Prediction of compression and deformation behaviours of gangue backfill materials under multi-factor coupling effects for strata control and pollution reduction.
Coal mining causes serious ecological and environmental damage. The crushed gangue is backfilled into underground goaf, which not only inhibits mining-induced subsidence but also reduces accumulation of waste on the ground: however, the effects of backfilling with gangue backfill materials in goaf are affected by a combination of multiple factors. To predict compression-induced deformation (CID) of gangue backfill materials, key factors influencing compression and deformation characteristics of gangue backfill materials in an underground confined space (lithology, particle size distribution, lateral stress and lateral loading times) were determined. Moreover, two key factors, namely, lithology and particle size distribution of gangue backfill materials, were quantified. Based on orthogonal test design, the compression characteristics of gangue backfill materials were measured under different stress levels and coupling effects of the four key factors by utilising a self-made bidirectional loading test system for bulk materials. Furthermore, through regression, the relationships of the four key factors and axial strain were determined as well as undetermined parameters in axial stress-axial strain equations and axial stress. Based on this, an equation for predicting stress-strain relationship during compression-induced deformation of gangue backfill materials under multi-factor coupling effects was established. Comparison with the orthogonal test results shows that this equation can predict compression-induced deformation of gangue backfill materials in goaf. This is beneficial to providing a basis for predicting strata movement and surface subsidence and guidance for designing backfilling process, thus protecting the surface environment.


Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours.
Lurbinectedin was approved by FDA and other health regulatory agencies for treating adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Safety profile at approved dose (3.2 mg/m2 every 3 weeks) was acceptable and manageable in 105 adult SCLC patients from a phase II basket trial. This study analyses safety data from several solid tumours treated at the lurbinectedin-approved dose. Data were pooled from 554 patients: 335 from all nine tumour-specific cohorts of the phase II basket trial and 219 from a randomised phase III trial (CORAIL) in platinum-resistant ovarian cancer. Events and laboratory abnormalities were graded using NCI-CTCAE v.4. Most common tumours were ovarian (n = 219, 40%), SCLC (n = 105, 19%) and endometrial (n = 73, 13%). Transient haematological laboratory abnormalities were the most frequent grade 3 or more events: neutropenia (41%), leukopenia (30%), anaemia (17%) and thrombocytopenia (10%). Most common treatment-emergent non-haematological events (any grade) were transient transaminase increases (alanine aminotransferase [66%], aspartate aminotransferase [53%]), fatigue (63%), nausea (57%), constipation (32%), vomiting (30%) and decreased appetite (25%). Dose reductions were mostly due to haematological toxicities, but most patients (79%) remained on full lurbinectedin dose. Serious events mostly consisted of haematological disorders. Eighteen treatment discontinuations (3%) and seven deaths (1%) were due to treatment-related events. This analysis confirms a manageable safety profile for lurbinectedin in patients with advanced solid tumours. Findings are consistent with those reported in patients with relapsed SCLC, Ewing sarcoma, germline BRCA1/2 metastatic breast cancer, neuroendocrine tumours and ovarian cancer.


Phylogenetic analysis using E2 gene of classical swine fever virus reveals a new subgenotype in China.
Outbreaks of classical swine fever (CSF) have caused serious economic consequences in China. Phylogenetic analysis based on full-length E2 gene sequences showed that five classical swine fever virus (CSFV) isolates collected from Hunan province in 2011 and 2012, together with seven other isolates from neighboring provinces, Guangdong (5) and Guangxi (2), could be classified as a new subgenotype 2.1c, which may have been endemic in the south of China for at least fourteen years. Subgenotype 2.1c isolates share 90.2-94.9% and 89.9-93.8% nucleotide sequence similarity separately with those of subgenotype 2.1a and 2.1b in E2 gene, which are lower than the nucleotide identities between subgenotype 2.1a and 2.1b (91.1-95.7%). Further analysis based on a partial E2 gene sequence (216 nt) indicated that subgenotype 2.1c isolates are also circulating in Thailand. Alignment of E2 amino acid sequences showed that subgenotype 2.1c isolates exhibit a SPA → TPV substitution at positions 777 and 779 compared with subgenotypes 2.1a and 2.1b.


Inflammation markers correlate with common carotid intima-media thickness in patients perinatally infected with human immunodeficiency virus 1.
To investigate common carotid intima-media thickness in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV-1). We conducted a cross-sectional observational study. Human immunodeficiency virus 1-infected patients were compared with age-, sex-, and body mass index-matched healthy participants. Common carotid intima-media thickness was measured in all participants on both sides of the neck, and the mean intima-media thickness was calculated. Metabolic parameters and markers of inflammation were measured only in HIV-1-infected patients. Statistical analysis was performed by multiple regression and by a matrix of Pearson correlation coefficients. The Student t test was used to compare mean common carotid intima-media thickness values between groups. Forty patients (21 female) with HIV-1 infection acquired from birth with a mean age ± SD of 16.3 ± 4.7 years and 27 healthy participants (11 female) with a mean age of 17.7 ± 4.6 years were included in the study. Mean common carotid intima-media thickness in the HIV-1-infected group (0.450 ± 0.088 mm) was significantly higher (P < .05) than in the control group (0.407 ± 0.079 mm). No significant association was found between intima-media thickness and a specific antiretroviral regimen, exposure to combined antiretroviral agents, and HIV status. In multiple regression analyses, higher levels of insulin (P= .007) and elevated levels of glycated hemoglobin (P= .01) were associated with intima-media thickness changes. Patients perinatally infected with HIV have increased common carotid intima-media thickness compared with healthy individuals. These changes were more pronounced with increasing age and inflammation markers. Interventions that improve cardiovascular risk profiles should be considered in HIV-infected young adults.


Quali-quantitative analysis of plastics and synthetic microfibers found in demersal species from Southern Tyrrhenian Sea (Central Mediterranean).
This study highlights plastics occurrence in five demersal fish species from the Southern Tyrrhenian Sea: the Red mullet Mullus barbatus barbatus, the Piper gurnard Trigla lyra, the Blackmouth catshark Galeus melastomus, the Lesser spotted dogfish Scyliorhinus canicula and the Brown ray Raja miraletus. Overall, 125 fish were examined: 21 Red mullets, 16 Piper gurnards, 75 Blackmouth catsharks, 72 Dogfish and 1 Brown ray. The percentage of fish with ingested plastics was 14.4% with 0.24 items per specimen. The majority of the debris were fibers and the application of infrared and Raman spectroscopy allowed the identification and discrimination of plastic and non-plastic fibers. The plastic debris isolated were mainly microplastics (94.1%), while macroplastics occurrence was very low (5.9%). The plastics were identified as polypropylene, Teflon, nylon, kraton G (triblock copolymer) and polyethylene. Also cellulose was detected. S. canicula was the species with the highest number of plastic pollutants.


Health underachievement and overachievement in English local authorities.
To identify English local authorities that "overachieve" and "underachieve" in health terms, given their level of deprivation, sociodemographic context, and region. Cross sectional study using data from the 1991 UK census and mortality data from 2000-2. England. 354 local authorities (total population 49 558 000). Life expectancy. Residual life expectancy after regression analysis. In general, the more materially deprived the population of a local authority was in 1991, the lower its life expectancy a decade later, with men being more sensitive to the effects of deprivation than women. Many local authorities, however, did not follow this general trend, and these shared common characteristics. Mining, Manufacturing and Industry, and Urban Fringe authorities collectively had lower life expectancies than predicted by their level of deprivation, as did authorities located in the north west. Outer London and Education Centres and Inner London authorities had much higher life expectancies than predicted, as did authorities located in the east, south east, and south west. Given their level of deprivation, sociodemographic context, and region, 11 local authorities significantly overachieved for male life expectancy and 10 underachieved, while 12 overachieved for female life expectancy and three underachieved. Life expectancy in English local authorities is strongly associated not only with material deprivation, but with the local sociodemographic context and the region where the authority is located. Some authorities defy their contexts, however, and overachieve in health terms, while others, including some in affluent areas, underachieve.


Sensory and Motor Behavior Evidences Supporting the Usefulness of Conditioned Medium from Dental Pulp-Derived Stem Cells in Spinal Cord Injury in Rats.
Experimental animal study. This study aimed to assess effects of conditioned medium (CM) of dental pulp-derived stem cells loaded in collagen hydrogel on functional recovery following spinal cord injury (SCI). SCI affects sensory and motor functions, and behavioral recovery is the most essential purpose of therapeutic intervention. Recent studies have reported that CM from dental pulp-derived stem cells has therapeutic benefits. In addition, collagen hydrogel acts as a drug delivery system in SCI experiments. Stem cells from human exfoliated deciduous teeth (SHEDs) were cultured, and SHED-CM was harvested and concentrated. Collagen hydrogel containing SHED-CM was prepared. The rats were divided into five groups receiving laminectomy, compressive SCI with or without intraspinal injection of biomaterials (SHED-CM), and collagen hydrogel with or without SHED-CM. Basso, Beattie, and Bresnahan (BBB) scoring, inclined plane, cold allodynia, and beam walk tests were performed for 6 weeks to assess locomotor, motor, sensory, and sensory-motor performances, respectively. Scores of the rats receiving SHED-CM loaded in collagen hydrogel were significantly better than those of the other injured groups at 1-week post-injury for BBB, 2 weeks for inclined plane, 2 weeks for cold allodynia, and 4 weeks for beam walk tests (p <0.05). The differences remained significant throughout the study. Intraspinal administration of SHED-CM loaded in collagen hydrogel leads to improved functional recovery and proposes a cell-free therapeutic approach for SCI.


An RNA Repair Operon Regulated by Damaged tRNAs.
Many bacteria contain an RNA repair operon, encoding the RtcB RNA ligase and the RtcA RNA cyclase, that is regulated by the RtcR transcriptional activator. Although RtcR contains a divergent version of the CARF (CRISPR-associated Rossman fold) oligonucleotide-binding regulatory domain, both the specific signal that regulates operon expression and the substrates of the encoded enzymes are unknown. We report that tRNA fragments activate operon expression. Using a genetic screen in Salmonella enterica serovar Typhimurium, we find that the operon is expressed in the presence of mutations that cause tRNA fragments to accumulate. RtcA, which converts RNA phosphate ends to 2', 3'-cyclic phosphate, is also required. Operon expression and tRNA fragment accumulation also occur upon DNA damage. The CARF domain binds 5' tRNA fragments ending in cyclic phosphate, and RtcR oligomerizes upon binding these ligands, a prerequisite for operon activation. Our studies reveal a signaling pathway involving broken tRNAs and implicate the operon in tRNA repair.


Corynebacterium glutamicum mechanosensitive channels: towards unpuzzling "glutamate efflux" for amino acid production.
Corynebacterium glutamicum has been utilized for industrial amino acid production, especially for monosodium glutamate (MSG), the food-additive for the "UMAMI" category of taste sensation, which is one of the five human basic tastes. Glutamate export from these cells is facilitated by the opening of mechanosensitive channels in the cell membrane within the bacterial cell envelope following specific treatments, such as biotin limitation, addition of Tween 40 or penicillin. A long-unsolved puzzle still remains how and why C. glutamicum mechanosensitive channels are activated by these treatments to export glutamate. Unlike mechanosensitive channels in other bacteria, these channels are not simply osmotic safety valves that prevent these bacteria from bursting upon a hypo-osmotic shock. They also function as metabolic valves to continuously release glutamate as components of a pump-and-leak mechanism regulating the cellular turgor pressure. Recent studies have demonstrated that the opening of the mechanosensitive channel, MscCG, mainly facilitates the efflux of glutamate and not of other amino acids and that the "force-from-lipids" gating mechanism of channels also applies to the MscCG channel. The bacterial types of mechanosensitive channels are found in cell-walled organisms from bacteria to land plants, where their physiological functions have been specialized beyond their basic function in bacterial osmoregulation. In the case of the C. glutamicum MscCG channels, they have evolved to function as specialized glutamate exporters.


Use of logistic regression in comparing multiple limiting dilution analyses of antigen-reactive T cells.
Traditionally, statistical analyses of multiple limiting dilution analyses have used linear regression in comparing the fit of each analysis to a single-hit Poisson model. Multiple analyses can, however, result in an inflated type I error leading to spurious rejection of the null hypothesis. Logistic regression was used as an umbrella statistic to analyze eight limiting dilution analyses for antigen-reactive T cells from two mouse strains (SJL/J; B10.S), at two priming doses of antigen, for each of two antigens (porcine myelin basic protein, PMBP; purified protein derivative of M. tuberculosis, PPD) used to induce experimental allergic encephalomyelitis (EAE). This proved superior to traditional methods: six of the eight strain/dose/antigen combinations were consistent with a viable model, whereas only three of eight were consistent with the Poisson single-hit model. Moreover, only three of the resultant 32 standardized residual values (four per group times eight groups) fell outside the 95% confidence interval. Logistic regression, therefore, is recommended when nominal dependent measures can be structured as a function of more than one independent variable.


Carcinomatous meningitis in a case of anaplastic meningioma.
Malignant meningiomas are associated with a high rate of local recurrence, but seldom give remote metastases. Here, we report a case with carcinomatous meningitis occurring 13 months after treatment of the initial tumor. MRI showed no significant abnormalities. CSF contained abnormal cells, and electronic microscopy after cytocentrifugation confirmed their identity with the initial tumor.


Factors influencing the time to administration of thrombolytic therapy with recombinant tissue plasminogen activator (data from the National Registry of Myocardial Infarction). Participants in the National Registry of Myocardial Infarction.
Very early administration of thrombolytic therapy for acute myocardial infarction (AMI) has significantly reduced mortality in eligible patients. The purpose of this study was to evaluate factors which influenced the time from symptom onset to hospital presentation and the time from hospital presentation to the onset of thrombolytic treatment in a large population of patients with AMI. This study included 212,990 patients from 904 hospitals that participated in the National Registry of Myocardial Infarction. The median time from symptom onset to hospital presentation for those treated was 1.5 hours versus 2.7 hours for those not receiving thrombolytic treatment. Older patients and women had increased delay times, as did those who arrived at the hospital during daytime hours. Of the 59,802 (28%) patients who received thrombolytic treatment, 23% were treated < 30 minutes from admission; 63%, < 60 minutes; and 83%, < 90 minutes. Time to treatment increased with age and was longer for women and for patients arriving between midnight and early morning. The most important factor associated with shorter time to treatment was the initiation of thrombolytic treatment in the emergency department rather than in the coronary care unit (47 vs 73 minutes, p < 0.0001). Hospital treatment times are much too long, given that quick identification and treatment of eligible patients are of primary importance in reducing mortality from AMI. To shorten these times, thrombolytic treatment should be initiated in the emergency department, and the effectiveness of hospital programs aimed at reducing time to treatment should be subject to continuing quality improvement surveillance.


Dermoid cyst of the mandibula: a case report.
Dermoid cysts are rare congenital lesions derived from pluripotential cells. We present a case of a female patient aged 30 years presenting for a lesion of the mandibula incidentally seen on a routine panoramic radiograph obtained for dental care. The instrumental, clinical and histological characteristics of the lesion are reported. Finally, a bibliographic revision of this pathology at the level of the oral cavity is reported. Dermoid cysts must be considered in the differential diagnosis of mandibula's lesions.


The Role of Invasive Pain Management Modalities in the Treatment of Chronic Pain.
Invasive analgesic therapies provide an alternative to medical management of chronic pain. With the increasing incidence of chronic pain not only in the United States but worldwide, more therapies have evolved to address the growing need for pain relief options. These therapies include spinal injections, nerve blocks, radiofrequency ablation, neurostimulation, and intrathecal drug delivery.


The discrepancy between the cross-reactivity of a monoclonal antibody to serotonin and its immunohistochemical specificity.
The rat monoclonal antibody YC5/45 has been shown to react specifically with serotonin containing neurones, and does not detect dopamine containing sites. On the other hand the monoclonal antibody recognizes dopamine, since it is capable of inhibiting the binding of 3H-YC5/45 to sheep red blood cells coated with serotonin albumin conjugate, or the direct agglutination of the same cells by the monoclonal antibody. Tryptamine and 5-methoxytryptamine are even better inhibitors, while derivatives with a modified-CH2-CH2-NH2 group are inactive. Treatment of the active compounds with paraformaldehyde increases their efficiency dramatically. The binding of antibody was also tested by cross linking with paraformaldehyde: dopamine, serotonin, tryptamine, 5-methoxytryptamine etc., to serum albumin. Only the serotonin derivative was active. The result shows that the discrimination specificity observed in immunohistochemistry is due to the paraformaldehyde fixation. It is concluded that for histochemical detection of serotonin by YC5/45, two reactive sites are necessary. The -CH2-CH2-NH2 group is probably modified by formaldehyde to produce a cyclic derivative to form the antibody recognition site. A different formaldehyde reactive site is required for cross linking to the tissue and this is provided by the presence of the 5-OH of serotonin which is absent in the others.


Solving teenage and young mothers' childhood immunization hesitance and non-compliance through mobile immunization friendly service for working mothers in Ibadan, Nigeria- A research note.
Mobile Immunization for working mothers (SheVaccs) is an intervention targeted at working mothers in the informal markets of Ibadan to address problem of vaccine hesitance and drop-out among different categories of mother. These mothers have great responsibilities-keeping their homes stable and their children healthy. But these mothers have challenges of different magnitudes that prevented them from immunizing their children, and for teenage mothers they are faced with socio-cultural and socio-economic obstacles and have not responded positively to childhood immunization. In relation to these challenges, SheVaccs intervention study provided friendly immunization, counselling services, and information around vaccination schedules to working mothers in Ibadan, Nigeria. The intervention covered adolescent and young mothers' population in the selected markets. Mobile clinic was set up in 3 different purposively selected markets in Ibadan. Data were collected through qualitative methods of observation and 21 in-depth interviews with teenage mothers, and 6 key informant interviews with their significant others. All data were subjected to content analysis. The age range of mothers involved in the study was between 17-23 years, almost all participants had no post- secondary school education. All mothers in this study find it difficult to attend conventional immunization centers, due to stigmatization, subtle hostility and embarrassment they experienced during pregnancy and after in some of these centers. Many of them were ignorant and have also been mis-socialized into motherhood and childcare. They preferred an immunization service that is mobile, with "strangers" who are friendly, understanding and will not judge them for ''being anti-social". Friendly Mobile immunization services targeted at teenage and young mothers will remove clog of stigmatization and hostility and minimize incidence of childhood Immunization Hesitance and non-compliance to schedule.


Presentation of primary hyperparathyroidism to a general medical unit.
Four patients with hyperparathyroidism who presented in atypical or uncommon ways to a general medical unit are described. The unusual features are discussed and the value of modern procedures for localization of a parathyroid tumour is confirmed.


Determination of Cytotoxicity.
Cytotoxicity assays are used for drug screening and cytotoxicity tests of chemicals. Nowadays, various reagents are used for cell viability detection. They are based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production and nucleotide uptake activity. Many have established methods such as colony formation method, crystal violet method, tritium-labelled thymidine uptake method, MTT and WST methods, which are used for counting the number of live cells. Moreover, trypan blue is a widely used assay for staining dead cells. In this method, cell viability must be determined by counting the unstained cells with a microscope or other instruments. This chapter is a collection of all these methods to be followed by researchers in a sequential manner.


Ethnic and genetic determinants of omeprazole disposition and effect.
To compare the pharmacokinetics and dynamics of omeprazole in white and Chinese subjects. This double-blind two-stage study, performed in the clinical research center of a university hospital, evaluated 15 healthy nonsmoking men (eight white subjects and seven Chinese extensive metabolizers of mephenytoin). Blood samples were obtained over 24 hours after the eighth omeprazole dose (40 mg/day). Omeprazole, omeprazole sulfone, and hydroxyomeprazole pharmacokinetics were calculated from the respective plasma concentration-time curves. Twelve- and 24-hour integrated plasma gastriun (AUCgas12 and AUCgas24) were calculated from the respective plasma gastrin concentrations. A week before the initiation of omeprazole the activities of CYP2D6, CYP2C19, and CYP3A4 were determined by previously established methods. Omeprazole concentrations were significantly lower (mean area under the plasma concentration time curve extrapolated to infinity [AUCO-infinity] +/- SEM; 7.53 +/- 1.21 versus 12.80 +/- 2.13 mumol.hr.L-1, respectively; p < 0.05) and its oral clearance greater (319 +/- 60 versus 183 +/- 35 ml/min, respectively; p < 0.05) in the white subjects than in the Chinese subjects. Omeprazole and omeprazole sulfone AUCO-infinity values were well correlated with the S/R mephenytoin ratio (r = 0.82 and r = 0.84, respectively; p < 0.001) and with urinary 4'-hydroxymephenytoin (r = -0.58 [p < 0.03] and r = -0.52 [p < 0.02], respectively). Fasting gastrin, AUCgas12, and AUCgas24 were significantly greater in the Chinese subjects than in the white subjects (30.0 +/- 6.4 versus 14.4 +/- 1.2 pmol, respectively [p < 0.02]; 661 +/- 114 versus 334 +/- 38 pmol.hr.L-1, respectively [p < 0.002]; and 1414 +/- 228 versus 747 +/- 99 pmol.hr.L-1, respectively [p < 0.004]). In addition, the S/R mephenytoin ratio and omeprazole AUCO-infinity correlated with the extent of omeprazole induced hypergastrinemia. The metabolism of omeprazole and the rise in gastrin concentration after its administration is genetically determined and ethnically dependent.


Cancer treatment and survivorship statistics, 2016.
The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. © 2016 American Cancer Society.


Case Studies in Physiology: Cardiopulmonary exercise testing and inspiratory muscle training in a 59-year-old, 4 years after an extrapleural pneumonectomy.
This case report characterizes the physiological responses to incremental cycling and determines the effects of 12 wk of inspiratory muscle training (IMT) on respiratory muscle strength, exercise capacity, and dyspnea in a physically active 59-yr-old female, 4 years after a left-sided extrapleural pneumonectomy (EPP). On separate days, a symptom-limited incremental exercise test and a constant work rate (CWR) test at 75% of peak work rate (WR) were completed, followed by 12 wk of IMT and another CWR test. IMT consisted of two sessions of 30 repetitions twice daily for 5 days per week. Physiological and perceptual variables were measured throughout each exercise test. The participant had a total lung capacity that was 43% predicted post-EPP. A rapid and shallow breathing pattern was adopted throughout exercise, and the ratio of minute ventilation to carbon dioxide output was elevated for a given work rate. Oxygen uptake was 71% predicted and WR was 88% predicted. Following IMT, maximal inspiratory pressure improved by 36% (-27.1 cmH2O) and endurance time by 31 s, with no observable changes in any submaximal or peak cardiorespiratory variables during exercise. The intensity and unpleasantness of dyspnea increased by 2 and 3 Borg 0-10 units, respectively, at the highest equivalent submaximal exercise time achieved on both tests. Despite having undergone a significant reduction in lung volume post-EPP, the participant achieved a relatively normal peak incremental WR, which may reflect a high level of physical conditioning. This case report also demonstrates that IMT can effectively increase respiratory muscle strength several years following EPP.NEW & NOTEWORTHY Constraints on tidal volume expansion and the adoption of a rapid and shallow breathing pattern result in a ventilatory limitation and increased ventilatory inefficiency during exercise in a patient several years after extrapleural pneumonectomy (EPP). Inspiratory muscle training can effectively increase respiratory muscle strength after EPP.


HLA-DRB1*1501 influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis.
Whether genetic factors influence the long-term course of multiple sclerosis (MS) is unresolved. To determine the influence of HLA-DRB1*1501 on long-term disease course in a homogeneous cohort of clinically isolated syndrome (CIS) patients. One hundred seven patients underwent clinical and MRI assessment at the time of CIS and after 1, 3, 5 and 15 years. HLA-DRB1*1501 status was determined using Sanger sequencing and tagging of the rs3135388 polymorphism. Linear/Poisson mixed-effects models were used to investigate rates of change in EDSS and MRI measures based on HLA-DRB1*1501 status. HLA-DRB1*1501 -positive (n = 52) patients showed a faster rate of disability worsening compared with the HLA-DRB1*1501 -negative (n = 55) patients (annualised change in EDSS 0.14/year vs. 0.08/year, p < 0.025), and a greater annualised change in T2 lesion volume (adjusted difference 0.45 mL/year, p < 0.025), a higher number of gadolinium-enhancing lesions, and a faster rate of brain (adjusted difference -0.12%/year, p < 0.05) and spinal cord atrophy (adjusted difference -0.22 mm2/year, p < 0.05). These findings provide evidence that the HLA-DRB1*1501 allele plays a role in MS severity, as measured by long-term disability worsening and a greater extent of inflammatory disease activity and tissue loss. HLA-DRB1*1501 may provide useful information when considering prognosis and treatment decisions in early relapse-onset MS.


The role of mesophyll conductance in the economics of nitrogen and water use in photosynthesis.
A recent resurgence of interest in formal optimisation theory has begun to improve our understanding of how variations in stomatal conductance and photosynthetic capacity control the response of whole plant photosynthesis and growth to the environment. However, mesophyll conductance exhibits similar variation and has similar impact on photosynthesis as stomatal conductance; yet, the role of mesophyll conductance in the economics of photosynthetic resource use has not been thoroughly explored. In this article, we first briefly summarise the knowledge of how mesophyll conductance varies in relation to environmental factors that also affect stomatal conductance and photosynthetic capacity, and then we use a simple analytical approach to begin to explore how these important controls on photosynthesis should mutually co-vary in a plant canopy in the optimum. Our analysis predicts that when either stomatal or mesophyll conductance is limited by fundamental biophysical constraints in some areas of a canopy, e.g. reduced stomatal conductance in upper canopy leaves due to reduced water potential, the other of the two conductances should increase in those leaves, while photosynthetic capacity should decrease. Our analysis also predicts that if mesophyll conductance depends on nitrogen investment in one or more proteins, then nitrogen investment should shift away from Rubisco and towards mesophyll conductance if hydraulic or other constraints cause chloroplastic CO2 concentration to decline. Thorough exploration of these issues awaits better knowledge of whether and how mesophyll conductance is itself limited by nitrogen investment, and about how these determinants of photosynthetic CO2 supply and demand co-vary among leaves in real plant canopies.


Miltefosine resistance in Leishmania donovani involves suppression of oxidative stress-induced programmed cell death.
Miltefosine (MIL), an alkylphospholipid, is the first orally administrable anti-leishmanial drug. But due to its long half-life, miltefosine is highly vulnerable for resistance. Hence it is important to understand the mechanism of resistance and to elucidate its action on Leishmania. Here we investigate the miltefosine induced process of programmed cell death in wild type (miltefosine sensitive) and in laboratory generated resistant strains of Leishmania donovani. Results indicate that miltefosine induced apoptosis like death in a time and dose dependent manner in wild-type cells, but not in MIL-resistant cell line. The miltefosine resistant cells remained protected against miltefosine-induced loss of mitochondrial membrane potential, gradual ATP loss and cytochrome C release from mitochondria into the cytosol. Comparative transcriptomic study showed significantly increased expression of FeSODA and SIR2 genes, putatively involved in oxidative stress associated apoptotic cell death. We hypothesize that oxidative stress mediated apoptosis as an alternative mechanism of miltefosine resistance.


Lymphopenia in acute nitrofurantoin pleuropulmonary reactions.
Each of 5 patients with acute nitrofurantoin pleuropulmonary reactions had profound lymphopenia and 4 had eosinophilia developing early in the clinical course after the drug was withdrawn. The 2 patients tested had only one third of the normal numbers of E rosettes (T lymphocytes) in the peripheral blood during recovery. Lymphoblastic transformation tests with purified nitrofurantoin were done in 3 patients and all of them were negative; responses to phytohemagglutinin, concanavalin A, and pokeweed were decreased but still normal. The diagnosis of various nitrofurantoin hypersensitivity reactions relies on clinical data. The mechanisms of these reactions presently remain unclear.


Nebulisers comparison with inhaled tobramycin in young children with cystic fibrosis.
This randomised cross-over pilot study was undertaken in 10 cystic fibrosis children aged 10 to 63 months to describe lung absorption of tobramycin delivered by the PariLC+/PariTurboboyN (Pari GmbH) and the disposable NL9M/AtomisorBoxPlus (Diffusion Technique Française) nebulising systems. Each child inhaled 300 mg tobramycin delivered with one or the other apparatus via a facemask in two separate and standardised sessions. Urine was collected for 6 h. Tobramycin concentrations determined by immunoprecipitation were expressed in mg per g of creatinine and compared by a Wilcoxon test for matched pairs. The influences of age, weight and Brasfield score on this parameter were evaluated by correlation tests, and those of sex, previous nebulisation treatment, and crying or coughing were evaluated by Student's t-test. The amount of tobramycin measured in urines was low and variable. Median values for urinary tobramycin concentration were 47.6 mg/g (14.9-79.6) with the PariLC+ and 42.6 mg/g (6.3-112.8) with the NL9M (p=0.6). PariLC+ delivered tobramycin in 22 min and NL9M in 12 min (p=0.005). Crying or coughing dramatically reduced the amount of tobramycin collected. This pilot study shows that evaluation of nebulisers based on tobramycin renal excretion is feasible in young children with cystic fibrosis.


D-penicillamine and macrophages: modulation of lymphocyte transformation by concanavalin A.
Pretreatment with D-Penicillamine of rat peritoneal macrophages markedly influences their ability to modulate Concanavalin A stimulated [3H]thymidine incorporation in non-adherent rat lymph node cells. Untreated macrophages added in high numbers to the lymphocytes (ratio lymphocytes/macrophage 7.5 : 1) depress their [3H]thymidine incorporation. Pretreatment with D-Penicillamine further reduces this response. Lower proportions of untreated macrophages (ratio 15 : 1) exert a stimulatory effect on the lymphocytes. This response is reversed by pretreatment of macrophages with D-Penicillamine. Addition of untreated macrophages in very low proportions (40 : 1 and 75 : 1) is without effect on the [3H]thymidine incorporation by the lymphocytes. This response is markedly stimulated by pretreatment of the macrophages with D-Penicillamine. The culture of macrophages in the presence of D-Penicillamine increases their incorporation of [3H]D-glucosamine, but it is without effect on their incorporation of [3H]L-leucine. It is suggested that D-Penicillamine enhances the functional activity of the macrophage in the regulation of the lymphocyte response to mitogens.


Exposing the cancer genome atlas as a SPARQL endpoint.
The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source.


Evaluation and follow-up of pancreatic arteriograms. A new role for angiography in the diagnosis of carcinoma of the pancreas.
Of over 300 pancreatic arteriograms done in this hospital group adequate follow-up was possible in only 103 patients, with carcinoma in 35 of them. Based on the prospective report there were three false negatives and seven false positive carcinoma diagnoses, an overall accuracy rate of 90.3%. A retrospective review could eliminate all but one false negative and one false positive diagnosis. Angiographic findings are reviewed separately for periampullary and truely pancreatic carcinoma. Subselective catheterisation and adequate opacification of the arterial network of the pancreas allows the reliable demonstration or exclusion of even 1--2 cm carcinomas, provided the clinical presentation of the patient has not been that of jaundice or pancreatitis. Taking into account the availability of newer non-invasive imaging techniques, clinical situations are listed in which the angiographic diagnosis of carcinoma is no longer required. The new purpose of angiography in pancreas carcinoma diagnosis is the demonstration of small and still curable lesions, the prerequisite for this being a much earlier clinical suspicion of the disease and an earlier referral for angiography.


Association of pentraxin-3 with the severity of rheumatic mitral valve stenosis.
Inflammation is involved in the pathogenesis of rheumatic mitral valve stenosis (RMVS). Pentraxin-3 (PTX3) indicates the inflammatory state of humans. However, circulating PTX3 levels in patients with RMVS, remain largely unknown. In this study, we investigated whether there is an association between the severity of RMVS and PTX3. All patients diagnosed as rheumatic mitral valvular stenosis between December 2013 and April 2014 were included in the study. We investigated circulating PTX3 and high-sensitivity C-reactive protein (hsCRP) levels in patients with RMVS and healthy controls. The study population included 72 subjects (41 patients with RMVS and 31 healthy subjects, 56 female) with a mean age of 40 +/- 13 years. Patients with RMVS had higher left atrial diameters than healthy subjects. PTX3 and hsCRP were significantly higher in patients with RMVS when compared to control subjects and this difference was more significant in PTX3 compared to hsCRP (3.37 +/- 1.11 vs 2.86 +/- 0.59, P = 0.014 and 2.36 +/- 1.48 vs. 1.72 +/- 0.73, P = 0.019, respectively). PTX3 was positively correlated with Wilkins score, mitral valvular area, mitral pressure gradient and left atrium diameter. We demonstrated that plasma PTX3 and hsCRP levels were increased in patients with RMVS. Compared to hsCRP, PTX3 was more closely related with the severity of mitral valve stenosis. These findings suggest that PTX3 may participate in the pathophysiology of RMVS.


Fine-structural and immunohistochemical study of anterior pituitary cells of Snell dwarf mice.
Snell dwarf mice display remarkable retardation of growth after birth and are known to lack prolactin (PRL), thyroid stimulating hormone (TSH) and growth hormone (GH). The aim of this study was to determine the reason for these hormonal deficiencies. We examined the fine structure of the gland and its immunohistochemical staining pattern with respect to antisera raised against PRL, TSH, GH, adrenocorticotrophic hormone (ACTH) and luteinizing hormone (LH). The gland of control mice reacted immunohistochemically against all antisera used, whereas only ACTH-producing cells (ACTH cells) and LH-producing cells (LH cells) were distinguished in the dwarf mice. ACTH cells in dwarf mice varied in cell shape, although they were similar in size to those of controls. The distribution of secretory granules in the cytoplasm varied from cell to cell. LH cells in the dwarf mice showed immature features, having poorly developed rough endoplasmic reticulum and Golgi apparatus. The cells were about half the size of controls, and secretory granules were smaller. In dwarf mice, non-granulated cells were encountered in addition to granulated ACTH and LH cells. Some of them formed small clusters, characteristic cell junctions being found between the cells; they thus appeared to be follicular cells. The above results suggest that hormone deficiency in Snell dwarf mice is a result of a defect in the hormone-producing cells in the gland.


Genetic variants in Protocadherin-1, bronchial hyper-responsiveness, and asthma subphenotypes in German children.
Recently, Protocadherin-1 (PCDH1) was reported as a novel susceptibility gene for bronchial hyper-responsiveness (BHR) and asthma. PCDH1 is located on chromosome 5q31-33, in the vicinity of several known candidate genes for asthma and allergy. To exclude that the associations observed for PCDH1 originate from the nearby cytokine cluster, an extensive linkage disequilibrium (LD) analysis was performed. Effects of polymorphisms in PCDH1 on asthma, BHR, and related phenotypes were studied comprehensively. Genotype information was acquired from Illumina HumanHap300Chip genotyping, MALDI-TOF MS genotyping, and imputation. LD was assessed by Haploview 4.2 software. Associations were investigated in a population of 1454 individuals (763 asthmatics) from two German study populations [MAGICS and International Study of Asthma and Allergies in Childhood phase II (ISAAC II)] using logistic regression to model additive effects. No relevant LD between PCDH1 tagging polymorphisms and 98 single nucleotide polymorphisms within the cytokine cluster was detected. While BHR was not associated with PCDH1 polymorphisms, significant associations with subphenotypes of asthma were observed. Protocadherin-1 polymorphisms may specifically affect the development of non-atopic asthma in children. Functional studies are needed to further investigate the role of PCDH1 in BHR and asthma development.


Sacral Neuromodulation for Bladder Atony - A Case Report.
In most cases, sacral neuromodulation is used as a treatment for urge incontinence and symptoms of urgency and frequency. It is most used in those who are refractory to traditional management. It is much less common to be used for bladder atony. In this report, we present a case of a 24-year-old woman with a history of urinary retention and bladder atony who failed medical management and subsequently had an InterStim sacral neuromodulator implanted. After implantation, she was able to discontinue intermittent catheterization and had a decrease in her postvoid residual from 848 to 72 mL.


Sleep during chronic ethanol administration and withdrawal in rats.
After a priming dose, ethanol was administered at a rate relative to behavioral impairment for 4 days and its effects on sleep were monitored by EEG. EEG's during withdrawal indicated an initial sleep loss followed by a return of total sleep and a REM sleep rebound several days later.


Quantitative detection of dopamine in human serum with surface-enhanced Raman scattering (SERS) of constrained vibrational mode.
Dopamine (DA) is a crucial neurotransmitter involved in the hormonal, nervous, and vascular systems being considered as an index to diagnose neurodegenerative diseases, including Parkinson's and Alzheimer's disease. Herein, we demonstrate the quantitative sensing of DA using the peak shift in surface-enhanced Raman scattering (SERS) of 4-mercaptophenylboronic acid (4-MPBA), resulting from the concentration of DA. To enable the signal enhancement of Raman scattering, Ag nanostructure was built with one-step gas-flow sputtering. 4-MPBA was then introduced using vapor-based deposition, acting as a reporter molecule for bonding with DA. The gradual peak-shift from 1075.6 cm-1 to 1084.7 cm-1 was observed with the increasing concentration of DA from 1 pM to 100nM. The numerical simulation revealed that DA bonding induced a constrained vibrational mode corresponding to 1084.7 cm-1 instead of a C-S-coupled C-ring in-plane bending mode of 4-MPBA corresponding to 1075.6 cm-1. Proposed SERS sensors depicted reliable DA detection in human serum and good selectivity against other analytes, including glucose, creatinine, and uric acid.


Hepatitis C virus infection: when silence is deception.
Hepatitis C virus (HCV) uses complex and unique mechanisms to prevent, evade or subvert innate and adaptive immune responses and to establish persistent infection and chronic hepatitis. Recently developed experimental systems have significantly facilitated the analysis of HCV replication, virus-host interaction and pathogenesis of chronic hepatitis and have provided new insights into the mechanisms of HCV clearance and persistence.


Ophthalmic manpower in India--need for a serious review.
An attempt has been made to estimate the number of ophthalmic surgeons (OSs) in India, their distribution amongst the constituent states/union territories, and imbalances in the urban (big and small cities) and rural areas. With an ophthalmic surgeon:population ratio of 1:107,000 (similar to that in the UK), an increasing amount of blindness in India, the output by ophthalmic surgeons continues to be low. Whereas the shortage of surgeons has been recognised as a critical problem by the National Programme for Control of Blindness, recommendations made at various forums have been restricted only to increasing production of existing surgeons. The key issues relating to OSs in India are uneven distribution, under utilisation and increasing demands on the ophthalmologist's time, due to advancement in clinical ophthalmology in recent years. Serious intervention to streamline distribution and improve utilisation of OSs in government and private sectors is necessary to effectively counter the current menace of blindness. Another option-creating an exclusive cadre of cataract surgeons trained to perform intracapsular cataract extraction (ICCE) for a period of four months in the medical colleges--has been recommended.


Template-assisted synthesis of molecularly imprinted polymers for the removal of methyl red from aqueous media.
This study entails the synthesis of molecularly imprinted polymers (MIPs) with good selectivity coefficients for azo dye as a potential sorbent material to extract azo dye from polluted aqueous media. A series of MIPs for methyl red (MR) as a template, were synthesized by changing the molar ratio of functional monomers, via precipitation polymerization format of non-covalent approach. Water-soluble functional monomer; acrylic acid (AA) was used to weave the frame work of polymers while ethylene glycol dimethacrylate (EGDMA) was utilized as crosslinking monomer. The impact of different experimental parameters, such as mole ratio of monomer (functional) to crosslinking monomer on the molecular recognition was investigated. The highly efficient and selective MR-MIP was used for the removal of spiked MR dye from different water samples. The selected imprinted polymer, MR1-MIP was able to selectively remove the MR molecules from aqueous media. A significant amount of dye was removed by MR1-MIP from the river water samples with a high degree of removal efficiency i.e. 92.25%. The imprinting factor of 3.75 for MR1-MIP indicated that the high selectivity in terms of adsorption for MR. A minimum loss of only ~ 3.35% in the removal efficiency within ten sequential cycles of adsorption-desorption study evidenced that MR-MIPs could be used as the most cost effective and best sorbent for the removal of MR from polluted water. Furthermore, the structural properties of MR-MIPs were characterized by FTIR and EDX, whereas TGA, SEM and BET were used to describe the thermal, morphological and surface structures of the particles, respectively.


Target sequence capture in the Brazil nut family (Lecythidaceae): Marker selection and in silico capture from genome skimming data.
Reconstructing species trees from multi-loci datasets is becoming a standard practice in phylogenetics. Nevertheless, access to high-throughput sequencing may be costly, especially with studies of many samples. The potential high cost makes a priori assessments desirable in order to make informed decisions about sequencing. We generated twelve transcriptomes for ten species of the Brazil nut family (Lecythidaceae), identified a set of putatively orthologous nuclear loci and evaluated, in silico, their phylogenetic utility using genome skimming data of 24 species. We designed the markers using MarkerMiner, and developed a script, GoldFinder, to efficiently sub-select the best makers for sequencing. We captured, in silico, all designed 354 nuclear loci and performed a maximum likelihood phylogenetic analysis on the concatenated sequence matrix. We also calculated individual gene trees with maximum likelihood and used them for a coalescent-based species tree inference. Both analyses resulted in almost identical topologies. However, our nuclear-loci phylogenies were strongly incongruent with a published plastome phylogeny, suggesting that plastome data alone is not sufficient for species tree estimation. Our results suggest that using hundreds of nuclear markers (i.e. 354) will significantly improve the Lecythidaceae species tree. The framework described here will be useful, generally, for developing markers for species tree inference.


Impacts of low peritoneal cancer index on the survival outcomes of patient with peritoneal carcinomatosis of colorectal origin.
The combination of cytoreductive surgery (CRS) and perioperative chemotherapy (PIC) have been proposed as an innovative technique for peritoneal carcinomatosis and is currently considered as a standard treatment for colorectal peritoneal carcinomatosis (CRPC) in selected patients. Peritoneal cancer index (PCI) has been suggested to be the most important prognostic factors for the outcomes of patients with CRPC. In this paper, we have studied patients with CRPC and a very low PCI of 5 or less and their survival outcomes. This is a retrospective study of prospectively collected data of 60 consecutive patients with CRPC and PCI ≤ 5, who underwent CRS and PIC by the same surgical team at St George hospital in Sydney, Australia between January 1996 and April 2015. Clinical outcomes of these patients were analysed. Hospital mortality was 0%. 14 patients (23.4%) had grade III/IV morbidity. The median follow-up was 22.2 months (range = 0.1-104.2). The median survival was 80.6 months (95% confidence interval (CI) = 35.1-126.1), with an overall 1-year, 3-year, and 5-year survival rate of 96.1%, 72.6% and 54.7% respectively. Among 60 patients, 31 patients experienced the recurrence of the disease (51.7%). The median disease-free survival was 10.8 months (95% CI = 7.2-14.4). This innovative approach combining CRS and PIC has shown encouraging outcomes and offers hope for patients with CRPC. Our results suggest that CRS and PIC can be performed safely to provide significant survival benefits for patients with low volume of disease. Early referral to specialist centre for evaluation is warranted for better survival outcomes.


Screening for pulmonary tuberculosis: an acceptable intervention for antenatal care clients and providers?
Five purposively sampled health facilities in Kasungu District, Malawi. To explore 1) the acceptability of introducing pulmonary tuberculosis (PTB) screening into antenatal care (ANC) clinics amongst ANC clients and ANC service providers; and 2) the acceptability of tuberculosis (TB) treatment during and after pregnancy among women registered for TB treatment. Fourteen focus group discussions and 40 in-depth interviews with ANC clients (15), ANC service providers (10) and women registered for TB treatment (15). Most clients found the introduction of PTB screening into ANC clinics acceptable. Some expressed concern at submitting a second sputum specimen, citing transportation/distance as the main obstacle. Other concerns were stigma and fear relating to the human immunodeficiency virus and the acquired immune-deficiency syndrome (HIV/AIDS) and taking TB treatment during pregnancy and breast-feeding. All ANC service providers supported the idea, but were concerned about increased workload. PTB screening in the ANC setting would be an acceptable intervention and could serve to increase PTB case notification in Malawi. However, alternative diagnostic strategies need to be explored. The negative associations with HIV/AIDS and some of the misconceptions surrounding TB treatment need to be addressed to avoid PTB screening becoming a potential barrier to seeking ANC. The main challenge will be whether over-stretched staff will be able to cope with this additional service.


Aspects of cellular physiology that influence DNA-mediate gene transfer in NIH3T3 cells.
Cellular physiology has a significant influence on the efficiency of various gene transfer procedures, as shown by the fact that transfection efficiency varies dramatically among different cell lines. However, the aspects of cellular physiology which influence the transfection process remain substantially uncharacterized. In this study, NIH3T3 cells were treated with inhibitors of protein synthesis, DNA synthesis, and RNA synthesis to determine the importance of these processes in the calcium-phosphate transfection process. The results suggest that protein synthesis during the first 4 h after DNA addition enhances transfection. In contrast, inhibition of RNA synthesis has no effect on transfection during the first 24 h post-DNA addition. The DNA synthesis inhibitor results remain inconclusive due to a secondary inhibition of an unknown cellular factor. Secondly, agents that destabilize microtubules, microfilaments, and the golgi apparatus were used to determine whether these elements play a role in the transfection process. The results suggest that microtubules are not involved in the transfection process, microfilaments are important but not necessary for the transfection process, and a functional golgi apparatus is essential early in the transfection process. These studies provide a foundation from which further investigations into the cellular processes involved in the uptake and expression of exogenous DNA can proceed.


Teaching Giants and Other Mentors of the Howard University: College of Medicine Class of 1952.
During the two decades following World War II, rapid changes occurred in medicine and in society as a whole in the United States including the establishment of the National Institutes of Health and the civil rights movement. This article profiles the teaching faculty of the Howard University College of Medicine that prepared the Class of 1952 for the decades that were to follow.


Mycotic abdominal aortic aneurysm induced by immunotherapy with bacille Calmette-Guérin vaccine for malignancy.
Successful surgical treatment of a mycotic abdominal aortic aneurysm infected with Mycobacterium bovis is described. The infecting organism can be traced to an intraneoplastic injection of bacille Calmette-Guérin (BCG) vaccine into a cutaneous malignant melanoma nodule 14 months before aneurysm detection (17 months before operation). Treatment consisted of aneurysm excision, in situ prosthetic graft placement, and antituberculous medications. This patient represents the first reported case of BCG-induced mycotic aortic aneurysm.


[Differential diagnostic value of B72.3, Ber-EP4 and calretinin in serous effusions].
To determine the diagnostic value of B72.3, BerEP4 and calretinin in differentiating metastatic carcinoma cells from reactive mesothelial cells (RMC) in serous effusions by using immunocytochemical method (ICC), and to investigate the feasibility of ThinPrep (TP) preparation for ICC. One hundred fifty eight serous effusion specimens were examined by ICC on cell block (CB) sections (CB-ICC) using antibodies against of B72.3, BerEP4 and calretinin. Fourty-nine of the samples, ICC on ThinPrep slides (TP-ICC) and CB-ICC were performed concurrently. The sensitivities of B72.3 and Ber-EP4 for detecting carcimoma cells were 76.9% and 69.2% respectively, and when combined the sensitivity was increased to 89.7%. The sensitivity and specificity of Calretinin for detecting mesothelial cells were 90.9% and 87.2% respectively. The sensitivity of B72.3 in differentiating cancer cells from reactive mesothelial cells by CB-ICC and TP-ICC was 78.9% and 68.4%. It was 78.9% and 68.4% of BerEP4 respectively. No statistical significance was observed between CB-ICC and TP-ICC in differentiating metastatic carcinoma cells from reactive mesothelial cells. The combination of antibodies of B72.3, Ber-EP4 and calretinin is quite helpful as an auxiliary in differentiating metastatic carcinoma cells from reactive mesothelial cells. ThinPrep preparation slides may effectively replace the cell block sections for ICC in differential diagnosis of serous effusions.


The rotating stretched curved planar reconstruction of 3D-FIESTA MR imaging for evaluating the anterior cruciate ligament of the knee joint.
To determine the feasibility of the rotating stretched curved planar reconstruction (CPR) of three-dimensional fast imaging with steady-state acquisition magnetic resonance imaging (3D-FIESTA MRI) for evaluating the anterior cruciate ligament of the knee joint. MRI of 40 knee joints in healthy volunteers was performed on a 3.0-T MR scanner and a phased-array extremity coil. The protocol consisted of oblique sagittal spin echo (SE) T1WI, coronal FS-PDWI, axial FS-FSE-T2WI, and 3D-FIESTA sequences. The rotating stretched curved planar reconstructions (CPR) of the ACL at angles of 0°, 30°, 60°, 90°, 120°, 150°, and 180° were generated from images of 3D-FIESTA sequences. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the 3D-FIESTA were compared with those of the oblique sagittal SE T1WI sequence. The presence of the tibial attachment, midportion, femoral attachment, and double bundles of the ACL on the oblique sagittal SE T1WI and CPR of 3D-FIESTA MR imaging were divided into two categories: visible and not visible. The ACL SNR efficiency of 3D-FIESTA sequences was significantly higher than that of oblique sagittal SE T1WI sequence (P < 0.05). The 3D-FIESTA sequences produced images with a significantly higher CNR between ACL and synovial fluid than did the oblique sagittal SE T1WI sequence (P < 0.05). CPR of 3D-FIESTA MRI generated an excellent visualization of the ACL. The CPR of 3D-FIESTA MRI was rated superior to oblique sagittal SE T1WI sequence in 60% and 65% of cases with regard to the tibial attachment and midportion of ACL, respectively (P < 0.05). CPR of 3D-FIESTA MR imaging was rated superior to oblique sagittal SE T1WI sequence in 80% and 85% of cases with regard to femoral attachment and double bundles of ACL, respectively (P < 0.05). The rotating stretched curved planar reconstruction of 3D-FIESTA sequences is significantly better than that of conventional 2D-MRI in evaluating the native ACL and its components, AM bundle and PL bundle, in healthy volunteers.


Prevention of TNFalpha-associated myocardial dysfunction resulting from cardiopulmonary bypass and cardioplegic arrest by glucocorticoid treatment.
Cardiac surgery on cardiopulmonary bypass (CPB) results in progressive myocardial dysfunction, despite unimpaired coronary blood flow, and is associated with increased myocardial tumor necrosis factor-alpha (TNFalpha) expression. We investigated whether anti-inflammatory treatment prevents increased TNFalpha expression and myocardial dysfunction after CPB. Baseline systemic hemodynamics, myocardial contractile function, aortic and coronary blood flow were measured in anesthetized pigs. Then, placebo (PLA; saline; n=7) or methylprednisolone (MP; 30 mg/kg; n=6) was infused intravenously and CPB was instituted. Global ischemia was induced for 10 min by aortic cross-clamping, followed by 1 h of cardioplegic cardiac arrest. After declamping and reperfusion, CPB was terminated after a total of 3 h. Measurements were repeated at 15 min, 4 h, and 8 h following termination of CPB. Systemic TNFalpha-plasma concentrations and left ventricular TNFalpha expression were analyzed. With unchanged coronary blood flow in both groups, a progressive loss of myocardial contractile function to 38+/-2% of baseline (p<0.01) and cardiac index to 48+/-6% of baseline (p<0.01) at 8 h after CPB in PLA was attenuated in MP (myocardial function: 72+/-3%, p<0.01 vs PLA; cardiac index: 78+/-6%, p<0.05 vs PLA). Systemic TNFalpha was increased at 8 h in PLA compared to MP (243+/-34 vs 90+/-34 pg/ml, p<0.05). Myocardial TNFalpha was increased at 8 h after CPB compared to baseline and MP (p<0.05). Myocardial TNFalpha immunostaining was more pronounced in PLA than in MP (p<0.05), with TNFalpha-mRNA localization predominantly to cardiomyocytes. Methylprednisolone attenuates both systemic and myocardial TNFalpha increases and progressive myocardial dysfunction induced by cardiac surgery, suggesting a key role for TNFalpha.


Laparoendoscopic single-site nephrectomy compared with conventional laparoscopic nephrectomy: a 5-year, single-surgeon experience.
Conventional laparoscopic nephrectomy (LN) is the gold standard approach for nephrectomy. An advance in minimally invasive nephrectomy is laparoendoscopic single-site nephrectomy (LESS-N). To compare 5-yr experience and outcomes of LESS-N to LN. Retrospective, case-control, single-surgeon series of 47 LESS-N cases matched in a 1:2 fashion by age, indication, and tumor size to 94 LN controls. LESS-N procedures were performed between August 2007 and February 2012 and LN procedures between December 1999 and 2009. LESS-N or LN. Categorical variables were compared by χ(2) analysis, and continuous variables were compared using the Mann-Whitney test. There were significantly more female patients (66% vs 46%; p = 0.023) and a significantly lower median body mass index (24 kg/m(2) vs 28 kg/m(2); p < 0.001) in the LESS-N group compared with the LN group. Surgical indication was benign in 69 patients (23 LESS-N and 46 LN) and malignant in 72 patients (24 LESS-N and 48 LN). There were no significant differences for the LESS-N and LN groups, respectively, in mean operative time (149 min vs 150 min; p = 0.9), change in hematocrit (5.6% vs 4.8%; p = 0.661), change in creatinine (0.18 mg/dl vs 0.49 mg/dl; p = 0.18), analgesic use (morphine equivalents) (18.4 vs 17.5; p = 0.81), or intraoperative complication rates (6.4% vs 2.1%; p = 0.20). Length of stay was shorter (49 h vs 70 h; p = 0.017) and estimated blood loss was lower (56 ml vs 137 ml; p = 0.002) for the LESS-N group. Over a mean follow-up of 3 yr, postoperative complications (12.8% vs 7.4%; p = 0.30), disease-free survival (95.8% vs 87.5%; p = 0.384), and overall survival (91.7% vs 95.8%; p = 0.123) were not significantly different. The most significant limitation of this study is the retrospective design. This series demonstrates that LESS-N is safe and durable in properly selected patients; however, multi-institutional randomized trials are required to confirm benefits.


Antitumor mechanism of cannabidiol hidden behind cancer hallmarks.
Cannabinoids have been utilized for recreational and therapeutic purposes for over 4,000 years. As the primary ingredient in exogenous cannabinoids, Cannabidiol (CBD) has drawn a lot of interest from researchers due to its negligible psychotropic side effects and potential tumor-suppressing properties. However, the obscure mechanisms that underlie them remain a mystery. Complex biological mechanisms are involved in the progression of cancer, and malignancies have a variety of acquired biological capabilities, including sustained proliferation, death evasion, neovascularization, tissue invasion and metastasis, immune escape, metabolic reprogramming, induction of tumor-associated inflammation, cancerous stemness and genomic instability. Nowadays, the role of CBD hidden in these hallmarks is gradually revealed. Nevertheless, flaws or inconsistencies in the recent studies addressing the anti-cancer effects of CBD still exist. The purpose of this review is to evaluate the potential mechanisms underlying the role of CBD in a range of tumor-acquired biological capabilities. We propose potential drugs that may have a synergistic effect with CBD and provide optional directions for future research.


Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated mice.
Oltipraz (4-methyl-5(pyrazinyl-2)-1-2-dithiole-3-thione), a promising cancer preventive agent, has an antioxidative activity and ability to enhance glutathione biosynthesis, phase II detoxification enzymes and multidrug resistance-associated protein-mediated efflux transporters. Oltipraz can protect against hepatotoxicity caused by carbon tetrachloride, acetaminophen and alpha-naphthylisothiocyanate. Whether oltipraz has hepato-protective effects on obstructive cholestasis is unknown. We administered oltipraz to mice for 5 days prior to bile duct ligation (BDL) for 3 days. Liver histology, liver function markers, bile flow rates and hepatic expression of profibrogenic genes were evaluated. Mice pretreated with oltipraz prior to BDL demonstrated higher levels of serum aminotransferases and more severe liver damage than in control mice. Higher bile flow and glutathione secretion rates were observed in unoperated mice treated with oltipraz than in control mice, suggesting that liver necrosis in oltipraz-treated BDL mice may be related partially to increased bile-acid independent flow and biliary pressure. Oltipraz treatment in BDL mice enhanced α-smooth muscle actin expression, consistent with activation of hepatic stellate cells and portal fibroblasts. Matrix metalloproteinases (Mmp) 9 and 13 and tissue inhibitors of metalloproteinases (Timp) 1 and 2 levels were increased in the oltipraz-treated BDL group, suggesting that the secondary phase of liver injury induced by oltipraz might be due to excessive Mmp and Timp secretions, which induce remodeling of the extracellular matrix. Oltipraz treatment exacerbates the severity of liver injury following BDL and should be avoided as therapy for extrahepatic cholestatic disorders due to bile duct obstruction.


SARS-CoV-2 Infection Risk Factors among Maintenance Hemodialysis Patients and Health Care Personnel In Outpatient Hemodialysis Centers.
Increased risk of SARS-CoV-2 infection was associated with community prevalence.Increased risk of SARS-CoV-2 infection was associated with exposure to infected family members and personal infection prevention measures.


Pharyngeal pH monitoring in infants with laryngitis.
To assess pharyngeal acid reflux (PAR) exposure with flexible laryngoscopy-guided pharyngeal pH monitoring in infants with laryngitis. Tertiary care children's hospital. Charts of 10 infants with laryngitis who underwent pharyngoesophageal pH monitoring were reviewed. Data included history, physical examination, and pharyngoesophageal pH monitoring findings. Six infants had PAR. Two patients were on acid suppressive therapy and exhibited PAR. The number of PAR observed in six infants ranged between 1 and 81. The percent acid exposure time (AET) in the pharynx was between 0.1% and 1.2%. Esophageal acid reflux documented in nine infants ranged between 5 and 173. The percent AET in the esophagus was between 0.1% and 4.8%. The majority of the studied infants with laryngitis had PAR. Not all esophageal acid reflux reached the pharynx. Pharyngeal pH monitoring provides additional information that cannot be obtained with esophageal pH monitoring in infants with laryngitis.


Growth hormone responses to pyridostigmine in normal adults and in normal and short children.
There is evidence indicating that the cholinergic system positively modulates GH release probably by inhibiting somatostatinergic tone. In the present study, the effects of cholinergic enhancement by pyridostigmine, (PD), a cholinesterases inhibitor, on GH release in normal adults (n = 14) (NA) and in both normal (n = 5) (NC) and short children (n = 19) (SC) with familial short stature (n = 7) or constitutional growth delay (n = 12) were studied. In SC the insulin hypoglycaemia (IH)-induced GH increase was also studied. In both NC and SC 60 mg orally PD induced a significant GH increase with mean peak at 90 min (mean +/- SEM 11.0 +/- 2.2 ng/ml in NC and 11.2 +/- 2.3 ng/ml in SC). The GH areas under response curve (AUC) were 379.3 +/- 76.6 and 327.8 +/- 43.2 ng/ml/h in NC and SC respectively. In NA 120 mg orally PD induced a significant GH increase with mean peak at 120 min (5.1 +/- 1.1 ng/ml) which was significantly lower (P less than 0.05) than that observed in both NC and SC. This statistical difference was strengthened by evaluating AUC (NA:205.6 +/- 33.7 ng/ml/h, P less than 0.05 vs NC and SC). The correlation of drug dosage with body area ruled out that this difference could be related to the different PD dose in adults and children. In SC, IH induced a GH increase significantly lower than that observed after PD (GH peak 7.8 +/- 0.6 vs 16.4 +/- 1.9 ng/ml P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


A clinicopathologic study in advanced non-Hodgkin's lymphomas treated with sequential non-cross-resistant regimens: comparison of the working formulation with the Rappaport and Kiel classifications.
One-hundred and ninety-four adult patients with histologically proven stage III and IV non-Hodgkin's lymphomas, treated with CVP (cyclophosphamide, vincristine and prednisone) alternated with ABP (adriamycin, bleomycin and prednisone), were analyzed to test the validity of the clinicoprognostic correlation offered by the working formulation in comparison with the Rappaport and Kiel classifications. Actuarial overall survival at 5 yr showed a significant difference among the three prognostic subgroups of the working formulation (low grade, 53.3%; intermediate grade, 47.5%; high grade, 27.7%). Overall survival of favorable subgroups of the Rappaport and Kiel classifications was superior to that of unfavorable prognostic groups. The percentage of systemic symptoms and bulky disease increased in patients with low-grade compared to those with intermediate-grade and intermediate-to-high-grade malignancy. The achievement of complete remission was not related to any of the prognostic groups of the Working Formulation, and no difference could be detected within the various prognostic groups of the Rappaport and Kiel classifications. Within the diffuse histiocytic lymphomas of the Rappaport classification, two groups with a different prognostic outcome were evidenced by the working formulation (G, with an overall survival of 50%, and H, with an overall survival of 26.7% at 5 yr) and by the Kiel classification. The possibility of reporting results in the three different groups of the working formulation instead of two can be considered a step forward. Within the diffuse histiocytic histology, the working formulation allows separation, as does the Kiel classification, into two main different prognostic subgroups.


The effect of medical grade honey on tensile strength, strain, and Young's modulus of synthetic absorbable suture material used in equine surgery.
Medical grade honey (MGH) has been introduced as a protective measure against surgical site infections in equine surgery, but the effect on suture material has not been investigated. To evaluate the effect of MGH on the tensile properties of three synthetic absorbable suture materials. In vitro experiments. Ten strands of Polydioxanone USP 2 (PD2), Polyglactin 910 USP 2 (PG2) and Polyglecaprone USP 2-0 (PC2-0) were incubated 1, 7, 14, 21 and 28 days in MGH, phosphate-buffered saline (PBS), equine plasma (EP) and MGH mixed with equine plasma (HP). Mechanical testing was performed recording maximum load at failure (N), strain at failure and Young's modulus (N/mm2 ). The results were reported from a Welch or regular ANOVA. PD2 in MGH had a significantly higher tensile strength compared to PD2 in EP (p < 0.05, mean difference (md) = 16.95 N, CI95% (9.19-24.70 N)) and PBS (p < 0.05, md = 14.48 N CI95% (6.73-22.23 N)) on day 7 and the remaining time points. PG2 incubated in MGH had a significantly higher tensile strength compared to EP (p < 0.05, md = 69.28 N CI95% (64.16-74.40 N)) and PBS (p < 0.05, md = 56.90 N CI95% (51.78-62.02 N)) until day 28. PC2-0 incubated in MGH had a significantly higher tensile strength compared to EP (p < 0.05 md = 12.40 N CI95% (4.59 N-20.20 N)) and PBS (p < 0.05 md = 11.23 CI95% (3.42-19.03 N)) on day 7 and the remaining time points. The sutures were unloaded during incubation and a single cycle to failure test was only performed, which does not reflect the in vivo environment where shear forces are present. MGH did not negatively affect the tensile strength of the suture material and can safely be applied in contact with suture materials commonly used in equine surgery.


Lysosomal stability, superoxide dismutase and zinc deficiency in regenerating rat liver.
1. Lysosomal stability was slightly increased in regenerating livers from rats receiving a zinc-deficient (less than 0.5 mg/kg) diet for 10 d before surgery. 2. The activity of superoxide dismutase (EC 188.8.131.52) was significantly reduced in the same tissues. 3. The results do not support the view that increased lysosomal fragility represents a major biochemical consequence of nutritional Zn deficiency in animals.


Small RNA asymmetry in RNAi: function in RISC assembly and gene regulation.
RNAi is a conserved gene-specific regulatory mechanism, which silences target gene expression transcriptionally and post-transcriptionally. The RNAi machinery converts the sequence specific information of a long double stranded RNAs (dsRNAs) into small 21-22 nt long dsRNAs (siRNAs, miRNAs) which assemble into an effector complex, the RNA induced silencing complex (RISC). RISC assembly is asymmetric; one strand of an siRNA or a miRNA preferentially incorporates into the RNA-protein complex. Here, I review the rules of the asymmetric RISC formation and discuss their possible regulatory function in several steps in RNAi.


Expression of pituitary adenylate cyclase-activating polypeptide and PACAP type 1 receptor in the rat gastric and colonic myenteric neurons.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to regulate gastric acid secretion and intestinal motility. In the present study, the pattern of distribution of PACAP and PACAP type 1 receptor (PAC1) immunoreactivities were examined in the rat stomach and distal colon using a specific polyclonal antibody raised against rat/human PAC1. Western blot of the membrane preparations of NIH/3T3 cells transfected with the human PAC1 obtained by using rabbit polyclonal anti-PAC1 antibody showed a protein band with a molecular mass of approximately 50 kDa. NIH/3T3 cells transfected with the human PAC1 and incubated with the anti-PAC1 antibody displayed surface cell-type immunoreactivity, which was internalized following ligand exposure. In gastric or colonic longitudinal muscle/myenteric plexus (LMMP) whole mount preparations as well as cryostat sections, PACAP immunoreactivity was observed in cell bodies within the myenteric ganglia and nerve fibers in the muscle layers and mucosa. PAC1 immunoreactivity was confined mainly on the surface of the nerve cells. PACAP and PAC1 immunoreactivities showed a similar pattern of distribution in gastric and colonic tissues. Adjacent sections or LMMP whole mount preparations labeled with protein gene product 9.5 (PGP 9.5) revealed the neuronal identity of myenteric cells bearing PAC1. The neuronal localization of PACAP and PAC1 receptors supports their role in the neural regulation of gastric acid secretion and gastrointestinal motor function.


Impact of Coronavirus disease 2019 (COVID-19) on contraception use in 2020 and up until the end of April 2021 in France.
To assess the impact of the COVID-19 pandemic on the use of reimbursed contraceptives in France after 15 months of the pandemic, according to age-group and updating previous data only pertaining to the first lockdown (2 months). We conducted a national register-based study by extracting all reimbursements of oral contraceptives (OC), emergency contraception (EC), intrauterine devices (IUD), and implants from the French National Health Insurance database (SNDS), which includes and covers 99.5% of the French population, in 2018, 2019, 2020 and from January 1, 2021 to April30, 2021. We calculated the expected use of contraceptives in 2020 and 2021 in the absence of the pandemic, based on 2018 and 2019 usage and taking annual trends into account. We assessed the difference between observed and expected dispensing rates by contraceptive type and by age-group (≤18 years old, 18< age ≤25, 25< age ≤35, >35). Dispensing of all contraceptives decreased compared to expect dispensing numbers: -2.0% for OC, -5.3% for EC, -9.5% for LNG-IUS, -8.6% for C-IUD, and -16.4% for implant. This decrease in the dispensing of contraceptives was observed in all age-groups, but mainly concerned women under the age of 18 years (-22% for OC, -10% for EC, -37.2% for LNG-IUS, -36.4% for C-IUD, -26.4% for implant) and those aged 18 to 25 (-5.1% for OC, -11.9% for EC, -18.1% for LNG-IUS, -15.9% for C-IUD, -17.6% for implants). Our study showed that the dispensing of contraceptives in France was markedly impacted by the COVID-19 pandemic. Prescriptions for long-acting contraceptive use and women under the age of 25 years were the most substantially impacted. Ensuring access to contraceptive methods during health emergencies must be a public health policy priority. The COVID-19 pandemic strongly impacted the dispensing of contraceptives in France with varying degrees of decreased dispensing according to the type of contraceptive, the age-group and the level of pandemic-related restrictions. The impact of these restrictions on unintended pregnancy at the population level remains undetermined.


Protein adsorption on colloidal alumina particles functionalized with amino, carboxyl, sulfonate and phosphate groups.
Colloidal oxide particles in biomedical or biotechnological applications immediately become coated with proteins of the biological medium, a process which is strongly influenced by the surface characteristics of the particles. Fundamental correlations between surface characteristics and the, so far mainly uncontrollable, protein adsorption are still not clear. In this study the surface of colloidal alumina particles (d(50)=179 ± 8 nm) was systematically adjusted with NH(2), COOH, SO(3)H and PO(3)H(2) functional groups to investigate the influence on the adsorption of the three model proteins, bovine serum albumin (BSA), lysozyme (LSZ) and trypsin (TRY). The surface functionalization is characterized and discussed in detail with regard to the morphology, isoelectric point, zeta potential, hydrophilic/hydrophobic properties, functional group density and stability. Protein-particle interaction was then assessed by evaluating the amount of protein adsorbed and the zeta potentials of protein-particle conjugates. Protein adsorption was found to be influenced by the type of functional group as well as the expected electrostatic forces under the given experimental conditions. The level of protein adsorption might, hence, be specifically controlled by the type of surface functionalization. Possible adsorption modes of BSA, LSZ and TRY on the particles are suggested by considering the spatial surface potential distribution of the proteins calculated from the protein database file. The particles presented provide an excellent prerequisite for further investigation of fundamental particle-protein interactions and the design of functionally graded materials for biomedical and biotechnological applications, e.g. as drug carriers or for protein purification.


On the feasibility of simple brain-computer interface systems for enabling children with severe physical disabilities to explore independent movement.
Children with severe physical disabilities are denied their fundamental right to move, restricting their development, independence, and participation in life. Brain-computer interfaces (BCIs) could enable children with complex physical needs to access power mobility (PM) devices, which could help them move safely and independently. BCIs have been studied for PM control for adults but remain unexamined in children. In this study, we explored the feasibility of BCI-enabled PM control for children with severe physical disabilities, assessing BCI performance, standard PM skills and tolerability of BCI. Patient-oriented pilot trial. Eight children with quadriplegic cerebral palsy attended two sessions where they used a simple, commercial-grade BCI system to activate a PM trainer device. Performance was assessed through controlled activation trials (holding the PM device still or activating it upon verbal and visual cueing), and basic PM skills (driving time, number of activations, stopping) were assessed through distance trials. Setup and calibration times, headset tolerability, workload, and patient/caregiver experience were also evaluated. All participants completed the study with favorable tolerability and no serious adverse events or technological challenges. Average control accuracy was 78.3 ± 12.1%, participants were more reliably able to activate (95.7 ± 11.3%) the device than hold still (62.1 ± 23.7%). Positive trends were observed between performance and prior BCI experience and age. Participants were able to drive the PM device continuously an average of 1.5 meters for 3.0 s. They were able to stop at a target 53.1 ± 23.3% of the time, with significant variability. Participants tolerated the headset well, experienced mild-to-moderate workload and setup/calibration times were found to be practical. Participants were proud of their performance and both participants and families were eager to participate in future power mobility sessions. BCI-enabled PM access appears feasible in disabled children based on evaluations of performance, tolerability, workload, and setup/calibration. Performance was comparable to existing pediatric BCI literature and surpasses established cut-off thresholds (70%) of "effective" BCI use. Participants exhibited PM skills that would categorize them as "emerging operational learners." Continued exploration of BCI-enabled PM for children with severe physical disabilities is justified.


The Outcome of Single Versus Double Nerve Transfers in Shoulder Reconstruction of Upper and Extended Upper-Type Brachial Plexus Injuries.
The objective of this study was to compare the outcomes of a single nerve transfer (SNT) with double nerve transfer (DNT) in the restoration of shoulder function in patients with upper (C5-6) or extended upper-type (C567) brachial plexus injuries. A retrospective review of patients with C5-6 or C567 brachial plexus injuries operated on with nerve transfers from January 1, 2005, to December 31, 2017, was completed. The outcomes between SNT and DNT groups were evaluated with the Filipino Version of the Disabilities of the Arm, Shoulder, and Hand (FIL-DASH) scores, pain scores, muscle strength recovery, and range of motion. A subgroup analysis on surgical delay (< or ≥ 6 months), diagnosis (C5-6 or C567), and length of follow-up (< or ≥ 24 months) was also performed. All statistical significance was set at P < .05. A total of 22 patients with SNT and 29 with DNT were included in this study. There was no significant difference between the SNT and DNT groups as to postoperative FIL-DASH scores, pain, recovery of ≥M4, and range of motion for shoulder abduction and external rotation, although the absolute values for shoulder function were greater in the DNT than the SNT group. There was no significant difference between the SNT and DNT groups for surgical delay, diagnosis, and length of follow-up. A stronger recovery of ≥M4 for external rotation was observed in the DNT group compared to the SNT group if nerve transfer was performed in less than 6 months (86% vs 41%). The outcomes for shoulder function between the 2 groups were similar, although the DNT group performed slightly better, especially with external rotation. Patients operated on less than 6 months from injury will benefit more from DNT for shoulder function, especially for external rotation. Double nerve transfer may result in improved shoulder function.


Aggregation determines the selectivity of membrane-active anticancer and antimicrobial peptides: The case of killerFLIP.
Host defense peptides selectively kill bacterial and cancer cells (including those that are drug-resistant) by perturbing the permeability of their membranes, without being significantly toxic to the host. Coulombic interactions between these cationic and amphipathic peptides and the negatively charged membranes of pathogenic cells contribute to the selective toxicity. However, a positive charge is not sufficient for selectivity, which can be achieved only by a finely tuned balance of electrostatic and hydrophobic driving forces. A common property of amphipathic peptides is the formation of aggregated structures in solution, but the role of this phenomenon in peptide activity and selectivity has received limited attention. Our data on the anticancer peptide killerFLIP demonstrate that aggregation strongly increases peptide selectivity, by reducing the effective peptide hydrophobicity and thus the affinity towards membranes composed of neutral lipids (like the outer layer of healthy eukaryotic cell membranes). Aggregation is therefore a useful tool to modulate the selectivity of membrane active peptides and peptidomimetics.


Complete revascularization for patients with multivessel coronary artery disease and ST-segment elevation myocardial infarction after the COMPLETE trial: A meta-analysis of randomized controlled trials.
The recently published COMPLETE trial has demonstrated that patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), who underwent successful percutaneous coronary intervention (PCI) of both culprit and non-culprit (vs. culprit-only) lesions had a reduced risk of major adverse cardiac events (MACE), but not of cardiovascular or total mortality. The aim of this meta-analysis was to assess the efficacy of complete revascularization on cardiovascular or total mortality reduction using available randomized controlled trials (RCTs) including the COMPLETE trial, in hemodynamically stable STEMI patients with MVD. PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov databases search identified 10 RCTs of 7033 patients with STEMI and MVD which compared complete (n = 3420) vs. only culprit lesion (n = 3613) PCI for a median 27.7 months follow-up. Random effect risk ratios were used to estimate for efficacy and safety outcomes. Complete revascularization reduced the risk of MACE (10.4% vs.16.6%; RR = 0.59, 95% CI: 0.47 to 0.74, p < 0.0001), CV mortality (2.87% vs. 3.72%; RR = 0.73, 95% CI: 0.56 to 0.95, p = 0.02), reinfarction (5.1% vs. 7.1%; RR = 0.67, 95% CI: 0.52 to 0.86, p = 0.002), urgent revascularization (7.92% vs.17.4%; RR = 0.47, 95% CI: 0.30 to 0.73, p < 0.001), and CV hospitalization (8.68% vs.11.4%; RR = 0.65, 95% CI: 0.44to 0.96, p = 0.03) compared with culprit only revascularization. All-cause mortality, stroke, major bleeding events, or contrast induced nephropathy were not affected by the revascularization strategy. The findings of this meta-analysis suggest that in patients with STEMI and MVD, complete revascularization is superior to culprit-only PCI in reducing the risk of MACE outcomes, including cardiovascular mortality, without increasing the risk of adverse safety outcomes.


Growth and senescence in plant communities exposed to elevated CO2 concentrations on an estuarine marsh.
Three high marsh communities on the Chesapeake Bay were exposed to a doubling in ambient CO2 concentration for one growing season. Open-top chambers were used to raise CO2 concentrations ca. 340 ppm above ambient over monospecific communities of Scirpus olneyi (C3) and Spartina patens (C4), and a mixed community of S. olneyi, S. patens, and Distichlis spicata (C4). Plant growth and senescence were monitored by serial, nondestructive censuses. Elevated CO2 resulted in increased shoot densities and delayed sensecence in the C3 species. This resulted in an increase in primary productivity in S. olneyi growing in both the pure and mixed communities. There was no effect of CO2 on growth in the C4 species. These results demonstrate that elevated atmospheric CO2 can cause increased aboveground production in a mature, unmanaged ecosystem.


Nodular fasciitis mimicking recurrent lymphoma on positron emission tomography-computed tomography.
20 year old female with no prior medical history presents with diffuse cervical lymphadenopathy. CT and subsequent positron emission tomography-computed tomography (PET/CT) demonstrated diffuse lymphatomous involvement of multiple lymph nodes in the neck, mediastinum, and retroperitoneum. The patient underwent ABVD therapy which resulted in the lymphoma being in remission for 2 years. The patient had a repeat PET/CT done after 2 years due to complaints of recurrent lymphadenopathy. The PET/CT revealed a new hypermetabolic focus by the right femur. MRI demonstrated an enhancing nodule in that region which raised suspicion for possible site of lymphoma recurrence. Percutaneous biopsy showed nodular fasciitis.


Depression during first episode psychosis and subsequent suicide risk: A systematic review and meta-analysis of longitudinal studies.
Evidence suggests first episode psychosis (FEP) is associated with suicide, and the influence of depression on suicidal behaviour in cross sectional studies is clear. However the influence of depression during FEP on longer-term mortality is not certain. Existing evidence was synthesised to understand the influence of depressive symptoms during FEP on subsequent suicidal behaviour. Medline, Embase, PsycINFO, Cochrane Library, Web of Science, OpenGrey, and NICE Evidence were searched from inception to Jan 25, 2017. Longitudinal observational studies assessing the relationship between depressive symptoms during FEP with a measure of s at a specified follow-up time were included. Summary estimates were extracted. The Downs and Black Instrument was used to appraise study quality. Odds ratio (OR) of suicidal behaviour were calculated using random effects meta-analyses. The study protocol was registered with PROSPERO (CRD42017055881). Of 4210 articles found, 23 fulfilled eligibility criteria. 13 were included in meta-analysis (n=3002). 428 participants demonstrated suicidal behaviour in the study periods. Odds of suicidal behaviour during follow-up were significantly higher among patients with depressive symptoms during FEP compared to those without (OR=1.59, 95% CI 1.14-2.21; I2=50.0%, p=0.02). Meta-regression demonstrated no evidence of influence of length of follow-up on results. Depressive symptoms during FEP are associated with increased longer-term risk of suicidal behaviour. This association should be acknowledged during early management planning. Large-scale clinical trials are needed to identify efficacious management of depression during FEP.


Selenium-Directed ortho-C-H Borylation by Iridium Catalysis.
An iridium-catalyzed selenium-directed ortho-C-H borylation of benzyl selenide derivatives was successfully developed. This is the first example where selenium is used as a directing group in C-H borylation. The reaction was carried out using the tricyclohexylphosphine ligand for an improved catalytic efficiency. Various substrates were tolerated and afforded either ortho-monoborylated products (substrates bearing ortho- or meta-substituents) or diborylated products (substrates bearing para-substituents) in good yields. This study provides an efficient synthetic method for the preparation of a variety of organoselenium compounds.


Autism: part I. Deficits, prevalence, symptoms, and environmental factors.
Autism is a neurodevelopmental disorder that is gaining the attention of public health, educators, and health care providers. This column reviews the deficits, prevalence, symptoms, and environmental factors.


Studies on compensatory adaptation of renal functions.
Changes in the excretion of water and electrolyte in one kidney after exclusion of its partner have been studied in anesthetized dogs and rabbits. Complete clamping of the contralateral kidney pedicle or ureter results in a rapid increase in the excretion of water, sodium, potassium, chloride, calcium, phosphate and bicarbonate. This response is also observed in denervated kidneys. Pretreatment with the loop inhibitor, furosemide, does not preclude adaptation which, however, is blunted by acetazolamide, an inhibitor of proximal sodium and bicarbonate reabsorption. Free-water reabsorption during hypertonic saline diuresis is normal in the remaining kidney. Compensatory adaptation, thus, appears to be located in the proximal tubule. The regulatory response to contralateral kidney exclusion is already fully developed in one-month-old rabbits. Compensatory adaptation of electrolyte excretion is not accounted for by changes in extracellular fluid volume, plasma composition, glomerular filtration rate, effective renal plasma flow, aldosterone or vasopressin.


Undeca- and octa-peptide antagonists for substance P, a study on the guinea pig trachea.
Undeca - and octa-peptide analogues of substance P (SP), acting as antagonists in the guinea pig ileum, have been tested on the guinea pig trachea. The antagonistic properties of several octapeptides, particularly of [pro4, trp7 ,9,10,Phe11]SP-(4-11) have been confirmed, while the undecapeptides have been found to be potent stimulants of the trachea. The contractions of the guinea pig trachea in response several undecapeptides , particularly [pro2, trp7 ,9, Leu11 ]SP, undergo rapid tachyphylaxis, are significantly reduced in the presence of diphenhydramine and are not influenced by octapeptide antagonists of SP. These contractions appear to be due to the activation of tissue sites mediating the release of intramural histamine and different from SP receptors. On repeated applications, the stimulant effects of undecapeptides are eliminated and the compounds can be tested as antagonists. Undecapeptide antagonists have been found to be more potent against eledoisin and kassinin than against SP or physalaemin, while the octapeptides are equally active against the four homologues. Both undeca - and octa-peptides seem however to exert a competitive type of antagonism against all the SP-related peptides tested in the present study. Differences of antagonistic affinities have been interpreted as indicative of the existence of two different receptor types for SP and related peptides in the guinea pig trachea. The two receptors are blocked by the octapeptide antagonists, which are not discriminatory, while undecapeptides are particularly active on the receptor subtype which shows high sensitivity for eledoisin and kassinin .


Stereoselective Synthesis and Characterization of Indenone Azine-Based Electron-Accepting π-Conjugated Systems.
Invited for the cover of this issue is the group of Aiko Fukazawa at Kyoto University. The image depicts a N-N component replacing the one originally located between the exocyclic C=C bond of a cross-conjugated dibenzofulvalene. Read the full text of the article at 10.1002/chem.202300181.