Status epilepticus: the interaction of epilepsy and acute brain disease.
We identified 217 patients with status epilepticus (SE), including all seizure types from all etiologies, over a 3-year period. There was a significant interaction between organic brain disease and a history of epilepsy in the development of SE. The majority of patients (59%) had no history of epilepsy. These patients were more likely to have acute precipitants associated with SE and less likely to have had prior brain disease. They were older, were more likely to have generalized convulsive seizures, and had a high proportionate mortality. Among the 88 patients with a history of epilepsy, a higher proportion had prior brain insults, but fewer had acute precipitants. These patients were younger and their mortality was low, but they often had recurrent SE before and after the identified episode. Significant acute or prior brain disease is an important factor in the development of SE, even in patients with a history of epilepsy.


Locomotor training in people with spinal cord injury: is this exercise?
Locomotor training holds tremendous appeal to people with spinal cord injury who are wheelchair dependent, as the reacquisition of gait remains one of the most coveted goals in this population. For the last few decades this type of training has remained primarily in the clinical environment, as it requires the use of expensive treadmills with bodyweight support or complex overhead suspension tracks to facilitate overground walking. The development of powered exoskeletons has taken locomotor training out of the clinic, both improving accessibility and providing a potential option for community ambulation in people with lower limb paralysis. A question that has yet to be answered, however, is whether or not locomotor training offers a sufficiently intense stimulus to induce improvements in fitness or health. As inactivity-related secondary health complications are a major source of morbidity and mortality in people with SCI, it would be important to characterize the potential of locomotor training to not only improve functional walking ability, but also improve health-related fitness. This narrative review will summarize the key literature in this area to determine whether locomotor training challenges the cardiovascular, muscular or metabolic systems enough to be considered a viable form of exercise.


Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma diagnosed by fluorodeoxyglucose positron emission tomography/computer tomography and laparoscopy.
Human herpes virus 8-unrelated primary effusion lymphoma (PEL)-like lymphoma is a rare type of large B cell lymphoma. This report presents the case of a male with abdominal pain and distension who was found to have massive ascites and enhanced peritoneum, mesenterium and greater omentum on enhanced computer tomography (CT) scan with negative ascitic cytology. The diagnosis of PEL-like lymphoma was established by fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and laparoscopic biopsy of the greater omentum. To the best of our knowledge, this is only the second case report to describe FDG PET/CT presentations of PEL-like lymphoma, and the first case report to use laparoscopy for diagnosis.


Integrating omics datasets with the OmicsPLS package.
With the exponential growth in available biomedical data, there is a need for data integration methods that can extract information about relationships between the data sets. However, these data sets might have very different characteristics. For interpretable results, data-specific variation needs to be quantified. For this task, Two-way Orthogonal Partial Least Squares (O2PLS) has been proposed. To facilitate application and development of the methodology, free and open-source software is required. However, this is not the case with O2PLS. We introduce OmicsPLS, an open-source implementation of the O2PLS method in R. It can handle both low- and high-dimensional datasets efficiently. Generic methods for inspecting and visualizing results are implemented. Both a standard and faster alternative cross-validation methods are available to determine the number of components. A simulation study shows good performance of OmicsPLS compared to alternatives, in terms of accuracy and CPU runtime. We demonstrate OmicsPLS by integrating genetic and glycomic data. We propose the OmicsPLS R package: a free and open-source implementation of O2PLS for statistical data integration. OmicsPLS is available at https://cran.r-project.org/package=OmicsPLS and can be installed in R via install.packages("OmicsPLS").


Combining facelift with SmartLipo 1064-nm system, technique overview and retrospective analysis of 56 patients.
This study reviews novel approach using SmartLipo 1064-nm system with short-flap facelift treatments focusing on 3 specific facial areas and specific target treatment endpoints. A retrospective review of 56 patients undergoing combined treatment is performed. Fifty-six consecutive patients undergoing SmartLipo with facelift were reviewed using pre-operative photographs as a baseline. The reviewed post-operative photographs were taken at 6 weeks and 6 months. Photographic review was performed by an independent board of physicians on the following scales: Wrinkle Severity Rating Scale, the Global Aesthetic Improvement Scale Assessment, and the Cervicomental Scale. The 53 primary and 3 revision facelift patients included in this study had a mean body mass index of 24.7, and a mean age of 65 years. These patients received an average of 5,050 joules of energy between three treatment areas which was delivered at 12 Watts and 40 Hz. No major complications were reported, including hematoma and dyspigmentation, even in combined cases with surface lasers. The 6 week and 6 month post-operative photographs showed marked improvements in outcomes in each of the reviewed scales according to the independent board of physicians. The SmartLipo 1064 nm is a safe and effective platform to combine with facelifts.


[Postoperative recurrence of varicosities at the level of the popliteal fossa. Anatomic data guiding the ultrasonographic exploration and surgical sequelae].
The results of surgery of the short saphenous vein are less consistent than those of the long saphenous vein. The difference has been clarified by anatomo-physio-pathological studies which, as a complement to clinical examination, first used the different phlebography techniques and now benefit from pulsed colour echodoppler. They have shown that, in varicose veins considered to be of the short saphenous system, incompetence at its termination, with its anatomical variations, does not account for all the findings. Thus, imaging and the findings at surgery, have revealed a genuine venous complex in the popliteal fossa situated in four areas: in the sapheno-aponeurotic area with a variable point of termination of the short saphenous vein and important tributaries along its convexity; in the area of the medial head of the gastocnemius muscle with a voluminous trunk formed by the medial gastrocnemial veins which may run towards the termination of the short saphenous vein or even drain into its concavity; in the deep plane of the popliteal vein, which is sometimes double; in the short saphenous network with its very variable vein in the popliteal fossa and the lateral gastrocnemial veins. In practice, this classification helps to identify congenital reduplications, abnormal of aberrant veins and to perform planned surgery aimed at preventing postoperative recurrences. This is so because the latter are due, albeit less frequently than at the saphenofemoral junction, to a "new vein" which is in fact simply a missed tributary. Recurrences are mainly associated with : a duplication of the terminal part of the vein which has been missed; a short saphenous stump fed by a trunk from the medial gastrocnemial veins which has a termination into the popliteal vein common with the short saphenous vein; incompetent large medial gastrocnemial veins draining separately; an incompetent popliteal fossa perforator. The last two occur not uncommonly together and it has also been noted that failure to strip the short saphenous trunk increases the likelihood of postoperative recurrences. Repeat surgery is indicated in the presence of recurrences when there are important sources of reflux which are fully identified and precisely located by imaging, which is essential to prevent recurrent failure.


Taxonomic changes in Synanthedonini from Madagascar, with description of two new genera and species (Lepidoptera: Sesiidae).
A checklist of the Synanthedonini of Madagascar is presented. The following taxonomic changes are suggested: Malgassesia pauliani Viette, 1955 syn. nov. is a junior synonym of Rodolphia hombergi Le Cerf, 1911a; Malgassesia biedermanni Viette, 1982 syn. nov. is a junior synonym of Malgassesia rufescens Le Cerf, 1922; Epitarsipus Le Cerf, 1922 stat. rev. is resurrected from the synonymy with Malgassesia Le Cerf, 1922, the earlier consisting of the single species E. rufithorax Le Cerf, 1922 comb. rev. The taxonomic position of three species, which were originally described in Chamaesphecia Spuler, 1910 and later excluded from this genus as "incertae sedis", remains unclear. These species are here transferred to Malgassesia: M. andrianony Viette, 1982 comb. nov.; M. lemur Le Cerf, 1957 comb. nov.; and M. ferdinandi nom. nov., a replacement name for Ch. seyrigi Le Cerf, 1957. Two new species and genera of Synanthedonini, Cinctosesia polistiformis and Nesosphecia mystica gen. nov. et sp. nov., are described from a submontane rainforest in the vicinity of Andasibe in the East of Madagascar.


Reciprocal associations between positive emotions and resilience predict flourishing among adolescents.
The broaden and build theory of positive emotions maintains that positive emotions serve to broaden individuals' thoughts and behaviours, resulting in the accrual of resources (e.g. resilience) that catalyze upward spirals of well-being. However, there is a relative dearth of research examining the upward spiral hypothesis in the context of adolescence. Adolescents (n = 4064) in participating Canadian high schools were surveyed annually for three years as part of the COMPASS study. Reciprocal associations between positive emotions and resilience were examined as predictors of flourishing. Adolescents who experienced positive emotions more frequently than usual reported higher levels of resilience one year later. Similarly, adolescents who had higher levels of resilience than usual reported more positive emotions the following year. Higher than usual levels of resilience and positive emotions positively predicted flourishing. Positive emotions result in a cascade of beneficial outcomes including increased resilience and enhanced well-being, catalyzing an upward spiral towards flourishing. Opportunities to enhance positive emotions early on in adolescence may help build resources that can set students on the path towards increased well-being.


[Perioperative changes of coagulation functions in the local advanced liver cancer patients receiving liver transplantation].
Liver transplantation is widely accepted as an effective therapy of hepatoma. Perioperative dynamic observation of coagulation function is important for graft-receivers. This study was to explore perioperative changes of coagulation functions in the local advanced liver cancer patients who received liver transplantation. Clinical data of 31 local advanced liver cancer patients, underwent liver transplantation from Sep. 2003 to Jan. 2007, were analyzed. Platelet (PLT) counting, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib) and international normalized ratio (INR) before operation, at anhepatic phase and the first week after operation were analyzed to evaluate congulation function. The coagulation functions of most patients were normal before operation. The six parameters varied significantly at anhepatic phase and on most days of the first week after operation when compared with the preoperative levels (P<0.05). The elevation of PT, APTT, TT and INR and the decrease of Fib and PLT were more apparent at anhepatic phase when compared with the preoperative levels [PT: (19.51+/-3.78) s vs. (14.16+/-1.46) sû APTT: (77.01+/-30.51) s vs. (40.19+/-4.11) sû TT: (27.50+/-15.10) s vs. (19.46+/-3.05) sû INR: 1.61+/-0.37 vs. 1.11+/-0.16û Fib: (1.73+/-0.70) g/L vs. (3.38+/-1.00) g/Lû PLT: (108+/-60)x10(9)/L vs. (184+/-108)x10(9)/L, all P<0.01]. In the first week after operation, the elevated PT, APTT, TT and INR levels decreased gradually, APTT was even lower than the preoperative level [(32.05+/-6.50) s vs. (40.19+/-4.11) s, P<0.01]. These changes appeared usually on 1-2 days after operation. Decreased PLT and Fib regained slowly at the first week after operation when compared with the preoperative levels [Fib: (2.13+/-0.53) g/L vs. (3.38+/-1.00) g/L, P<0.01û PLT: (145+/-90)x10(9)/L vs. 184+/-108]x10(9)/L, P<0.05], but the values were normal. According to stratification analysis, the hypocoagulability was more obvious in the patients with moderate or severe cirrhosis and those with Child-Pugh B level than in their counterparts. The coagulation functions of local advanced liver cancer patients shift from hypocoagulatory to hypercoagulatory or normal in perioperative period, therefore, prevention of bleeding should be focused on at anhepatic phase and on 1-2 days after operation while prevention of thrombosis should be focused on after the first week after operation. The degree of liver cirrhosis and Child-Pugh level could help to evaluate postoperative coagulation disorder.


Splanchnic nerve neurolysis via the transdiscal approach under fluoroscopic guidance: a retrospective study.
Neurolytic celiac plexus block (NCPB) is a typical treatment for severe epigastric cancer pain, but the therapeutic effect is often affected by the variation of local anatomical structures induced by the tumor. Greater and lesser splanchnic nerve neurolysis (SNN) had similar effects to the NCPB, and was recently performed with a paravertebral approach under the image guidance, or with the transdiscal approach under the guidance of computed tomography. This study observed the feasibility and safety of SNN via a transdiscal approach under fluoroscopic guidance. The follow-up records of 34 patients with epigastric cancer pain who underwent the splanchnic nerve block via the T11-12 transdiscal approach under fluoroscopic guidance were investigated retrospectively. The numerical rating scale (NRS), the patient satisfaction scale (PSS) and quality of life (QOL) of the patient, the dose of morphine consumed, and the occurrence and severity of adverse events were recorded preoperatively and 1 day, 1 week, 1 month, and 2 months after surgery. Compared with the preoperative scores, the NRS scores and daily morphine consumption decreased and the QOL and PSS scores increased at each postoperative time point (P < 0.001). No patients experienced serious complications. SNN via the transdiscal approach under flouroscopic guidance was an effective, safe, and easy operation for epigastric cancer pain, with fewer complications.


The role of ultrafast structural dynamics with physical and chemical changes in polydimethylsiloxane thin films by two-dimensional IR spectroscopy.
Fourier transform infrared (FTIR) and two-dimensional IR (2D-IR) spectroscopies were applied to polydimethylsiloxane (PDMS) cross-linked elastomer films. The vibrational probe for the systems studied was a silicon hydride mode that was covalently bound to the polymer chains. The structure and dynamics reported by this mode were measured in response to a wide range of chemical and physical perturbations, including elevated curing temperature, increased curing agent concentration, mechanical compression, and cooling to near the glass transition temperature. The FTIR spectra were found to be relatively insensitive to all of these perturbations, and 2D-IR spectroscopy revealed that this was due to the overwhelming influence of heterogeneity on the spectral line shape. Surprisingly, the deconvoluted spectral line shapes showed that there were only slight differences in the heterogeneous and homogeneous dynamics even with the drastic macroscopic changes occurring in different systems. In the context of modeling polymer behavior, the results confirm that dynamics on the ultrafast time scale need not be included to properly model PDMS elasticity.


Breathing pattern and lung volumes during exercise.
The interrelationships of ventilation (V), tidal volume (VT), inspiratory (T1), expiratory (TE) and total breath (Ttot) durations, mean inspiratory (VT/TI) and expiratory (VT/TE) flows, and lung volumes were studied in normal subjects at rest and during exercise on a cycle ergometer. The ergometric load was increased by 10 W every minute, from zero W to 200 W. The TI/Ttot ratio increased with V in the range 15 to 60 1 X min-1, indicating that with increasing V the rate of increase of VT/TI decreased whereas that of VT/TE increased. Possible mechanisms responsible for the difference in behaviour of VT/TI and VT/TE are discussed. The VT-TI and VT-TE relationships both displayed three ranges with breakpoints at tidal volumes of about 1.4 and 2.4 1. The relations of TI and TE to end-inspiratory volume were approximately linear over the entire VT range studied, whereas the relations of TI and TE to end-expiratory volume showed three ranges with different characteristics. We conclude that the termination of inspiration during cycle exercise is dependent on volume-related afferent feedback from the lungs and/or chest walls, not only in the high but also in the low volume range.


Surgery for ischaemic heart disease in the patient aged 40 and younger.
A group of 128 patients with a mean age of 36 years, operated on between 1971 and 1986, were followed up over a period of up to 15 years. Their five-year survival was 90%, and 10-year survival 60%. The main cause of death was progression of ischaemic heart disease. The only factor affecting long-term survival is resection of a left ventricular aneurysm: patients who undergo this procedure exhibit a shorter survival (p less than 0.05). The number of vessels involved, performance of complete or incomplete revascularization, or ejection fraction data had no effect on patient survival. To improve the results of 10-year and longer follow-up, the patient must comply with the principles of secondary prevention of atherosclerosis, and the internal mammary artery should be used for reconstruction.


Aggressive male APP23 mice modeling behavioral alterations in dementia.
In addition to cognitive deterioration, Alzheimer's disease patients exhibit behavioral and psychological signs and symptoms of dementia. Behavioral alterations are a major source of caregiver stress and an important contributor in the decision to institutionalize patients. The amyloid precursor protein (APP) 23 transgenic mouse model develops amyloid plaques from the age of 6 months onward and exhibits tau pathology, which is absent in most other amyloid-based models. Besides mimicking the demented patients' memory deficits, these transgenic mice present with various behavioral disturbances, thereby approximating the clinical situation remarkably well. Using an isolation-induced/resident-intruder paradigm of aggression, the authors revealed increased aggressiveness in male APP23 mice at the ages of 6 and 12 months. The presence of aggressive disturbances in this valuable mouse model opens perspectives to evaluate aggression-modulating therapies.


Alternate polypurine tracts affect rous sarcoma virus integration in vivo.
When the endogenous polypurine tract (PPT) of the Rous sarcoma virus (RSV)-derived vector RSVP(A)Z was replaced with alternate retroviral PPTs, the fraction of unintegrated viral DNA with the normal consensus ends significantly decreased and the retention of part of the PPT significantly increased. If the terminus of the U3 long terminal repeat (LTR) is aberrant, RSV integrase can correctly process and integrate the normal U5 LTR into the host genome. However, the canonical CA is not involved in joining the aberrant U3 LTR to the host DNA, generating either large duplications or deletions of the host sequences instead of the normal 5- or 6-bp duplication.


Inhibitory control moderates the quadratic association between resting respiratory sinus arrhythmia and prosocial behaviors in children.
Resting respiratory sinus arrhythmia (RSA) is thought to be an important physiological correlate of prosocial behaviors. A negative quadratic association between resting RSA and prosocial behaviors has been found in recent studies. However, it remains unknown whether inhibitory control (IC), as an aspect of cognitive regulation, moderates this quadratic association. This issue was examined in the present study. One hundred and forty-eight children (81 girls, 54.7%) aged 7-8 years completed a go/no-go task to assess their IC, and the children's parents completed the Strengths and Difficulties Questionnaire-Chinese version (SDQ-CV) to assess children's prosocial behaviors. Resting RSA was calculated by electrocardiogram (ECG) data collected during a resting period in the laboratory. The results showed a significant quadratic association between resting RSA and children's prosocial behaviors. More importantly, IC had a significant moderating effect on the quadratic association between resting RSA and prosocial behaviors. Specifically, the quadratic effect of resting RSA on prosocial behaviors was observed only among children with low and average IC and disappeared in children with better IC. The findings suggest that IC interacts with resting RSA to contribute to prosocial behaviors in children. High levels of IC could attenuate the negative impact of high and low resting RSA on prosocial behaviors.


Comparative pharmacokinetics of norfloxacin nicotinate in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after oral administration.
Comparative pharmacokinetics of norfloxacin nicotinate (NFXNT) was investigated in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after a single oral dose of 10 mg/kg body weight (b.w.). Analyses of plasma samples were performed using ultra-performance liquid chromatography (UPLC) with fluorescence detection. After oral dose, plasma concentration-time curves of common carp and crucian carp were best described by a two-compartment open model with first-order absorption. The pharmacokinetic parameters of common carp were similar to those of crucian carp. The distribution half-life (t1/2α ), elimination half-life (t1/2β ), peak concentration (Cmax ), time-to-peak concentration (Tmax ), and area under the concentration-time curve (AUC) of common carp were 1.58 h, 26.33 h, 6069.79 μg/L, 1.08 h, and 103072.36 h·μg/L, respectively, and those corresponding to crucian carp were 1.36 h, 26.55 h, 9586.06 μg/L, 0.84 h, and 126604.4 h·μg/L, respectively. These studies demonstrated that 10 mg NFXNT/kg body weight in common carp and crucian carp following oral dose presented good pharmacokinetic characteristics.


Distribution of isotopic label after the oral administration of free and bound 14C-labelled glucosamine in rats.
The metabolic fate of [1-(14)C]glucosamine, of N-acetyl[1-(14)C]glucosamine and of glycoproteins labelled with [1-(14)C]glucosamine was studied in rats for a period of 24hr. after these materials were given orally or injected. When [1-(14)C]glucosamine was injected 26.3% of the label was excreted in the urine, 19.7% was expired as carbon dioxide and 12.7% was incorporated into plasma proteins. When the same compound was given orally, 49.2% of the label was expired as carbon dioxide, with little appearing in the urine or in the plasma. When N-acetyl[1-(14)C]glucosamine was injected, 51.3% of the label was excreted in the urine with 12.3% appearing in carbon dioxide, but there was little incorporation into plasma protein. When this compound was given orally, 46.5% of the label was expired as carbon dioxide, 7.4% was recovered in the urine and 1.7% was incorporated into plasma protein. After the injection of (14)C-labelled glycoprotein 21.0% of the label was expired as carbon dioxide, whereas when it was given orally 49.8% of the label was recovered in carbon dioxide. The differences observed between the metabolic fate of the amino sugars when they were given orally and their fate when injected could not be accounted for by the action of the intestinal microflora or by the rate of administration of the material. It is concluded that amino sugars undergo metabolic alteration or degradation during absorption.


Catalyst-Free Synthesis of Pyrrolo[1,2-a]quinolines via Dehydration/[3 + 2] Cycloaddition Directly from 2-Methylquinolines, Aldehydes, and Alkynoates.
A simple and efficient catalyst-free synthesis of pyrrolo[1,2-a]quinoline derivatives from 2-methylquinolines, aldehydes, and alkynoates via dehydration/[3 + 2] cycloaddition has been developed. The reaction conditions are tolerant to air, and H2O is the only byproduct of this transformation, thus offering an environmentally benign process with a wide range of potential applications in organic synthesis and medicinal chemistry.


[The effects of sodium salicylate on the expression of GABAalpha, NR1 and hearing response properties of inferior colliculus neurons in mice].
To study the effects of sodium salicylate on the expression of GABAalpha NR1 and hearing response properties of inferior colliculus neurons in mice. Thirty-six kunming mice were divided into three groups (A, B, C,). The expression of GABAalpha NR1 were measured by using RT-PCR. The intensity-rates functions, intensity-latency functions and frequency-turning curves were recorded by extracellular electrophysiological recording techniques. (1) The expression of GABAalpha mRNA of B group was decreased remarkably than the control group (A group, P < 0.05), there weren't noticeable differences between A group and C group (P > 0.05). The expression of NR1 mRNA of B group was increased remarkably than the control group (A group, P < 0.01), there were noticeable differences between A group and C group P < 0.05). (2) The intensity-rates functions, intensity-latency functions were monotonic while the frequency-turning curves were more broad when sodium salicylate was given. (3) The intensity-rates functions, intensity-latency functions were non-monotonic while the frequency-turning curves were sharpened after lidocaine was given. (1) The results suggested that administration of sodium salicylate decreased the expression of GABAalpha while increased the expression of NR1mRNA. (2) The intensity-rates functions, intensity-latency functions were monotonic, the frequency-turning curves were more broad when salicylate was given and the changes above could be reversed by given lidocaine.


Accuracy of Antibiotic Prescription Dosing for Urinary Tract Infections in a Regional Pediatric Ambulatory Care Setting.
Antibiotics are the most common class of medication prescribed in pediatrics, with the majority of prescriptions occurring in the outpatient setting. Our objective was to evaluate the accuracy of antibiotic dose, frequency, and formulation prescribed for urinary tract infections (UTIs) in the pediatric ambulatory care setting. This was a retrospective review of electronic medical records conducted at 2 suburban pediatric practices in a mid-sized metropolitan region. Encounter-related prescriptions were identified using UTI-associated International Classification of Diseases, 10th Revision codes. Patients aged 2 months through 18 years were included if they had been prescribed an oral antibiotic for the treatment of UTI. Antibiotic dose, frequency, and formulation were considered accurate if consistent with clinical guidelines and tertiary dosing references. Nearly 1 in 4 prescriptions had dosing inaccuracies. The proportion of errors was highest with amoxicillin-clavulanate (75%; 9/12) and amoxicillin (52%; 33/64). The most common reasons for dosing incorrectly were "low dose" or "unnecessarily high dose." Additionally, 55% of the included prescriptions were for oral suspensions, and 1 in 4 of these were dosed incorrectly. Inaccuracies in antibiotic prescribing for pediatric UTI are common, including for frequently prescribed agents and oral formulations. To address these missed opportunities for stewardship in the outpatient setting, key educational sessions with providers should include reviewing optimal antibiotic dosing for uropathogens and highlighting common errors when oral suspensions are prescribed.


[Endothelial factors and cardiac insufficiency].
The endothelium produces several vasodilating factors such as prostacyclin or nitric oxide and also vasoconstricting agents such as endothelin. These factors play an important role in the regulation of vascular tone and tissue perfusion. Several recent studies have evaluated the role of endothelin and NO in the pathophysiology of congestive heart failure. This paper reviews the data suggesting that endothelin and NO contribute to the neuro-hormonal compensatory mechanisms in patients with heart failure and that specific blockade of endothelin receptors could be an effective new approach for the treatment of patients with severe congestive heart failure.


Transcriptomic Analysis in Human Macrophages Infected with Therapeutic Failure Clinical Isolates of Leishmania infantum.
Leishmaniasis is one of the neglected tropical diseases with a worldwide distribution, affecting humans and animals. In the absence of an effective vaccine, current treatment is through the use of chemotherapy; however, existing treatments have frequent appearance of drug resistance and therapeutic failure (TF). The identification of factors that contribute to TF in leishmaniasis will provide the basis for a future therapeutic strategy more efficient for the control of this disease. In this article, we have evaluated the transcriptomic changes in the host cells THP-1 after infection with clinical Leishmania infantum isolates from leishmaniasis patients with TF. Our results show that distinct L. infantum isolates differentially modulate host cell response, inducing phenotypic changes that probably may account for parasite survival and TF of patients. Analysis of differential expression genes (DEGs), with a statistical significance threshold of a fold change ≥ 2 and a false discovery rate value ≤ 0.05, revealed a different number of DEGs according to the Leishmanialine. Globally, there was a similar number of genes up- and downregulated in all the infected host THP-1 cells, with exception of Hi-L2221, which showed a higher number of downregulated DEGs. We observed a total of 58 DEGs commonly modulated in all infected host cells, including upregulated (log2FC ≥ 1) and downregulated (log2FC ≤ -1) genes. Based on the results obtained from the analysis of RNA-seq, volcano plot, and GO enrichment analysis, we identified the most significant transcripts of relevance for their possible contribution to the TF observed in patients with leishmaniasis.


Intentional weight loss in overweight and obese patients with severe mental illness: 8-year experience of a behavioral treatment program.
Obesity is 2 to 3 times more common among people with severe mental illness and has adverse effects on physical and psychological health. We report the experience from the first 8 years of a self-referring weight management clinic. From 2000 to 2008, 113 patients with severe mental illness (according to ICD-10 criteria) with a mean +/- SE age of 43.8 +/- 1.7 years (range, 22-71 years) referred themselves to this clinic. The patients were seen in weekly group sessions lasting 1 hour that involved weight measurement, discussion, and education. The response to the program was assessed by the paired Student t test and linear analysis corrected for repeated measures. Mean +/- SE baseline weight was 90.1 +/- 1.6 kg (body mass index [BMI] = 32.2 +/- 0.5 kg/m(2)). Fifty subjects of the 142 total patient episodes (35%) dropped out within the first 3 months. Sixty-four subjects completed 1 year of the program, and 35 have attended for 2 years or longer. There were progressive statistically significant reductions in mean weight and BMI throughout the duration of monitoring, with no suggestion of a plateau. The mean +/- SE final weight loss was 7.2 +/- 0.6 kg. Weight loss was correlated only with the number of sessions attended (r = 0.42, P < .0001). Lifestyle advice within a group setting may be effective in long-term management of obese and overweight patients with severe mental illness.


Telehealth Adoption by Mental Health and Substance Use Disorder Treatment Facilities in the COVID-19 Pandemic.
The study examined temporal and geographic trends in telehealth availability at U.S. behavioral health treatment facilities and risk factors for not offering telehealth. Longitudinal data on 15,691 outpatient behavioral health treatment facilities were extracted daily from the Substance Abuse and Mental Health Services Administration's Behavioral Health Treatment Services Locator between January 20, 2020, and January 20, 2021. Facilities operated by the Department of Veterans Affairs were excluded. Bivariate analyses were used to assess trends in telehealth availability in 2020 and 2021. Multivariable regression analysis was used to examine facility- and county-level characteristics associated with telehealth availability in 2021. Telehealth availability increased by 77% from 2020 to 2021 for mental health treatment facilities and by 143% for substance use disorder treatment facilities. By January 2021, 68% of outpatient mental health facilities and 57% of substance use disorder treatment facilities in the sample were offering telehealth. Mental health and substance use disorder treatment facilities that did not accept Medicaid as a form of payment were less likely to offer telehealth in 2021, compared with facilities that accepted Medicaid. Mental health and substance use disorder treatment facilities that accepted private insurance were more likely to offer telehealth in 2021, compared with facilities that did not accept private insurance. Although 2020 saw a dramatic increase in telehealth availability at behavioral health treatment facilities, 32% of mental health treatment facilities and 43% of substance use disorder treatment facilities did not offer telehealth in January 2021, nearly 1 year into the pandemic.


Amelioration of mitochondrial dysfunction and apoptosis of two-cell mouse embryos after freezing and thawing by the high frequency liquid nitrogen infusion.
Liquid nitrogen (LN2) infusions are currently used in a slow controlled-rate freezing during cryopreservation. The effects of two different LN2 infusion frequencies (conventional, slow 50 infusions/min and high 120 infusions/min) were studied with frozen-thawed two-cell mouse embryos and their subsequent development to blastocysts. The embryos that were subjected to the high frequency LN2 infusion (HFLI) showed a significantly higher survival rate over the low frequency LN2 infusion (LFLI) (50.7 vs. 34.6%, P < 0.05). The blastocyst formation was also higher in HFLI (76.7%) than LFLI (44.0%, P < 0.05) with respective to the number of cells in a blastocyst of 71.6 8.0 (n = 20) and 62.5 +/- 4.7 (n = 20) (P < 0.05). The relative amount of H2O2 in an embryo that was assessed by a fluorescence intensity of 2',7'-dichlorofluorecein (DCF) showed a difference between the procedures with 16.6 +/- 1.6 (n = 21) and 23.4 +/- 1.8 (n = 24) for HFLI and LFLI, respectively (P < 0.05). Mitochondrial staining by Rhodamine 123 showed that the number and distribution of viable mitochondria were similar in both procedures, but fewer mitochondria were observed with a marked aggregation in the arrested embryos, indicating a mitochondrial disintegration. The mitochondrial membrane potential was visualized by a membrane potential-sensitive fluorescent probe, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). There was a decrease in the number of mitochondria that had a high membrane potential, and they showed a peripheral redistribution along the cell membrane in LFLI. A fluorescent staining of the actin filaments revealed a discontinuity that was noticeably at the peripheral "actin band" in LFLI. The DNA fragmentation was assessed by the dUTP nick end-labeling (TUNEL). The results showed a higher DNA fragmentation of blastocyst nuclei in LFLI compared to HFLI (65.6 vs. 36.0%, P < 0.05). Based on these observations, it was concluded that HFLI was better than LFLI in the case of freezing the mouse 2-cell embryos for preserving cytoskeletons and mitochondrial integrities. This could subsequently lead to a higher survival and developmental rate of the cryopreserved mouse embryos.


VIRTUAL AVATARS, GAMING, AND SOCIAL MEDIA: DESIGNING A MOBILE HEALTH APP TO HELP CHILDREN CHOOSE HEALTHIER FOOD OPTIONS.
Rapid growth in Smartphone use among children affords potential opportunities to target health behaviors such as dietary habits; however, few mobile health applications are specifically designed with these individuals in mind. This brief report describes our step-by-step approach towards developing a mobile health application for targeting nutrition behaviors among children. Descriptions of the 10 most popular paid and 10 most popular free Smartphone applications available on the Apple iTunes store for ages 4 and up as of March 2012 were qualitatively analyzed. The relevance of key characteristics found in these applications was then further explored for their potential to improve dietary behaviours amongst children, and a mobile application was developed. Three prominent characteristics of the most popular applications emerged: 1) virtual avatars or characters (observed in 50% of the applications); 2) gaming (observed in 75% of the applications); and 3) social media (observed in 45% of the applications). These features were then incorporated into the design of a mobile health application called Avafeed, which uses a virtual avatar and gaming to help make choosing healthier food options easier among children. The application was successfully released onto the Apple iTunes Store in September 2012. In this unconventional approach, evidence-based research was combined with information procured from a qualitative review of popular applications available on the Apple iTunes Store in order to design a potentially relevant and popular mobile health application for use among children.


Observation of long-term efficacy of corneal limbal conjunctival autografts in microscopy treatments of pterygium.
To compare the long-term efficacy of a corneal limbal conjunctival autograft combined with pterygium excision in the treatment of primary pterygium. This random control study included 63 patients (63 eyes) with primary pterygium. These were randomly divided into a group with corneal limbal conjunctival autograft combined with pterygium excision (group A) and a group with pterygium excision with exposed sclera (group B) and subjected to long-term follow up. The surgical outcomes were classified and evaluated (grade I-IV). Several indexes were analyzed, including ocular surface irritation symptom, tear film stability, surgical complication, and recurrence rate. The follow up ranged from 24 to 38 months, (26.9+/-3.4) months on average. No recurrence was noted at 6 weeks postoperatively. At 6 months postoperatively, the recurrence rate of pterygium was 5.2% in group A and 8.0% in group B. At 1 year postoperatively, the recurrence rate in group A was 10.5% and 20.0% in group B. At the end of follow up, the recurrence rates were 13.1% in group A and 24.0% in group B. No statistical significance was found between two groups regarding the recurrence rates at each time point (P>0.05). After the follow up (> 2 years), the severity of ocular surface conditions was significantly milder in patients in group A than in group B (P<0.01). No statistically significant differences were noted between the two groups at 6 weeks, 6 months, and 1 year after surgery. No statistically significant differences were observed between the two groups regarding postoperative tear film break-up time. Fewer postoperative complications and milder ocular surface irritation symptoms occurred in patients in group A. Corneal limbal conjunctival autograft combined with pterygium excision yields sound long-term efficacy and a low recurrence rate and induces only mild damage on the ocular surface when used as a treatment for pterygium.


Bronchial Epithelial Cells from Asthmatic Patients Display Less Functional HLA-G Isoform Expression.
Not all asthmatic patients adequately respond to current available treatments, such as inhaled corticosteroids or omalizumab®. New treatments will aim to target the bronchial epithelium-immune response interaction using different pathways. HLA-G is involved in immunomodulation and may promote epithelial cell differentiation and proliferation. HLA-G protein has several isoforms generated by alternative splicing that might have differential functionalities. HLA-G protein expression and genetic polymorphisms have been reported to be associated with asthma. Our hypothesis is that bronchial epithelium from asthmatic patients displays less functional HLA-G isoforms. HLA-G transcriptional isoforms were quantified by real-time PCR in human bronchial epithelium cells (HBEC) grown in air-liquid interface culture obtained from five healthy controls (HC), seven patients with mild asthma (MA), and seven patients with severe asthma (SA). They were re-differentiated, and IL-13 exposure was used as a proxy for a pro-inflammatory cytokine. HLA-G protein expression was assessed by western blot analysis. HLA-G allele was typed by direct sequencing. Our results showed that both MA and SA display less functional HLA-G isoforms than HC (p < 0.05); in vitro HBEC re-differentiation from SA displays a particular isoform expression profile compared to MA and HC (p = 0.03); HLA-G*01:06 frequency in MA and SA was significantly higher than in the healthy population (p = 0.03 and p < 0.001, respectively); and IL-13 exposure had no impact on HLA-G expression. Our results support that an impaired expression of HLA-G isoforms in asthmatic patients could contribute to the loss of inflammation control and epithelium structural remodeling. Therefore, HLA-G might be an interesting alternative target for asthmatic patients not adequately responding to current drugs.


Why is there heterogeneity in the effect of dental checkups? Assessing cohort effect.
To evaluate age as a potential effect modifier of the relation between frequency of dental check-up and oral health. Data from a Brazilian oral health survey carried out in 2002-2003 was obtained for three age groups: 15-19-year-old (n=16411); 35-44-year-old (n=13269); and 65-74-year-old (n=5 300). Individuals were examined by dentists and followed to an interview. Self-reported time since last dental visit was measured as 'less than 1 year'; 'from 1 to 2 years'; '3 or more years' or 'never'. Outcomes modelled with negative binomial regression were DMFT index and DT, MT and FT. Visiting the dentist more recently was associated with fewer teeth with untreated dental caries (DT) and more teeth with fillings (FT) across all age groups. Among the 15-19-year-old, the longer the time since last visit the lower the DMFT and MT. On the other hand, among the 35-44 and the 65-74-year-old the longer the time since last dental visit the higher the DMFT and MT, though this trend reverted in the 'never visited' group. Age modified the effect of dental visits on DMFT and MT. In younger cohorts, the low frequency of dental check-up among those with good oral health may reflect the fact that these young people do not feel they need to go to the dentist very often, while in older cohorts, the current low frequency of dental check-up associated with bad oral health may be a reflection of a lifetime of high disease incidence coupled with access barriers. Questions regarding the time and frequency of dental visits may capture different dimensions of utilization of dental services, and so pooled estimates are not appropriate. Our results may help explaining contrasting results in previously published studies.


A highly conserved sequence associated with the HIV gp41 loop region is an immunomodulator of antigen-specific T cells in mice.
Modulation of T-cell responses by HIV occurs via distinct mechanisms, 1 of which involves inactivation of T cells already at the stage of virus-cell fusion. Hydrophobic portions of the gp41 protein of the viral envelope that contributes to membrane fusion may modulate T-cell responsiveness. Here we found a highly conserved sequence (termed "ISLAD") that is associated with the membranotropic gp41 loop region. We showed that ISLAD has the ability to bind the T-cell membrane and to interact with the T-cell receptor (TCR) complex. Furthermore, ISLAD inhibited T-cell proliferation and interferon-γ secretion that resulted from TCR engagement through antigen-presenting cells. Moreover, administering ISLAD (10 µg per mouse) to an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis reduced the severity of the disease. This was related to the inhibition of pathogenic T-cell proliferation and to reduced pro-inflammatory cytokine secretion in the lymph nodes of ISLAD-treated EAE mice. The data suggest that T-cell inactivation by HIV during membrane fusion may lie in part in this conserved sequence associated with the gp41 loop region.


Mild hypothermia combined with neural stem cell transplantation for hypoxic-ischemic encephalopathy: neuroprotective effects of combined therapy.
Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27-28°C) can increase the survival rate of neural stem cells (1.0 × 10(5)/μL) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hypothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and anti-apoptotic mechanisms.


Clinicopathologic significance of CXCR4 and Nrf2 in colorectal cancer.
The CXCR4 and Nrf2 signaling pathways are abnormally activated in response to cellular stress in various types of human cancers. In this study, we examined the expression of CXCR4 and Nrf2 in colorectal cancer (CRC) tissue specimens and investigated their correlation with patient clinicopathologic characteristics. We determined CXCR4 and Nrf2 expression in 76 CRC tissue specimens and paired normal tissue specimens by immunohistochemistry and real-time PCR. We found that the protein and mRNA transcript levels of CXCR4 were significantly higher in CRC tissue specimens than in paired normal tissues, while the expressions of Nrf2 protein and mRNA were increased in CRC tissues compared to distant non-cancerous tissues. High expression level of CXCR4 was positively correlated with poorly differentiated (P = 0.031), more advanced tumor-node-metastasis (TNM) stage (P = 0.019), lymph node metastasis (P = 0.007) and distant metastasis (P = 0.018). However, the expression of Nrf2 protein was positively correlated with larger tumor size (P = 0.049), more advanced TNM stage (P = 0.013), lymph node metastasis (P = 0.016) and distant metastasis (P = 0.023). Moreover, there was a strong relationship between CXCR4 and Nrf2 expression in CRC tissues, indicating that high Nrf2 expression may contribute to CXCR4 overexpression. In addition, combined expression of CXCR4 and Nrf2 strongly correlated with lymph node metastasis and distant metastasis (P = 0.003). Furthermore, we found that combined high expression of CXCR4 and Nrf2 had stronger correlation with lymph node metastasis and distant metastasis than any single molecule did. This study indicated that the abnormal expression of CXCR4 and Nrf2 contributed to the progression of CRC.


Visual integration difficulties in a 9-year-old girl with Turner syndrome: parallel verbal disabilities?
Turner syndrome (TS) is a genetic disorder in females that arises from the loss of X chromosome material. Affected individuals demonstrate a characteristic neuropsychological profile of strengths in verbal processing and weaknesses in visuospatial processing, consistent with the Nonverbal Learning Disabilities syndrome. Previous research has described a wide range of visuospatial deficits in TS; however, their verbal abilities are less extensively studied. The present paper describes the processing difficulties of a 9-year-old girl with TS who demonstrated problems in integrating details of a complex visual display and using organizational terms to describe visual scenes or events. Her specific cognitive disabilities were thought to underlie some of the social and behavioral problems she was currently experiencing. Her pattern of results is consonant with the neuropsychological pattern that others have attributed to right hemisphere dysfunction and/or white matter abnormality.


Joubert syndrome with associated corpus callosum agenesis.
In 1969, Joubert et al. studied a family where four of six children had a severe clinical condition with episodic alternate hyperpnoea and apnoea, hypotonia, ataxia, psychomotor delay, and abnormal ocular movements. Two of the four had agenesis of the posterior-inferior part of the cerebellar vermis and two had complete agenesis of the vermis. We report a 5-month-old girl with Joubert syndrome in whom MRI shows both features typical of this condition and associated corpus callosum agenesis. To our knowledge, complete callosal agenesis has been infrequently reported in children with Joubert syndrome; consequently, it might be regarded as a casual finding. Nevertheless, the hypothesis of a developmental abnormality of midline structures extended to the supratentorial compartment is rather attractive.


Real-time quantitative PCR measurement of circulatory rhodopsin mRNA in healthy subjects and patients with diabetic retinopathy.
Diabetic retinopathy is the commonest complication of diabetes and is the biggest single cause of registered blindness in the UK. No biochemical tests exist to determine the precise state and rate of change of the eyes in the diabetic patient. In the present study, using real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we measured mRNA encoding the retina-specific pigment protein rhodopsin (RHO) in the peripheral blood of healthy individuals (n = 20) and diabetic patients (n = 46) with and without retinopathy. Beta-actin mRNA was also assayed and results are expressed as a ratio of RHO to beta-actin mRNA. Peripheral blood was taken by venipucture directly into PAXgene Blood RNA collection tubes and RNA extracted by use of the PAXgene Blood RNA extraction kit, as per the manufacturer's (Qiagen) instructions. Diabetic patients were divided into three groups defined by the severity of retinopathy as assessed by fundoscopy: A, diabetic without retinopathy; B, background retinopathy; and C, preproliferative retinopathy. Medians of the ratios between groups were compared. RHO mRNA was successfully detected and quantified in peripheral blood in all healthy and diabetic groups, with levels shown to be significantly higher in diabetic patients than in healthy controls (2.54 x 10(-5) vs. 1.29 x 10(-5); P = 0.002). Significant differences in RHO mRNA levels were also seen between healthy control subjects and diabetic groups A (2.52 x 10(-5); P = 0.022), B (1.98 x 10(-5); P = 0.028), and C (5.08 x 10(-5); P = 0.002). The results suggest that there is an increase in circulatory RHO mRNA with the severity of diabetic retinopathy.


Modulation of rat liver protein kinase C during "in vivo" CC14-induced oxidative stress.
Rat intoxication with a single dose of the hepatotoxin carbon tetrachloride induces a significant modification of liver protein kinase C total activity which depends on the degree of the intrahepatocyte oxidative unbalance provoked by various concentrations of the haloalkane. Low carbon tetrachloride amounts stimulate total protein kinase C activity, while one order of magnitude higher amounts exert strong enzyme inhibition. The latter effect is due to an early inactivation followed with progress of time by a proteolytic degradation of the enzyme. A pathological recruitment of the calcium-dependent protein kinase C regulatory enzymes calpain and calpastatin appears responsible for protein kinase C loss. The prolonged excess of cytosolic calcium which characterizes the single high dose carbon tetrachloride poisoning also leads to inactivation of calpain II and calpastatin in a time-dependent manner.


Mitoxantrone: a replacement for doxorubicin?
Doxorubicin (Adriamycin) is an unquestionably effective anticancer agent for many types of tumors, including advanced breast cancer. However, cardiotoxic effects of the drug have limited its use. Methods of reducing or preventing doxorubicin-induced cardiotoxicity have been suggested, including an investigational doxorubicin analog, mitoxantrone ( Novantrone ). Mitoxantrone was developed to reduce the cardiotoxicity associated with doxorubicin while maintaining effective antitumoral effects. Initial reports suggested that mitoxantrone might lack cardiotoxic potential; however, recent studies indicate that the drug can produce adverse cardiac effects (congestive heart failure), perhaps with similar frequency to that observed with doxorubicin. It is doubtful that mitoxantrone will be a significant advance over doxorubicin if direct comparative studies reveal a similar incidence of cardiomyopathy.


Size of outbreaks near the epidemic threshold.
The spread of infectious diseases near the epidemic threshold is investigated. Scaling laws for the size and the duration of outbreaks originating from a single infected individual in a large susceptible population are obtained. The maximal size of an outbreak n(*) scales as N(2/3) with N the population size. This scaling law implies that the average outbreak size [n]scales as N(1/3). Moreover, the maximal and the average duration of an outbreak grow as t(*) approximately N(1/3) and [t] approximately ln N, respectively.


Removal of acetone and methylacetate mixtures from waste gases by a trickle-bed air biofilter.
The biofilter process is a relatively new technology that has been proven more cost-effective than traditional technologies for treating low-strength and some high-strength volatile organic compounds (VOCs) from waste gases. Acetone (AT) and methylacetate (MA) mixtures are commonly encountered from the manufacture of artificial rubber or polyurethane resin. This research attempts to employ a trickle-bed air biofilter (TBAB) for treating AT and MA mixtures under different influent carbon loadings. In the pseudo-steady-states, the elimination capacities of AT and MA increased but the removal efficiencies decreased with increased influent carbon loading. The removal efficiencies of MA were higher than those of AT showing that MA is a preferred substrate in the ATMA waste gas and the differences were enhanced at a high carbon loading. Greater than 95% AT removal and nearly complete MA removal were achieved with influent carbon loadings of AT and MA below 20 and 27 g m(-1) h(-1), respectively. The TBAB appears very efficient for treating ATMA emission with low to medium carbon loadings.


Tools Clinicians Can Use to Help Get Patients Active.
An epidemic of physical inactivity has given rise to a population struggling with early mortality and an increase in chronic non-communicable diseases such as cardiovascular disease, diabetes, and cancer. Primary care providers as well as other clinicians are in a position to help overcome this epidemic of physical inactivity. The goal of this commentary is to provide clinicians with resources and recommendations from the recent literature to help overcome barriers to physical activity counseling and help patients become physically active. Theory-based interventions from communication and exercise prescriptions to wearables and mobile health technology are discussed. Limitations and future directions are explored.


Digesters in traditional Persian medicine.
Functional gastrointestinal diseases are common in general populations and comprise more than 40% visits to gastroenterologists. Treatment options of gastrointestinal diseases have been limited. There are a few medications for functional gastrointestinal diseases and some of medications are not available in the market or in the place where the patient lives. Traditional Persian medicine (TPM) is a branch of alternative and traditional medicine based on individual viewpoint and humoral theory, focuses on lifestyle modification and uses natural products to manage the patients. In this study, a set of compound drugs known as digesters (jawarishes) and other applications are described based on main TPM text books. Jawarishes have different formulations containing various medicinal herbs used for better food digestion and improved gastric functions and also used for other disorders including reinforcing the brain, heart, liver and some therapeutic approaches. By reviewing medieval Persian pharmaceutical manuscripts, we can conclude that many herbs are effective in different systems of the body and improve gastric functions. Zingiber officinalis and Piper nigrum are mixed together to get various formulations. The variety of jawarishes formulations and their different clinical applications can indicate continuity of their use.


Friends or foes: social anxiety, peer affiliation, and drinking in middle school.
The relation between social anxiety and alcohol consumption suggests aspects of both risk and protection, but most research has focused on late adolescents and emerging adults. We investigated the synergistic impact of social anxiety, a need for affiliation with others, and perceived peer alcohol use on drinking in a sample of more than 1,500 early adolescents from southern California (48% girls). Via school-wide surveys, middle school students completed the Social Anxiety Scale for Children-Revised, a modified version of the Interpersonal Orientation Scale, as well as measures of perceived peer drinking and self-reported lifetime and current drinking. For socially anxious youths, high levels of perceived peer use in conjunction with high levels of affiliation need was associated with greater alcohol use on average and more frequent episodic drinking. Specific to heavy episodic drinking, the interaction of social anxiety and perceived peer drinking seemed to affect girls and boys differentially. Sex differences emerged for the moderation of social anxiety's influence on drinking initiation by perceived peer influence. These findings suggest that alcohol-related risks associated with social anxiety might be gender specific and more important in earlier stages of alcohol use than previously believed.


Sixty years on: the price of assembling military gas masks in 1940.
Between 1940 and 1944 military gas masks with filter pads containing 20% crocidolite were assembled in a Nottingham factory. Records supplied by the late Professor Stephen Jones were of 1154 persons, mainly women, who had worked in the factory during this period; they included many deaths from mesothelioma. A systematic effort was therefore made to establish causes of death for the whole cohort. Of 640 employees with full name and sex recorded, 567 (89%) were traced. Of these, 491 had died, including 65 from mesothelioma, though only 54 were certified as such. After exclusion of these 54, standardised mortality ratios were significantly raised for respiratory cancer (SMR 2.5) and carcinomatosis (SMR 3.2). The pattern of mortality in the remaining 514 employees without full identification was similar, but a low tracing rate (40%) did not justify their further analysis. The first death from mesothelioma was in 1963 (22 years after first exposure) and the last in 1994, whereas a further 5.0 cases would have been expected between 1996 and 2003 (p = 0.0065). These findings in a cohort followed over 60 years after brief exposure to crocidolite confirm a high and specific risk of mesothelioma (28% peritoneal) and perhaps of lung cancer some 20-50 years later. The statistically significant absence of further mesothelioma cases during the past eight years suggests that crocidolite, though durable, is slowly removed.


Muscle-specific expression of the RNA-binding protein Staufen1 induces progressive skeletal muscle atrophy via regulation of phosphatase tensin homolog.
Converging lines of evidence have now highlighted the key role for post-transcriptional regulation in the neuromuscular system. In particular, several RNA-binding proteins are known to be misregulated in neuromuscular disorders including myotonic dystrophy type 1, spinal muscular atrophy and amyotrophic lateral sclerosis. In this study, we focused on the RNA-binding protein Staufen1, which assumes multiple functions in both skeletal muscle and neurons. Given our previous work that showed a marked increase in Staufen1 expression in various physiological and pathological conditions including denervated muscle, in embryonic and undifferentiated skeletal muscle, in rhabdomyosarcomas as well as in myotonic dystrophy type 1 muscle samples from both mouse models and humans, we investigated the impact of sustained Staufen1 expression in postnatal skeletal muscle. To this end, we generated a skeletal muscle-specific transgenic mouse model using the muscle creatine kinase promoter to drive tissue-specific expression of Staufen1. We report that sustained Staufen1 expression in postnatal skeletal muscle causes a myopathy characterized by significant morphological and functional deficits. These deficits are accompanied by a marked increase in the expression of several atrophy-associated genes and by the negative regulation of PI3K/AKT signaling. We also uncovered that Staufen1 mediates PTEN expression through indirect transcriptional and direct post-transcriptional events thereby providing the first evidence for Staufen1-regulated PTEN expression. Collectively, our data demonstrate that Staufen1 is a novel atrophy-associated gene, and highlight its potential as a biomarker and therapeutic target for neuromuscular disorders and conditions.


Exosomes from primed MSCs can educate monocytes as a cellular therapy for hematopoietic acute radiation syndrome.
Acute radiation syndrome (ARS) is caused by acute exposure to ionizing radiation that damages multiple organ systems but especially the bone marrow (BM). We have previously shown that human macrophages educated with exosomes from human BM-derived mesenchymal stromal cells (MSCs) primed with lipopolysaccharide (LPS) prolonged survival in a xenogeneic lethal ARS model. The purpose of this study was to determine if exosomes from LPS-primed MSCs could directly educate human monocytes (LPS-EEMos) for the treatment of ARS. Human monocytes were educated by exosomes from LPS-primed MSCs and compared to monocytes educated by unprimed MSCs (EEMos) and uneducated monocytes to assess survival and clinical improvement in a xenogeneic mouse model of ARS. Changes in surface molecule expression of exosomes and monocytes after education were determined by flow cytometry, while gene expression was determined by qPCR. Irradiated human CD34+ hematopoietic stem cells (HSCs) were co-cultured with LPS-EEMos, EEMos, or uneducated monocytes to assess effects on HSC survival and proliferation. LPS priming of MSCs led to the production of exosomes with increased expression of CD9, CD29, CD44, CD146, and MCSP. LPS-EEMos showed increases in gene expression of IL-6, IL-10, IL-15, IDO, and FGF-2 as compared to EEMos generated from unprimed MSCs. Generation of LPS-EEMos induced a lower percentage of CD14+ monocyte subsets that were CD16+, CD73+, CD86+, or CD206+ but a higher percentage of PD-L1+ cells. LPS-EEMos infused 4 h after lethal irradiation significantly prolonged survival, reducing clinical scores and weight loss as compared to controls. Complete blood counts from LPS-EEMo-treated mice showed enhanced hematopoietic recovery post-nadir. IL-6 receptor blockade completely abrogated the radioprotective survival benefit of LPS-EEMos in vivo in female NSG mice, but only loss of hematopoietic recovery was noted in male NSG mice. PD-1 blockade had no effect on survival. Furthermore, LPS-EEMos also showed benefits in vivo when administered 24 h, but not 48 h, after lethal irradiation. Co-culture of unprimed EEMos or LPS-EEMos with irradiated human CD34+ HSCs led to increased CD34+ proliferation and survival, suggesting hematopoietic recovery may be seen clinically. LPS-EEMos are a potential counter-measure for hematopoietic ARS, with a reduced biomanufacturing time that facilitates hematopoiesis.


Hypocretins, sleep, and maternal behavior.
The postpartum period is a demanding time during which mothers experience numerous physiological adaptations that enable them to care for their offspring while maintaining their wellbeing. Hypocretins, also known as orexins, are neuropeptides synthesized by hypothalamic neurons that play a fundamental role in several functions, including the promotion of wakefulness and motivated behaviors, such as maternal care. In this regard, several findings suggest that the activity of the hypocretinergic system increases in the early postpartum period and begins to decline as weaning approaches. In particular, hypocretins within the medial preoptic area, a crucial region during this period, modulate both maternal behavior and sleep. Although further studies are necessary to obtain a comprehensive understanding of the role of hypocretins in lactating females, current research suggests that this system participates in promoting active components of maternal behavior and regulating wakefulness and sleep adjustments during the postpartum period, potentially leading to increased wakefulness during this stage. These adaptive adjustments enable the mother to cope with the continuously changing demands of the pups.


Membrane depolarization-triggered responsive diversification leads to antibiotic tolerance.
Bacterial populations are known to harbor a small fraction of so-called persister cells that have the remarkable ability to survive treatment with very high doses of antibiotics. Recent studies underscore the importance of persistence in chronic infections, yet the nature of persisters remains poorly understood. We recently showed that the universally conserved GTPase Obg modulates persistence via a (p)ppGpp-dependent mechanism that proceeds through expression of hokB. HokB is a membrane-bound toxin that causes the membrane potential to collapse. The resulting drop in cellular energy levels triggers a switch to the persistent state, yielding protection from antibiotic attack. Obg-mediated persistence is conserved in the human pathogen Pseudomonas aeruginosa, making Obg a promising target for therapies directed against bacterial persistence.


The burden of neck pain: its meaning for persons with neck pain and healthcare providers, explored by concept mapping.
To empirically define the concept of burden of neck pain. The lack of a clear understanding of this construct from the perspective of persons with neck pain and care providers hampers adequate measurement of this burden. An additional aim was to compare the conceptual model obtained with the frequently used Neck Disability Index (NDI). Concept mapping, combining qualitative (nominal group technique and group consensus) and quantitative research methods (cluster analysis and multidimensional scaling), was applied to groups of persons with neck pain (n = 3) and professionals treating persons with neck pain (n = 2). Group members generated statements, which were organized into concept maps. Group members achieved consensus about the number and description of domains and the researchers then generated an overall mind map covering the full breadth of the burden of neck pain. Concept mapping revealed 12 domains of burden of neck pain: impaired mobility neck, neck pain, fatigue/concentration, physical complaints, psychological aspects/consequences, activities of daily living, social participation, financial consequences, difficult to treat/difficult to diagnose, difference of opinion with care providers, incomprehension by social environment, and how person with neck pain deal with complaints. All ten items of the NDI could be linked to the mind map, but the NDI measures only part of the burden of neck pain. This study revealed the relevant domains for the burden of neck pain from the viewpoints of persons with neck pain and their care providers. These results can guide the identification of existing measurements instruments for each domain or the development of new ones to measure the burden of neck pain.


Ultrastructural study of crossbands occurring in the stalks of Caulobacter crescentus.
An ultrastructural study of crossbands isolated from Caulobacter crescentus Sk1 418 stalks permitted a view of these structures in a plane other than the perpendicular view normally presented in the electron microscope. These crossbands were composed of concentrically arranged, alternating light and dark bands when stained with phosphotungstic acid. Evidence supports the hypothesis that crossbands appear to compose a structural barrier extending the width of the stalk and may function to support unit membrane extending the length of the stalk.


The power of interval mapping of quantitative trait loci, using selected sib pairs.
The interval-mapping procedure of Fulker and Cardon for analysis of a quantitative-trait loci (QTL) is extended for application to selected samples of sib pairs. Phenotypic selection of sib pairs, which is known to yield striking increases in power when a single marker is used, provides further increases in power when the interval-mapping approach is used. The greatest benefits of the combined approach are apparent with coarse maps, where QTLs of relatively modest (15%-20%) heritability can be detected with widely spaced markers (40-60 cM apart) in reasonably sized sibling samples. Useful information concerning QTL location is afforded by interval mapping in both selected and unselected samples.


[Hemodilution in the treatment of acute cerebral thrombosis].
11 cases of acute cerebral thrombosis were treated with a combination of venesection (400-800 ml of blood being let out at a time) and administration of an equal volume of low-molecular weight dextran solution Thereafter 500 ml of the dextran solution was given to each patient every day for 15 days. A comparison was made between this group and another group of patients who received just dextran. In the venesection group the mean value of hemoglobin was reduced from 15 g% to 13 g%, that of hematocrit from 44.6% to 40%, and that of the whole blood viscosity from 5.15 to 4.40. The neurological scores showed marked changes after three days of venesection. On the 21st day the scores in the venesection group increased by 31.6% (20.1 points) and that in the control group increased by 12.6% (7.7 points). Evidently the venesection group resulted in much better recovery (P less than 0.001).


Trans-ungual Delivery of AR-12, a Novel Antifungal Drug.
AR-12 is a novel small molecule with broad spectrum antifungal activity. Recently, AR-12 was found to be highly active against Trichophyton rubrum, one of the predominantly responsible organisms that cause onychomycosis. The primary objective of this project was to investigate the ability of AR-12 to penetrate into and across the human nail plate followed by improving its trans-ungual permeation using different penetration enhancers. TranScreen-N™, a high throughput screening method was utilized to explore the potential nail penetration enhancers to facilitate the drug delivery through the nail. This screen demonstrated that dexpanthenol and PEG 400 were the most efficient enhancers. The in vitro permeation studies were performed across the human cadaver nail plates for 7 days with three AR-12 (5% w/v) formulations containing 10% w/v dexpanthenol (Formulation A), 10% w/v PEG 400 (Formulation B), and a combination of 10% w/v dexpanthenol + 10% w/v PEG 400 (Formulation C). The in vitro studies concluded that dexpanthenol and PEG 400 were able to deliver a significant amount of AR-12 into and across the nail plate that was found to be more than MIC 50 level of the drug.


Nitrato-Functionalized Task-Specific Ionic Liquids as Attractive Hypergolic Rocket Fuels.
Hypergolic ionic liquids (HILs) as potential replacements for hydrazine derivatives have attracted increasing interest over the last decade. Previous studies on HILs have mostly concentrated on the anionic innovations of ionic liquids to shorten the ignition delay (ID) time, but little attention has been paid to cationic modifications and their structure-property relationships. In this work, we present a new strategy of cationic functionalization by introducing the energetic nitrato group into the cationic units of HILs. Interestingly, the introduction of oxygen-rich nitrato groups into the cationic structure significantly improved the combustion performance of HILs with larger flame diameters and duration times. The density-specific impulse (ρIsp ) of these novel HILs are all above 279.0 s g cm-3 , much higher than that of UDMH (215.7 s g cm-3 ). In addition, the densities of these HILs are in the range of 1.22-1.39 g cm-3 , which is much higher than that of UDMH (0.79 g cm-3 ), showing their higher loading capacity than hydrazine-derived fuels in a propellant tank. This promising strategy of introducing nitrato groups into the cationic structures has provided a new platform for developing high-performing HILs with improved combustion properties.


Liquid-liquid phase separation in an inhomogeneous ternary colloid-polymer mixture.
Suspended colloids are often considered as models for molecules, which are sufficiently big so that they can be observed directly in (light) microscopes and for which the effective interaction among each other can be tailored. The Asakura-Oosawa model of ideal colloid-polymer mixtures captures the idea of tuning the interaction between the colloids via a potential, which possesses a range set by the size of the polymers and an attractive strength characterized by the (reservoir) number density of the polymers, which plays the role of an inverse temperature. The celebrated Asakura-Oosawa depletion potential allows one to recreate the bulk phase diagram of a simple fluid by employing a colloid-polymer mixture. This has been verified in theory, by computer simulations, and via experiments. Here, we study the phase behavior of a confined colloid-polymer mixture with two polymer species. The sizes and densities are chosen such that the resulting bulk phase diagram exhibits a second stable critical point within the framework of the classical density functional theory. Our results suggest that a suitably tuned colloid-polymer mixture can be an interesting model system to study fluids with two critical points.


Clomethiazole (Astra Arcus AB).
Clomethiazole has been marketed for several years as a sedative/antiepileptic. Astra is now developing it for the potential treatment of stroke. An NDA is expected to be filed in 1999/2000. A North American phase III trial for large stroke has commenced. This will include 1200 patients. Two other smaller scale phase III studies with clomethiazole have also commenced in North America for intracerebral hemorrhage (n=200) and safety in combination with TPA (n=100 to 200) (Genentech). A large-scale phase III trial has been completed in which clomethiazole was evaluated for its ability to reduce nerve damage in acute cerebrovascular ischemia. The multicenter, international trial, called CLASS (Clomethiazole Acute Stroke Study), analyzed 1360 patients and found no significant treatment effect. However, a subgroup of patients who presented with large stroke, experienced a significant benefit. Of these (n=545), 41% treated patients were functionally independent after 90 days, compared to 30% patients on placebo. Clomethiazole reduced functional disability and brain damage in the marmoset permanent MCAO model. Clomethiazole is thought to act through a GABAergic pathway, whereby it augments GABA's depressive effect on the CNS, giving the drug both hypnotic and neuroprotectant properties.


Ferromagnetic half-metal with high Curie temperature in Cr P nanoribbons: good material for spintronic applications.
In this work, the stability, and electronic, magnetic, and transport characteristics of chromium phosphorus nanoribbons (CrPNRs) have been investigated. The results, obtained from the non-equilibrium Green's function and density functional theory, indicate that the nanoribbon is stable in terms of binding energies as well as dynamically. The calculated electronic structure shows that this nanoribbon has an indirect band gap of about 1.67 eV for the spin-down channel and is metallic for the spin-up channel. The metallicity of the spin-up channel originates from the P-3p orbitals and the magnetic properties are due to the Cr-3d orbitals. The obtained transport properties indicate the value of the current for the spin-up state is about 50 μA. The negative differential resistance (NDR) phenomenon and also a 100% spin filtering effect are seen between voltages of 0.4 and 0.5 V. The results showed that CrPNRs have a high Curie temperature of more than 690 K, indicating that this nanoribbon is a useful ferromagnetic material for nanoelectronic devices and spintronic applications at ambient temperature.


The Roles of Population, Place, and Institution in Student Diversity in American Higher Education.
Student racial and ethnic diversity in higher education is an important and timely topic, as institutions, policy-makers, and economists increasingly recognize the value that accrues at many levels of having a skilled and diverse student body and workforce. Students benefit from learning in a diverse environment; firms may benefit from a diverse workforce; and more demographically diverse regions make experience higher rates of economic growth. However, the forces governing institution-level student diversity are poorly understood, as little prior research on the topic exists. This paper uses school enrollment data to parse out the contribution institutional characteristics, geographical setting, and local demographic characteristics make to student body diversity at each level of study. Results indicate that geographical location and local demographic composition play a role in student body diversity, as do the type and orientation of the institution. Institutional characteristics explain a lot of the variation in student body diversity and actual location of schools matters less than the demographic composition of young people around that location. Two broad conclusions emerge with regard to schools seeking to increase their student diversity. First, some may find their efforts hampered by circumstances outside their control (location, for example). Second, the influence of public/private status and even school size suggest further research on the ways in which these factors influence student diversity so that eventual policy action can be more effective.


[Delirium attributed to the use of metoprolol].
A 53-year-old man with a known history of alcohol abuse was admitted to hospital after a minor collapse. He had a laceration to the forehead and three rib fractures. Laboratory blood-analysis showed raised non-cholestatic liver-enzyme levels suggesting alcohol-abuse. On history taking the patient was shown to have been suffering from personality changes and multiple hallucinogenic episodes for the previous two years. He had been seen and evaluated by a neurologist to that effect. The patient's family had accepted the situation and thought of it as dementia, probably caused by alcohol abuse. He had been treated for atrial flutter and was taking acenocoumerol, atorvastatin, quinapril and metoprolol 50 mg twice daily as medication. During admission the patient appeared to be suffering from a delirium with complex visual and auditory hallucinations, for which he was given haloperidol. Revision of medication use led to the stopping of metoprolol, which had been started two years earlier. Within 24 hours the delirium had disappeared completely. There was spontaneous fall in the liver enzymes. At his last follow-up, the patient had had no psychiatric symptoms for 6 months. The relationship between stopping metoprolol and the disappearance of the psychosis appeared to be a causal one and this is supported by the limited literature available on this subject.


Revisiting the promise, practice and progress of resuscitative endovascular balloon occlusion of the aorta.
The use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) to temporarily control bleeding and improve central perfusion in critically injured trauma patients remains a controversial topic. In the last decade, select trauma services around the world have gained experience with REBOA. We discuss the recent observational data together with the initial results of the first randomized control trial and provide a view on the next steps for REBOA in trauma resuscitation. While the observational data continue to be conflicting, the first randomized control trial signals that in the UK, in-hospital REBOA is associated with harm. Likely a result of delays to haemorrhage control, views are again split on whether to abandon complex interventions in bleeding trauma patients and to only prioritize transfer to the operating room or to push REBOA earlier into the post injury phase, recognizing that some patients will not survive without intervention. Better understanding of cardiac shock physiology provides a new lens in which to evaluate REBOA through. Patient selection remains a huge challenge. Invasive blood pressure monitoring, combined with machine learning aided decision support may assist clinicians and their patients in the future. The use of REBOA should not delay definitive haemorrhage control in those patients without impending cardiac arrest.


Elevation of serum alpha-fetoprotein in anemic patients.
Alpha-fetoprotein (AFP) is present in the serum of normal healthy adults; an increase in level has been found as a rule in patients with diseases that can affect the liver. In the course of routine examination, we encountered a moderate increase in serum AFP in some patients with acute bleeding anemia, not accompanied by elevation of serum transaminase levels. We examined the relationship between anemia and serum AFP levels, using CIS kits for the assay. The least detectable concentration of below 0.25 ng/ml, which was two standard deviations outside the value obtained for the zero-dose response, was measurable by a two-step incubation: pre-incubation of serum and antiserum followed by addition of [125I]AFP and further incubation. The mean AFP level in 75 normal control sera was 2.4 1.6 ng/ml. There was a significant increase in the mean value of serum AFP levels in acutely anemic patients with no evidence of liver involvement. The increase was moderate, many of the patient samples being within the normal range. The reticulocyte counts did not correlate with the elevated AFP levels, indicating low significance of extra-hepatic AFP synthesis. A moderate increase in AFP production might occur in acutely anemic patients with no detectable hepatic cell damage.


Genetic characterization of Trypanosoma cruzi DTUs in wild Triatoma infestans from Bolivia: predominance of TcI.
The current persistence of Triatoma infestans (one of the main vectors of Chagas disease) in some domestic areas could be related to re-colonization by wild populations which are increasingly reported. However, the infection rate and the genetic characterization of the Trypanosoma cruzi strains infecting these populations are very limited. Of 333 wild Triatoma infestans specimens collected from north to south of a Chagas disease endemic area in Bolivia, we characterized 234 stocks of Trypanosoma cruzi using mini-exon multiplex PCR (MMPCR) and sequencing the glucose phosphate isomerase (Gpi) gene. Of the six genetic lineages ("discrete typing units"; DTU) (TcI-VI) presently recognized in T. cruzi, TcI (99.1%) was overdominant on TcIII (0.9%) in wild Andean T. infestans, which presented a 71.7% infection rate as evaluated by microscopy. In the lowlands (Bolivian Chaco), 17 "dark morph" T. infestans were analyzed. None of them were positive for parasites after microscopic examination, although one TcI stock and one TcII stock were identified using MMPCR and sequencing. By exploring large-scale DTUs that infect the wild populations of T. infestans, this study opens the discussion on the origin of TcI and TcV DTUs that are predominant in domestic Bolivian cycles.


What Are We Curious about?
What are we curious about? Dubey and Griffiths propose a rational theory of curiosity that unifies previously contradictory novelty-based and complexity accounts. It also paves the way for future investigations, such as studying approximate models of curiosity as well as what causes abnormal levels of exploration.


Combined application of arsenic trioxide and lithium chloride augments viability reduction and apoptosis induction in human rhabdomyosarcoma cell lines.
Rhabdomyosarcomas (RMS) are the most prevalent soft tissue sarcomas affecting children and adolescents. Despite intensive treatment consisting of multimodal chemotherapy and surgery RMS patients diagnosed with metastatic disease expect long term survival rates of only 20%. Often multidrug resistance arises upon initial response emphasizing the need for new therapeutic drugs to improve treatment efficiency. Previously, we demonstrated the efficacy of the FDA approved drug arsenic trioxide (ATO) specifically inhibiting viability and clonal growth as well as inducing cell death in human RMS cell lines of different subtypes. In this study, we combined low dose ATO with lithium chloride (LiCl), which is approved as mood stabilizer for the treatment of bipolar disorder, but also inhibits growth and survival of different cancer cell types in pre-clinical research. Indeed, we could show additive effects of LiCl and ATO on viability reduction, decrease of colony formation as well as cell death induction. In the course of this, LiCl induced inhibitory glycogen synthase kinase-3β (GSK-3β) serine 9 phosphorylation, whereas glioma associated oncogene family 1 (GLI1) protein expression was particularly reduced by combined ATO and LiCl treatment in RD and RH-30 cell lines, showing high rates of apoptotic cell death. These results imply that combination of ATO with LiCl or another drug targeting GSK-3 is a promising strategy to enforce the treatment efficiency in resistant and recurrent RMS.


Whether early stage pancreatic ductal adenocarcinoma patients could benefit from the post-operation chemotherapy regimens: a SEER-based propensity score matching study.
To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). A total of 5280 stage ⅠA -ⅡB PDAC patients diagnosed from 2010 to 2015 were selected from surveillance,epidemiology,and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage ⅠB, ⅡA and ⅡB patients. However, for stage ⅠA patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (=283) and without chemotherapy (=229) (57.4% vs 55.6%, vs all >0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in survival rate and mOS between patients with and without chemotherapy (all >0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, vs all <0.05). Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage ⅠA PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.


A MEN1 Patient Presenting With Multiple Parathyroid Adenomas and Transient Hypercortisolism: A Case Report and Literature Review.
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by mutations in MEN1 tumor suppressor gene. A 53-year-old Chinese female was admitted to Division of Endocrinology, Tongji Hospital, for hypercalcemic crisis. Increased level of parathyroid hormone (PTH) was confirmed by laboratory tests, and imaging examination showed multiple parathyroid adenomas. Based on gene analysis, the patient was diagnosed as MEN1 associated hyperparathyroidism (HPT) by gene analysis with c.1378C>T (p.Arg460Ter) mutation in MEN1 gene. Her condition was complicated by transient hypercortisolism, mammary mass and uterine leiomyoma. After subtotal parathyroidectomy, PTH and serum calcium levels returned to normal. HPT with multiple parathyroid adenomas is an indication of MEN1 gene mutation. Serum cortisol and its circadian rhythm can be abnormal in the presence of hypercalcemia and high PTH. These parameters can return to normal after parathyroidectomy.


[B Streptococcus and other pathogenic bacteria colonization in hospitals in the Gdańsk Metro Area].
A survey of group B Streptococcus and other pathogenic bacteria colonization was carried out on 658 neonates in 8 neonatal wards of hospitals in the Gdańsk Metro Area and the district of Gdańsk. Out of pathogenic bacteria Haemophilus and enteric bacteria the most frequently were isolated. The percentage of Staphylococcus aureus was relatively low (19.4). The group B Streptococcus frequency in throat was established as 3.8% and ranging from 1.7 to 8.8% in particular wards. In two cases group B streptococcus were not isolated. In probes taken from anus of newborn tested typical enteric flora dominated and E coli and Klebsiella sp were the most frequently encountered. Profile and frequency of bacterial colonization indicated that epidemiological situation in majority of particular wards in similar.


Endemic tropical spastic paraparesis associated with human T-lymphotropic virus type I: a clinical and seroepidemiological study of 25 cases.
Tropical spastic paraparesis (TSP) is a common myeloneuropathy with primary and predominant involvement of the pyramidal tract and minimal sensory loss. The epidemic form of TSP is related to toxic nutritional factors, but the endemic form occurs in clusters in tropical areas, especially in India, Africa, the Seychelles, Colombia, and areas of the Caribbean. We describe the clinical and epidemiological features of 25 TSP patients from Martinique (French West Indies) with serum antibodies to human T-lymphotropic virus type I (HTLV-I). Furthermore, all 11 patients who were seropositive for HTLV-I had specific HTLV-I antibodies in their CSF. All were women. The age of onset varied from 25 to 60 years (mean, 45 years). The main clinical features are spastic paraparesis or paraplegia with spasticity of the upper limbs, minimal sensory loss, and bladder dysfunction. Minimal estimated incidence and prevalence are 1 per 100,000 inhabitants per year and 8 per 100,000, respectively. Seventeen percent of the relatives of patients with HTLV-I-associated TSP have HTLV-I antibodies (1 husband and 7 children). In Martinique, the prevalence of HTLV-I antibodies in the general population is about 2% and reaches 10% for neurological disorders other than TSP. Since our initial report, the association between spastic paraparesis and HTLV-I has been confirmed in Jamaica, Colombia, and Japan, suggesting the neurotropism of this lymphotropic human retrovirus.


Near-Patient Sampling to Assist Infection Control-A Case Report and Discussion.
Air sampling as an aid to infection control is still in an experimental stage, as there is no consensus about which air samplers and pathogen detection methods should be used, and what thresholds of specific pathogens in specific exposed populations (staff, patients, or visitors) constitutes a true clinical risk. This case report used a button sampler, worn or held by staff or left free-standing in a fixed location, for environmental sampling around a child who was chronically infected by a respiratory adenovirus, to determine whether there was any risk of secondary adenovirus infection to the staff managing the patient. Despite multiple air samples taken on difference days, coinciding with high levels of adenovirus detectable in the child's nasopharyngeal aspirates (NPAs), none of the air samples contained any detectable adenovirus DNA using a clinically validated diagnostic polymerase chain reaction (PCR) assay. Although highly sensitive, in-house PCR assays have been developed to detect airborne pathogen RNA/DNA, it is still unclear what level of specific pathogen RNA/DNA constitutes a true clinical risk. In this case, the absence of detectable airborne adenovirus DNA using a conventional diagnostic assay removed the requirement for staff to wear surgical masks and face visors when they entered the child's room. No subsequent staff infections or outbreaks of adenovirus have so far been identified.


Novel nitric oxide-releasing derivatives of pyranocarbazole as antitumor agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
In this study, a series of novel furoxan-based nitric oxide (NO) releasing derivatives of pyranocarbazole alkaloids were designed, synthesized, and biologically evaluated against human cancer cell lines. The derivatives showed considerable antiproliferative activities (IC50 = 0.05-7.55 μM) and most compounds showed higher activity in MDA-MB-231 than H460 and HeLa. Especially, the most active derivative 7a (IC50 = 0.05 μM) against MDA-MB-231 was about 60 times stronger than lead compound, as well as equivalent to positive control taxol, and produced high levels of NO in MDA-MB-231. Furthermore, 7a could significantly inhibit the growth of MDA-MB-231 tumors in vivo with low toxicity and the PI3K/Akt signaling pathway. These results indicated that compound 7a could be a promising lead for further studies.


Infrared Image-Enhancement Algorithm for Weak Targets in Complex Backgrounds.
Infrared small-target enhancement in complex contexts is one of the key technologies for infrared search and tracking systems. The effect of enhancement directly determines the reliability of the monitoring equipment. To address the problem of the low signal-to-noise ratio of small infrared moving targets in complex backgrounds and the poor effect of traditional enhancement algorithms, an accurate enhancement method for small infrared moving targets based on two-channel information is proposed. For a single frame, a modified curvature filter is used in the A channel to weaken the background while an improved PM model is used to enhance the target, and a modified band-pass filter is used in the B channel for coarse enhancement followed by a local contrast algorithm for fine enhancement, based on which a weighted superposition algorithm is used to extract a single-frame candidate target. The results of the experimental data analysis prove that the method has a good enhancement effect and robustness for small IR motion target enhancement in complex backgrounds, and it outperforms other advanced algorithms by about 43.7% in ROC.


Transformation of a primitive myxoid mesenchymal tumor of infancy to an undifferentiated sarcoma: a first reported case.
An 8-month-old girl underwent surgical resection of a cervical mass with histologic diagnosis of a primitive myxoid mesenchymal tumor of infancy (PMMTI). More than 5 years after the initial surgical intervention, the tumor recurred locally, with numerous distant metastases. The histologic morphology of this tumor was compatible with a diagnosis of an undifferentiated high-grade sarcoma. PMMTI is a recently described poorly differentiated fibroblastic soft-tissue tumor of infancy, of at least borderline biological behavior, characterized by local recurrence and a potential to metastasize. We present here the first case of a transformation of a PMMTI into an undifferentiated high-grade sarcoma.


High frequency of coeliac disease in adult patients with type-I diabetes.
Anti-reticulin antibodies were measured by an indirect immunofluorescence method in 195 consecutive patients with insulin-dependent diabetes mellitus, and positive titres were found in 8 patients. A jejunal biopsy was performed in these patients, all of whom had small-intestinal atrophy. Thus the frequency of coeliac disease in adult diabetes patients was 4.1%. The patients had no signs of malabsorption or of significant abdominal complaints. We conclude that coeliac disease is commoner in type-I diabetes than in the normal population, and measurement of anti-reticulin antibodies seems to be a suitable screening method.


Estrogen receptors in colorectal adenocarcinomas and in other large bowel diseases.
Seventy-two patients with tumor and ten with non-neoplastic colon disease were studied for the presence of estrogen receptors (ER) by three different methods. Only seven specimens (six primary adenocarcinomas and one recurrent cancer) had an ER concentration above 3 fm/mg of cytosolic protein, with no sex, age and tumor stage correlation. Our results suggest that the large bowel does not contain a cytosolic receptor for estradiol.