targeted fluorescence in situ hybridization (FISH), and chromosomal microarray analysis. More recently, cytogenomic mapping, whole-exome sequencing, and bioinformatic mining have led to the identification of novel candidate genes, including genes involved in neuritogenesis, dendrite maintenance, and synaptic plasticity. Greater understanding of the roles of these putative ID genes and their functional interactions might boost investigations into determining the plausible link between cellular and behavioral alterations as well as the mechanisms contributing to the cognitive impairment observed in ID. Genetic data combined with histological abnormalities, clinical presentation, and transgenic animal models provide support for the primacy of dysregulation in dendrite structure and function as the basis for the cognitive deficits observed in ID. In this review, we highlight the importance of dendrite pathophysiology in the etiologies of four prototypical ID syndromes, namely Down Syndrome (DS), Rett Syndrome (RTT), Digeorge Syndrome (DGS) and Fragile X Syndrome (FXS). Clinical characteristics of ID have also been reported in individuals with deletions in the long arm of chromosome 10 (the q26.2/q26.3), a region containing the gene for the collapsin response mediator protein 3 (CRMP3), also known as dihydropyrimidinase-related protein-4 (DRP-4, DPYSL4), which is involved in dendritogenesis. Following a discussion of clinical and genetic findings in these syndromes and their preclinical animal models, we lionize CRMP3/DPYSL4 as a novel candidate gene for ID that may be ripe for therapeutic intervention.


Altered global modular organization of intrinsic functional connectivity in autism arises from atypical node-level processing.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by restricted interests and repetitive behaviors as well as social-communication deficits. These traits are associated with atypicality of functional brain networks. Modular organization in the brain plays a crucial role in network stability and adaptability for neurodevelopment. Previous neuroimaging research demonstrates discrepancies in studies of functional brain modular organization in ASD. These discrepancies result from the examination of mixed age groups. Furthermore, recent findings suggest that while much attention has been given to deriving atlases and measuring the connections between nodes, within node information may also be crucial in determining altered modular organization in ASD compared with typical development (TD). However, altered modular organization originating from systematic nodal changes are yet to be explored in younger children with ASD. Here, we used graph-theoretical measures to fill this knowledge gap. To this end, we utilized multicenter resting-state fMRI data collected from 5 to 10-year-old children-34 ASD and 40 TD obtained from the Autism Brain Image Data Exchange (ABIDE) I and II. We demonstrate that alterations in topological roles and modular cohesiveness are the two key properties of brain regions anchored in default mode, sensorimotor, and salience networks, and primarily relate to social and sensory deficits in children with ASD. These results demonstrate that atypical global network organization in children with ASD arises from nodal role changes, and contribute to the growing body of literature suggesting that there is interesting information within nodes providing critical markers of functional brain networks in autistic children.


Grid-enhanced X-ray coded aperture microscopy with polycapillary optics.
Polycapillary devices focus X-rays by means of multiple reflections of X-rays in arrays of bent glass capillaries. The size of the focal spot (typically 10-100 μm) limits the resolution of scanning, absorption and phase-contrast X-ray imaging using these devices. At the expense of a moderate resolution, polycapillary elements provide high intensity and are frequently used for X-ray micro-imaging with both synchrotrons and X-ray tubes. Recent studies have shown that the internal microstructure of such an optics can be used as a coded aperture that encodes high-resolution information about objects located inside the focal spot. However, further improvements to this variant of X-ray microscopy will require the challenging fabrication of tailored devices with a well-defined capillary microstructure. Here, we show that submicron coded aperture microscopy can be realized using a periodic grid that is placed at the output surface of a polycapillary optics. Grid-enhanced X-ray coded aperture microscopy with polycapillary optics does not rely on the specific microstructure of the optics but rather takes advantage only of its focusing properties. Hence, submicron X-ray imaging can be realized with standard polycapillary devices and existing set-ups for micro X-ray fluorescence spectroscopy.


Inhibition of the interaction of G protein G(o) with calcium channels by the calcium channel beta-subunit in rat neurones.
1. The beta-subunit has marked effects on the biophysical and pharmacological properties of voltage-dependent calcium channels. In the present study we examined the ability of the GABAB agonist (-) -baclofen to inhibit calcium channel currents in cultured rat dorsal root ganglion neurones following depletion of beta-subunit immunoreactivity, 108-116 h after microinjection of a beta-subunit antisense oligonucleotide. 2.We observed that, although the calcium channel current was markedly reduced in amplitude following beta-subunit depletion, the residual current (comprising both N- and L-type calcium channel currents) showed an enhanced response to application of (-) -baclofen. Therefore, it is possible that there is normally competition between activated G protein G(o) and the calcium channel beta-subunit for binding to the calcium channel alpha 1-subunit; and this competition shifts in favour of the binding of activated G(o) following depletion of the beta-subunit, resulting in increased inhibition. 3. This hypothesis is supported by evidence that an antibody against the calcium channel beta-subunit completely abolishes stimulation of the GTPase activity of G(o) by the dihydropyridine agonist S-(-) -Bay K 8644 in brain membranes. This stimulation of GTPase is thought to result from an interaction of G(o) alpha-subunit (G alpha o) with its calcium channel effector which may operate as a GTPase-activating protein. 4. These data suggest that the calcium channel beta-subunit when complexed with the beta 1-subunit normally inhibits its association with activated G(o). It may function as a GTPase-activating protein to reduce the ability of activated G(o) to associate with the calcium channel, and thus limit the efficacy of agonists such as (-) -baclofen.


Refining diagnosis of Parkinson's disease with deep learning-based interpretation of dopamine transporter imaging.
Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies.


Neuroprotection by Mucuna pruriens in Neurodegenerative Diseases.
The medicinal plant Mucuna pruriens (Fabaceae) is widely known for its anti-oxidative and anti-inflammatory properties. It is a well-established drug in Ayurveda and has been widely used for the treatment of neurological disorders and male infertility for ages. The seeds of the plant have potent medicinal value and its extract has been tested in different models of neurodegenerative diseases, especially Parkinson's disease (PD). Apart from PD, Mucuna pruriens is now being studied in models of other nervous systems disorders such as Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS) and stroke because of its neuroprotective importance. This review briefly discusses the pathogenesis of PD, AD, ALS and stroke. It aims to summarize the medicinal importance of Mucuna pruriens in treatment of these diseases, and put forward the potential targets where Mucuna pruriens can act for therapeutic interventions. In this review, the effect of Mucuna pruriens on ameliorating the neurodegeneration evident in PD, AD, ALS and stroke is briefly discussed. The potential targets for neuroprotection by the plant are delineated, which can be studied further to validate the hypothesis regarding the use of Mucuna pruriens for the treatment of these diseases.


Adult polio-like syndrome following Enterovirus 70 conjunctivitis (natural history of the disease).
During the Indian EV 70 conjunctivitis epidemic in 1981, 79 patients with neurological complications were evaluated by clinical, electrophysiological, histopathological and virological studies. The disease was heralded by an attack of conjunctivitis and was followed, after a variable latent period, by a pre-paralytic, paralytic, and post-paralytic stage of slow recovery. The above events occurred in an orderly sequence. The paralysis affected the cranial nerves, limbs or both. The clinical course closely simulated poliomyelitis, without any evidence of radiculopathy or myelopathy. Cranial nerve palsies were seen in approximately half of the patients. The electrophysiological and histologicl studies pointed towards the affection of anterior horn cells. The raised neutralizing antibody titres to Enterovirus 70, confirmed the aetiology of the disease. On the available data, we believe that this nosological entity should be considered under the general title of "polio-like syndrome" following EV 70 conjunctivitis. On account of two epidemics in 1971 and 1981 with unfavourable prognosis and high resultant disability, and because of lack of specific therapy, it has become imperative to develop, as a top priority, a vaccine for immunization.


Valvular surgery in Western Australia: a 15-year review.
Between 1970 and 1984, 1138 patients underwent the insertion of 1300 prosthetic heart valves in Western Australia; 56% received an aortic-valve replacement; 34% received a mitral-valve replacement and 10% had more than one valve replaced. Mechanical valves were used in 93% of patients before 1977, in 20% of patients between 1978 and 1982 and in 70% of patients from 1983 onwards. The 30-day mortality was 18% before 1973 and has been below 6% since 1974. The over-all, 15-year actuarial survival rate was 67%; this was not affected by age, sex, race, valvular position or the type of prosthesis. Both the 30-day mortality and 15-year survival rates were significantly worse in patients who underwent multiple valvular replacements (13% and 54%, respectively) or reoperation (16% and 58%, respectively). The major causes of death were cardiac failure and myocardial infarction (65%); endocarditis (13%); cancer (6%); and thromboembolism and bleeding (6%). The hazard rate for reoperation was low and fairly constant in patients with mechanical valves, but increased markedly after four years in patients with tissue valves. Although our experience so far suggests that survival rates are not affected by the choice of prosthesis, this may not be so in the future, as more patients with tissue valves undergo reoperation and so become exposed to an increased risk of mortality.


Clinical observation and mechanism study on treatment of senile dementia with Naohuandan.
To observe the therapeutic effect and mechanism of Naohuandan (NHD) in treating senile dementia (SD). Clinical study: Fifty-eight patients with SD, whose diagnosis conforms to the Diagnostic Standard of DSM-IV issued by American Association of Psychiatry, were enrolled and randomly assigned into two groups. The 30 patients in the treated group were treated with NHD, 4 capsules each time, 3 times daily. The 28 patients in the control group were treated with Piracetam, 1.6 g each time, 3 times daily. The therapeutic course for both groups was 3 months. The therapeutic efficacy was estimated and compared by comprehensive scores of memory and cognition, scores of Mini-mental State Examination (MMSE) and Activities of Daily Living (ADL). Experimental study: Rats were divided into the control group, the model group and the high-dosage and low-dosage NHD treated groups. The protective effect of NHD on the per-oxidative damage of hippocampal neurons in beta-amyloid protein induced SD model was observed and the related criteria were determined. Clinical study showed that both NHD and Piracetam could improve the clinical symptoms of patients, the two medicines showing insignificant difference in total effective rate. But NHD was better in elevating MMSE score and lowering ADL score in patients than Piracetam (P < 0.05 and P < 0.01). Experimental study showed that (1) 24 and 72 hrs after modeling, the activity of SOD and GSH were lower and the level of MDA higher in the model group than those in the control group (P < 0.05 or P < 0.01). Compared with the model group at the corresponding time points, in the high-dosage NHD group, SOD and GSH were higher, MDA was lower (P < 0.05 or P < 0.01); but in the low-dosage NHD group, SOD at the 72nd hr was higher (P < 0.05) and MDA at 24th and 72nd hrs was lower (P < 0.01). And most of the criteria in the high-dosage NHD group was improved better than that in the low-dosage NHD group. (2) The survival rates of neurons in various groups were not different significantly (P > 0.05) 24 hrs after modeling, but that in the high-dosage NHD group was significantly higher than that in the model group (P < 0.01) and in the low-dosage NHD group 72 hrs after modeling (P < 0.05). NHD is an effective Chinese herbal preparation for treatment of SD, and its mechanism is related with its inhibition on peroxidative injury and protection on neurons.