A case of Sjögren syndrome and anti-neutrophil cytoplasmic antibody-associated vasculitis.
Sjögren's syndrome (SS) is a rare disease with the highest reported prevalence of 0.01-0.09%. Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is another rare auto-immune disease (prevalence of 0.0009-0.01%). The co-occurrence of these two separate clinical entities in one patient might rarely be encountered as an overlap syndrome. Here, we present the case of a 60-year-old female patient who had complaints of headache, nausea, weakness, gritty sensation in her eyes, and dry mouth [unstimulated saliva production of 0.033 mL/minute (normal; >0.1 mL/minute)] with a blood pressure of 190/110 mmHg, hypertensive retinopathy, proteinuric kidney disease, positivity of myeloperoxidase anti-neutrophil cytoplasmic antibodies, anti-Ro-52, anti-Ro, and anti-La antibodies. Pauci-immune crescentic proliferative glomerulonephritis was found in a kidney biopsy and successfully treated with cyclophosphamide and methylprednisolone. The co-occurrence of these diseases was first reported in 1992 by Böttinger et al. Since then, nearly 37 cases of SS and AAV have been reported. By reporting this case of primary SS and AAV, we emphasize the importance of auto-antibody tests in searching for the etiology of patients with proteinuria.


Short communication: detection of quantitative trait loci influencing somatic cell score in Spanish Churra sheep.
Eleven half-sib ovine families, including 1,421 Spanish Churra ewes, were analyzed for 181 microsatellite markers spanning the entire autosomic ovine genome. Using a multimarker regression method, a daughter experimental design was used to identify putative quantitative trait loci (QTL) affecting the somatic cell score (SCS). Chromosome-wise significance thresholds were set empirically by permuting the phenotypic data. Marker order and genetic distances of the autosomic linkage map built for this commercial population were in accordance with the published ovine linkage map. An across-family association analysis revealed a region on chromosome 20 suggestive of evidence for a QTL. Segregation of the QTL into 2 families was inferred from the within-family analysis, and differences in the position of the suggested QTL were found between the 2 half-sib groups. This could be the result of incomplete information associated with the markers for the significant families. The location of the major histocompatibility complex in proximity to the across-family effect suggests this region may harbor a segregating QTL for the SCS in the Churra population. Studies in dairy cattle examining the SCS have reported linkage associations on corresponding bovine orthologous regions, supporting the validity of our findings.


Near-Space TOPSAR Large-Scene Full-Aperture Imaging Scheme Based on Two-Step Processing.
Free of the constraints of orbit mechanisms, weather conditions and minimum antenna area, synthetic aperture radar (SAR) equipped on near-space platform is more suitable for sustained large-scene imaging compared with the spaceborne and airborne counterparts. Terrain observation by progressive scans (TOPS), which is a novel wide-swath imaging mode and allows the beam of SAR to scan along the azimuth, can reduce the time of echo acquisition for large scene. Thus, near-space TOPS-mode SAR (NS-TOPSAR) provides a new opportunity for sustained large-scene imaging. An efficient full-aperture imaging scheme for NS-TOPSAR is proposed in this paper. In this scheme, firstly, two-step processing (TSP) is adopted to eliminate the Doppler aliasing of the echo. Then, the data is focused in two-dimensional frequency domain (FD) based on Stolt interpolation. Finally, a modified TSP (MTSP) is performed to remove the azimuth aliasing. Simulations are presented to demonstrate the validity of the proposed imaging scheme for near-space large-scene imaging application.


A comparison of pulse oximetry and cerebral oxygenation in children with severe sleep apnea-hypopnea syndrome: a pilot study.
Near infrared spectroscopy (NIRS) has been used to assess the impact of obstructive sleep apnea-hypopnea syndrome (OSAHS) on cerebral oxygenation. However, the relationship between the variations in the cerebral tissue oxygen saturation (ΔTOI) and pulse oximetry (ΔSpO2 ) has not been assessed in children with OSAHS. Consecutive clinically stable children with severe OSAHS [apnea-hypopnea index (AHI) >15 events h-1 ] diagnosed during a night-time polygraphy with simultaneous recording of cerebral oxygenation with NIRS (NIRO-200NX, Hamamatsu Photonics KK) were included between September 2015 and June 2016. Maximal ΔSpO2 (SpO2 drop from the value preceding desaturation to nadir) and concomitant variations in transcutaneous carbon dioxide (ΔPtcCO2 ), maximal ΔTOI and maximal variations in cerebral oxygenated (O2 Hb) and deoxygenated (HHb) haemoglobin were reported. The relationships between ΔSpO2 , ΔPtcCO2 and ΔTOI, ΔO2 Hb and ΔHHb were investigated. The data from five children (three boys, aged 9.6 ± 6.7 years, AHI 16-91 events h-1 ) were analysed. Strong correlations were found between ΔSpO2 and ΔTOI (r = 0.887, P < 0.001), but also with ΔO2 Hb and ΔHHb with a particular pattern in the youngest child with a dark skin pigmentation. Mean ΔSpO2 was 20 ± 17% and mean ΔTOI was 8 ± 7%. Maximal ΔSpO2 of approximately 70% were coupled with ΔTOI of no more than 35%. ΔPtcCO2 correlated only weakly with the cerebral oxygenation indexes. This pilot study shows a strong relationship between pulse oximetry and cerebral oxygenation in children with OSAHS, with lower changes in TOI compared to SpO2 . Future studies should address the clinical impact of respiratory events on cerebral oxygenation and its consequences.


[The influence of smoking habits of Chilean physicians on the use of the structured medical advice about smoking].
Structured medical advice on smoking is the prevention strategy with better cost-effectiveness ratio. To evaluate smoking among health care providers affect the application of this preventive strategy. We surveyed 235 physicians working in public and private hospitals in different cities over the country, about their smoking habits, their views on smoking as cardiovascular risk factor and the implementation of three key points of the structured medical advice about smoking. Physicians aged less than 44 years had the lower frequency of smoking and the higher frequency of ex-smokers concentrated among those aged 60 years or more. All surveyed physicians agreed that smoking is a cardiovascular risk factor. However, 21% considered that this risk appears only among those that smoke more than three cigarettes per day. Independent of their smoking habits, 18% of physicians not always ask their patients about smoking, 25% do not warn about the risk of smoking and 22% not always give advice about quitting. This last action is carried out with a significantly lower frequency by smoking physicians. To improve physician's compliance with their preventive role in clinical practice, it is essential to consider their own smoking habits, and the information and attitudes that they have towards smoking as a cardiovascular risk factor.


A retrospective review of adenocarcinoma-in-situ and glandular atypia of the uterine cervix.
Between 1978 and 1985, 19 cases of adenocarcinoma-in-situ and 12 cases of glandular atypia have been identified at the Birmingham and Midland Hospital for Women. In 19 cases an associated dysplastic squamous element was identified, 20 of 28 pre-diagnosis smears correctly predicted a glandular lesion, 5 of 17 colposcopically directed biopsies predicted the findings in a larger biopsy (cone biopsy or hysterectomy). Colposcopy provided no additional information with regard to diagnosis. Twelve of 13 patients managed by cone biopsy and 16 of 17 by abdominal hysterectomy have been treated successfully as defined by subsequent normal cytology.


Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.
Standardised MedDRA Queries (SMQs) have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA). We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed. A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process. SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.


The effect of anti-thrombotics on the postoperative bleeding rate in patients undergoing craniotomy for brain tumor.
The peak prevalence of many brain tumors is in elderly patients. These patients are often treated with platelet inhibitors (PIs) or anticoagulants (ACs), creating a challenge for neurosurgeons concerning the perioperative management. The aim of this study is to analyze the effect of PI/AC treatment on the postoperative bleeding rates in patients undergoing craniotomy due to a brain tumor. Retrospective analysis of 415 consecutive patients undergoing craniotomy/craniectomy due to a brain tumor. Ninety-nine patients with PI/AC treatment (PI/AC group consisting of 64 PI, 29 AC, and six multiple) and 316 patients without PI/AC (control group) were primarily compared for hemorrhage rate. Secondary outcome measures were clinical outcome and mortality. The association between short preoperative discontinuation (≤5 days), early postoperative resumption time (≤5 days), as well as short total discontinuation time (≤5 days) of PI/AC and postoperative bleeding rates was analyzed. Postoperative bleeding rates were comparable between the groups (12.2% and 13.5% in the PI/AC and control group, respectively; p=.74). The majority of bleeds were asymptomatic (85.2%). No significant difference in the postoperative mortality rate was observed (1.0% and 1.6% in the PI/AC and the control group, respectively; p=.67). Shorter discontinuation time of PI/AC was not significantly associated with higher postoperative bleeding rates (preoperative: 12.1% vs. 12.3%; p=.94, postoperative: 11.1% vs. 12.5%, respectively; p=.87, total: 16.7% vs. 12%, respectively; p=.73). Patients treated with PI/AC undergoing craniotomy for the resection of brain tumor do not seem to have increased rates of postoperative bleeding or mortality. We did not find a significant correlation between short discontinuation time of PI/AC in the perioperative period and postoperative bleeding.


Schiff-Sherrington phenomenon in a cat with complete spinal cord transection from traumatic dorsocranial luxation of the second lumbar vertebra.
A young stray entire female domestic shorthair cat was presented with symmetrical forelimb extensor rigidity, neck hyperextension and hindlimb paraplegia, characteristic of Schiff-Sherrington phenomenon (SSP), within 30 min of a motor vehicle accident. Radiographic and post-mortem studies disclosed complete transection of the spinal cord from traumatic dorsocranial luxation of the second lumbar vertebra, displacement of the sacrum from the ilium, seventh lumbar and first caudal vertebrae and multiple pelvic fractures. Other causes of forelimb extensor rigidity and neck hyperextension such as decerebrate and decerebellate rigidity were excluded by a lack of neurological signs consistent with these entities and unremarkable findings on post-mortem examination of the cranial cavity and brain and histological examination of the cerebrum, brainstem and cerebellum. To the best of the author's knowledge, this is the first report of SSP in the cat outside the experimental arena of decerebrate or non-decerebrate preparations following post-brachial spinal cord transection/cold block.


The Function of NF-Kappa B During Epilepsy, a Potential Therapeutic Target.
The transcriptional regulator nuclear factor kappa B (NF-κB) modulates cellular biological activity by binding to promoter regions in the nucleus and transcribing various protein-coding genes. The NF-κB pathway plays a major role in the expressing genes related to inflammation, including chemokines, interleukins, and tumor necrosis factor. It also transcribes genes that can promote neuronal survival or apoptosis. Epilepsy is one of the most common brain disorders and it not only causes death worldwide but also affects the day-to-day life of affected individuals. While epilepsy has diverse treatment options, there remain patients who are not sensitive to the existing treatment methods. Recent studies have implicated the critical role of NF-κB in epilepsy. It is upregulated in neurons, glial cells, and endothelial cells, due to neuronal loss, glial cell proliferation, blood-brain barrier dysfunction, and hippocampal sclerosis through the glutamate and γ-aminobutyric acid imbalance, ion concentration changes, and other mechanisms. In this review, we summarize the functional changes caused by the upregulation of NF-κB in the central nervous system during different periods after seizures. This review is the first to deconvolute the complicated functions of NF-κB, and speculate that the regulation of NF-κB can be a safe and effective treatment strategy for epilepsy.


The Wessex Dementia Friendly Pharmacy Framework.
To develop and launch a dementia friendly framework for community pharmacies in the Wessex region of England. A framework consisting of essential (mandatory) and additional (non-mandatory) criteria were devised by local stakeholders and external scrutiny from the Alzheimer's Society. The framework was designed to allow pharmacy teams to achieve essential criteria without the need for approval by others (e.g. authorisation from internal company management structures). In total, 38 essential criteria across seven domains were devised. All essential criteria had to be met for pharmacies to be awarded dementia friendly status. Engagement events were organised to launch the framework detailing what it was and how pharmacies could meet each criterion. Pharmacies self-certified compliance with the framework criteria via an online platform, and validation activity was subsequently undertaken to see if pharmacies had appropriately self-certified against all essential criteria. Three hundred and fifty-five pharmacies (n = 504, 70%) engaged with the initiative, of which 330 uploaded self-certifications met all essential criteria of the framework. Validation visits showed self-certification to be appropriate in all but one visit (n = 11/12). Staff comments revealed that engaging with the framework had allowed them to be more aware of how better to support people with dementia. A dementia friendly framework was devised and implemented with a subsequent high level of uptake by community pharmacy.


Hendra virus V protein inhibits interferon signaling by preventing STAT1 and STAT2 nuclear accumulation.
The V protein of the recently emerged paramyxovirus, Nipah virus, has been shown to inhibit interferon (IFN) signal transduction through cytoplasmic sequestration of cellular STAT1 and STAT2 in high-molecular-weight complexes. Here we demonstrate that the closely related Hendra virus V protein also inhibits cellular responses to IFN through binding and cytoplasmic sequestration of both STAT1 and STAT2, but not STAT3. These findings demonstrate a V protein-mediated IFN signal evasion mechanism that is a general property of the known Henipavirus species.


Monoclinic and triclinic forms of bis[2-hydroxy-2,2-bis(2-pyridyl)ethanoato-O(1),N,N']nickel(II).
Reaction of pyridoin with nickel nitrate in methanol in air gives crystals of two forms of the title compound, [Ni(C(12)H(9)N(2)O(3))(2)]; a triclinic form with the Ni atom on an inversion centre and a monoclinic form with one molecule in a general position in the asymmetric unit. Both forms show an octahedral nickel centre coordinated by two facial tridentate ligands with their O-atom donors trans.


Involving patients in discussions of do-not-resuscitate orders.
Despite continued investment in training and equipment, the chance of a good outcome following the invasive technique of cardiopulmonary resuscitation in hospital remains low. Given these facts, early and full discussion of do-not-resuscitate orders with certain patients and their relatives and the use of advance directives will help to clarify this issue.


Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families.
Hereditary xerocytosis (HX) is a rare disorder caused by defects of RBC permeability, associated with haemolytic anaemia of variable degree and iron overload. It is sometimes misdiagnosed as hereditary spherocytosis or other congenital haemolytic anaemia. Splenectomy is contraindicated due to increased risk of thromboembolic complications. We report the clinical, haematological, and molecular characteristics of four patients from two unrelated Italian families affected by HX, associated with beta-thalassemia trait and heterozygous pyruvate kinase deficiency, respectively. Two patients had been splenectomised and displayed thrombotic episodes. All patients had iron overload in the absence of transfusion, two of them requiring iron chelation. The diagnosis of HX was confirmed by LoRRca Osmoscan analysis showing a left-shifted curve. PIEZO1 gene sequencing revealed the presence of mutation p.E2496ELE, showing that this is one of the most frequent mutations in this disease. The concomitant defects did not aggravate the clinical phenotype; however, in one patient, the initial diagnosis of pyruvate kinase deficiency delayed the correct diagnosis of HX for many years and resulted in splenectomy followed by thrombotic complications. The study underlines the importance of a precise diagnosis in HX, particularly in view of splenectomy, and the need of a molecular confirmation of suspected RBC enzymopathy.


[Advanced breast cancer in a patient achieving long-term SD after letrozole administration for liver metastasis developing during anastrozole therapy].
We report a 69-year-old woman with breast cancer who was effectively treated with letrozole as a second-line therapy after becoming resistant to anastrozole. Her chief complaint at presentation was back pain. Physical examination and imaging studies showed a left breast tumor with skin invasion, multiple intramammary lesions, enlarged left axillary lymph node, and multiple bone metastases. Needle biopsy revealed invasive ductal carcinoma(scirrhous carcinoma)that was ER+/PgR+/ HER2-. The administration of anastrozole and bisphosphonate for 13 months resulted in a 33% reduction of the longest diameters of the breast tumors, but a liver metastasis developed. The treatment was changed to letrozole administration from January 2007.T he optimal effect of letrozole as determined by measurement on CT images was long-term SD maintained for about 13 months. No significant side effects were observed, and the QOL was favorable.


N,N'-Bis[(2-methyl-phenyl)sulfon-yl]adipamide.
The asymmetric unit of the title compound, C(20)H(24)N(2)O(6)S(2), comprises one half-mol-ecule, the remaining portion being generated via an inversion centre. The dihedral angle between the plane of the benzene ring and the SO(2)-NH-C(O)-C-C segment is 89.9 (1)°. In the crystal, inter-molecular N-H⋯O(S) hydrogen bonds link the mol-ecules into infinite chains in [101].


Influence of psychological and clinical factors on postoperative pain and narcotic consumption.
Demographic, psychological and clinical factors influencing postoperative pain and narcotic analgesic requirements in 162 patients undergoing elective operations under general anesthesia were studied. Eysencks Personality Questionnaire, Foulds Hostility Questionnaire, Zung's Anxiety-Depression (self-rating) Scales and the 43 Item Life Events Inventory by Holmes and Rahe were used. Clinical correlates such as surgical department, outcome of the operation, patient's knowledge of the diagnosis, were studied. Using multiple regression analysis the following results were obtained: postoperative pain levels increase with higher score of extroverted hostility (p = 0.038), abdominal surgery (p = 0.004), longer stay at hospital postoperatively (p = 0.15) and higher educational status (p = 0.13). Postoperative narcotic requirements increase with increased postoperative pain levels (p = 0.039) and preoccupation with pain postoperatively (p = 0.025), preoperative analgesic drug use (p = 0.017), abdominal surgery (p = 0.009) and longer stay at hospital preoperatively (p = 0.016). Also the department in which the patients were hospitalized influenced narcotic consumption.


Graphene oxide/ferroferric oxide/polyethylenimine nanocomposites for Congo red adsorption from water.
Graphene oxide/ferroferric oxide/polyethylenimine (GO/Fe3O4/PEI) nanocomposites were synthesized by an in situ growth of Fe3O4 nanoparticles on GO sheets, and then modified by PEI. The GO/Fe3O4/PEI nanocomposites showed extremely high removal efficiency for anionic dye Congo Red (CR) due to the positively charged PEI molecules (methylene blue was also tested but with low adsorption capacity due to its cationic property). The CR removal capacity was 574.7 mg g-1, higher than most of reported results. The adsorption kinetics could be well described by a pseudo-second-order model. Furthermore, GO/Fe3O4/PEI nanocomposites could be easily recycled by magnetic separation. The removal efficiency remained above 70% after five cycles.


ADAM-17/FHL2 colocalisation suggests interaction and role of these proteins in colorectal cancer.
FHL2 is a multifunctional scaffolding protein; its expression is associated with poor prognosis in colorectal cancer. ADAM-17 is a metalloprotease implicated in ectodomain shedding. FHL2 regulates ADAM-17 plasma membrane localisation, and FHL2 deficiency leads to decreased activity of ADAM-17 in mouse macrophages. Presence and relationship of the ADAM-17/FHL2 complex with colorectal cancer progression is unknown. We studied FHL2 and ADAM-17 expression in several colon cancer cell lines by immunocytochemistry and western blot. To highlight the interaction between both molecules, we used the Duolink® kit for proximity ligation assay on SW480 cells. We also performed proximity ligation assay on biopsies and surgical specimens of colorectal adenocarcinoma and on matched normal mucosa. Furthermore, biopsies of colorectal adenoma with matched normal mucosa were selected. For quantification, pictures of the malignant, adenomatous and normal tissues were taken. Proximity ligation assay signals were quantified. Mean numbers of proximity ligation assay signals and of proximity ligation assay signals/nucleus were calculated. All cell lines showed FHL2 immunoreactivity; strongest positivity was observed in SW480 cells. ADAM-17 was expressed in all cell lines. Proximity ligation assay signals were present in SW480 cells. Quantitative analysis revealed that the interaction between FHL2 and ADAM-17 is more frequent in malignant than in normal tissue (p = 0.005). The mean number of ADAM-17/FHL2 proximity ligation assay signals was higher in colorectal adenocarcinoma than in adenoma with low-grade dysplasia (p = 0.0004). FHL2 interacts with ADAM-17 in normal, dysplastic and malignant colon epithelial cells. Colocalisation of these proteins is more frequent in malignant than in normal and dysplastic cells, suggesting a role for ADAM-17/FHL2 complex in the development of colorectal cancer.


Narratives of transphobic violence in the Mexican province of Colima: A psychosocial analysis.
Mexico has the second-highest index of crimes motivated by transphobia in the world. Transphobic violence manifests in a pervasive and complex manner in a country where violence permeates all aspects of social life. Some progress has been made to improve transgender rights and fight discrimination, but this has had an unequal impact in different geopolitical and cultural contexts within the country, particularly outside of metropolitan centers. The study explores how transphobia is experienced in the conservative province of Colima and how transphobic practices play a part in shaping transgender subjective experience and identity construction. A psychosocial theoretical framework is adopted to attend to the relationship between cultural, institutional and interpersonal practices in this process. A qualitative approach is used to explore how different forms of transphobic violence are experienced by trans women in Colima. A purposive sample of 12 trans women, aged 22-38 years took part in narrative interviews which were analyzed thematically. Findings: The analysis is organized into three themes: (a) narratives of gender identity construction (b) gender expression and experiences of transphobic violence in Colima (c) sites for social support and change. We argue that the psychosocial processes related to transphobia are context-specific shaping transgender identities and limiting and regulating gender expression. Family, education, LGBT community and the police were identified as key sites for support against or source of transphobic violence. Despite the challenging socio-political context interventions are needed in policy and institutional practices to tackle stigma, transphobia and, trans-misogyny and improve the lives of transgender people living in regional areas in the global south.


Residential social vulnerability among healthcare personnel with and without severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in Five US states, May-December 2020.
To characterize residential social vulnerability among healthcare personnel (HCP) and evaluate its association with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection. Case-control study. This study analyzed data collected in May-December 2020 through sentinel and population-based surveillance in healthcare facilities in Colorado, Minnesota, New Mexico, New York, and Oregon. Data from 2,168 HCP (1,571 cases and 597 controls from the same facilities) were analyzed. HCP residential addresses were linked to the social vulnerability index (SVI) at the census tract level, which represents a ranking of community vulnerability to emergencies based on 15 US Census variables. The primary outcome was SARS-CoV-2 infection, confirmed by positive antigen or real-time reverse-transcriptase- polymerase chain reaction (RT-PCR) test on nasopharyngeal swab. Significant differences by SVI in participant characteristics were assessed using the Fisher exact test. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) for associations between case status and SVI, controlling for HCP role and patient care activities, were estimated using logistic regression. Significantly higher proportions of certified nursing assistants (48.0%) and medical assistants (44.1%) resided in high SVI census tracts, compared to registered nurses (15.9%) and physicians (11.6%). HCP cases were more likely than controls to live in high SVI census tracts (aOR, 1.76; 95% CI, 1.37-2.26). These findings suggest that residing in more socially vulnerable census tracts may be associated with SARS-CoV-2 infection risk among HCP and that residential vulnerability differs by HCP role. Efforts to safeguard the US healthcare workforce and advance health equity should address the social determinants that drive racial, ethnic, and socioeconomic health disparities.


Preclinical characterization of three transient receptor potential vanilloid receptor 1 antagonists for early use in human intradermal microdose analgesic studies.
The transient receptor potential vanilloid receptor 1 (TRPV1) is a nonselective cation channel involved in the mediation of peripheral pain to the central nervous system. As such, the TRPV1 is an accessible molecular target that lends itself well to the understanding of nociceptive signalling. This study encompasses preclinical investigations of three molecules with the prospect to establish them as suitable analgesic model compounds in human intradermal pain relief studies. The inhibitory effectiveness was evaluated by means of in vitro assays, TRPV1 expressing Chinese hamster ovary cells (CHO-K1) and rat dorsal root ganglion cultures in fluorescent imaging plate reader and whole cell patch clamp systems, as well as in vivo by capsaicin-evoked pain-related behavioural response studies in rat. Secondary pharmacology, pharmacokinetics and preclinical safety were also assessed. In vitro, all three compounds were effective at inhibiting capsaicin-activated TRPV1. The concentration producing 50% inhibition (IC50 ) determined was in the range of 3-32 nmol/L and 10-501 nmol/L using CHO-K1 and dorsal root ganglion cultures, respectively. In vivo, all compounds showed dose-dependent reduction in capsaicin-evoked pain-related behavioural responses in rat. None of the three compounds displayed any significant activity on any of the secondary targets tested. The compounds were also shown to be safe from a toxicological, drug metabolism and pharmacokinetic perspective, for usage in microgram doses in the human skin. The investigated model compounds displayed ideal compound characteristics as pharmacological and translational tools to address efficacy on the human native TRPV1 target in human skin in situ. This work details the pharmaceutical work-up of three TRPV1-active investigational compounds, to obtain regulatory approval, for subsequent use in humans. This fast and cost-effective preclinical development path may impact research beyond the pain management area, as it allows human target engagement information gathering early in drug development.


The role of syndecan-1 in cellular signaling and its effects on heparan sulfate biosynthesis in mesenchymal tumors.
Proteoglycans (PGs) and in particular the syndecans are involved in the differentiation process across the epithelial-mesenchymal axis, principally through their ability to bind growth factors and modulate their downstream signaling. Malignant tumors have individual proteoglycan profiles, which are closely associated with their differentiation and biological behavior, mesenchymal tumors showing a different profile from that of epithelial tumors. Syndecan-1 is the main syndecan of epithelial malignancies, whereas in sarcomas its expression level is generally low, in accordance with their mesenchymal phenotype and highly malignant behavior. This proteoglycan is often overexpressed in adenocarcinoma cells, whereas mesothelioma and fibrosarcoma cells express syndecan-2 and syndecan-4 more abundantly. Increased expression of syndecan-1 in mesenchymal tumors changes the tumor cell morphology to an epithelioid direction whereas downregulation results in a change in shape from polygonal to spindle-like morphology. Although syndecan-1 plays major roles on the cell-surface, there are also intracellular functions, which are not very well studied. On the functional level, syndecan-1 affects mesenchymal tumor cell proliferation, adhesion, migration and motility, and the effect varies with the different domains of the core protein. Syndecan-1 may exert stimulatory or inhibitory effects, depending on the concentration of various mitogens, enzymes, and signaling molecules, the ratio between the shed and membrane-associated syndecan-1 and histological grade of the tumour. Growth factor signaling seems to be delicately controlled by regulatory loops involving the syndecan expression levels and their sulfation patterns. Overexpression of syndecan-1 modulates the biosynthesis and sulfation of heparan sulfate and it also affects the expression of other PGs. On transcriptomic level, syndecan-1 modulation results in profound effects on genes involved in regulation of cell growth.


Hematology references for three laboratory mice strains.
The paper contains reference data for the main haematologic indicators from three strains of conventional mice: Balb/c, C57BL/6 and CD1. These data listed include the mean and the standard deviation of the studied values. The animals used were divided by sex (sex ratio 1:1) and age. The study was performed in standard conditions. These strains were chosen as they are widely used for preclinical evaluations. Therefore, our data are expected to be useful for investigators conducting qualitative and quantitative toxicity studies in these mice.


Measurements of selected parameters of the guinea pig temporal bone.
On the basis of dissections of 32 temporal bones of the guinea pig, measurements were taken of selected size parameters of the temporal bone. The measurements performed included external and internal size parameters of the bone. Among these were the following: the length, width and height of the external and internal auditory meatus, the length of the incudomallear complex, the height of the attic, the full length and height of the tympanic cavity and the parameters characterising the localisation of the external orifice of the facial nerve. The semicircular canals are relatively large, the lateral canal being the largest and the posterior the smallest. The length of the spiral canal of the cochlea does not exceed 16 mm. It is worth noting that both the vertical and horizontal dimensions of the scala vestibuli and scala tympani only exceed 1 mm in the basal turn, decreasing significantly in the further turns to as little as decimal parts of a millimetre. This should be taken into account during all tests which require the introduction of examining instruments into the cochlear scala.


Aligning for accountable care: Strategic practices for change in accountable care organizations.
Alignment within accountable care organizations (ACOs) is crucial if these new entities are to achieve their lofty goals. However, the concept of alignment remains underexamined, and we know little about the work entailed in creating alignment. The aim of this study was to develop the concept of aligning by identifying and describing the strategic practices administrators use to align the structures, processes, and behaviors of their organizations and individual providers in pursuit of accountable care. We conducted 2-year qualitative case studies of four ACOs that have assumed full risk for the costs and quality of care for defined populations. Five strategic aligning practices were used by all four ACOs. Informing both aligns providers' understandings with the goals and value proposition of the ACO and aligns the providers' attention with the drivers of performance. Involving both aligns ACO leaders' understandings with the realities facing providers and aligns the policies of the ACO with the needs of providers. Enhancing both aligns the operations of individual provider practices with the operations of the ACO and aligns the trust of providers with the ACO. Motivating aligns what providers value with the goals of the ACO. Finally, evolving is a metapractice of learning and adapting that guides the execution of the other four practices. Our findings suggest that there are second-order cognitive (e.g., understandings and attention) and cultural (e.g., trust and values) levels of alignment, as well as a first-order operational level (organizational structures, processes, and incentives). A well-aligned organization may require ongoing repositioning at each of these levels, as well as attention to both cooperative and coordinative dimensions of alignment. Implications for research and practice are discussed.


The crosstalk between AXL and YAP promotes tumor progression through STAT3 activation in head and neck squamous cell carcinoma.
Receptor tyrosine kinases (RTKs) and Yes-associated protein (YAP) are critical driving factors in tumors. Currently, the regulation of RTKs in the Hippo-YAP pathway has been recognized as an important issue. However, the relationship between AXL, one of the RTKs, and YAP in head and neck squamous cell carcinoma (HNSCC) remains unknown. In this study, the crosstalk between AXL and YAP was thoroughly investigated in vitro and in vivo. We determined that there was a positive correlation between AXL and YAP in the HNSCC tissue samples and the Cancer Genome Atlas (TCGA) dataset, and high co-expression was associated with poor prognosis. Inhibiting YAP decreased AXL expression in HNSCC cells, while YAP overexpression increased AXL. Moreover, ectopic expression of AXL reversed tumor suppressor phenotypes mediated by YAP silencing. This reversal effect was also confirmed in vivo. In addition, AXL overexpression and Gas6, a ligand of AXL, stimulated YAP dephosphorylation, nuclear translocation, and target gene transcription. AXL inhibition decreased YAP dephosphorylation and nuclear translocation. Mechanistically, Gas6 induced a competitive binding to phosphorylated signal transducers and activators of transcription 3 (STAT3) with large tumor suppressor kinase 1 (LATS1) and inhibited the Hippo pathway. This study revealed a novel non-transcriptional effect of STAT3 in Gas6/AXL-induced YAP activity, suggesting that STAT3 acted as a critical "molecular switch" during the mutual promotion between AXL and YAP, which might be a promising therapeutic target in HNSCC.


The influence of electrostimulation on the circulation of the remaining leg in patients with one-sided amputation.
The aim of the authors' study was to investigate, in patients with one leg amputated, the influence of electrostimulation on the arterial circulation of the other lower limb and on the ability of a leg with deteriorated blood flow to perform work. The study encompassed 50 patients who were admitted to the rehabilitation center to obtain a leg prosthesis and learn to walk after amputation of 1 lower limb because of severe circulatory disturbance. The patients were randomly divided into 2 groups. The first group contained 25 patients treated with a standard exercise program for patients with limb amputation (control group, C). In this control group, according to the Fontaine's classification of peripheral arterial occlusive disease (PAOD), 15 patients were in stage I and 10 patients were in stage II. In the second group, the electro stimulated (ES) group, there were also 25 patients that had the same rehabilitation program, to which electrostimulation of the gastrocnemius muscle of the remaining leg was added. In this group, 14 patients were in stage I, 10 patients were in stage II, and 1 patient was in stage III of PAOD. For electrostimulation, biphasic charge-balanced asymmetrical current stimuli with a pulse duration of 0.25 ms were used. The electrostimulation program consisted of 2 hours of electrostimulation per day for 8 weeks. Each patient was examined at the start of the rehabilitation program (examination I), at the end of the 8-week program (examination II) and at the end of a 1-year follow-up period (examination III). The effects of the treatment were followed using clinical examination, determination of the ankle-brachial index (ABI), and by measuring the partial oxygen pressure (TcPO2) on the skin surface of the diseased leg at rest and during exercise. After 8 weeks of treatment, in 3 patients of the ES group, claudication disappeared, and they thus moved from clinical stage II to stage I. In the control group, there were no changes in the clinical stages of PAOD. At the end of the observation period, 6 patients in group C and 5 patients in the ES group registered a progression of PAOD. During the observation period, 3 patients in group C and 1 patient in the ES group had below-knee amputations of the remaining leg (p<0.01). Perfusion pressures and ABI of investigated legs were comparable between groups and did not change during treatment. After 1 year of observation, there was a trend to ABI decrease in both groups. The capability of the diseased leg for performing work increased significantly during treatment only in the ES group. During treatment, TcPO2 at rest on the dorsum of the foot increased nonsignificantly in the ES group but in group C a trend of decrease in its value was indicated. After 8 weeks of treatment, total and partial oxygen drop during exercise significantly decreased in the ES group; whereas, in group C, there was no significant change. During the 1-year observation period, these effects of electrostimulation disappeared; however, fewer amputations in the ES group favor the presumption that this could be a positive effect of electrostimulation. The results of the authors' study showed that electrostimulation improved oxygen delivery to a leg with disturbed arterial circulation and increased its work load capacity. The changes are probably caused by improvement of microcirculation.


Influence of seasonal variations on in-vitro fertilization success.
This study was designed to investigate the influence of seasonal variations on the number of retrieved ova, fertilization rate, embryo quality rates and pregnancy rate in IVF cycles. Prospective cohort study was conducted on a total number of 2140 cycles in infertile patients undergoing their first IVF cycle between 2000 and 2007 in IVF policlinic. Chi2-test, Pearson's correlation coefficient and one-way analysis of variance were used for statistical analyses. Overall fertilization rate was 77.96% and pregnancy rate 29.15 +/- 2.72% per cycle. Seasonal prevalence of pregnancy rate was highest during fall 33.8 +/- 4.5% and lowest during summer 23.4 +/- 6.2%, but these differences did not reach statistical significance. The study did not show any statistically significant differences in the number of retrieved oocyte, fertilization, and embryo quality according to season. Therefore seasonal changes should not be taken into account in everyday IVF practice.


Feasibility evaluation of novel AI-based deep-learning contouring algorithm for radiotherapy.
To evaluate the clinical feasibility of the Siemens Healthineers AI-Rad Companion Organs RT VA30A (Organs-RT) auto-contouring algorithm for organs at risk (OARs) of the pelvis, thorax, and head and neck (H&N). Computed tomography (CT) datasets from 30 patients (10 pelvis, 10 thorax, and 10 H&N) were collected. Four sets of OARs were generated on each scan, one set by Organs-RT and the others by three experienced users independently. A physician (expert) then evaluated each contour by assigning a score from the following scale: 1-Must Redo, 2-Major Edits, 3-Minor Edits, 4-Clinically usable. Using the highest-scored OAR from the human users as a reference, the contours generated by Organs-RT were evaluated via Dice Similarity Coefficient (DSC), Hausdorff Distance (HDD), Mean Distance to Agreement (mDTA), Volume comparison, and visual inspection. Additionally, each human user recorded the time to delineate each structure set and time-saving efficiency was measured. The average DSC obtained for the pelvic OARs ranged between (0.81 ± 0.06)Rectum and (0.94 ± 0.03)Bladder . (0.75 ± 0.09)Esophagus to ( 0.96 ± 0.02 ) Rt . Lung ${( {0.96 \pm 0.02} )}_{{\mathrm{Rt}}.{\mathrm{\ Lung}}}$ for the thoracic OARs and (0.66 ± 0.07)Lips to (0.83 ± 0.04)Brainstem for the H&N. The average HDD in cm for the pelvis cohort ranged between (0.95 ± 0.35)Bladder to (3.62 ± 2.50)Rectum , (0.42 ± 0.06)SpinalCord to (2.09 ± 2.00)Esophagus for the thoracic set and ( 0.53 ± 0.22 ) Cerv _ SpinalCord ${( {0.53 \pm 0.22} )}_{{\mathrm{Cerv}}\_{\mathrm{SpinalCord}}}$ to (1.50 ± 0.50)Mandible for the H&N region. The time-saving efficiency was 67% for H&N, 83% for pelvis, and 84% for thorax. 72.5%, 82%, and 50% of the pelvis, thorax, and H&N OARs were scored as clinically usable by the expert, respectively. The highest agreement registered between OARs generated by Organs-RT and their respective references was for the bladder, heart, lungs, and femoral heads, with an overall DSC≥0.92. The poorest agreement was for the rectum, esophagus, and lips, with an overall DSC⩽0.81. Nonetheless, Organs-RT serves as a reliable auto-contouring tool by minimizing overall contouring time and increasing time-saving efficiency in radiotherapy treatment planning.


The Effect of High Temperature on Cardiovascular Autonomic Function Tests in Steel Plant Furnace Worker.
The high temperature in the working environment could be one of the risk factors for cardiovascular diseases in steel plant workers. The excessive high temperature at the working place leads to altered autonomic activity and is related to more cardiovascular risk. The effect of high temperature on cardiovascular autonomic function tests in steel plant furnace worker. This was a case-control study for which 50 steel plant furnace workers and 50 controls were selected. The cardiovascular sympathetic function status in worker and control were analyzed by three tests: (i) Blood pressure (BP) response to sustained isometric handgrip test, (ii) BP response to the cold pressor test, and (iii) BP response to standing from a supine position (orthostasis). Statistical analysis was done by using an independent t-test. Diastolic BP (DBP) response to sustained isometric handgrip and systolic BP (SBP) and DBP response to the cold pressor test showed that the increase BP in workers were more than controls but the difference was not statistically significant (P > 0.05). SBP response to standing from the supine position showed statistically significant (P < 0.001) greater fall in steel plant workers. The sympathetic autonomic dysfunction was seen in steel furnace workers in response to environmental stressor-excessive heat.


Photochemical properties of a myoglobin-CdTe quantum dot conjugate.
A myoglobin-cadmium telluride quantum dot conjugate was constructed using an artificial heme modified with a thiol moiety as a linker. Irradiation of the myoglobin-cadmium telluride conjugate generated the photoreduced ferrous myoglobin via an electron transfer from the photoexcited quantum dot, leading to the formation of CO-bound myoglobin under a CO atmosphere.


Barriers to accessing free condoms at public health facilities across South Africa.
Lack of access to public sector condoms still presents a fundamental barrier to condom use in most of South Africa. This study investigated the determinants of condom procurement at public health facilities in order to inform improved public sector condom distribution and promotion strategies. Cross-sectional study. Twelve health facilities in four health regions of South Africa: Boland/Overberg, Empangeni/Jozini, Kimberley, and Pretoria. Consecutive individuals procuring condoms and a sample of individuals not procuring condoms were interviewed on their recent sexual behaviour and condom-related knowledge and attitudes. Factors associated with condom procurement. Across all facilities, 554 individuals procuring condoms and a comparison group of 261 individuals not procuring condoms were interviewed. Eighty-three (33%) of those interviewed who were not procuring condoms stated that they would like to do so. Several potential barriers to condom procurement, including female gender and perceived risk of HIV, showed substantially different associations in different study regions. Only two factors, negative partner attitudes towards condoms and the use of other forms of contraception, were consistently associated with a decreased probability of condom procurement across all regions. These results suggest that the barriers to condom procurement may vary considerably across South Africa. This heterogeneity suggests that national-level interventions to promote condom procurement and use may be less appropriate than specialised interventions addressing locally relevant factors, including those identified here.


Cytochemical studies on the relation of nucleoside triphosphatase activity to ribonucleoproteins in isolated rat liver nuclei.
Cytochemical tests for nucleosidetriphosphatase (NTPase) and Bernhard's preferential staining for ribonucleoproteins (RNP) were applied to isolated rat liver nuclei. The strongest and most easily reproducible positive reaction for NTPase was detected at pH 7.7 with ATP and GTP. This reaction was activated by Mg2+ and Ca2+ and inhibited by Be2+, Zn2+, quercetin, and ribonuclease. The major sites of enzyme reaction were intranuclear RNA-containing structures. Incubation of nuclei in ATP-stimulated RNA-release medium eliminated a considerable part of the material showing both NTPase reaction and staining for RNP; the perichromatin granules disappeared, while interchromatin granules remained. NTPase activity in the nuclear envelope seems to be associated with the annular part of nuclear pore complexes (permanent component) and with RNP particles translocated through nuclear pores or attached to the surface of nuclei (transitional component). From a morphological point of view, these observations support previous biochemical data suggesting the existence of a connection between NTPase activity and the translocation of RNP particles through the nuclear envelope.


Use of technologies in intravenous therapy: contributions to a safer practice.
To identify what are the difficulties of the nursing staff in the management of technologies during intravenous therapy (IVT) and discuss the difficulties identified under the perspective of patient's safety. Descriptive study of qualitative approach with data collected by semi-structured interview and analyzed by the Alceste software. The greatest difficulty of cognitive and technical emphasis was the lack of training; and regarding administrative emphasis, the greatest difficulty was the lack of material and human resources. Infusion pumps and their proper use were highlighted as the technological resource that most contributed to patient safety. The lack of training is presented as the greatest difficulty of nursing professionals and permeates safety issues of both patient and professional when using the hard technologies in IVT. Training is essential to the development of techniques, considered nursing tools.


Relation of body mass index to risk of developing inflammatory bowel disease amongst women in the Danish National Birth Cohort.
Crohn's disease (CD) has traditionally been associated with weight loss and low BMI, yet paradoxically obesity has recently been suggested as a risk factor for CD, but not for ulcerative colitis (UC). We therefore hypothesized that the relation between BMI and CD is U shaped. To conduct a large population-based prospective cohort study of BMI and later risk of IBD, taking age at IBD diagnosis into account. A cohort of 74,512 women from the Danish National Birth Cohort, with BMI measured pre-pregnancy and 18 months after delivery, was followed for 1,022,250 person-years for development of IBD, according to the Danish National Patient Register. Associations were tested by Cox regression. Overweight subjects (25≤BMI<30 kg/m2) had the lowest risk of CD, whereas obesity (BMI≥30kg/m2) increased the risk of CD at all ages, and low BMI (BMI<18.5kg/m2) associated with CD diagnosed at age 18-<40 years. Hence, using normal weight subjects as the reference, adjusted HRs for risk of developing CD (at age 18-<40 years) were 1.8(95%CI, 0.9-3.7) for underweight, 0.6(0.3-1.2) for overweight, and 1.5(0.8-2.7) for obese individuals (pre-pregnancy BMI). HRs were greater for BMI determined 18 months after delivery. Splines for CD risk according to waist:height ratio confirmed a U-shaped relationship with CD occurring <40 years, and a linear relationship with CD diagnosed at age 40+. There was no relationship between BMI and risk of UC. For the first time, we demonstrate that both high BMI and low BMI are risk factors for CD. Underweight may be a pre-clinical manifestation of disease being present many years before onset with obesity being a true risk factor. This raises the question as to whether there may be two distinct forms of CD.


A population-based cohort study of Mycobacterium tuberculosis Beijing strains: an emerging public health threat in an immigrant-receiving country?
Mycobacterium tuberculosis Beijing strains are frequently associated with tuberculosis outbreaks and drug resistance. However, contradictory evidence and limited study generalizability make it difficult to foresee if the emergence of Beijing strains in high-income immigrant-receiving countries poses an increased public health threat. The purpose of this study was to determine if Beijing strains are associated with high risk disease presentations relative to other strains within Canada. This was a retrospective population-based study of culture-confirmed active TB cases in a major immigrant-receiving province of Canada in 1991 through 2007. Of 1,852 eligible cases, 1,826 (99%) were successfully genotyped. Demographic, clinical, and mycobacteriologic surveillance data were combined with molecular diagnostic data. The main outcome measures were site of disease, lung cavitation, sputum smear positivity, bacillary load, and first-line antituberculosis drug resistance. A total of 350 (19%) patients had Beijing strains; 298 (85%) of these were born in the Western Pacific. Compared to non-Beijing strains, Beijing strains were significantly more likely to be associated with polyresistance (aOR 1.8; 95% CI 1.0-3.3; p = 0.046) and multidrug-resistance (aOR 3.4; 1.0-11.3; p = 0.049). Conversely, Beijing strains were no more likely than non-Beijing strains to be associated with respiratory disease (aOR 1.3; 1.0-1.8; p = 0.053), high bacillary load (aOR 1.2; 0.6-2.7), lung cavitation (aOR 1.0; 0.7-1.5), immediately life-threatening forms of tuberculosis (aOR 0.8; 0.5-1.6), and monoresistance (aOR 0.9; 0.6-1.3). In subgroup analyses, Beijing strains only had a significant association with multidrug-resistant tuberculosis (aOR 6.1; 1.2-30.4), and an association of borderline significance with polyresistant tuberculosis (aOR 1.8; 1.0-3.5; p = 0.062), among individuals born in the Western Pacific. Other than an increased risk of polyresistant or multidrug-resistant tuberculosis, Beijing strains appear to pose no more of a public health threat than non-Beijing strains within a high-income immigrant-receiving country.


Leukocyte adhesion-deficient neutrophils fail to amplify phagocytic function in response to stimulation. Evidence for CD11b/CD18-dependent and -independent mechanisms of phagocytosis.
Stimulation of PMN with inflammatory mediators markedly augments Fc and CR1 receptor-mediated ingestion. However, CD11/CD18-deficient PMN from three patients with complete leukocyte adhesion deficiency (LAD) failed to recruit phagocytic function in response to phorbol esters, cytokine, or Arg-Gly-Asp-containing ligand stimulation. Because stimulated ingestion is protein kinase C (PKC)-dependent, our data indicate that LAD PMN exhibit only PKC-independent phagocytosis. The defect in PKC-dependent ingestion is specific for CD11b/CD18 and not secondary to the chronic or recurrent infections which occur in this disease. The LAD phenotype for phagocytic function can be reproduced in normal PMN by the anti-CD11b MAbs OKM1 and OKM10. In contrast, MAb Mo1 (anti-CD11b) and MAb IB4 (anti-CD18) inhibit both CD11b/CD18-dependent and -independent mechanisms of ingestion by normal PMN. Their ability to inhibit CD11b/CD18-independent ingestion may be mediated by cAMP, as shown by experiments with a protein kinase A inhibitor HA1004 and by direct measurement of cAMP levels in immune complex- and FMLP-stimulated PMN. These data indicate that CD11b/CD18-independent and -dependent mechanisms of phagocytosis exist and that some effects of anti-CD11b/CD18 MAbs may be mediated by alterations in cAMP levels.


[Surgical correction of post-traumatic kyphosis: a thoracoscopic approach].
Conservative treatment of an unstable spinal fracture can give lead to post-traumatic kyphosis, and may give rise to serious back pain. Surgical correction can alleviate the problem in patients with this deformity. Operative correction of kyphotic deformities of the thoracic spine and deformities at the level of the thoracolumbar junction are often performed via a thoracotomy or a thoraco-phrenico-laparotomy, respectively. There are also some correction techniques that are only performed via a posterior approach. In accordance with general surgical trends, spinal surgery tries to use minimally invasive intervention in order to reduce operative trauma, postoperative pain and complications. In the authors' hospital, patients with unstable spinal fractures have been undergoing surgery using a thoracoscopic approach for the past few years; now patients with post-traumatic kyphosis are also being treated using a minimally invasive approach. The thoracoscopic approach has been used in major centres abroad for some time, but has not previously been described in the Netherlands.


Association of the Number of Years Since Menopause with Metabolic Syndrome and Insulin Resistance in Chinese Urban Women.
This study aimed to assess the prevalence of metabolic syndrome (MetS) and the association of years since menopause with MetS and Insulin Resistance (IR) in Chinese women. A total of 4436 Chinese subjects aged 40-80 years participated in the study; 790 were premenopausal women, and 3646 were postmenopausal women. IR was arbitrarily defined as a homeostasis model assessment-IR index (HOMA-IR) value above the 75th percentile of normal glucose tolerance (NGT). MetS was defined according to the International Diabetes Federation consensus definition. To test whether there was an association between the number of years since menopause and MetS, multivariate logistic analysis was conducted. Premenopausal women were used as a comparison group in regression analyses. After adjustment for age, body mass index (BMI), and γ-glutamyltransferase (GGT), more years since menopause was highly associated with an increased risk of MetS (p for trend <0.05) ; the number of years since menopause was not correlated with fasting insulin and HOMA-IR. Postmenopausal women with 10 to 14 years since menopause had the highest risk (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.52-2.89, p < .05) of MetS, high triglycerides (TG; OR, 1.80; 95% CI, 1.34-2.42, p < .05) and high glucose (OR, 1.52; 95% CI, 1.14-2.05, p < .05) and low high-density lipoprotein cholesterol (HDL-C; OR, 1.38; 95% CI, 1.18-2.32, p < .05). Postmenopausal women with more than 15 years since menopause had the highest risk of abdominal obesity (OR, 1.69; 95% CI, 1.05-2.71, p < .05). In China, more years since menopause was highly associated with an increased risk of MetS. Menopausal history may help identify women with increased risk of developing MetS.


Pseudomonas aeruginosa LD-carboxypeptidase, a serine peptidase with a Ser-His-Glu triad and a nucleophilic elbow.
LD-Carboxypeptidases (EC 126.96.36.199) are named for their ability to cleave amide bonds between l- and d-amino acids, which occur naturally in bacterial peptidoglycan. They are specific for the link between meso-diaminopimelic acid and d-alanine and therefore degrade GlcNAc-MurNAc tetrapeptides to the corresponding tripeptides. As only the tripeptides can be reused as peptidoglycan building blocks, ld-carboxypeptidases are thought to play a role in peptidoglycan recycling. Despite the pharmaceutical interest in peptidoglycan biosynthesis, the fold and catalytic type of ld-carboxypeptidases are unknown. Here, we show that a previously uncharacterized open reading frame in Pseudomonas aeruginosa has ld-carboxypeptidase activity and present the crystal structure of this enzyme. The structure shows that the enzyme consists of an N-terminal beta-sheet and a C-terminal beta-barrel domain. At the interface of the two domains, Ser(115) adopts a highly strained conformation in the context of a strand-turn-helix motif that is similar to the "nucleophilic elbow" in alphabeta-hydrolases. Ser(115) is hydrogen-bonded to a histidine residue, which is oriented by a glutamate residue. All three residues, which occur in the order Ser-Glu-His in the amino acid sequence, are strictly conserved in naturally occurring ld-carboxypeptidases and cannot be mutated to alanines without loss of activity. We conclude that ld-carboxypeptidases are serine peptidases with Ser-His-Glu catalytic triads.


Incidence and consequence of falls in inpatient rehabilitation of stroke patients.
The incidence rate, location, and timing of falls and performance of activities of daily living (ADLs) in 256 patients with stroke admitted to an 88-bed rehabilitation ward was observed with information on falls and level of ADLs upon admission extracted from patients' records. Of 273 falls among 121 of the 256 patients, 229 occurred in the patient's room or lavatory and 147 within 4 weeks of admission. Significant differences were detected between motor subscores under 64 and over 65 on the Functional Independence Measure (FIM) in fall proportional analysis. The mean fall rate in motor subclass of 26 to 38 was higher than in other subgroups. Those with cognitive subscore on the FIM lower than 29 were prone to fall. Also, deteriorated motor and cognitive functions were associated with a high risk of falls.


Unexplained cough: it is time to rule out Sjogren's syndrome.
Sjogren's syndrome is associated with chronic cough, but sicca symptoms are missing from cough evaluation guidelines. We evaluated patients with unexplained cough for undiagnosed Sjogren's syndrome. Patients referred to our pulmonary clinic (Sheba Medical Center, 2009 to 2012) with unexplained cough and concomitant dry eyes were selected for evaluation. Unexplained cough was defined as chronic cough of unknown etiology despite algorithm-based evaluation and treatment. Patients were evaluated in a dedicated clinic by a pulmonologist, rheumatologist, and ophthalmologist specializing in autoimmune disease. Patients completed the Leicester Cough Questionnaire, spirometry, antibody testing for anti Ro/La, ophthalmologic examination with visual acuity, eyelid, ocular surface fluorescein staining, tear break-up time and Schirmer's test, full slit lamp, and fundus examinations. Four-year follow-up was conducted by telephone questionnaire. We identified 24 patients among which 22 (21 females) agreed for evaluation. Eight patients (36%), seven initially, and one during follow-up were diagnosed with Sjogren's syndrome (SS) (six secondary and two primary SS). At 4-year follow-up, cough tended to persist and improve in only 37% with SS. These include 2 (Scl and RA) who received rituximab and 1 (stage 1 sarcoidosis) with spontaneous improvement. In contrast, cough improved in most (64%) patients without SS; the majority (eight/nine) report intensified disease-specific treatment (five allergic and three GERD). We describe patients in whom unexplained chronic cough was associated with dry eyes. Focused workup revealed undiagnosed Sjogren's syndrome in 36%. Dry eyes, with or without SS, is under-recognized and should be added to diagnostic algorithms for unexplained cough.


Etiological study of lymphadenopathy in HIV-infected patients in a tertiary care hospital.
Human immunodeficiency virus (HIV) infection has become a global pandemic. Persistent generalized lymphadenopathy (PGL) is very common manifestation of HIV infection. Moreover, different opportunistic infections such as tuberculosis (TB) and malignancies may present with lymphadenopathy. Mycobacterium avium complex (MAC) infection is most common with cluster of differentiation (CD)4+ count ≤50 cells/μL. Fine-needle aspiration cytology (FNAC) offers a simple and effective modality for obtaining a representative sample of the material from lymph nodes, permitting cytological evaluation and other investigations. The aim of this study is to find out the different etiologies of lymphadenopathy in HIV-infected patients and to establish a possible correlation with CD4+ count. A total of 100 HIV-infected patients having significant (>1 cm) extrainguinal lymphadenopathy were studied in 1 year at the Department of Pathology by FNAC and the stains used were Leishman-Giemsa, Ziehl-Neelsen (ZN), Papanicoloau, and Gram stains. For tubercular culture, Löwenstein-Jensen (LJ) medium was used. CD4+count was done by flow cytometer. The present study revealed four types of cytomorphological variants in lymphadenopathy cases by FNAC, which include: Reactive hyperplasia and caseation necrosis; caseation necrosis and ill-formed granuloma; well-formed granuloma without any necrosis; and non-Hodgkin lymphoma (NHL). The highest acid-fast bacilli (AFB) positivity was among the patients showing caseation necrosis. Tubercular culture in LJ media turned out as a more sensitive method for diagnosis than routine ZN staining. The 2 cases that showed well-formed epithelioid granuloma without any necrosis turned out to be histoplasmosis and cryptococcosis, respectively. In this study, we found 2 cases of NHL. The study also revealed that caseation necrosis and AFB positivity along with opportunistic infections increases with decreased CD4+ count.


Performance of CarbaNP and CIM tests in OXA-48 carbapenemase-producing Enterobacteriaceae.
This study applied two phenotypic tests, namely "Carbapenemase Nordmann-Poirel" (CarbaNP) test and "Carbapenem Inactivation Method" (CIM), against the isolates carrying the carbapenem resistance genes. The study included 83 carbapenem-resistant Enterobacteriaceae isolates producing oxacillinase-48 (OXA-48) and 30 carbapenem-sensitive Enterobacteriaceae isolates. Out of the total isolates studied, 77 isolates (92.77%) were identified as Klebsiella pneumoniae and six isolates (7.23%) were identified as Escherichia coli by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. Polymerase chain reaction (PCR) method used to detect resistance genes found that 74 isolates (89.16%) produced OXA-48 carbapenemase, whereas nine isolates (10.84%) produced both OXA-48 and New Delhi metallo-beta-lactamase-1 (NDM-1). The isolates producing both OXA-48 and NDM-1 were found to be positive by both phenotypic tests. Among isolates carrying only blaOXA-48 gene alone, nine isolates (13.04%) for CarbaNP test and two isolates for CIM test (2.90%) displayed false negative results, respectively. The sensitivity of CarbaNP and CIM tests was found to be 89.16% and 97.59%, respectively, whereas the specificity was determined to be 100% for both tests. These findings suggest that CarbaNP and CIM tests are useful tools to identify the carbapenemase producers. Molecular methods like PCR are recommended to verify false negative tests predicted to have OXA-48 activity.


Molecular identification of Gemella species from three patients with endocarditis.
Gemella morbillorum and Gemella haemolysans are opportunistic pathogens which cause endocarditis and other severe infections. We report on three patients with endocarditis, one with endocarditis caused by G. haemolysans and two with endocarditis caused by G. morbillorum. The paucity of reports concerning these bacteria is probably related to the difficulties associated with their identification. For example, one of the strains reported in this study was originally sent to our laboratory with a preliminary characterization as a short "gram-negative" coccobacillus, highlighting the specific problem associated with Gram staining of these bacteria. The usefulness of 16S rRNA gene amplification, partial sequencing, and comparison of the nucleotide sequence to those in databases when standard phenotypic identification schemes are not helpful is emphasized. We also suggest that the use of simple tests, such as testing susceptibility to vancomycin for gram-negative bacteria and colistin for gram-positive bacteria, could prevent misinterpretation of Gram staining in gram-variable bacteria such as Gemella spp.


Biomechanical influences on head posture and the respiratory movements of the chest.
The head represents 6% of total body weight, therefore it can significantly affect the biomechanics of human posture control, movements and activities. When set out of vertical body axis, head position interferes with the work of the other links in the kinematic chain. The aim of our study was to evaluate the effect of head posture on the breathing activities of the chest. The research was conducted on a group of 65 patients (51 years ± 9.8 years), including 48 women and 17 men. Head posture and chest movements were assessed using a photogrammetric method. The results confirmed the existence of a negative correlation between head position in the sagittal plane and movements of lower ribs. Forward head posture resulted in lower amplitude of costal arch motion: for the transverse plane Spearman's R = -0.296, for the frontal plane; -0.273, -0.289. Tilting the head in the frontal plane also influenced the change in the biomechanics of breathing and contributed to a reduction of respiratory movements of the lower ribs Spearman's R = -0.260. Changing the position of the head causes disturbances in the three-dimensional shape of the chest and its respiratory movements.


Serial biopsy results in prostate cancer screening study.
We evaluated prostate biopsy results in men with elevated prostate specific antigen (PSA) levels and/or suspicious digital rectal examination whose initial biopsies did not reveal cancer. A total of 2,526 volunteers 40 years old or older underwent 1 or more prostate biopsies for serum PSA concentrations greater than 4.0 ng./ml. (before May 1995) or greater than 2.5 ng./ml. (after May 1995), or digital rectal examination suspicious of cancer. We evaluated compliance with the biopsy recommendation and the cancer detection rate with regard to digital rectal examination results and increasing PSA levels. Of the men who underwent up to 10 biopsy procedures the serial cancer detection rates were 29%, 17%, 14%, 11%, 9% and 7%, respectively, on biopsy procedures 1 through 6. No significant difference in the yield of cancer on serial biopsies was observed between the groups using the greater than 4.0 ng./ml. and greater than 2.5 ng./ml. cutoff. There was a trend for more cancers detected through serial screening to be organ confined compared with those detected on initial screening (78% versus 69%, p = 0.05). Also, more cancers detected using the greater than 2.5 ng./ml. cutoff were organ confined (80% versus 66%, p = 0.004). Only approximately 1% of the cancers fulfilled the published criteria for clinically insignificant tumors. Nearly a quarter of prostate cancers detected in this screening study were missed by the initial biopsy. Of the 962 prostate cancers detected 77% were detected with 1, 91% with 2, 97% with 3 and 99% with 4 biopsy procedures. Serial biopsies detect more organ confined cancers without over detecting clinically unimportant tumors. Future studies are needed to determine whether obtaining more biopsy cores initially would provide earlier prostate cancer detection and avoid unnecessary repeat biopsies.


The fate of selected heavy metals and arsenic in a constructed wetland.
The fate of Cd, Pb, Cu, Zn, Ni, Cr, and As in a horizontal subsurface flow-constructed wetland was studied. The concentrations of the risk elements in treated municipal wastewater, wetland sediments, and Phragmites australis biomass were determined. Most of the studied elements were removed from the wastewater with fair efficiencies. On the other hand, As was released to treated water in the wetland bed. The removal efficiencies obtained for the individual elements were as follows: 64.2, 48.7, 70.0, 93.9, 63.6, 63.8, and -236.2%, respectively. The concentrations measured in sediments were the highest for samples taken 1 m from the inflow zone. They were 4.11, 2.01, 6.01, 4.85, 3.39, 9.30, and 3.17 times higher as compared to the samples taken in the distance of 10 m. The pollutants were preferentially deposited at the front part of the wetland bed where anaerobic conditions predominated and sulfate reduction took place. There were no significant differences in the concentrations of the studied elements in the aboveground biomass (Phragmites australis) samples taken in the distances of 1, 5, and 10 m from the inflow zone. However, the concentrations measured in the belowground biomass samples were significantly higher for samples taken at the front part of the wetland bed. The individual element concentration ratios between the below- and aboveground biomass measured for samples taken 1 m from the inflow zone were 4.97, 5.97, 2.21, 1.58, 2.26, 5.70, and 2.66 for Cd, Pb, Cu, Zn, Ni, Cr, and As, respectively.


[The laparoscopic Vecchietti technique for vaginal agenesis].
To evaluate feasibility and surgical long term, anatomic and functional results of the laparoscopic Vecchietti procedure to treat women with vaginal agenesis. We reported six cases of patients with a Mayer-Rokitansky-Küster-Hauser syndrome. The surgical procedure was the same for all patients. The results have been evaluated on the operative time, the intra and postoperative complications, the antalgic drugs consumption, the transit recovery, the hospital stay, the neovagina length, and the post operative sexual satisfaction. The mean operative time was 77.5 minutes. The mean paracetamol consumption was: 9.8 g. The mean transit recovery, and hospital stay were: 2 days, 9.8 days, respectively. No intra or postoperative complication occurred. The mean neovagina length evaluated at one year follow-up visit was 7.5 cm. Five patients have regular sexual activity. Three of them reported sexual satisfaction and showed having orgasm (clitoral: 3 cases, clitoral and vaginal: 2 cases). The 2 remaining patients reported dyspareunia. The global satisfaction index was of 71.6%. This surgical technique appeared to be safe, effective and reproducible. It allowed to obtain a neovagina with enough length and have encouraging results on sexual functioning Laparoscopy reduces the psychological and aesthetic consequences of surgery, especially for these young patients already distressed by their malformation.


Hydrochorous Seed Transport in the Lower Traisen River before and after Riverbed Restoration.
Hydrological restoration was carried out in a Lower Traisen, a small river within the floodplain of the Danube. The main goal was the reestablishment of typical riparian plant communities by using the potential of natural dispersal processes. We studied the transport of plant diaspores in the river water before and after the reconstruction of the riverbed. Aquatic seed traps were placed upstream and downstream of the restoration site. We identified the transported species and tested the viability of propagules. Functional species traits were analyzed to predict the probability of successful hydrochorous dispersal and changes in the transport pool due to the restoration. One-third of the local species pool was detected as being diaspores in the river. We observed a significant increase of ruderal species and neophytes, while the competitors and stress-tolerant competitors declined. Hydrochory is an important dispersal pathway for numerous plant species in the study area, including those without specific adaptations to this vector. Hydrochorous transport appears to be a sink for large-seeded species, primarily adapted to endozoochory. Follow-up management should be recommended to control the invasive species and to improve the structural and biological diversity of the Traisen Valley by supporting target species, which are also represented in the transport pool.


Resolution rate of pulmonary sarcoidosis and its related factors in a Japanese population.
A number of previous studies have reported on the rate of resolution of pulmonary sarcoidosis and its associated factors. However, most of the studies were conducted several decades ago and no similar surveys have been conducted in recent years. The aim of this study was to evaluate the rate of resolution of pulmonary sarcoidosis and its related factors in recently diagnosed patients, and to compare the results with those from previous studies. This study included 306 patients who had been newly diagnosed with pulmonary sarcoidosis between 2000 and 2009 in Sapporo, Japan. Chest radiographical findings were assessed at the initial visit and at the 2- or 5-year observation points. The rates of resolution on chest radiographs and the association with clinical manifestations were evaluated. The resolution rates were 17.9% at the 2-year and 29.9% at the 5-year observation point. These rates were lower than those reported in the earlier surveys. Younger subjects (aged <40 years) showed resolution more often (P < 0.05). The absence of extra-pulmonary organ involvement was associated with resolution at 5 years (P < 0.05). The clinical course of pulmonary sarcoidosis may be changing, showing a tendency not to resolve. At least in part, this may be due to the ageing of the Japanese population.


Prevalence of neural tube defects in the Yorkshire Region.
The birth prevalence of neural tube defects (NTD) in the Yorkshire Region was determined for 1985 and 1986 by ascertainment of cases in live-and stillborn babies and of pregnancies terminated for NTD. Sixty-seven cases of anencephaly, 82 of spina bifida and 11 others were identified, a prevalence of 1.54 per 1000 total births. Eighty-eight per cent of pregnancies associated with anencephaly and 48 per cent of those with spina bifida were terminated.


Embolization of cardiac myxomas masquerading as polyarteritis nodosa.
Cardiac myxomas are rare tumors which can mimic other diseases. We describe a 19-year-old man who presented clinically with polyarteritis nodosa (PAN). Muscle biopsy showed vasculitis, but corticosteroid and immunosuppressive therapy was initially effective. Cardiac myxomas were found by echocardiogram when the disease relapsed and were resected surgically. Segmental arterial aneurysms and stenoses were found on angiography after leg ischemia. We suggest that echocardiography should be performed in all cases of clinically suspected PAN.


DNA Methylation as Surrogate Marker For Gastric Cancer.
Stomach cancer remains, stubbornly, highly prevalent in East Asia. Still, stomach cancer has few biomarkers by which it can be predicted. Helicobacter pylori infection, a known carcinogen of stomach cancer, usually goes undetected prior to cancer diagnosis, due to the poor mucosal environments that its related gastric atrophy causes. We propose, herein, an endoscopic-biopsy-based cancer-predicting DNA methylation marker. We semi-quantitatively examined the methylation-variable sites near the CpG-island margins by radioisotope-labeling methylation-specific polymerase chain reaction in association with H. pylori, which increases age-related over-methylation in CpG islands of gastric mucosa. These age-related methylation patterns of the transitional-CpG sites are proposed as useful surrogate markers for stomach cancer. It would be helpful for setting the optimal screening interval for high-risk subjects as well as for estimating the prognosis and the predictability for recurrence of early gastric cancer in patients having undergone endoscopic submucosal dissection. New screening-interval guidelines for gastric cancer should be suggested considering individual risk based on age, severity of atrophy, H. pylori status, and DNA methylation pattern.


The Convention on Human Rights and Biomedicine of the Council of Europe.
The Convention on Human Rights and Biomedicine developed by the Council of Europe, now undergoing ratification, is the first international treaty focused on bioethics. This article describes the background of the Convention's development and its general provisions and provides a comparison of its requirements with those of federal regulations governing research with human subjects. Although most provisions are comparable, there are significant differences in scope and applicability, for example, in the areas of compensation for injury, research participation by persons with limited capacity to consent, assisted reproduction, organ transplantation, and research in emergency situations. The Convention represents a milestone in international bioethics and protection of human rights that will probably be referred to with increasing frequency.


Tunable polarization-independent and angle-insensitive broadband terahertz absorber with graphene metamaterials.
In this paper, we design a polarization-independent and angle-insensitive broadband THz graphene metamaterial absorber based on the surface plasmon-polaritons resonance. Full-wave simulation is conducted, and the results show that the designed metamaterial absorber has an absorption above 99% in the frequency range from 1.23 THz to 1.68 THz, which refers to a very high standard. Furthermore, the absorber has the properties of tunability, and the absorption can be nearly adjusted from 1% to 99% by varying the Fermi energy level of the graphene from 0 eV to 0.7 eV. In the simulation, when the incident angles of TE and TM waves change from 0° to 60°, the average absorption keeps greater than 80%. The proposed absorber shows promising performance, which has potential applications in developing graphene-based terahertz energy harvesting and thermal emission.


Anticoagulation and Antiplatelet Agent Resumption Timing following Traumatic Brain Injury.
Traumatic brain injury (TBI) is a major global health concern. Due to the increase in TBI incidence and the aging population, an increasing number of patients with TBI are taking antithrombotic agents for their underlying disease. When TBI occurs in patients with these diseases, there is a conflict between the disease, which requires an antithrombotic effect, and the neurosurgeon, who must minimize intracranial hemorrhage. Nevertheless, there are no clear guidelines for the reversal or resumption of antithrombotic agents when TBI occurs in patients taking antithrombotic agents. In this review article, we intend to classify antithrombotic agents and provide information on them. We also share previous studies on the reversal and resumption of antithrombotic agents in patients with TBI to help neurosurgeons in this dilemma.


Comparative Study on the Outcomes of Elective-Start versus Urgent-Start Peritoneal Dialysis Catheter Placement.
The aim of this study is to compare the outcomes of the elective-start versus urgent-start use of peritoneal dialysis (PD) catheters using percutaneous radiologic or laparoscopic techniques. Patients having their first peritoneal dialysis catheter placed and used between January 2005 and January 2018 were identified, and their medical records were retrospectively reviewed. Two groups were identified: elective-start (n = 211) and urgent-start (n = 29). Patient's demographics were similar between the two groups with the exception of age, which was higher in the elective-start group. The catheter complication rates and catheter removal rates at 3 and 12 months, mean days-to-first complication, mean days-to-catheter removal, and overall patient survival at 12 months were analyzed. Catheter complication rates at 3 and 12 months were similar between the two groups (27.8% and 48.9%, respectively, in the elective-start group versus 35.9% and 54.2%, respectively, in the urgent-start group, p=0.415). The catheter removal rates at 3 and 12 months were also similar between the two groups (p=0.088). Catheter leak was higher in the urgent-start group (13.8% versus 3.3%, respectively, p=0.011). There was no difference between the elective-start and the urgent-start groups in the mean days-to-first complication (95 vs 69, p=0.086), mean days-to-catheter removal (145 vs 127, p=0.757), and overall patient survival at 12 months (100% vs 97%, p=0.41). In conclusion, apart from catheter leak, there were similar rates of catheter complication and removal for PD catheter used for the elective-start compared to the urgent-start PD. Furthermore, the technique of placement did not affect the outcomes.


Translation initiation factor eIF2Bε promotes Wnt-mediated clonogenicity and global translation in intestinal epithelial cells.
Modulation of global mRNA translation, which is essential for intestinal stem cell function, is controlled by Wnt signaling. Loss of tumor supressor APC in stem cells drives adenoma formation through hyperactivion of Wnt signaling and dysregulated translational control. It is unclear whether factors that coordinate global translation in the intestinal epithelium are needed for APC-driven malignant transformation. Here we identified nucleotide exchange factor eIF2Bε as a translation initiation factor involved in Wnt-mediated intestinal epithelial stemness. Using eIF2BεArg191His mice with a homozygous point mutation that leads to dysfunction in the enzymatic activity, we demonstrate that eIF2Bε is involved in small intestinal crypt formation, stemness marker expression, and secreted Paneth cell-derived granule formation. Wnt hyperactivation in ex vivo eIF2BεArg191His organoids, using a GSK3β inhibitor to mimic Apc driven transformation, shows that eIF2Bε is essential for Wnt-mediated clonogenicity and associated increase of the global translational capacity. Finally, we observe high eIF2Bε expression in human colonic adenoma tissues, exposing eIF2Bε as a potential target of CRC stem cells with aberrant Wnt signaling.


Care diaries: a way of increasing head and neck cancer patient's involvement in their own care and the communication between clinicians.
Head and neck (H&N) cancer patients and their families meet a large number of clinicians during their long treatment period and many of them find it difficult to understand all the information given concerning their illness, treatment, and care. We have developed a care diary for these patients and their families, used also by the clinicians involved, to improve communication and patient involvement. The present survey was an evaluation of the helpfulness of those diaries. Anonymous answered questionnaires were collected from 42 H&N cancer patients, 28 family members, and 47 clinicians of different categories. Altogether 85% of the respondents stated that the care diaries had a positive effect on information, in general, and communication. It is recommended that care diaries should be implemented in the standard care for H&N cancer patients and their families. To improve the clinical value, it is particularly important to inform the clinicians on how to use the care diaries. The content and layout of the care diaries needs to be developed according to suggestions given from the respondents in this survey.


Shisha (waterpipe) smoking initiation among youth in Malaysia and global perspective: a scoping review (2006-2015).
To explore the initiating factors of waterpipe tobacco smoking (WTS) among youth. The analytic framework for this scoping review was performed using the methodology outlined by Arksey and O'Malley, which includes identification of the research question, study selection, charting the data, collating, summarizing and reporting the results that were primarily guided by the research question; 'what is known about the initiation of shisha smoking among youth?' Electronic databases such as Cochrane, MEDLINE and PsycINFO were used to search for relevant articles. Articles included were all in English and published within the year of 2006 to 2015. Inclusion criteria; i) age range of 10 to 29 years; ii) examined the reasons why youth started or tried WTS; iii) in full text. Therefore, 26 articles were included in this scoping review. This review has identified and classified the initiating factors of WTS among youth in four subtopics: individual factors, interpersonal influences, cigarettes and alcohol use, and media influences. Individual factors and interpersonal influences played an important role in initiation factors of WTS among youth. This study concludes that public health professionals within the Southeast Asia region need to promote innovative preventive measures through peer-to-peer led interventions that are also easily assessable on social media platforms. The public health messages need to address the misconceptions of risk associated to WTS use.


Pulmonary manifestations in adult T-cell leukemia at the time of diagnosis.
Adult T-cell leukemia (ATL) is an underlying immunodeficient condition which often leads to various kinds of pulmonary diseases. We have analyzed 35 consecutive patients (18 male, 17 female) with ATL to see to what extent pulmonary complications were involved at the time of diagnosis. Over one-third presented with respiratory symptoms and 14 (40%) patients had significant findings on chest radiographs on the first admission in which reticulo-nodular shadows were predominant in 10 patients, suggesting that overt ATL is preceded by interstitial pulmonary disease. In addition, bacterial pneumonia and pneumocystosis were experienced in over two-thirds of the patients during the clinical course, and more than half of the patients subsequently died of pulmonary complications suggesting that early institution of diagnostic procedures and treatment for pulmonary conditions is needed in ATL patients.


Rhodnius amazonicus Almeida, Santos & Sposina, 1973, bona species, close to R. pictipes Stål, 1872 (Heteroptera, Reduviidae, Triatominae).
The discovery of two atypical specimens of Rhodnius pictipes Stål, 1872 in French Guiana and the examination of the female holotype of R. amazonicus Almeida, Santos & Sposina, 1973, the only specimen of this species so far known, lead us to propose the rehabilitation of R. amazonicus synonymized with R. pictipes. The male is described for the first time and the female redescribed. Both external characters and genitalia distinguish R. amazonicus from R. pictipes. R. amazonicus shows affinities not only with pictipes but also with R. stali Lent, Jurberg & Galvão, 1993 and R. paraensis Sherlock, Guitton & Miles, 1977. A key is provided for these four species forming, in all likelihood, a natural group, i.e. the "pictipes group".


Qualitative exploration of perspectives of the pharmacists working in public-sector hospitals during COVID-19 pandemic.
The COVID-19 pandemic, a serious global health threat, has excruciating social and economic implications given its transmissibility, lack of therapy, and severity. In such a situation, pharmacists as frontline healthcare professionals hold a significant position to tackle. This study was designed to explore the perception and preparedness of pharmacists working in public sector hospitals amid such a pandemic in Pakistan. A total of 11 pharmacists were interviewed for this qualitative study design through a semi-structured interview guide. The interviews were recorded and transcribed verbatim. The thematic content analysis yielded six major themes; understanding of COVID-19, perceptions towards COVID-19, preventive aspects, management aspects, changes to lifestyle, and psychological aspects. Though efficient preparedness and approach to fighting against such pandemics were reported, pharmacists were found susceptible to infection and psychological stress. They also expressed lockdown as an effective measure to prevent the disease from spreading but still were concerned about its economic and social impact. Adequate planning and facilities from the national level should be made available for strengthening the hospital pharmacy service that helps improve the overall healthcare system of low- and middle-income countries like Pakistan. The provision of a protective facility, incentives, and occupational health surveillance packages are deemed necessary to boost the self-esteem and morale of hospital pharmacists that safeguard the early and effective management of such disasters.


[Surgical treatment of dumping by the Lygidakis' method].
Dumping is a common adverse effect of gastrectomy and severe dumping is one of the most intractable conditions in gastroenterology. When medical treatment and diet are insufficient, different operative techniques have been tried, all with an unsatisfactory rate of success. The Lygidakis technique for operative treatment of postgastrectomy-dumping is presented, and results from operations on four patients presented. The results obtained are promising, and Lygidakis operation may be considered as an important alternative to wellknown operative techniques when medical treatment or diet is without effect on severe dumping.


Nifedipine inhibits angiotensin II-induced cardiac fibrosis via downregulating Nox4-derived ROS generation and suppressing ERK1/2, JNK signaling pathways.
Nifedipine, a classic L-type dihydropyridine calcium channel blocker (CCB), has been reported to possess multiple cardioprotective properties. However, little is known about the effects of nifedipine on cardiac fibrosis induced by angiotensinII (AngII) and the detailed molecular mechanisms. In this study, we found that nifedipine attenuated AngII-induced cardiac fibrosis in vitro via inhibiting the proliferation, differentiation of cardiac fibroblasts and antagonizing the upregulation of extracellular matrix (ECM) protein fibronectin (FN) and the pro-fibrotic cytokine connective tissue growth factor (CTGF). Furthermore, nifedipine suppressed the upregulation of NAD(P)H oxidase 4 (Nox4) and the production of reactive oxygen species (ROS) induced by AngII. In addition, it markedly inhibited the phosphorylation of extracellular signal-regulate kinases 1/2 (ERK1/2) and c-Jun NH(2)-terminal kinase (JNK) stimulated by AngII. However, nifedipine exhibited no effect on the variation of intracellular Ca2+ concentration ([Ca2+]i). These results suggested that (1) nifedipine inhibited cardiac fibrosis induced by AngII; (2) the anti-fibrotic effects of nifedipine may be mediated by interfering with the production of ROS and the activation of ERK1/2 and JNK signaling pathways; (3) the classic calcium channel blocking action of nifedipine may not be involved in the anti-fibrotic activities.


Hyoscine vs glycopyrronium for drying respiratory secretions in dying patients.
The 'death rattle' is a common symptom among dying people, and causes a great deal of anxiety and upset to relatives and carers, including nurses. A mini-review was carried out to evaluate the effectiveness of two drugs--hyoscine hydrobromide and glycopyrronium--in drying up respiratory secretions in terminally ill patients. Searches were made of the Cochrane Library, Medline, Embase, Cinahl and Pharmline. Reference lists, trial databases and professional colleagues were also consulted. There was a scarcity of research material directly comparing the effects of the two drugs in the clinical setting. Two papers were used for comparison in the review but these produced conflicting results. Many discrepancies existed in terms of research methods, and in results. One paper demonstrated that hyoscine hydrobromide was the more effective drug; the other favoured glycopyrronium. There is no clear evidence to support the choice of one drug over the other, based on the clinical outcome selected for this review. Although clinical trials are difficult to conduct in this vulnerable patient group, more research is needed to facilitate the best management of this distressing symptom and allow clinical guidelines to be produced.


Risk of myocardial infarction and ischaemic stroke in adults with polymyositis and dermatomyositis: a general population-based study.
Limited data are available on the risk of cardiovascular disease in DM and PM. The purpose of this study was to estimate the risk of incident myocardial infarction (MI) and ischaemic stroke in adults with incident PM/DM at the general population level. We assembled a retrospective cohort of all adults with incident PM/DM in British Columbia, and we matched up to 10 adults randomly selected from the general population. We estimated the incidence rates (IRs) per 1000 person-years for MI and stroke. We calculated hazard ratios (HRs), adjusting for potential confounders. Among 774 new cases of inflammatory myopathies, 424 had PM (59% female, mean age 60 years) and 350 had DM (65% female, mean age 56 years). IRs for MI and stroke in PM were 22.52 and 10.15 events per 1000 person-years, respectively, vs 5.50 and 5.58 events in the comparison cohort, respectively. Fully adjusted HRs (95% CI) were 3.89 (95% CI: 2.28, 6.65) for MI and 1.76 (95% CI: 0.91, 3.40) for stroke. The age-, sex- and entry time-matched HRs for MI and stroke were highest in the first year after PM diagnosis (6.51, [95% CI: 3.15, 13.47] and 3.48 [95% CI: 1.26, 9.62], respectively). Similar trends were seen for DM. Our study demonstrates that PM and DM are both associated with an increased risk of MI but not ischaemic stroke. Our findings support increased vigilance in cardiovascular prevention, surveillance and risk modification in adults with PM and DM.