Bronchiolitis obliterans organizing pneumonia in cancer: a case series.
Bronchiolitis obliterans with organizing pneumonia (BOOP) is an infrequently encountered clinical condition that can mimic a number of other pathologic lung processes. The presentation of this treatable condition in cancer patients has not been described in any large series. We conducted a retrospective study of patients with BOOP at Memorial Sloan-Kettering Cancer Center, NewYork, NY, U.S.A. from January 1992 to December 1999. The type and treatment of primary cancer, clinical and radiographic features of initial BOOP presentation, and outcome following therapy were recorded. Forty-three patients with an underlying diagnosis of cancer were found on lung biopsy to have BOOP as an isolated entity. BOOP was encountered in patients with a variety of clinical presentations, and many types of malignancies. The symptom patterns were non-specific, as were the physiological abnormalities. The only clear relationship between the underlying malignancyand the diagnosis of BOOP at presentation was in the chest radiographic findings. Patients with solid organ tumors were more likely to have nodular or mass like radiographic abnormalities (81%) than to have diffuse infiltrates (19%). We observed the opposite pattern in patients with hematologic malignancies (22% vs.67%). The vast majority of patients recovered from this condition. In conclusion, For cancer patients, BOOP represents a treatable cause of lung disease with protean manifestations. BOOP can mimic pulmonary malignancy and pulmonary infection. In cancer patients, the evaluation of new pulmonary symptoms accompanied by radiographic changes should include a consideration of this diagnosis.


Phytochemical analysis and broad spectrum antimicrobial activity of ethanolic extract of Jasminum mesnyi Hance leaves and its solventpartitioned fractions.
Jasminum mesnyi Hance (yellow jasmine, Family Oleaceae) belongs to an important subclass of Jasminum family whose biological significance is under explored. The current study pertains to isolation of various solvent extracts fractions and their anti-bacterial effects on the Gram-positive and Gram-negative bacterial pathogens. Ethanolic extract of J. mesnyi Hance leaves was subjected to further partitioning using different solvents with increasing polarity to get different solvent fractions. Different extracts were analysed for their phytochemical constitutents and were evaluated for their antibacterial activity against a number of diseases causing bacteria. Diethylether fraction (DEF) showed remarkable inhibition of growth of Aeromonas hydrophila and Vibrio parahaemolyticus with inhibition zones of 17 and 19mm, respectively at 250 μg. On the other hand, the hexane fraction (HF) was found to be more effective against Gram- positive test bacterial pathogens (Bacillus anthracis and Bacillus subtilis) with inhibition zones of 19.6 mm and 17.5 mm, respectively. The phytochemical screening of different test fractions revealed the predominant presence of cardiac glycosides, sterols and terpenoids in DEF and HF, while Ethylacetate fraction (EAF) and methanol fractions (MF) were found rich in flavonoids and phenols with moderate amount of other reference metabolites.


Assessing Communicative Resilience in Suicide Prevention for LGBTQ+ Communities: A Qualitative Analysis of Community Conversations.
Since LGBTQ + communities experience disproportionate rates of suicidality; it is important to identify strategies for suicide prevention. Research shows that supportive interpersonal communication and identity affirmation helps prevent suicide. The purpose of this analysis is to explore the role of communicative resilience in suicide prevention among LGBTQ + communities. This analysis is part of a community-based participatory research project. In November 2021, a Community-Academic Partnership hosted a virtual town hall, via Zoom, immediately followed by five Community Conversation (CC) groups. Participants were aged 18 years or older and identified as an LGBTQ + community member or active ally. We define active ally as an individual who, through their personal relationships, service to the community, or professional work, actively advocates for and supports members of LGBTQ + communities. CC groups were audio-recorded and transcribed (n= 25 participants). Transcripts were inductively coded for thematic analysis and identified themes were deductively coded using Communication Theory of Resilience (CTR) to identify observations of communicative resilience (MaxQDA2020). Themes aligned with CTR, including importance of peer and professional support, affirming identities, reducing stigma, cultivating hope, and advocating for equitable policies. Findings demonstrate that through communication, members of LGBTQ + communities enact processes of resilience that support and promote suicide prevention. These findings support community mobilization, communicative resilience, and advocacy to help save lives.


hoc: An Arabidopsis mutant overproducing cytokinins and expressing high in vitro organogenic capacity.
A novel Arabidopsis thaliana mutant, named hoc, was found to have an high organogenic capacity for shoot regeneration. The HOC locus may be involved in cytokinin metabolism leading to cytokinin-overproduction. In vitro, hoc root explants develop many shoots in the absence of exogenous growth regulators. The mutant displays a bushy phenotype with supernumerary rosettes and with normal phyllotaxy, resulting from precocious axillary meristem development. Genetic and molecular analyses show that the high shoot regeneration and the bushy phenotype are controlled by a recessive single gene, located on chromosome I, next to the GAPB CAPS marker. The mapping data and allelism tests reveal that the hoc mutant is not allelic to other reported Arabidopsis growth-regulator mutants. In darkness the hoc mutant is de-etiolated, with a short hypocotyl, opened cotyledons and true leaves. Growth regulator assays reveal that the mutant accumulates cytokinins at about two- and sevenfold the cytokinin level of wild-type plants in its aerial parts and roots, respectively. Consequently, the elevated amounts of endogenous cytokinins in hoc plants are associated with high organogenic capacity and hence bushy phenotype. Thus hoc is the first cytokinin-overproducing Arabidopsis mutant capable of auto-regenerating shoots without exogenous growth regulators.


Non-Antidepressant Psychopharmacologic Treatment of Specific Phobias.
Specific phobias are among the most frequently diagnosed disorders in community with a twelve-month prevalence of 8.7% and a lifetime prevalence of 12.5%. Exposure-based therapies constitute the most effective treatment for this type of anxiety disorders. However, pharmacotherapies can still be considered for patients suffering from specific phobias in case they were non-adherent or resistant to exposure-based therapies or in case this kind of therapies was not accessible for them. Few data support the use of antidepressant in the treatment of specific phobias. A literature search via MedLine has been done in order to review all available studies in the domain of nonantidepressant pharmacotherapy of specific phobias. The importance of benzodiazepines such as diazepam, alprazolam and midazolam resides in the short-term reduction of subjective selfreported fear during the exposure to the feared object or situation. General anesthesia for the treatment of dental phobia does not seem to be efficient unless conducted with the inhalation anesthetic nitrous oxide which seems to be efficient on the short and on the long-term. Beta-adrenergic antagonists have been essayed with conflicting results. Cognitive enhancers such as D-cycloserine, glucocorticoids and yohimbine hydrochloride, seem to be more effective than placebo after a short term period of follow-up in treating specific phobia sympotms. In conclusion, promising efficient pharmacotherapies for specific phobias consists of drugs that enhance the efficacy of exposure-based therapies sessions by reducing anticipating phobia-related fear and/or by enhancing cognition during these sessions.


Synthesis and photophysical properties of doubly β-to-β bridged cyclic Zn(II) porphyrin arrays.
A series of doubly β-to-β bridged cyclic Zn(II) porphyrin arrays were prepared by a stepwise Suzuki-Miyaura coupling reaction of borylated Zn(II) porphyrin with different bridge groups. The coupling of the building block of β,β'-diboryl Zn(II) porphyrin 1 with different bridges provided the doubly β-to-β carbazole-bridged Zn(II) porphyrin array 3, the fluorene-bridged Zn(II) porphyrin array 5, the fluorenone-bridged Zn(II) porphyrin array 7, and the three-carbazole-bridged Zn(II) porphyrin ring 8. The structural assignment of 3 was confirmed by the X-ray diffraction analysis, which revealed a highly symmetrical and remarkably bent syn-form structure. The incorporation of bridge units with different electronic effects results in different photophysical properties of the cyclic Zn(II) porphyrin arrays. Comprehensive photophysical studies demonstrate that the electron-withdrawing bridge fluorenone has the largest electronic interaction with the Zn(II) porphyrin unit among the series, thus resulting in the highest two-photon absorption cross-section values (σ((2))) of 6570±60 GM for 7. The present work provides a new strategy for developing porphyrin-based optical materials.


Bladder endocervicosis: Recurrent presentations during pregnancy.
Bladder endocervicosis describes the ectopic presence of endocervical tissue within the bladder. It is a rare condition with an unclear aetiology. We report the case of a 29-year-old woman who presented with bladder endocervicosis during her first pregnancy with recurrence during her second pregnancy. On both occasions, the patient was treated with transurethral resection and the lesion recurred. This is the first case in the literature of bladder endocervicosis presenting during pregnancy and suggests a hormonal stimulus is important in its development.


Unusually large complex odontoma in maxillary sinus associated with unerupted tooth. Report of case and review of literature.
An unusual case of a large complex odontoma with an associated impacted tooth is presented. Odontomas are hamartomatous growths of enamel, dentin, cementum and pulp tissue. Although they are usually tooth-sized or smaller, occasionally, the complex variant can exhibit considerable growth, as was seen in the case presented here. It occupied most of the maxillary sinus and displaced the floor of the orbit and the medial and posterior walls of the left maxillary sinus. Panoramic radiographs, as well as axial and coronal CT studies, showed the extent of the lesion in various dimensions. A differential diagnosis of various calcifying tumors was formulated on the basis of these findings. The lesion was surgically excised, and histologic analysis confirmed the radiographic impression. Although odontomas of this magnitude are rare, this case demonstrates the value of imaging, radiographic histopathologic diagnosis and surgical treatment planning prior to any definitive treatment.


The Assessment of Nursing Staff Knowledge and Barriers Regarding Aseptic Techniques in Khartoum Teaching Hospital, Sudan.
Background Aseptic techniques are crucial in preventing healthcare-associated infections, which are an integral part of standard precautions, and encompass a range of practices designed to safeguard patients from healthcare-associated infections. Objective The objective of this study was to evaluate the level of knowledge and identify the barriers faced by nursing staff in implementing aseptic techniques. Methodology This study employed a stratified random sampling technique to ensure the representation of the research sample. A cross-sectional, descriptive research design was used to assess the knowledge and barriers of nursing staff in maintaining aseptic techniques in their medical practice at Khartoum Teaching Hospital, Sudan. The nursing staff members were divided into different units, and a proportionate number of participants were randomly selected from each stratum. A total of 83 nursing staff members were recruited for this study. Data collection was conducted using a structured questionnaire specifically designed for this study. The questionnaire consisted of items that assessed the nursing staff's knowledge and barriers to aseptic technique implementation. Results The study findings revealed that the mean knowledge score of nursing staff was 14.12, with a median score of 15. The knowledge score had a standard deviation of 3.22. Approximately two-thirds of the nurses (66.3%) had an average level of knowledge, while 33.7% had a below-average level of knowledge. The chi-square analysis indicated a significant association between educational level, years of experience, and knowledge scores (P value=0.010) at a significance level of 0.05. Additionally, 65% of the participants reported facing multiple challenges in maintaining aseptic techniques, including insufficient training, limited resources, and inadequate support. Conclusion In conclusion, the evaluation revealed that a significant proportion of participants felt that their unit lacked adequate training and resources for aseptic techniques. Many had observed colleagues not adhering to aseptic practices, and the participants faced multiple challenges in maintaining aseptic techniques, including insufficient training, limited resources, time constraints, and inadequate support.


Apolipoprotein B and E genetic polymorphisms in the Cayapa Indians of Ecuador.
Three DNA polymorphisms (XbaI, EcoRI, and Ins/Del) of the apolipoprotein B (APOB) gene and the CfoI polymorphism of the APOE gene were investigated in a sample of 96 Cayapa Indians from Ecuador. The frequencies of the X+ (0.182), R+ (1.000), and Del alleles (0.432) at the three APOB sites were found to be higher than and to differ significantly from those reported for East Asians. No comparisons could be made between the Cayapa and other native Americans because of the lack of data on these sites. We observed in our sample that, like native American populations but unlike East Asians, the APOE allele frequencies were characterized by the absence of the APOE*2 allele and by a high frequency of the APOE*4 allele (0.280). Besides a probable drift effect, the high APOE*4 value was tentatively attributed to an effect of selection. Because this allele enhances the absorption of cholesterol by the intestine, it could confer an advantage to carriers in an unfavorable environment (i.e., diet poor in cholesterol).


The control of chondrogenesis.
Chondrogenesis is the earliest phase of skeletal development, involving mesenchymal cell recruitment and migration, condensation of progenitors, and chondrocyte differentiation, and maturation and resulting in the formation of cartilage and bone during endochondral ossification. This process is controlled exquisitely by cellular interactions with the surrounding matrix, growth and differentiation factors, and other environmental factors that initiate or suppress cellular signaling pathways and transcription of specific genes in a temporal-spatial manner. Vertebrate limb development is controlled by interacting patterning systems involving prominently the fibroblast growth factor (FGF), bone morphogenetic protein (BMP), and hedgehog pathways. Both positive and negative signaling kinases and transcription factors, such as Sox9 and Runx2, and interactions among them determine whether the differentiated chondrocytes remain within cartilage elements in articular joints or undergo hypertrophic maturation prior to ossification. The latter process requires extracellular matrix remodeling and vascularization controlled by mechanisms that are not understood completely. Recent work has revealed novel roles for mediators such as GADD45beta, transcription factors of the Dlx, bHLH, leucine zipper, and AP-1 families, and the Wnt/beta-catenin pathway that interact at different stages during chondrogenesis.


Structure of a transmission blocking antibody in complex with Outer surface protein A from the Lyme disease spirochete, Borreliella burgdorferi.
319-44 is a human monoclonal antibody capable of passively protecting mice against tick-mediated infection with Borreliella burgdorferi, the bacterial genospecies responsible for Lyme disease in North America. In vitro, 319-44 has complement-dependent borreliacidal activity and spirochete agglutinating properties. Here, we report the 2.2 Å-resolution crystal structure of 319-44 Fab fragments in complex with Outer surface protein A (OspA), the ~30 kDa lipoprotein that was the basis of the first-generation Lyme disease vaccine approved in the United States. The 319-44 epitope is focused on OspA β-strands 19, 20, and 21, and the loops between β-strands 16-17, 18-19, and 20-21. Contact with loop 20-21 explains competition with LA-2, the murine monoclonal antibody used to estimate serum borreliacidal activities in the first-generation Lyme disease vaccine clinical trials. A high-resolution B-cell epitope map of OspA will accelerate structure-based design of second generation OspA-based vaccines.


Do children with uncomplicated severe acute malnutrition need antibiotics? A systematic review and meta-analysis.
Current (1999) World Health Organization guidelines recommend giving routine antibiotics (AB) for all children with severe acute malnutrition (SAM), even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation. OVID-MEDLINE, EMBASE, COCHRANE, GLOBAL-HEALTH, CINAHL, POPLINE, AFRICA-WIDE-NiPAD, and LILACS were searched for AB efficacy, bacterial resistance, and infection rates in SAM. Following PRISMA guidelines, a systematic review and meta-analysis were performed. Three randomised controlled trials (RCT), five Cochrane reviews, and 37 observational studies were identified. One cohort-study showed no increase in nutritional-cure and mortality in uncomplicated SAM where no AB were used. (p>0.05). However, an unpublished RCT in this setting did show mortality benefits. Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27-55%) vs 22% (IQR 17-23%) and population-weighted-means 52.9% (range 23-57%) vs 35.4% (range 6.7-42%). Susceptibilities to second-line AB were better, above 80%. Prevalence of serious infections in SAM, pooled from 24 studies, ranged from 17% to 35.2%. No study infered any association of infection prevalence with AB regimens in SAM. The evidence underlying current antibiotic recommendations for uncomplicated SAM is weak. Susceptibility-studies favour amoxicillin over cotrimoxazole. However, given that these antibiotics have side-effects, costs, and risks as well as benefits, their routine use needs urgent testing. With reliable monitoring, we believe that there is sufficient equipoise for placebo controlled RCTs, the only robust way to demonstrate true efficacy.


Persistence of vancomycin-resistant Enterococcus faecium gastrointestinal tract colonization in antibiotic-treated mice.
Colonization with vancomycin-resistant Enterococcus faecium (VREF) is strongly associated with previous antimicrobial therapy. The gastrointestinal (GI) tract appears to be the major reservoir for this organism. We used antibiotic-treated Swiss Webster mice to study GI tract colonization with a characterized strain of VREF (E. faecium 228). Mice were pretreated with antibiotics in their daily drinking water and inoculated with 10(9) colony-forming units (CFU) of E. faecium 228 by oral gavage. We were able to establish persistent colonization with high concentrations of E. faecium 228 (> 8.0 log10 CFU/g of feces) in animals treated with 5 mg/ml of streptomycin plus 1 mg/ml of cefotetan. RP 59500, a streptogramin antibiotic with good in vitro activity against VREF, was administered orally in mice (n = 8) colonized with E. faecium 228. After 14 days of treatment VREF was undetectable in feces of all treated mice (< 3.0 CFU/g). Seven days after discontinuation of RP 59500, VREF was present in the feces of all animals. VREF isolates recovered after treatment remained susceptible to RP 59500. Attempts to eradicate E. faecium 228 colonization by oral administration of a vancomycin-sensitive E. faecium strain (SF68) or Lactobacillus spp. were unsuccessful as long as animals continued to receive streptomycin and cefotetan. Recovery of E. faecium 228 from cultures of livers and gallbladders in some animals with persistent GI tract colonization suggests that the organisms may also colonize the hepatobiliary system.


Diseases of the small airways.
The respiratory tree is involved in a wide range of pathological conditions. The consequences of these processes vary from negligible to severe airflow obstruction with resultant hypoxia and respiratory failure. Although almost all of the processes described herein are associated with activation of cytokines, ecosanoids, or peptide hormones, detailed descriptions of these interactions are beyond the scope of this article.


Review of sequencing platforms and their applications in phaeochromocytoma and paragangliomas.
Genetic testing is recommended for patients with phaeochromocytoma (PCC) and paraganglioma (PGL) because of their genetic heterogeneity and heritability. Due to the large number of susceptibility genes associated with PCC/PGL, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. New generations of DNA sequencing technologies facilitate the development of comprehensive genetic testing in PCC/PGL at a lower cost. Whole-exome sequencing and targeted NGS are the preferred methods for screening of PCC/PGL, both having precise mutation detection methods and low costs. RNA sequencing and DNA methylation studies using NGS technology in PCC/PGL can be adopted to act as diagnostic or prognostic biomarkers as well as in planning targeted epigenetic treatment of patients with PCC/PGL. The designs of NGS having a high depth of coverage and robust analytical pipelines can lead to the successful detection of a wide range of genomic defects in PCC/PGL. Nevertheless, the major challenges of this technology must be addressed before it has practical applications in the clinical diagnostics to fulfill the goal of personalized medicine in PCC/PGL. In future, novel approaches of sequencing, such as third and fourth generation sequencing can alter the workflow, cost, analysis, and interpretation of genomics associated with PCC/PGL.


Accounting for neutron exposure in the Japanese atomic bomb survivors.
The Japanese atomic bomb survivors that were directly exposed to both γ rays and neutrons have been followed by the Radiation Effects Research Foundation (RERF). The estimation of the γ-ray risks requires some adjustment for the greater biological effect of the neutrons per unit dose. Because the small neutron doses and the predominant γ-ray doses are highly correlated, the neutron relative biological effectiveness (RBE) cannot be reliably estimated from the survivors' data and information from radiobiology must be invoked. As data became available on neutron doses, RERF has used a constant neutron RBE value of 10, even though radiobiological studies indicate that the RBE values appear to have considerably larger values at low doses. The approximation RBE = 10 assumes that if the RBE is variable it takes roughly this value in the range of total dose most relevant for linear risk estimation, namely about 1 Gy. We consider some possible RBE functions to explain the correct use and the impact of a dose-dependent RBE. However, we do not advocate any particular choice or even that a variable RBE be employed. Rather we show that the assumed neutron RBE, within a wide range of choices, is far less important to the outcome of risk assessment of the RERF data than generally believed. Some of these misperceptions have been related to the consideration of variable RBE functions, and without due attention to the fact that in the case of the A-bomb survivors' data, the mixed field of neutrons and γ rays must be considered. Therefore, the RBE value of neutrons is much lower than the RBE in pure neutron fields that are used in radiobiological experiments. Thus, applying the pure neutron field RBE to the mixed-field A-bomb radiation can lead to an overestimation of the actual neutron RBE for moderate total dose levels of 1 Gy by a factor of more than four. While in a pure neutron exposure the RBE depends on the neutron dose, in the mixed field it depends on both components of exposure, and in particular, we show that in the RERF setting the RBE depends mainly on the accompanying γ-ray dose.


Perioperative interstitial CT-based brachytherapy boost in breast cancer patients with breast conservation after neoadjuvant chemotherapy.
Intraoperative placement of catheters in the tumor bed during breast-conserving surgery (BCS) enables postponed targeted boost irradiation in high risk breast cancer patients. Twenty-three patients with high risk breast cancer underwent neoadjuvant chemotherapy and multifractionated perioperative brachytherapy as a boost to the tumor bed using three-dimensional (3D) CT-based planning. Plastic catheters for brachytherapy were implanted during surgery and targeted irradiation was delivered in the course of 2-3 weeks. Acute and late toxicities were scored according to the RTOG Common Toxicity Criteria. Cosmetic outcomes were assessed using the Harvard criteria. No major perioperative complications were recorded. Circumscribed wound infection occurred in one patient (4.3%). Only 3 patients (13%) experienced acute skin toxicity Grade 1. We observed no teleangiectasias or pigmentations. The cosmetic outcome at last follow-up visit was rated as excellent/good, in 82.6%, fair, in 13% and poor in 4.4% of patients, respectively. There was no evidence of disease recurrence after median follow-up of 43. 4 months. Systematic integration of the perioperative fractionated 3D CT-based HDR brachytherapy as a boost for patients with breast cancer after BCS is feasible and seems safe. It might be beneficial especially for women with high risk of local recurrence.


Feasibility of a Dual Evaluation/Intervention Program for Morbidly Obese Adolescents.
In the absence of evidence-based guidelines for screening adolescent candidates for bariatric surgery, or improving their adherence to preoperative recommendations, we designed a dual-phase multidisciplinary program aiming for observation-based preoperative assessment/ intervention, as well as for post-operative/ conservative follow up. This study focused on the preoperative 3-month phase. Fifteen morbidly obese adolescents attending the eating disorders unit of a pediatric hospital underwent the program protocol consisting of medical examinations/ tests, psychological measures, self-monitoring, tailored diet, physical activity schedule, individual and group cognitive behavior-oriented therapy, and psycho educational parent training. All patients completed the preoperative phase. Most of them (70%) followed the structured diet with a significant reduction in BMI. The patients complied with self-monitoring, and body dissatisfaction score improved. Parental participation in therapy was poor. Four patients with low adherence were found ineligible for surgery. The findings support the feasibility of our dual screening/intervention protocol. Measures to improve parental participation are warranted.


Membrane and cytosolic interleukin-1 alpha and beta in normal human epidermal cells: variability of epitope exposure in immunohistochemistry.
Previous studies have shown that interleukin-1 (IL-1) is present in normal human epidermis. However, with immunohistochemical techniques, epidermal IL-1 immunoreactivity has been found in only a limited number of epidermal cells. In the present study, we show that both IL-1 alpha and beta immunoreactivities can be detected in all epidermal cell layers, provided optimal processing of tissue samples is used. The use of isolated epidermal cells showed that keratinocytes at various stages of maturation display both membrane-associated and cytosolic IL-1 alpha and beta immunoreactivities. After protease treatment of tissue sections, the IL-1 beta immunoreactivity of the granular cell layer was enhanced by some antibodies used, whereas in the other cell layers it was clearly lower. We a) suggest a different cellular localization, processing, and/or binding to subcellular structures of IL-1 during the differentiation process of human keratinocytes and b) outline the technical difficulties in any immunohistologic approach to IL-1 status in diseased skin.


Impact of neurological and medical complications on 3-month outcomes in acute ischaemic stroke.
To evaluate the impact of neurological and medical complications on 3-month outcomes in acute ischaemic stroke patients. We prospectively investigated complications for all the consecutive acute ischaemic stroke patients admitted within 7 days from onset in four university hospitals during a 1-year period. Baseline data and 3-month outcomes were collected. Poor outcome was defined as a modified Rankin Scale score 3-6. A total of 1 254 patients were recruited: 264 (21.1%) and 303 (24.2%) patients experienced one or more neurological and medical complications, respectively. The most common complications were ischaemic stroke progression (17.1%) and pneumonia (12.0%). Of 1 233 patients with available 3-month outcomes, 34.9% had a poor outcome. Multivariate analysis revealed that neurological (odds ratio, 95% confidence interval; 5.47, 3.63-8.24) and medical (3.47, 2.30-5.23) complications were independent predictors of the poor outcome. For the individual complications, ischaemic stroke progression (7.48, 4.73-11.84), symptomatic hemorrhagic transformation (3.57, 1.33-9.54), pneumonia (4.44, 2.20-8.99), extracranial bleeding (4.45, 1.88-10.53), and urinary tract infection (2.72, 1.32-5.60) were independently associated with the poor outcome. Outcome after ischaemic stroke is adversely influenced by complications, especially ischaemic stroke progression, symptomatic hemorrhagic transformation, pneumonia, extracranial bleeding, and urinary tract infection. Interventions to prevent those complications might improve ischaemic stroke outcome.


Prevalence of selected dental anomalies in Saudi children from Gizan region.
The present report gives prevalence values for a selected group of developmental dental anomalies in 2393 Saudi children aged 4-12 yr from Gizan region, Saudi Arabia. The anomalies selected in this study were those involving the number and shape of the dentition. The following anomalies were identified: congenitally missing teeth (2.2%), supernumerary teeth (0.50%), gemination (0.08%), and peg-shaped lateral incisors (0.37%).


Should all elective knee radiographs requested by general practitioners be performed weight-bearing?
The aims of this study were to: [1] Assess the number of patients with suspected knee osteoarthritis that underwent repeat weight-bearing(WB) knee radiographs in the orthopaedic clinic following initial non-WB radiograph requested by their general practitioner (GP). [2] Confirm whether repeating WB knee views changed radiology reports. [3] Determine the number of London trusts with protocols for routinely performing WB views. A Retrospective cohort study of 1968 patients aged >40 years referred to a London teaching hospital for knee radiographs over 12 months. Radiographs were identified as WB/non-WB. Subsequent repeat WB views performed in those that went on to have an orthopaedic consultation were also documented. A consultant musculoskeletal radiologist reported both images. A proforma containing a likert scale of severity for commonly reported abnormalities in knee osteoarthritis and criteria from the Kellgren and Lawrence scale was used for reporting. London NHS Trusts were surveyed to identify if protocols were in place for performing WB views. A total of 1,968 patients underwent knee radiographs, of which 1922 (97.7%) had initial non-WB radiographs. Of the 56 patients in this group that underwent required repeat WB radiographs, joint space narrowing was reported as more severe on WB versus non-WB radiographs (p = 0.035). Only 54% of departments routinely performed WB radiographs. Few patients (2.3%) referred by GPs have WB radiographs requested. Some of those referred for a specialist opinion required repeat WB views. Nearly half of London hospitals do not routinely perform WB radiographs. This represents a significant financial burden to the NHS, increased radiation exposure and wasted patient/clinician time. We propose that all GP requested knee radiographs be performed as WB unless otherwise stated.


Reliability of three versus five saliva sampling times for assessing the cortisol awakening response.
The cortisol awakening response (CAR) describes the sharp increase in cortisol secretion within 60 min after awakening. A summary of the CAR, the area under the cortisol curve above the awakening cortisol value (AUCi) is a widely used biomarker in health research. Estimation of the AUCi rely on a number of collected salivary samples at fixed time intervals (i.e., 5 samples in 15 min intervals) starting from awakening. Little empirical work has been executed to investigate the impact of reducing sampling times on AUCi estimation, which could potentially improve participant compliance and reduce operational costs. This study aimed to assess the reliability and validity of using 3-sample AUCi versus 5-sample AUCi, i.e., systematic and random fluctuations based on a large dataset from healthy and case individuals (total n = 537). We showed that the ideal timing of 3-sampling times was 0-30-60 min with a median difference in AUCi of - 8 nmol*h/L and interquartile range of 65 nmol*h/L among healthy individuals, and - 12 nmol*h/L and 78 nmol*h/L among case individuals. We subsequently validated the 3-sample AUCi by re-analyzing three published association studies. Overall, we obtained similar p-values with 3-sample AUCi when compared to 5-sample AUCi, while smaller effect sizes and standard errors were observed. In conclusion, despite a less precise estimation of the AUCi itself, our data support that the AUC measure of the CAR, based on three samples collected at 0-30-60 min from awakening, provides reliable results in association studies.


Comparison of four microwave ablation devices: an experimental study in ex vivo bovine liver.
To compare volume, sphericity, and short-axis diameter of the coagulation zone of four commercially available microwave ablation systems with three technical concepts in an ex vivo setting and to formulate mathematical models to predict these quantities. Two high-power systems (systems A and B), a system that enables simultaneous use of three antennas (system C), and a non-perfusion-cooled system that automatically adapts power and frequency (system D) were tested in ex vivo bovine livers (108 ablations). Coagulation volume, sphericity, and mean short-axis diameter were assessed, and mathematical functions were fitted for each system and assessed with the coefficient of determination (R(2)). Analysis of variance and Tukey post hoc tests were used for interdevice comparison after 5 and 10 minutes and after maximum recommended ablation time. Volume and short-axis diameter were determined by using a mathematical model for every system, with coefficients of determination of 0.75-0.98 and 0.70-0.97, respectively. Correlation for determination of sphericity was lower (R(2) = 0.01-0.68). Mean results with ablation performed according to manufacturer recommendations were as follows: Volume, sphericity, and short-axis diameter were 57.5 cm(3), 0.75, and 43.4 mm, respectively, for system A; 72.3 cm(3), 0.68, and 45.5 mm, respectively, for system B; 17.1 cm(3), 0.58, and 26.8 mm, respectively, for system C (one antenna); 76.5 cm(3), 0.89, and 50.6 mm, respectively, for system C (three antennas); and 56.0 cm(3), 0.64, and 40.9 mm, respectively, for system D. Systems A (mean volume, 52.4 cm(3) ± 4.5 [standard deviation]) and B (39.4 cm(3) ± 1.7) reach large ablation zones with 5-minute ablation. The largest ablation zone is obtained with systems B and C (three antennas) under maximum recommended ablation duration and with system A under short ablation time. The most spherical zone is obtained with system C (three antennas).


Expression and localization of gonadotropin-releasing hormone receptor in the rat oviduct during pregnancy.
A recent study from our laboratory has shown cellular and ultrastructural distribution of the gonadotropin-releasing hormone (GnRH) and the relative expression of its mRNA in the rat oviduct during the postimplantation period of pregnancy (days 7, 9, 16, and 20). To determine the possible autocrine/paracrine involvement of the oviductal GnRH during pregnancy in rats, the present investigation aims at the study of the relative expression of GnRH receptor (GnRHR) mRNA by real-time PCR followed by immunolocalization of the peptide in the oviduct during pregnancy. Semiquantitative analysis of the oviductal GnRHR expression by Western blot was done by densitometry of the signal intensity. Our results indicate the expression of GnRHR mRNA in the rat oviduct throughout the postimplantation period of pregnancy with no significant difference in expression between the selected time points. Immunoreactive GnRHR peptide was localized predominantly in the cytoplasm of the luminal epithelial cells, with less expression in the cytoplasm of the stromal cells and the smooth muscles throughout the oviduct. Signal intensity of GnRHR was significantly lower during day 16 when compared to days 7 and 20. These results, for the first time, support the transcription of GnRHR mRNA and its translation to protein in the rat oviduct throughout the postimplantation period of pregnancy. The lower protein content of GnRHR by day 16 may be indicative of ligand-induced downregulation of the receptor expression. The present investigation thus strengthens our previously postulated hypothesis regarding the receptor-mediated autocrine/paracrine role of oviductal GnRH during pregnancy in rats.


UNC-18 promotes both the anterograde trafficking and synaptic function of syntaxin.
The SM protein UNC-18 has been proposed to regulate several aspects of secretion, including synaptic vesicle docking, priming, and fusion. Here, we show that UNC-18 has a chaperone function in neurons, promoting anterograde transport of the plasma membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein Syntaxin-1. In unc-18 mutants, UNC-64 (Caenorhabditis elegans Syntaxin-1) accumulates in neuronal cell bodies. Colocalization studies and analysis of carbohydrate modifications both suggest that this accumulation occurs in the endoplasmic reticulum. This trafficking defect is specific for UNC-64 Syntaxin-1, because 14 other SNARE proteins and two active zone markers were unaffected. UNC-18 binds to Syntaxin through at least two mechanisms: binding to closed Syntaxin, or to the N terminus of Syntaxin. It is unclear which of these binding modes mediates UNC-18 function in neurons. The chaperone function of UNC-18 was eliminated in double mutants predicted to disrupt both modes of Syntaxin binding, but it was unaffected in single mutants. By contrast, mutations predicted to disrupt UNC-18 binding to the N terminus of Syntaxin caused significant defects in locomotion behavior and responsiveness to cholinesterase inhibitors. Collectively, these results demonstrate the UNC-18 acts as a molecular chaperone for Syntaxin transport in neurons and that the two modes of UNC-18 binding to Syntaxin are involved in different aspects of UNC-18 function.


WTAP mediates the anti-inflammatory effect of Astragalus mongholicus polysaccharide on THP-1 macrophages.
Background: Astragalus mongholicus polysaccharides (APS) have anti-inflammatory, antioxidant and immunomodulatory effects. Recent studies have demonstrated the epigenetic regulation of N6-methyladenosine (m6A) in the development of inflammation. However, the effect of APS on m6A modification is unclear. Here, for the first time, we investigate the mechanism of m6A modification in APS regulation of THP-1 macrophage inflammation. Methods: We treated LPS-induced THP-1 macrophages with APS at different concentrations and times, and detected IL-6 mRNA and protein levels by quantitative real-time PCR (qRT-PCR) and western blot, respectively. The m6A modification level was detected by m6A quantification kit. The proteins that regulate m6A modification were screened by western blot. Wilms' tumor 1-associating protein (WTAP) was overexpressed in APS-treated THP-1 macrophages and the m6A modification level and IL-6 expressions were detected. Results: These findings confirmed that APS significantly abolished LPS-induced IL-6 levels in THP-1 macrophages. Meanwhile, APS reduced m6A modification levels and WTAP gene expression in THP-1 macrophages. Further overexpression of WTAP can significantly reverse APS-induced m6A modification level and IL-6 expression. Mechanistically, APS regulates IL-6 expression through WTAP-mediated p65 nuclear translocation. Conclusion: Overall, our study suggested that WTAP mediates the anti-inflammatory effect of APS by regulating m6A modification levels in THP-1 macrophages. This study reveals a new dimension of APS regulation of inflammation at the epigenetic level.


Deep Brain Stimulation in a Patient with Parkinson's Disease and Cortical Superficial Siderosis.
Cortical superficial siderosis (cSS) is a rare condition that is regarded as a potential magnetic resonance marker of cerebral amyloid angiopathy (CAA). We describe the case of a 68-year-old man with cSS and Parkinson's disease (PD) who subsequently exhibited incidental microhemorrhages, which were only detected on magnetic resonance imaging (MRI), at one week after deep brain stimulation (DBS) surgery. cSS is now considered to be a significant risk factor for CAA and future bleeding. Therefore, because DBS surgery is invasive and may increase the risk of intracerebral hemorrhage, the procedure should be performed carefully when managing patients with PD and CAA.


Early endosomes, late endosomes, and lysosomes display distinct partitioning strategies of inheritance with similarities to Golgi-derived membranes.
The pattern of inheritance of compartments of the endocytic pathway has been rarely reported, and the precise mechanism(s) are yet to be elucidated. We used antibodies reactive to early endosomes (anti-EEA1), late endosomes (anti-LBPA and anti-LAMP-1), lysosomes (anti-LAMP-1) and trans-Golgi network (TGN) (anti-GOLGA4) to examine the inheritance of these compartments in fixed human HEp-2 cells. Prior to entering M phase, these compartments display a perinuclear bias in their cytoplasmic distribution with areas of local accumulation juxtaposed to the centrosome. The location of these compartments during mitosis was examined relative to each other, the chromosomes, centrosomes and the microtubule network. During M phase early endosomes and TGN-derived compartments share overlapping subcellular distributions. A portion of these compartments display discernible clustering around the separated and migrating centrosomes in prophase. At metaphase these compartments co-localise with the mitotic spindle, are absent at the metaphase plate and do not overlay the astral microtubules. At anaphase these compartments are concentrated between shortening kinetochore microtubules and centrosomes. In addition, they appear distributed over the elongating polar microtubules in the body of the cell. From telophase and into cytokinesis these compartments concentrate around the minus ends of the constricted remnants of polar spindle microtubules and re-establish a prominent presence juxtaposed to the centrosome. In contrast, there is little evidence of movement of late endosomes and lysosomes with migrating centrosomes in prophase, and these compartments are excluded from the mitotic spindle at metaphase. However, by the end of telophase, the subcellular distribution of a portion of late endosomes and lysosomes share overlapping distributions with that of early endosomes. We conclude a portion of endosomal compartments and Golgi-derived membranes undergo ordered partitioning based on the centrosome and mitotic spindle.


PM2.5 exposure in highly polluted cities: A case study from New Delhi, India.
Personal exposure (PE) to air pollutants is driven by a combination of pollutant concentrations in indoor and outdoor environments, and time-activity pattern of individuals. The objectives of this study were to estimate personal exposure to PM2.5 and black carbon (BC), and assess the representability of ambient air quality monitoring stations to serve as surrogates for PE in New Delhi. Personal exposure to air pollutants (PM2.5-PE and BCPE) was measured using portable, battery-operated instruments (PM2.5- pDR1500 and BC- microAethalometer AE51) in a small cohort of healthy adults (n=12 in summer, n=6 in winter) with no occupational exposure. Average PM2.5-PE and BCPE (µg/m3) were 53.9±136 and 3.71±4.29 respectively, in summer and 489.2±209.2 and 23.3±14.9 respectively, in winter. Activities associated with highest exposure levels were cooking and indoor cleaning for PM2.5, and commuting for BC. Within transport microenvironments, autorickshaws were found to be the most polluted, and lowest BC exposure was registered in public buses. Comparison of fixed-site ambient monitoring data showed a higher correlation with personal exposure dataset in winter compared to summer (r2 of 0.51 (winter) and 0.21 (summer); 51% (winter) and 20% (summer)). This study highlights the need for detailed assessment of PE to air pollutants in Indian cities, and calls for a denser network of monitoring stations for better exposure assessment.


Geographical distribution of lung cancer in the USSR.
During recent years medico-geographical studies on lung cancer in the USSR have been intensified. The results of these studies are reflected in works on the geographical distribution of lung cancer and on the influence of unfavourable natural-economic factors upon lung cancer incidence. The steady increase in lung cancer morbidity and mortality throughout the world is one of the urgent problems of today. Numerous studies have been carried out, and these have identified several aetiological factors which play a certain role in lung cancer development (smoking, occupational hazards, air pollution by industry and traffic). These studies have shown lung cancer to be one of the cancers most closely associated with environmental conditions. Lung cancer is considered to be a disease of the male population inhabiting highly industrialized cities and countries. However, lung cancer incidence has also been increasing recently in the female population of different countries. (V. Merabishvili, G. Tserkovny, 1981) Different levels of morbidity and mortality from lung cancer throughout the world make it necessary to undertake comprehensive studies on the complicated and ever-changing relations between the health status of the population and the effect of natural and economic factors.


Stent sizing strategies in renal artery stenting: the comparison of conventional invasive renal angiography with renal computed tomographic angiography.
Randomized trials comparing invasive treatment of renal artery stenosis with standard pharmacotherapy did not show substantial benefit from revascularization. One of the potential reasons for that may be suboptimal procedure technique. To compare renal stent sizing using two modalities: three-dimensional renal computed tomography angiography (CTA) versus conventional angiography. Forty patients (41 renal arteries), aged 65.1 ±8.5 years, who underwent renal artery stenting with preprocedural CTA performed within 6 months, were retrospectively analyzed. In CTA analysis, reference diameter (CTA-D) and lesion length (CTA_LL) were measured and proposed stent diameter and length were recorded. Similarly, angiographic reference diameter (ANGIO_D) and lesion length (ANGIO_LL) as well as proposed stent dimensions were obtained by visual estimation. The median CTA_D was 0.5 mm larger than the median ANGIO_D (p < 0.001). Also, the proposed stent diameter in CTA evaluation was 0.5 mm larger than that in angiography (p < 0.0001). The median CTA_LL was 1 mm longer than the ANGIO_LL (p = NS), with significant correlation of these variables (r = 0.66, p < 0.0001). The median proposed stent length with CTA was equal to that proposed with angiography. The median diameter of the implanted stent was 0.5 mm smaller than that proposed in CTA (p < 0.0005) and identical to that proposed in angiography. The median length of the actual stent was longer than that proposed in angiography (p = 0.0001). Renal CTA has potential advantages as a tool adjunctive to angiography in appropriate stent sizing. Careful evaluation of the available CTA scans may be beneficial and should be considered prior to the planned procedure.


3-Month Results from Denmark within the Globally Prospective and Observational Study to Evaluate Insulin Detemir Treatment in Type 1 and Type 2 Diabetes: The PREDICTIVE Study.
PREDICTIVEtrade mark is a large, multi-national, open-label, prospective, observational study to assess the efficacy and safety of insulin detemir in clinical practice. We report 3-month follow-up data from 389 patients with type 1 (n = 312) and type 2 (n = 77) diabetes from Denmark. Insulin detemir improved glycemic control in type 1 patients, with decreases in mean HbA1c (-0.2%, p = 0.0026), fasting glucose (-1.7 mmol/l, p = 0.0033) and within-patient fasting glucose variability (-0.6 mmol/l, p = 0.0472). Non-significant reductions in glycemic parameters were observed in type 2 patients (-0.3% for HbA1c and -2.7 mmol/l for fasting glucose). There was a decrease in mean body weight in both type 1 and type 2 patients (-0.6 kg, p = 0.025 and -1.0 kg, p = 0.0361, respectively). Three patients (0.8%) reported 4 serious adverse drug reactions, including major hypoglycemia. The incidence of major hypoglycemic episodes was reduced from 3.9/patient-years at baseline to 0.4/patient-years at follow-up in type 1 patients (p < 0.0001), and from 1.0 to 0.0/patient-years in type 2 patients (p = 0.1250). In addition, the mean incidence of total and nocturnal hypoglycemic episodes was reduced in both type 1 (-37.4 and -17.7/patient-years, p < 0.0001 for both) and type 2 patients (-17.7 and -7.8/patient-years, p = 0.0012 and p = 0.0020, respectively). The observations from the Danish cohort of the PREDICTIVE study support the overall findings of PREDICTIVE, i.e. insulin detemir improves glycemic control, with a reduced risk of hypoglycemia and no weight gain.


"Introduction to the special issue on neuroethology": Correction to Simmons and Moss (2019).
Reports an error in "Introduction to the special issue on neuroethology" by Cynthia F. Moss and Andrea M. Simmons (Behavioral Neuroscience, 2019[Jun], Vol 133[3], 265-266). In the original article, the order of authors was reversed. The correct order of authors is Andrea M. Simmons and Cynthia F. Moss. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2019-29253-001.) This special issue highlights some recent advances in neuroethology based on research presented at the 13th International Congress of Neuroethology and associated satellite symposia in Brisbane, Australia, on July 15-20, 2018. The discipline of neuroethology combines methods and concepts from ethology with those from neurobiology to develop a comparative analysis of the mechanisms of behavior that takes into account a species' ecology and evolutionary history. In his 1951 book The Study of Instinct, Nobel Prize winner Niko Tinbergen called on ethologists and neurophysiologists to join forces to search for mechanisms of motivated behaviors. He used the term "ethophysiology" to describe this integrative research approach, which he felt was crucial for developing a full understanding of behavior in all its complexities. At that time, "the ethologists were as naive about the neurophysiological significance of their findings as the neurophysiologists were about the behavioral implications of theirs" (Hoyle, 1984, p. 371). To rectify these limitations and to move forward, some of the earliest neuroethological research focused on understanding cellular mechanisms underlying the ethological concepts of releasers (sign stimuli) and fixed action patterns in species such as locusts and toads (Ewert, 1980; Hoyle, 1984). The breadth of neuroethological research soon expanded to include many other species, particularly those with distinct sensory or motor specializations (echolocating bats, electric fish, barn owls; Ewert, Capranica, & Ingle, 1983), as well as to understand neural mechanisms of more "general" behaviors, such as learning, memory, navigation, and communication. Molecular genetic, anatomical, and computational approaches are also part of the neuroethologist's toolbox. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Vascular anatomy of normal and undescended testes: surgical assessment of anastomotic channels between testicular and deferential arteries.
To demonstrate the vascular anatomy of the normal and undescended testes, emphasizing the surgical importance of the anastomotic channels between the testicular and deferential arteries in the undescended testis. This study was performed on four normal testes obtained from adult cadavers and the undescended testes taken from men undergoing unilateral orchiectomy. To show the arteries and their connections, we used the injection-corrosion casting technique. The normal and undescended testes measured 36.3 +/- 9.2 mm x 21.2 +/- 4.3 mm x 14.3 +/- 5.4 mm and 19 x 16 x 9 mm, respectively. The testis and epididymis had an unusual shape in the undescended testes. The undescended testes were round, with a semilunar epididymis that was over the testis. All the testes, including the undescended testes, had testicular, deferential, and cremasteric arteries. The testicular, deferential, and cremasteric arterial diameter was 1.7 +/- 0.4, 1.1 +/- 0.3, and 0.5 +/- 0.3 mm in the normal testes and 1.5, 0.7, and 0.6 mm in the undescended testes, respectively. Communication among the three arteries was illustrated consistently by retrograde filling of the two noninjected arteries. Clearly visible anastomotic channels were present between the testicular and deferential arteries in the normal and undescended testes. We suggest that the original Fowler and Stephans concept (high ligation of the testicular artery) is valid to preserve vascularity to the testis when vascular transection orchiopexy is performed, although the number of our specimens was not enough to prove this definitively.


Calcium based non-viral gene delivery: an overview of methodology and applications.
Application of therapeutic gene transfer in the treatment of genetic diseases is a notable progress but there are some disadvantages and limitations in it. The process of overcoming these barriers is a drastic change in gene delivery. Recently, calcium phosphate nanoparticles alone, or in combination with viral and nonviral vectors, were found to have a positive effect on gene transfer especially when incorporated in the colloidal particulate systems. This review elaborates on various successful methods of using calcium phosphate nanoparticles in gene delivery, which are considered an advancing approach to gene delivery.


Leptospirosis as a cause of fever associated with jaundice in the Democratic Republic of the Congo.
Fever with jaundice is a common symptom of some infectious diseases. In public health surveillance within the Democratic Republic of the Congo (DRC), yellow fever is the only recognized cause of fever with jaundice. However, only 5% of the surveillance cases are positive for yellow fever and thus indicate the involvement of other pathogens. Leptospira spp. are the causative agents of leptospirosis, a widespread bacterial zoonosis, a known cause of fever with jaundice. This study aimed to determine the seropositivity of anti-Leptospira antibodies among suspected yellow fever cases and map the geographical distribution of possible leptospirosis in the DRC. We conducted a retrospective study using 1,300 samples from yellow fever surveillance in the DRC from January 2017 to December 2018. Serum samples were screened for the presence of IgM against Leptospira spp. by a whole cell-based IgM ELISA (Patoc-IgM ELISA) at the Institut National de Recherche Biomedicale in Kinshasa (INRB) according to World Health Organization (WHO) guidance. Exploratory univariable and multivariable logistic regression analyses were undertaken to assess associations between socio-demographic factors and the presence of Leptospira IgM. Of the 1,300 serum samples screened, 88 (7%) showed evidence of IgM against Leptospira spp. Most positive cases (34%) were young adult males in the 20-29-year group. There were statistically significant associations between having Leptospira IgM antibodies, age, sex, and living area. Observed positive cases were mostly located in urban settings, and the majority lived in the province of Kinshasa. There was a statistically significant association between seasonality and IgM Leptospira spp. positivity amongst those living in Kinshasa, where most of the positive cases occurred during the rainy season. This study showed that leptospirosis is likely an overlooked cause of unexplained cases of fever with jaundice in the DRC and highlights the need to consider leptospirosis in the differential diagnosis of fever with jaundice, particularly in young adult males. Further studies are needed to identify animal reservoirs, associated risk factors, and the burden of human leptospirosis in the DRC.


Manufacture of Highly Transparent and Hazy Cellulose Nanofibril Films via Coating TEMPO-Oxidized Wood Fibers.
Traditionally, inorganic nanoparticles (SiO₂, TiO₂) have been utilized to tune the optical haze of optoelectronic devices. However, restricted to complex and costly processes for incorporating these nanoparticles, a simple and low-cost approach becomes particularly important. In this work, a simple, effective, and low-cost method was proposed to improve optical haze of transparent cellulose nanofibril films by directly depositing micro-sized 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized wood fibers ("coating" method). The obtained films had a high total transmittance of 85% and a high haze of 62%. The film samples also showed a high tensile strength of 80 MPa and excellent thermal stability. Dual sides of the obtained films had different microstructures: one side was extremely smooth (root-mean-square roughness of 6.25 nm), and the other was extremely rough (root-mean-square roughness of 918 nm). As a reference, micro-sized TEMPO-oxidized wood fibers and cellulose nanofibrils were mixed to form a transparent and hazy film ("blending" method). These results show that hazy transparent films prepared using the "coating" method exhibit superior application performances than films prepared using the "blending" method.


Deoxyribonucleotide metabolism and cyclic AMP resistance in hydroxyurea-resistant S49 T-lymphoma cells.
We investigated the cell cycle regulation of deoxyribonucleoside triphosphate (dNTP) metabolism in hydroxyurea-resistant (HYUR) murine S49 T-lymphoma cell lines. Cell lines 10- to 40-fold more hydroxyurea-resistant were selected in a stepwise manner. These HYUR cells exhibited increased CDP reductase activity (5- to 8-fold) and increased dNTP pools (up to 5-fold) that appeared to result from increased activity of the M2 subunit (binding site of hydroxyurea) of ribonucleotide reductase. These characteristics remained stable when the cells were grown in the absence of hydroxyurea for up to 2 years. In both wild type and hydroxyurea-resistant cell populations synchronized by elutriation, dCTP and dTTP pools increased in S phase, whereas dATP and dGTP pools generally remained the same or decreased, suggesting that allosteric effector mechanisms were operating to regulate pool sizes. Additionally, CDP reductase activity measured in permeabilized cells increased in S phase in both wild type and hydroxyurea-resistant cells, suggesting a nonallosteric mechanism of increased ribonucleotide reductase activity during periods of active DNA synthesis. While wild type S49 cells could be arrested in the G1 phase of the cell cycle by dibutyryl cyclic AMP, hydroxyurea-resistant cell lines could not be arrested in the G1 phase by exogenous cyclic AMP or agents that elevate the concentration of endogenous cyclic AMP. These data suggest that cyclic AMP-generated G1 arrest in S49 cells might be mediated by the M2 subunit of ribonucleotide reductase.


Lymphomatoid papulosis: a cutaneous T-cell pseudolymphoma.
It was the purpose of this study to further define the nature of the dermal infiltrates in lymphomatoid papulosis (LP) means of enzyme cytochemistry (acid phosphatase and esterase), immunology (rosetting techniques, immunoperoxidase technique on cryostat sections), and by semithin and ultrathin sections. The studies performed on biopsy samples with clinically and histologically typical LP indicated that most lymphoid cells display markers for T-lymphocytes, which were helper T-cells in the one case studied with monoclonal antibodies. Regarding the typical benign self-involutive clinical course, LP is considered to be a cutaneous pseudolymphoma of T-cell type.


Characterization of immunological depression in mice exposed to normobaric oxygen.
Immunological cell functions were evaluated during 24, 48 and 96 h O2 exposure in C57Bl/6 mice. A normobaric O2 exposure resulted in depression of delayed type hypersensitivity (DTH) to oxazolone and Staphylococcus aureus antigens. This effect was proportional to the duration of O2 exposure. The antibody response of splenic cells was more rapidly (24 h O2 exposure) and markedly depressed using a T-dependent antigen (sheep red blood cell, SRBC) than with a T-independent antigen (trinitrophenylated lipopolysaccharide, TNP-LPS). While mitogen-induced proliferative responses of spleen cells to Con A and PHA were inhibited after 72 h of O2 exposure, proliferative responses to LPS were inhibited after 96 h. A dissociated antigen and mitogen responses was observed after a short time of O2 exposure (48 h): the antigen specific responses were impaired with a more pronounced effect on T lymphocytes, whereas the DNA synthesis in response to mitogen remained normal.


Peritoneal carcinomatosis of colorectal origin.
Peritoneal carcinomatosis is, after liver metastases, the second most frequent cause of death in colorectal cancer patients and at the present time, is commonly inserted and treated as a stage IV tumour. Because there is no published data that outlines the impact of new therapeutic regimens on survival of patients with peritoneal surface diffusion, the story of carcinomatosis can be rewritten in light of a new aggressive approach based on the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Also if these treatment perhaps allow to obtain better results than standard therapies, we suggest, that a large prospective randomised control trial is needed to compare long-term and progression-free survival under the best available systemic therapy with or without cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.


Methamphetamine use in Central Germany: protocol for a qualitative study exploring requirements and challenges in healthcare from the professionals' perspective.
The synthetic drug methamphetamine with its high addiction potential is associated with substantial adverse health effects. In Germany, especially Central Germany, the increase in the consumption of methamphetamine has exceeded that of other illegal drugs. The treatment system and service providers are facing new challenges due to this rise in consumption. This qualitative study will explore the demand created by the increasing healthcare needs of methamphetamine-addicted persons in Central Germany, and the difficulty of rehabilitating addicted people. The collection of empirical data will take place in a consecutive, two-stage process. In the first part of data collection, the experiences and perspectives of 40 professionals from numerous healthcare sectors for methamphetamine-addicted persons will be explored with the help of semistructured face-to-face interviews and probed by the research team. These findings will be discussed in 2 focus groups consisting of the participants of the face-to-face interviews; these group discussions comprise the second part of the data collection process. The interviews will be audio recorded, transcribed, and then subjected to qualitative content analysis. All interviewees will receive comprehensive written information about the study, and sign a declaration of consent prior to the interview. The study will comply rigorously with data protection legislation. The research team has obtained the approval of the Ethical Review Committee at the Martin Luther University Halle-Wittenberg, Germany. The results of the study will be published in high-quality, peer-reviewed international journals, presented at several congresses and used to design follow-up research projects. VfD_METH_MD_15_003600.


Comparison of Minnesota antilymphoblast globulin and Upjohn antithymocyte globulin for induction immunosuppression of human renal allografts.
An analysis of heterologous polyclonal antisera in first renal transplants was continued after replacement of Minnesota antilymphoblast globulin (MALG) with antithymocyte globulin (ATGAM), testing the hypothesis that these are functionally equivalent drugs. Sequential induction immunosuppression used MALG (20 mg/kg/day, n = 33) or ATGAM (15 mg/kg/day, n = 14), corticosteroids, azathioprine and cyclosporine. White blood cell, platelet, and T-cell subsets were measured. Percent of patients with and time to first rejection were determined. Anti-horse antibody was measured by enzyme-linked immunosorbent assay. Minimum follow-up after transplantation was 1 year. Human leukocyte antigen mismatch, peak and current panel reactive antibodies, age, gender, percent cadaver donors and diabetic recipients were similar. Depletion of CD2, CD3, CD4, and CD8 T-cell subsets and platelet and white blood cells was similar. Early renal function was better with MALG than with ATGAM (p = 0.005, ANOVA), but by 2 weeks the groups were similar. The percent of patients receiving MALG versus patients receiving ATGAM with cytomegalovirus (28 versus 50), anti-horse antibodies (50 versus 62), and rejection (58 versus 50) and the median day of first rejection (48 versus 47) were similar. Three grafts were lost. MALG and ATGAM are equally effective in eliminating T cells and preventing and delaying the onset of renal allograft rejection.


Renal cortical pyruvate depletion during AKI.
Pyruvate is a key intermediary in energy metabolism and can exert antioxidant and anti-inflammatory effects. However, the fate of pyruvate during AKI remains unknown. Here, we assessed renal cortical pyruvate and its major determinants (glycolysis, gluconeogenesis, pyruvate dehydrogenase [PDH], and H2O2 levels) in mice subjected to unilateral ischemia (15-60 minutes; 0-18 hours of vascular reflow) or glycerol-induced ARF. The fate of postischemic lactate, which can be converted back to pyruvate by lactate dehydrogenase, was also addressed. Ischemia and glycerol each induced persistent pyruvate depletion. During ischemia, decreasing pyruvate levels correlated with increasing lactate levels. During early reperfusion, pyruvate levels remained depressed, but lactate levels fell below control levels, likely as a result of rapid renal lactate efflux. During late reperfusion and glycerol-induced AKI, pyruvate depletion corresponded with increased gluconeogenesis (pyruvate consumption). This finding was underscored by observations that pyruvate injection increased renal cortical glucose content in AKI but not normal kidneys. AKI decreased PDH levels, potentially limiting pyruvate to acetyl CoA conversion. Notably, pyruvate therapy mitigated the severity of AKI. This renoprotection corresponded with increases in cytoprotective heme oxygenase 1 and IL-10 mRNAs, selective reductions in proinflammatory mRNAs (e.g., MCP-1 and TNF-α), and improved tissue ATP levels. Paradoxically, pyruvate increased cortical H2O2 levels. We conclude that AKI induces a profound and persistent depletion of renal cortical pyruvate, which may induce additional injury.


[Issues on package inserts of percutaneous tracheostomy kits].
Percutaneous tracheostomy using a dedicated kit, which has been a common surgical procedure in intensive care settings, must be carefully performed with sufficient knowledge regarding both the technique and the kit. The aim of this study was to investigate the accuracy and adequacy of information contained in package inserts of kits, as the primary official documents for providing information on safe and sure performance of the procedure. We investigated the contents of package inserts for three percutaneous tracheostomy kits available in Japan, and ascertained whether the distributors of the kits showed the contents on the Internet. Package inserts did not necessarily provide accurate and sufficient information in terms of generic names, warnings, contraindications, indication for use, instructions for use and/or handling, cautions or clinical records. Not all distributors followed the ordinance from the Pharmaceuticals and Medical Devices Agency to show this information to the public. The importance of package inserts in safety measures related to medical devices has been growing since the enforcement of the revised Pharmaceutical Affairs Law in 2005. The significance of package inserts must be emphasized, and distributors of kits need to be encouraged to improve inserts.


Malignant schwannoma of the vulva. A case report.
A woman was treated for a primary malignant schwannoma of the vulva. The initial treatment of this unusual tumor should entail radical excision of the primary. Regional lymphadenectomy probably is not helpful since metastases are generally hematogenous rather than lymphatic. Radiotherapy is ineffective as primary therapy.


Preventing alcohol use post-bariatric surgery: patient perspectives on a technology-based approach.
Nearly two-thirds of patients engage in alcohol use after bariatric surgery, while a substantial number meet criteria for alcohol use disorder after their procedure. Given that pre-surgical education may not be sufficient, alternative methods of preventing post-surgical drinking are needed. We sought feedback on a proposed technology-based intervention to reduce alcohol use for individuals who have undergone bariatric surgery. Twenty patients who consumed alcohol post-surgery completed qualitative interviews where they provided opinions on sample intervention content, delivery method, timing, and other aspects of a two-session web-based intervention followed by tailored text messaging for 6 months. Interviews were recorded, transcribed, and coded using thematic analysis principles. Participants strongly endorsed using technology to deliver an alcohol intervention, citing the interactivity and personal tailoring available in the proposed software. Education about the effects of post-surgical drinking and learning new coping strategies for social situations were the two most salient themes to emerge from questions about intervention content. Throughout the interviews, participants strongly highlighted the importance of measuring patient readiness to change alcohol use and matching intervention content to such motivation levels. Respondents felt that text messages could extend what they had learned, but also requested additional non-alcohol content (e.g., recipes, exercise tips). Most participants agreed that an online forum consisting of peers and professionals with whom they could ask questions and interact would be useful. Web- and text message-based interventions may be an acceptable approach to prevent alcohol use post-bariatric surgery.


Right Tegmental Hemorrhage with Urinary Retention: A Case Report.
The upper brainstem tegmentum is dense and complex, making it difficult to localize functions to specific subregions. In particular, the precise location and possible laterality of subregions supporting basic functions like consciousness and urinary continence remain unclear. Here, we describe a patient who presented with a right pontine tegmental syndrome caused by intraparenchymal hemorrhage. Despite hemorrhage extension into the fourth ventricle and expansion of both hemorrhage and edema into a large region of the caudal midbrain and right-sided pontine tegmentum, this patient did not lose consciousness. Instead, he developed new and total urinary retention, with residual bladder volumes of more than 1,000 mL. We conclude that injury to the right pontine tegmentum is sufficient to disrupt the micturition reflex pathway.


Pattern of encephaloceles: a case series.
Encephalocele is the protrusion of the cranial contents beyond the normal confines of the skull through a defect in the calvarium and is far less common than spinal dysraphism. The exact world wide frequency is not known. A substantial proportion of children especially those born with a large encephaloceles are physically and intellectually disabled. Our objective of this descriptive case series was to determine the patterns and surgical outcomes in various types of encephalocele in our setting. The study was carried at Department of Neurosurgery, Liaquat University Hospital, Jamshoro, Sindh, Pakistan during year 2005 to 2007. Patients with encephalocele (occipital, Scincipital, parietal) admitted during year 2005 to 2007 were evaluated for their clinical features. Complete base line investigations were performed including ultrasound, CT scan and MRI of brain. Other congenital anomalies were also noted in record. Written consent was taken. Operative and postoperative records were maintained. Statistical analysis was done by SPSS method. 25 children with encephalocele were selected during the years 2005-2007. Out of these 19 (76%) were male and 6 (24%) female. Age range was 06 days to 2 years. Most common type of encephalocele was occipital 20 (80%). All patients underwent surgery. Out of 25 only one patient was died. Postoperative follow up showed uneventful results. Most common type of encephalocele is occipital in our set up. Contents of the sac of encephaloceles are dysplastic brain tissue and there is no harm to sacrifice it.


Evaluating evidence-based interventions in low socio-economic-status populations.
Socio-economic-status (SES) has rarely been reported or investigated in eating disorders (EDs) research. This Research Forum considers, from various perspectives, how SES may impact on evaluating evidence-based treatments for EDs. We first reviewed previous literature that informs how SES impacts prevalence of EDs, help-seeking, and treatment outcome. We then present findings from a case series effectiveness study of an early intervention program in low SES areas for EDs and discuss implications about the impact of SES on the effectiveness of evidence-based interventions. Finally, we examine barriers to conducting rigorous evaluations in this population and discuss directions for future treatment outcome research. Evidence suggests a higher level of disordered eating but less help seeking in lower SES groups. In our case series, 96 participants started treatment and completed a mean of 13.85 sessions, 84 (87.5%) completed a mean of 6.40 sessional measures on ED cognitions and behaviors, but only 31% completed more extensive pre-treatment and post-treatment measures. The completer effect size decrease for the global Eating Disorder Examination-Questionnaire score was 2.05 (95% CI: 1.43, 2.68) commensurate with other effectiveness studies in mixed SES groups. The high rates of missing data related to more extensive assessment present a barrier to evaluating evidence-based treatments in this population. Evidence from the present study revealed individuals from low SES can achieve similar treatment outcomes to other populations when receiving evidence-based ED treatment. Future studies should investigate a range of approaches to maximizing data collection, including use of shorter sessional measures.


Intracellular bacillary burden reflects a burst size for Mycobacterium tuberculosis in vivo.
We previously reported that Mycobacterium tuberculosis triggers macrophage necrosis in vitro at a threshold intracellular load of ~25 bacilli. This suggests a model for tuberculosis where bacilli invading lung macrophages at low multiplicity of infection proliferate to burst size and spread to naïve phagocytes for repeated cycles of replication and cytolysis. The current study evaluated that model in vivo, an environment significantly more complex than in vitro culture. In the lungs of mice infected with M. tuberculosis by aerosol we observed three distinct mononuclear leukocyte populations (CD11b(-) CD11c(+/hi), CD11b(+/lo) CD11c(lo/-), CD11b(+/hi) CD11c(+/hi)) and neutrophils hosting bacilli. Four weeks after aerosol challenge, CD11b(+/hi) CD11c(+/hi) mononuclear cells and neutrophils were the predominant hosts for M. tuberculosis while CD11b(+/lo) CD11c(lo/-) cells assumed that role by ten weeks. Alveolar macrophages (CD11b(-) CD11c(+/hi)) were a minority infected cell type at both time points. The burst size model predicts that individual lung phagocytes would harbor a range of bacillary loads with most containing few bacilli, a smaller proportion containing many bacilli, and few or none exceeding a burst size load. Bacterial load per cell was enumerated in lung monocytic cells and neutrophils at time points after aerosol challenge of wild type and interferon-γ null mice. The resulting data fulfilled those predictions, suggesting a median in vivo burst size in the range of 20 to 40 bacilli for monocytic cells. Most heavily burdened monocytic cells were nonviable, with morphological features similar to those observed after high multiplicity challenge in vitro: nuclear condensation without fragmentation and disintegration of cell membranes without apoptotic vesicle formation. Neutrophils had a narrow range and lower peak bacillary burden than monocytic cells and some exhibited cell death with release of extracellular neutrophil traps. Our studies suggest that burst size cytolysis is a major cause of infection-induced mononuclear cell death in tuberculosis.


Perception of airway obstruction in asthma: sequential daily analyses of symptoms, peak expiratory flow rate, and mood.
Studies have demonstrated a weak correlation between the degree of airways obstruction and the severity of asthma symptoms. Although the causes for this disparity are probably multiple, mood has been hypothesized to modulate symptoms. This investigation was designed to evaluate the effect of mood and other patient characteristics on the perception of airways obstruction. We compared mood variables, symptom severity, albuterol use, and peak expiratory flow rate (PEFR) measured three times daily over a 21-day period in 21 adults with moderate to severe asthma. Electronic equipment was used for data collection. Analyses included both individual patient assessments and a within-subjects, time series, pooled regression of concurrent and time-lag data. After pooling 1323 observations, there was a weak concurrent relationship between symptoms and PEFR (beta = -0.17, p < 0.001). Only five patients (24%) were accurate perceivers, defined by a statistically significant relationship between symptoms and PEFR across time. Higher forced expiratory flow at 25% to 75% of capacity predicted perception accuracy (p = 0.004); active mood was marginally associated with accuracy (p = 0.06). These two variables together explained 41% of the variation in perception accuracy (p = 0.004). Mood did not independently predict symptoms, but conversely, increased symptoms predicted less pleasant mood (beta = 0.08, p < 0.001), less active mood (beta = -0.11, p < 0.001), and less active-pleasant mood (beta = 0.06, p < 0.001). PEFR did not predict mood, and only pleasant mood independently predicted higher PEFR (beta = 0.04, p < 0.05). Symptoms, but not PEFR, were concurrently associated with albuterol use (beta = 0.24, p < 0.001). The relationship between changes in PEFR and symptoms over time was generally poor. Those patients with lower FEF25-75 values tended to be less accurate perceivers. Mood states were influenced by asthma symptoms, but the converse was not true.


Bringing cell therapy to tumors: considerations for optimal CAR binder design.
Chimeric antigen receptor (CAR)-T cells have revolutionized the immunotherapy of B-cell malignancies and are poised to expand the range of their impact across a broad range of oncology and non-oncology indications. Critical to the success of a given CAR is the choice of binding domain, as this is the key driver for specificity and plays an important role (along with the rest of the CAR structure) in determining efficacy, potency and durability of the cell therapy. While antibodies have proven to be effective sources of CAR binding domains, it has become apparent that the desired attributes for a CAR binding domain do differ from those of a recombinant antibody. This review will address key factors that need to be considered in choosing the optimal binding domain for a given CAR and how binder properties influence and are influenced by the rest of the CAR.


Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia.
Overexpression of the breast cancer resistance protein (BCRP) efflux pump in human cancer cell lines results in resistance to a variety of cytostatic agents. The aim of this study was to analyze BCRP protein expression and activity in acute myeloid leukemia (AML) samples and to determine whether it is up-regulated due to clonal selection at relapse/refractory disease. BCRP protein expression was measured flow cytometrically with the monoclonal antibodies BXP-34 and BXP-21 in 20 paired samples of de novo and relapsed/refractory AML. BXP-34/immunoglobulin G1 ratios were observed of 1.6 +/- 0.5 (mean +/- SD, range 0.8-2.7) and BXP-21/immunoglobulin G2a ratios of 4.9 +/- 3.0 (range 1.1-14.5) in the patient samples versus 9.8 +/- 6.8 and 6.5 +/- 2.4, respectively, in the MCF-7 cell line. BCRP activity was determined flow cytometrically by measuring mitoxantrone accumulation in absence and presence of the inhibitor fumitremorgin C. Mitoxantrone accumulation, expressed as mean fluorescence intensity (MFI), varied between 44 and 761 MFI (227 +/- 146 MFI) and correlated inversely with BCRP expression (r = -0.58, P <.001). Addition of fumitremorgin C showed a small increase in mitoxantrone accumulation (11 +/- 29 MFI, n = 40) apart from the effect of PSC833 and MK-571. No consistent up-regulation of BCRP expression or activity was observed at relapse/refractory disease; some cases showed an increase and other cases a decrease at relapse. Relatively high BCRP expression correlated with immature immunophenotype, as determined by expression of the surface marker CD34 (r = 0.54, P =.001). In conclusion, this study shows that BCRP protein is expressed at low but variable levels in AML, especially in immature CD34(+) cells. BCRP was not consistently up-regulated in relapsed/refractory AML.


Sweet Electronics: Honey-Gated Complementary Organic Transistors and Circuits Operating in Air.
Sustainable harnessing of natural resources is key moving toward a new-generation electronics, which features a unique combination of electronic functionality, low cost, and absence of environmental and health hazards. Within this framework, edible electronics, of which transistors and circuits are a fundamental component, is an emerging field, exploiting edible materials that can be safely ingested, and subsequently digested after performing their function. Dielectrics are a critical functional element of transistors, often constituting their major volume. Yet, to date, there are only scarce examples of electrolytic food-based materials able to provide low-voltage operation of transistors at ambient conditions. In this context, a cost-effective and edible substance, honey, is proposed to be used as an electrolytic gate viscous dielectric in electrolyte-gated organic field-effect transistors (OFETs). Both n- and p-type honey-gated OFETs (HGOFETs) are demonstrated, with distinctive features such as low voltage (<1 V) operation, long-term shelf life and operation stability in air, and compatibility with large-area fabrication processes, such as inkjet printing on edible tattoo-paper. Such complementary devices enable robust honey-based integrated logic circuits, here exemplified by inverting logic gates and ring oscillators. A marked device responsivity to humidity provides promising opportunities for sensing applications, specifically, for moisture control of dried or dehydrated food.


Review of image-guided radiation therapy.
Image-guided radiation therapy represents a new paradigm in the field of high-precision radiation medicine. A synthesis of recent technological advances in medical imaging and conformal radiation therapy, image-guided radiation therapy represents a further expansion in the recent push for maximizing targeting capabilities with high-intensity radiation dose deposition limited to the true target structures, while minimizing radiation dose deposited in collateral normal tissues. By improving this targeting discrimination, the therapeutic ratio may be enhanced significantly. The principle behind image-guided radiation therapy relies heavily on the acquisition of serial image datasets using a variety of medical imaging platforms, including computed tomography, ultrasound and magnetic resonance imaging. These anatomic and volumetric image datasets are now being augmented through the addition of functional imaging. The current interest in positron-emitted tomography represents a good example of this sort of functional information now being correlated with anatomic localization. As the sophistication of imaging datasets grows, the precise 3D and 4D positions of the target and normal structures become of great relevance, leading to a recent exploration of real- or near-real-time positional replanning of the radiation treatment localization coordinates. This 'adaptive' radiotherapy explicitly recognizes that both tumors and normal tissues change position in time and space during a multiweek course of treatment, and even within a single treatment fraction. As targets and normal tissues change, the attenuation of radiation beams passing through these structures will also change, thus adding an additional level of imprecision in targeting unless these changes are taken into account. All in all, image-guided radiation therapy can be seen as further progress in the development of minimally invasive highly targeted cytotoxic therapies with the goal of substituting remote technologies for direct contact on the part of an operator or surgeon. Although data demonstrating clear-cut superiority of this new high-tech paradigm compared with more conventional radiation treatment approaches are scant, the emergence of preliminary data from several early studies shows that interest in this field is broad based and robust. As outcomes data accumulate, it is very likely that this field will continue to expand greatly. Although at present most of the work is being performed at major academic centers, the enthusiastic adoption of many of the devices and approaches being developed for this field suggest a rapid penetration into the community and the use of the technology by teams of specialists in the fields of radiation medicine, radiation physics and various branches of surgery. A recent survey of practitioners predicted very widespread adoption within the next 10 years.


Bionectins A-C, epidithiodioxopiperazines with anti-MRSA activity, from Bionectra byssicola F120.
Three new epidithiodioxopiperazine compounds, bionectins A (1), B (2), and C (3), along with a known compound, verticillin D (4), have been isolated from the mycelium of liquid fermentation cultures of the fungus Bionectra byssicola F120. The structures of compounds 1-3 were assigned on the basis of MS and NMR data. Compounds 1 and 2 incorporate a dioxopiperazine moiety with a disulfide bridge in their molecules, while 3 contains a dioxopiperazine ring with two methylsulfanyl groups. Compounds 1 and 2 exhibited antibacterial activity against S. aureus including methicillin-resistant S. aureus (MRSA) and quinolone-resistant S. aureus (QRSA), with MIC values of 10-30 microg/mL, while 3 showed no antibacterial activity even at 100 microg/mL.


Adaptive striping watershed segmentation method for processing microscopic images of overlapping irregular-shaped and multicentre particles.
Oversegmentation is a major drawback of the morphological watershed algorithm. Here, we study and reveal that the oversegmentation is not only because of the irregular shapes of the particle images, which people are familiar with, but also because of some particles, such as ellipses, with more than one centre. A new parameter, the striping level, is introduced and the criterion for striping parameter is built to help find the right markers prior to segmentation. An adaptive striping watershed algorithm is established by applying a procedure, called the marker searching algorithm, to find the markers, which can effectively suppress the oversegmentation. The effectiveness of the proposed method is validated by analysing some typical particle images including the images of gold nanorod ensembles.


Degenerative Nucleus Pulposus Cells Derived Exosomes Promoted Cartilage Endplate Cells Apoptosis and Aggravated Intervertebral Disc Degeneration.
Intervertebral disc (IVD) degeneration is a complex multifactorial disease model, which pathogenesis has not been fully defined. There are few studies on the information interaction between nucleus pulposus (NP) cells and cartilage endplate (CEP) cells. Exosomes, as a carrier of information communication between cells, have become a research hotspot recently. The purpose of this study was to explore whether degenerative NP cells-derived exosomes promoted CEP cells apoptosis and aggravated IVD degeneration. The degenerative NP cells model was induced by TNFα. NPC exosomes were isolated from the supernatant of the NP cell culture medium. The viability of NP cells and CEP cells was examined by CCK-8 assays. The exosomes were identified by TEM, NTA, and western blot. Extracellular matrix (ECM) metabolism was measured by cellular immunofluorescence and qRT-PCR. Apoptosis was detected by flow cytometry and TUNEL. X-ray and magnetic resonance imaging (MRI), as well as hematoxylin-eosin (H&E), Safranine O-Green staining was adopted to evaluate IVD degeneration grades. TNFα had a minor impact on NPC viability but inhibited ECM synthesis and promoted ECM degradation. TNFα-NPC-Exo had less effect on CEPC proliferation but promoted CEPC apoptosis and affect ECM metabolism, inhibiting aggrecan and collagen II expression and enhancing MMP-3 expression. TNFα-NPC-Exo aggravates IVD degeneration in a rat model and promoted CEPC apoptosis. In conclusion, this study demonstrated that degenerated NPC-exosome could induce apoptosis of CEPCs, inhibit ECM synthesis, and promote ECM degradation. In addition, it was proved that degenerated NPC-exosome aggravates IVD degeneration.


Does Deep Bradycardia Increase the Risk of Arrhythmias and Syncope in Endurance Athletes?
The aim of this study was to evaluate whether endurance athletes who exhibit deep bradycardia are more prone to arrhythmias and reflex syncope than their non-bradycardic peers. 46 healthy men (ages 19-35) were divided into 3 groups based on whether they were sedentary (SED,<2 h/week) or endurance trained (ET,>6 h/week), and non-bradycardic (NB, resting heart rate (HR)≥60 bpm) or bradycardic (B, resting HR<50 bpm). Resting HR was lower in ETB vs. ETNB and SED (43.8±3.1, 61.3±3.3, 66.1±5.9 bpm, respectively; p<0.001). Thus, 16 SED, 13 ETNB and 17 ETB underwent resting echocardiography, maximal exercise test, tilt test (TT) and 24 h-Holter ECG. Subjects were followed-up during 4.7±1.1 years for training, syncope and cardiac events. Our results showed that incidence of arrhythmias and hypotensive susceptibility did not differ between groups. During follow-up, no episode of syncope or near-syncope was reported. However, cardio-inhibitory syncope occurrence tended to be higher in ETB. Left ventricular end-diastolic diameter index was increased in ETB vs. ETNB and was correlated with resting HR (r=- 0.64; p<0.001). As a result, athletes with deep bradycardia do not present more arrhythmias and more hypotensive susceptibility than their non-bradycardic peers. Cardiac enlargement and autonomic alteration both seem to be involved in an athlete's bradycardia.


Elemental gesture dynamics are encoded by song premotor cortical neurons.
Quantitative biomechanical models can identify control parameters that are used during movements, and movement parameters that are encoded by premotor neurons. We fit a mathematical dynamical systems model including subsyringeal pressure, syringeal biomechanics and upper-vocal-tract filtering to the songs of zebra finches. This reduces the dimensionality of singing dynamics, described as trajectories (motor 'gestures') in a space of syringeal pressure and tension. Here we assess model performance by characterizing the auditory response 'replay' of song premotor HVC neurons to the presentation of song variants in sleeping birds, and by examining HVC activity in singing birds. HVC projection neurons were excited and interneurons were suppressed within a few milliseconds of the extreme time points of the gesture trajectories. Thus, the HVC precisely encodes vocal motor output through activity at the times of extreme points of movement trajectories. We propose that the sequential activity of HVC neurons is used as a 'forward' model, representing the sequence of gestures in song to make predictions on expected behaviour and evaluate feedback.


Ultrasound and partial coherence interferometry with measurement of central corneal thickness.
To compare noncontact pachymeter measurements with ultrasound pachymeter measurements and assess their reproducibility. Central corneal thickness was measured in 104 eyes of 56 patients with three laser interference pachymeters (OLCR [Haag Streit, Könitz, Switzerland], OCP [4optics AG, Lübeck, Germany], and ACMaster [Carl Zeiss Meditec, Jena, Germany]) and an ultrasound pachymeter (Tomey AL2000 [Tomey Corp, Nagoya, Japan]). Compared to the ultrasound measurements, the mean difference for the laser interference pachymeter measurements were +8.8 microm (standard deviation [SD] 5.68) for the OLCR, -8.0 microm (SD 5.39) for the OCP, and -0.12 microm (SD 5.88) for the ACMaster. Reproducibility could only be estimated as not all of the devices allowed access to individual measurements. For all laser interference devices, reproducibility was estimated to be approximately 2 microm. Ultrasound measurements yielded a reproducibility of approximately 3.4 microm. Although ultrasound pachymeter measurements differed significantly from OLCR and OCP measurements, agreement was considered good because the mean differences were <10 microm, and the results can be regarded as clinically interchangeable.


Effect of high-frequency ventilation versus conventional mechanical ventilation on ICP in head-injured dogs.
Changes in intrathoracic pressure may influence intracranial pressure (ICP), presumably by affecting venous return. High-frequency ventilation (HFV) has been associated with lower intrapleural and airway pressures and has the potential to lower ICP. To evaluate the effects of HFV compared to conventional ventilation on ICP, normocarbia was maintained in nine dogs while alternating between conventional ventilation and HFV at 200 breaths/min. The mean ICP was raised from 6.3 +/- 6.1 to 24.7 +/- 1.04 mm Hg by inflation of Fogarty balloons implanted in the epidural space. The ICP peaks associated with positive inflation pressures were eliminated with HFV, but mean ICP was not significantly different between the two ventilatory modes (23.4 +/- 9.7 mm Hg for the conventional system versus 26.0 +/- 10.0 mm Hg for HFV). Four dogs exhibited neurogenic pulmonary edema: they developed elevated pulmonary artery and intrathoracic pressures and required increased inspiratory flow with HFV to maintain normocarbia. The authors conclude that, in this head-injury model, there did not seem to be an advantage of HFV over conventional ventilation.


Treatment priorities and current prescribing patterns in hypertension: results of GRASP, an international physician survey.
The GRASP (Global Research on Attitudes about hypertension and Stroke Prevention) survey, conducted in 11 countries and involving 825 physicians, was designed to investigate physician perceptions and priorities in the treatment of hypertension and influences on choice of antihypertensive therapy. The prevention of stroke was identified as a major priority in this survey, but there appeared to be some degree of mismatch between the evidence from large controlled trials and current patterns of prescribing for stroke prevention. The results of GRASP confirm the desirability of research to identify methods and strategies that will facilitate the integration of clinical trial results into general practice treatment of hypertension.