Postoperative brachial artery entrapment associated with pediatric supracondylar fracture of the humerus: a case report.
Severely displaced supracondylar fractures of the humerus in children are frequently associated with complications including neurovascular injuries, non-union, or compartment syndrome. In the current literature, no report exists about postoperative brachial artery entrapment in combination with an inconspicuous preoperative neurovascular examination. We present a case of a 6-year-old white boy with a pulseless radial and ulnar artery after open reduction and internal fixation of a severely displaced supracondylar fracture of his right humerus (Gartland type III) using four K-wires. Remarkably, the preoperative neurovascular examination was inconspicuous. Doppler ultrasound of his brachial artery revealed no pulse when his elbow was in flexion and a faint pulse when it was in full extension 10 hours postoperatively. Revision surgery was performed immediately. On intraoperative examination, a kinking of his brachial artery caused by an entrapment of the tunica externa in the reduced fracture was seen and the artery was released by microsurgical arteriolysis immediately. At the final follow-up examination, positive palpable pulse with good capillary filling and, according to Flynn's criteria, an excellent recovery of elbow function was observed 3 months postoperatively. This case demonstrates a rare complication of postoperative artery entrapment with inconspicuous preoperative neurovascular examination. It strongly emphasizes the need for a standardized postoperative neurovascular assessment with fully flexed as well as fully extended elbow.


Copper proteins and copper enzymes.
The copper proteins that function in homeostasis, electron transport, dioxygen transport and oxidation are discussed. Particular emphasis is placed on the role of the ligands, their type and disposition which, in conjunction with other residues in the active site, determine the role of the copper ion. It is proposed that copper proteins can be considered in four groups. Those in Group I contain a single copper ion in an approximately tetrahedral environment with nitrogen and sulphur-containing ligands. Group II proteins have a single copper ion in a square-planar-like arrangement. Group III proteins have two copper ions in close proximity. Group IV consists of multi-copper proteins, composed of sites representative of the other three groups.


Hybrid external iliac selective endarterectomy surgical technique and outcomes.
Long or multisegmental external iliac-to-femoral arterial lesions treated by angioplasty and stenting have achieved disappointing results. Conventional, open approaches are often complicated by significant morbidity, and endovascular stenting alone typically requires additional outflow procedures. We hypothesized that a hybrid approach, combining endovascular techniques with remote selective external iliac endarterectomy, produces superior outcomes in terms of patency compared with stenting alone, with minimal associated morbidity. We performed a retrospective review of all patients having undergone hybrid-based retrograde iliofemoral endarterectomy from 2010 to 2014 at St. Joseph Mercy in Ann Arbor, Michigan. Patient demographics, presenting complaints, operative details, and complications were analyzed. Postoperative patency was assessed by comparison of ankle-brachial index values and qualitative patient improvement. Data were analyzed by way of paired Student t-test with significance defined as P < .05. A total of 40 limbs were intervened upon on 33 patients. In 20 limbs, the procedure was performed for critical limb ischemia (rest pain, n = 9; tissue loss/gangrene, n = 11). By TransAtlantic Inter-Society Consensus II criteria, 83% of iliac lesions were class D. A more even distribution was noted in TransAtlantic Inter-Society Consensus II classification for femoral and popliteal disease. Seventeen percent of patients had one-vessel infrageniculate runoff. In 21 limbs (54%), external iliac artery (EIA) stenting was performed at the time of procedure, 18 (46%) had common iliac artery (CIA) stenting, and 7 (18%) had a bridging stent from the CIA to EIA. The modal EIA stent diameter was 10 mm (range, 8-10 mm), modal CIA stent diameter 8 mm (range, 7-9 mm). The preintervention ankle-brachial index was 0.45 ± 0.24 (n = 33 limbs) and significantly improved to 0.75 ± 0.27 (n = 29 limbs; P < .001). In addition, preintervention toe pressure of 34 ± 28 (n = 28 limbs) improved to 58 ± 26 (n = 23 limbs; P < .001). No intraoperative complications occurred, which necessitated abdominal or retroperitoneal exposure. Average follow-up after the intervention was 13 ± 14.6 months. One limb (3%) required an additional outflow bypass. The incidence of ipsilateral hypogastric occlusion increased from 35% to 55% postoperatively; however, no patients reported pelvic or buttock ischemia. One patient who had the procedure done bilaterally presented 655 days after the procedure with bilateral iliac artery thrombosis and underwent aortobifemoral bypass. No other patient needed subsequent primary assisted patency or additional infrainguinal revascularization. Hybrid-based external iliac and femoral endarterectomy provides a minimally invasive approach to EIA occlusive disease comparable with aortofemoral bypass. Dramatic inflow improvement was observed in our series, and the need for additional outflow revascularization was minimal. The procedure was deemed technically feasible and safe, with a low number of adverse sequela and excellent primary patency achieved more than 1 year after the intervention.


Industrial use of immobilized enzymes.
Although many methods for enzyme immobilization have been described in patents and publications, relatively few processes employing immobilized enzymes have been successfully commercialized. The cost of most industrial enzymes is often only a minor component in overall process economics, and in these instances, the additional costs associated with enzyme immobilization are often not justified. More commonly the benefit realized from enzyme immobilization relates to the process advantages that an immobilized catalyst offers, for example, enabling continuous production, improved stability and the absence of the biocatalyst in the product stream. The development and attributes of several established and emerging industrial applications for immobilized enzymes, including high-fructose corn syrup production, pectin hydrolysis, debittering of fruit juices, interesterification of food fats and oils, biodiesel production, and carbon dioxide capture are reviewed herein, highlighting factors that define the advantages of enzyme immobilization.


Developing a scholarship community.
To report the results of a multidisciplinary, interinstitutional writing support group established to facilitate faculty scholarly productivity. ORGANIZING CONCEPT: The road to scholarship can be filled with many obstacles, among them time constraints, teaching and meeting demands, student needs, office interruptions, and lack of colleagueship. The problems associated with lack of colleagueship, in particular, can be compounded for faculty who work in isolated contexts with few, if any, senior faculty to serve as mentors. METHODS OF DEVELOPMENT: The Western Writers Coercion Group evolved over a 2-year period from a small group of nursing faculty at a single institution to include, by its second year, 21 faculty from five western university campuses and three academic disciplines. The group met biweekly via teleconference with the objectives of defining and accomplishing realistic individual scholarship goals and providing a forum for the critical exchange of ideas. The ongoing support and mentoring of the group led to significant writing outcomes in the form of manuscripts submitted for publication, abstracts submitted for conference presentation, grant proposals developed, and collegial relationships formed. Although the benefits of group participation varied somewhat for faculty at different points in the career trajectory, they seemed to accrue at all levels of development. Group members underscored the many less quantifiable advantages of group participation: exposure to broader professional perspectives, the formation of key professional relationships, the enrichment of multidisciplinary input, and individualized assistance with time management, goal setting, and actual drafts. The structure and experience of this group, which continues to meet regularly, might be a model to guide other groups of scholars who face geographic isolation and who struggle with balancing time and work and finding motivation for the process of writing.


Temperature and pH/CO(2) modulate respiratory activity in the isolated brainstem of the bullfrog (Rana catesbeiana).
The effects of temperature and pH/CO(2) were examined in isolated brainstem preparations from adult North American bullfrogs (Rana catesbeiana). These experiments were undertaken to determine the effects of temperature on fictive breathing, central pH/CO(2) chemoreception, and to examine potential alphastat regulation of respiration in vitro. Adult bullfrog brainstem preparations were isolated, superfused with an artificial cerebrospinal fluid (aCSF) and respiratory-related neural activity was recorded from cranial nerves V, X and XII. In Series I experiments (N=8), brainstem preparations were superfused with aCSF equilibrated with 2% CO(2) at temperatures ranging from 10 to 30 degrees C. Neural activity was present in all preparations in the temperature range of 15-25 degrees C, but was absent in most preparations when aCSF was at 10 or 30 degrees C. The absence of fictive breathing at high (30 degrees C) temperatures was transient since fictive breathing could be restored upon returning the preparation to 20 degrees C. In Series II experiments (N=10), preparations were superfused with aCSF equilibrated with 0%, 2% and 5% CO(2) at temperatures of 15, 20 and 25 degrees C. Fictive breathing frequency (f(R)) was significantly dependent upon aCSF pH at all three temperatures, with slopes ranging from -0.82 min(-1) pH unit(-1) (15 degrees C) to -3.3 min(-1) pH unit(-1) (20 degrees C). There was a significant difference in these slopes (P<0.02), indicating that central chemoreceptor sensitivity increased over this temperature range. Fictive breathing frequency was significantly dependent upon the calculated alpha-imidazole (alpha(Im)) ionization (P<0.05), consistent with the alphastat hypothesis for the effects of temperature on the regulation of ventilation. However, most of the variation in f(R) was not explained by alpha(Im) (R(2)=0.05), suggesting that other factors account for the regulation of fictive breathing in this preparation. The results indicate that the in vitro brainstem preparation of adult bullfrogs has a limited temperature range (15-25 degrees C) over which fictive breathing is consistently active. Although there is a close correspondence of ventilation in vitro and in vivo at low temperatures, these data suggest that, as temperature increases, changes in ventilation in the intact animal are likely to be more dependent upon peripheral feedback which assumes a greater integrative role with respect to chemoreceptor drive, respiratory frequency and tidal volume.


Microbiological and Sensory Quality of Fresh Ready-to-Eat Artichoke Hearts Packaged under Modified Atmosphere.
In recent years the sales of minimally processed vegetables have grown exponentially as a result of changes in consumer habits. The availability of artichoke buds as a ready-to-eat product would be, therefore, highly advantageous. However, minimally processed artichoke hearts are difficult to preserve because of their rapid browning and the proliferation of naturally occurring microorganisms. We developed artichoke hearts prepared as ready-to-eat products that maintain the characteristics of the fresh product. The microbiological stability, sensory qualities, and shelf life of the processed artichoke hearts were determined. During the shelf life, Salmonella, Listeria monocytogenes, and Escherichia coli counts were below the limits legally established by European regulations for minimally processed vegetables. The pH played an important role in microbial growth. Artichoke hearts had lower microbial counts in experiments conducted at pH 4.1 than in experiments conducted at pH 4.4, although the recommended threshold value for total plate count (7 log CFU/g) was not exceeded in either case. Sensory parameters were affected by the microorganisms, and artichoke products at lower pH had better sensory qualities. Vacuum impregnation techniques, modified atmosphere packaging, and low storage temperature were very effective for increasing the shelf life of minimally processed artichokes. The average shelf life was approximately 12 to 15 days.


Implementation of the mental health Gap Action Programme (mhGAP) within the Fijian Healthcare System: a mixed-methods evaluation.
To facilitate decentralisation and scale-up of mental health services, Fiji's Ministry of Health and Medical Services committed to implementing the World Health Organization's mental health Gap Action Programme (mhGAP). mhGAP training has been prolific; however, it remains unclear, beyond this, how successfully Fiji's national mental health program has been implemented. We aim to evaluate Fiji's mental health program to inform Fiji's national mental health program and to develop an evidence-base for best practice. The study design was guided by the National Implementation Research Network and adhered to the Consolidated Framework for Implementation Research. CFIR constructs were selected to reflect the objectives of this study and were adapted where contextually necessary. A mixed-methods design utilised a series of instruments designed to collect data from healthworkers who had undertaken mhGAP training, senior management staff, health facilities and administrative data. A total of 66 participants were included in this study. Positive findings include that mhGAP was considered valuable and easy to use, and that health workers who deliver mental health services had a reasonable level of knowledge and willingness to change. Identified weaknesses and opportunities for implementation and system strengthening included the need for improved planning and leadership. This evaluation has unpacked the various implementation processes associated with mhGAP and has simultaneously identified targets for change within the broader mental health system. Notably, the creation of an enabling context is crucial. If Fiji acts upon the findings of this evaluation, it has the opportunity to not only develop effective mental health services in Fiji but to be a role model for other countries in how to successfully implement mhGAP.


Utility and safety of ultrasound-guided fine-needle aspiration of salivary gland masses including a cytologist's review.
To evaluate the utility and safety of ultrasound-guided fine-needle aspiration of the salivary glands for diagnosis of focal masses in the salivary glands, including the prevalence of nondiagnostic sampling, the impact of the presence of a cytologist during the procedure, and the usefulness of flow cytometry. A retrospective analysis of 43 ultrasound-guided fine-needle aspirations of the salivary glands from 36 lesions in 33 patients was performed. Fine-needle aspirations were obtained under sonographic guidance, and 1 to 6 punctures were made with 20- to 25-gauge needles. Ultrasound-guided fine-needle aspirations obtained in the presence of a cytologist were compared with those performed without a cytologist regarding the adequacy of the specimen and the number of punctures performed. Postprocedural complications and the frequency with which flow cytometry was performed were noted. Cytopathologic diagnosis was correlated with clinical follow-up (n = 33) and surgical pathologic findings (n = 10). Cytologic diagnosis was made in 31 (94%) of 33 patients, confirming a neoplastic process in 18 (50%) of 36 and a non-neoplastic process in 16 (44%) of 36. Although the presence of a cytologist at the bedside resulted in a higher prevalence of diagnostic sampling (P < .05), it did not alter the number of punctures performed (mean, 3 punctures). No complications were encountered except for pain in 2 patients. Flow cytometry was helpful in 8 (22%) of 36 patients. Ultrasound-guided fine-needle aspiration of the salivary glands is a safe procedure with a low prevalence of nondiagnostic sampling. Approximately 44% of patients can be spared surgical intervention through diagnosis of a non-neoplastic process. The presence of a cytologist increases the likelihood of obtaining a diagnostic sample. Flow cytometry was helpful in 22% of patients.


Sitosterolemia: A Case Report and a Concise Literature Review.
Sitosterolemia is a relatively rare metabolism lipid disorder, with about 110 cases worldwide and only a few known cases from the Middle East. Sitosterolemia is characterized by excessive uptake of phytosterols and their deposition in various tissues, leading to complications. Mutations in the ABCG5 and ABCG8 genes are associated with pathological changes in sitosterolemia. Case Presentation. An adult patient from Saudi Arabia with dyslipidemia who did not respond to statin therapy. Based on genetic testing, the patient was eventually diagnosed with sitosterolemia. Ezetimibe significantly improved his cholesterol levels. The diagnosis of sitosterolemia is confirmed by the detection of high-phytosterol levels and pathological mutation in the ABCG5 and ABCG8 genes. Treatment of sitosterolemia is based on dietary changes and drugs to inhibit cholesterol absorption, such as ezetimibe.


Case of human rabies despite post-exposure prophylaxis (PEP) and complete recovery after intrathecal rabies immunoglobulin (RIG).
Rabies, a fatal viral zoonotic disease, has become a public health concern in Sarawak, Malaysia. Despite pre-exposure and post-exposure prophylaxis being available, there has been limited progress in developing treatments for rabies, emphasising the pressing need for productive solutions. We present a laboratory-confirmed human rabies case in which the patient survived without neurological sequelae after receiving intrathecal rabies immunoglobulin.


Cardiovascular Risk Factors in 7-13 Years Old Children from Vojvodina (Serbia).
Atherosclerosis is a chronic inflammatory disease which starts early in life and depends on many factors, an important one being dyslipoproteinemia. According to several studies, atherosclerotic plaques or their precursors could be seen in children younger than 10 years. During later life, interaction with a sedentary way of life, as well as unhealthy nutrition, smoking, alcohol consumption, obesity and family history of cardiovascular disease cause the burden of atherosclerotic disease. Study included 624 children (316 boys, 308 girls), aged from 7-13 years. We analysed socio-demographic data (BMI, blood pressure, cardiovascular family history, smoking status), as well as lipid status with lipoprotein little a-Lp(a), and apolipoproteins: Apo AI, Apo B-100 for all children. This enabled us to calculate new atherogenic indices Tg/HDL-c, lipid tetrad index (LTI) and lipid pentad index (LPI). Cardiovascular risk for later life was estimated by using modified Risk Score for Young Individuals (RS), which divided the subjects according to the score level: low, medium and higher risk. The older children (13 y) had better lipid status than the younger children, i.e. significantly lower total cholesterol, LDL-C, triglycerides and non-HDL-C concentration and significantly higher HDL-C concentration than the younger children and this was in accordance with the RS level. Children with a positive family history of CV disease had significantly higher Lp(a) concentration and blood pressure. LPI was significantly higher in children with a higher RS. The results of our work could be used for cardiovascular risk assessment in apparently healthy children to provide preventive measures which could control the changeable risk factors.


[LH and FSH responses to synthetic LH-RH in various estradiol levels of anovulatory women (author's transl)].
Synthetic LH releasing hormone (LH-RH) is effective in increasing both serum LH and FSH in humans. Therefore, LH-RH is used to clarify the function of the hypothalamic pituitary ovarian axis in adult women. Variations in response to synthetic LH-RH during different phases of the menstrual cycle are known. These variations may be due to changes in the ovarian secretion of sex streoid hormones during the menstrual cycle. In the present study, effects of serum estradiol (Ed) on pituitary gonadotropin response to synthetic LH-RH were studied in 55 subjects without ovulation. Serum levels of LH, FSH and Ed were determined before and at 30 min after intramuscular administration of 100 mug LH-RH. LH and FSH levels in the serum were measured by the double antibody method of radioimmunoassay. Ed levels were determined by the radioimmunoassay method of T. Makino, using the antiserum against Ed-6-oxime-BSA donated by Dr. T. Makino and applied to the microcolumn of sephadex LH 20. Preliminary evidence about Ed levels during the normal menstrual cycle and in anovulatory women suggested that an Ed level under 30 pg/ml indicates the presence of a small amount of Ed. Therefore, 55 patients were divided into 2 groups; the low Ed group that showed low basal Ed levels (under 30 pg/ml) and the Ed normal group that showed normal basal Ed levels (over 30 pg/ml). Pituitary gonadotropin responses to synthetic LH-RH were studied in these two groups. No statistical difference was shown between the two groups studied for basal LH level and FSH level. After LH-RH injection in the Ed normal group, serum LH level was significantly higher and serum FSH level was significantly lower than that in the low Ed group. Then, in order to clarify the difference in two groups, the ratio of LH to FSH (LH/FSH) before and after administration of LH-RH was examined. The ratio in the Ed normal group was significantly higher than one in the low Ed group before and after administration of LH-RH. Moreover, the percentage increase of the ratio was significantly larger in the Ed normal group than that in the low Ed group. A positive correlation (r=0.4228, p less than 0.01) was found between LH/FSH following administration of LH-RH and circulating the Ed level. These results suggest that the response of pituitary gonadotropins to LH-RH is changed by serum Ed and that serum Ed causes a differential release of LH and FSH in response to LH-RH. The data seem to demonstrate that LH-RH and serum Ed show a complex interplay in releasing LH and FSH.


Oxygenation of anoxic sediments triggers hatching of zooplankton eggs.
Many coastal marine systems have extensive areas with anoxic sediments and it is not well known how these conditions affect the benthic-pelagic coupling. Zooplankton lay their eggs in the pelagic zone, and some sink and lie dormant in the sediment, before hatched zooplankton return to the water column. In this study, we investigated how oxygenation of long-term anoxic sediments affects the hatching frequency of dormant zooplankton eggs. Anoxic sediments from the brackish Baltic Sea were sampled and incubated for 26 days with constant aeration whereby, the sediment surface and the overlying water were turned oxic. Newly hatched rotifers and copepod nauplii (juveniles) were observed after 5 and 8 days, respectively. Approximately 1.5 × 10(5) nauplii m(-2) emerged from sediment turned oxic compared with 0.02 × 10(5) m(-2) from controls maintained anoxic. This study demonstrated that re-oxygenation of anoxic sediments activated a large pool of buried zooplankton eggs, strengthening the benthic-pelagic coupling of the system. Modelling of the studied anoxic zone suggested that a substantial part of the pelagic copepod population can derive from hatching of dormant eggs. We suggest that this process should be included in future studies to understand population dynamics and carbon flows in marine pelagic systems.


Homeobox-D 1 and FTO form a transcriptional-epigenetic feedback loop to promote head and neck cancer proliferation.
Transcription factors (TFs) and N6-methyladenosine (m6A) modifiers are involved in tumor progression through transcriptional regulation and posttranscriptional regulation of genes, respectively. However, the crosstalk and role of these two types of gene expression regulators in head and neck squamous cell carcinoma (HNSC) remains poorly understood. In this study, we demonstrate that the TF homeobox-D1 (HOXD1) and the m6A demethylase fat mass and obesity-associated protein (FTO) form a positive feedback loop to promote cell proliferation and survival in HNSC. Clinically, HOXD1 expression is dysregulated in multiple cancer types and is associated with worse prognosis in patients with HNSC, stomach adenocarcinoma, uterine corpus endometrial carcinoma, and pheochromocytoma and paraganglioma. Mechanistically, FTO is overexpressed in HNSC tumor samples and positively regulates HOXD1 expression in an m6A-dependent manner. Functionally, deficiency of HOXD1 relieved the resistance of HNSC cells to apoptosis and arrested tumor cells at the G0/G1 phase, thereby inhibiting cell growth, whereas overexpression of HOXD1 caused the opposite effect. Furthermore, HOXD1 activates the transcription of the oncogenic factor FTO by directly targeting its promoter. Downregulation of FTO mimicked the biological effect of HOXD1 knockdown on HNSC. Importantly, overexpression of HOXD1 significantly rescued the proliferation inhibition and apoptosis promotion of HNSC cells induced by deficiency of FTO. Together, our findings reveal HOXD1 as a novel prognostic predictor and a potential target for HNSC, providing mechanistic insights into the role of the HOXD1-FTO circuit in this cancer.


[Risk factors for not benefiting from palliative care in end-of-life geriatric patients].
Palliative care should represent good medical practice for all clinicians. Their still exist many barriers to good palliative care in general and in geriatrics in particular. The present observational study aimed to identify these barriers. During the six months study period, patients hospitalized in a Belgian geriatric hospital and benefiting from palliative care were prospectively compared to those who died without palliative care. Nearly half of our patients died without access to palliative care. Compared to the patients who had received palliative care, these patients showed less often pain and more often dyspnea. Invasive medical interventions and use of antibiotics were more frequent in patients who died without access to palliative care. Benzodiazepines were used less frequently compared to palliative care patients. In patients who died without access to palliative care, communication with the patient was inferior as compared to palliative care patients. The former group showed more often cognitive impairment, social isolation, and a more rapid, unanticipated death. We identified the following risk factors for not benefiting from palliative care in geriatrics: absence of identified pain syndrome; presence of dyspnea; absence of oncologic diagnosis; social isolation and poor communication with the patient and her/his family; cognitive dysfunction and unexpected death.


Involved node radiation therapy in the combined modality treatment for early-stage Hodgkin lymphoma: Analysis of relapse location and long-term outcome.
Involved node radiation therapy (INRT) in the combined modality treatment for early-stage Hodgkin lymphoma (ESHL) has reduced the irradiated volume dramatically. Limiting the irradiated volume further based on initial disease bulk, 18F-fluoro-deoxy-glucose (FDG)-avidity, or residual computed tomography (CT) abnormality after chemotherapy seems attractive. In a cohort of patients treated with INRT a meticulous pattern-of-relapse analysis was performed to examine these options. Patients treated for ESHL in our institution from 2005 to 2014 who achieved complete remission with chemotherapy were included. Patient characteristics, treatment details and clinical outcome were registered. For relapsed patients, rigid co-registration of the positron emission tomography/computed tomography-scans from the time of diagnosis and at relapse was done to visually assess the relapse location relative to initial involvement and, if irradiated, the irradiated volume. Size and maximum Standardized Uptake Value of the initial node(s) with later relapse, and residual CT abnormalities after chemotherapy in those locations were measured. We included 182 patients. Twelve (6.6%) patients relapsed, five in previously involved nodes (two irradiated, three not irradiated). Relapses did not occur preferentially in initially bulky disease, in lymph node(s) with the highest FDG-uptake, or in residual CT abnormalities after chemotherapy. Modern treatment with brief chemotherapy and limited radiotherapy provides excellent long-term disease control in ESHL. Neither bulk, high FDG-uptake, nor residual CT abnormality after chemotherapy could predict initially involved lymph nodes with a high risk of relapse.


Neoadjuvant chemotherapy followed by surgery versus surgery alone for colorectal cancer: meta-analysis of randomized controlled trials.
Effects of neoadjuvant chemotherapy (NAC) on colorectal cancer (CRC) have been largely studied, while its survival and surgical benefits remain controversial. This study aimed to perform a meta-analysis of randomized controlled trials (RCTs), comparing efficacy and safety of NAC plus surgery with surgery alone (SA) for CRC. We searched systematically databases of MEDLINE, EMBASE, and the Cochrane Library for RCTs comparing NAC and surgery with SA for treating CRC. References of relevant articles and reviews, conference proceedings, and ongoing trial databases were also screened. Primary outcomes included overall and disease-free survivals, total and perioperative mortalities, recurrence, and metastasis. Meta-analysis was performed where possible comparing parameters using relative risks (RRs). Safely analysis was then performed. Outcomes for stages II and III tumors were also meta-analyzed, respectively. Our study was conducted according to intention-to-treat analysis. A total of 6 RCTs comparing NAC (n=1393) with SA (n=1358) published from 2002 to 2012 were identified. Compared with SA, NAC tended to reduce overall recurrences (21.86% vs 25.15%, RR: 0.70, 95% confidence interval [CI]: 0.32-1.56, P=0.09), and prevent vascular invasion (32.30% vs 43.12%, RR: 0.73, 95% CI: 0.53-1.00, P=0.05); and significantly lowered distant metastasis (15.58% vs 23.80%, RR: 0.66, 95% CI: 0.50-0.86, P=0.002), especially liver metastasis rate (13.00% vs 18.25%, RR: 0.71, 95% CI: 0.51-0.99, P=0.04), and associated with higher incidence of ypT0-2 cases upon resection (13.04% vs 6.42%, RR: 2.36, 95% CI: 1.02-5.44, P=0.04). All other parameters were comparable. NAC-related side-effects were generally mild. NAC mainly benefited patients with stage III disease. NAC could prevent recurrence and metastasis, associates with better tumor stages upon resection, and potentially impedes vascular invasion among CRC patients. NAC does not contribute to significant survival benefits for CRC, and compares favorably with SA in tumor-free resection rates, nodal status upon resection, and postsurgical complications. This level 1a evidence does not support NAC to obviously outweigh SA in terms of survival and surgical benefits for CRC currently.


Summary of hunting injuries in central Wisconsin: a 4-year experience at a rural referral center.
Surveillance of hunting-associated injuries was performed over a 4-year period at a rural Emergency Department in central Wisconsin. Over that period of time, 125 individuals sought treatment for hunting-related injuries. The majority of injuries were related to autumn deer hunting and included both gun and bow and arrow hunting. Over half of the persons injured while hunting with a bow and arrow fell from a height. The admission rate for persons in the immediate area was 35.1%, but for those from outside the area, it was 64.8%. The effects of the referral bias result in severe injuries being seen in rural Emergency Departments during hunting seasons, necessitating such departments to be prepared for a wide range of injuries.


Mouse embryonic stem cells resist c-Jun induced differentiation when in suspension.
The oncogene c-Jun plays a key role in development and cancer. Yet, its role in cell fate decision remains poorly understood at the molecular level. Here we report that c-Jun confers different fate decisions upon mouse embryonic stem cells (mESCs) in adhesion vs suspension culture. We developed a Tet-on system for temporal induction of c-Jun expression by Doxycycline treatment in mESCs. We show that mESCs carrying the inducible c-Jun TetOn remain pluripotent and grow slowly in suspension when c-Jun expression is induced, whilst when the cells adhere they undergo differentiation and show normal proliferative potential upon c-Jun induction. Our data indicates that c-Jun pushes mESCs in suspension into cell cycle arrest at G1/S, by activating the cell cycle inhibitors Cdkn1a/b and Cdkn2/a/b/c. Despite this cell cycle arrest, they can still re-enter the cell cycle upon transfer to an adhesive surface, and grow into typical mESC colonies, albeit at a lower efficiency. These results demonstrate that mESCs respond to induced c-Jun overexpression differently in suspension or adherent cultures. Our results suggest that cells in suspension may be more resistant to differentiation than when they adhere.


Single polymeric microfiber waveguide platform for sensitive detection and discrimination of DNA methylation.
The development of a rapid and sensitive detection platform for DNA and DNA methylation in complex biological environments has attracted considerable attention. Herein, we describe a detection platform for p16 and p16 methylation in buffer and serum based on a single polymeric fluorescent microfiber waveguide with sandwich-structured hybridization designs. The target p16 could be captured by oligonucleotides conjugated on the surface of polymeric microfibers and oligonucleotides conjugated with gold nanoparticles, resulting in quenching the out-coupled tip emission of the microfiber waveguide. Then the restriction digestion enzyme HpaII was applied to specifically recognize the unmethylated 5'-CCGG-3' site and cut the formed sandwich structure. The gold nanoparticles could be removed from the surface of chitosan fiber so that the out-coupled tip emission of the polymeric fluorescent microfiber would be partially recovered. It is noteworthy that the proposed polymeric microfiber waveguide platform exhibited selective and sensitive detection of p16 with a low limit of 2 pM and excellent analytical performance of methylation as low as 5% difference. This strategy avoids the use of traditional PCR-based amplification and tedious operative processes, and we envisage that this technique could be extended to various DNA methylation analyses, which is meaningful for early clinical diagnosis of diseases.


Synergistic effect of adrenergic and muscarinic receptor activation on [Ca2+]i in rabbit ciliary body epithelium.
1. Changes in cytosolic free calcium concentration ([Ca2+]i) in response to cholinergic and adrenergic agents alone and in combination were investigated using fura-2 fluorescence imaging in intact non-pigmented epithelial cells of rabbit ciliary body. 2. Resting ('baseline') [Ca2+]i was 147 +/- 6 nM (mean +/- S.E.M.). Acetylcholine (ACh, 10 microM) doubled [Ca2+]i, and adrenaline (1 microM) increased it by about 36%. When ACh (10 microM) and adrenaline (1 microM) were applied together [Ca2+]i was transiently increased to 1160 +/- 160 nM, about 7 times the response induced by ACh alone. 3. Noradrenaline and 5-bromo-6-(2-imidazolin-2-yl-amino)-quinoxaline (UK 14304) had effects similar to adrenaline in enhancing the response to ACh. Phenylephrine (Phe) had a relatively smaller effect and none was observed for methoxamine and isoprenaline (Iso). 4. The response to ACh and adrenaline could be blocked by atropine (1 microM, 87 +/- 5%), yohimbine (1 microM, 73 +/- 8%), and to a lesser degree by prazosin (1 microM). Propranolol had no effect. 5. Lowering the extracellular calcium concentration to 3 nM dropped the baseline [Ca2+]i by half and reduced the response to ACh and adrenaline to a small and transient rise in [Ca2+]i. Addition of La3+ to Ca(2+)-containing solution also lowered [Ca2+]i and largely reduced the response. 6. We conclude that simultaneous activation of muscarinic and alpha 2-adrenergic receptors induces a large increase in [Ca2+]i, which is the result of both Ca2+ release and influx.


Ligand recognition and helical stacking formation are intimately linked in the SAM-I riboswitch regulatory mechanism.
Riboswitches are noncoding mRNA elements that control gene expression by altering their structure upon metabolite binding. Although riboswitch crystal structures provide detailed information about RNA-ligand interactions, little knowledge has been gathered to understand how riboswitches modulate gene expression. Here, we study the molecular recognition mechanism of the S-adenosylmethionine SAM-I riboswitch by characterizing the formation of a helical stacking interaction involving the ligand-binding process. We show that ligand binding is intimately linked to the formation of the helical stacking, which is dependent on the presence of three conserved purine residues that are flanked by stacked helices. We also find that these residues are important for the formation of a crucial long-range base pair formed upon SAM binding. Together, our results lend strong support to a critical role for helical stacking in the folding pathway and suggest a particularly important function in the formation of the long-range base pair.


Intraoperative Extubation Post Arterial Switch Operation for Transposition of the Great Arteries With Intact Ventricular Septum: A One-Year, Single Center Experience.
We sought to examine the clinical impact of intraoperative extubation (IE) in neonates undergoing the arterial switch operation (ASO) for D-transposition of the great arteries with intact ventricular septum (dTGA/IVS). This was a single center retrospective study of patients who underwent ASO for dTGA/IVS in the 12 months after an institutional change in practice favoring IE when clinically feasible. A control group was obtained by identifying the same number of consecutive patients with dTGA/IVS who underwent ASO immediately prior to this institutional change in practice, none of whom were extubated intraoperatively. Primary outcome measures included morbidity, mortality, length of hospital and intensive care unit stay and reintubation rates. There were no significant differences in the preoperative and operative characteristics between the 2 groups. Of the 10 patients who underwent ASO for dTGA/IVS in the 12 months post institutional change in practice, all (100%) were extubated intraoperatively and none (0%) required reintubation. The median length of intensive care unit stay was 2 days for both the intraoperative and non-IE groups (mean 2.2 and 3 days respectively). The median length of stay in hospital was 4 days in the IE group and 5.5 days in the non-IE group (mean 4.5 and 6 days respectively). No patients died and there was no significant difference in morbidity between the 2 groups. Our data suggests IE post ASO for dTGA/IVS is safe and displays a statistically insignificant trend toward earlier discharge from hospital.


The role of economic and cultural status as risk indicators for alcohol and marijuana use among adolescents.
A number of reports suggest that Aboriginal cultural status is a major risk indicator for drug and alcohol use. The primary purpose of the present paper was to determine whether Aboriginal cultural status is independently associated with risk behaviours, such as marijuana use and alcohol abuse, among youth after multivariate adjustment for other factors, such as socioeconomic status. Every student between grades 5 and 8 in Saskatoon, Saskatchewan, was asked to complete a questionnaire in February 2007. Logistic regression was used to determine the independent risk indicators associated with alcohol abuse and marijuana use. Four thousand ninety-three youth participated in the school health survey. At the cross-tabulation level, cultural status and neighbourhood income were both strongly associated with alcohol and marijuana use. After multivariate adjustment, the association between Aboriginal cultural status and alcohol abuse was not statistically significant (crude OR=3.52 to adjusted OR=0.80). For marijuana use, the association was significantly reduced (crude OR=9.91 to adjusted OR=2.79). After controlling for all other variables, results showed that low-income youth were 103% more likely to get drunk at least once and were 163% more likely to have tried marijuana at least once. To be more successful, future policies directed toward reducing risk behaviours among youth should consider neighbourhood income characteristics.


Diacylglycerol kinase-zeta localization in skeletal muscle is regulated by phosphorylation and interaction with syntrophins.
Syntrophins are scaffolding proteins that link signaling molecules to dystrophin and the cytoskeleton. We previously reported that syntrophins interact with diacylglycerol kinase-zeta (DGK-zeta), which phosphorylates diacylglycerol to yield phosphatidic acid. Here, we show syntrophins and DGK-zeta form a complex in skeletal muscle whose translocation from the cytosol to the plasma membrane is regulated by protein kinase C-dependent phosphorylation of the DGK-zeta MARCKS domain. DGK-zeta mutants that do not bind syntrophins were mislocalized, and an activated mutant of this sort induced atypical changes in the actin cytoskeleton, indicating syntrophins are important for localizing DGK-zeta and regulating its activity. Consistent with a role in actin organization, DGK-zeta and syntrophins were colocalized with filamentous (F)-actin and Rac in lamellipodia and ruffles. Moreover, extracellular signal-related kinase-dependent phosphorylation of DGK-zeta regulated its association with the cytoskeleton. In adult muscle, DGK-zeta was colocalized with syntrophins on the sarcolemma and was concentrated at neuromuscular junctions (NMJs), whereas in type IIB fibers it was found exclusively at NMJs. DGK-zeta was reduced at the sarcolemma of dystrophin-deficient mdx mouse myofibers but was specifically retained at NMJs, indicating that dystrophin is important for the sarcolemmal but not synaptic localization of DGK-zeta. Together, our findings suggest syntrophins localize DGK-zeta signaling complexes at specialized domains of muscle cells, which may be critical for the proper control of lipid-signaling pathways regulating actin organization. In dystrophic muscle, mislocalized DGK-zeta may cause abnormal cytoskeletal changes that contribute to disease pathogenesis.


Loss of heterozygosity at the NAD(P)H: quinone oxidoreductase locus associated with increased resistance against mitomycin C in a human bladder carcinoma cell line.
The human bladder carcinoma cell line RT112 and the mitomycin C-resistant cell line RT112MMC, derived from RT112 cells, were examined for their expression of NAD(P)H:quinone oxidoreductase (NQOR) and glutathione S-transferases (GSTs). RT112 cells were 40-fold more sensitive towards mitomycin C than RT112MMC cells. The NQOR mRNA level in RT112MMC cells was decreased to 15% as compared to RT112 cells. NQOR enzyme activity was 391 +/- 140 mU/mg protein in RT112 cells, whereas NQOR activity in RT112MMC cells was not measurable. As shown by a fast PCR-based assay and DNA-sequencing, the cell line RT112 is heterozygous, whereas RT112MMC is homozygous for a null allele of the NQOR gene without enzymatic activity. Accordingly, both wild-type and null allele mRNAs were present in RT112 cells, whereas only null allele mRNA was found in RT112MMC. The lack of NQOR enzyme activity in RT112MMC cells was thus associated with loss of heterozygosity at the NQOR locus. By a PCR-RFLP assay, three kidney carcinoma patients without measurable NQOR enzyme activity were shown to be homozygous for the null allele. The PCR assay described here is useful for examination of large numbers of samples. The relative amount of GST-Pi mRNA was decreased by 30% in RT112MMC as compared to RT112, contributing to a diminished level of GST enzyme activity, using CDNB as a substrate, from 95 +/- 62 mU/mg protein in RT112 to 26 +/- 6 mU/mg protein in RT112MMC.


Asymmetrical introgression between two Morus species (M. alba, M. rubra) that differ in abundance.
Asymmetrical introgression is an expected genetic consequence of hybridization when parental taxa differ in abundance; however, evidence for such effects in small populations is scarce. To test this prediction, we estimated the magnitude and direction of hybridization between red mulberry (Morus rubra L.), an endangered species in Canada, and the introduced and more abundant white mulberry (Morus alba L.) using nuclear (randomly amplified polymorphic DNA) and cytoplasmic (chloroplast DNA sequence) markers. Parentage of 184 trees (n = 42 using cpDNA) from four sympatric populations was estimated using a hybrid index and related to six morphological characters and population frequencies of the parental classes. Overall, the frequency of nuclear hybrids was 53.7% (n = 99) and ranged from 43% to 67% among populations. The parental and hybrid taxa differed with respect to all of the morphological traits. Sixty-seven percent of all hybrids contained more nuclear markers from M. alba than M. rubra (hybrid index x = 0.46); among populations, the degree of M. alba bias was correlated with the frequency of M. alba. In addition, the majority of hybrids (68%) contained the chloroplast genome of white mulberry. These results suggest that introgression is bidirectional but asymmetrical and is related, in part, to the relative frequency of parental taxa.


Probing the mer- to fac-isomerization of tris-cyclometallated homo- and heteroleptic (C,N)3 iridium(III) complexes.
We have developed techniques which allow for covalent tethering, via a "hetero" cyclometallating ligand, of heteroleptic tris-cyclometallated iridium(III) complexes to polymeric supports (for application in light-emitting diode technologies). This involved the selective synthesis and thorough characterization of heteroleptic [Ir(C,N) 2(C',N')] tris-cyclometallated iridium(III) complexes. Furthermore, the synthesis and characterization of heteroleptic [Ir(C,N) 2OR] complexes is presented. Under standard thermal conditions for the synthesis of the facial ( fac) isomer of tris-cyclometallated complexes, it was not possible to synthesize pure heteroleptic complexes of the form [Ir(C,N) 2(C',N')]. Instead, a mixture of homo- and heteroleptic complexes was acquired. It was found that a stepwise procedure involving the synthesis of a pure meridonial ( mer) isomer followed by photochemical isomerization of this mer to the fac isomer was necessary to synthesize pure fac-[Ir(C,N) 2(C',N')] complexes. Under thermal isomerization conditions, the conversion of mer-[Ir(C,N) 2(C',N')] to fac-[Ir(C,N) 2(C',N')] was also not a clean reaction, with again a mixture of homo- and heteroleptic complexes acquired. An investigation into the thermal mer to fac isomerization of both homo- and heteroleptic tris-cyclometallated complexes is presented. It was found that the process is an alcohol-catalyzed reaction with the formation of an iridium alkoxide [Ir(C,N) 2OR] intermediate in the isomerization process. This catalyzed reaction can be carried out between 50 and 100 degrees C, the first such example of low-temperature mer-fac thermal isomerization. We have synthesized analogous complexes and have shown that they do indeed react so as to give fac-tris-cyclometallated products. A detailed explanation of the intermediates (and all of their stereoisomers, in particular when systems of the generic formula [M(a,b) 2(a',b')] are synthesized) formed in the mer to fac isomerization process is presented, including how the formed intermediates react further, and the stereoisomeric products they yield.


Evaluating new and traditional methods for aminoglycoside dosing in patients with various degrees of renal function.
Aminoglycosides are widely used, and clinicians continue to seek newer and better methods for initial dosing of these agents. Recently, three new methods were introduced: Thomson, Reesor Nimmo, and dosing in renopathy by easy-to-use multipliers (DREM). In comparing them with older, traditional dosing methods in patients with various degrees of renal function, the pharmacokinetic variables of gentamicin were determined from steady-state peak (Cmax) and trough (Cmin) serum concentrations using individualized regimens in 88 patients. Dosages were determined in each patient using the method of Hull-Sarubbi, rule of eights, and the three new methods, and the resultant Cmax and Cmin values were calculated from dosages generated by each method. The daily doses and Cmax values derived with the Hull-Sarubbi, Thomson, and Reesor Nimmo methods were not significantly different (p > 0.05). The Hull-Sarubbi was the most precise (root mean squared prediction error 1.3) and least biased (mean prediction error -0.05) of the five methods in predicting target gentamicin serum peak concentrations (Cmax 6.5 mg/L). The Hull-Sarubbi (69%), Thomson (86%), and Reesor Nimmo (70%) methods yielded therapeutic Cmax (5-8 mg/L) in a significantly higher percentage of patients than did the rule of eights (32%) and DREM (35%), (p < 0.05). Therefore, if gentamicin serum concentrations are not available, the first three appear to be reasonable methods for initiating gentamicin dosage regimens, but the last two may not be desirable to use in a clinical setting. These conclusions are based on the assumption that patients are adults with stable renal function and relatively stable clinical conditions.


Probabilistic shaping and forward error correction scheme employing uneven segmentation mapping for data center optical communication.
The combination of probabilistic shaping (PS) technology and forward error correction (FEC) technology can significantly boost the performance of a transmission system. In this paper, we propose a probabilistic shaping distribution matching algorithm employing uneven segmentation for data center optical networks, while keeping extremely low computational complexity for both encoding and decoding. Based on the proposed probabilistic shaping distribution matching algorithm, we develop a novel integrated scheme of PS and FEC coding that lifts the restrictions on the use of FEC technology and increases the use of interleaver. An experiment used to evaluate the probabilistically shaped data transmission is successfully conducted over a 25 km standard single-mode fiber (SSMF) with 16 quadrature amplitude modulation (16-QAM). Simultaneously, we use a simulation software to analyze the bit error rate performance at higher resolution. The results show that the joint coding scheme can achieve a 0.4dB performance improvement compared with the single FEC system.


Dihydrostreptomycin Directly Binds to, Modulates, and Passes through the MscL Channel Pore.
The primary mechanism of action of the antibiotic dihydrostreptomycin is binding to and modifying the function of the bacterial ribosome, thus leading to decreased and aberrant translation of proteins; however, the routes by which it enters the bacterial cell are largely unknown. The mechanosensitive channel of large conductance, MscL, is found in the vast majority of bacterial species, where it serves as an emergency release valve rescuing the cell from sudden decreases in external osmolarity. While it is known that MscL expression increases the potency of dihydrostreptomycin, it has remained unclear if this effect is due to a direct interaction. Here, we use a combination of genetic screening, MD simulations, and biochemical and mutational approaches to determine if dihydrostreptomycin directly interacts with MscL. Our data strongly suggest that dihydrostreptomycin binds to a specific site on MscL and modifies its conformation, thus allowing the passage of K+ and glutamate out of, and dihydrostreptomycin into, the cell.


Validity of verbal autopsy in determining causes of adult deaths.
A verbal autopsy (VA) questionnaire, which had an open-ended description of the deceased's illness followed by a series of close-ended questions on specific symptoms and signs, was used by three trained field workers to interview relatives of the deceased who had died in a Chandigarh hospital in previous year. The sensitivity and specificity of the cause of death assigned by physician from the verbal autopsy was calculated against the cause of death derived from the hospital records. Of the 262 verbal autopsies, 60% were males and 23% belonged to rural area. Specificity of VA cause of death was high (>95%) for all broad cause groups except cardiovascular (79%) diseases. Sensitivity was highest for injuries (85%) and it was in the range of 60% to 65% for circulatory diseases, neoplasms, and infectious diseases. Sensitivity was low (20% to 40%) for respiratory, digestive and endocrine diseases. Cause specific proportionate mortality for major cause groups by the VA were statistically similar to the causes of deaths derived from the hospital records (p>0.05). Therefore, VA can be used for determining causes of adult deaths.


Vascular calcification: an update on mechanisms and challenges in treatment.
Vascular calcification is highly associated with cardiovascular disease mortality, particularly in high-risk patients with diabetes and chronic kidney diseases (CKD). In blood vessels, intimal calcification is associated with atherosclerosis, whereas medial calcification is a nonocclusive process which leads to increased vascular stiffness and reduced vascular compliance. In the valves, calcification of the leaflets can change the mechanical properties of the tissue and result in stenosis. For many decades, vascular calcification has been noted as a consequence of aging. Studies now confirm that vascular calcification is an actively regulated process and shares many features with bone development and metabolism. This review provides an update on the mechanisms of vascular calcification including the emerging roles of the RANK/RANKL/OPG triad, osteoclasts, and microRNAs. Potential treatments adapted from osteoporosis and CKD treatments that are under investigation for preventing and/or regressing vascular calcification are also reviewed.


Cardiac function and central circulation in lysine-vasopressin treatment of experimental burns.
Anesthetized piglets were subjected to a standardized full thickness skin burn, covering one third of the body surface area, and given fluid treatment. One group was also submitted to early excision of the burned area 5 h after the burn and another group was excised and given lysine-vasopressin by continuous infusion. In both the excised groups there was earlier circulatory restitution compared with the conservatively treated animals. After 24 h, cardiac function was best in the pigs treated with vasopressin and excision. The mechanisms by which vasopressin treatment and excision might have favourable circulatory effects in burn treatment are discussed.


The influence of prenatal exposure to trans-fatty acids for development of childhood haematopoietic neoplasms (EnTrance): a natural societal experiment and a case-control study.
Little is known about the causes of childhood cancer, partly as not many children develop cancer, although childhood cancer is a leading cause of death by disease in the young. The young age of the children suggests that risk factors for childhood cancer may be present during pregnancy. Previous studies have shown that exposure to trans-fat, a type of unsaturated fat common in industrially produced foods (iTFA), has adverse health effects in adults, including the risk of developing cancer. Haematopoietic neoplasms are the most common cancer types among European children under the age of 15 years. This study will bring new knowledge as to whether trans-fat and other fatty acids may also increase the risk of developing haematopoietic neoplasms during childhood. We will investigate if the Danish iTFA legislation ban, which radically reduced the use of iTFA in foodstuffs, influenced the risk of childhood haematopoietic neoplasms in children born either before or after the change in legislation, adjusting for relevant secular trends. Further, in a case-control study, we will examine if levels of fatty acids in dried blood spots from newborns can predict the risk of developing childhood haematopoietic neoplasms. Permission from the Danish Data Protection Agency and the Ethical Committee has been granted. The results from this study will provide important information about fatty acids in the mother's diet as a contributor to development of haematopoietic neoplasms during childhood, which may result in relevant preventive action. Not relevant.


Metagenomics of infective canaliculitis: The Lacriome paper 3.
To study the metagenomics of the microbes isolated from the canaliculus of patients with infective canaliculitis. A prospective study was performed on five consecutive canalicular samples obtained for the metagenomic analysis from the patients with infective canaliculitis who underwent non-incisional canalicular curettage at a tertiary care Dacryology service. The canalicular concretions were collected intraoperatively soon after a canalicular curettage and immediately transported on ice to the laboratory. Following DNA extraction and library preparation, a whole shotgun metagenome sequencing was performed on the Illumina™ platform. The downstream processing and bioinformatics of the samples were performed using multiple software packaged in SqueezeMeta™ pipeline or MG-RAST™ pipeline. The taxonomic hit distribution across the samples showed that bacteria were the most common isolates (mean-80.5%), followed by viruses (mean-0.74%), and archaea (0.01%). The five major phyla identified across the samples of infective canaliculitis were, Fusobacteria, Bacteroidetes, Proteobacteria, Actinobacteria, and Firmicutes. The prevalent organisms include Fusobacterium nucelatum, Fusobacterium periodonticum, Parvimonas micra, Prevotella oris, Selonomonas noxia, Pseudopropionobacterium propoinicum, Campylobacter showae, and Streptococcus anginosus, amongst few others. Actinomycetes israelii was noted in all the samples, though it was not the most abundant. The microbial gene mapping and protein prediction demonstrated proteins with known functions to range from 69.91% to 87.09% across the samples. The functional subsystem profiling demonstrated genes associated with carbohydrate, amino acid, and co-enzyme transport and metabolism, cell wall or cell membrane biogenesis, energy production and conversion, transcription, translation, and cellular communications. This is the first whole metagenome sequencing of infective canaliculitis. Infected canaliculi harbor diverse microbial communities, including bacteria, viruses, and archaea. Functional analysis has provided newer insights into the ecosystem dynamics and strategies of microbial communities.


BIG LEAF is a regulator of organ size and adventitious root formation in poplar.
Here we report the discovery through activation tagging and subsequent characterization of the BIG LEAF (BL) gene from poplar. In poplar, BL regulates leaf size via positively affecting cell proliferation. Up and downregulation of the gene led to increased and decreased leaf size, respectively, and these phenotypes corresponded to increased and decreased cell numbers. BL function encompasses the early stages of leaf development as native BL expression was specific to the shoot apical meristem and leaf primordia and was absent from the later stages of leaf development and other organs. Consistently, BL downregulation reduced leaf size at the earliest stages of leaf development. Ectopic expression in mature leaves resulted in continued growth most probably via sustained cell proliferation and thus the increased leaf size. In contrast to the positive effect on leaf growth, ectopic BL expression in stems interfered with and significantly reduced stem thickening, suggesting that BL is a highly specific activator of growth. In addition, stem cuttings from BL overexpressing plants developed roots, whereas the wild type was difficult to root, demonstrating that BL is a positive regulator of adventitious rooting. Large transcriptomic changes in plants that overexpressed BL indicated that BL may have a broad integrative role, encompassing many genes linked to organ growth. We conclude that BL plays a fundamental role in control of leaf size and thus may be a useful tool for modifying plant biomass productivity and adventitious rooting.


An epidemiological perspective of obsessive-compulsive disorder in children and adolescents.
Obsessive-compulsive disorder (OCD) is reviewed from an epidemiological perspective. OCD is defined according to the DSM-IV and ICD-10, with differences noted between these two classification systems. The epidemiological rubrics of quantity (prevalence), location (genetic methods and gender differences), cause (genetic etiology), and causal mechanisms (natural history and clinical course) are reviewed. The review concludes that more research is needed to further understand the epidemiology of OCD in children and adolescents, both from a Canadian and worldwide perspective.


Impaired in vitro fertilization outcomes following testosterone treatment improve with washout in a mouse model of gender-affirming hormone treatment.
The impact of gender-affirming testosterone on fertility is poorly understood, with ovarian histopathologic studies showing variable results, some with a detrimental effect on reproductive capacity and uncertain reversibility. Assisted reproductive outcome data are restricted to small case series that lack the ability to inform clinical practice guidelines and limit fertility preservation counseling for transgender and nonbinary individuals. This study aimed to determine the impact of current testosterone and testosterone washout on in vitro fertilization outcomes in a mouse model for gender-affirming hormone treatment. We hypothesized that current or previous testosterone treatment would not affect in vitro fertilization outcomes. C57BL/6N female mice (n=120) were assigned to 4 treatment groups: (1) current control, (2) current testosterone, (3) control washout, and (4) testosterone washout. Testosterone implants remained in situ for 6 or 12 weeks, representing the short- and long-term treatment arms, respectively. Current treatment groups underwent ovarian stimulation with implants in place, and washout treatment groups were explanted and had ovarian stimulation after 2 weeks. Oocytes were collected, fertilized, and cultured in vitro, with one arm continuing to the blastocyst stage and the other having transfer of cleavage-stage embryos. Statistical analysis was performed using GraphPad Prism, version 9.0 and R statistical software, version 4.1.2, with statistical significance defined by P<.05. Current long-term testosterone treatment impaired in vitro fertilization outcomes, with fewer mature oocytes retrieved (13.7±5.1 [standard deviation] vs 28.6±7.8 [standard deviation]; P<.0001) leading to fewer cleavage-stage embryos (12.1±5.1 vs 26.5±8.2; P<.0001) and blastocysts (10.0±3.2 vs 25.0±6.5; P<.0001). There was recovery of in vitro fertilization outcomes following washout in the short-term treatment cohort, with incomplete reversibility in the long-term cohort. Testosterone did not negatively affect maturity, fertilization, or blastulation rates. In a mouse model of gender-affirming hormone treatment, testosterone negatively affected oocyte yield without affecting oocyte quality. Our findings suggest that testosterone reversibility is duration-dependent. These results demonstrate the feasibility of in vitro fertilization without testosterone discontinuation while supporting a washout period for optimization of mature oocyte yield.


A sensitive molecular assay for mutagenesis in mammalian cells: reversion analysis in cells with a mutant shuttle vector gene integrated into chromosomal DNA.
We have developed a system for the molecular analysis of mutations in mammalian cells. This system is based upon the use of mammalian cell lines containing mutant shuttle vector genes integrated into chromosomal DNA. The target for mutation was the Escherichia coli gpt gene, coding for the enzyme xanthine (guanine) phosphoribosyltransferase (GPT; EC 188.8.131.52). We have previously isolated a large number of cell lines containing mutant gpt genes with single base changes. From these lines, revertants were selected on the basis of the reappearance of GPT activity. In general, the frequency of revertants was below 10(-7). The gpt genes were recovered from 32 revertants and sequenced to determine the nature of the base changes associated with reversion. In the majority of the revertants, there was a base change within the originally mutated codon, leading to either restoration of the wild-type amino acid sequence or substitution of a different amino acid at the original mutated site. In no case did reversion of a base substitution mutant involve an amino acid residue other than that affected by the original mutation. The results have demonstrated a number of sites in the GPT polypeptide at which amino acid substitutions are compatible with enzyme activity and one site at which the loss of an amino acid is compatible with enzyme activity. This study establishes reversion analysis as a sensitive molecular assay for mutagenesis in mammalian cells.


Properties of skin stem cells and their potential clinical applications in modern dermatology.
Stem cells play an important role in medical science, and scientists are investing large sums in order to perform sophisticated studies designed to establish potential clinical applications of stem cells. Growing experience has enabled researchers to determine the precise nature of stem cell division. Although the properties of this particular population of cells have been known and used for some time, mainly with regards to bone marrow-derived mesenchymal stem cell transplantation, we now face a significant challenge in implementing the practical use of skin-derived precursors, making it possible to avoid the necessity for patients to undergo invasive procedures in order to obtain stem cells from bone marrow. Multiple trials have so far been performed, bringing hope for the treatment of disorders previously considered untreatable. Patients suffering from a number of dermatological diseases, including malignant melanoma, systemic lupus erythematosus, vitiligo, alopecia or junctional epidermolysis bullosa, may benefit from treatment based on stem cells. The aim of this review is to summarize available data on stem cells and their potential applications in the treatment of dermatological disorders. The work described is based on data published up to the end of September 2016.


Application of Plasmid Engineering to Enhance Yield and Quality of Plasmid for Vaccine and Gene Therapy.
There is an increased interest in plasmid DNA as therapeutics. This is evident in the number of ongoing clinical trials involving the use of plasmid DNA. In order to be an effective therapeutic, high yield and high level of supercoiling are required. From the bioprocessing point of view, the supercoiling level potentially has an impact on the ease of downstream processing. We approached meeting these requirements through plasmid engineering. A 7.2 kb plasmid was developed by the insertion of a bacteriophage Mu strong gyrase-binding sequence (Mu-SGS) to a 6.8 kb pSVβ-Gal and it was used to transform four different E. coli strains, and cultured in order to investigate the Mu-SGS effect and dependence on strain. There was an increase of over 20% in the total plasmid yield with pSVβ-Gal398 in two of the strains. The supercoiled topoisomer content was increased by 5% in both strains leading to a 27% increase in the overall yield. The extent of supercoiling was examined using superhelical density (σ) quantification with pSVβ-Gal398 maintaining a superhelical density of -0.022, and pSVβ-Gal -0.019, in both strains. This study has shown that plasmid modification with the Mu-phage SGS sequence has a beneficial effect on improving not only the yield of total plasmid but also the supercoiled topoisomer content of therapeutic plasmid DNA during bioprocessing.


Herbicide selection of Italian ryegrass under different levels of UVB radiation.
Ultraviolet-B radiation is an environmental stress for plants and this situation could become aggravated in the next decades. In this study we used Italian ryegrass (Lolium multiflorum Lam.) as a model system to test whether an environmental stress derived from global change, such as UVB, can influence the efficacy of control procedures and evolution toward herbicide resistance. We grew three generations of Italian ryegrass plants with and without UVB light and subjected them to a series of diclofop-methyl [(+/-)-2-[4-(2,4-dichlorophenoxy) phenoxy] propanoic acid, methyl ester] doses. The effect of selection history was tested with herbicide dose response. The effect of herbicide application on plant survival and biomass varied significantly among herbicide doses and with absence or presence of UVB light. In the absence of herbicide, the decrease in individual fecundity with increasing plant density was similar under both no-UVB and UVB light treatments. Only plants growing without UVB light increased production of reproductive structures in response to the decrease in density caused by herbicide application. Our study shows that UVB light was a weak stress factor for the ryegrass plants. However, when herbicide selection pressure was high, UVB light reduced the evolution toward herbicide tolerance. When selection pressure on the parental plants was lower, the two stress factors had a synergistic effect, causing changes in herbicide efficacy that in turn had demographic and evolutionary consequences. In the field, these interactions between stress factors might be of significance for annual weeds in which seed output is a major determinant in fitness.


Collective bargaining among nurses: current issues and future prospects.
Collective bargaining has made substantial progress in the health care industry in recent years, especially among nurses. It is important for health care administrators to consider the underlying issues and the future prospects for collective bargaining by this critical group of health care providers.


Prevalence and Associated Factors of Anxiety and Depressive Symptoms Among Bereaved Family Members of Cancer Patients in Korea: A Nation-Wide Cross-Sectional Study.
Bereaved family members of cancer patient are at risk of having psychological problems such as anxiety and depression. However, prevalence and associated factors of anxiety and depressive symptoms among this population have not been explored in Korea.We conducted a nation-wide cross-sectional questionnaire survey of 3522 bereaved family members of cancer patients who died at 44 hospice palliative care unit (HPCU) in Korea in 2012. The questionnaire comprised the Hospital Anxiety and Depression Scale (HADS) and Good Death Inventory (GDI). Deceased patient's age, sex, primary site of cancer, duration of stay at HPCU, awareness of terminal status, bereaved family member's age, sex, and relation to the deceased were collected from Korean Terminal Cancer Patients Information System.1121 returned questionnaires were analyzed (response rate, 31.8%). Using a cut-off value of 8 for HADS subscale, the prevalence of anxiety and depressive symptoms was 48.0% and 57.6%, respectively. Mean scores for HADS-A and HADS-D were 7.88 ± 4.87 and 8.91 ± 4.82, respectively. Among the bereaved, older age, being a spouse to the deceased, family members of younger patient, and negative score for a few GDI items were significantly associated with an increased risk of having anxiety or depressive symptoms in the multivariate logistic analysis.In conclusion, we noted the high prevalence of anxiety and depressive symptoms among the bereaved of cancer patients and identified associated factors for these psychological morbidities. Systematic efforts are needed to improve the mental health of the bereaved family members of cancer patients.


Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats.
Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures.


Serum cystatin C reliably detects renal dysfunction in patients with various renal diseases.
A clinical investigation was conducted to clarify the reliability and efficacy of serum cystatin C measurement for estimation of the glomerular filtration rate (GFR). Two hundred twelve patients with various renal diseases enrolled in the study. All patients were evaluated for 24-hour creatinine clearance (24 h C(Cr)) and the standard sodium thiosulfate clearance test (C(Thio)) within a week of blood sample collection. Serum cystatin C concentration was determined by a particle-enhanced immunonephelometry method. C(Thio) and 1/cystatin C, 24 h C(Cr), 1/beta2-microglobulin and 1/creatinine were well correlated. The correlation coefficients for C(Thio) obtained by 24 h C(Cr) and 1/cystatin C were comparable to each other (0.701 vs. 0.679). Receiver-operated characteristic (ROC) analysis revealed that 24 h C(Cr) showed the highest area under the curve when C(Thio) = 60 ml/min or C(Thio) = 100 ml/min were applied as the discrimination point. However, the ROC value obtained by cystatin C was slightly greater than 24 h C(Cr) when C(Thio) = 80 ml/min was used as the discrimination point. Patient age, gender, glucose tolerance, presence of proteinuria, systemic inflammation, lupus, or systemic use of steroids did not interfere in the relationship between C(Thio) and 1/cystatin C. In conclusion, serum cystatin C measurement is an excellent diagnostic test for detecting patients with subclinical renal dysfunction.


Adductor insertion avulsion syndrome with stress fracture of femoral shaft: MRI findings.
Chronic vague hip pain may be caused by stress-related injury in the proximal or mid-femoral diaphysis. This has been described as an entity called adductor insertion avulsion syndrome, or thigh splints. In the appropriate clinical setting, the radiologist interpreting the magnetic resonance imaging must be aware of this condition as its imaging findings are subtle. The diagnosis will help the clinician plan the appropriate management. Magnetic resonance imaging can also depict the complications such as stress fracture.


Tobacco smoking and risk of 36 cardiovascular disease subtypes: fatal and non-fatal outcomes in a large prospective Australian study.
Tobacco smoking is a leading cause of cardiovascular disease (CVD) morbidity and mortality. Evidence on the relation of smoking to different subtypes of CVD, across fatal and non-fatal outcomes, is limited. A prospective study of 188,167 CVD- and cancer-free individuals aged ≥ 45 years from the Australian general population joining the 45 and Up Study from 2006 to 2009, with linked questionnaire, hospitalisation and death data up to the end of 2015. Hazard ratios (HRs) for hospitalisation with or mortality from CVD among current and past versus never smokers were estimated, including according to intensity and recency of smoking, using Cox regression, adjusting for age, sex, urban/rural residence, alcohol consumption, income and education. Population-attributable fractions were estimated. During a mean 7.2 years follow-up (1.35 million person-years), 27,511 (crude rate 20.4/1000 person-years) incident fatal and non-fatal major CVD events occurred, including 4548 (3.2) acute myocardial infarction (AMI), 3991 (2.8) cerebrovascular disease, 3874 (2.7) heart failure and 2311 (1.6) peripheral arterial disease (PAD) events. At baseline, 8% of participants were current and 34% were past smokers. Of the 36 most common specific CVD subtypes, event rates for 29 were increased significantly in current smokers. Adjusted HRs in current versus never smokers were as follows: 1.63 (95%CI 1.56-1.71) for any major CVD, 2.45 (2.22-2.70) for AMI, 2.16 (1.93-2.42) for cerebrovascular disease, 2.23 (1.96-2.53) for heart failure, 5.06 (4.47-5.74) for PAD, 1.50 (1.24-1.80) for paroxysmal tachycardia, 1.31 (1.20-1.44) for atrial fibrillation/flutter, 1.41 (1.17-1.70) for pulmonary embolism, 2.79 (2.04-3.80) for AMI mortality, 2.26 (1.65-3.10) for cerebrovascular disease mortality and 2.75 (2.37-3.19) for total CVD mortality. CVD risks were elevated at almost all levels of current smoking intensity examined and increased with smoking intensity, with HRs for total CVD mortality in current versus never smokers of 1.92 (1.11-3.32) and 4.90 (3.79-6.34) for 4-6 and ≥ 25 cigarettes/day, respectively. Risks diminished with quitting, with excess risks largely avoided by quitting before age 45. Over one third of CVD deaths and one quarter of acute coronary syndrome hospitalisations in Australia aged < 65 can be attributed to smoking. Current smoking increases the risk of virtually all CVD subtypes, at least doubling the risk of many, including AMI, cerebrovascular disease and heart failure. Paroxysmal tachycardia is a newly identified smoking-related risk. Where comparisons are possible, smoking-associated relative risks for fatal and non-fatal outcomes are similar. Quitting reduces the risk substantially. In an established smoking epidemic, with declining and low current smoking prevalence, smoking accounts for a substantial proportion of premature CVD events.


[Proteomic expression analysis of colonic mucosa in a rat model of irritable bowel syndrome].
To explore the pathogenesis of irritable bowel syndrome (IBS) and the regulation of the network relationship between differential proteins. Sixteen female SD rats of clean grade were randomly divided into IBS group (n = 8) and control group (n = 8). A rat model of IBS was established by a special odor of mothball as a conditional stimulation and colorectal distension plus the classic conditions of physical restraint as a non-conditional stimulation in turn. The total proteins were extracted from colon mucosa of two different rat groups. After preparation of total proteins, solubilized proteins were separated by two-dimensional differential gel electrophoresis. Those differential protein spots were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). The identified proteins were classified through an online web gene ontology tool. Some of the valuable differently expressed proteins were chosen for further verification by Western blotting. Intensity changes of 19 spots were detected among 1396 protein spots. A total of 13 different proteins were identified by MALDI-TOF MS successfully; eight of these were up-regulated and five down-regulated in colon mucosa of IBS rat. The eight over-expressed proteins were cytokeratin 8, protein disulfide isomerase A3 (PDIA3), peroxiredoxin-6, cathepsin S, heterogeneous nuclear ribonucleoprotein F, eukaryotic translation initiation factor, carbonyl reductase 1, glyoxalase I; five under-expressed proteins were alpha-enolase, transgelin, serpinB5, cardiac alpha-actin 1 and 40S ribosomal protein SA. The results of Western blotting confirmed that PDIA3 was indeed over-expressed in colonic mucosa of IBS rat. Some proteins related to immunity of intestinal tract, inflammation and nerve are differently expressed in colonic mucosa of IBS rat. It is suggested that immunity, inflammation and neuro-endocrine network in gut are associated with the pathogenesis of IBS.


Distinct effector mechanisms in the development of autoimmune neuropathy versus diabetes in nonobese diabetic mice.
NOD mice deficient for the costimulatory molecule B7-2 (NOD-B7-2KO mice) are protected from autoimmune diabetes but develop a spontaneous autoimmune peripheral neuropathy that resembles human diseases Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Similar observations have now been made in conventional NOD mice. We have shown previously that this disease was mediated by autoreactive T cells inducing demyelination in the peripheral nervous system. In this study, we analyzed the molecular pathways involved in the disease. Our data showed that neuropathy developed in the absence of perforin or fas, suggesting that classic cytotoxicity pathways were dispensable for nerve damage in NOD-B7-2KO mice. In contrast, IFN-gamma played an obligatory role in the development of neuropathy as demonstrated by the complete protection from disease and infiltration in the nerves in NOD-B7-2KO mice deficient for IFN-gamma. This result was consistent with the inflammatory phenotype of T cells infiltrating the peripheral nerves. Importantly, the relative role of perforin, fas, and IFN-gamma appears completely different in autoimmune diabetes vs neuropathy. Thus, there are sharp contrasts in the pathogenesis of autoimmune diseases targeting different tissues in the same NOD background.


[Friedreich's disease, diabetes and pregnancy. Description of a case].
Birth of an infant at term to a diabetic woman with a severe form of Friedreich's disease is reported. The aetiopathogenesis of the cardiac deformities that led to the death of the child on day seven of life is discussed.


[Diagnosis of Ebstein's anomaly with transesophageal echocardiography].
We describe a 63-year old female patient presenting with increasing dyspnea on exertion. The chest X-ray was suggestive but not compelling for Ebstein's anomaly. Although Ebstein's anomaly is most often discovered first in childhood, rare cases, such as ours, are described in late adulthood, however. Obesity may be one reason why it was not possible in our patient to detect the characteristic features in transthoracic echocardiography. The diagnosis of Ebstein's anomaly could be established only by transesophageal echocardiography: There the right atrium was grossly enlarged due to the distal insertion of the septal tricuspid valve leaflet. Colour flow echocardiography clearly demonstrated severe tricuspid valve incompetence. No additional congenital or acquired cardiac disorder could be detected. Cardiac catheterization confirmed the echocardiographical findings, whereas magnetic resonance tomography did not show the abnormal insertion of the tricuspid valve leaflet. If Ebstein's anomaly is suspected and cannot be ascertained by transthoracic echocardiography, transesophageal echocardiography can be employed to definitely diagnose this fairly rare form of congenital heart disease in an adult population.


Comparison of intranasal and transdermal estradiol on nasal mucosa in postmenopausal women.
To compare nasal symptomatology and function and local concentrations of estradiol (E2), estradiol receptor (ERalpha), vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20 postmenopausal women complaining of paradoxical nasal stuffiness before and after treatment with intranasal or transdermal E2. Twenty healthy postmenopausal women willing to start hormone therapy (HT) were allocated to one of two groups, using a computer-generated randomization list. Ten postmenopausal women were treated with transdermal 17beta-estradiol 50 microg daily plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group A). Ten postmenopausal women were treated with intranasal 17beta-estradiol 300 microg/day (one spray delivery of 150 microg per nostril) plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen fertile women undergoing nasal mucosa biopsy during plastic surgery were used as controls for the immunohistochemical evaluation (Group C). All women in groups A and B underwent evaluation of nasal stuffiness score, mucociliary transport time, rhinoscopy, and active anterior rhinomanometry at the beginning of the study and after, VIP, SP, and 6 months of HT. Nasal biopsies and evaluation of local concentrations of E2, ERalpha NPY were performed in groups A and B before and after 6 months of HT and in group C. Both intranasal and transdermal HT improve nasal symptomatology and nasal mucosa appearance and reduce mean mucociliary transport time. The effectiveness of intranasally administered therapy at improving nasal function is significantly better than transdermal therapy. In comparison with premenopausal controls, untreated postmenopausal women of group A and B showed significantly decreased immunopositivity for E2, ERalpha, and SP. HT induced a significant increase in E2, ERalpha, VIP, and SP and a decrease in NPY immunopositivity. Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP. HT improves nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered HT is more effective at improving nasal function than transdermal HT.


Microwave-assisted one-step patterning of aqueous colloidal silver.
A new approach of utilizing microwave to pattern gradient concentric silver nanoparticle ring structures has been presented. The width and height of a single ring and the space between adjacent rings can be adjusted by changing the silver colloidal concentration and the microwave output power. By simply enhancing the ambient vapour pressure to the saturated value during microwave-assisted evaporation, sub-100 nm rings can be deposited in between adjacent micro-rings over a distance of millimetres. Combined with microwave sintering, this approach can also create conductive silver tracks in a single step, showing huge potential in fabricating micro- and nano-electronic devices in an ultra-fast and cost-effective fashion.


Intimate partner violence against married and cohabiting women in sub-Saharan Africa: does sexual autonomy matter?
Literature shows that women's sexual autonomy, which refers to women's capacity to refuse sex and ask a partner to use condom, has significant implications on the sexual and reproductive health outcomes and sexual-and-gender based violence. Nevertheless, there is scarcity of empirical evidence to support the association between women's sexual autonomy and intimate partner violence (IPV) in sub-Saharan Africa. Data for the study were extracted from the recent Demographic and Health Surveys in 24 countries in sub-Saharan Africa between 2010 and 2019. Bivariable and multivariable binary logistic regression analyses were performed to examine the association between sexual autonomy and IPV in all the studied countries. Statistical significance was set at p < 0.05. The pooled prevalence of IPV and sexual autonomy in the 24 countries were 38.5% and 73.0% respectively. Overall, the odds of exposure to IPV were higher among women with sexual autonomy, compared to those without sexual autonomy even after controlling for covariates (age, level of education, marital status, current working status, place of residence, wealth quintile and media exposure). At the country-level, women from Angola, Cameroon, Chad, Gabon, Cote d'lvoire, Gambia, Mali, Nigeria, Kenya, Comoros, Zambia, and South Africa who had sexual autonomy were more likely to experience IPV whilst those in Burundi were less likely to experience IPV. The study showed that sexual autonomy increases women's exposure to IPV and this occurred in many countries except Burundi where women with sexual autonomy were less likely to experience IPV. The findings highlight the need for serious programs and policies to fight against IPV in the sub-region. Additionally, laws need to be passed and implemented, with law enforcement agencies provided with the necessary resources to reduce intimate partner violence among women with sexual autonomy.


Coupled local mode method for simulating vibrational spectroscopy.
Experimental and theoretical studies have highlighted protonated water clusters (PWCs) as important models of the excess proton in aqueous systems. A significant focus has been characterizing the spectral signatures associated with different excess proton solvation motifs. Accurate vibrational frequency calculations are crucial for connecting the measured spectra to the structure of PWCs. In this paper, we extend and characterize a coupled local mode (CLM) approach for calculating the infrared spectra of PWCs using the H+(H2O)4 cluster as a benchmark system. The CLM method is relatively low cost and incorporates the anharmonicity and coupling of OH vibrations. Here, we demonstrate the accuracy of the technique compared to experiments. We also illustrate the dependence of calculated spectral features on the underlying electronic structure theory and basis sets used in the local mode frequency and coupling calculations.


The epidermal-dermal junction.
Ultrastructurally, the epidermal-dermal junction is composed of four component areas:(1) the basal cell plasma membrane with its specialized attachment devices or hemidesmosomes, (2) an electron-lucent area, the lamina lucida, (3) the basal lamina, and (4) the sub-basal lamina fibrous components, including anchoring fibrils, dermal microfibril bundles, and collagen fibers. The light microscopic "basement membrane" comprises only the sub-basal lamina fibrous zone. Other cell types, including melanocytes and Merkel cells, are also found at the epidermal-dermal junction. Structures at the junction derive their origin from the epidermis and dermis: the basal lamina is primarily of epidermal origin, the anchoring fibrils of dermal origin. The junction serves the following functions: (1) epidermal-dermal adherence, (2) mechanical support for the epidermis, and (3) a barrier to the exchange of cells and of some large molecules across the junction.


A Unified Model for BDS Wide Area and Local Area Augmentation Positioning Based on Raw Observations.
In this study, a unified model for BeiDou Navigation Satellite System (BDS) wide area and local area augmentation positioning based on raw observations has been proposed. Applying this model, both the Real-Time Kinematic (RTK) and Precise Point Positioning (PPP) service can be realized by performing different corrections at the user end. This algorithm was assessed and validated with the BDS data collected at four regional stations from Day of Year (DOY) 080 to 083 of 2016. When the users are located within the local reference network, the fast and high precision RTK service can be achieved using the regional observation corrections, revealing a convergence time of about several seconds and a precision of about 2-3 cm. For the users out of the regional reference network, the global broadcast State-Space Represented (SSR) corrections can be utilized to realize the global PPP service which shows a convergence time of about 25 min for achieving an accuracy of 10 cm. With this unified model, it can not only integrate the Network RTK (NRTK) and PPP into a seamless positioning service, but also recover the ionosphere Vertical Total Electronic Content (VTEC) and Differential Code Bias (DCB) values that are useful for the ionosphere monitoring and modeling.


Dynamics of the Humoral Immune Response to a Prime-Boost Ebola Vaccine: Quantification and Sources of Variation.
The Ebola vaccine based on Ad26.ZEBOV/MVA-BN-Filo prime-boost regimens is being evaluated in multiple clinical trials. The long-term immune response to the vaccine is unknown, including factors associated with the response and variability around the response. We analyzed data from three phase 1 trials performed by the EBOVAC1 Consortium in four countries: the United Kingdom, Kenya, Tanzania, and Uganda. Participants were randomized into four groups based on the interval between prime and boost immunizations (28 or 56 days) and the sequence in which Ad26.ZEBOV and MVA-BN-Filo were administered. Consecutive enzyme-linked immunosorbent assay (ELISA) measurements of the IgG binding antibody concentrations against the Kikwit glycoprotein (GP) were available for 177 participants to assess the humoral immune response up to 1 year postprime. Using a mathematical model for the dynamics of the humoral response, from 7 days after the boost immunization up to 1 year after the prime immunization, we estimated the durability of the antibody response and the influence of different factors on the dynamics of the humoral response. Ordinary differential equations (ODEs) described the dynamics of antibody response and two populations of antibody-secreting cells (ASCs), short-lived (SL) and long-lived (LL). Parameters of the ODEs were estimated using a population approach. We estimated that half of the LL ASCs could persist for at least 5 years. The vaccine regimen significantly affected the SL ASCs and the antibody peak but not the long-term response. The LL ASC compartment dynamics differed significantly by geographic regions analyzed, with a higher long-term antibody persistence in European subjects. These differences could not be explained by the observed differences in cellular immune response.IMPORTANCE With no available licensed vaccines or therapies, the West African Ebola virus disease epidemic of 2014 to 2016 caused 11,310 deaths. Following this outbreak, the development of vaccines has been accelerated. Combining different vector-based vaccines as heterologous regimens could induce a durable immune response, assessed through antibody concentrations. Based on data from phase 1 trials in East Africa and Europe, the dynamics of the humoral immune response from 7 days after the boost immunization onwards were modeled to estimate the durability of the response and understand its variability. Antibody production is maintained by a population of long-lived cells. Estimation suggests that half of these cells can persist for at least 5 years in humans. Differences in prime-boost vaccine regimens affect only the short-term immune response. Geographical differences in long-lived cell dynamics were inferred, with higher long-term antibody concentrations induced in European participants.


Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells.
Tumor-initiating cells constitute a population within a tumor mass that shares properties with normal stem cells and is considered responsible for therapy failure in many cancers. We have previously demonstrated that knockdown of the nuclear envelope component Lamin A/C in human neuroblastoma cells inhibits retinoic acid-mediated differentiation and results in a more aggressive phenotype. In addition, Lamin A/C is often lost in advanced tumors and changes in the nuclear envelope composition occur during tumor progression. Based on our previous data and considering that Lamin A/C is expressed in differentiated tissues, we hypothesize that the lack of Lamin A/C could predispose cells toward a stem-like phenotype, thus influencing the development of tumor-initiating cells in neuroblastoma. This paper demonstrates that knockdown of Lamin A/C triggers the development of a tumor-initiating cell population with self-renewing features in human neuroblastoma cells. We also demonstrates that the development of TICs is due to an increased expression of MYCN gene and that in neuroblastoma exists an inverse relationship between LMNA and MYCN expression.


[Carcinoid tumor of the ampulla of Vater. Morphology, diagnosis and therapy of a rare papilla tumor].
We report on a patient with a carcinoid tumour of the ampulla of Vater and review the 33 known cases of the literature with regard to clinical presentation, morphology and therapy. As it is apparent from the location of the tumour, obstructive jaundice, pancreatitis and nonspecific upper abdominal complaints are the most frequent symptoms. The ampullary carcinoid belongs histogenetically to the APUD cell system with the ability of multiple endocrine activity. The expression of somatostatin peptide and neuron-specific enolase are the most common histopathological findings. A systemic function of these hormones, however, has not yet been shown. For diagnostic purposes in surgical pathology we found synaptophysin and chromogranin A to be important markers. For surgical treatment, partial duodenopancreatectomy remains the current therapy of choise, if the tumour exceeds two centimeters in diameter.