Community-academic partnerships: how can communities benefit?
In answer to the question of how academic institutions will meet medical education needs and public health challenges of the 21st century, a strong, vibrant, and sustained community partnership has been developed to teach public health, address community public health needs, and develop health policy to sustain these improvements, all with a practical approach. In this paper, the partnership between the University of Vermont College of Medicine and various community agencies is described from the perspective of how the community can benefit from educational efforts in public health. Particular focus is given to the community-academic partnership model in public health, a strong and sustained partnership between the University of Vermont College of Medicine and the United Way of Chittenden County Volunteer Center that began in 2004. Public health projects are designed, through partnerships with community nonprofit agencies, to be effective in addressing community issues while helping prepare students to become problem-solvers in population health. Examples of benefits seen by the community are used to illustrate the success of this approach. Project examples and a brief case study illustrate how community-academic partnerships in medical education can serve as a "catalyst" to improving community health.


3D X-ray ultra-microscopy of bone tissue.
We review the current X-ray techniques with 3D imaging capability at the nano-scale: transmission X-ray microscopy, ptychography and in-line phase nano-tomography. We further review the different ultra-structural features that have so far been resolved: the lacuno-canalicular network, collagen orientation, nano-scale mineralization and their use as basis for mechanical simulations. X-ray computed tomography at the micro-metric scale is increasingly considered as the reference technique in imaging of bone micro-structure. The trend has been to push towards increasingly higher resolution. Due to the difficulty of realizing optics in the hard X-ray regime, the magnification has mainly been due to the use of visible light optics and indirect detection of the X-rays, which limits the attainable resolution with respect to the wavelength of the visible light used in detection. Recent developments in X-ray optics and instrumentation have allowed to implement several types of methods that achieve imaging that is limited in resolution by the X-ray wavelength, thus enabling computed tomography at the nano-scale. We review here the X-ray techniques with 3D imaging capability at the nano-scale: transmission X-ray microscopy, ptychography and in-line phase nano-tomography. Further, we review the different ultra-structural features that have so far been resolved and the applications that have been reported: imaging of the lacuno-canalicular network, direct analysis of collagen orientation, analysis of mineralization on the nano-scale and use of 3D images at the nano-scale to drive mechanical simulations. Finally, we discuss the issue of going beyond qualitative description to quantification of ultra-structural features.


Metallisation of Biolox Delta® ceramic head: What's wrong?
Since the recent failure of certain coating models, hybrid implants (coated acetabular inserts with conventional stems) and stems with modular necks, there has been growing interest in the consequences of the generation and release of metal particles at the prosthetic interfaces. The use of ceramic heads has recently been described as an option for reducing the production of metal ions and their consequences. The present case report describes the first complete metallisation of a ceramic head secondary to an excessive release of metal ions at the head-neck junction. We believe this to have occurred due to the use of 12/14 cones of different manufacturers.


Abnormal group I metabotropic glutamate receptor expression and signaling in the frontal cortex in Pick disease.
Group I metabotropic glutamate receptors (mGluR1) regulate synaptic transmission through the stimulation of phospholipase Cbeta1 (PLCbeta1) and then by the activation of protein kinase C (PKC). Considering these properties, it is conceivable that major cortical functional deficits may be attributed to abnormal mGluR processing and signaling. The present work examines mGluRI expression and signaling in the frontal cortex (area 8) of 3 cases with Pick disease (PiD), a neurodegenerative disease with abnormal phospho-tau accumulation, in comparison with 3 age-matched controls by means of glutamate binding assays, enzymatic activity, gel electrophoresis and Western blotting, solubility and immunoprecipitation assays, and confocal microscopy. Reduced expression levels of PLCbeta1 and reduced PLCbeta1 activity have been found in PiD. The expression levels of the nonrelated phospholipase PLCgamma, a substrate of tyrosine kinase, are also reduced in PiD. This is accompanied by a marked decrease in the expression of cPKCalpha and increased expression of the inner band (76 kDa) of the nPKCdelta doublet at the expense of a decrease of the phosphorylated (active) form (78 kDa). In contrast, L-[3H]glutamate-specific binding to mGluRs is augmented in PiD cases, mainly because of the higher mGluR1 and mGluRs expression levels detected. No modifications in PLCbeta1 solubility have been observed in PiD and no interactions between PLCbeta1 and tau have been demonstrated in diseased and control cases. Moreover, double-labeling immunofluorescence and confocal microscopy have shown no colocalization of phospho-tau (AT8 antibody) and PLCbeta1 in phospho-tau inclusions, including Pick bodies. These results demontrate for the first time abnormal mGluR signaling in the cerebral cortex in PiD and selective vulnerability of phospholipases and PKC to PiD.


Evaluation of the Virulence of Aggregatibacter actinomycetemcomitans Through the Analysis of Leukotoxin.
Aggregatibacter actinomycetemcomitans is frequently isolated from localized aggressive periodontitis and periodontitis associated with systemic diseases. A. actinomycetemcomitans produces a leukotoxin, which induces apoptosis in human leukocytes. The leukotoxin expression is dependent on the upstream sequence, likely including the promoter, of the gene encoding leukotoxin; strains with the truncated/short upstream sequence express more leukotoxin than strains with the general/long upstream. This chapter addresses the determination of the type of the leukotoxin promoter by PCR analysis, and detection of the apoptosis in the coculture of human monocyte cell line (THP-1) with A. actinomycetemcomitans by the DNA ladder formation, membrane perturbation, and lactate dehydrogenase release.


Effects of cognitive behavioral therapy on sleep disturbances and quality of life among adults with type 2 diabetes mellitus: A randomized controlled trial.
Cognitive behavioral therapy (CBT) is recommended as the first-line nonpharmacotherapy for sleep complaints. However, there are no studies that tested CBT for improving sleep quality and increasing quality of life (QOL) in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aims to test the effect of CBT on sleep disturbances and QOL in patients with T2DM. In total, 187 participants with T2DM and comorbid poor sleep quality were included in the analysis with the control group of 93 receiving usual care (UC) only and the intervention group of 94 receiving CBT with aerobic exercise plus UC, The Pittsburgh Sleep Quality Index (PSQI), the Diabetes-Specific Quality of Life Scale (DSQLS) and the glycated hemoglobin (HbA1C) values were collected at baseline, after the 2-month intervention, and 6 months of follow-up. The CBT group had 3.03 points lower PSQI scores (95% confidence interval [CI]: 2.07-4.00, P < 0.001) and 7.92 points lower total DSQLS scores (95% CI: 4.98-10.87, P < 0.001) than the control group after 6-month follow-up. No difference was found in HbAlc between the two groups (t = -0.47, P = 0.64) after 2-month intervention, while the CBT group had 0.89 units lower HbAlc (95% CI: 0.49-1.28, P < 0.001) than the control group after 6-month follow-up. CBT is effective for sleep disturbances and can also improve sleep quality, increase QOL, and decrease glycemic levels in participants with T2DM. Chinese Clinical Trials Registration (Practical study of the appropriate technique for improvement of quality of life of the patients with type 2 diabetes in communities: ChiCTR-IOP-16008045).


Timing of excessive pregnancy-related weight gain and offspring adiposity at birth.
To evaluate whether the timing of excessive maternal weight gain in a cohort of women following current guidelines for healthy living during pregnancy affects neonatal adiposity at birth. One hundred seventy-two healthy women who were at least 18 years old with body mass indexes (BMIs) of at least 18.5 were recruited between 16 weeks and 20 weeks of gestation. The cohort followed healthy living guidelines during pregnancy and were retrospectively grouped according to 2009 Institute of Medicine guidelines for weight gain in the first and second halves of pregnancy: 1) appropriate gestational weight gain (ie, within Institute of Medicine recommendations) in the first and second halves of pregnancy ("overall appropriate"); 2) appropriate gestational weight gain in the first half of pregnancy and excessive gestational weight gain in the second half of pregnancy ("late excessive"); 3) excessive gestational weight gain in the first half of pregnancy and appropriate gestational weight gain in the second half of pregnancy ("early excessive"); and 4) excessive gestational weight gain throughout pregnancy ("overall excessive"). Primary measures included neonatal weight, length, BMI, and body fat at birth measured 6-18 hours after delivery. Neonatal body fat greater than 14% was considered excessive. Neonates of women who gained excessively in the first half of pregnancy exhibited greater heel-crown length, birth weight, and excessive body fat ("early excessive" 17.5±3.1%, "overall excessive" 18.7±3.3%) compared with those born to women who gained appropriately ("overall appropriate" 13.2±4.1%; "late excessive" 14.7±3.3%; P<.01). Neonates of women who gained excessively in the first half of pregnancy had an increased risk (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.35-5.17) of elevated body fat at birth compared with neonates of women with total excessive weight gain (OR 1.49, 95% CI 0.80-2.79). Timing of excessive weight gain is an important factor influencing neonatal morphometrics. Prevention of early excessive weight gain should be encouraged in the period before conception and reinforced early in pregnancy. II.


Environmental enrichment during early stages of life reduces the behavioral, neurochemical, and molecular effects of cocaine.
It is known that negative environmental conditions increase vulnerability to drugs, whereas little is known on whether positive environmental conditions such as enriched environments (EE) have protective effects against addiction. We have previously found that EE consisting of bigger cages containing several toys that were changed once per week reduce cocaine-induced increases in locomotor activity. Here, we also show that the rewarding effects of cocaine are blunted in mice reared from weaning to adulthood in EE compared to mice reared in standard environments (SE). In addition, although both EE and SE mice develop behavioral sensitization to cocaine, EE mice show less activation in response to repeated administration of cocaine injections and reduced responses to cocaine challenges. In vivo microdialysis experiments demonstrate that the protective effects of EE do not depend on reduced cocaine-induced increases in the dopamine levels in the ventral or dorsal striatum. On the other hand, they were associated with reduced cocaine-induced expression of the immediate early gene zif-268 in the nucleus accumbens (shell and core) of EE mice. Finally, basal levels of Delta-Fos B, a transcription factor known to be increased by sustained activation of striatal neurons, are higher in the striatum of EE compared to SE mice and repeated administration of cocaine increases Delta-Fos B levels in SE mice but decreases them in EE mice. Altogether our results demonstrate that exposure to complex environments during early stages of life produce dramatic changes in the striatum that result in reduced reactivity to drugs of abuse.


Growth Arrest Line Mimicking Lymphoma Involvement: The Findings of (99m)Tc-MDP Bone SPECT/CT and Serial Bone Scan in a Child with Non-Hodgkin's Lymphoma.
Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on (99m)Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth.


Displacement of the mandible during intermaxillary fixation after oblique sliding osteotomy. A stereometric and cephalometric radiographic study.
The X-ray stereometric method was applied for the first time to a series of consecutive patients to record operative repositioning of the mandible during oblique sliding osteotomy and postoperative displacement of the mandible during intermaxillary fixation. Comparison with cephalometric measurements was presented. The operative repositioning pattern was presented. Postoperatively a posterior displacement pattern was found with incisor extrusion in both jaws. Correlation between operative repositioning and postoperative displacement and between the two measurement methods was assessed. The stereometric method offers information on displacement on all three planes and a higher degree of accuracy. To avoid incisor extrusion, besides intermaxillary dental fiscation also skeletal fixation is recommended.


Molecular and Immunologic Signatures are Related to Clinical Benefit from Treatment with Vocimagene Amiretrorepvec (Toca 511) and 5-Fluorocytosine (Toca FC) in Patients with Glioma.
High-grade gliomas (HGGs) are central nervous system tumors with poor prognoses and limited treatment options. Vocimagene amiretrorepvec (Toca 511) is a retroviral replicating vector encoding cytosine deaminase, which converts extended release 5-fluorocytosine (Toca FC) into the anticancer agent, 5-fluorouracil. According to preclinical studies, this therapy kills cancer cells and immunosuppressive myeloid cells in the tumor microenvironment, leading to T-cell-mediated antitumor immune activity. Therefore, we sought to elucidate this immune-related mechanism of action in humans, and to investigate potential molecular and immunologic indicators of clinical benefit from therapy. In a phase I clinical trial (NCT01470794), patients with recurrent HGG treated with Toca 511 and Toca FC showed improved survival relative to historical controls, and some had durable complete responses to therapy. As a part of this trial, we performed whole-exome DNA sequencing, RNA-sequencing, and multiplex digital ELISA measurements on tumor and blood samples. Genetic analyses suggest mutations, copy-number variations, and neoantigens are linked to survival. Quantities of tumor immune infiltrates estimated by transcript abundance may potentially predict clinical outcomes. Peak values of cytokines in peripheral blood samples collected during and after therapy could indicate response. These results support an immune-related mechanism of action for Toca 511 and Toca FC, and suggest that molecular and immunologic signatures are related to clinical benefit from treatment.


Supporting student nurses on placement in nursing homes: the challenges for the link-tutor role.
Practice-based learning has always been a key feature of nursing education, and the quality of student learning is heavily influenced by the quality of the clinical experience. In addition, with an ageing population, nurses will need to better develop the particular clinical skills related to meeting the needs of older people in diverse settings. Increasingly, health care faculties in universities are turning to nursing homes to provide clinical placements for student nurses. This paper examines the literature related to the benefits and challenges of using nursing homes as placement areas for student nurses, with particular reference to the challenges that nursing home placements present for link tutors. The paper concludes with a proposal for a model for the link-tutor role in nursing homes.


Effects of Bacillus subtilis, butyrate, mannan-oligosaccharide, and naked oat (ß-glucans) on growth performance, serum parameters, and gut health of broiler chickens.
Four nonantibiotic alternative growth promoters for broiler chickens were evaluated. Ross 308 chicks were fed a control diet (mainly corn and soybean meal) or a diet supplemented with a probiotic (Bacillus subtilis Gallipro DSM 17299), encapsulated butyric acid (Novyrate C), mannan-oligosaccharide (Actigen MOS) or formulated with 20% naked oat (starter diet) and 30% naked oat (grower and finisher). The study was carried out as a complete random blocked design with 10 pens for each diet, 45 birds per pen. Compared to the control, the naked oat diet improved the average daily gain by 16% during the starter phase (up to d 10). The probiotic did so during the grower phase as did butyric acid in the finisher phase (up to d 34). For the experiment overall, the probiotic decreased average daily gain slightly. The best improvement in feed conversion ratio was obtained in the butyrate group (5%). No significant treatment effect on crop pH or on mortality was observed. The naked oat diet gave a slightly lower cecum pH on d 34. The MOS supplement decreased jejunal mass on d 34 and increased villus length (34%) and villus height/crypt depth ratio (32%) measured on d 10. Naked oat, butyric acid and MOS diets all reduced serum endotoxin levels. The probiotic increased serum C-reactive protein. All noncontrol diets reduced serum malondialdehyde. The naked oat diet reduced d 34 litter pH by about 0.3. Some effects of the proposed non-antibiotic growth promoters have been observed and could contribute to livestock performance. Their exact modes of action remained to be defined.


Preparation, characterization, and potential application of an immobilized glucose oxidase.
A simple, one-step process, using 0.25 M p-benzoquinone dissolved in 20% dioxane at 50 degrees C for 24 h was applied to the activation of polyacrylamide beads. The activated beads were reacted with glucose oxidase isolated from Aspergillus niger. The coupling reaction was performed in 0.1 M potassium phosphate at pH 8.5 and 0-4 degrees C for 24 h. The protein concentration was 50 mg/mL. In such conditions, the highest activity achieved was about 100 U/g solid. The optimum pH for the catalytic activity was shifted by about 1 pH unit in the acidic direction to pH 5.5. Between 35 and 50 degrees C, the activity of the immobilized form depends on the temperature to a smaller extent than that of the soluble form. Above 50 degrees C, the activity of immobilized glucose oxidase shows a sharper heat dependence. The enzyme-substrate interaction was not profoundly altered by the immobilization of the enzyme. The heat resistance of the immobilized enzyme was enhanced. The immobilized glucose oxidase is most stable at pH 5.5. The practical use of the immobilized glucose oxidase was tested in preliminary experiments for determination of the glucose concentration in blood sera.


Effect of screw-access channels on the fracture resistance of 3 types of ceramic implant-supported crowns.
Access channels for retrieving ceramic implant-supported screw-retained crowns may decrease their fracture resistance. The purpose of this in vitro study was to evaluate the effect of screw-access channels on 3 types of ceramic implant-supported crowns. Sixty computer-aided designed and computer-aided manufactured (CAD-CAM) ceramic implant-supported screw-retained maxillary premolar crowns were fabricated, 30 with an occlusal screw-access channel and 30 without access channels. Each group was further divided into the following 3 subgroups of 10 specimens each: monolithic zirconia, veneered zirconia, and lithium disilicate. Identical milled titanium implant abutments were fabricated. Crowns were fabricated with standardized thicknesses and subjected to cyclic loading until failure occurred. Data analysis was performed using 1-way analysis of variance test of significance followed by Tukey honest significant difference (HSD) test (α=.05). No significant differences in fracture resistance were found between access channel groups and corresponding groups without access channels (P>.05). Among the subgroups, monolithic zirconia recorded the highest fatigue failure mean load values (2047.8 ±83.2 N for crowns with access channels and 2028.7 ±104.5 N for crowns without access channels), which was significantly higher (P<.05) than values for the lithium disilicate group (605.4 ±37.9 N for crowns with access channels and 615.3 ±76.6 N for crowns without access channels) and the veneered zirconia group (411 ±34.4 N for crowns with access channels and 461.2 ±72.7 N for crowns without access channels), which recorded the lowest fatigue failure load mean values. Screw-access channels did not affect the fatigue failure load of monolithic zirconia, monolithic lithium disilicate, or veneered zirconia ceramic crowns. Monolithic zirconia crowns recorded significantly higher fatigue failure load among the 3 types of crowns tested.


Single-molecule imaging in the primary cilium.
The primary cilium is an important signaling organelle critical for normal development and tissue homeostasis. Its small dimensions and complexity necessitate advanced imaging approaches to uncover the molecular mechanisms behind its function. Here, we outline how single-molecule fluorescence microscopy can be used for tracking molecular dynamics and interactions and for super-resolution imaging of nanoscale structures in the primary cilium. Specifically, we describe in detail how to capture and quantify the 2D dynamics of individual transmembrane proteins PTCH1 and SMO and how to map the 3D nanoscale distributions of the inversin compartment proteins INVS, ANKS6, and NPHP3. This protocol can, with minor modifications, be adapted for studies of other proteins and cell lines to further elucidate the structure and function of the primary cilium at the molecular level.


The novel exon, exon T, of the human progesterone receptor gene and the genomic organization of the gene.
Recently, we have cloned the novel isoform of the progesterone receptor (PR) cDNA (PR isoform S cDNA) from the human testicular cDNA library. The isoform S cDNA consists of the novel exon (termed the exon S of the PR gene) and the exons 4-8 of the PR gene. In order to investigate the existence of the other isoform of the human PR cDNA, the human testicular cDNA library was screened by the exons 4-8 corresponding sequence of the human PR cDNA in the present study. As a result, we have identified a novel isoform of the PR cDNA (termed the PR isoform T cDNA (PR-T cDNA)), which consisted of a previously unidentified 5'-sequence and the exons 4-8 of the PR gene. The structure of this isoform T cDNA is essentially similar to that of the isoform S cDNA. By the genomic cloning, the 5'-sequence of the PR isoform T mRNA was demonstrated to originate from a novel independent exon, exon T, which was located in the 5'-upstream region of the exon S.


Chronic constipation due to Hirschsprung's disease and desmosis coli in a family.
Five members of a family are described, all of whom suffered from chronic constipation and megacolon. Detailed clinical and histologic evaluation of each member revealed that two individuals have histologic evidence of desmosis coli and three have Hirschsprung's disease, one of whom also has desmosis coli. The latter combination has never been described before, either in a family or in a single patient. Genetic studies of the family did not reveal an increase in the number of shared markers for the RET proto-oncogene, suggesting that this previously undescribed familial association is likely not caused by a mutation in the RET gene, but by other genetic abnormalities.


Clinical consequences of an increasing trend of preferential use of cultured villi for molecular diagnosis by CVS.
To compare the use of uncultured versus cultured villus cells for DNA-based prenatal diagnosis. A retrospective review of molecular testing of chorionic villus sampling (CVS) cases from 1988-2007. Method of analysis, gestational age (GA) at CVS and at diagnosis, time from procedure to results, results of maternal contamination studies, and the laboratory employed were abstracted from patient charts. Trends in laboratory practices over time were analyzed. Time from CVS to diagnosis was longer when cultured cells were used. Average GA at diagnosis was 14-6/7 weeks with cultured cells vs 13-0/7 weeks with uncultured villi (p < 0.001). Recently, laboratories are more frequently requiring cultured cells, resulting in significantly greater delays in time to diagnosis and GA at results. 'Direct' DNA extraction saves 2 weeks from CVS to results. More women are afforded the option of an earlier, safer pregnancy termination if uncultured villi are used for molecular diagnosis. Implementation of standardized DNA extraction protocols and sample-size requirements can optimize the use of uncultured villi for molecular prenatal diagnosis. Increased awareness of the importance of rapid results and the advantages of 'direct' DNA extraction from uncultured villi can lead to improvements that are of clinical significance for patients undergoing early prenatal diagnosis.


Synthesis and SAR optimization of quinazolin-4(3H)-ones as poly(ADP-ribose)polymerase-1 inhibitors.
We have demonstrated that quinazolin-4(3H)-one, a nicotinamide (NI) mimic with PARP-1 inhibitory activity in the high micromolar range (IC(50) = 5.75 μM) could be transformed into highly active derivatives with only marginal increase in molecular weight. Convenient one to two synthetic steps allowed us to explore extensive SAR at the 2-, and 5- through 8-positions of the quinazolin-4(3H)-one scaffold. Substitutions at the 2- and 8-positions were found to be most favorable for improved PARP-1 inhibition. The amino group at 8-position resulted in compound 22 with an IC(50) value of 0.76 μM. Combination of the 8-amino substituent with an additional methyl substituent at the 2-position provided the most potent compound 31 [8-amino-2-methylquinazolin-4(3H)-one, IC(50) = 0.4 μM] in the present study. Compound 31 inhibited the proliferation of Brca1-deficient cells with an IC(50) value of 49.0 μM and displayed >10-fold selectivity over wild type counterparts. Binding models of these derivatives within the active site of PARP-1 have further supported the SAR data and will be useful for future lead optimization efforts.


Bronchoscopic utilization of the Nd:YAG laser for obstructing lesions of the trachea and bronchi.
The combination of recent technological developments in earlier detection of lung cancer, together with the simultaneous introduction of new palliative therapeutic tools, including the Nd:YAG laser, offers new hope in the treatment of lung carcinomas. Endobronchial usage of the Nd:YAG laser has provided a new technique to treat otherwise untreatable, obstructive malignant tumors, as well as the means to avoid the need for more extensive surgical procedures for benign lesions. It is important to quantify and translate this information to advanced science for optimal development and use.


Bioinspired synthesis of protein/polysaccharide-decorated folate as a nanocarrier of curcumin to potentiate cancer therapy.
Curcumin is a promising anticancer agent, but its clinical utilization has been hindered by its low solubility and bioaccessibility. To overcome these obstacles, we developed a natural protein-polysaccharide nanocomplex made from casein nanoparticles coated with a double layer of alginate and chitosan and decorated with folic acid (fCs-Alg@CCasNPs) for use as a nanocarrier for curcumin. The developed nanoformulation showed a drug encapsulation efficiency = 75%. The measured size distribution of fCs-Alg@CCasNPs was 333.8 ± 62.35 nm with a polydispersity index (PDI) value of 0.179. The recorded zeta potential value of fCs-Alg@CCasNPs was 28.5 mV. Morphologically, fCs-Alg@CCasNPs appeared spherical, as shown by transmission electron microscopy (TEM). The successful preparation of fCs-Alg@CCasNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy of all the constituents forming the nanoformulation. Further in vitro investigations indicated the stability of fCs-Alg@CCasNPs as well as their controlled and sustained release of curcumin in the tumor microenvironment. Compared with free curcumin, fCs-Alg@CCasNPs induced a higher cytotoxic effect against a pancreatic cancer cell line. The in vivo pharmacokinetics of fCs-Alg@CCasNPs showed a significant AUC0-24 = 2307 ng.h/ml compared to 461 ng.h/ml of free curcumin; these results indicated high curcumin bioavailability in plasma. The in vivo results of tumor weight, the amount of DNA damage measured by comet assay and histopathological examination revealed that treating mice with fCs-Alg@CCasNPs (either intratumorally or intraperitonially) prompted higher therapeutic efficacy against Ehrlich carcinoma than treatment with free curcumin. Therefore, the incorporation of curcumin with protein/polysaccharide/folate is an innovative approach that can synergistically enhance curcumin bioavailability and potentiate cancer therapy with considerable biosafety.


Development and validation of the while-in-bed-smartphone-use-induced sleep procrastination scale (WSPS) in Chinese undergraduates with/without problematic smartphone use.
Problematic smartphone use (PSU) has become a global public health problem. Excessive while-in-bed smartphone use may result in sleep procrastination and other negative outcomes. The present study aimed to develop and validate a new scale called WSPS to assess while-in-bed-smartphone-use-induced sleep procrastination among undergraduates. In total, 910 Chinese undergraduates completed the collection of WSPS, smartphone addiction scale-short version (SAS-SV), bedtime procrastination scale, Pittsburgh sleep quality index, and Zung self-rating depression scale. The whole sample were randomly splited in the exploratory factor analysis (EFA) sample (n = 455) and confirmatory factor analysis (CFA) sample (n = 455). 40 undergraduates with PSU (SAS-SV > 31) and 40 without PSU were asked to keep sleep diary for 2 weeks and complete the WSPS again. EFA and CFA supported a six-item unidimensional structure of the WSPS. The WSPS demonstrated acceptable internal consistency among undergraduates. The WSPS showed good concurrent validity with other relevant variables including PSU, BP, sleep quality, and depression. Scalar invariance of the WSPS between undergraduates with/without PSU was supported, as well as scalar invariance across gender. The WSPS showed good convergent validity with self-report everyday while-in-bed smartphone use duration and good discriminant validity with sleep duration and sleep onset latency recorded by sleep diary. The WSPS also presented good test-retest reliability among undergraduates with/without PSU. The WSPS is a reliable and valid measure of while-in-bed-smartphone-use-induced sleep procrastination in undergraduates with/without PSU.


Manifestation of a sellar hemangioblastoma due to pituitary apoplexy: a case report.
Hemangioblastomas are rare, benign tumors occurring in any part of the nervous system. Most are found as sporadic tumors in the cerebellum or spinal cord. However, these neoplasms are also associated with von Hippel-Lindau disease. We report a rare case of a sporadic sellar hemangioblastoma that became symptomatic due to pituitary apoplexy. An 80-year-old, otherwise healthy Caucasian woman presented to our facility with severe headache attacks, hypocortisolism and blurred vision. A magnetic resonance imaging scan showed an acute hemorrhage of a known, stable and asymptomatic sellar mass lesion with chiasmatic compression accounting for our patient's acute visual impairment. The tumor was resected by a transnasal, transsphenoidal approach and histological examination revealed a capillary hemangioblastoma (World Health Organization grade I). Our patient recovered well and substitutional therapy was started for panhypopituitarism. A follow-up magnetic resonance imaging scan performed 16 months postoperatively showed good chiasmatic decompression with no tumor recurrence. A review of the literature confirmed supratentorial locations of hemangioblastomas to be very unusual, especially within the sellar region. However, intrasellar hemangioblastoma must be considered in the differential diagnosis of pituitary apoplexy.


Correction: Structural and spectral properties of generative models for synthetic multilayer air transportation networks.
[This corrects the article DOI: 10.1371/journal.pone.0258666.].


Primary care clinicians' perspectives on clinical decision support to enhance outcomes of online obesity treatment in primary care: A qualitative formative evaluation.
Online behavioral treatment for obesity produces clinically-meaningful weight losses among many primary care patients. However, some patients experience poor outcomes (i.e., failure to enroll post-referral, poor weight loss, or premature disengagement). This study sought to understand primary care clinicians' perceived utility of a clinical decision support system (CDSS) that would alert clinicians to patients' risk for poor outcome and guide clinician-delivered rescue interventions to reduce risk. Qualitative formative evaluation was conducted in the context of an ongoing pragmatic clinical trial implementing online obesity treatment in primary care. Interviews were conducted with 14 nurse care managers (NCMs) overseeing patients' online obesity treatment. Interviews inquired about the potential utility of CDSS in primary care, desired alert frequency/format, and priorities for alert types (non-enrollment, poor weight loss, and/or early disengagement). We used matrix analysis to generate common themes across interviews. Nearly all NCMs viewed CDSS as potentially helpful in clinical practice. Alerts for patients at risk for disengagement were of highest priority, though all alert types were generally viewed as desirable. Regarding frequency and delivery mode of patient alerts, NCMs wanted to balance the need for prompt patient intervention with minimizing clinician burden. Concerns about CDSS emerged, including insufficient time to respond promptly and adequately to alerts and the need to involve other support staff for patients requiring ongoing rescue intervention. NCMs view CDSS for online obesity treatment as potentially feasible and clinically useful. For optimal implementation in primary care, CDSS must minimize clinician burden and facilitate collaborative care.


Overproduction of protein kinase C causes disordered growth control in rat fibroblasts.
We have generated a series of rat fibroblast cell lines that stably overexpress a full-length cDNA encoding the beta 1 form of protein kinase C (PKC). These cell lines contain a 20- to 53-fold increase in PKC activity and exhibit dramatically enhanced morphologic changes following exposure to the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA). They grow to a high saturation density in monolayer cultures and, when maintained at postconfluence, develop small, dense foci. In contrast to control cells, which display complete anchorage dependence, PKC-overproducing cells form small colonies in soft agar in the absence of TPA and large colonies in the presence of TPA. Thus, the mere overproduction of a single form of PKC is sufficient to confer multiple growth abnormalities in rat fibroblasts. These results provide direct evidence that PKC plays a critical role in growth control and that it mediates several of the cellular effects of the phorbol ester tumor promoters. They also suggest that the activation of PKC may be of central importance in the process of multistage carcinogenesis.


One hospital's clinical evaluation of brushless scrubbing.
BRUSHLESS SCRUBBING rapidly is becoming an accepted method for surgical hand scrubbing. AN EVALUATION was undertaken at an acute care hospital in the southeastern United States to examine brushless scrubbing before laminectomy, craniotomy, and colectomy procedures. PATIENTS DID NOT SHOW an increase in postoperative surgical site infections when the brushless scrubbing product was used. SATISFACTION AND COMPLIANCE among users of the product was positive.


Improving selective hydrogenation of carbonyls bond in α, β-unsaturated aldehydes over Pt nanoparticles encaged within the amines-functionalized MIL-101-NH2.
The high selectivity in the hydrogenation reactions of α, β-unsaturated aldehydes is always a demanding task. Precious Pt-based catalysts play a pivotal role in selective catalytic hydrogenation of α, β-unsaturated aldehydes, but controlling the selectivity is still a great challenge. Herein, the Pt nanoparticles were encaged within the mesopores of amines (-NH2) functionalized MOFs via polyol reduction method as an efficient approach to enhance the selectivity of desired carbonyls bond reduction. The as-prepared 3-Pt/MOF-NH2(x) catalysts retained the inherent properties of MOF-NH2(x) supports such as crystallinity, surface area, pore texture, and surface acidity. Remarkably, the amines modified MOFs supported Pt-based catalysts (3-Pt/MOF-NH2(x)) improved the selective hydrogenation of carbonyls (CO) bond in cinnamaldehyde (CAL) and Furfural (FFL) with a higher selectivity (≥80 %) under mild conditions as compared to other reported catalysts. The improved catalytic performance for the selective hydrogenation of carbonyls (CO) bond is credited to the nitrogen (N) heteroatom of the amines group existing in the skeleton of MOFs and somewhat to the steric effect induced by mesopores of MOFs. The N heteroatom not only helps in the high uniform dispersion and stabilization of small-sized Pt nanoparticles (≈2nm) but also adjust the electron movement (electronic density) via synergistic effect resulting from the N to the vacant d-orbital of active Pt nanoparticles confined within MOFs, leading to more new interfacial electrophilic and nucleophilic sites, which are beneficial for selective hydrogenation of CO bond. Besides, the steric effect induced by mesopores of MOFs, encaging Pt nanoparticles, can also enhance the selective adsorption of the CO bond to interact with the catalyst active sites, resulting in higher selective hydrogenation of CO bond.


Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study.
Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut. In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated. Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants. Current Controlled Trials ISRCTN16211826.


Tissue iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women.
We previously showed that iron supplementation significantly improves iron status and maximal work capacity in previously untrained, marginally iron-deficient women with a baseline serum transferrin receptor concentration > 8.0 mg/L. However, the effect of transferrin receptor status on adaptation in endurance capacity after aerobic training in these subjects has not been fully explored. Our objective was to examine the effect of baseline serum transferrin receptor status on adaptations in endurance capacity. Forty-one untrained, iron-depleted, nonanemic women were randomly assigned to receive either 100 mg FeSO(4) or a placebo for 6 wk in a double-blind trial. All subjects trained on cycle ergometers 5 d/wk for the last 4 wk of the study. Endurance capacity was assessed at baseline and after treatment by using a 15-km time trial conducted on a cycle ergometer. Significant treatment effects were observed for time to complete the 15-km time trial, work rate, and percentage of maximal oxygen uptake in subjects with a baseline serum transferrin receptor concentration > 8.0 mg/L. No significant treatment effects were observed in subjects with a normal baseline transferrin receptor concentration. Our findings suggest that, in the presence of overt tissue iron deficiency, iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women. This impairment can be corrected with iron supplementation.


Caspase-3 and prostaglandins signal for tumor regrowth in cancer therapy.
Chemo- and radio-therapeutic regimens frequently kill cancer cells by inducing apoptosis, a cell-death subroutine that involves the activation of a particular class of proteases called caspases. In a recent issue of Nature Medicine, Huang et al. (2011) show that caspase activation in dying tumor cells causes the release of soluble lipid messengers, notably prostaglandin E(2), that stimulate tumor cell proliferation. In this short review, we will discuss the clinical and therapeutic implications of these findings.


A structure- and chemical genomics-based approach for repositioning of drugs against VCP/p97 ATPase.
Valosin-containing protein (VCP/p97) ATPase (a.k.a. Cdc48) is a key member of the ER-associated protein degradation (ERAD) pathway. ERAD and VCP/p97 have been implicated in a multitude of human diseases, such as neurodegenerative diseases and cancer. Inhibition of VCP/p97 induces proteotoxic ER stress and cell death in cancer cells, making it an attractive target for cancer treatment. However, no drugs exist against this protein in the market. Repositioning of drugs towards new indications is an attractive alternative to the de novo drug development due to the potential for significantly shorter time to clinical translation. Here, we employed an integrative strategy for the repositioning of drugs as novel inhibitors of the VCP/p97 ATPase. We integrated structure-based virtual screening with the chemical genomics analysis of drug molecular signatures, and identified several candidate inhibitors of VCP/p97 ATPase. Importantly, experimental validation with cell-based and in vitro ATPase assays confirmed three (ebastine, astemizole and clotrimazole) out of seven tested candidates (~40% true hit rate) as direct inhibitors of VCP/p97 and ERAD. This study introduces an effective integrative strategy for drug repositioning, and identified new drugs against the VCP/p97/ERAD pathway in human diseases.


Free energy potential for aggregation of mixed phosphatidylcholine/phosphatidylserine lipid vesicles in glucose polymer (dextran) solutions.
The energetics of lipid vesicle-vesicle aggregation in dextran (36,000 mol wt) solutions have been studied with the use of micromechanical experiments. The affinities (free energy reduction per unit area of contact) for vesicle-vesicle aggregation were determined from measurements of the tension induced in an initially flaccid vesicle membrane as it adhered to another vesicle. The experiments involved controlled aggregation of single vesicles by the following procedure: two giant (approximately 20 micron diam) vesicles were selected from a chamber on the microscope stage that contained the vesicle suspension and transferred to a second chamber that contained a dextran (36,000 mol wt) salt solution (120 mM); the vesicles were then maneuvered into position for contact. One vesicle was aspirated with sufficient suction pressure to create a rigid sphere outside the pipette; the other vesicle was allowed to spread over the rigid vesicle surface. The aggregation potential (affinity) was derived from the membrane tension vs. contact area. Vesicles were formed from mixture of egg lecithin (PC) and phosphatidylserine (PS). For vesicles with a PC/PS ratio of 10:1, the affinity showed a linear increase with concentration of dextran; the values were on the order of 10(-1) ergs/cm2 at 10% by weight in grams. Similarly, pure PC vesicle aggregation was characterized by an affinity value of 1.5 X 10(-1) ergs/cm2 in 10% dextran by weight in grams. In 10% by weight in grams solutions of dextran, the free energy potential for vesicle aggregation decreased as the surface charge (PS) was increased; the affinity extrapolated to zero at a PC/PS ratio of 2:1. When adherent vesicle pairs were transferred into a dextran-free buffer, the vesicles did not spontaneously separate. They maintained adhesive contact until forceably separated, after which they would not read here. Thus, it appears that dextran forms a "cross-bridge" between the vesicle surfaces.


Atypical Hemolytic Uremic Syndrome Occurring After Receipt of mRNA-1273 COVID-19 Vaccine Booster: A Case Report.
Atypical hemolytic uremic syndrome (aHUS) is a subtype of thrombotic microangiopathy (TMA) characterized by a dysregulation of the alternative complement pathway. Here, we report a previously healthy 38-year-old woman in whom aHUS developed after a COVID-19 vaccine booster. One day after receipt of a booster dose of mRNA-1273 vaccine, she felt ill. Because of persistent headache, nausea, and general malaise, she went to her general practitioner, who referred her to the hospital after detecting hypertension and acute kidney injury. A diagnosis of TMA was made. Her treatment consisted of blood pressure control, hemodialysis, plasma exchange, and respiratory support. Kidney biopsy confirmed the diagnosis of acute TMA. The patient was referred for treatment with eculizumab, and kidney function improved after initiation of this therapy. Genetic analysis revealed a pathogenic C3 variant. SARS-CoV-2 infection as a trigger for complement activation and development of aHUS has been described previously. In addition, there is one reported case of aHUS occurring after receipt of the adenovirus-based COVID-19 vaccine ChAdOx1 nCoV-19, but, to our knowledge, this is the first case of aHUS occurring after a booster dose of an mRNA COVID-19 vaccine in a patient with an underlying pathogenic variant in complement C3. Given the time frame, we hypothesize that the vaccine probably was the trigger for development of aHUS in this patient.


Establishing Institution-Specific Normative Data for the BREAST-Q Reconstruction Module: A Prospective Study.
Breast satisfaction in general female populations is relatively unknown and prior research populations do not reflect our community. We sought to assess breast satisfaction in a cohort of female participants utilizing the BREAST-Q and determine the impact of participant-related factors. Females with no history of breast cancer or breast surgery attending gynecology appointments completed preoperative BREAST-Q reconstruction modules and demographic forms in this prospective, single-center, patient-reported outcomes study. We also assessed participant-related factors capable of influencing BREAST-Q scores. Three hundred females were included. Increasing body mass index had significant associations with lower Satisfaction with Breasts and Psychosocial Well-being scores. Increasing age was associated with significantly lower Sexual Well-being scores. African Americans had significantly higher scores for Satisfaction with Breasts, Psychosocial Well-being, and Sexual Well-being compared with Caucasians. Bra cup sizes A and C were associated with significantly higher Psychosocial Well-being scores than other sizes. Bra cup sizes A, B, and C were associated with significantly higher Sexual Well-being and Physical Well-being: Chest scores than larger sizes. Bra cup sizes B and C were associated with significantly higher Physical Well-being: Abdomen scores than size DD. Bra cup size A was associated with significantly higher Satisfaction with Breasts scores than sizes DD and >DD. Bra cup size C was associated with significantly higher Satisfaction with Breasts scores than larger sizes. Body mass index, age, race, and bra cup sizes significantly impact BREAST-Q scores in our population. Determining normative BREAST-Q scores in female populations could represent important baselines for breast outcomes research. Level of Evidence: 2.


Synthesis, DNA binding, and cytotoxicity of 1,4-bis(2-amino-ethylamino)anthraquinone-amino acid conjugates.
Two series of 1,4-bis(2-amino-ethylamino)anthraquinone-amino acid conjugates (BACs), ametantrone (AT)-amino acid conjugates (AACs) and mitoxantrone (MX)-amino acid conjugates (MACs), were designed and synthesized. The DNA binding of BACs was evaluated by DNA thermal denaturation experiment. In the series, the methionine-substituted BACs had the weakest DNA binding, while the lysine-substituted BACs had the highest T(m) values. The abilities of BACs to inhibit the growth of MCF-7, NCI-H460, SF-268, and PC-3 cell lines were determined. l-Met-MAC 16 and l-Lys-MAC 20 were the most potent growth inhibitors. MAC 16 was more cytotoxic than MX, whereas the T(m) of MAC 16 was much lower than that of MX. In contrast to MAC 16, l-Lys-MAC 20 demonstrated higher T(m) than MX. These data suggested that Met-BACs possessed a different pharmacological profile, in which the ability to stabilize DNA is not parallel to the ability to kill cancer cells, from that of AT and MX. The primary mechanism of cytotoxicity for MAC 16 was most likely through TOP2 poisoning. Therefore, MAC 16 may provide a lead for the development of novel generations of anthraquinone-type antitumor agents.


Role of pulmonary stretch receptors during breathing in rabbits, cats and dogs.
In order to mimic and then modify the input to the respiratory centre from pulmonary stretch receptors, the central ends of the cut cervical vagus nerves were electrically stimulated with a frequency determined by transpulmonary pressure through a voltage to frequency converter. At appropriate end-expiratory stimulation frequency and gain of the voltage to frequency converter, such stimulation restored the pre-vagotomised patterns of breathing in rabbits, cats and dogs. Mimicking the changes in activity from pulmonary stretch receptors that would be produced by such manoeuvres as hypercapnia, inflations and deflations, reproduced the responses in inspiratory duration that occurred with natural stimuli in the same animals with intact. There were some differences between the responses of expiratory durations to the natural and mimicked interventions; these may be related to the presence of increased expiratory muscle activity in the former. The results demonstrate that transpulmonary pressure-controlled stimulation of the afferent vagus nerves is a satisfactory method of mimicking and controlling the pulmonary stretch receptor feedback mechanism in studies on the control of breathing.


Surgical repair of congenital aortic regurgitation by aortic root reduction: A finite element study.
During surgical reconstruction of the aortic valve in the child, the use of foreign graft material can limit durability of the repair due to inability of the graft to grow with the child and to accelerated structural degeneration. In this study we use computer simulation and ex vivo experiments to explore a surgical repair method that has the potential to treat a particular form of congenital aortic regurgitation without the introduction of graft material. Specifically, in an aortic valve that is regurgitant due to a congenitally undersized leaflet, we propose resecting a portion of the aortic root belonging to one of the normal leaflets in order to improve valve closure and eliminate regurgitation. We use a structural finite element model of the aortic valve to simulate the closed, pressurized valve following different strategies for surgical reduction of the aortic root (e.g., triangular versus rectangular resection). Results show that aortic root reduction can improve valve closure and eliminate regurgitation, but the effect is highly dependent on the shape and size of the resected region. Only resection strategies that reduce the size of the aortic root at the level of the annulus produce improved valve closure, and only the strategy of resecting a large rectangular portion-extending the full height of the root and reducing root diameter by approximately 12% - is able to eliminate regurgitation and produce an adequate repair. Ex vivo validation experiments in an isolated porcine aorta corroborate simulation results.


Effect of glutaurine, a newly discovered parathyroid hormone on rat thymus cultures.
Under the effect of the recently discovered parathyroid hormone, gamma-L-glutamyl-taurine (Glutaurine) growth of thymus cultures increased in all tested age groups. Epithelial growth was prominent and signs of activation of the macrophage cells appeared. In cell cultures the nuclei and nucleoli increased in size.


Image registration method using representative feature detection and iterative coherent spatial mapping for infrared medical images with flat regions.
In the registration of medical images, nonrigid registration targets, images with large displacement caused by different postures of the human body, and frequent variations in image intensity due to physiological phenomena are substantial problems that make medical images less suitable for intensity-based image registration modes. These problems also greatly increase the difficulty and complexity of feature detection and matching for feature-based image registration modes. This research introduces an automatic image registration algorithm for infrared medical images that offers the following benefits: effective detection of feature points in flat regions (cold patterns) that appear due to changes in the human body's thermal patterns, improved mismatch removal through coherent spatial mapping for improved feature point matching, and large-displacement optical flow for optimal transformation. This method was compared with various classical gold standard image registration methods to evaluate its performance. The models were compared for the three key steps of the registration process-feature detection, feature point matching, and image transformation-and the results are presented visually and quantitatively. The results demonstrate that the proposed method outperforms existing methods in all tasks, including in terms of the features detected, uniformity of feature points, matching accuracy, and control point sparsity, and achieves optimal image transformation. The performance of the proposed method with four common image types was also evaluated, and the results verify that the proposed method has a high degree of stability and can effectively register medical images under a variety of conditions.


Turnover Intention and Associated Factors Among Midwives in Jimma, Southwest Ethiopia.
Midwife turnover is a major problem and challenge for health-care leaders in Ethiopia. However, to date, little has been documented on turnover intention and its associated factors among midwifery professionals in southwest Ethiopia. Therefore, this study was conducted to fill the information gap on turnover intention and the factors influencing turnover intention among midwives in southwest Ethiopia. This study aimed to determine the turnover intention and associated factors among midwives, southwest Ethiopia/2022. An institutional-based cross-sectional study design was conducted among one hundred twenty one (121) midwives using structured self-administered and a pre-tested questionnaire from May 19/2022-June to 6/2022. Data were entered into Epi-data 126.96.36.199 edited, coded, categorized and entered into the data analysis. Data were analyzed using the statistical package for social science (SPSS) version 24, and the results are presented using figure, tables, and statements. Bivariate and multivariate logistic regression analyses were conducted to determine the factors associated with turnover intention at significance level of 0.25 and 0.05, respectively. In this study, from 121 midwives included in the analysis, approximately 48.76% (95% CI: 39.86-57.74) of midwives had a turnover intention from their current health-care institution, and 53.72% (95% CI: 44.68-62.52) of midwives did not have job satisfaction. Being male (AOR: 2.9 (95% CI: 1.14-7.39)), working in Health center (AOR: 0.20 (95% CI: 0.06-0.70)) and not having mutual support (AOR: 0.17 (95% CI: 0.07-0.44)) were associated factors of turnover intention among midwives. In this study, the turnover intention among midwives was higher than that among other local and national figures. Gender, mutual support and type of working institution were factors associated with turnover intention among midwives. Therefore, public health organizations should review their maternity staff to establish teamwork and mutual support.


[Anatomic features of posterior septum of knee joint and its application in posterior trans-septal portal for arthroscopic surgery].
To summarize the anatomic features of the posterior septum of the knee joint and its application in posterior trans-septal portal for arthroscopic surgery. The literature related to posterior septum of the knee joint and arthroscopic surgery was extensively reviewed and analyzed. The posterior septum of the knee joint has more mechanoreceptors and blood vessels in the upper part, which are close to arteria popliteal at the tibial plateau level; the posterior compartment is divided into wider posteromedial and narrower posterolateral compartments. A safe arthroscopic trans-septal portal is established, in the knee flexion of 90 degrees, in a lateral-to-medial direction, and with an inserting location below the middle of posterior septum. The establishment method of posterior trans-septal portal is not uniform and all the features of posterior septum should be considered to decrease the complications.


[Effect of selective activation of central serotoninergic systems on the course of the early post-traumatic period].
The central administration of the serotonin agonists of receptors type 1A (Campiron) and type 2 (1-(2,4,5-trimethoxy)-2-aminopropanome) was experimentally demonstrated to cause a significant decrease in mortality rates and cardiovascular disorders in white rats traumatized according to Kennon. This effect was realized by maximally activating the hypothalamo-neurohypophysis, hypothalamo-hypophysis-adrenocortical systems and blocking activation of the hypothalamo-hypophysis-thyroidal system.


Hypoxia-reduced nitric oxide synthase activity is partially explained by higher arginase-2 activity and cellular redistribution in human umbilical vein endothelium.
Hypoxia relates with altered placental vasodilation, and in isolated endothelial cells, it reduces activity of the endothelial nitric oxide synthase (eNOS) and l-arginine transport. It has been reported that arginase-2 expression, an alternative pathway for l-arginine metabolism, is increased in adult endothelial cells exposed to hypoxia as well as in pre-eclamptic placentae. We studied in human umbilical vein endothelial cells (HUVEC) whether hypoxia-reduced NO synthesis results from increased arginase-mediated l-arginine metabolism and changes in subcellular localization of eNOS and arginase-2. In HUVEC exposed (24 h) to 5% (normoxia) or 2% (hypoxia) oxygen, l-arginine transport kinetics, arginase activity (urea assay), and NO synthase (NOS) activity (l-citrulline assay) were determined. Arginase-1, arginase-2 and eNOS expression were determined by RT-PCR and Western blot. Subcellular localization of arginase-2 and eNOS were studied using confocal microscopy and indirect immunofluorescence. Experiments were done in absence or presence of S-(2-boronoethyl)-l-cysteine-HCl (BEC, arginase inhibitor) or N(G)-nitro-l-arginine methyl ester (l-NAME). Hypoxia-induced reduction in eNOS activity was associated with a reduction in eNOS phosphorylation at Serine-1177 and increased phosphorylation at Threonine-495. This was paralleled with an induction in arginase-2 expression and activity, and decreased l-arginine transport. In hypoxia the arginase inhibition, restored NO synthesis and l-arginine transport, without changes in the eNOS post-translational modification status. Hypoxia increased arginase-2/eNOS colocalization, and eNOS redistribution to the cell periphery. Altogether these data reinforce the thought that eNOS cell location, post-translational modification and substrate availability are important mechanisms regulating eNOS activity. If these mechanisms occur in pregnancy diseases where feto-placental oxygen levels are reduced remains to be clarified.


A neuroplastic deafferentation hypothesis for bipolar disorder.
Bipolar disorder, characterised by extreme cyclical variations in mood between depression and mania, is a common, debilitating and sometimes fatal psychiatric condition with an unclear aetiology. In this paper we propose a hypothesis for the development of bipolar disorder through which neuroplastic changes in response to an index depressive episode leads to the amplification of subthreshold pleasurable stimuli that then drive conversion into a manic state. This 'pleasure deafferentation hypothesis' is reached through a discussion of the neuroscientific basis of deafferentation at the level of the neuron and its role in the development of various neurological and psychiatric phenomena before a case for deafferentation as applied to bipolar disorder is justified and its implications discussed.


The sanitary indoor environment-a potential source for intact human-associated anaerobes.
A healthy human microbiome relies on the interaction with and exchange of microbes that takes place between the human body and its environment. People in high-income countries spend most of their time indoors and for this reason, the built environment (BE) might represent a potent source of commensal microbes. Anaerobic microbes are of particular interest, as researchers have not yet sufficiently clarified how the human microbiome acquires oxygen-sensitive microbes. We sampled the bathrooms in ten households and used propidium monoazide (PMA) to assess the viability of the collected prokaryotes. We compared the microbiome profiles based on 16S rRNA gene sequencing and confirmed our results by genetic and cultivation-based analyses. Quantitative and qualitative analysis revealed that most of the microbial taxa in the BE samples are human-associated. Less than 25% of the prokaryotic signatures originate from intact cells, indicating that aerobic and stress resistant taxa display an apparent survival advantage. However, we also confirmed the presence of intact, strictly anaerobic taxa on bathroom floors, including methanogenic archaea. As methanogens are regarded as highly sensitive to aerobic conditions, oxygen-tolerance experiments were performed with human-associated isolates to validate their survival. These results show that human-associated methanogens can survive oxic conditions for at least 6 h. We collected strong evidence that supports the hypothesis that obligate anaerobic taxa can survive in the BE for a limited amount of time. This suggests that the BE serves as a potential source of anaerobic human commensals.


Development of a core set of domains for data collection in cohorts of patients with ankylosing spondylitis receiving anti-tumor necrosis factor-alpha therapy.
To create a core set of measurement concepts for use in the creation and maintenance of anti-tumor necrosis factor-alpha patient registries in ankylosing spondylitis (AS). A Delphi-based approach was used to identify elements that best identify a patient's clinical state, disease progression, and potential drug-related toxicities. Decision-making was based on systematic literature reviews and clinical experience and expertise. A core set of measurement domains was defined including disease activity and physical function outcomes. Comparison with domains used in existing AS registries showed excellent agreement with current practice. This core set is a basis for data collection across AS populations.


A DCM-based NIR sensor for selective and sensitive detection of Zn2+ in living cells.
Zinc ion is the 2nd abundant transition metal element in human's body. It is responsible for many physiological and biological functioning in the body, such as growth of people, immunity, endocrine, etc. The deficiency of zinc could result in an increasing risk for growth retardation, neurological disorder and infectious disease. Thus, developing a nondestructive method for detecting Zn2+ in living systems is important. Here we reported a 2-(2-methyl-4H-ylidene)- malononitrile (DCM)-based NIR probe DF-Zn for selective and sensitive detection of Zn2+. The probe DF-Zn is cell-permeable and stable at broad pH range. DF-Zn showed a fast response to Zn2+, big stock's shift, and "nude-eye" recognition for Zn2+. Moreover, the selective binding of probe DF-Zn to Zn2+ was reversible. With the addition of EDTA in buffer solution, reversible response of probe to Zn2+ could be observed in MCF-7 cells imaging.


Association of the mcrD gene product with methyl coenzyme M reductase in Methanococcus vannielii.
The mcrD gene, subcloned from the methyl coenzyme M reductase (MR) encoding mcrBDCGA operon in Methanococcus vannielii, has been expressed at a high level in Escherichia coli. Rabbit antibodies, raised against the product of this gene (rgpmcrD, recombinant gene product of mcrD) purified from E. coli, have been used to quantitate gpmcrD in M. vannielii and to follow its fate during MR purification. The molar ratio of gpmcrD to MR was found to be approx. 1:15 in cells of M. vannielii taken from batch cultures at all stages of growth. Sedimentation of lysates of M. vannielii cells through sucrose gradients and analyses of the fractions obtained by Western blotting and immunoprecipitation have demonstrated the presence of a macromolecular complex containing both gpmcrD and MR. Addition of mcrD antibodies or removal of gpmcrD from lysates of M. vannielii cells by immunoprecipitation decreased the rates of methanogenesis in vitro by approx. 20%. Addition of purified rgpmcrD to these lysates did not stimulate methanogenesis.


Diastatotropis arofaniana sp. nov. from eastern Madagascar, a new species close to D. rubra Frieser, with a redescription of the type of the latter, and notes on morphology (Coleoptera: Anthribidae).
Diastatotropis arofaniana Trzna Baa sp. nov. (Anthribidae: Anthribinae: incertae sedis) is described as new from eastern Madagascar. Male and female genitalia are studied and illustrated, and colour photographs are provided. The new species is morphologically similar to D. rubra Frieser, 1992. A redescription of the female holotype of D. rubra, with the first illustrations of its habitus and genitalia are presented. Ecological notes, including colour photographs of the habitat of the new species, are provided. The curculionid type of hemisternites without toothed plates found in Diastatotropis is also discussed.


Immunofluorescent evidence of prior herpes simplex virus type-2 infection in prostate carcinoma.
The finding of herpes simplex virus type-2 (HSV-2) particles in prostatic carcinoma (PCa) tissue has led to speculation that the virus might cause this disease. We studied 27 PCa and 33 benign prostatic hyperplasia (BPH) specimens for the presence of HSV-2 antigens by indirect immunofluorescent staining to HSV-2 using commercially prepared rabbit anti-HSV-2 and fluorescein-tagged goat and anti-rabbit antibody. The slides were randomly number coded by an impartial referee then read independently by each investigator. In cases of disagreement, new slides were prepared and read until agreement. The code was then broken. Seven of 27 PCa specimens and 8 of 33 BPH specimens showed positive staining. By contingency table analysis, the results were not statistically different (chi 2 = 0.0224; p greater than 0.8). In our series, there is no difference in the prevalence of HSV-2 staining between PCa and BPH. Further examination of our data failed to show any difference in the prevalence of staining for HSV-2 based on whether the source of the tissue was surgical or autopsy. We conclude that HSV-2 infection of the prostate is common (15/60 = 25%) but probably has no causal relationship to PCa.


[Suprapubic Nicolau syndrome following subcutaneous injection of glatiramer acetate].
Subcutaneous glatiramer acetate, commercialized under the name of Copaxone®, is licensed for the treatment of relapsing multiple sclerosis. Its major adverse effects are skin reactions at the injection site. Nicolau syndrome is a rare but serious iatrogenic accident. Herein we report a case seen in a setting of change of dosage and administration rate of Copaxone®. A 64-year-old woman, treated since 2010 with daily sub-cutaneous injections of Copaxone® 20mg/L, reported the appearance of a painful, indurated and erythematous plaque in the suprapubic area following changeover to 40mg/mL injections three times weekly. The suprapubic injections were continued and ugly greyish spots with stellate purpuric borders appeared. Fournier gangrene was ruled out by means of a soft tissue scan. We report this latest case of Nicolau syndrome to alert readers to the non-exceptional nature of this complication associated with use of glatiramer acetate, particularly at a dosage of 40mg/L injections three times weekly. In our case, onset of Nicolau syndrome appears to have been favored by continued injection in areas already showing inflammation. Re-injection of the drug in these areas should thus be proscribed.


Identifying pitfalls in chest tube insertion: improving teaching and performance.
Chest tube thoracostomies are common surgical procedures, but little is known about how practitioners learn the skill. This study evaluates the frequency with which correctly performed tasks are executed by subjects during chest tube thoracostomies. In this prospective study, we developed a mobile-learning module, containing stepwise multimedia guidance on chest tube insertion. Next, we developed and tested a 14-item checklist, modeled after key skills in the module. Participants, defined as "novice" (fewer than 10 chest tubes placed) or "expert" (10 or more placed), were assigned to either the video or control group. A trained clinician used the checklist to rate participants while they inserted a chest tube on a TraumaMan simulator. University of Miami, Miller School of Medicine, a tertiary care academic institution. Current medical students, residents, and the United States Army Forward Surgical Team members rotating through the institution. One hundred twenty-eight subjects entered and finished the study. One hundred twenty-eight subjects enrolled in the study; 86 (67%) were residents or US Army Forward Surgical Team members, 66 (77%) were novices, and 20 (23%) were experts. Novices most frequently connected the tube to suction (91%), adequately dissected the soft tissue (82%), and scrubbed or anesthetized appropriately (80%). They least frequently completed full finger sweeps (33%), avoided the neurovascular bundle (35%), and performed a controlled pleural puncture (39%). Comparing the novice video group with the novice control group, the video group was more likely to correctly perform a finger sweep (42%, p<0.001) and clamp the distal end of the chest tube (42%, p<0.001). Of all the steps, experts least frequently completed full finger sweeps (70%) and avoided the neurovascular bundle (75%). Comparing the expert video group with the expert control group, the video group was more likely to correctly perform finger sweeps, the incision, and clamping the distal chest tube (20%, p = not significant). Avoiding the neurovascular bundle, controlled pleural entry, and finger sweeps are most often performed incorrectly among novices. This information can help instructors to emphasize key didactic steps, possibly easing trainees' learning curve.


Frailty as a Predictor of Negative Health Outcomes in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.
To perform a comprehensive evidence synthesis to summarize the impact of frailty on health outcomes in patients with chronic kidney disease (CKD). Systematic reviews and meta-analysis. Electronic searches in PubMed, Embase, Web of Science, CNKI, VIP, CBM, and Wanfang Database were performed. The methodological quality was evaluated using the Newcastle Ottawa Scale (NOS). Patients with chronic kidney disease (CKD). Potential clinical outcomes due to frailty. Eighteen cohort studies incorporating a total of 22,788 participants were included. The overall risk of bias was low. The median reported prevalence of frail and prefrail individuals with CKD was 41.8% (range 2.8-81.5%) and 43.9% (range 19.1-62.7%), respectively. Prefrailty and frailty related to mortality indicated an increased hazard ratio (HR), with a pooled HR of 1.68 [95% confidence interval (CI) 1.46-1.94; P < .001] and 1.48 (95% CI 1.21-1.81; P < .001), respectively. Prefrailty and frailty related to hospitalization with the pooled HR/risk ratio (RR) of 1.56 (95% CI 1.37-1.76; P < .001) and 1.21 (95% CI 0.79-1.85; P = .38), respectively. Similarly, the pooled HR demonstrated a strong correlation between frailty and falls in patients with CKD with HR 1.83 (95% CI 1.40-2.37; P < .001) and no statistical correlation between prefrailty and falls in these patients with pooled HR 1.19 (95% CI 0.44-3.22; P = .73), respectively. Frailty is predictive of negative outcomes in patients with CKD, including all-cause mortality, all-cause hospitalization, and falls. Therefore, frailty should be routinely assessed among patients with CKD to prevent poor prognosis, reduce fatality rate, and provide evidence to support future targeted interventions. However, because of the limited amount of information currently in the literature, additional prospective studies are needed to explore the role of prefrailty in predicting adverse outcomes for patients with CKD.


Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis patients: A post hoc analysis of the randomized CombiRx trial.
CombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies. This analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse. RRMS patients treated with IM IFN beta-1a 30 µg weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included. A linear mixed model compared sNfL values over time. Cox regression models analyzed baseline sNfL and gadolinium-enhancing (Gd+) lesions as predictors of relapse. In all treatment arms, the proportion of patients with sNfL ≥16 pg/mL decreased significantly from baseline to 6 months and was maintained at 36 months. A significantly higher percentage of patients with both baseline sNfL ≥16 pg/mL and ≥1 Gd+ lesion experienced relapses within 90 days compared to patients with sNfL <16 pg/mL and/or no Gd+ lesions. sNfL levels were reduced within 6 months and remained low at 36 months. Results suggest that the combination of lesion activity and sNfL was a stronger predictor of relapse than either factor alone.


Understanding surgical care delivery in Sub-Saharan Africa: a cross-sectional analysis of surgical volume, operations, and financing at a tertiary referral hospital in rural Tanzania.
Access to surgical care in Low- and Middle-Income Countries (LMICs) such as Tanzania is extremely limited. Northern Tanzania is served by a single tertiary referral hospital, Kilimanjaro Christian Medical Centre (KCMC). The surgical volumes, workflow, and payment mechanisms in this region have not been characterized. Understanding these factors is critical in expanding access to healthcare. The authors sought to evaluate the operations and financing of the main operating theaters at KCMC in Sub-Saharan Africa. The 2018 case volume and specialty distribution (general, orthopaedic, and gynecology) in the main operating theaters at KCMC was retrieved through retrospective review of operating report books. Detailed workflow (i.e. planned and cancelled cases, lengths of procedures, lengths of operating days) and financing data (patient payment methods) from the five KCMC operating theater logs were retrospectively reviewed for the available five-month period of March 2018 to July 2018. Descriptive statistics and statistical analysis were performed. In 2018, the main operating theaters at KCMC performed 3817 total procedures, with elective procedures (2385) outnumbering emergency procedures (1432). General surgery (1927) was the most operated specialty, followed by orthopaedics (1371) and gynecology (519). In the five-month subset analysis period, just 54.6% of planned operating days were fully completed. There were 238 cancellations (20.8% of planned operations). Time constraints (31.1%, 74 cases) was the largest reason; lack of patient payment accounted for as many cancellations as unavailable equipment (6.3%, 15 cases each). Financing for elective theater cases included insurance 45.5% (418 patients), and cash 48.4% (445 patients). While surgical volume is high, there are non-physical inefficiencies in the system that can be addressed to reduce cancellations and improve capacity. Improving physical resources is not enough to improve access to care in this region, and likely in many LMIC settings. Patient financing and workflow will be critical considerations to truly improve access to surgical care.


Survival rates for pre- and postmenopausal Danish women with mammary carcinoma.
Survival rates for mammary carcinoma, based on the data of the Danish Cancer Registry for women admitted 1960 to 1966, show about the same values for women aged under 55 in stage I, whether surgical treatment has been combined with radiation therapy or not. For women aged over 55, combined treatment is followed by better survival rates than surgery or radiation therapy alone. For stage II, this applies both to younger and older women.


Antifatigue effects of Panax ginseng C.A. Meyer: a randomised, double-blind, placebo-controlled trial.
The present study investigated the antifatigue effects of Panax ginseng C.A. Meyer in 90 subjects (21 men and 69 women) with idiopathic chronic fatigue (ICF) in a randomised, double-blind, placebo-controlled and parallel designed trial. A bespoke 20% ethanol extract of P. ginseng (1 g or 2 g day(-1)) or a placebo was administered to each group for 4 weeks, and then fatigue severity was monitored using a self-rating numeric scale (NRS) and a visual analogue scale (VAS) as a primary endpoint. Serum levels of reactive oxygen species (ROS), malondialdehyde (MDA), total glutathione (GSH) contents and glutathione reductase (GSH-Rd) activity were determined. After 4-week, P. ginseng administration decreased the total NRS score, but they were not statistically significant compared with placebo (P>0.05). Mental NRS score was significantly improved by P. ginseng administrations as 20.4 ± 5.0 to 15.1 ± 6.5 [95% CI 2.3 ~ 8.2] for 1 g and 20.7 ± 6.3 to 13.8 ± 6.2 [95% CI -0.1 ~ 4.2] for 2 g compared with placebo 20.9 ± 4.5 to 18.8 ± 2.9 [95% CI 4.1 ~ 9.9, P<0.01]. Only 2 g P. ginseng significantly reduced the VAS score from 7.3 ± 1.3 to 4.4 ± 1.8 [95% CI 0.7∼1.8] compared with the placebo 7.1 ± 1.0 to 5.8 ± 1.3 [95% CI 2.2 ~ 3.7, P<0.01]. ROS and MDA levels were lowered by P. ginseng compared to placebo. P. ginseng 1 g increased GSH concentration and GSH-Rd activity. Our results provide the first evidence of the antifatigue effects of P. ginseng in patients with ICF, and we submit that these changes in antioxidant properties contribute in part to its mechanism. Clinical Research Information Service (CRIS) KCT0000048.


Local people's perceptions as decision support for protected area management in Wolong Biosphere Reserve, China.
This paper examines local people's knowledge, attitudes and perceptions towards Wolong Biosphere Reserve (WBR) and its management policies. Pertinent data were collected through a questionnaire survey and group discussions. This study revealed that local people's perceptions were affected by many factors, including education, gender, residence location, household size and acreage of land owned. Although most respondents had limited knowledge about WBR because of their absence in WBR management, they held a positive attitude towards WBR. An in-depth analysis of their attitudes and perceptions showed that two potential conflicts might affect biodiversity conservation and protected area management. One of them was the imbalance between the limited cropland holding and the oversupply of the labor force, and the other one was the increase in electricity price versus the decrease in economic incentives for the Natural Forest Protection Project. The study also revealed that relocation was considered unacceptable to most respondents. However, those residing far from the main road were willing to relocate more than those near the main road. Based on our studies, some recommendations are given for improvement of WBR management.


Community Assessment of Extreme Heat Preparedness in Milwaukee, Wisconsin.
This article describes the first Community Assessment for Public Health Emergency Response (CASPER) rapid needs assessment project to be conducted in Wisconsin. The project focused on extreme heat preparedness. Fifteen teams conducted household surveys in 30 census blocks in the city of Milwaukee, Wisconsin. Survey results indicated that the majority of households were unaware of the location of a nearby cooling center. Although the vast majority of households reported some form of air conditioning in their house, over half felt too hot inside their home sometimes, most of the time, or always. The community partnerships ensured that this project was conducted with local partner input and that the data could be used to inform extreme heat response.


Effects of 2-acetyl-4-tetrahydroxybutylimidazole exposure during gestation and lactation on maternity and offspring immune function in Balb/c mice.
2-Acetyl-4-tetrahydroxybutylimidazole (THI), a by-product of Class Ⅲ caramel color, is generally recognized to cause lymphopenia in mammals. However, it remains unknown whether THI exposure during gestation and lactation causes damage to the immune system of offspring. In this study, pregnant Balb/c mice were gavaged with 0, 0.5, 2.5 and 12.5 mg/kg THI from gestation day (GD) 6 to postanal day (PND) 21, after which we treated another batch of dams from GD6 to PND21 and the offspring for 3 weeks after weaning with 0, 2, 10, 50 mg/L THI in drinking water respectively, and investigated the immunological anomalies of dams and offspring. The results showed that lymphopenia was observed in dams but not in weaning pups on PND21, which were exposed to THI during gestation and lactation. 2 mg/L THI and 2.5 mg/kg THI began to cause a remarkable reduction of the numbers of white blood cells and lymphocytes in dams. Besides both the cellular and the humoral immune response was not affected in weaning pups, which were measured by plaque-forming cell (PFC) assay and delayed-type hypersensitivity (DTH) assay respectively. Furthermore, THI could be detected in the plasma of dams with a dose-dependent manner, but not in that of both female and male weaning pups. In both male and female offspring being treated with 10 and 50 mg/L THI for another 3 weeks after weaning, lymphocytopenia was observed and T lymphocytes including CD4+ and CD8+ cells were significantly reduced in their spleens except lymph nodes. 10 and 50 mg/L THI treatment increased CD4+ and CD8+ single positive cells in thymus of female and male weaning mice. Mitogen-induced proliferation ability of T cells in the spleen and lymph nodes was impaired in female weaning mice exposed 50 mg/L THI, while male weaning mice treated with 10 and 50 mg/L THI showed impairment in the spleen but not lymph nodes. Based on the results in this study, no observed adverse effect level (NOAEL) for 3-week THI treatment in weaning mice was considered to be 2 mg/L (0.30 mg/kg bw for female mice and 0.34 mg/kg bw for male mice). And NOAEL for THI treatment in dams might be set to 0.5 mg/kg bw/day. Collectively from the perspective of NOAEL, offspring are not more sensitive than dams or adult mice.


Pemphigus vulgaris and paraneoplastic pemphigus.
The history, epidemiology, pathophysiology, clinical presentation, diagnostic work-up, histopathology, and treatment of PV and PNP have been presented. These life-threatening, autoimmune, mucocutaneous bullous conditions may be encountered first by oral health providers and, therefore, deserve keen understanding and attention by the oral and maxillofacial surgeon. Great diagnostic and management strides have been made, but morbidity and life quality issues remain a reality for these chronically ill patients.


Degradation of polypropylene in the human eye: a SEM-study.
A polypropylene surgical suture, which had served as fixation suture for an IOL for a period of 6.5 years, was removed from the eye of a Dutch patient because it had broken at one end and thus formed a potential risk for a corneal touch syndrome. After careful rinsing in 50% ethanol, to remove adhering debris, it was prepared for SEM. A virgin piece of polypropylene material from a surgical package underwent the same preparative procedure. The fixation suture showed cracks perpendicular to the longitudinal axis of the suture; part of the surface layer was nearly detached or completely missing; while the diameter of the suture was decreased towards both ends by over 50% in comparison with the original diameter. The exposed subsurface layer showed a fibrillar structure. The degradation phenomena are considered to be caused by the enzymatic action of tissue-fluids. Virgin material did not show any of the phenomena observed on the fixation suture under consideration.


Genome-wide characterization and analysis of bZIP transcription factor gene family related to abiotic stress in cassava.
The basic leucine zipper (bZIP) transcription factor family plays crucial roles in various aspects of biological processes. Currently, no information is available regarding the bZIP family in the important tropical crop cassava. Herein, 77 bZIP genes were identified from cassava. Evolutionary analysis indicated that MebZIPs could be divided into 10 subfamilies, which was further supported by conserved motif and gene structure analyses. Global expression analysis suggested that MebZIPs showed similar or distinct expression patterns in different tissues between cultivated variety and wild subspecies. Transcriptome analysis of three cassava genotypes revealed that many MebZIP genes were activated by drought in the root of W14 subspecies, indicating the involvement of these genes in the strong resistance of cassava to drought. Expression analysis of selected MebZIP genes in response to osmotic, salt, cold, ABA, and H2O2 suggested that they might participate in distinct signaling pathways. Our systematic analysis of MebZIPs reveals constitutive, tissue-specific and abiotic stress-responsive candidate MebZIP genes for further functional characterization in planta, yields new insights into transcriptional regulation of MebZIP genes, and lays a foundation for understanding of bZIP-mediated abiotic stress response.


Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates.
The endocannabinoids 2-arachidonoyl glycerol (2-AG) and N-arachidonoyl ethanolamine (anandamide) are principally degraded by monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), respectively. The recent discovery of O-aryl carbamates such as JZL184 as selective MAGL inhibitors has enabled functional investigation of 2-AG signaling pathways in vivo. Nonetheless, JZL184 and other reported MAGL inhibitors still display low-level cross-reactivity with FAAH and peripheral carboxylesterases, which can complicate their use in certain biological studies. Here, we report a distinct class of O-hexafluoroisopropyl (HFIP) carbamates that inhibits MAGL in vitro and in vivo with excellent potency and greatly improved selectivity, including showing no detectable cross-reactivity with FAAH. These findings designate HFIP carbamates as a versatile chemotype for inhibiting MAGL and should encourage the pursuit of other serine hydrolase inhibitors that bear reactive groups resembling the structures of natural substrates.


Race and risk of maternal vascular malperfusion lesions in the placenta.
The biological mechanisms that underlie racial disparities in placenta-mediated pregnancy complications remain unknown. Placental evidence of maternal vascular malperfusion (MVM), a common pathologic feature of these outcomes, represents hypoxic-ischemic damage to the placenta. We sought to separately estimate the risk of MVM and individual lesions associated with maternal race. This was a retrospective cohort study of black and white women with singleton live births and placental pathology data at Magee-Womens Hospital during 2008-2012 (n = 15,581). MVM consisted of ≥1 individual lesions: low placental weight, decidual vasculopathy, accelerated villous maturation, infarcts, and fibrinoid deposition. We separately compared the incidence of MVM and individual lesions in black and white women using logistic regression with generalized estimating equations. After adjusting for covariates, black women had increased risks of MVM (aOR 1.14, 95% CI 1.05-1.23), low placental weight (aOR 1.41, 95% CI 1.28-1.55), and decidual vasculopathy (aOR 1.58, 95% CI 1.36-1.83), also observed in uncomplicated, preterm, and term births. Conversely, black women had decreased risk of infarcts (aOR 0.84, 95% CI 0.75-0.95) compared with white women, also observed in uncomplicated and full-term births. Race was not associated with accelerated villous maturation or fibrinoid deposition. Inverse probability weighting to account for potential selection bias generated similar results. Our findings suggest that excess risks of MVM, specifically low placental weight and decidual vasculopathy in black women may be due to a pathological susceptibility to an underlying high-risk vascular phenotype. The clinical significance of race differences in the occurrence of infarcts warrants further investigation.


Role of adipocyte-derived lipoprotein lipase in adipocyte hypertrophy.
A major portion of available fatty acids for adipocyte uptake is derived from lipoprotein lipase (LPL)-mediated hydrolysis of circulating lipoprotein particles. In vivo studies aimed at identifying the precise role of adipocyte-derived LPL in fat storage function of adipose tissue have been unable to provide conclusive evidence due to compensatory mechanisms that activate endogenous fatty acid synthesis. To address this gap in knowledge, we have measured the effect of reducing adipocyte LPL expression on intracellular lipid accumulation using a well-established cultured model of adipocyte differentiation. siRNA specific for mouse LPL was transfected into 3T3-L1 adipocytes. Expression of LPL was measured by quantitative real-time PCR and cell surface-associated LPL enzymatic activity was measured by colorimetric detection following substrate (p-nitrophenyl butyrate) hydrolysis. Apolipoprotein CII and CIII expression ratios were also measured by qRT-PCR. Intracellular lipid accumulation was quantified by Nile Red staining. During differentiation of 3T3-L1 pre-adipocytes, LPL mRNA expression increases 6-fold resulting in a 2-fold increase in cell surface-associated LPL enzymatic activity. Parallel to this increase in LPL expression, we found that intracellular lipids increased ~10-fold demonstrating a direct correlation between adipocyte-derived LPL expression and lipid storage. We next reduced LPL expression in adipocytes using siRNA transfections to directly quantify the contributions of adipocyte-derived LPL to lipid storage, This treatment reduced LPL mRNA expression and cell surface-associated LPL enzymatic activity to ~50% of non-treated controls while intracellular lipid levels were reduced by 80%. Exogenous addition of purified LPL (to restore extracellular lipolytic activity) or palmitate (as a source of free fatty acids) to siRNA-treated cells restored intracellular lipid levels to those measured for non-treated controls. We also found that adipocytes express apolipoprotein CII and CIII and, in addition, the apoCII/apoCIII ratio remains largely unchanged in cells with reduced LPL expression. We provide evidence that adipocyte-derived LPL is required for efficient fatty acid uptake and storage, and that adipocytes express their own source of apoCII and apoCIII for regulating extracellular LPL activity. These findings demonstrate that adipocytes are capable of producing the necessary enzymatic components and co-factors for efficient lipid storage independent of vascular sources.


Interpretation and clinical significance of the QRS axis of the electrocardiogram.
The frontal plane QRS axis of the standard 12-lead electrocardiogram (ECG) is easily and accurately measured by the clinician. A simple method of estimating this axis is discussed. This axis is age-dependent. We reviewed the literature to determine if evidence exists of an association between an "abnormal" QRS axis and clinically significant myocardial disease. We also examined the literature for clinical correlation of a "normal" QRS axis with the absence of myocardial pathology. We found that although an abnormal QRS axis (falling outside the limits of +30 degrees and +90 degrees) occurs in a small number of normal individuals, its presence should prompt a thorough evaluation of all the parameters of the ECG to look for myocardial disease.


Sostdc1 Regulates NK Cell Maturation and Cytotoxicity.
NK cells are innate-like lymphocytes that eliminate virally infected and cancerous cells, but the mechanisms that control NK cell development and cytotoxicity are incompletely understood. We identified roles for sclerostin domain-containing-1 (Sostdc1) in NK cell development and function. Sostdc1-knockout (Sostdc1 -/-) mice display a progressive accumulation of transitional NK cells (tNKs) (CD27+CD11b+) with age, indicating a partial developmental block. The NK cell Ly49 repertoire in Sostdc1 -/- mice is also changed. Lower frequencies of Sostdc1 -/- splenic tNKs express inhibitory Ly49G2 receptors, but higher frequencies express activating Ly49H and Ly49D receptors. However, the frequencies of Ly49I+, G2+, H+, and D+ populations were universally decreased at the most mature (CD27-CD11b+) stage. We hypothesized that the Ly49 repertoire in Sostdc1 -/- mice would correlate with NK killing ability and observed that Sostdc1-/- NK cells are hyporesponsive against MHC class I-deficient cell targets in vitro and in vivo, despite higher CD107a surface levels and similar IFN-γ expression to controls. Consistent with Sostdc1's known role in Wnt signaling regulation, Tcf7 and Lef1 levels were higher in Sostdc1 -/- NK cells. Expression of the NK development gene Id2 was decreased in Sostdc1-/- immature NK and tNK cells, but Eomes and Tbx21 expression was unaffected. Reciprocal bone marrow transplant experiments showed that Sostdc1 regulates NK cell maturation and expression of Ly49 receptors in a cell-extrinsic fashion from both nonhematopoietic and hematopoietic sources. Taken together, these data support a role for Sostdc1 in the regulation of NK cell maturation and cytotoxicity, and identify potential NK cell niches.