Characterizing initial COVID-19 vaccine attitudes among pregnancy-capable healthcare workers.
Healthcare workers were prioritized for COVID-19 vaccination roll-out because of the high occupational risk. Vaccine trials excluded individuals who were trying to conceive and those who are pregnant and lactating, necessitating vaccine decision-making in the absence of data specific to this population. This study aimed to determine the initial attitudes about COVID-19 vaccination in pregnancy-capable healthcare workers by reproductive status and occupational exposure. We performed a structured survey distributed via social media of US-based healthcare workers involved in patient care since March 2020 who were pregnancy-capable (biologic female sex without history of sterilization or hysterectomy) from January 8, 2021 to January 31, 2021. Participants were asked about their desire to receive the COVID-19 vaccine and their perceived safety of the COVID-19 vaccine using 5-point Likert items with 1 corresponding to "I strongly don't want the vaccine" or "very unsafe for me" and 5 corresponding to "I strongly want the vaccine" or "very safe for me." We categorized participants into the following 2 groups: (1) reproductive intent (preventing pregnancy vs attempting pregnancy, currently pregnant, or currently lactating), and (2) perceived COVID-19 occupational risk (high vs low). We used descriptive statistics to characterize the respondents and their attitudes about the vaccine. Comparisons between reproductive and COVID-19 risk groups were conducted using Mann-Whitney U tests. Our survey included 11,405 pregnancy-capable healthcare workers: 51.3% were preventing pregnancy (n=5846) and 48.7% (n=5559) were attempting pregnancy, currently pregnant, and/or lactating. Most respondents (n=8394, 73.6%) had received a vaccine dose at the time of survey completion. Most participants strongly desired vaccination (75.3%) and very few were strongly averse (1.5%). Although the distribution of responses was significantly different between respondents preventing pregnancy and those attempting conception or were pregnant and/or lactating and also between respondents with a high occupational risk and those with a lower occupational risk of COVID-19, the effect sizes were small and the distribution was the same for each group (median, 5; interquartile range, 4-5). Most of the healthcare workers desired vaccination. Negative feelings toward vaccination were uncommon but were significantly higher among those attempting pregnancy and those who are pregnant and lactating and also among those with a lower perceived occupational risk of contracting COVID-19, although the effect size was small. Understanding healthcare workers' attitudes toward vaccination may help guide interventions to improve vaccine education and uptake in the general population.


5,10-Methylenetetrahydrofolate reductase deficiency with progressive polyneuropathy in an infant.
5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most prevalent inborn error of folate metabolism, and has variable clinical manifestations from asymptomatic to severe psychomotor retardation, microcephalus and seizure. In untreated infantile cases, it predominantly affects the central nervous system, which is sometimes fatal. On the other hand, peripheral nerve involvement is uncommon. We present a severe infantile case of MTHFR deficiency that manifested unilateral phrenic nerve palsy with communicating hydrocephalus, developmental delay and died at 11months of age. An enzymatic study confirmed MTHFR deficiency with residual activity of 0.75% of mean control values in cultured fibroblasts. Mutation analysis of the MTHFR gene revealed homozygous, tandem missense mutations c.[446G>T; 447C>T] in exon 3 of the MTHFR gene converting glycine to valine (Gly149Val). In MTHFR deficiency, betaine may improve the symptoms if started immediately after birth by reducing the level of serum homocysteine and increasing that of methionine. Our results show that we should be aware of possible inborn errors of folate metabolism such as MTHFR deficiency, in infants with unexplained developmental delay manifesting rapidly progressive polyneuropathy.


Bi(III)-Catalyzed Synthesis of Substituted Furans from Hydroxy-oxetanyl Ketones: Application to Unified Total Synthesis of Shikonofurans J, D, E, and C.
We report an improved synthetic protocol for hydroxy methyl-derived polysubstituted furans employing Bi(III)-catalyzed dehydrative cycloisomerization of α-hydroxy oxetanyl ketones. This procedure provides rapid access (within 5 min) to highly substituted furans with exceptional functional group diversity, excellent yields, generality, scalability, and operationally simple reaction conditions. Further, it demonstrated the utility of this method in the first enantioselective total synthesis of furyl-hydroquinone-derived biologically potent natural products shikonofurans J, D, E, and C in seven linear steps, starting from readily available building blocks of 2,5-dihydroxy acetophenone and 3-oxetanone employing chiral-phosphoric acid (TRIP)-catalyzed asymmetric prenylation as a key step to induce the chirality.


Endovascular repair of a pseudoaneurysm of the abdominal aorta secondary to translumbar aortography.
This report describes an incidental finding of a pseudoaneurysm of the abdominal aorta on a computed tomography (CT) renal angiogram during investigation of chronic renal failure in a 73-year-old man. The patient had undergone a translumbar aortogram 20 years previously. An increase in the size of the aneurysm by 7 mm over 6 months prompted treatment and the aneurysm underwent successful endovascular repair with a custom-made stent-graft.


Elevation of glutathione in phenylalanine mustard-resistant murine L1210 leukemia cells.
Murine L1210 leukemia cells resistant to the antineoplastic agent L-phenylalanine mustard have a 1.5-2.0-fold elevation in their cellular GSH and GSSG content as compared to drug-sensitive cells. Cellular uptake of L-[U-14C]cystine and its incorporation into GSH of the resistant tumor are correspondingly elevated. Synthesis of gamma-glutamylcysteine, GSH, and GSSG is elevated 1.5-2.0-fold in cell-free preparations of the resistant tumor. This increased synthesis of GSH is attributed to increased cellular content (1.6-fold) of gamma-glutamylcysteine synthetase. GSH synthetase activity is equivalent in both drug-sensitive and -resistant cells. Investigation into the hydrolysis of selected peptides by cell-free preparations of both sensitive and resistant tumors suggest that aminopeptidase M participates in the formation of L-cysteine from L-Cys-Gly. This is supported by the observation that these preparations readily degrade L-Leu-p-nitroanilide and L-Ala-L-Ala-L-Ala, known substrates for aminopeptidase M, but not dipeptidase. The failure of the tumors to degrade Gly-D-Ala, a dipeptidase substrate, and the marked inhibition of L-Ala-Gly, L-Cys-Gly, and L-Ala-L-Ala-L-Ala hydrolysis by Bestatin further support a role for aminopeptidase M in the generation of L-cysteine from L-Cys-Gly. These results suggest that the drug-resistant tumor cell has developed an efficient mechanism for maintenance of elevated GSH which involves both gamma-glutamyl transpeptidase-initiated catabolism of GSH to cysteine and its reutilization by gamma-glutamylcysteine synthetase.


Disturbance Rejection for Underwater robotic vehicle based on adaptive fuzzy with nonlinear PID controller.
In this paper, an adaptive fuzzy with a nonlinear PID (AFNLPID) controller is suggested to solve and eliminate the effect of the disturbances regularly caused by the ocean currents and the unknown uncertainties of the underwater robotic vehicle (URV) dynamics. The main principle of the AFNLPID controller is to estimate the unknown dynamics parameters of the URV and estimate the unknown disturbances. Two types of disturbances are presented that are deepwater wave disturbances and near-surface shallow water wave disturbances. The outstanding properties of the AFNLPID were evaluated by comparing the designed controller with other existing works that are adaptive fuzzy PID (AFPID, AFPID2) controllers, conventional PID controllers, and nonlinear fractional-order PID (NLFOPID) controllers. At the end, the collected results show that the AFNLPID controller improved the efficiency of the URV for deepwater disturbances by 42.0663%, 37.0490%, 24.4449%, 64.7356%, and 51.7643% for AFPID, AFPID2, AFNLPID2, PID, and NLFOPID controllers, respectively. At the same time, the AFNLPID improved the efficiency of the URV for near-surface wave disturbances by 45.0911%, 32.2492%, 20.3839%, 56.5498%, and 51.3964% for AFPID, AFPID2, AFNLPID2, PID, and NLFOPID controllers, respectively.


Upregulation of Periostin expression in the pathogenesis of ameloblastoma.
Ameloblastoma(AB) is an aggressive and slow-growing tumor with high recurrence rate, which arises from odontogenic epithelium. AB mostly shows osteolytic growth, but the specific pathogenesis is not yet clear. Periostin is a considered a prominent oncogene, which was mainly produced by osteoblasts and their precursors cells, it have been proved that Periostin play an important role in bone lysis. However, the precise role of Periostin in AB progression remains unknown. In this article, the surgical specimens from cases of AB were collected, and the Periostin expression was tested and the results were analyzed for possible correlations with clinical characteristics. In addition, the proliferation、cell cycle and migration of AM-1 cells were evaluated after transfection of siPeriostin. The results showed that Periostin levels were significantly higher in patients with AB than in controls. Moreover, Periostin levels in patients with AB were significantly associated with the number of disease. Furthermore, the results suggested that Periostin expression significantly promoted the proliferation and migration, in addition to cell cycle progression of AM-1 cells. The present study demonstrated that Periostin may be important in the pathogenesis and progression of AB and indicated its potential therapeutic value.


Effect of palonosetron on postanesthetic shivering after propofol-remifentanil total intravenous anesthesia.
The authors conducted a prospective, randomized, double-blind study to evaluate the anti-shivering efficacy of palonosetron for patients after gynecological laparoscopy under total intravenous propofol-remifentanil anesthesia. Sixty female patients were randomly assigned to one of two groups and administered palonosetron 0.075 mg (palonosetron group, n = 30) or the same volume of normal saline (control group, n = 30) immediately after anesthesia induction. Anesthesia was induced and maintained with propofol and remifentanil, using a target-controlled infusion device. Esophageal and index finger temperatures were measured immediately after anesthesia induction (baseline) and at 15-min intervals until the end of the surgery. Postanesthetic shivering and side effects were assessed in a postanesthetic care unit. Incidence of shivering was comparable in the control and palonosetron groups (10/30 vs. 8/30, respectively, P = 0.779). No significant intergroup differences were observed between esophageal and index finger temperatures. Compared with baseline values, esophageal temperatures decreased immediately after pneumoperitoneum in the control group and from 30 min after pneumoperitoneum in the palonosetron group. Use of palonosetron (0.075 mg) did not reduce the incidence of postanesthetic shivering after gynecological laparoscopy under propofol-remifentanil anesthesia. Further study including other 5-HT3 antagonists or male patients would elucidate the effect of palonosetron on shivering after propofol-remifentanil anesthesia.


The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function.
2-Hydroxyglutarate (2HG) is a byproduct of the tricarboxylic acid (TCA) cycle and is readily detected in the tissues of healthy individuals. 2HG is found in two enantiomeric forms: S-2HG and R-2HG. Here, we investigate the differential roles of these two enantiomers in cluster of differentiation (CD)8+ T cell biology, where we find they have highly divergent effects on proliferation, differentiation, and T cell function. We show here an analysis of structural determinants that likely underlie these differential effects on specific α-ketoglutarate (αKG)-dependent enzymes. Treatment of CD8+ T cells with exogenous S-2HG, but not R-2HG, increased CD8+ T cell fitness in vivo and enhanced anti-tumor activity. These data show that S-2HG and R-2HG should be considered as two distinct and important actors in the regulation of T cell function.


A cyclic GMP-dependent histone kinase bound to liver nucleoli.
A method of steady-state electrophoresis in polyacrylamide gels was used to analyze the presence of cyclic nucleotide binding components in cell extracts. Multiple cyclic AMP and cyclic GMP binding components were detected in soluble cytoplasmic and nuclear extracts derived from avian liver, but only a single cyclic GMP binding protein was found in the 0.3 M NaCl extract of liver nucleoli. In the presence of cyclic GMP, this protein phosphorylated efficiently a calf thymus histone mixture and an endogenous nucleolar protein, which migrated identically with histone H4 in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The isoelectric point of the cyclic GMP-binding protein was 4.8. Addition of cyclic GMP did not influence the activity of the endogenous nucleolar RNA polymerase.


Chondrosarcoma and myositis ossificans.
To discuss the clinical radiographic findings in a 70-yr-old woman suffering from chondrosarcoma. The patient experienced right SI pain present initially only at night. She later developed morning numbness. An X-ray examination revealed a flocculent calcification in the right buttock region. Computed tomographic scans confirmed the diagnosis. Initial palliative care continued until surgery was performed to resect the area. Chondrosarcoma is a severe disease that must be differentiated from myositis ossificans.


Digital visual acuity test using calculator-type numerals with geometric gradation.
The authors have developed a visual acuity test using numeric optotypes with dimensions similar to numerals used in liquid crystal displays (LCDs) or light-emitting diodes (LEDs). Each optotype has the same external configuration to minimize variation in recognition difficulty. The test is designed with geometric gradation and an equal number of optotypes per line, which facilitates the recording of acuity in decimal notation. This allows convenient data entry and computer analysis of acuity results. Chart inversion provides greater flexibility by altering the numeric sequence. This new digital acuity test (DAT) compares favorably to acuity tests that have Sloan or Snellen letters as optotypes.


Comparison of techniques for vesicourethral anastomosis: simple direct versus modified Vest traction sutures.
Radical retropubic prostatectomy has become a mainstay surgical procedure in the treatment of cancer of the prostate. There has been controversy, however, regarding the most appropriate method of vesicourethral reconstruction. We examined the records of 692 consecutive patients who underwent a radical retropubic prostatectomy from 1978 through 1984 at the Mayo Clinic. Of these, 416 patients underwent a modified Vest procedure, and in 276 patients a direct simple anastomosis was fashioned. In comparing these two methods, our review showed no substantial difference in complications, including the rate of urinary incontinence.


The role of prostaglandins in aldosterone and corticosterone secretion by isolated perfused rat zona glomerulosa cells.
The effect of PGE2 and PGA1 on aldosterone and corticosterone biosynthesis by isolated perfused rat zona glomerulosa cells has been studied. Incremental doses of each of the prostaglandins tested produced a progressive rise in aldosterone (3-4 fold increase for PGE2 and 2-3 fold increase for PGA1) and corticosterone (4-8 fold for PGE2 and 2-4 fold for PGA1). The cyclo-oxygenase inhibitors indomethacin and meclofenamate however produced no effect on basal steroidogenesis. PGE2 produced a marked potentiation of angiotensin II-induced aldosterone secretion (45.7 +/- 13.6 to 144.3 +/- 19.4 pg/ml with angiotensin II alone and 78.4 +/- 16.6 to 269.9 +/- 39.5 pg/ml with angiotensin II + PGE2). In contrast, there was no effect of PGE2 on ACTH or serotonin-induced aldosterone secretion. These data show that PGE2 and PGA1 can directly stimulate rat adrenal steroidogenesis and suggest that PGE2 may play a role in mediating angiotensin II-induced aldosterone secretion by rat zone glomerulosa cells.


Effect of Naltrexone on photoperiodic regulation of testicular steroidogenesis in adult golden hamster, Mesocricetus auratus.
Photoperiodic regulation of testicular steroidogenesis through modulation of MT1R expression and local melatonin content is well established. However, additional mediators besides local melatonergic system in photoperiodic control of testicular steroidogenesis in golden hamster have not been studied in detail. Endogenous opioid peptides (EOP) are known to regulate reproduction via acting at multiple levels of the hypothalamus-pituitary-gonadal (HPG) axis. The presence of β-endorphin, a naturally occurring opioid peptide, and its receptor (μ-opioid receptor, μOR) has been reported in rat testes; however the functional significance of photoperiodic regulation μOR in testicular steroidogenesis is not clear. In the present study, we assessed the effect of Naltrexone (Nal), a μOR antagonist, in photoperiodic regulation of testicular steroidogenesis. Immunohistochemical (IHC) localization and expression of μOR along with the expression of steroidogenic markers in testes was analyzed through western blot analyses. IHC suggest immunoreactivity for μOR in Leydig cells with strong immunoreactivity under SD (short-day) condition, whereas weak immunoreactivity was observed under LD (long-day). The expression of μOR was significantly decreased following Nal administration in both the photoperiodic conditions. The localization and differential photoperiodic regulation of μOR in Leydig cells suggests its involvement in testicular steroidogenesis. Further, Nal administration significantly increased the expression of steroidogenic markers (AR, StAR, P450SCC, LH-R, 3β-HSD and 17-HSD) and plasma testosterone concentration under SD condition as compared to SD-control. We may therefore suggest that photoperiod differentially regulates the expression of μOR which thereby mediates the inhibitory effect of melatonin on testicular steroidogenesis.


Human hexosaminidase isozymes. IV. Effects of oral contraceptive steroids on serum hexosaminidase activity.
Data from a mass screening program for identification of persons who are heterozygous for Tay-Sachs disease have been analyzed for the effects of oral contraceptive steroids on the activity in serum of hexosaminidase (hex) and the various hex isozymes. Women using oral contraceptives show a significantly higher total serum hex activity, reflecting mainly an increase in the heat-stable hex isozyme (hex I), and a smaller increase in the heat-labile hex A than do women using no medications. The changes in women using oral contraceptives are qualitatively similar to those observed during pregnancy. The distribution of responses to oral contraceptives is unimodal, and some of the variations may be related to differences in amount of steroid ingested. In addition, underlying genetic variation may contribute to the observed differences in enzyme activities.


ERS/EBAP European Accreditation of Training Centres in Adult Respiratory Medicine: how could it benefit your centre?
Find out about the benefits of the ERS/EBAP European Accreditation of Training Centres in Adult Respiratory Medicine http://ow.ly/R0dXo.


Comparative analysis of the stellacyanins (SCs) family and focus on drought resistance of PtSC18 in Populus trichocarpa.
Stellacyanin (SC) is a type I (blue) copper protein, which plays a crucial role in plant growth and stress response. However, the comprehensive analysis and functional research of SCs in the woody plant is still lacking. Here, a total of 74 SCs were collected and identified from Arabidopsis, papaya, grape, rice and poplar. Bioinformatics was used to analyze the gene structure, protein structure and evolutionary relationship of 74 genes, especially 19 SCs in Populus trichocarpa. Based on the RNA-seq data, expression pattern of SCs in poplar under cold, high temperature, drought and salt stress were further analyzed. Subsequently, a key candidate gene PtSC18 that strongly responded to drought stress was screened. Subcellular localization experiment exhibited that PtSC18 was localized in the nucleus and plasma membrane. Overexpression of PtSC18 enhanced drought tolerance of transgenic Arabidopsis by improving water retention and reducing oxidative damage. Measurements of physiological indicators, including chlorophyll, H2O2, malondialdehyde content, peroxidase and catalase enzyme activities and electrical conductivity, all supported this conclusion. More importantly, PtSC18 enhanced the expression of some stress-related genes in transgenic Arabidopsis. Overall, our results lay a foundation for understanding the structure and function of PtSCs and provide useful gene resources for breeding through genetic engineering.


Correlating cell transfectability and motility on materials with different physico-chemical properties.
Gene delivery into cells can be facilitated by adding plasmid DNA/transfection reagent complexes in culture medium or pre-adsorbing the complexes on the substrate before cell seeding. Using transfection reagents, however, often causes cytotoxicity. Effective delivery of naked plasmid without any transfection reagent remains a challenge. In this study, we cultured human umbilical cord derived mesenchymal stem cells (hMSCs) on different biomaterial substrates with different physico-chemical properties and examined the transfectability of naked plasmid. Specifically, we synthesized a negatively charged polyurethane (PU) to mimic the hyaluronan-modified chitosan (CS-HA) membranes previously found to promote the transfection of naked plasmid. We observed that the PU membranes were as effective as CS-HA membranes in substrate-mediated delivery of naked plasmid into hMSCs. PU membranes with surface microgrooves further increased the gene delivery efficiency to a similar level as the commercial transfection reagent but without the harmful effect. The gene delivery efficiency was associated with the extent of activation of cellular integrins β1 and α5 on different substrates. Moreover, the delivery efficiency was positively correlated with the cell migration rate on various substrates. The substrate-mediated gene delivery by synthetic polymeric substrates supports that integrin activation and cell behavior (e.g. migration and transfectability) changes can be modulated by synthetic polymer surface with microfeatures. The transfection by PU microgrooves is easy, nontoxic, and as effective as the commercial transfection reagent.


Contribution of root respiration to soil respiration in a C3/C4 mixed grassland.
The spatial and temporal variations of soil respiration were studied from May 2004 to June 2005 in a C3/C4 mixed grassland of Japan. The linear regression relationship between soil respiration and root biomass was used to determine the contribution of root respiration to soil respiration. The highest soil respiration rate of 11.54 micro mol m-2 s-1 was found in August 2004 and the lowest soil respiration rate of 4.99 micro mol m-2 s-1 was found in April 2005. Within-site variation was smaller than seasonal change in soil respiration. Root biomass varied from 0.71 kg m-2 in August 2004 to 1.02 in May 2005. Within-site variation in root biomass was larger than seasonal variation. Root respiration rate was highest in August 2004 (5.7 micro mol m-2 s-1) and lowest in October 2004 (1.7 micro mol m-2 s-1 ). Microbial respiration rate was highest in August 2004 (5.8 micro mol m-2 s-1 ) and lowest in April 2005 (2.59 micro mol m-2 s-1 ). We estimated that the contribution of root respiration to soil respiration ranged from 31% in October to 51% in August of 2004, and from 45% to 49% from April to June 2005.


An interesting case of pyoderma gangrenosum with immature hystiocytoid neutrophils.
We present a unique case of a 36-year-old male who developed more than 20 pyoderma gangrenosum (PG) ulcers showing on histopathology a dense inflammatory infiltrate composed of histiocytoid mononuclear immature cells with a strong positivity for myeloperoxidase and Leder stain, suggesting a myeloid lineage in the absence of a concomitant myeloproliferative disorder. Histiocytoid Sweet syndrome (SS) is now recognized as a histological subtype of SS. Although PG and SS belong to the spectrum of neutrophilic diseases, to the best of our knowledge, this is the first case of a "Histiocytoid pyoderma gangrenosum" encompassing immature granulocytes in the absence of leukemia cutis.


Biofunctional magnesium-coated Ti6Al4V scaffolds promote autophagy-dependent apoptosis in osteosarcoma by activating the AMPK/mTOR/ULK1 signaling pathway.
The recurrence of osteosarcoma (OS) after reconstruction using Ti6Al4V prostheses remains a major problem in the surgical treatment of OS. Modification of the surfaces of Ti6Al4V prostheses with antitumor functions is an important strategy for improving therapeutic outcomes. Magnesium (Mg) coating has been shown to be multifunctional: it exhibits osteogenic and angiogenic properties and the potential to inhibit OS. In this study, we determined the proper concentration of released Mg2+ with respect to OS inhibition and biosafety and evaluated the anti-OS effects of Mg-coated Ti6Al4V scaffolds. We found that the release of Mg2+ during short-term and long-term degradation could significantly inhibit the proliferation and migration of HOS and 143B cells. Increased cell apoptosis and excessive autophagy were also observed, and further evidence of AMPK/mTOR/ULK1 signaling pathway activation was obtained both in vitro and in vivo, which suggested that the biofunctional scaffolds induce OS inhibition. Our study demonstrates the ability of an Mg coating to inhibit OS and may contribute to the further application of Mg-coated Ti6Al4V prostheses.


Clinical studies on elevation of serum CPK activity in patients with drug intoxication.
Elevation of serum creatine phosphokinase (CPK), known to occur in only cerebral, cardiac and muscular diseases, was encountered in 34 patients with drug intoxication. The mechanism of hyper-CPKemia in drug intoxication was examined by determining the correlations between CPK variations and underlying factors. Liver function, WBC, serum total protein, albumin and blood sugar indicated correlations with serum CPK. It seemed that increased blood sugar, decreased protein, decreased albumin and increased WBC were associated with hyper-CPKemia and reflected severe acute stress to the nervous, endocrine and metabolic systems collapsing the systemic physiological homeostasis.


Beyond the embolus: "do not miss" diffusion abnormalities of ischaemic and non-ischaemic neurological disease.
Given the rapid evolution and technological advances in the diagnosis and treatment of acute ischaemic stroke (AIS), including the proliferation of comprehensive stroke centres and increasing emphasis on interventional stroke therapies, the need for prompt recognition of stroke due to acute large vessel occlusion has received significant attention in the recent literature. Diffusion-weighted imaging (DWI) is the gold standard for the diagnosis of acute ischaemic stroke, as images appear positive within minutes of ischaemic injury, and a high signal-to-noise ratio enables even punctate infarcts to be readily detected. DWI lesions resulting from a single arterial embolic occlusion or steno-occlusive lesion classically lateralise and conform to a specific arterial territory. When there is a central embolic source (e.g. left atrial thrombus), embolic infarcts are often found in multiple vascular territories. However, ischaemic disease arising from aetiologies other than arterial occlusion will often not conform to an arterial territory. Furthermore, there are several important entities unrelated to ischaemic disease that can present with abnormal DWI and which should not be confused with infarct. This pictorial review explores the scope and typical DWI findings of select neurologic conditions beyond acute arterial occlusion, which should not be missed or misinterpreted. • DWI abnormalities due to acute arterial occlusion must be promptly identified. • DWI abnormalities not due to arterial occlusion will often not conform to an arterial territory. • Several important non-ischaemic entities can present on DWI and should not be confused with infarct.


Preventable Iatrogenic Disability in Elderly Patients During Hospitalization.
In older patients, hospitalization is often associated with new or worsening disability. This hospitalization-associated disability may be explained in part by the cumulative effect of aging, frailty, comorbidities, and illnesses that led to hospitalization but may also result from health care management issues and the hospital environment. Our objective was to determine the frequency, causes, and the preventability of disability induced by the processes of care or "iatrogenic disability." A total of 503 patients, aged 75 years and older, hospitalized in the 105 medical and surgical units of Toulouse University Hospital between October 2011 and March 2012, with a minimal length of stay of 2 days, were included. Hospitalization-associated disability was defined as a loss of 0.5 points or more in the Katz Activity of Daily Living Score between the time of hospital admission and discharge. To determine the iatrogenic component of hospitalization-associated disability, an expert panel in geriatric medicine reviewed each medical chart using a standardized record review and identified precipitating iatrogenic adverse events resulting in functional decline. Incidence of iatrogenic disability was 11.9% (95% confidence interval, 9.2%-15.1%). Of the 60 cases of iatrogenic disability, 49 (81.7%, 95% confidence interval, 69.6%-90.5%) were judged to be potentially preventable. The most common health management issues identified in patients with preventable iatrogenic disability were low mobilization [by excessive bed rest (26.5%) and lack of physical therapist intervention (55.1%)], overuse of diapers (49.0%), and transurethral urinary catheterization (30.6%). The present study suggests that a significant proportion of hospitalization-associated disability may be induced by iatrogenic events, and that most of them are potentially preventable. Health care professionals need to be educated on the specific needs of elderly hospitalized patients and should consider hospitalization-associated disability as an outcome of care.


New clamp for intraoperative chest tube placement.
We describe an instrument designed specifically to avoid the pitfalls of intraoperative chest tube placement.


Morphometric analysis of corneal endothelial giant cells in normal and traumatized corneas.
Corneal endothelial cells from normal and traumatized human, primate, cat and rabbit eyes were studied by specular microscopy. Morphometric analysis was performed on micrographs of corneal endothelium using a semi-automated image analysis system. The results showed that under normal conditions the corneal endothelium of all four species exhibit major morphological similarities (mean cell areas: human 317 +/- 32 microns 2, primate 246 +/- 22 microns2, cat 357 +/- 25 microns 2, rabbit 308 +/- 35 microns 2). The normal corneal endothelium in man was found to be more polymegethous than that of the other species. Trauma to cat, primate and human corneas resulted in a long-term reduction in endothelial cell density and enhanced polymegethism. In contrast, the reparative response of the rabbit ensured the reformation of an essentially normal monolayer following injury. Endothelial giant cells were a normal inclusion in the rabbit corneal endothelium but were only significant in cat, primate and man following trauma. The presence of corneal endothelial giant cells in amitotic corneas may therefore represent a compensatory response in the absence of mitotic potential.


Nutritional Aspects of Late Eating and Night Eating.
The timing of food intake has been investigated as a novel factor in the etiology, maintenance, and treatment of obesity. Indeed, consuming a large proportion of food later in the day and into the night has been associated with higher body weight and may even impair weight loss. The diet quality of late-eaters may be a factor involved in these relationships. Moreover, the nutritional characteristics of the foods consumed during the night may negatively affect metabolic and circadian rhythms that are required for optimal health. This review will first examine the diet quality of late-eaters and describe common foods consumed as nocturnal snacks. Second, this review will briefly acknowledge the potential adverse metabolic and circadian effects of consuming certain foods very late in the evening or during the night.


Independence estimators for re-randomisation trials in multi-episode settings: a simulation study.
Re-randomisation trials involve re-enrolling and re-randomising patients for each new treatment episode they experience. They are often used when interest lies in the average effect of an intervention across all the episodes for which it would be used in practice. Re-randomisation trials are often analysed using independence estimators, where a working independence correlation structure is used. However, research into independence estimators in the context of re-randomisation has been limited. We performed a simulation study to evaluate the use of independence estimators in re-randomisation trials. We focussed on a continuous outcome, and the setting where treatment allocation does not affect occurrence of subsequent episodes. We evaluated different treatment effect mechanisms (e.g. by allowing the treatment effect to vary across episodes, or to become less effective on re-use, etc), and different non-enrolment mechanisms (e.g. where patients who experience a poor outcome are less likely to re-enrol for their second episode). We evaluated four different independence estimators, each corresponding to a different estimand (per-episode and per-patient approaches, and added-benefit and policy-benefit approaches). We found that independence estimators were unbiased for the per-episode added-benefit estimand in all scenarios we considered. We found independence estimators targeting other estimands (per-patient or policy-benefit) were unbiased, except when there was differential non-enrolment between treatment groups (i.e. when different types of patients from each treatment group decide to re-enrol for subsequent episodes). We found the use of robust standard errors provided close to nominal coverage in all settings where the estimator was unbiased. Careful choice of estimand can ensure re-randomisation trials are addressing clinically relevant questions. Independence estimators are a useful approach, and should be considered as the default estimator until the statistical properties of alternative estimators are thoroughly evaluated.


Do serum GDNF levels correlate with severity of Alzheimer's disease?
A growing body of evidence that glial cell line-derived neurotrophic factor (GDNF) levels are probably involved in pathogenesis and disease course of Alzheimer's disease (AD) suggested that its blood levels could potentially be used as a biomarker of AD. The aim of this study was to compare serum GDNF levels in patients with AD and age-matched controls. Serum concentrations of GDNF were compared in 25 AD patients and 25 healthy volunteers using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Severity of the disease in AD patients was assessed using Functional Assessment Staging (FAST). Cognitive assessment of the patients was done using the Mini-Mental State Examination (MMSE). Mean GDNF levels were found to be 2.45 ± 0.93 ng/ml in AD patients and 4.61 ± 3.39 ng/ml in age-matched controls. There was a statistically significant difference in GDNF serum levels in patients with AD compared to age-matched controls (p = 0.001). Moreover, GDNF serum levels were significantly correlated with disease severity (p < 0.001) and cognitive impairment (p < 0.001). This study showed that serum levels of GDNF are significantly decreased in AD patients in comparison with age-matched controls, thus suggesting a potential role of GDNF as a disease biomarker. However, a comprehensive study of changes in serum levels of multiple neurotrophic factors reflective of different neurobiological pathways in large-scale population studies is recommended.


Preparation and characterization of carboxymethyl cellulose containing quaternized chitosan for potential drug carrier.
The objective of this study was to synthesize and characterize cystamine dihydrochloride (CYS) crosslinked carboxymethyl cellulose/quaternized chitosan (CMC/HACC) composite hydrogel film. Firstly, the glycidyl-based quaternary ammonium chitosan derivative (HACC) was synthesized using nucleophilic substitution reaction. Then HACC was analyzed by FTIR, 1HNMR spectra and the composite films at different blending ratio of CMC and HACC were studied by rheology measurement, mechanical and swelling tests. When the composite films were prepared under optimized conditions (CMC: HACC = 7:1), they showed excellent mechanical properties (with improved 93.3% tensile strength and 2.3% elongation at break) and swellability (equilibrium swelling ratio increased 270%) compared to pure CMC film. 5-Fluorouracil (5-FU) was used as drug model which has broad-spectrum anticancer properties. The 5-FU/CMC/HACC composite films showed redox and pH responsive of drug release properties along with well biocompatibility. The in vitro cytotoxicity and cell apoptosis studies showed the drug loaded composite films with obvious toxicity against HepG2 cells especially in the presence of GSH. In addition, CMC/HACC composite films showed good antibacterial against S. aureus and E. coli, while pure CMC film had no antimicrobial activities. It can be concluded that CMC/HACC composite films can be potentially used as targeted drug delivery system.


Comparison of biomarkers of exposure among US adult smokers, users of electronic nicotine delivery systems, dual users and nonusers, 2018-2019.
The harm caused by cigarette smoking is overwhelmingly due to byproducts of tobacco combustion. Electronic Nicotine Delivery Systems (ENDS) provide nicotine to users without combustion, and may support tobacco harm reduction among cigarette smokers who would not otherwise quit in the near term. Analyses of Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study compared biomarkers of exposure (BOE) levels for nicotine, 3 metals, 2 tobacco-specific nitrosamines and 14 smoking-related volatile organic compounds in 151 exclusive ENDS users, 1341 exclusive cigarette smokers, 115 dual users (cigarettes and ENDS), and 1846 past 30-day nonusers of tobacco, adjusting for demographics. Nicotine exposure in ENDS users and dual users did not significantly differ from smokers. Among ENDS users, 16 of 18 other BOEs were significantly lower than smokers'; 9 BOEs were not significantly different from nonusers. Among dual users smoking < 10 cigarettes/day, 15 of 18 non-nicotine BOEs were significantly lower than smokers', whereas in dual users smoking ≥ 10 cigarettes per day none of the BOEs significantly differed from smokers'. In this representative sample of US adults, exclusive use of ENDS (vs. cigarette smoking) was associated with much lower exposures to many harmful chemicals associated with smoking-related disease. BOE levels in dual users were directly related to their cigarette consumption. These BOE data provide further evidence that ENDS expose users to substantially lower levels of toxicants than combustible cigarettes, confirming their potential for harm reduction.


Naftifine: a review.
Naftifine is a topical allylamine that is effective and safe in the management of superficial dermatomycoses. Naftifine is fungicidal in vitro against a broad spectrum of dermatophyte fungi and provides good activity against Candida and Aspergillus species. It is also effective against gram-negative and gram-positive bacteria. To provide a review of the pharmacologic properties and clinical efficacy of topical naftifine preparations. A review of the medical literature was performed using PubMed (1965-2006) using the search term "naftifine." All available English-language articles discussing the pharmacology and clinical use of naftifine were reviewed for the article. Naftifine causes interruption of fungal ergosterol synthesis and accumulation of squalene in fungal organisms. Naftifine also has demonstrated anti-inflammatory properties such as a reduction in superoxide production and a reduction in polymorphonuclear leukocyte chemotaxis/endothelial adhesion. Naftifine has shown good efficacy and safety for a variety of conditions and is a useful treatment that provides both antifungal action and relief of inflammatory signs and symptoms. Few adverse events have been noted with naftifine use, the most frequent being mild and transient burning, stinging, or itching in the application area. Naftifine remains a reliable multifunctional agent for a variety of superficial infections.


Modification of TSH-stimulated adenylate cyclase activity of bovine thyroid by manipulation of membrane phospholipid composition with a nonspecific lipid transfer protein.
The lipid composition of bovine thyroid plasma membranes was modified using the nonspecific lipid transfer protein from bovine liver. Incubation of plasma membranes with transfer protein and phosphatidylinositol-containing liposomes caused a strong, concentration dependent, inhibition of TSH-stimulated adenylate cyclase activity. Other phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidic acid were two to four times less effective as inhibitors of TSH-stimulation. The phosphatidylinositol-induced inhibition was not reversed when more than 80% of phosphatidylinositol incorporated was removed using phosphatidylinositol-specific phospholipase C. Incorporation of phosphatidylinositol in plasma membranes provoked no significant change in the fluorescence anisotropies of the fluorophores 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(14-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), indicating that the inhibition was not due to changes in membrane fluidity. At phosphatidylinositol concentrations causing a 66% reduction in TSH-stimulated adenylate cyclase activity cholera toxin- and forskolin-stimulated activity as well as basal activity were decreased by maximally 10%. Since TSH binding to bovine thyroid plasma membranes was not affected it is suggested that phosphatidylinositol can act as a negative modulator of the TSH activation of adenylate cyclase and this probably by interfering with the coupling between the occupied TSH receptor and the stimulatory GTP-binding regulatory protein of the adenylate cyclase complex.


Analysis of mitochondrial DNA sequence variants in patients with polycystic ovary syndrome.
To understand the role of mitochondrial DNA (mtDNA) mutations in patients with polycystic ovary syndrome (PCOS). A total of 57 women with PCOS and 38 controls were recruited in this study, mutational analysis of mitochondrial genome was performed using polymerase chain reaction and under a direct sequence analysis. Sequence characterization of mitochondrial genome showed a distinct set of polymorphisms mainly focused on oxidative phosphorylation (OXPHOS) complex, in addition, six variants in mitochondrial tRNA genes, including tRNA(Gln), tRNA(Cys), tRNA(Asp), tRNA(Lys), tRNA(Arg) and tRNA(Glu) were also identified in PCOS patients. Interestingly, these variants occurred at highly conserved nucleotides of corresponding tRNAs, which are important for tRNA stability level and biochemical function. Mutations in mtDNA, especially the OXPHOS complex and tRNAs, may be associated with PCOS patients, thus, our results shed new insight into the pathogenesis of PCOS.


Oncologic outcomes after laparoscopic versus open multivisceral resection for local advanced colorectal cancer: A meta-analysis.
Laparoscopic (lap) colectomies for advanced colorectal cancer (CRC) often require resection of other organs. We systematically reviewed currently available literature on lap multi-visceral resection for CRC, with regard to short- and long-term oncological outcomes, and compared them with open procedures. We performed a systematic literature search in MEDLINE, EMBASE, Google Scholar and PubMed from inception to November 30, 2020. The aim of this study was to synthesize short-term and oncological outcomes associated with laparoscopic versus open surgery. Pooled proportions and risk ratios (RRs) were calculated using an inverse variance method. We included six observational cohort studies published between 2012 and 2020 (lap procedures: n = 262; open procedures: n = 273). Collectively, they indicated that postoperative complications were significantly more common after open surgeries than lap surgeries (RR: 0.53; 95% confidence interval [CI]: 0.39-0.72; P < 0.00001), but the two approaches did not significantly differ in positive resection margins (RR: 0.75; 95% CI: 0.38-1.50; P = 0.42), local recurrence (RR: 0.66; 95% CI: 0.28-1.62; P = 0.37), or (based on two evaluable studies) 5-year OS (RR: 0.70; 95% CI: 0.46-1.04; P = 0.08) or 5-year DFS (RR: 0.86; 95% CI: 0.67-1.11) for T4b disease. In conclusion, laparoscopic and open multi-visceral resections for advanced CRC have comparable oncologic outcomes. Although a randomized study would be ideal for further research, no such studies are currently available.


The Burn Wound.
Skin serves as a protective barrier against infection, prevents excessive fluid and electrolyte losses, performs crucial thermoregulation, and provides tactile feedback of surroundings. The skin also plays an essential role in human perception of body image, personal appearance, and self-confidence. With these many diverse functions, understanding normal anatomic composition of skin is pivotal to evaluating the extent of its disruption from burn injury. This article discusses the pathophysiology, initial evaluation, subsequent progression, and healing of burn wounds. By delineating the various microcellular and macrocellular alterations of burn injury, this review also augments providers' capacity to deliver patient-centered, evidence-based burn care.


Mathematical expertise: the role of domain-specific knowledge for memory and creativity.
In contrast to traditional expertise domains like chess and music, very little is known about the cognitive mechanisms in broader, more education-oriented domains like mathematics. This is particularly true for the role of mathematical experts' knowledge for domain-specific information processing in memory as well as for domain-specific and domain-general creativity. In the present work, we compared 115 experts in mathematics with 109 gender, age, and educational level matched novices in their performance in (a) a newly developed mathematical memory task requiring encoding and recall of structured and unstructured information and (b) tasks drawing either on mathematical or on domain-general creativity. Consistent with other expertise domains, experts in mathematics (compared to novices) showed superior short-term memory capacity for complex domain-specific material when presented in a structured, meaningful way. Further, experts exhibited higher mathematical creativity than novices, but did not differ from them in their domain-general creativity. Both lines of findings demonstrate the importance of experts' knowledge base in processing domain-specific material and provide new insights into the characteristics of mathematical expertise.


Investigation of the cause of geographic disparities in IDEXX ELISA sensitivity in serum samples from Mycobacterium bovis-infected cattle.
Accurately identifying Mycobacterium bovis-infected cattle is critical for bovine tuberculosis prevention and control. One method for identifying infected cattle is an ELISA developed by IDEXX laboratories, which detects antibodies to two M. bovis proteins, MPB70 and MPB83. The assay's sensitivity varies by geographic region, with sensitivities of 77%, 45%, and 9% in bovine serum samples from the United Kingdom (n = 126), the United States (n = 146), and Mexico (n = 128), respectively. We hypothesized that geographically-biased sequence variation in mpb70 and mpb83, or in the genes that regulate their expression (sigK and rskA), may explain these differing sensitivities. This hypothesis was tested by comparing the sequences of these four genes in 455 M. bovis strains isolated from cattle in the aforementioned countries. For each gene, a single, common sequence was identified in most genomes of the M. bovis strains collected in all three countries. Twelve of the 455 strains were isolated from infected cattle for which the IDEXX ELISA was also performed. Five of the seven ELISA-positive genomes and three of the five ELISA-negative genomes contained the most common sequence of all four genes. Thus, sequence variation in mpb70, mpb83, sigK, and rskA does not explain the geographic disparities in IDEXX ELISA sensitivity.


Arbovirus isolations from, and serological studies on, wild and domestic vertebrates from Kano Plain, Kenya.
Arbovirus infection and presence of haemagglutination-inhibiting antibodies in small mammals, birds and livestock were examined over a period of five years on the Kano Plain in western Kenya. Eleven isolations were made from mammals and birds. The viruses were identified as Arumowot and Germiston while three different agents could not be shown to be related to 188 African arboviruses. Prevalence of antibodies against arboviruses suspected of occurring in the area was generally low.


How auditory selectivity for sound timing arises: The diverse roles of GABAergic inhibition in shaping the excitation to interval-selective midbrain neurons.
Across sensory systems, temporal frequency information is progressively transformed along ascending central pathways. Despite considerable effort to elucidate the mechanistic basis of these transformations, they remain poorly understood. Here we used a novel constellation of approaches, including whole-cell recordings and focal pharmacological manipulation, in vivo, and new computational algorithms that identify conductances resulting from excitation, inhibition and active membrane properties, to elucidate the mechanisms underlying the selectivity of midbrain auditory neurons for long temporal intervals. Surprisingly, we found that stimulus-driven excitation can be increased and its selectivity decreased following attenuation of inhibition with gabazine or intracellular delivery of fluoride. We propose that this nonlinear interaction is due to shunting inhibition. The rate-dependence of this inhibition results in the illusion that excitation to a cell shows greater temporal selectivity than is actually the case. We also show that rate-dependent depression of excitation, an important component of long-interval selectivity, can be decreased after attenuating inhibition. These novel findings indicate that nonlinear shunting inhibition plays a key role in shaping the amplitude and interval selectivity of excitation. Our findings provide a major advance in understanding how the brain decodes intervals and may explain paradoxical temporal selectivity of excitation to midbrain neurons reported previously.


Experimental studies on cardiac muscle cell adaptation to insult.
Studies were carried out in rats on myocardial adaptation to injury produced by left coronary artery ligation. In the ischemic zone, open collaterals were present as shown by studies using the fine structural extracellular protein tracer, horseradish peroxidase (HRP). This phenomenon may explain the inhomogeneous cardiac muscle cell alteration in the early phase of coronarogenic myocardial injury. Reperfusion, as evidenced by the influx of HRP into the damaged cells, unmasked sarcolemmal membrane injury. Cardiac muscle cell stimulation modifies the binding of macromolecules to cell components and may influence the repair processes. In the surviving myocardium, correlative enzyme histochemical and ultrastructural studies demonstrated the development of alternative metabolic pathways and morphological signs of adaptation explaining increasing resistance of such cardiac muscle cells to subsequent insult.


A case of Langerhans' cell histiocytosis associated with Hodgkin's lymphoma: Fine-needle aspiration cytologic and histopathological features.
Langerhans cell histiocytosis (LCH) can be associated with a variety of malignant neoplasms, the most common being malignant lymphoma, especially Hodgkin's lymphoma (HL). In this report, we describe the fine needle aspiration (FNA) cytologic features of a case with concurrent LCH and HL in a lymph node. A 20-year-old man presented with an enlarged left upper cervical lymph node. FNA smears from the swelling revealed numerous CD1a+ and S-100+ Langerhans-type cells (LCs) along with many eosinophils, neutrophils, and lymphocytes; there were also large atypical cells with enlarged nuclei having prominent nucleoli. The cytodiagnosis was LCH and the possibility of association with or trans-differentiation into a lymphoma was suggested. The histopathological diagnosis of the excised left cervical lymph node was classical HL-nodular sclerosis type (CHL-NS) with LCH. The lacunar type Reed-Sternberg (RS) cells were positive for CD30 and CD15, and the LCs were positive for CD1a and S-100 protein. PET/CT imaging demonstrated hypermetabolic lymph nodes in neck, abdomen, thorax and pelvis as well as pulmonary nodules and a splenic mass. The patient received 13 courses of chemotherapy and two years later, the enhanced CT revealed regressive course of the disease.


De-escalation of axillary surgery in patients outside Z0011 criteria.
Over the past 2 decades, axillary surgical management for breast cancer patients has been reshaped after several practice-changing randomized clinical trials provided evidence to support the de-escalation of axillary surgery, specifically the omission of axillary lymph node dissection, for patients with positive axillary lymph nodes. One such practice-changing trial was the American College of Surgeons Oncology Group Z0011 trial, which showed that patients with clinical T1-2 breast tumors and limited nodal disease (1-2 positive sentinel lymph nodes) who underwent upfront breast-conserving therapy could be safely spared the morbidity of axillary lymph node dissection. American College of Surgeons Oncology Group Z0011 has been criticized as several important groups were excluded, such as patients who underwent a mastectomy, patients with >2 positive sentinel lymph nodes, or patients with imaging-detected lymph node metastases. These exclusions have led to unclear guidelines and very difficult management decisions for many patients with breast cancer who are just outside the Z0011 criteria. Several subsequent trials that investigated sentinel lymph node biopsy alone or sentinel lymph node biopsy plus axillary radiation versus axillary lymph node dissection enrolled patients with higher volumes of disease than American College of Surgeons Oncology Group Z0011, such as mastectomy patients or patients with >2 positive sentinel lymph nodes. The goal of this review is to describe the findings of these trials and to discuss the current best practices regarding axillary management in patients who are candidates for upfront surgery but were excluded from American College of Surgeons Oncology Group Z0011, with a particular focus on patients undergoing mastectomy, patients with >2 positive sentinel lymph nodes, patients with large or multifocal tumors, and patients with imaging-detected biopsy-proven lymph node metastases.


Synergistic action of protein kinase C and calcium for histamine release from rat peritoneal mast cells.
When rat mast cells were stimulated by concanavalin A, phosphatidylinositol turnover was induced. Concurrently, several cytosol proteins were phosphorylated and histamine was released. 1-Oleoyl-2-acetyl-glycerol ( OAG ) and 12-O-tetradecanoylphorbol-13-acetate (TPA), known as direct activators of protein kinase C in intact cells, induced phosphorylation of the same spectrum of proteins. These proteins also served in vitro as preferable substrates for protein kinase C. The simultaneous addition of OAG or TPA and A23187 synergistically enhanced histamine release from mast cells. It is suggestive that protein kinase C activation and Ca2+ mobilization play essential roles for this cellular response.


Effects of non-ionic surfactants N-alkyl-N,N-dimethylamine-N-oxides on the structure of a phospholipid bilayer: small-angle X-ray diffraction study.
Effects of non-ionic surfactants N-alkyl-N,N-dimethylamine-N-oxides (C(n)NO, n is the number of alkyl carbons) on the structure of egg yolk phosphatidylcholine (EYPC) bilayers in the lamellar fluid phase was studied by small-angle X-ray diffraction as a function of H(2)O:EYPC and C(n)NO:EYPC molar ratios. The bilayer thickness d(L) and the lipid surface area at the bilayer-aqueous interface S(L) were calculated from the repeat period, d of the lamellar phase, based on the model that water and EYPC + CnNO molecules form separated layers and that their molecular volumes are additive. In the studied range of m=CnNO:EYPC molar ratios up to 1:1, d(L) and S(L) change linearly. The slopes Delta L = delta dL/ delta m and Delta S= delta S L / delta m are equal to -0.876 +/- 0.027 nm and 0.347 +/- 0.006 nm2 for C(6)NO, -1.025+/-0.060 nm and 0.433+/-0.025 nm(2) for C(8)NO, -0.836+/-0.046 nm and 0.405+/-0.018 nm(2) for C(10)NO, -0.604+/-0.015 nm and 0.375+/-0.007 nm(2) for C(12)NO, -0.279+/-0.031 nm and 0.318+/-0.005 nm(2) for C(14)NO, -0.0865+/-0.070 nm and 0.2963 +/-0.014 nm(2) for C(16)NO, and -0.040+/-0.022 nm and 0.297+/- 0.002 nm(2) for C(18)NO, respectively, at full bilayer hydration. The peak-peak distance in the bilayer electron density profile, which relates to the P-P distance d(PP), obtained from the first four diffraction peaks by the Fourier transform also depends linearly on m, and the slope Delta PP = delta dPP/delta m is -0.528+/-0.065 nm for C(6)NO, -0.680+/-0.018 nm for C(8)NO, -0.573+/-0.021 nm for C(10)NO, -0.369+/-0.075 nm for C(12)NO, -0.190+/-0.015 for C(14)NO, -0.088+/-0.016 nm for C(16)NO and -0.094+/-0.016 nm for C(18)NO. The effects of C(n)NO on Delta(L), Delta(S) and Delta(PP) are the results of C(n)NO insertion into EYPC bilayers and depend on the hydrophobic mismatch between C(n)NO and EYPC hydrocarbon chains and on the lateral interactions of C(n)NO and EYPC in the bilayer.


Respiratory mechanics in infants and young children before and after repair of left-to-right shunts.
In an attempt to investigate the relationship between respiratory mechanics and pulmonary hemodynamics, we evaluated pulmonary function in 31 infants with left-to-right shunts and subsequent high pulmonary blood flow, undergoing cardiac surgery. Measurements were performed 1 d before and repeated 10 d and 4-5 wk after correction. The age of the patients ranged from 4 d to 24 mo, body weight from 2.7 to 11.8 kg. Pulmonary artery pressure, assessed by Doppler echocardiography, was preoperatively elevated in 23 patients (group 1), whereas it was within normal values in eight infants (group 2). Respiratory mechanics were measured using the single-breath occlusion technique in sedated infants. To evaluate specific compliance, functional residual capacity was determined by using an open circuit nitrogen washout technique. A reduced preoperative compliance value (mean with 95% confidence interval) was found in group 1: 34.8 (26.5-43.1) mL.kPa-1. After hemodynamic correction, a progressive significant (p < 0.01) improvement was demonstrated at 10 d and 1 mo with values of 47.5 (39.2-55.8) mL.kPa-1 and 56.5 (45.6-67.4) mL.kPa-1, respectively. A similar trend was noted evaluating specific compliance with values of 0.27 (0.24-0.30) kPa-1 and 0.44 (0.42-0.46) kPa-1, respectively before and after surgery. Preoperative functional residual capacity value was 130 (100-160) mL. In group 2, normal preoperative compliance values were obtained, without significant changes after surgery. In both groups, resistance was within the normal range both before and after surgical correction, and functional residual capacity did not change either. No correlations were found between compliance and pulmonary artery pressure and pulmonary blood flow values.(ABSTRACT TRUNCATED AT 250 WORDS)


No evidence for antibodies to mycobacterial A60 antigen in Crohn's disease sera by enzyme-linked immunoabsorbent assay (ELISA).
Sera from patients with Crohn's disease were tested with an ELISA system for antibodies to antigen A60 prepared from Mycobacterium bovis (BCG), M. avium and M. paratuberculosis. No evidence was found for significantly high titres of antibody to these antigens.


Effects of ischemia and reperfusion on pyruvate dehydrogenase activity in isolated rat hearts.
The effects of myocardial ischemia and reperfusion on pyruvate dehydrogenase (PDH) activity were studied in isolated rat hearts. PDH remained largely (80%) in the active form during 10 min of whole heart ischemia in hearts receiving 11 mM glucose as substrate. With reperfusion, PDH was converted to the inactive form (45% by 2 min) and then returned slowly to control levels. Addition of pyruvate (10 mM) to the glucose containing perfusate during reperfusion prevent the reperfusion inactivation of PDH (96% active). The maintenance of a high percent of PDH in the active form during ischemia occurred in spite of high mitochondrial ratios of NADH/NAD and acetyl CoA/CoA and was related to a very low mitochondrial ATP/ADP ratio. The low ATP and high ADP would restrict PDH kinase phosphorylation and inactivation of PDH during ischemia. Reperfusion resulted in a rapid increase in mitochondrial ATP/ADP ratio and the increased availability of ATP as substrate for the kinase coupled with continued high levels of NADH and acetyl CoA which stimulate kinase activity may have accounted for the early inactivation of PDH with reperfusion. Addition of pyruvate to the perfusate probably inhibited the PDH kinase and prevent the reperfusion inactivation of PDH.


A review of medication reconciliation issues and experiences with clinical staff and information systems.
Medication reconciliation was developed to reduce medical mistakes and injuries through a process of creating and comparing a current medication list from independent patient information sources, and resolving discrepancies. The structure and clinician assignments of medication reconciliation varies between institutions, but usually includes physicians, nurses and pharmacists. The Joint Commission has recognized the value of medication reconciliation and mandated implementation in 2006; however, a variety of issues have prevented simple, easy, and universal implementation. This review references issues related to the development and the implementation of medication reconciliation including: - the need of a system or standard for accurate drug identification to create a definitive 'gold standard' patient medication list, - identifying stakeholders of medication reconciliation within the institution and contrasting staff interest and participation with institutional resources, - observations and opportunities of integrating medication reconciliation with the electronic patient health record, and - summarizing a series of institutions experiences developing and implementing medication reconciliation. Last, as medication reconciliation becomes a regular process within medical centers, key concepts for effective implementation are discussed.


Dissociation studies of DNA/anti-DNA complexes in relation to anti-DNA avidity.
Antibodies to dsDNA differ in their avidity towards the antigen. The electrostatic interaction between DNA and anti-DNA is sensitive to increases in pH and/or ionic strength and therefore, elution studies employing either of these permit discrimination between anti-dsDNA populations that differ in avidity. Another way to determine anti-dsDNA avidity is the calculation of Farr/PEG ratios. These are obtained by division of the amount of anti-DNA measured with the Farr assay (which does not detect low avidity anti-dsDNA) by the amount measured with the PEG assay (which does detect low avidity anti-dsDNA). With these separate approaches, we compared the sera of 17 SLE patients with nephritis with the sera of 17 patients with central nervous system (CNS) involvement. Farr/PEG ratios and sensitivity to high pH elution of anti-dsDNA in the sera of these patients both permitted discrimination between the two groups of patients. The anti-dsDNA of patients with nephritis was found to have a significantly higher avidity towards DNA than anti-dsDNA of patients with cerebral disease. We also observed a significant correlation between Farr/PEG ratios and the salt lability of anti-dsDNA.


Electrolyte transport across a simple epithelium. Steady-state and transient analysis.
A simple transporting epithelium is represented as a cellular compartment, compliant in all dimensions, and a paracellular channel, of arbitrary shape, between well-stirred mucosal ans serosal baths. The equations for mass balance, Poiseuille flow, and the Nernst-Planck equation are used to describe the continuous behavior of the system along cell and channel, whereas passive transport across membranes is given by the relations of Kedem and Katchalsky. Time-dependent terms are retained to permit study of transient phenomena. Boundary conditions at the baths demand only mass conservation and specify no a priori estimates of the system variables. A numerical model containing Na+,K+,Cl-, and impermeant cellular anions is formulated with membrane parameters taken from the literature on Necturus gallbladder. The differential equations are represented as a finite difference scheme and solved using Newton's method. It appears that apical cellular NaCl cotransport is necessary to obtain a reasonable cell chloride concentration. Investigation of the osmolality of the transepithelial flow shows that at steady state a leaky epithelium cannot separate baths of substantially different tonicity, although this does not guarantee isotonic transport between equiosmolar media. Changes in bath pressure, application of transepithelial electrical potential, and simulation of ion-substitution experiments are performed to understand the role of membrane permeabilities in determining the dynamic behavior of the epithelium.


In vitro comparison of antimicrobial effect of sodium hypochlorite solution and Zataria multiflora essential oil as irrigants in root canals contaminated with Candida albicans.
This study compared the antifungal effect of Zataria multiflora essential oil (EO) with that of sodium hypochlorite (NaOCl) as an irrigant for root canals infected with Candida albicans. Sixty mandibular premolars were infected with C. albicans suspension. After 72 h of incubation, the samples were divided into four groups. Teeth in Group 1 were irrigated with minimum fungicidal concentration (MFC) of Z. multiflora EO, in Group 2 with twice the MFC of Z. multiflora, in Group 3 with MFC of NaOCl, and in Group 4 with distilled water (DW). Pre- and post-operative samples were cultured, and fungal colony count of each specimen was obtained. Data were analyzed using Kruskal-Wallis and Mann-Whitney tests (P < 0.05). NaOCl at MFC and Z. multiflora EO at twice the MFC showed the highest antifungal efficacy, with no significant difference (P > 0.05). However, antifungal efficacies of these irrigants were significantly different from those of Z. multiflora EO at MFC and DW (P < 0.05). Our results showed that Z. multiflora EO at twice the MFC had the same antifungal efficacy as NaOCl at MFC.


The frequency of blood-born viral infections in a population of multitransfused Brazilian patients.
The frequency of viral markers for hepatitis B (HBV) and C (HCV), human immunodeficiency virus-1 (HIV-1) and human T-lymphotropic virus-1 (HTLV-1) was evaluated in 32 Brazilian beta-thalassemia multitransfused patients. Additionally the serum concentrations of ferritin and alanine aspartate transaminase (ALAT) were determined. The results show a high prevalence of markers of infection by HBV (25.0%) and HCV (46.8%) and a low prevalence of markers for HIV-1 and HTLV-1. No correlations were demonstrated between the presence of the hepatitis markers and the number of units transfused or the serum concentrations of ferritin and ALAT.


Aluminosilicate Nanocomposite on Genosensor: A Prospective Voltammetry Platform for Epidermal Growth Factor Receptor Mutant Analysis in Non-small Cell Lung Cancer.
Lung cancer is one of the most serious threats to human where 85% of lethal death caused by non-small cell lung cancer (NSCLC) induced by epidermal growth factor receptor (EGFR) mutation. The present research focuses in the development of efficient and effortless EGFR mutant detection strategy through high-performance and sensitive genosensor. The current amplified through 250 µm sized fingers between 100 µm aluminium electrodes indicates the voltammetry signal generated by means of the mutant DNA sequence hybridization. To enhance the DNA immobilization and hybridization, ∼25 nm sized aluminosilicate nanocomposite synthesized from the disposed joss fly ash was deposited on the gaps between aluminium electrodes. The probe, mutant (complementary), and wild (single-base pair mismatch) targets were designed precisely from the genomic sequences denote the detection of EGFR mutation. Fourier-transform Infrared Spectroscopy analysis was performed at every step of surface functionalization evidences the relevant chemical bonding of biomolecules on the genosensor as duplex DNA with peak response at 1150 cm-1 to 1650 cm-1. Genosensor depicts a sensitive EGFR mutation as it is able to detect apparently at 100 aM mutant against 1 µM DNA probe. The insignificant voltammetry signal generated with wild type strand emphasizes the specificity of genosensor in the detection of single base pair mismatch. The inefficiency of genosensor in detecting EGFR mutation in the absence of aluminosilicate nanocomposite implies the insensitivity of genosensing DNA hybridization and accentuates the significance of aluminosilicate. Based on the slope of the calibration curve, the attained sensitivity of aluminosilicate modified genosensor was 3.02E-4 A M-1. The detection limit of genosensor computed based on 3σ calculation, relative to the change of current proportional to the logarithm of mutant concentration is at 100 aM.


Response to pudendal nerve block in women with pudendal neuralgia.
To examine the evolution of pain and the duration of numbness after neural blockade of the pudendal nerve in women with pudendal neuralgia and correlate with clinical and historical data. Prospective, single arm, open label study. University hospital and outpatient clinic. Eighty-two adult female patients were recruited from November 8, 2008 to February 14, 2010. Patients were selected based on the presence of spontaneous or provoked pain in the distribution of the pudendal nerve. Subjects underwent a standardized pudendal nerve block. Visual analog pain scores and the presence of numbness were recorded before and for 64 hours after the pudendal nerve block. A complete clinical history and examination were documented. Sixty-six patients completed the study. About 86.9% had a reduction in one or more pain symptom, while 44.3% found that more than one of their pain symptoms did not return. About 69.7% of patients reported numbness lasting up to 16 hours or longer. Previous gynecological surgery was recorded in 75.8%, previous traumatic obstetric events in 47.0% of cases. Prolonged history of pain correlated with a reduced chance of positive outcome of the pudendal nerve block. In patients with pudendal neuralgia, the pudendal nerve block has a variable response, but may have a beneficial effect in a subset of women. Surgical and obstetrical trauma are common historical antecedents.


HIV-Tat elicits microglial glutamate release: role of NAPDH oxidase and the cystine-glutamate antiporter.
Excitotoxicity and/or microglial reactivity might underlie neurologic dysfunction in HIV patients. The HIV regulatory protein Tat is both neurotoxic and pro-inflammatory, suggesting that Tat might participate in the pathogenesis of HIV-associated neurocognitive disorders (HAND). The present study was undertaken to evaluate if Tat can increase extracellular glutamate, and was specifically designed to determine the degree to which, and the mechanisms by which Tat could drive microglial glutamate release. Data show that application of Tat to cultured primary microglia caused dose-dependent increases in extracellular glutamate that were exacerbated by morphine, which is known to worsen Tat cytotoxicity. Tat-induced glutamate release was decreased by inhibitors of p38 and p42/44 MAPK, and by inhibitors of NADPH oxidase and the x(c)(-) cystine-glutamate antiporter. Furthermore, Tat increased expression of the catalytic subunit of x(c)(-) (xCT), but Tat-induced increases in xCT mRNA were not affected by inhibition of NADPH oxidase or x(c)(-) activity. Together, these data describe a specific and biologically significant signaling component of the microglial response to Tat, and suggest that excitotoxic neuropathology associated with HIV infection might originate in part with Tat-induced activation of microglial glutamate release.


Reprogramming and transdifferentiation - two key processes for regenerative medicine.
Regenerative medicine based on transplants obtained from donors or foetal and new-born mesenchymal stem cells, encounter important obstacles such as limited availability of organs, ethical issues and immune rejection. The growing demand for therapeutic methods for patients being treated after serious accidents, severe organ dysfunction and an increasing number of cancer surgeries, exceeds the possibilities of the therapies that are currently available. Reprogramming and transdifferentiation provide powerful bioengineering tools. Both procedures are based on the somatic differentiated cells, which are easily and unlimitedly available, like for example: fibroblasts. During the reprogramming procedure mature cells are converted into pluripotent cells - which are capable to differentiate into almost any kind of desired cells. Transdifferentiation directly converts differentiated cells of one type into another differentiated cells type. Both procedures allow to obtained patient's dedicated cells for therapeutic purpose in regenerative medicine. In combination with biomaterials, it is possible to obtain even whole anatomical structures. Those patient's dedicated structures may serve for them upon serious accidents with massive tissue damage but also upon cancer surgeries as a replacement of damaged organ. Detailed information about reprogramming and transdifferentiation procedures as well as the current state of the art are presented in our review.


Hypoglycaemic episodes in patients with type 2 diabetes--risk factors and associations with patient-reported outcomes: The PANORAMA Study.
To explore the frequency of hypoglycaemic episodes, their risk factors, and associations with patient-reported outcomes in patients with type 2 diabetes enrolled in the PANORAMA cross-sectional study. Five thousand seven hundred and eighty-three patients aged ≥ 40 years with type 2 diabetes duration ≥ 1 year were recruited in nine European countries. Patients reported severe and non-severe hypoglycaemic episodes during the past year at a single study visit. Patient-reported outcomes were measured by the Audit of Diabetes-Dependent Quality of Life, Diabetes Treatment Satisfaction Questionnaires, Hypoglycaemia Fear Survey-II, and EQ-5D Visual Analog Scale. During the previous year, 4.4% of the patients experienced ≥ 1 severe hypoglycaemic episode; among those without severe hypoglycaemia, 15.7% experienced ≥ 1 non-severe episode. Patients experiencing any hypoglycaemic episode reported a greater negative impact of diabetes on quality of life, greater fear of hypoglycaemia, less treatment satisfaction and worse health status than those with no episodes. In multivariate analyses hypoglycaemia was significantly associated with longer diabetes duration; presence of microvascular and, to a lesser extent, macrovascular complications; treatment with insulin, glinides or sulfonylureas; and use of self-monitoring blood glucose. In patients with type 2 diabetes, severe hypoglycaemic episodes were not uncommon and one in five experienced some form of hypoglycaemia during the previous year. Hypoglycaemia was associated with more negative patient-reported outcomes. The risk of hypoglycaemia increased with diabetes duration, presence of diabetes-related complications, use of self-monitoring blood glucose, insulin secretagogues, and insulin treatment.


Harmony seeking and the risk of prostate cancer: a prebioptic study.
This semiprospective case-control study was performed to investigate the relationship between harmony-seeking personality and the occurrence of prostate cancer. Out of 217 consecutive participants admitted to hospital for biopsy, 86 and 81 were classified into the case and control groups, respectively, based on their initial diagnosis and eligibility criteria. The participants answered several questionnaires after admission. The logistic regression model was used for multivariate analyses to assess the association. "Harmony-seeking personality" was selected as the only psychological variable significantly contributing to the model, while "family history of prostate cancer" as the only somatic variable. "Harmony-seeking" maintained a significant contribution to the model, also including "family history" and even to the model adjusted by "patient prediction of cancer diagnosis" and "prostate-specific antigen" (PSA), probably related to the consequences of the disease. The harmony-seeking personality could differentiate between groups of men with and without prostate cancer.


Emergency department visits--a statewide survey.
In a review by questionnaire of the emergency visits to 185 Florida hospitals, the number of annual estimated visits appears to exceed national estimates. In addition, the concept that in excess of 75% of patients are not true emergencies is not borne out. In spite of changes in the emergency medical services system, only 10% of patients came by ambulance or rescue vehicle. These patients were more likely to be seriously ill as attested to by the fact that 50% required hospitalization. Definitive care was provided for 80% of patients. Some 40% of Florida's emergency departments have full-time emergency physicians. Although nearly 70% of the emergency patients were seen by these physicians, 2.4% were seen by interns only, and a total of 10% were seen by house officers only. There was a great variety of referral patterns among the Health Service Agencies.


Polysaccharide based bionanocomposite hydrogels reinforced with cellulose nanocrystals: Drug release and biocompatibility analyses.
Cellulose nanocrystals (CNCs) reinforced, bionanocomposite (BNC) has shown great potential in tissue engineering and drug delivery applications due to the low toxicity, low density, and high aspect ratio. In this work, BNC hydrogels reinforced with CNCs were fabricated from xanthan (XG) solutions and chitosan (CS) in presence of green acidifying agent through electrostatic and hydrogen bonding interactions. As developed BNC hydrogels were characterized for complex formation, morphology, and mechanical behavior. The mechanical performance of BNC hydrogels was improved significantly as increased CNC content (from 2 to 10wt%). 5-Flurouracil as model chemotherapeutic agent was loaded into these BNC hydrogels for evaluating their drug release properties. The BNC hydrogels showed excellent cytocompatability and ability to release of chemotherapeutic agent that shows the suitability to be used in tissue engineering as well as drug delivery applications.


A unified account of cognitive impairments following frontal lobe damage: the role of working memory in complex, organized behavior.
A computer model is presented that performs 4 tasks sometimes impaired by frontal damage: motor sequencing, the Stroop task, the Wisconsin Card Sorting Test, and a context memory task. In each task, patterns of performance typical of frontal-damaged patients are shown to result from the same type of damage to the model, specifically, weakening of associations among elements in working memory. The simulation shows how a single underlying type of damage could result in impairments on a variety of seemingly distinct tasks. Furthermore, the hypothesized damage affects the processing components that carry out the task rather than a distinct central executive.


The Effectiveness of Methadone Maintenance Therapy Among Opiate - Dependants Registered with Hospital Raja Perempuan Zainab II Kota Bharu, Kelantan.
The objective of this study was to determine the effectiveness of MMT program among injecting drug users (IDUs) in Kota Bharu, Kelantan. The study was a retrospective study based on the records of injecting drug users (IDUs) involved in the MMT program from November 2005 to 31st Jan 2008, registered at the Psychiatric Clinic of Hospital Raja Perempuan Zainab II. Opiate Treatment Index (OTI) was used as the research instrument. Repeated measures ANCOVA was used to compare the mean scores during the entry period and after completing twelve months of MMT program after adjusted for age, marital status, and level of education. A total of 117 file records were reviewed. There was significant reduction in the mean scores after 12 months of heroin Q score, HIV Risk-taking Behavior Scale and health scale after adjusted for age, marital status, and level of education. For Heroin Q score, mean difference was 2.01 (95% CI: 1.45, 2.56), for HIV Risk-taking Behavior Scale, mean difference was 7.64 (95% CI: 6.03, 9.26), and for health scale, mean difference was 5.35(95% CI: 3.90, 6.79). This study supports the evidence that MMT program is effective in treating heroin and opiate dependence.


Morbid obesity in total shoulder arthroplasty: risk, outcomes, and cost analysis.
A rate of obesity in the US population and the rate of total shoulder arthroplasty (TSA) has increased over the past decade. Little information exists concerning the number of morbidly obese patients undergoing TSA or how these patients compare with their non-obese counterparts. The goal of this study was to determine whether morbidly obese patients exhibit greater rates of postoperative in-hospital complications, mortality, or utilization of resources. We used the Nationwide Inpatient Sample to analyze 31,924 patients undergoing TSA between 1998 and 2008. Multivariate analysis with logistic regression modeling was used to compare patients based on body mass index for various outcomes. Among morbidly obese patients, predictors of death included age (odds ratio, 1.06; 95% confidence interval, 1.01-1.11) and Deyo score. A comparison of hospital costs among patients showed that increased patient body mass index led to increased hospital charges independent of physician charges ($38,103.88 in morbidly obese patients vs $33,521.66 in non-obese patients, P = .0001). An increased length of stay was observed in morbidly obese patients (2.84 days vs 2.52 days in obese patients and 2.56 days in non-obese patients, P = .003). Respiratory dysfunction occurred more commonly in morbidly obese patients than in non-obese patients (1.2% vs 0.7%; odds ratio, 1.61; P < .01). Obese patients tend to have longer hospital stays, an increased risk of postoperative respiratory complications, and higher costs. Although there was a trend toward an increased early postoperative mortality rate, obesity was not associated with an increased incidence of most complications. These findings should be supplemented with further research to assist patient counseling and risk adjustment for obese patients undergoing TSA.


Blockade of SOX4 mediated DNA repair by SPARC enhances radioresponse in medulloblastoma.
SPARC is a matricellular glycoprotein and a putative radioresistance-reversal-gene. We therefore explored the possibility of SPARC expression on medulloblastoma radiosensitivity in vitro and in vivo. The combined treatment of the SPARC and irradiation resulted in increased cell death when compared to cells treated with irradiation alone in vitro and in vivo. SPARC expression prior to irradiation suppressed checkpoints-1,-2 and p53 phosphorylation and DNA repair gene XRCC1. We also demonstrate that SPARC expression suppressed irradiation induced SOX-4 mediated DNA repair. These results provide evidence of the anti-tumor effect of combining SPARC with irradiation as a new therapeutic strategy for the treatment of medulloblastoma.


Chronic inhibition of glutamine synthetase is not associated with impairment of learning and memory in mice.
The convulsant methionine sulfoximine (MSO) is a byproduct of the agenized flour commonly used for feeding domestic animals decades ago. MSO is a powerful glycogenic and epileptogenic agent, and it is an irreversible inhibitor of glutamine synthetase. This latter effect was hypothesized to be responsible for the increase in the incidence of some neuropathologies in humans, such as Alzheimer's disease or Parkinson's disease. In order to test this hypothesis, we chronically administered MSO to two inbred strains of mice, C57BL/6J and BALB/cJ, and analyzed possible alterations in learning and memory features of these mice. Mice were given 20 mg/kg of MSO three times a week for 10 weeks. Spatial learning capabilities assessed with a radial maze were not affected by the long-term MSO treatment, although activity was significantly decreased in BALB/cJ mice. Thus, our data suggest that long-term administration of non-convulsive and non-glycogenic doses of MSO do not alter the spatial memory of mice. Our results do not support the hypothesis that chronic treatment with MSO influences hippocampus-dependent learning abilities in mice.


The Adolescent Birth Experience: A Comparison of Three Diverse Groups.
Recognized risk factors influencing the birth experience and subsequent poor mental health are not addressed among childbearing adolescents, especially minority teens. Our study purpose was to compare birth experiences of three adolescent groups by prevalence and influence of selected risk factors as moderated by racial/ethnic background. Using a birth rating scale and the Impact of Event Scale, birth perception and stress were examined among an equal number of Black, White, and Hispanic adolescents. Surveys completed at 72 hours postpartum showed Black adolescents most at risk for a negative birth experience. Contributing risk factors included depression, trauma, parity, and operative childbirth. Risk factors occur before and after birth; therefore, childbirth educators can promote a positive birth experience via perinatal assessments and interventions.


Recurrent Carotid artery blow out in a head & neck patient.
Carotid artery blowout syndrome is a rare complication of head and neck cancer treatment. It defines a rupture of the carotid artery wall through vessel wall necrosis. This is typically precipitated by radiotherapy, direct tumour invasion, or a combination of these factors. We describe a rare case of three consecutive carotid artery blowouts in a head and neck cancer patient. A 58-year-old man with a history of T3NO hypopharyngeal squamous cell carcinoma (SCC) treated with chemotherapy and radiation presented with a four-month history of progressive dysphagia and right sided neck pain. Flexible nasendoscopy revealed laryngeal oedema and slough. A panendoscopy and biopsy showed no evidence of tumour recurrence. The patient was discharged and represented with worsening dyspnoea. He subsequently experienced a large volume hemorrhage necessitating ligation of his right external carotid artery. He underwent pharyngolaryngectomy indicated due to the extent of laryngeal radiation necrosis. Thereafter he suffered two additional acute carotid bleeds from his right common carotid necessitating ligation in theatre. This case report illustrates the key issues to be considered in patients with locally advanced hypopharyngeal squamous cell carcinoma and subsequent management of acute carotid blowout syndrome, which without prompt management, can be fatal.


Off-Target V(D)J Recombination Drives Lymphomagenesis and Is Escalated by Loss of the Rag2 C Terminus.
Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification.


Torque generation of kinesin motors is governed by the stability of the neck domain.
In long-range transport of cargo, prototypical kinesin-1 steps along a single protofilament on the microtubule, an astonishing behavior given the number of theoretically available binding sites on adjacent protofilaments. Using a laser trap assay, we analyzed the trajectories of several representatives from the kinesin-2 class on freely suspended microtubules. In stark contrast to kinesin-1, these motors display a wide range of left-handed spiraling around microtubules and thus generate torque during cargo transport. We provide direct evidence that kinesin's neck region determines the torque-generating properties. A model system based on kinesin-1 corroborates this result: disrupting the stability of the neck by inserting flexible peptide stretches resulted in pronounced left-handed spiraling. Mimicking neck stability by crosslinking significantly reduced the spiraling of the motor up to the point of protofilament tracking. Finally, we present a model that explains the physical basis of kinesin's spiraling around the microtubule.


Preoperative magnetic resonance imaging of vena caval tumor thrombi: experience with 5 cases.
Magnetic resonance scans were performed preoperatively in 5 patients who underwent surgical removal of renal or adrenal tumors with direct extension of the tumor into the vena cava. Of the patients 4 had renal cell carcinoma and 1 had adrenocortical carcinoma. Magnetic resonance imaging staged correctly the level of vena caval tumor thrombus involvement in 4 patients and missed the presence of right atrial tumor extension in 1. This noninvasive imaging modality can be used instead of contrast venography in most patients to assess the presence and extent of vena caval tumor involvement by renal cell carcinoma. Contrast venography should be used for those patients with suspected cardiac involvement and for those whose tumor thrombus extent remains unclear after magnetic resonance imaging.


A formative assessment of gender awareness and ability of staff based on the service programs of the All-China Women's Federation: The case of the "3861 My Home" program.
In order to achieve "gender mainstreaming" which is a global strategy to promote the development of women, it has in recent years been a major task for the All-China Women's Federation (ACWF) to improve the gender awareness and ability of policy makers and implementers. Thus, researchers should constantly propose and evaluate various possible attempts to improve gender awareness and the ability of individuals. There are few empirical studies on the assessment of gender awareness and the improvement of the ability of staff who have been trained and educated. Research studies focusing on the promotion of gender-sensitive awareness and ability of staff by participating in programs are even rarer. This study presents a specific case, namely the evaluation of promoting social service workers' gender awareness and ability within the implementation of the "3861 My Home" program. Based on this case, this study examines how to promote gender awareness and ability of social service workers through the implementation of the service program of Women's Federation, and also assesses the quality of the results of this implementation. Moreover, this study also contributes to the literature pertaining to assessing the development of social service workers' gender awareness and ability. In addition, the study provides an option for enhancing the gender awareness and ability of social service workers in addition to training: The participatory learning or action pertaining to gender awareness and ability based on the Women's Federation programs are able to effectively improve the gender awareness and ability of staff.


[Presbyopia Correction with Intraocular Lenses].
Surgical correction of presbyopia can be performed by refractive lens exchange, replacing the lens with a monofocal, a multifocal or an extended-depth-of-focus (EDOF) intraocular lens (IOL). Option 1, a monofocal IOL, must be combined with monovision, otherwise presbyopia cannot be corrected. Monovision in this context means one eye for distance and one eye targeted for - 1.5 D. With this concept glasses are still required for near (30 - 40 cm) and for driving, but intermediate distances and everyday life is usually possible without glasses. Option 2, a multifocal IOL, results in spectacle independence. Current multifocal IOL typically use three foci and are therefore called trifocal IOL. Distance vision and near vision are typically good, intermediate vision still acceptable but lower than distance and near, resulting in occasional problems while working on a computer. Option 3, EDOF-IOL, provide good distance and intermediate vision without glasses but near vision typically requires reading glasses.


Reliability of transcutaneous measurement of renal function in various strains of conscious mice.
Measuring renal function in laboratory animals using blood and/or urine sampling is not only labor-intensive but puts also a strain on the animal. Several approaches for fluorescence based transcutaneous measurement of the glomerular filtration rate (GFR) in laboratory animals have been developed. They allow the measurement of GFR based on the elimination kinetics of fluorescent exogenous markers. None of the studies dealt with the reproducibility of the measurements in the same animals. Therefore, the reproducibility of a transcutaneous GFR assessment method was investigated using the fluorescent renal marker FITC-Sinistrin in conscious mice in the present study. We performed two transcutaneous GFR measurements within three days in five groups of mice (Balb/c, C57BL/6, SV129, NMRI at 3-4 months of age, and a group of 24 months old C57BL/6). Data were evaluated regarding day-to-day reproducibility as well as intra- and inter-strain variability of GFR and the impact of age on these parameters. No significant differences between the two subsequent GFR measurements were detected. Fastest elimination for FITC-Sinistrin was detected in Balb/c with significant differences to C57BL/6 and SV129 mice. GFR decreased significantly with age in C57BL/6 mice. Evaluation of GFR in cohorts of young and old C57BL/6 mice from the same supplier showed high consistency of GFR values between groups. Our study shows that the investigated technique is a highly reproducible and reliable method for repeated GFR measurements in conscious mice. This gentle method is easily used even in old mice and can be used to monitor the age-related decline in GFR.


The Wilms tumor protein WT1 stimulates transcription of the gene encoding insulin-like growth factor binding protein 5 (IGFBP5).
Insulin-like growth factor (IGF) binding proteins (IGFBPs) constitute a family of six secreted proteins that regulate the signaling of insulin-like growth factors (IGFs). IGFBP5 is the most conserved family member in vertebrates and the major IGF binding protein in bone. IGFBP5 is required for normal development of the musculoskeletal system, and various types of cancer frequently express high levels of IGFP5. Here we identify the gene encoding IGFBP5 as a novel downstream target of the Wilms tumor protein WT1. IGFBP5 and WT1 are expressed in an overlapping pattern in the condensing metanephric mesenchyme of embryonic murine kidneys. Down-regulation of WT1 by transfection with antisense vivo-morpholino significantly decreased Igfbp5 transcripts in murine embryonic kidney explants. Likewise, silencing of Wt1 in a mouse mesonephros-derived cell line reduced Igfbp5 mRNA levels by approximately 80%. Conversely, induction of the WT1(-KTS) isoform, whose role as transcriptional regulator has been firmly established, significantly increased IGFBP5 mRNA and protein levels in osteosarcoma cells. IGFBP5 expression was not significantly changed by WT1(+KTS) protein, which exhibits lower DNA binding affinity than the WT1(-KTS) isoform and has a presumed role in post-transcriptional gene regulation. Luciferase reporter constructs harboring 0.8 and 1.6 kilobases of the murine Igfbp5 promoter, respectively, were stimulated approximately 5-fold by co-transfection of WT1(-KTS). The WT1(+KTS) variant had no significant effect on IGFBP5 promoter activity. Binding of WT1(-KTS), but not of WT1(+KTS) protein, to the IGFBP5 promoter in human osteosarcoma cells was proven by chromatin immunoprecipitation (ChIP) and confirmed by electrophoretic mobility shift assay. These findings demonstrate that WT1 activates transcription of the IGFBP5 gene with possible implications for kidney development and bone (patho)physiology.