Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas.
Patients with diabetes mellitus often develop corneal complications and delayed wound healing. How diabetes might alter acute inflammatory responses to tissue injury, leading to delayed wound healing, remains mostly elusive. Using a streptozotocin-induced type I diabetes mellitus mice and corneal epithelium-debridement wound model, we discovered that although wounding induced marked expression of IL-1β and the secreted form of IL-1 receptor antagonist (sIL-1Ra), diabetes suppressed the expressions of sIL-1Ra but not IL-1β in healing epithelia and both in whole cornea. In normoglycemic mice, IL-1β or sIL-1Ra blockade delayed wound healing and influenced each other's expression. In diabetic mice, in addition to delayed reepithelization, diabetes weakened phosphatidylinositol 3-kinase-Akt signaling, caused cell apoptosis, diminished cell proliferation, suppressed neutrophil and natural killer cell infiltrations, and impaired sensory nerve reinnervation in healing mouse corneas. Local administration of recombinant IL-1Ra partially, but significantly, reversed these pathological changes in the diabetic corneas. CXCL10 was a downstream chemokine of IL-1β-IL-1Ra, and exogenous CXCL10 alleviated delayed wound healing in the diabetic, but attenuated it in the normal corneas. In conclusion, the suppressed early innate/inflammatory responses instigated by the imbalance between IL-1β and IL-1Ra is an underlying cause for delayed wound healing in the diabetic corneas. Local application of IL-1Ra accelerates reepithelialization and may be used to treat chronic corneal and potential skin wounds of diabetic patients.


Reproducible Speech Research With the Artificial Intelligence-Ready PERCEPT Corpora.
Publicly available speech corpora facilitate reproducible research by providing open-access data for participants who have consented/assented to data sharing among different research teams. Such corpora can also support clinical education, including perceptual training and training in the use of speech analysis tools. In this research note, we introduce the PERCEPT (Perceptual Error Rating for the Clinical Evaluation of Phonetic Targets) corpora, PERCEPT-R (Rhotics) and PERCEPT-GFTA (Goldman-Fristoe Test of Articulation), which together contain over 36 hr of speech audio (> 125,000 syllable, word, and phrase utterances) from children, adolescents, and young adults aged 6-24 years with speech sound disorder (primarily residual speech sound disorders impacting /ɹ/) and age-matched peers. We highlight PhonBank as the repository for the corpora and demonstrate use of the associated speech analysis software, Phon, to query PERCEPT-R. A worked example of research with PERCEPT-R, suitable for clinical education and research training, is included as an appendix. Support for end users and information/descriptive statistics for future releases of the PERCEPT corpora can be found in a dedicated Slack channel. Finally, we discuss the potential for PERCEPT corpora to support the training of artificial intelligence clinical speech technology appropriate for use with children with speech sound disorders, the development of which has historically been constrained by the limited representation of either children or individuals with speech impairments in publicly available training corpora. We demonstrate the use of PERCEPT corpora, PhonBank, and Phon for clinical training and research questions appropriate to child citation speech. Increased use of these tools has the potential to enhance reproducibility in the study of speech development and disorders.


The Effect of Acupressure Applied to Point LI4 on Perceived Labor Pains.
Controlling labor pain is one of the basic goals for caregivers during the birthing process. There are many pharmacological and nonpharmacological methods that are used for controlling pain and helping the mother to cope with pain and have a favorable labor. The study was planned as a randomized, controlled experimental study to detect the effect of acupressure applied to Point LI4 on perceived labor pains. The study sample comprised 88 pregnant women (44 acupressure group, 44 control group), who complied with the study guidelines, agreed with the conditions of the study, and signed the informed consent. Acupressure was applied to the study group when cervical dilatation reached 4 to 5 cm and again when cervical dilation was 7 to 8 cm. Acupressure was applied to Point LI4 on both the hands at the same time from the beginning to the end of the contraction (16 times). Evaluation with the visual analog scale was made 6 times: when the pregnant woman was first admitted to the hospital, before and after acupressure, and within 2 hours after delivery. The control group received routine care. There were statistically significant differences between the groups in subjective labor pain scores (P < .0001). There was a significant difference between the groups in terms of total duration of labor. As shown from our study, applying acupressure to Point LI4 was found to be effective in decreasing the perception of labor pains and shortening the labor (P < .05). Mothers were pleased with this treatment, but they found it insufficient to control their pain.


The standard of neutrality: still flapping in the breeze?
Abstract Neutrality plays an important role as a null model in evolutionary biology. Recent theoretical advances suggest that neutrality is not a unitary concept, and we identify three distinct forms of neutrality. Eu-neutrality means that types do not differ in any measurable way and is thus the idealized form of neutrality. However, individuals or species that do differ in important ways can behave neutrally under some circumstances, both broadening and complicating the applicability of the concept of neutrality. Our second two types of neutrality address two quite different forms of context-dependent neutrality. Circum-neutrality means that two character states have the same direct effect on fitness but do not evolve neutrally because of differences in their circumstances. Iso-neutrality means that two types are equivalent in some population or ecological contexts but not in others, producing an isocline. Confounding of these different definitions has created significant confusion about which models are truly neutral, why some models behave neutrally even when there are large differences in reproductive outputs, and what these different views of neutrality mean to practicing biologists. These complications call into question the acceptance of neutral models as null models and suggest that a better approach is to compare the predictions of models that differ in sources of stochasticity and degree of selection.


Twenty-five years of ecological recovery of East Fork Poplar Creek: review of environmental problems and remedial actions.
In May 1985, a National Pollutant Discharge Elimination System permit was issued for the Department of Energy's Y-12 National Security Complex (Y-12 Complex) in Oak Ridge, Tennessee, USA, allowing discharge of effluents to East Fork Poplar Creek (EFPC). The effluents ranged from large volumes of chlorinated once-through cooling water and cooling tower blow-down to smaller discharges of treated and untreated process wastewaters, which contained a mixture of heavy metals, organics, and nutrients, especially nitrates. As a condition of the permit, a Biological Monitoring and Abatement Program (BMAP) was developed to meet two major objectives: demonstrate that the established effluent limitations were protecting the classified uses of EFPC, and document the ecological effects resulting from implementing a Water Pollution Control Program at the Y-12 Complex. The second objective is the primary focus of the other papers in this special series. This paper provides a history of pollution and the remedial actions that were implemented; describes the geographic setting of the study area; and characterizes the physicochemical attributes of the sampling sites, including changes in stream flow and temperature that occurred during implementation of the BMAP. Most of the actions taken under the Water Pollution Control Program were completed between 1986 and 1998, with as many as four years elapsing between some of the most significant actions. The Water Pollution Control Program included constructing nine new wastewater treatment facilities and implementation of several other pollution-reducing measures, such as a best management practices plan; area-source pollution control management; and various spill-prevention projects. Many of the major actions had readily discernable effects on the chemical and physical conditions of EFPC. As controls on effluents entering the stream were implemented, pollutant concentrations generally declined and, at least initially, the volume of water discharged from the Y-12 Complex declined. This reduction in discharge was of ecological concern and led to implementation of a flow management program for EFPC. Implementing flow management, in turn, led to substantial changes in chemical and physical conditions of the stream: stream discharge nearly doubled and stream temperatures decreased, becoming more similar to those in reference streams. While water quality clearly improved, meeting water quality standards alone does not guarantee protection of a waterbody's biological integrity. Results from studies on the ecological changes stemming from pollution-reduction actions, such as those presented in this series, also are needed to understand how best to restore or protect biological integrity and enhance ecological recovery in stream ecosystems. With a better knowledge of the ecological consequences of their decisions, environmental managers can better evaluate alternative actions and more accurately predict their effects.


Convergent phenotypic evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic-resistant mutants.
The rise of antibiotic resistance and the reduced amount of novel antibiotics support the need of developing novel strategies to fight infections, based on improving the use of the antibiotics we already have. Collateral sensitivity is an evolutionary trade-off associated with the acquisition of antibiotic resistance that can be exploited to tackle this relevant health problem. However, different works have shown that patterns of collateral sensitivity are not always conserved, thus precluding the exploitation of this evolutionary trade-off to fight infections. In this work, we identify a robust pattern of collateral sensitivity to fosfomycin in Pseudomonas aeruginosa antibiotic-resistant mutants, selected by antibiotics belonging to different structural families. We characterize the underlying mechanism of the collateral sensitivity observed, which is a reduced expression of the genes encoding the peptidoglycan-recycling pathway, which preserves the peptidoglycan synthesis in situations where its de novo synthesis is blocked, and a reduced expression of fosA, encoding a fosfomycin-inactivating enzyme. We propose that the identification of robust collateral sensitivity patterns, as well as the understanding of the molecular mechanisms behind these phenotypes, would provide valuable information to design evolution-based strategies to treat bacterial infections.


Mental health and firearms in community-based surveys: implications for suicide prevention.
Suicide rates are higher among those who own a handgun and among those who [corrected] live in a household with a hand gun. This article examines the association between [corrected] gun ownership and mental health, another risk factor for suicide. Data from the General Social Survey, a series of surveys of U.S. adults, are analyzed to compare general emotional and mental health, sadness and depression, functional mental health, and mental health help seeking among gun owners, persons who do not own but live in a household with a gun, and those who do not own a gun. After taking into account a few basic demographic characteristics associated with both variables, there appears to be no association between mental health and gun ownership. Nor is there any association between mental health and living in a household with a firearm. Findings suggest that the high risk of suicide among those who own or live in a household with a gun is not related to poor mental health. Implications for prevention are discussed.


Relationship between hypoxia and response to antiangiogenic therapy in metastatic colorectal cancer.
Colorectal cancer remains a major public health problem worldwide. Despite the introduction of antiangiogenic drugs for the treatment of metastatic disease, a large number of issues remains unresolved. In particular, studies on predictive biomarkers of response and pathways of resistance to these agents are lacking, making it difficult to accurately select candidates for treatment. Hypoxia is the prime driving force for tumor angiogenesis and a vicious cycle between hypoxia and angiogenesis can be observed in tumors. Anti-angiogenic drugs act inhibiting tumor vasculature and, as consequence, inducing hypoxia. However, hypoxia could, in turn, induce an increase of metastatic potential of cells and a series of phenomena that could induce drug resistance. In the present review biological mechanisms of hypoxia and its relation with angiogenesis, and resistance to antiangiogenic therapy will be discussed. Moreover, data from clinical trials on antiangiogenic drugs in metastatic colorectal cancer will be reviewed, and the role of hypoxia in monitoring the response to treatment will be analysed. Combination strategies using anti-angiogenic and hypoxia inhibiting drugs are also discussed as they constitute promising field of research.


Opioid Use After Common Sports Medicine Procedures: A Systematic Review.
The prescription of opioids after elective surgical procedures has been a contributing factor to the current opioid epidemic in North America. To examine the opioid prescribing practices and rates of opioid consumption among patients undergoing common sports medicine procedures. A systematic review of the electronic databases EMBASE, MEDLINE, and PubMed was performed from database inception to December 2018. Two investigators independently identified all studies reporting on postoperative opioid prescribing practices and consumption after arthroscopic shoulder, knee, or hip surgery. A total of 119 studies were reviewed, with 8 meeting eligibility criteria. Systematic review. Level 4. The quantity of opioids prescribed and used were converted to milligram morphine equivalents (MMEs) for standardized reporting. The quality of each eligible study was evaluated using the Methodological Index for Non-Randomized Studies. A total of 8 studies including 816 patients with a mean age of 43.8 years were eligible for inclusion. A mean of 610, 197, and 613 MMEs were prescribed to patients after arthroscopic procedures of the shoulder, knee, and hip, respectively. At final follow-up, 31%, 34%, and 64% of the prescribed opioids provided after shoulder, knee, and hip arthroscopy, respectively, still remained. The majority of patients (64%) were unaware of the appropriate disposal methods for surplus medication. Patients undergoing arthroscopic rotator cuff repair had the highest opioid consumption (471 MMEs), with 1 in 4 patients receiving a refill. Opioids are being overprescribed for arthroscopic procedures of the shoulder, knee, and hip, with more than one-third of prescribed opioids remaining postoperatively. The majority of patients are unaware of the appropriate disposal techniques for surplus opioids. Appropriate risk stratification tools and evidence-based recommendations regarding pain management strategies after arthroscopic procedures are needed to help curb the growing opioid crisis.


Prolonged QTc interval predicts all-cause mortality in patients with rheumatoid arthritis: an association driven by high inflammatory burden.
RA associates with an increased rate of sudden cardiac death (SCD). A prolonged QTc interval has been associated with arrhythmogenic and SCD in patients with long QT syndrome. Despite the previously reported contemporary association of CRP with SCD, thus far no studies have examined the association of QTc with mortality in RA, a condition characterized by high inflammatory burden. The aim of this study was to examine the role of electrocardiography (QT corrected interval) in predicting all-cause mortality in patients with RA who have an increased rate of SCD and a high inflammatory burden. Three hundred and fifty-seven RA patients with detailed baseline clinical characterization and 12-lead ECGs were followed up for a mean of 73.0 (S.D. 18.3) months. Linear and Cox regression analyses were used to identify variables that associate with QTc and examine its association with all-cause mortality. The patients' mean age was 60.6 (S.D. 12.0) years, 267 (74.8%) were females and 54 (15.1%) died during the follow-up period. Age (β = 0.231, P < 0.001), gender (β = 0.137, P = 0.008) and CRP (β = 0.144, P = 0.006) associated independently with QTc in RA patients. The crude hazard ratio (HR) for total mortality per 50-ms increase in QTc was 2.17 (95% CI 1.21, 3.90). This association remained significant [HR = 2.18 (95% CI 1.09, 4.35)] after adjustment for identified confounders (cardiovascular and RA specific), but was lost [HR = 1.73 (95% CI 0.83, 3.62)] when CRP was included in the model. A 50-ms increase in QTc interval associates with a doubling of the hazard for all-cause mortality in patients with RA. The observed contemporary association of QTc with CRP levels indicates a potentially hazardous interplay between inflammation and arrhythmogenesis. Future studies are needed to confirm the above findings and explore underlying mechanisms.


Phylogenetic positions of Clostridium chauvoei and Clostridium septicum based on 16S rRNA gene sequences.
The sequences of the 16S rRNA genes (rrs genes) of Clostridium chauvoei, the causative agent of blackleg in cattle, and the phenotypically related organism Clostridium septicum were determined. After amplification of 1,507-bp PCR fragments from the corresponding rrs genes, the sequences were determined in a single round of sequencing by using conserved region primers. A sequence similarity analysis of the sequences revealed the close phylogenetic relationship of C. chauvoei and C. septicum in Clostridium cluster I (M. D. Collins, P. A. Lawson, A. Willems, J. J. Cordoba, J. Fernandez-Garayzabal, P. Garcia, J. Cai, H. Hippe, and J. A. E. Farrow, Int. J. Syst. Bacteriol. 44:812-826, 1994), which includes Clostridium carnis, Clostridium perfringens, Clostridium botulinum, and Clostridium tetani. We found that 99.3% of the nucleotides in the genes of C. chauvoei and C. septicum are identical.


Transjugular intrahepatic portosystemic shunt versus distal splenorenal shunt--a comparative study.
No general consensus exists regarding the proper surgical management of recurrent variceal bleeding due to hepatic cirrhosis. Transjugular intrahepatic portosystemic shunt and distal splenorenal shunt are increasingly being performed in the management of these patients. The present study was undertaken to compare the efficacy, complications and survival rate of these two procedures. Sixty-seven patients with alcoholic liver cirrhosis of Child-Pugh's class A (n = 22) and class B (n = 45) with recurrent variceal bleeding not controlled by conservative means underwent either transjugular intrahepatic portosystemic shunt placement (n = 35) or a distal splenorenal shunt operation (n = 32). These patients were followed for a mean of 887 +/- 189 days. Both groups were compared with respect to the rates of survival, recurrence of gastrointestinal bleeding, encephalopathy, ascitis, shunt blockade and other relevant biochemical parameters. Patients who underwent a distal splenorenal shunt operation had lower rates of recurrence of gastrointestinal bleeding (6.25% vs. 25.71%), encephalopathy (18.75% vs. 42.86%) shunt blockade (6.25% vs. 68.57%) and lower mean fasting blood ammonia levels (56.70 +/- 7.10 mumol/L vs. 61.70 +/- 5.70 mumol/L). However the rate of ascitis was higher amongst these patients (40.63% vs. 11.43%). There was no significant difference in the midterm survival rates between these groups (81.25% vs. 80.00%). Both procedures were effective in controlling functional renal failure, splenomegaly and features of hypersplenism. Distal splenorenal shunt operation is a better therapeutic option than transjugular intrahepatic portosystemic shunt placement for control of recurrent variceal bleeding due to hepatic cirrhosis.


Relationship between diffraction peak, network topology, and amorphous-forming ability in silicon and silica.
The network topology in disordered materials is an important structural descriptor for understanding the nature of disorder that is usually hidden in pairwise correlations. Here, we compare the covalent network topology of liquid and solidified silicon (Si) with that of silica (SiO2) on the basis of the analyses of the ring size and cavity distributions and tetrahedral order. We discover that the ring size distributions in amorphous (a)-Si are narrower and the cavity volume ratio is smaller than those in a-SiO2, which is a signature of poor amorphous-forming ability in a-Si. Moreover, a significant difference is found between the liquid topology of Si and that of SiO2. These topological features, which are reflected in diffraction patterns, explain why silica is an amorphous former, whereas it is impossible to prepare bulk a-Si. We conclude that the tetrahedral corner-sharing network of AX2, in which A is a fourfold cation and X is a twofold anion, as indicated by the first sharp diffraction peak, is an important motif for the amorphous-forming ability that can rule out a-Si as an amorphous former. This concept is consistent with the fact that an elemental material cannot form a bulk amorphous phase using melt quenching technique.


A review of pathological diagnoses made from 87 canine splenic biopsies.
The pathological findings in 87 cases of canine splenic abnormality recognised clinically by abdominal palpation or radiography, or at exploratory laparotomy, are presented. The most common diagnosis was of splenic neoplasia (n = 38) and the most frequently recognised canine splenic neoplasm was haemangiosarcoma (17 of 38 cases). Benign splenic enlargement secondary to nodular hyperplasia (n = 6), haematoma (n = 16) or non-specific changes including congestion, haemorrhage, extramedullary haemopoiesis and haemosiderin deposition (n = 14) was also recognised. A diagnosis of non-specific pathology was more frequently recorded when portions of spleen, as opposed to the entire organ, were submitted for assessment. Splenic infarction, with (n = 3) or without (n = 7) torsion, abscessation (n = 2) and focal mast cell proliferation (n = 1) accounted for the remainder of the cases. Clinical follow-up was available for 35 cases and revealed good long-term survival in cases of splenic haematoma or haemangioma, with relatively poor survival with a diagnosis of splenic haemangiosarcoma or anaplastic sarcoma. A range of splenic disorders was recognised in dogs of the labrador breed (16 of 87 cases) and three of 17 cases of haemangiosarcoma occurred in German shepherd dogs. The possible predisposition of dogs of these breeds to splenic disorders is discussed.


Scribble modulates the MAPK/Fra1 pathway to disrupt luminal and ductal integrity and suppress tumour formation in the mammary gland.
Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression.


Intra- and extra-cranial effects of transient blood pressure changes on brain near-infrared spectroscopy (NIRS) measurements.
Brain near-infrared spectroscopy (NIRS) is an emerging neurophysiological tool that combines straightforward activity localization with cost-economy, portability and patient compatibility. NIRS is proving its empirical utility across specific cognitive and emotional paradigms. However, a potential limitation is that it is not only sensitive to haemodynamic changes taking place in the cortex, and task-related cardiovascular responses expressed in the perfusion of extracranial layers may be confounding. Existing literature reports correlations between brain NIRS and systemic blood pressure, yet it falls short of establishing whether in normal participants the blood pressure changes encountered in experimental settings can have confounding effects. Here, we tested this hypothesis by performing two experimental manipulations while recording from superficial occipital cortex, encompassing striate and extrastriate regions. Visual stimulation with reversing chequerboards evoked cortical haemodynamic responses. Simultaneously and independently, transient systemic blood pressure changes were generated through rapid arm-raising. Shallow-penetration NIRS recordings, probing only extra-cerebral tissues, highlighted close haemodynamic coupling with blood pressure. A different coupling pattern was observed in deep-penetration recordings directed at haemodynamic signals from visual cortex. In absence of blood-pressure changes, NIRS signals tracked differences in visual stimulus duration. However when blood pressure was actively manipulated, this effect was absent and replaced by a very large pressure-related response. Our observations demonstrate that blood pressure fluctuations can exert confounding effects on brain NIRS, through expression in extracranial tissues and within the brain itself. We highlight the necessity for continuous blood pressure monitoring alongside brain NIRS, and for further research on methods to correct for physiological confounds.


Balanitis and balanoposthitis: a review.
To give an overview of the literature on balanitis, with a special emphasis on infective causes. A data search was performed using the OVID CD plus Medline 1967-1995, using balanitis and balanoposthitis as textword search strategy. Specific subjects such as anaerobic infection, Zoon's balanitis were sought separately and subgroups combined. Original articles and abstracts were referenced to illustrate each condition. These were mainly English language articles, but included appropriate non-English language papers. Balanitis is a common condition among genitourinary medicine clinic attendees, the cause often remaining undiagnosed. Many cases are caused by infection, with candida being the most frequently diagnosed. However, gardnerella and anaerobic infections are common, and there are a wide variety of other rarer infective causes. In addition irritant balanitis is probably a contributing factor in many cases. Balanitis which persists and in which the cause remains unclear warrants biopsy.


The influence of input material properties on hot melt granules prepared using a counter-rotating batch mixer.
The objective of this study was to develop a method that enabled granulation in a counter-rotating batch mixer to emulate large scale dry twin screw granulation trials. Four granulations were prepared using counter rotating batch mixing for formulations containing a mixture of different particle sizes of the API (70% w/w) and polymer (30% w/w). Milled theophylline (MTHF; fine API) was blended with coarse hydroxypropyl cellulose (HPC MF; coarse polymer), theophylline (THF; coarse API) with fine hydroxypropyl cellulose (HPC EXF, fine polymer), and the other two formulations consisted of both components in the blend being fine or coarse. The formulations selected for granulation had the lowest friction coefficient, f, as a function of drug load determined by the iShear® powder flow rheometer. Despite the non-uniform chaotic and random nature of thermal granulation, each formulation granulated reproducibly, though the evolution for each was different. This work highlighted that, firstly it is possible to measure plastic and frictional energy dissipation as product temperature. Secondly, granule growth and density were found to be proportional to the onset of polymer molecular mobility activated by the heat liberated from interparticle velocity differences via mechanical work (torque) required to move agglomerates through the mixer for the duration of each run.


SBOLDesigner 2: An Intuitive Tool for Structural Genetic Design.
As the Synthetic Biology Open Language (SBOL) data and visual standards gain acceptance for describing genetic designs in a detailed and reproducible way, there is an increasing need for an intuitive sequence editor tool that biologists can use that supports these standards. This paper describes SBOLDesigner 2, a genetic design automation (GDA) tool that natively supports both the SBOL data model (Version 2) and SBOL Visual (Version 1). This software is enabled to fetch and store parts and designs from SBOL repositories, such as SynBioHub. It can also import and export data about parts and designs in FASTA, GenBank, and SBOL 1 data format. Finally, it possesses a simple and intuitive user interface. This paper describes the design process using SBOLDesigner 2, highlighting new features over the earlier prototype versions. SBOLDesigner 2 is released freely and open source under the Apache 2.0 license.


Fatal outcome in a liver transplant recipient with COVID-19.
Liver injury is common in patients with COVID-19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID-19 in a patient who underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID-19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.


Nutritional status of Kuwaiti elementary school children aged 6-10 years: comparison with the NCHS/CDC reference population.
The objective of this cross-sectional sampling survey was to assess the nutritional status of Kuwaiti elementary school children aged 6-10 years in comparison with the NCHS/CDC American reference population. The study comprised a multistage stratified random sample of 8957 children (4401 males and 4556 females) which amounts to about 12% of the target population. Weights and heights of children were measured. Obesity was defined as weight-for-height (W/H) 2.00 to 5.00 standard deviation (SD) scores of the reference population. Underweight and short stature were defined as weight-for-height (W/H) and height-for-age (H/A) -4.00 to -2.00 and -5.00 to -2.00 SD scores, respectively. The results of this study showed that obesity was found to be significantly (P < 0.01) higher in males (15.7%) than in females (13.8%). Underweight was found to be almost equally prevalent among both genders (3.7% in males and 3.8% in females). Short stature (H/A) -5.00 to -2.00 SD scores) was found to be 7.1% (9.5% in males and 4.6% in females). When compared with an earlier study, changes in W/H were significant across most of the centile categories. However, significant changes in H/A were noted with less frequency than W/H; mostly in the upper centiles for both genders. More significant changes, however, were noted among males than females. In conclusion, Kuwaiti children were found to be heavier and shorter than American children. Moreover, the children were found to be fatter and slightly taller but nonetheless more nutritionally sound than a decade earlier.


Comparison of patient satisfaction with services of vision centers in rural areas of Andhra Pradesh, India.
To compare the satisfaction of patients with the services of Vision Center services (primary eye care) in large village (s) and small village (s) in rural settings in Andhra Pradesh state, India. We have administered standard questionnaires to randomly selected patients to assess patient satisfaction when assessing Vision Center Services. We used the Chi-square ( P <0.05) to explore differences in satisfaction of patients with Vision Center services located in the large village (s) and small village (s) rural settings. Vision Center patients at the large village (s) expressed higher levels of satisfaction (median 78%) than patients treated at the Vision Center at small village (s) (median 69%). The difference was statistically significant (Chi square P value ranging from <0.001 to 0.03) for all the items except two - 'easy to identify vision center location' and 'spectacles dispensing time' as compared to other (privately run optometry) facilities (Chi square P value=0.498 and 0.993 respectively). The location of the Vision Center, convenience of journey, ophthalmic technician's behavior with patients, are some of the most important factors that determined the patient perception about Vision Center services. The overall satisfaction levels of the Vision Center experience at 78% and 69% were good. However, continual improvement is to be made in service time, staff performance, cost and quality of vision care, especially at more remote primary eye Care Centers.


A phylogenomic and molecular markers based analysis of the phylum Chlamydiae: proposal to divide the class Chlamydiia into two orders, Chlamydiales and Parachlamydiales ord. nov., and emended description of the class Chlamydiia.
The phylum Chlamydiae contains nine ecologically and genetically diverse families all placed within a single order. In this work, we have completed a comprehensive comparative analysis of 36 sequenced Chlamydiae genomes in order to identify shared molecular characteristics, namely conserved signature insertions/deletions (CSIs) and conserved signature proteins (CSPs), which can serve as distinguishing characteristics of supra-familial clusters within the phylum Chlamydiae. Our analysis has led to the identification of 32 CSIs which are specific to clusters within the phylum Chlamydiae at various phylogenetic depths. Importantly, 17 CSIs and 98 CSPs were found to be specific for the family Chlamydiaceae while another 3 CSI variants and 15 CSPs were specific for a grouping of the families Criblamydiaceae, Parachlamydiaceae, Simkaniaceae and Waddliaceae. These two clusters were also found to be distinguishable in 16S rRNA based phylogenetic trees, concatenated protein based phylogenetic trees, character compatibility based phylogenetic analyses, and on the basis of 16S rRNA gene sequence identity and average amino acid identity values. On the basis of the identified molecular characteristics, branching in phylogenetic trees, and the genetic distance between the two clusters within the phylum Chlamydiae we propose a division of the class Chlamydiia into two orders: an emended order Chlamydiales, containing the family Chlamydiaceae and the closely related Candidatus family Clavichlamydiaceae, and the novel order Parachlamydiales ord. nov. containing the families Parachlamydiaceae, Simkaniaceae and Waddliaceae and the Candidatus families Criblamydiaceae, Parilichlamydiaceae, Piscichlamydiaceae, and Rhabdochlamydiaceae. We also include a brief discussion of the reunification of the genera Chlamydia and Chlamydophila.


Analysis of the desialidation process of the haemagglutinin protein of influenza B virus: the host-dependent desialidation step.
It was reported previously that haemadsorption by the haemagglutinin (HA) protein of influenza B virus required that the protein must undergo desialidation. When MDCK and COS cells were infected with influenza B/Kanagawa/73 virus in the presence of a neuraminidase (NA) inhibitor, Zanamivir, haemadsorption on MDCK cells was inhibited but that on COS cells was not. The activity of the NA protein of the two types of infected cells was similar and both were inhibited by Zanamivir in a dose-dependent manner. A comparison of the desialidation of the HA protein was made on MDCK and COS cells in the presence of bacterial NA and both cells were found to have similar sensitivity. On the accumulation of the HA and NA proteins in the trans-Golgi network of MDCK cells by means of low-temperature treatment, desialidation of the HA protein in the presence of Zanamivir was detected by two-dimensional gel electrophoresis. Because this agent was reported to be unable to penetrate cells, these data suggest that, in MDCK cells, desialidation of the HA protein occurs on the cell surface but, in COS cells, the HA and NA proteins might accumulate in the trans-Golgi network, thus allowing NA desialidation before their migration to the cell surface.


Acceptance of male registered nurses by female registered nurses.
To investigate attitudes of acceptance toward male registered nurses by female registered nurses. Randomized descriptive design using 105 female registered nurses from a large midwestern state in the US. Data were collected using an attitude inventory and analyzed using t test, chi square, Spearman rho, Pearson correlation, Mann-Whitney U and multiple regression tests. Acceptance was normally distributed. No difference in acceptance was found between rural and urban participants. The length of time working with a male nurse explained significant variance in acceptance scores. City or town of socialization was not related to acceptance scores. Rural participants were less likely than were urban participants to believe that female nurses are ready to accept large numbers of men into the profession. The relationship of the distribution of acceptance of male registered nurses found in this study to the perceptions of acceptance by male registered nurses is unclear and requires further investigation.


Characterization of zebrafish primordial germ cells: morphology and early distribution of vasa RNA.
Research into germ line development is of conceptual and biotechnologic importance. In this study, we used morphology at the level of light and electron microscope to characterize the primordial germ cells (PGCs) of the zebrafish throughout embryonic and larval development. The study was complemented by the detailed analysis of mRNA expression of a putative germ line marker vasa. By morphology alone PGCs were identified at the earliest at the 5-somite stage in the peripheral endoderm in contact with the yolk syncytial layer. Subsequently, they move from lateral to medial positions into the median mesoderm and from there by means of the dorsal mesentery into the gonadal anlage at day 5 postfertilization (pf), to establish gonads with mesenchymal cells by day 9 pf. Ultrastructural analysis of the 4-day-old zebrafish larvae demonstrates the presence of the germ line-specific structures, nuage, and annulate lamellae. vasa RNA-positive cells can be followed during zebrafish embryogenesis from the 32-cell stage onward (Yoon et al., 1997). Upon completion of gastrulation, the RNA is exclusively present in the cells of the hypoblast, which as a consequence of convergence and extension movements first arrange themselves in a V-shaped string-like conformation to end up, by late somitogenesis, as a string of cells on each side of the midline. We show that the localization of maternal vasa RNA in the ovary changes from cytoplasmic, in the previtellogenic oocytes, to cortical in the vitellogenic oocytes, to concentrate at the boundary of the yolk and cytoplasm in the one cell stage zygote. These results demonstrate that the cortical vasa RNA localization precedes its cleavage furrow-associated localization in the embryos and is presumably cytoskeleton dependent. vasa RNA localization changes from asymmetric subcellular at the sphere stage, to become entirely cytoplasmic at the dome stage. These data suggest a close resemblance in modes of segregation of the germ plasma in the frog and vasa mRNA in the fish during cleavage stages. Based on the significantly larger size and the stereotype and similar position of morphologically distinct cells, presumed to be PGCs, and their vasa RNA-positive counterparts, we conclude that vasa RNA-positive cells are the PGCs and vasa RNA represents a definitive germ line marker in the fish. Dev Dyn 1999;216:153-167.


Lack of impact of radioiodine therapy in tg-positive, diagnostic whole-body scan-negative patients with follicular cell-derived thyroid cancer.
Several reports have suggested a benefit from radioactive iodine (RAI) therapy in Tg-positive, whole-body scan-negative patients with follicular cell-derived thyroid cancer, who were said to have high rates of visualization of uptake in metastases after therapeutic doses of RAI. We sought to evaluate the rate of visualization of RAI uptake in these patients and determine the effect of such therapy on tumor progression and Tg levels. We studied 24 consecutive patients who had been treated with high-dose RAI, four of whom had no evidence of metastasis or persistent cancer. Our results showed that four patients had some uptake in posttherapy scans: in the neck, lung, and mediastinal metastases in one patient, in the thyroid remnant in two, and in a possible neck microrecurrence in one. In 13 patients with macrometastases-tumors 1 cm or greater-tumors progressed and serum Tg increased; five have died of thyroid cancer. The disease remained stable in the seven patients with micrometastases. We concluded that in high-risk patients with follicular cell-derived thyroid cancer with high Tg levels and negative diagnostic whole-body scans, only a small number showed meaningful uptake after high doses of RAI. Therefore, widespread use of empiric RAI therapy for such patients who have a large tumor burden should not be encouraged.


Antecedents of intimate partner violence among gay and bisexual men.
Examinations of gay and bisexual men's (GBM) perceptions of intimate partner violence (IPV), including their perceptions of events likely to precipitate IPV, are lacking. Focus group discussions with GBM (n = 83) yielded 24 unique antecedents, or triggers, of IPV in male-male relationships. Venue-recruited survey participants (n = 700) identified antecedents that were likely to cause partner violence in male-male relationships, including antecedents GBM-specific currently absent from the literature. Chi-square tests found significant variations in antecedent endorsement when tested against recent receipt of IPV. Linear regression confirmed that men reporting recent IPV endorsed significantly more IPV antecedents than men without recent IPV (beta = 1.8155, p < .012). A better understanding of the IPV event itself in male-male couples versus heterosexual couples, including its antecedents, can inform and strengthen IPV prevention efforts.


SGLT1-Mediated Transport in Caco-2 Cells Is Highly Dependent on Cell Bank Origin.
The human colon adenocarcinoma (Caco-2) cell line is a well-established in vitro model for studying transport phenomena for prediction of intestinal nutrient and drug absorption. However, substances depending on transporters such predictions are complicated due to variable transporter expression and limited knowledge about transporter function during multiple cell passaging and cell thawings. In the case of sodium glucose transporter 1 (SGLT1), a key transporter of oral absorption of d-glucose, one reason for compromised prediction could be inadequate expression of SGLT1 in Caco-2 cells and thereby limited sensitivity in the determination of SGLT1-mediated permeability (PSGLT1). Here, the objective is to characterize and compare SGLT1-mediated uptake in Caco-2 cells obtained from different cell banks. SGLT1-mediated uptake of the standard SGLT1 substrate, methyl-α-d-glucopyranoside, in Caco-2 cells was shown to be highly dependent on cell bank origin. The most robust and reliable SGLT1 functionality was identified in Caco-2 cells from Deutsche Sammlung für Mikroorganismen und Zellkulturen (DSMZ), whereas cells from the American Type Culture Collection and European Collection of Authenticated Cell Cultures have lower SGLT1 transport activity. Transepithelial PSGLT1 across Caco-2 cells from DSMZ showed that PSGLT1 likely accounts for approximately 97% of absorptive methyl-α-d-glucopyranoside Papp(a-b). In conclusion, Caco-2 cells from DSMZ provide a robust in vitro model for studying SGLT1-mediated uptake and transport-over multiple cell passages and independent cell stock thawings.


The MT2 melatonin receptor subtype is present in human retina and decreases in Alzheimer's disease.
The pineal and retinal melatonin regulates endogenous circadian rhythms, and has various physiological functions including neuromodulatory and vasoactive actions, antioxidative and neuroprotective properties. We have previously demonstrated that the melatonin 1a-receptor (MT(1)) is localized in human retinal cells and that the expression of MT(1) is increased in Alzheimer's disease (AD) patients. We now present the first immunohistochemical evidence for the cellular distribution of the second melatonin receptor, MT(2), in the human retina and in AD patients. In elderly controls, MT(2) was localized to ganglion and bipolar cells in the inner nuclear layer, and to the inner segments of the photoreceptor cells. In addition, cellular processes in inner and outer plexiform layers were strongly positive for MT(2). In AD patients the overall intensity of MT(2)-staining was distinctly decreased in all observed cellular localizations. Our results indicate that MT(2) in the humans, similar to MT(1), may indeed be involved in transmitting melatonin's effects in the retina, and AD pathology may impair MT(2) expression. Since our previous results showed an increase in MT(1) expression in AD retina, the two melatonin receptor subtypes appear to be differentially affected by the course of the neurodegenerative disorder.


Genetically Predicted Circulating C-Reactive Protein Concentration and Colorectal Cancer Survival: A Mendelian Randomization Consortium Study.
A positive association between circulating C-reactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically predicted CRP concentrations and colorectal cancer-specific survival. We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic-risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Because of the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically predicted CRP concentrations and colorectal cancer-specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components. Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to colorectal cancer. Genetically predicted CRP concentration was not associated with colorectal cancer-specific survival (HD, -1.15; 95% CI, -2.76 to 0.47 per 100,000 person-years; P = 0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location. Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on colorectal cancer-specific survival. Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.


Functional genomic and advanced genetic studies reveal novel insights into the metabolism, regulation, and biology of Haloferax volcanii.
The genome sequence of Haloferax volcanii is available and several comparative genomic in silico studies were performed that yielded novel insight for example into protein export, RNA modifications, small non-coding RNAs, and ubiquitin-like Small Archaeal Modifier Proteins. The full range of functional genomic methods has been established and results from transcriptomic, proteomic and metabolomic studies are discussed. Notably, Hfx. volcanii is together with Halobacterium salinarum the only prokaryotic species for which a translatome analysis has been performed. The results revealed that the fraction of translationally-regulated genes in haloarchaea is as high as in eukaryotes. A highly efficient genetic system has been established that enables the application of libraries as well as the parallel generation of genomic deletion mutants. Facile mutant generation is complemented by the possibility to culture Hfx. volcanii in microtiter plates, allowing the phenotyping of mutant collections. Genetic approaches are currently used to study diverse biological questions-from replication to posttranslational modification-and selected results are discussed. Taken together, the wealth of functional genomic and genetic tools make Hfx. volcanii a bona fide archaeal model species, which has enabled the generation of important results in recent years and will most likely generate further breakthroughs in the future.


Diurnal secretion of ghrelin, growth hormone, insulin binding proteins, and prolactin in normal weight and overweight subjects with and without the night eating syndrome.
The regulatory peptide ghrelin has been proposed to help mediate both hunger and sleep. The neuroendocrine circadian patterns in the night eating syndrome (NES) have been distinguished by an attenuated nocturnal rise in the plasma concentrations of melatonin and leptin and a greater increase in the concentrations of cortisol. In this study we wanted to test the hypothesis that night eaters have disturbances in the circadian levels of ghrelin, growth hormone (GH) and associated regulatory peptides. In 12 female night eaters (6 normal weight and 6 overweight), and 25 healthy controls (12 normal weight and 13 overweight), blood was sampled over a 24-hour period. Four meals were served from 8 AM to 8 PM, and blood samples were drawn every second hour for determination of plasma ghrelin concentrations and GH by radioimmunoassay (RIA). Analysis of serum GH, IGF-1, IGFBP-3 and prolactin were performed by ELISA. In healthy normal weight subjects there was a slight but non significant nocturnal increase of ghrelin, whereas a more or less flat curve was observed for healthy overweight, NES normal weight and NES overweight patients. The RMANOVA analysis showed a significant independent lowering effect of overweight on the grand mean of ghrelin. No direct effects on NES normal weight and overweight subjects were found, but a near-significant interaction was found between healthy overweight and overweight NES subjects. There were independent significant lowering effects of overweight and NES on the serum GH levels. During the time course no changes in the serum levels of IGF-1 or IGFB-3 were observed. Independent significant lowering effects of overweight and NES on the levels of IGF-1 were detected, whereas a near significant reduction in the global levels of IGFBP-3 was observed in both NES groups. Finally, significant nocturnal changes were observed for serum levels of prolactin in all four subgroups. Grand mean levels tended to be higher in NES subjects whereas the opposite was observed in healthy overweight (ns). We conclude that in both NES groups and in healthy overweight subjects more or less attenuated ghrelin and GH secretions were observed, whereas divergent secretions were observed for prolactin.


Referral criteria and clinical decision support: radiological protection aspects for justification.
Advanced imaging technology has opened new horizons for medical diagnostics and improved patient care. However, many procedures are unjustified and do not provide a net benefit. An area of particular concern is the unnecessary use of radiation when clinical evaluation or other imaging modalities could provide an accurate diagnosis. Referral criteria for medical imaging are consensus statements based on the best-available evidence to assist the decision-making process when choosing the best imaging procedure for a given patient. Although they are advisory rather than compulsory, physicians should have good reasons for deviation from these criteria. Voluntary use of referral criteria has shown limited success compared with integration into clinical decision support systems. These systems support good medical practice, can improve health service delivery, and foster safer, more efficient, fair, cost-effective care, thus contributing to the strengthening of health systems. Justification of procedures and optimisation of protection, the two pillars of radiological protection in health care, are implicit in the notion of good medical practice. However, some health professionals are not familiar with these principles, and have low awareness of radiological protection aspects of justification. A stronger collaboration between radiation protection and healthcare communities could contribute to improve the radiation protection culture in medical practice.


Standardized Volume Dosing Protocol of 23.4% Hypertonic Saline for Pediatric Critical Care: Initial Experience.
Background: Standardized volume dosing of 23.4% hypertonic saline (HTS) exists for adults, but the concentration, dosing and administration of HTS in pediatrics is variable. With emerging pediatric experience of 23.4% HTS, a standard volume dose approach may be helpful. Objective: To describe initial experience with a standardized 23.4% HTS weight-based volume dosing protocol of 10, 20, or 30 mL in the pediatric intensive care unit. Methods: Standard volume doses of 23.4% HTS were developed from weight dosing equivalents of 3% HTS. Pre and post sodium and intracranial pressure (ICP) measurements were compared with paired t-test or Wilcoxon rank-sum test. The site of administration and complications were noted. Results: A total of 16 pediatric patients received 37 doses of 23.4% HTS, with the smallest patient weighing 11 kg. For protocol compliance, 17 doses (46%) followed recommended dosing, 19 were less volume than recommended (51%), and 1 dose (3%) was more than recommended. Mean increase in sodium was 3.5 mEq/L (95% CI = 2-5 mEq/L); P < 0.0001. The median decrease in ICP was 10.5 mm Hg (interquartile range [IQR] 8.3-19.5) for a 37% (IQR 25%-64%) reduction. Most doses were administered through central venous access, although peripheral intravenous administrations occurred in 4 patients without complication. Conclusion and Relevance: Three standard-volume dose options of 23.4% HTS based on weight increases sodium and reduces ICP in pediatric patients. Standard-volume doses may simplify weight-based dosing, storage and administration for pediatric emergencies, although the optimum dose, and safety of 23.4% HTS in children remains unknown.


Toward a useful standard for hospitalizing pretrial jail detainees.
Severely mentally ill jail detainees require an adequate spectrum of mental health services during detainment. For some this means a limited period of treatment in a mental hospital, just as some mentally ill individuals in the community occasionally require hospital treatment. Unfortunately, this appropriate level of treatment is often denied or neglected for jail detainees with adverse consequences for them. Among the reasons for this neglect, may be standards for hospital transfer that are no longer practical and can be easily skirted by policymakers and administrators with little interest in ensuring this level of care for mentally ill jail inmates. A more realistic standard and justification would recognize the need for hospitalization for the mentally disordered detainee who because of psychotic anosognosia refuses appropriate treatment including medications and/or whose severely decompensated condition is worsening or failing to improve despite attempts at treatment in the jail.


An unusual death by transcranial stab wound: homicide or suicide?
Penetrating stab wounds of the brain are uncommonly seen in modern times and occur almost exclusively in homicides. We report an unusual death by self-stabbing. A 24-year-old man was found dead at home, the handle of a kitchen knife protruding from his forehead. Data such as the psychiatric history of the victim, the multiplicity and site of wounds, the implement used, the presence of hesitation, and defense wounds were studied to elucidate the manner of death, and the suicidal nature of the event was established after police investigation. Atypical injuries require a careful forensic investigation, and medico-legal aspects of the differentiation between homicide and suicide are discussed in this particular case. A review of the literature revealed few cases of suicidal transcranial stab wounds.


Nursing Care on HIV/AIDS-Positive Men Who Have Sex with Men: A Qualitative Descriptive Study of Nurse's Perspective in Indonesia.
HIV/AIDS-positive men who have had sex with men (MSM) account for roughly one-third of new infections in the region, with numerous nations facing a high and rising prevalence. They often face stigmatization and discrimination from society, including nurses. This study aims to explore nurses' perspectives on caring for HIV/AIDS-infected MSM. A descriptive qualitative design was utilized. Fifteen nurses who cared for HIV/AIDS-positive MSM in the two hospitals in Jakarta, Indonesia, were recruited with purposive sampling techniques. A semi-structured and in-depth interview was conducted. Data were analyzed using thematic analysis. We emerged three superordinate and nine subordinate themes: (1) negative nurse perceptions in the early phase of treatment, (2) nurse attitudes contrasting with negative perceptions, and (3) nurses with knowledge of HIV/AIDS. The negative perceptions appeared only at the beginning of the treatment phase, and thereafter, they were followed by a positive attitude. Nurses appeared to develop a better understanding after interacting with their patients and receiving training on HIV/AIDS. Therefore, intensive training is expected to not only increase their knowledge but to encourage a positive attitude.


The WHO ultrasonography protocol for assessing morbidity due to Schistosoma haematobium. Acceptance and evolution over 14 years. Systematic review.
In 2000, the World Health Organization (WHO) published an ultrasound field protocol for assessing morbidity due to schistosomiasis. The present study aims to review the acceptance of the WHO protocol for Schistosoma haematobium. A PubMed literature research using the keywords "ultrasound OR ultrasonography (US) AND schistosomiasis," "US AND S. haematobium," "US AND urinary schistosomiasis" from 2001 through 2014 was performed. Thirty-eight eligible publications reporting on 17,861 patients from 13 endemic and 2 non-endemic countries were analysed. Of these, 33 referred to field studies on 17,317 patients. The Niamey protocol was applied to 15,367/17,317 (88.74%) patients in 23/33 (69.70%) of field studies (all studies: 15,649/17,861 [87.61%] patients (25/38 [68.42%] studies). The acceptance of the protocol by single country in field studies varied from 0 to 100%. It varied over time between 55.56% (5/9) in the period from 2001 to 2004, to 87.50% (7/8) from 2005 to 2008, to 62.50% (5/8) from 2009 to 2011 and 75.00% (6/8) from 2012 through 2014 (all studies: 50% [5/10], 88.89% [8/9], 62.50% [5/8], 63.64% [7/11], respectively). The Niamey protocol was applied also in 2/5 hospital studies in 282/544 (51.84%) patients.The usefulness of the WHO protocol for S. haematobium infections is confirmed by its worldwide acceptance. Some simplifications might facilitate its use also for focused ultrasound examinations performed by less skilled examiners. Organ abnormalities due to schistosomiasis detectable by ultrasonography not yet covered by the WHO protocol should be added to the additional investigations section.


Habitual consumption of long-chain n-3 PUFAs and fish attenuates genetically associated long-term weight gain.
A growing amount of data suggests that n-3 (ω-3) polyunsaturated fatty acid (PUFA) intake may modify the genetic association with weight change. We aimed to prospectively test interactions of habitual consumption of n-3 PUFAs or fish, the major food source, with overall genetic susceptibility on long-term weight change. Gene-diet interactions were examined in 11,330 women from the Nurses' Health Study (NHS), 6773 men from the Health Professionals Follow-Up Study (HPFS), and 6254 women from the Women's Health Initiative (WHI). In the NHS and HPFS cohorts, food-sourced long-chain n-3 PUFA intake showed directionally consistent interactions with genetic risk score on long-term changes in BMI (P-interaction = 0.01 in the HPFS, 0.15 in the NHS, and 0.01 in both cohorts combined). Such interactions were successfully replicated in the WHI, an independent cohort (P-interaction = 0.02 in the WHI and 0.01 in the combined 3 cohorts). The genetic associations with changes in BMI (in kg/m2) consistently decreased (0.15, 0.10, 0.07, and -0.14 per 10 BMI-increasing alleles) across the quartiles of long-chain n-3 PUFAs in the combined cohorts. In addition, high fish intake also attenuated the genetic associations with long-term changes in BMI in the HPFS (P-interaction = 0.01), NHS (P-interaction = 0.03), WHI (P-interaction = 0.10), and the combined cohorts (P-interaction = 0.01); and the differences in BMI changes per 10 BMI-increasing alleles were 0.16, 0.06, -0.08, and -0.18, respectively, across the categories (≤1, 1∼4, 4∼6, and ≥7 servings/wk) of total fish intake. Similar interactions on body weight were observed for fish intake (P-interaction = 0.003) and long-chain n-3 PUFA intake (P-interaction = 0.12). Our study provides replicable evidence to show that high intakes of fish and long-chain n-3 PUFAs are associated with an attenuation of the genetic association with long-term weight gain based on results from 3 prospective cohorts of Caucasians.


Eliminating false positive C4 sugar tests on New Zealand Manuka honey.
Carbon isotope analyses (delta(13)C) of some New Zealand Manuka honeys show that they often fail the internationally recognised Association of Official Analytical Chemists sugar test (AOAC method 998.12) which detects added C(4) sugar, although these honeys are from unadulterated sources. Failure of these high value products is detrimental to the New Zealand honey industry, not only in lost export revenue, but also in brand and market reputation damage. The standard AOAC test compares the carbon isotope value of the whole honey and corresponding protein isolated from the same honey. Differences between whole honey and protein delta(13)C values should not be greater than +1.0 per thousand, as it indicates the possibility of adulteration with syrups or sugars from C(4) plants such as high fructose corn syrup or cane sugar.We have determined that during the standard AOAC method, pollen and other insoluble components are isolated with the flocculated protein. These non-protein components have isotope values which are considerably different from those of the pure protein, and can shift the apparent delta(13)C value of protein further away from the delta(13)C value of the whole honey, giving a false positive result for added C(4) sugar. To eliminate a false positive C(4) sugar test for Manuka honey, prior removal of pollen and other insoluble material from the honey is necessary to ensure that only the pure protein is isolated. This will enable a true comparison between whole honey and protein delta(13)C isotopes. Furthermore, we strongly suggest this modification to the AOAC method be universally adopted for all honey C(4) sugar tests.


Cerebral oximetry desaturation during shoulder surgery performed in a sitting position under regional anesthesia.
Hypotension in the sitting position may reduce cerebral perfusion and oxygenation. We prospectively determined the incidence of cerebral oximetry (rSO2) desaturation in seated patients undergoing ambulatory shoulder arthroscopy. A cohort of 99 patients received regional anesthesia and intravenous sedation, and their blood pressure was recorded every five minutes. Hypotension was defined as the occurrence of any of the following: > 30% decline in mean arterial pressure (MAP), systolic blood pressure < 90 mmHg, or MAP <66 mmHg. Cerebral desaturation was defined as a > 20% decrease in rSO2 from baseline. The association of rSO2 desaturation with potential risk factors was examined by the generalized estimating equation to account for within patient correlation and multiple observations per patient. We fitted desaturation with three models: 1) unadjusted (i.e., hypotension as sole regressor); 2) time-trend adjusted; and 3) baseline-factors adjusted model. Hypotension occurred in 76% of observations (mean duration 4,261 sec), but cerebral desaturation was seen in only 0.77% of observations (mean duration 426 sec). Ninety-nine percent of patients experienced hypotension, but cerebral desaturation occurred in only 10%. By unadjusted modelling, hypotension was associated with cerebral desaturation (odds ratio = 3.21; P = 0.02). Once time-trend adjusted, cerebral desaturation was associated with time from baseline but not with hypotension (P = 0.14). When adjusted for baseline factors, the analysis demonstrated a non-significant association with hypotension (P = 0.34) but a significant association with the presence of risk factors for cerebrovascular disease (P = 0.01). Despite frequent hypotension in the sitting position, rSO2 desaturation was uncommon during shoulder arthroscopy performed in the sitting position with regional anesthesia.


Effect of myopia on the progression of primary open-angle glaucoma.
To evaluate the effect of myopia on the progression of primary open-angle glaucoma. In this retrospective cohort study, eyes were classified into nonmyopic (NMG, >0 diopters [D]), mild to moderate (MMG, 0 to -6 D), and highly myopic glaucoma (HMG, <-6 D) groups according to the level of spherical equivalent. Glaucoma progression was determined either by optic disc/retinal nerve fiber layer (RNFL) photographs or by serial visual field (VF) data. Cox's proportional hazard models were used to detect associations between potential risk factors and glaucoma progression. Among 369 eyes from 369 glaucoma patients (average follow-up, 4.4 years), 54 of 178 eyes (30.3%) in the NMG, 49 of 151 eyes (32.5%) in the MMG, and 8 of 40 eyes (20.0%) in the HMG showed progression. When VF was used as a progression criterion, thinner baseline RNFL (hazard ratio [HR]: 0.942, P < 0.001) was predictive of progression. When optic disc/RNFL photographs were used, worse baseline visual field mean deviation (VF MD) and thinner RNFL were associated. The HMG category was a preventive factor for optic disc/RNFL photographic progression (HR: 0.323, P = 0.031). No levels of myopia were associated with glaucoma progression in our study. High myopia was a protective factor for optic disc/RNFL progression. These results may be interpreted as a lower progression detection rate because of the difficulty in detecting changes in the optic disc/RNFL in HMG, or as a consequence of some of highly myopic eyes that may not be true cases of glaucoma.


Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.
Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.


Constitutive overexpression of cyclin D1 does not prevent inhibition of hormone-responsive human breast cancer cell growth by antiestrogens.
Cyclin D1 is a target for positive regulation by estrogens in growth-responsive cells, in which it mediates their mitogenic effects. Amplification and overexpression of the cyclin D1 gene (CCND1) might thus represent a genetic lesion inducing hormone-independent growth of transformed cells. Indeed, cyclin D1 overexpression has been found in up to 50% of primary breast cancers, and in about one-third of these cases, this is linked to amplification of the 11q13 chromosomal region, which also includes the CCND1 gene. These tumors are predominantly estrogen receptor-positive, and for this reason, these patients are often selected for adjuvant antiestrogen therapy. No information is available, however, as to whether cyclin D1 overexpression due to gene amplification might interfere with and reduce antiestrogen efficacy. This was investigated here by taking advantage of an experimental model that reproduces cyclin D1 overexpression resulting from increased CCND1 gene dosage in hormone-responsive human breast cancer cells. For this, MCF-7 cells stably transfected with a tet-inducible cyclin D1 expression vector were tested for their in vitro response to steroidal (ICI 182,780) and nonsteroidal (trans-4-hydroxytamoxifen) antiestrogens under condition of low (endogenous only) or high (exogenous) cyclin D1 levels. Results show that although cyclin D1 overexpression seems to interfere with the early cell cycle effects of antiestrogens, it does not prevent their cytostatic actions, so that growth of cyclin-overexpressing MCF-7 cells is still efficiently inhibited in vitro by these drugs.


Nerve injury and repair in a ketogenic milieu: A systematic review of traumatic injuries to the spinal cord and peripheral nervous tissue.
Dietary interventions such as intermittent fasting and the ketogenic diet have demonstrated neuroprotective effects in various models of neurological insult. However, there has been a lack of evaluation of these interventions from a surgical perspective despite their potential to augment reparative processes that occur following nerve injury. Thus, we sought to analyze the effects of these dietary regimens on nerve regeneration and repair by critical appraisal of the literature. Following PRISMA guidelines, a systematic review was performed to identify studies published between 1950 and 2020 that examined the impact of either the ketogenic diet or intermittent fasting on traumatic injuries to the spinal cord or peripheral nerves. Study characteristics and outcomes were analyzed for each included article. A total of 1,890 articles were reviewed, of which 11 studies met inclusion criteria. Each of these articles was then assessed based on a variety of qualitative parameters, including type of injury, diet composition, timing, duration, and outcome. In total, seven articles examined the ketogenic diet, while four examined intermittent fasting. Only three studies examined peripheral nerves. Neuroprotective effects manifested as either improved histological or functional benefits in most of the included studies. Overall, we conclude that intermittent fasting and the ketogenic diet may promote neuroprotection and facilitate the regeneration and repair of nerve fibers following injury; however, lack of consistency between the studies in terms of animal models, diet compositions, and timing of dietary interventions preclude synthesis of their outcomes as a whole.


Multicenter assessment of venous reflux by duplex ultrasound.
This prospective multicenter investigation was conducted to define the repeatability of duplex-based identification of venous reflux and the relative effect of key parameters on the reproducibility of the test. Repeatability was studied by having the same technologist perform duplicate tests, at the same time of the day, using the same reflux-provoking maneuver and with the patient in the same position. Reproducibility was examined by having two different technologists perform the test at the same time of the day, using the same reflux-provoking maneuver and with the patient in the same position. Facilitated reproducibility was studied by having two different technologists examine the same patients immediately after an educational intervention. Limits of agreement between two duplex scans were studied by changing three elements of the test: time of the day (morning vs afternoon), patient's position (standing vs supine), and reflux initiation (manual vs automatic compression-decompression). The study enrolled 17 healthy volunteers and 57 patients with primary chronic venous disease. Repeatability of reflux time measurements in deep veins did not significantly differ with the time of day, the patient's position, or the reflux-provoking maneuver. Reflux measurements in the superficial veins were more repeatable (P < .05) when performed in the morning with the patient standing. The agreement between the clinical interpretations significantly depended on a selected cut point (Spearman's ρ, -0.4; P < .01). Interpretations agreed in 93.4% of the replicated measurements when a 0.5-second cut point was selected. The training intervention improved the frequency of agreement to 94.4% (κ = 0.9). Alternations of the time of the duplex scan, the patient's position, and the reflux-provoking maneuver significantly decreased reliability. This study provides evidence to develop a new standard for duplex ultrasound detection of venous reflux. Reports should include information on the time of the test, the patient's position, and the provoking maneuver used. Adopting a uniform cut point of 0.5 second for pathologic reflux can significantly improve the reliability of reflux detection. Implementation of a standard protocol should elevate the minimal standard for agreement between repeated tests from the current 70% to at least 80% and with more rigid standardization, to 90%.


Large-area 2D periodic crystalline silicon nanodome arrays on nanoimprinted glass exhibiting photonic band structure effects.
Two-dimensional silicon nanodome arrays are prepared on large areas up to 50 cm² exhibiting photonic band structure effects in the near-infrared and visible wavelength region by downscaling a recently developed fabrication method based on nanoimprint-patterned glass, high-rate electron-beam evaporation of silicon, self-organized solid phase crystallization and wet-chemical etching. The silicon nanodomes, arranged in square lattice geometry with 300 nm lattice constant, are optically characterized by angular resolved reflection measurements, allowing the partial determination of the photonic band structure. This experimentally determined band structure agrees well with the outcome of three-dimensional optical finite-element simulations. A 16% photonic bandgap is predicted for an optimized geometry of the silicon nanodome arrays. By variation of the duration of the selective etching step, the geometry as well as the optical properties of the periodic silicon nanodome arrays can be controlled systematically.


Nutritional intake, body mass index, and activity in postacute traumatic brain injury: a preliminary study.
In the United States, traumatic brain injury (TBI) remains a serious health problem contributing to lifelong disability. Little has been written about nutrition problems experienced postrehabilitation discharge. Our objective was to describe the nutrition and weight management characteristics of TBI survivors after discharge from rehabilitation and to identify characteristics of individuals at risk for weight control issues. Twenty-six TBI survivors admitted to a freestanding rehabilitation hospital were followed for 1 year postdischarge. Data on height, weight, disability rating, diet and activity were collected at admission, 3, 6, 9 and 12 months after discharge. Approximately 30% of the participants showed an increasing body mass index from discharge to 1-year follow up. Two patients had more complete long-term data and are highlighted. The case studies provide insight into the need for rehabilitation nurses to provide nutrition education to TBI survivors that will accommodate changes in lifestyle and activity after discharge.


Natural killer cells and antifungal host response.
As a result of improved experimental methodologies and a better understanding of the immune system, there is increasing insight into the antifungal activity of natural killer (NK) cells. Murine and human NK cells are able to damage fungi of different genera and species in vitro, and they exert both direct and indirect antifungal activity through cytotoxic molecules such as perforin and through cytokines and interferons, respectively. On the other hand, recent data suggest that fungi exhibit immunosuppressive effects on NK cells. Whereas clear in vivo data are lacking in humans, the importance of NK cells in the host response against fungi has been demonstrated in animal models. Further knowledge of the interaction of NK cells with fungi might help to better understand the pathogenesis of invasive fungal infections and to improve treatment strategies.


A descriptive study of self-medication practices among Palestinian medical and nonmedical university students.
The implications of self-medication practices are increasingly recognized around the world; however, little has been reported on the extent of self-medication practiced in Palestine. To determine the reasons, extent, and correlates of self-medication practices among university students in Palestine. A self-administered questionnaire eliciting self-medication practices was distributed to university students in a cross-sectional design. The 4 variables, sex, type of school, self-care orientation, and medication knowledge, were investigated for possible correlation with self-medication practices. Multiple logistic regression and Chi-square statistics were used in data analysis. Self-medication practices were reported by 98% of the surveyed students (n=1581). Approximately two thirds of the respondents reported a high self-care orientation and one third reported "good" medication knowledge. Multiple logistic regressions indicted that self-care orientation, medication knowledge, and sex were insignificant predictors of self-medication practices, whereas the type of school (P=.012) was a significant predictor. A significant relation between the 4 variables and the type of therapeutic class used in self-medication was observed. For example, males were more inclined to use antiallergic medications (OR=1.48) than females. Medical students were more likely to use laxatives/antidiarrheal agents (OR=1.49) than nonmedical students. Respondents with high a self-care orientation were more inclined to use headache relievers (OR=2.22) compared to those with low self-care orientation. The most commonly reported reason for self-medication practices was simplicity of the illness encountered. Self-medication practices were common among the university students studied. Sex, type of school, self-care orientation, and medication knowledge are important personal factors that are associated with the selection of certain types of therapeutic classes used in self-medication.


Postoperative management of lung transplant recipients.
Despite advances in surgical technique, lung transplantation is associated with worse survival when compared with other solid organ transplantations. Graft dysfunction and infection are the leading causes of mortality in the first 30 days following transplantation. Primary graft dysfunction (PGD) is a form of reperfusion injury that occurs early after transplantation. Management of PGD is mainly supportive with use of lung protective ventilation. Inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation may be used in severe cases. Bacterial pneumonias are the most common infectious complication in the immediate post transplant period, but invasive fungal infections may also occur. Other potential complications in the postoperative period include atrial arrhythmias and neurologic complications such as stroke. There is a lack of multicenter, randomized trials to guide ventilation strategies, infection prophylaxis, and treatment of atrial arrhythmias, therefore prevention and management of post-transplant complications vary by transplant center.


Nucleotide sequence analysis of isolates of human T-lymphotropic virus type 1 of diverse geographical origins.
Nucleotide sequences for long terminal repeat (LTR), gag, the protease gene, and pol of a human T-lymphotropic virus type 1 (HTLV-1) isolate of probable Caribbean origin (HTLV-1CH) and a Zairian isolate (HTLV-1EL) were determined providing complete proviral sequences for these isolates. These sequences were compared with those available from previously analyzed isolates. Nucleotide sequence differences of 1.2-3.3% were identified among isolates for which complete genetic information was available. Nucleotide sequence diversity was distributed relatively evenly over the genome with 1.3-5.2% differences in the LTR, 1.1-2.9% differences in gag, 0.7-2.1% differences in the protease gene, 0.9-2.5% differences in pol, 0.9-2.4% differences in env, 0.0-1.4% differences in rex, and 0.1-2.6% differences in tax. There were 1.2-2.3% amino acid differences overall, with 0.8-1.6% nonconservative amino acid alterations. Nucleotide differences were not found in regions of the LTR which are important for transcriptional activity or Tax response. Within the Rex-response element, nucleotide differences were found predominantly in loop rather than stem structures, thus, maintaining the overall secondary structure necessary for Rex activity. Evolutionary tree analysis of the sequence differences suggests a predominant clustering of different HTLV1 strains according to geographical origin. An open reading frame was also identified on the minus DNA strand situated between the env and rex/tax genes which exhibits 0.1-6.9% nucleotide sequence variation among HTLV1 strains. The limited sequence variation among HTLV-1 strains is in striking contrast to the extensive heterogeneity seen among human immunodeficiency virus (HIV) strains.


An intervention for enhancing public health crisis response willingness among local health department workers: a qualitative programmatic analysis.
This study evaluated the impact of a novel multimethod curricular intervention using a train-the-trainer model: the Public Health Infrastructure Training (PHIT). PHIT was designed to 1) modify perceptions of self-efficacy, response efficacy, and threat related to specific hazards and 2) improve the willingness of local health department (LHD) workers to report to duty when called upon. Between June 2009 and October 2010, eight clusters of US LHDs (n = 49) received PHIT. Two rounds of focus groups at each intervention site were used to evaluate PHIT. The first round of focus groups included separate sessions for trainers and trainees, 3 weeks after PHIT. The second round of focus groups combined trainers and trainees in a single group at each site 6 months following PHIT. During the second focus group round, participants were asked to self-assess their preparedness before and after PHIT implementation. Focus groups were conducted at eight geographically representative clusters of LHDs. Focus group participants included PHIT trainers and PHIT trainees within each LHD cluster. Focus groups were used to assess attitudes toward the curricular intervention and modifications of willingness to respond (WTR) to an emergency; self-efficacy; and response efficacy. Participants reported that despite challenges in administering the training, PHIT was well designed and appropriate for multiple management levels and disciplines. Positive mean changes were observed for all nine self-rated preparedness factors (p < 0.001). The findings show PHIT's benefit in improving self-efficacy and WTR among participants. The PHIT has the potential to enhance emergency response willingness and related self-efficacy among LHD workers.


Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy.
The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients. However, despite crizotinib's efficacy, patients almost invariably progress, with the central nervous system being one of the most common sites of relapse. Different mechanisms of acquired resistance have been identified, including secondary ALK mutations, ALK copy number alterations and activation of bypass tracks. Different highly potent and brain-penetrant next-generation ALK inhibitors have been developed and tested in NSCLC patients with ALK rearrangements. Ceritinib, a structurally distinct and selective ALK inhibitor, showed 20 times higher potency than crizotinib in inhibiting ALK and had activity against the most common crizotinib-resistant mutations, including L1196M and G1269A, in preclinical models. In Phase I and II studies, ceritinib demonstrated pronounced activity in both crizotinib-naïve and crizotinib-refractory patients, with responses observed regardless of the presence of ALK resistance mutations. Ceritinib was the first ALK inhibitor to be approved for the treatment of crizotinib-refractory, ALK-rearranged NSCLC, and recent results from a Phase III study have demonstrated superior efficacy compared to standard chemotherapy in the first- and second-line setting. We provide an extensive overview of ceritinib from the design of the compound through preclinical data until efficacy and toxicity results from Phase I-III clinical studies. We review the molecular alterations associated with resistance to ceritinib and highlight the importance of obtaining tumor biopsy at progression to tailor therapy based upon the underlying resistance mechanism. We finally provide an outlook on novel rational therapeutic combinations.


Serum levels of scc, cea, ca-125 and tpa in the management of cervical-carcinoma.
Serum levels of squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), CA 125 and tissue polypeptide antigen (TPA) were serially determined in 116 patients with cervical carcinoma. Serum levels of SCC or TPA levels were elevated in the 12 patients with residual tumour after primary therapy. In patients who were clinically in complete remission, SCC and TPA levels were elevated in 7/69 and 5/70 patients, respectively. Three of the 7 with positive SCC and 4 of the 5 patients with positive TPA levels had a recurrence during follow-up. Elevated levels of SCC or CA 125 or TPA preceded the clinical detection of recurrence in 13 of 18 patients (median time was 7 months for SCC and 6 months for CA 125 and TPA).


Experimental latent and recrudescent bovine herpesvirus-1 infections in calves.
Latent bovine herpesvirus-1 (BHV-1) infection was established in 6 calves and was demonstrated by reinduction of virus shedding after administration of corticosteroids. Latently infected calves failed to transmit BHV-1 during 4 weeks' contact with sentinel calves. Infected calves were killed and necropsied during latency or induced recrudescence. The BHV-1 DNA was demonstrated intranuclearly in trigeminal ganglion neurons by in situ hybridization. The BHV-1 antigen was demonstrated by immunofluorescence in trigeminal ganglion neurons during recrudescence. By electron microscopy, changes in the appearance of the Nissl bodies and a high frequency of nuclear bodies were observed in trigeminal ganglion neurons.


Ultrasound-guided subclavian vein cannulation in infants and children: a novel approach.
Central venous cannulation in infants remains challenging even for experienced paediatric anaesthesiologists. Ultrasound (US)-guidance techniques are proven to be safer for internal jugular vein catheterization. But the subclavian vein (SCV) is often the preferred site for long-term central venous catheterization in children. We describe a novel US-guided approach for SCV cannulation in infants and children. The principle of this technique is to place the US probe at the supraclavicular level to obtain a longitudinal view of the SCV, and to gain access to the vein via the usual infraclavicular route to cannulate it under ultrasonic control. Details and pitfalls of this technique are described. The prospectively collected results of our first 25 punctures are reported. Patients' weight and age range were 2.2-27 kg and 1 day to 9 yr, respectively: 76% of the children weighed less than 10 kg. The success rate at the first attempt was 84% and 100% after two attempts. An asymptomatic thrombus in the SCV could also be detected with this technique. This US-guided approach of the SCV offers a new possibility for central venous catheterization in children. This technique seems promising for children less than 10 kg and probably also for older children. It provides good quality needle guidance and allows to check the vessel patency before puncture.


Practical methods for increasing light interception efficiency and root growth in soybean.
Determining the effect of different sources of nitrogen and weeds on two varieties of soybean, an experiment was conducted out at research station of Tabriz University, Iran. Treatments were two varieties (Williams and Harcor), four nitrogen levels (two levels of symbiotic bacteria and two levels of urea) and weeds (with and without control). Results showed that three various factors can significantly change the Photosynthetically Active Radiation (PAR) amount at different layers of canopy. Solar radiation decreased in a vertical profile of canopy because of increasing Leaf Area Index (LAI). At the bottom level of canopy only 6% of total arrived PAR was recorded. Increasing LAI caused a sharp decrease in Light Interception Efficiency (LIE) in the canopy. Weeds significantly affected root nodules in dry and fresh weights. So, in weedy condition of soybean canopy, accumulation of dry matter decreases due to decline in LIE. On the other hand, weeds can strongly affect on nodules activity and decrease potential of nitrogen fixation by symbiosis bacteria.


Comparative metagenomics of three Dehalococcoides-containing enrichment cultures: the role of the non-dechlorinating community.
The Dehalococcoides are strictly anaerobic bacteria that gain metabolic energy via the oxidation of H2 coupled to the reduction of halogenated organic compounds. Dehalococcoides spp. grow best in mixed microbial consortia, relying on non-dechlorinating members to provide essential nutrients and maintain anaerobic conditions.A metagenome sequence was generated for the dechlorinating mixed microbial consortium KB-1. A comparative metagenomic study utilizing two additional metagenome sequences for Dehalococcoides-containing dechlorinating microbial consortia was undertaken to identify common features that are provided by the non-dechlorinating community and are potentially essential to Dehalococcoides growth. The KB-1 metagenome contained eighteen novel homologs to reductive dehalogenase genes. The metagenomes obtained from the three consortia were automatically annotated using the MG-RAST server, from which statistically significant differences in community composition and metabolic profiles were determined. Examination of specific metabolic pathways, including corrinoid synthesis, methionine synthesis, oxygen scavenging, and electron-donor metabolism identified the Firmicutes, methanogenic Archaea, and the ∂-Proteobacteria as key organisms encoding these pathways, and thus potentially producing metabolites required for Dehalococcoides growth. Comparative metagenomics of the three Dehalococcoides-containing consortia identified that similarities across the three consortia are more apparent at the functional level than at the taxonomic level, indicating the non-dechlorinating organisms' identities can vary provided they fill the same niche within a consortium. Functional redundancy was identified in each metabolic pathway of interest, with key processes encoded by multiple taxonomic groups. This redundancy likely contributes to the robust growth and dechlorination rates in dechlorinating enrichment cultures.


The effect of leukocyte interleukin injection (Multikine) treatment on the peritumoral and intratumoral subpopulation of mononuclear cells and on tumor epithelia: a possible new approach to augmenting sensitivity to radiation therapy and chemotherapy in oral cancer--a multicenter phase I/II clinical Trial.
The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection). Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent). Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker. Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P <.05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P <.05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P <.05) increase in the number of cycling tumor cells, as compared with control values. The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.