Chronic hepatitis C therapy: a rare complication revisited.
The combined regimen of peg-interferon α2a plus ribavirin along with protease inhibitors (boceprevir or telaprevir) is considered as a very portent and effective therapy for hepatitis C infections. However, this combined therapy has been associated with a side effect that can make the course of the disease more complicated. In this case, a 50-year-old man developed insulin-dependent diabetes soon after initiating triple hepatitis C therapy. The treatment had to be stopped and the course of his hepatitis C infection has been challenged with this rare side effect.


Skin diseases in alcoholics.
Alcohol abuse is associated with many health problems, especially skin changes. As a small, water- and lipid-soluble molecule, alcohol reaches all tissues of the body and affects most vital functions. Cutaneous diseases are now emerging as useful markers of alcoholism detectable at an early and possibly reversible stage of the disease, thus being of substantial importance to dermatologists and general practitioners. The most common skin manifestations of alcoholism presented in this review article are urticarial reactions, porphyria cutanea tarda, flushing, cutaneous stigmata of cirrhosis, psoriasis, pruritus, seborrheic dermatitis, and rosacea.


Defect-driven antiferromagnetic domain walls in CuMnAs films.
Efficient manipulation of antiferromagnetic (AF) domains and domain walls has opened up new avenues of research towards ultrafast, high-density spintronic devices. AF domain structures are known to be sensitive to magnetoelastic effects, but the microscopic interplay of crystalline defects, strain and magnetic ordering remains largely unknown. Here, we reveal, using photoemission electron microscopy combined with scanning X-ray diffraction imaging and micromagnetic simulations, that the AF domain structure in CuMnAs thin films is dominated by nanoscale structural twin defects. We demonstrate that microtwin defects, which develop across the entire thickness of the film and terminate on the surface as characteristic lines, determine the location and orientation of 180∘ and 90∘ domain walls. The results emphasize the crucial role of nanoscale crystalline defects in determining the AF domains and domain walls, and provide a route to optimizing device performance.


Hypertrophic gastropathy associated with gastric sarcoma in a dog.
A 14-y-old spayed female Labrador Retriever was presented with an 8-mo history of chronic vomiting. Abdominal ultrasound and gastrointestinal endoscopy revealed a mass protruding into the gastric lumen, with cytologic features suggestive of sarcoma. A partial gastrectomy was performed; the gastric body and antrum were thickened, with a cerebriform appearance of the mucosal surface. Histologic examination revealed a submucosal neoplastic proliferation of fusiform cells variably arranged in irregular bundles and scattered whorls. Fusiform cells strongly reacted to antibodies against vimentin, S100, and neuron-specific enolase; glial fibrillary acidic protein was moderately and multifocally expressed. Pancytokeratin, KIT, α-smooth muscle actin, and desmin were nonreactive. Histologic and immunohistochemical findings suggested a diagnosis of gastric sarcoma with features referable to a non-GIST (gastrointestinal stromal tumor), non-smooth muscle NIMT (non-angiogenic, non-lymphogenic intestinal mesenchymal tumor). The overlying gastric mucosa was thickened by elongated and dilated gastric glands, predominantly lined by intensely periodic acid-Schiff-stained mucous cells. This altered mucosal architecture was suggestive of Ménétrier-like disease. Although this disease has been hypothesized to predispose to gastric adenocarcinoma in dogs, an association with gastric sarcoma has not been documented previously in the veterinary literature, to our knowledge.


Molecular design of cholesterols as inhibitors of DNA polymerase alpha.
The triterpenoid structure is a promising motif for the molecular design of DNA polymerase inhibitors.(1) In this study, 2-(cholesteryloxy)acetic acid (3), 2-(cholestanyl)acetic acid (7), and 2-(stigmasteryl)acetic acid (11) were found to selectively affect only DNA polymerase alpha (pol.alpha). The presence of a carboxyl group at position 28 appears to be essential for the inhibition of the pol.alpha activity. With pol.alpha, these compounds acted by competing with the template-primer DNA and noncompetitively with the substrate.


The Tendency of Having MSH2 and MSH6 Microsatellite Instability among Clinicopathological Features in Patients with Colorectal Cancer
Objective: This study aimed to identify micro-satellite instability (MSI) based on the expression of MMRp (MSH2 and MSH6) and to evaluate the association of MSI and with clinicopathological features in patients with colorectal cancer (CRC). Methods: MMRp expression in 80 tissue samples from patients with adenocarcinoma CRC were evaluated by using anti-MSH2 and -MSH6 antibodies. Loss of MSH2 and/or MSH6 expression was stated as MSI. The association between MSI status and clinicopathological features were analyzed by using binary logistic regression (p<0.05). Results: The frequency of MSI in patients with CRC varied, corresponding to 8.3% (6/72) MSH2 MSI, 36.1% (26/72) MSH6 MSI and 6.9% (5/72) MSH2-MSH6 MSI. Male patients (OR=1.98), with tumor located in colon (OR=1.47) and late stage tumor (OR=1.48) have a tendency of having MSH2 MSI. Male patients (OR=1.4), with tumor located in colon (OR=2.53) and poor tumor differentiation (OR=3.02) have a tendency to encounter MSH6 MSI. Male patients (OR=4.93) with late stage tumor (OR=1.69) have a tendency of having MSH2-MSH6 MSI. Conclusion: Patients more likely to have MSH2 MSI are males, and/or having tumor located in colon, and /or having late stage tumor. Patients more likely to have MSH6 MSI are males, and/or having tumor located in colon, and/or having tumor with poor differentiation. Patients who have greater tendency to have MSH2 and MSH6 MSI are males, and/or having late stage tumor.


[Quality control and discrimination of angelica different processed products based on HPLC fingerprints combined chemometrics methods].
To establish a chemical fingerprint method for reorganizing and validating angelica different processed products. A high-performance liquid chromatographic method was developed to establish the fingerprint. Principal component analysis, hierarchical cluster analysis and discriminate analysis were applied to study HPLC finger printing and chemical pattern reorganization. There were difference of characteristic peaks and its relative peak area of HPLC fingerprints between different processed products. Fish's discriminate functions were generated by using six selected predictor variables, the tested samples of different processed products were classified with 100% accuracy, and discriminate analysis plots for the five groups were well-resolved. The developed HPLC finger print, combined with chemometrics, can accurately identify and validate angelica different processed products, the research provide theoretical basis for the processing mechanism and quality assess of angelica different processed products.


Phase I/II trial of dexverapamil, epirubicin, and granulocyte-macrophage-colony stimulating factor in patients with advanced pancreatic adenocarcinoma.
The purpose of this study was to determine the maximum tolerated dose (MTD) of a cytotoxic regimen consisting of the second-generation chemosensitizer dexverapamil (DVPM), high dose epirubicin, and recombinant human granulocyte-macrophage-colony stimulating factor (GM-CSF) in pancreatic carcinoma. Twenty-eight previously untreated patients with locally advanced or metastatic adenocarcinoma of the pancreas were studied. Treatment consisted of oral DVPM at a dose of 1000-1200 mg/day for 3 days, epirubicin administered as an intravenous bolus injection on Day 2 with an initial dose of 90 mg/m2, and a dose of GM-CSF of 400 micrograms administered subcutaneously from Day 5s through 14. Epirubicin dose escalation levels were 90, 105, 120 and 135 mg/m2. Consecutive cohorts of four to eight patients were planned at each dose level. Treatment cycles were repeated every 3 weeks. Hematologic toxicity, specifically granulocytopenia, constituted the dose-limiting toxicity with an MTD of 120 mg/m2 for epirubicin. Despite routine supportive therapy with GM-CSF, four, two, and five patients experienced Grade 4 granulocytopenia during their first two treatment courses at levels 105, 120, and 135 mg/m2, respectively. Grade 4 granulocytopenia was observed in two, three, and one additional patients during subsequent courses with these levels. Nonhematologic toxicity was uncommon, generally modest, and did not correlate clearly with the anthracycline dose. Dexverapamil-related cardiovascular symptoms occurred frequently, but they never resulted in serious toxicity requiring active medical intervention or permanent discontinuation of therapy. Nine of 28 patients achieved partial responses to this therapy. Stable disease was observed in nine patients, and tumor progress occurred in 10. The MTD of epirubicin for this regimen with DVPM and GM-CSF was 120 mg/m2 every 3 weeks. Though it remains uncertain whether the encouraging response activity observed in this disease-oriented Phase I study was, in fact, due to successful modulation of multidrug resistance, these results suggest that this regimen is likely to be an effective and tolerable treatment strategy for patients with pancreatic cancer, which should be evaluated further.


Combined laparoscopic and endoscopic approach in patients with cholelithiasis and choledocholithiasis.
The Optimal management of common bile duct stones in patients undergoing laparoscopic cholecystectomy remains controversial. A prospective study was conducted in 145 of the 481 patients who had a preoperative endoscopic retrograde cholangiogram before their laparoscopic cholecystectomy. Endoscopic retrograde cholangiogram was successful in 138 patients (95%), and common duct calculi were found in 72 (50%) of them. Endoscopic sphincterotomy with ductal clearance was achieved in 62 of 67 patients during a mean of 1.4 sessions (range, 1 to 5). Five (3.4%) patients had complications after endoscopic intervention, all of which resolved uneventfully . Fourteen patients underwent laparoscopic common duct exploration, five had failed endoscopic extraction, five had their common duct stones left intentionally for laparoscopic intervention, and, in addition, four of the seven patients who had a failed endoscopic retrograde cholangiogram had stones identified by intraoperative cholangiogram. Ten of these 14 patients underwent a successful laparoscopic common duct exploration. Laparoscopic cholecystectomy was successfully completed in 134 of the 145 patients, and none had major intraoperative or postoperative complications. The mean postoperative stay was 2.7 days for those patients who underwent a successful laparoscopic procedure. The overall mean number of admissions for completing the treatment was 2.3. Combined laparoscopic and endoscopic approach is a viable option for patients with gallstones and choledocholithiasis.


Improved tracheal allograft viability in immunosuppressed rats.
Airway ischemia has been a common cause of morbidity and mortality in clinical lung transplantation. The present study examined the effects of cyclosporin A (CsA) and methylprednisolone (MP) on the viability of the devascularized trachea after heterotopic transplantation and omentopexy. Thirty-six tracheal segments were harvested from 18 donor Lewis rats, wrapped in omentum, and heterotopically implanted into the abdomen of recipient rats. Tracheal segments were randomly allocated into one of six recipient groups (n = 6): Lewis syngeneic controls, and five groups of Brown Norway recipients, receiving either no treatment, CsA alone (5 mg.kg-1.day-1 or 15 mg.kg-1.day-1), or CsA in combination with MP (5 mg CsA + 1 mg MP per kg/day or 15 mg CsA + 2 mg MP per kg/day, respectively). After 14 days, the tracheal segments were histologically evaluated. Epithelial thickness and the degree of epithelial regeneration were significantly different (p < 0.05) between the syngeneic control group and the untreated Brown Norway group. Without immunosuppression there was virtually no epithelium, whereas low-dose immunosuppression yielded intermediate viability, and with high dose CsA and MP we observed improved tracheal viability. In this high-dose group, the epithelium was thicker than in even the syngeneic control group. These results indicate that, in heterotopic tracheal allografts, viability may be improved with an optimum combination of CsA and MP.


Different HCV Exposure Drives Specific miRNA Profile in PBMCs of HIV Patients.
Micro RNAs (miRNAs) are essential players in HIV and HCV infections, as both viruses modulate cellular miRNAs and interact with the miRNA-mediated host response. We aim to analyze the miRNA profile of HIV patients with different exposure to HCV to explore specific signatures in the miRNA profile of PBMCs for each type of infection. We massively sequenced small RNAs of PBMCs from 117 HIV+ infected patients: 45 HIV+ patients chronically infected with HCV (HIV/HCV+), 36 HIV+ that spontaneously clarified HCV after acute infection (HIV/HCV-) and 36 HIV+ patients without previous HCV infection (HIV). Thirty-two healthy patients were used as healthy controls (HC). Differential expression analysis showed significantly differentially expressed (SDE) miRNAs in HIV/HCV+ (n = 153), HIV/HCV- (n = 169) and HIV (n = 153) patients. We found putative dysregulated pathways, such as infectious-related and PI3K signaling pathways, common in all contrasts. Specifically, putatively targeted genes involved in antifolate resistance (HIV/HV+), cancer-related pathways (HIV/HCV-) and HIF-signaling (HIV) were identified, among others. Our findings revealed that HCV strongly influences the expression profile of PBMCs from HIV patients through the disruption of its miRNome. Thus, different HCV exposure can be identified by specific miRNA signatures in PBMCs.


An atypical primary malignant melanoma arising from the cervical nerve root: A case report and review of literture.
Primary melanomas affecting the central nervous system are very rare, and melanomas originating in the spinal canal or origin of the spinal nerve root are even rarer. As a consequence, not much is known about this. Here we report a case of primary malignant melanoma originating in the cervical spinal cord nerve root. A 64-year-old woman presented with symptoms of numbness in the right side of the neck, pain, and hypoesthesia in the right upper limb which persisted for 1 year. Neurological examination showed that the superficial sensation in the right upper limb had decreased with muscle strength of grade 4. Magnetic resonance imaging examination revealed a mass (approximately 2.5 cm × 1.4 cm × 1 cm) in the right side of the spinal canal in the C-2 plane. Based on findings obtained during operation, perioperative examination, pathological diagnosis, and the diagnostic criteria of primary central melanoma proposed by Hayward, the mass was confirmed to be a melanoma of intraspinal nerve root origin. This is the first case of primary malignant melanoma originating from cervical spinal cord nerve roots and spread along the inside and outside of the spinal canal. The clinical relevance of this case is discussed to provide new insights into the differential diagnosis of intraspinal tumours. Further studies are needed to better understand the mechanisms driving the growth pattern and development of this type of tumour.


Acute effects of naturalistic THC vs. CBD use on recognition memory: a preliminary study.
The ratio of ∆9-tetrahydrocannabinol (THC) to cannabidiol (CBD) varies widely across cannabis strains. CBD has opposite effects to THC on a variety of cognitive functions, including acute THC-induced memory impairments. However, additional data are needed, especially under naturalistic conditions with higher potency forms of cannabis, commonly available in legal markets. The goal of this study was to collect preliminary data on the acute effects of different THC:CBD ratios on memory testing in a brief verbal recognition task under naturalistic conditions, using legal-market Colorado dispensary products. Thirty-two regular cannabis users consumed cannabis of differing THC and CBD levels purchased from a dispensary and were assessed via blood draw and a verbal recognition memory test both before (pretest) and after (posttest) ad libitum home administration in a mobile laboratory. Memory accuracy decreased as post-use THC blood levels increased (n = 29), whereas performance showed no relationship to CBD blood levels. When controlling for post-use THC blood levels as a covariate, participants using primarily THC-based strains showed significantly worse memory accuracy post-use, whereas subjects using strains containing both THC and CBD showed no differences between pre- and post-use memory performance. Using a brief and sensitive verbal recognition task, our study demonstrated that naturalistic, acute THC use impairs memory in a dose dependent manner, whereas the combination of CBD and THC was not associated with impairment.


Influence of methodology on glycosylated hemoglobin values in Nigerian subjects with sickle cell hemoglobinopathy.
The determination of glycosylated hemoglobin (GHb) has been found useful in the medium term assessment of diabetic control. Levels of GHb have been shown to be influenced by hematological abnormalities and methodology amongst other factors. Hemoglobinopathies are common in Nigerians and other people of African descent. No work, to our knowledge, has been done in Nigeria to study the effect of hemoglobinopathies on the levels of GHb in Nigerians or Africans. In this study, GHb levels in non-diabetic Nigerians (with hemoglobin genotypes AA, AS, and SS) were determined by short column chromatography and thiobarbituric acid colorimetry. Levels of GHb obtained by the microchromatographic method were significantly different from one another in the three subject groups. The group mean GHb level was highest in subjects with sickle cell anaemia and lowest in subjects with sickle cell trait. However, using the colorimetric method, the mean GHb level of the normal subjects with hemoglobin genotype AA was not significantly different from that of subjects with hemoglobin genotype AS or SS. Results of GHb determinations by microchromatography (for which several commercial kits are available) in subjects with sickle cell anemia or trait must be interpreted with caution. The colorimetric method, though more tedious, gives more reliable results and should be the method of choice in subjects with concurrent diabetes and sickle cell anemia or trait.


Type of anesthesia and quality of recovery in male patients undergoing lumbar surgery: a randomized trial comparing propofol-remifentanil total i.v. anesthesia with sevoflurane anesthesia.
Previous studies have shown that women achieve a better quality of postoperative recovery from total intravenous anesthesia (TIVA) than from inhalation anesthesia, but the effect of anesthesia type on recovery in male patients is unclear. This study therefore compared patient recovery between males undergoing lumbar surgery who received TIVA and those who received sevoflurane anesthesia. Eighty male patients undergoing elective one- or two-level primary transforaminal lumbar interbody fusion (TLIF) were randomly divided into two groups: the TIVA group (maintenance was achieved with propofol and remifentanil) or sevoflurane group (SEVO group: maintenance was achieved with sevoflurane and remifentanil). The quality of recovery-40 questionnaire (QoR-40) was administered before surgery and on postoperative days 1 and 2 (POD1 and POD2). Pain scores, postoperative nausea and vomiting, postoperative hospital stay, anesthesia consumption, and adverse effects were recorded. The QoR-40 scores were similar on the three points (Preoperative, POD1 and POD2). Pain scores were significantly lower in the SEVO group than in the TIVA group on POD1 (30.6 vs 31.4; P = 0.01) and POD2 (32 vs 33; P = 0.002). There was no significant difference in the postoperative hospital stay or complications in the postanesthesia care unit between the TIVA group and the SEVO group. This study demonstrates that the quality of recovery is not significantly different between male TLIF surgery patients who receive TIVA and those who receive sevoflurane anesthesia. Patients in the TIVA group had better postoperative analgesic effect on POD2. This was registered at http://www.chictr.org.cn (registration number ChiCTR-IOR-16007987, registration date: 24/02/2016).


"MAURITIUS": tumour dose in patients with advanced carcinoma.
Radioimaging of various human tumours by means of somatostatin analogues and vasoactive intestinal peptide has been introduced into clinical practice in recent years. The finding that human tumours express various subtypes of somatostatin receptors has led to the development and characterization of a novel peptide tracer, termed MAURITIUS. MAURITIUS identifies a broad range of somatostatin receptors with high binding affinity, and somatostatin receptor 1 with low binding affinity. In order to evaluate patients for tumour radiotherapy with 90Y-MAURITIUS, tumour dose calculation is performed with 111In-MAURITIUS [111In-DOTA-lanreotide]. Treatment is initiated in patients presenting a tumour uptake of > or = 10 Gy/GBq (i.e., standard dose for 1 treatment cycle with 90Y-MAURITIUS). In 25 patients with advanced cancer refractory to conventional antineoplastic treatment 111In-MAURITIUS (approximately 150 MBq; 10 nmol/patient), scintigraphy and dosimetry was performed. Dosimetry data were calculated based on scintigraphic results as well as urine, faeces and blood data. In all patients, at least one tumour site was visualized during the initial few minutes of application. Additional tumour sites not seen on conventional imaging (computerized tomography, magnetic resonance imaging bone scan) could be detected in 6 patients with carcinoids, one patient with prostate cancer and one patient with lymphoma. Liver metastases were visualized in all patients with gastrointestinal cancers, while the primary tumour was not detected in 2 patients with pancreatic, and in 1 patient with rectal, cancer. The calculated radiation dose for tumours and/or metastases ranged between 3-60 Gy/GBq for 90Y-MAURITIUS. MAURITIUS is a universal receptor ligand for a large variety of different human tumours, and is suitable for treatment when labelled with 90Y.


Acute myeloid leukemia with del(X)(p21) and cryptic RUNX1/RUNX1T1 from ins(8;21)(q22;q22q22) revealed by atypical FISH signals.
A 57-yr-old woman was diagnosed with acute myeloid leukemia (AML) with maturation, based on morphological and cytochemical/immunophenotypic findings on bone marrow studies. Conventional cytogenetic analysis using bone marrow cells revealed terminal deletion of the short arm of an X chromosome as 46,X,del(X)(p21)[8]/46,XX[12]. On the other hand, fluorescence in situ hybridization (FISH) for the RUNX1/RUNX1T1 (formerly AML1/ETO) rearrangement revealed 86% interphase nuclei with one fusion signal, which was found to be on the long arm of chromosome 8 on metaphase FISH, indicating the RUNX1/RUNX1T1 rearrangement by cryptic insertion of the RUNX1 gene. Molecular genetic study by reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the presence of the chimeric transcript. The final karyotype was 46,X,del(X)(p21).ish ins(8;21)(q22;q22q22)(RUNX1T1+,RUNX1+;RU NX1+,RUNX1T1-)[8]/46,XX[12]. In addition to the cryptic RUNX1/RUNX1T1 rearrangement, this is the first report of partial deletion of an X chromosome as an additional cytogenetic aberration in AML with RUNX1/RUNX1T1.


Prevalence of insomnia in various psychiatric diagnostic categories.
Sixty percent of 536 new referrals to a psychiatric clinic at a general hospital complained of insomnia. Prevalence was high in all psychiatric categories, especially in physiologic disorders, somatoform disorders and mood disorders, followed by epilepsy. Complaints of difficulty in falling asleep were high in the physiologic and somatoform disorder groups. Complaints of nocturnal awakening were high in the anxiety and physiologic disorder groups, while complaints of early morning awakening were high in the organic and mood disorder groups. Prescription rates of hypnotics was most prevalent in the mood and adjustment disorder groups, whereas a non-pharmacological approach, including psychological education and behavioral therapy, was applied mainly to the physiologic disorder group.


Total reorganization of a Nursing Policy and Procedure Manual.
This article describes the process of reorganizing an existing Nursing Policy and Procedure Manual. The process of restructuring the Nursing Policy and Procedure Committee and clarifying its priorities is also described. This discussion has significance for staff development educators because this type of project is often entrusted to them and few detailed guidelines exist for completing this task.


Outcome of surgical treatment of primary and secondary glaucoma in young children.
To describe a paediatric cohort surgically treated for primary or secondary glaucoma (PG/SG), with regard to incidences, visual outcome and control of intraocular pressure (IOP). All children (n = 29, 42 eyes in total) surgically treated for PG or SG at the age of 4 years or younger between January 2002 and December 2010 at Sahlgrenska University Hospital in Mölndal were retrospectively studied through medical records. Median follow-up time after initial surgery was 5.9 years (range 2.4-11.2 years). The incidence of primary congenital glaucoma was 4.3 cases per 100 000 live births in the county of Västra Götaland. For glaucoma secondary to cataract surgery, the incidence was 13% with a median postoperative duration to diagnosis of glaucoma of 3.8 months (range 1.6 months to 4.3 years). Preoperative mean IOP was 31.5 (SD 8.1) mmHg, and mean IOP at last visit was 17.1 (SD 4.4) mmHg. For the entire cohort, 30% of the glaucoma eyes required more than two IOP-lowering surgical procedures during the study period. BCVA was ≥0.3 (decimal) in 45% of glaucomatous eyes at last follow-up with no statistically significant difference between PG and SG. Analysis of functional visual outcome, that is BCVA in the better eye, showed that 83% of all patients attained a BCVA of ≥0.5. The incidences and outcome of surgically treated paediatric glaucoma were in accordance with previous studies. Chamber angle surgery, and if necessary, tube implantation without the use of antimetabolites, is a favourable approach leaving most sites needed for future glaucoma surgery unaffected.


Identification of Mycobacterium shimoidei in a tuberculosis-like cavity by 16S ribosomal DNA direct sequencing.
A new, well-documented case of Mycobacterium shimoidei infection is reported. This bacterium was isolated from a patient with preexisting pulmonary lesions who developed a tuberculosis-like cavity in the lung. Isolation of fewer than ten strains, not epidemiologically related, has been reported worldwide; all originated from human pulmonary samples. Identification of the strain described here was first accomplished by 16S rDNA direct sequencing after in vitro amplification. This method allows rapid identification of unusual bacteria. The identification was confirmed by specific phenotypical tests and by chromatographic methods.


Obstructive sleep apnea, shift work and cardiometabolic risk.
Obstructive Sleep Apnea (OSA) is one of the most common sleep disorders, and invokes numerous negative health-related outcomes and physiopathological processes. Understanding the mechanisms by which OSA potentiates cardiometabolic risk of patients remains a current challenge. Sleep disruption is highly prevalent among shift workers and shift work (SW) is an important modulator of circadian rhythms, with health consequences intimately related to cardiometabolic health. Since the circadian timing system (CTS) interacts with the normal functioning of the ANS, CTS impact on OSA patients should be closely assessed. This review raises the question of whether SW-induced circadian misalignment potentiates the cardiometabolic risk of OSA patients, providing a novel perspective on the role of autonomic modulation as a key downstream mechanism linking cardiometabolic risk with both OSA and CTS misalignment.


Use of phage surface expression to analyze regions of human V4-34(VH4-21)-encoded IgG autoantibody required for recognition of DNA: no involvement of the 9G4 idiotope.
The V4-34 gene encodes the majority of autoanti-red cell Abs of I/i specificity. It also encodes a proportion of autoanti-DNA Abs found in patients with systemic lupus erythematosus. Nucleotide sequence analysis of mAbs that use this gene has indicated a role for CDR3 in discrimination between these autoantigens. Specifically, anti-DNA activity may require basic amino acids, such as arginine, found in this region. To investigate this requirement, we have expressed VH and VL sequences from a patient's IgG anti-DNA mAb, as Fab molecules at the surface of phage. Expressed Fab bound strongly to DNA, whereas control VH and VL pairs from an anti-red cell mAb did not. Replacement of the homologous mutated V4-34 sequence by germ-line sequence did not affect binding, indicating that somatic mutations in VH did not contribute significantly. In contrast, replacement of the basic CDR3 by an anti-red cell CDR3 abrogated anti-DNA activity, confirming its major role. However, an influence of VL was revealed by replacing homologous mutated V kappa IIIb by an unmutated V kappa IIIb sequence, reducing binding by approximately 50%. This influence was apparent only with homologous VH since the mutated V kappa was unable to generate anti-DNA activity when combined with anti-red cell VH. The 9G4 idiotope, which arises from FWR1, was expressed by all constructs. Substitution of Trp by Ser at position 7 in FWR11 caused complete loss of idiotope expression, with no effect on recognition of DNA, indicating no influence of idiotope expression on anti-DNA activity. Phage surface expression provides a powerful and rapid technique for assessing sequences relevant for Ab specificity or idiotope expression.


Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results.
The comet assay is a widely used test for the detection of DNA damage and repair activity. However, there are interlaboratory differences in reported levels of baseline and induced damage in the same experimental systems. These differences may be attributed to protocol differences, although it is difficult to identify the relevant conditions because detailed comet assay procedures are not always published. Here, we present a Consensus Statement for the Minimum Information for Reporting Comet Assay (MIRCA) providing recommendations for describing comet assay conditions and results. These recommendations differentiate between 'desirable' and 'essential' information: 'essential' information refers to the precise details that are necessary to assess the quality of the experimental work, whereas 'desirable' information relates to technical issues that might be encountered when repeating the experiments. Adherence to MIRCA recommendations should ensure that comet assay results can be easily interpreted and independently verified by other researchers.


Phytochemical Characterization of Rhus coriaria L. Extracts by Headspace Solid-Phase Micro Extraction Gas Chromatography, Comprehensive Two-Dimensional Liquid Chromatography, and Antioxidant Activity Evaluation.
Rhus coriaria L. (Anacardiaceae), commonly known as sumac, has been used since ancient times for many different applications, and nowadays is used mostly as a spice obtained from its in the Mediterranean and the Middle ground fruits and employed for flavoring and garnishing food, predominantly Eastern regions. Traditionally, sumac has been also used in popular medicine for the treatment of many ailments including hemorrhoids, wound healing, diarrhea, ulcers, and eye inflammation. Sumac drupes are indeed rich in various classes of phytochemicals including organic acids, flavonoids, tannins, and others, which are responsible of their powerful antioxidant capacity, from which treatment of many common diseases such as cardiovascular disease, diabetes, and cancer could benefit. In this work we evaluated the influence of fruit ripeness, conservation, and processing. To this aim, a phytochemical characterization of six different samples of Rhus coriaria L. was carried out. Specifically, headspace solid-phase micro extraction gas chromatography coupled to mass spectrometry and comprehensive two-dimensional liquid chromatography coupled to photodiode array and mass spectrometry detection, were employed. A total of 263 volatile compounds, including terpene hydrocarbons, acids, and aldehydes, as well as 83 polyphenolic compounds, mainly gallic acid derivatives, were positively identified. All samples showed a significant antioxidant activity by means of oxygen radical absorbance capacity, in line with their polyphenolic content and composition. Such findings set a solid ground to support the utilization of this plant as an attractive target for novel nutraceutical approaches and for drug discovery.


Prevalence of sleep apnoea and capnographic detection of nocturnal hypoventilation in amyotrophic lateral sclerosis.
This retrospective study aimed to investigate whether overnight oxymetry and early morning blood gas analysis predict nocturnal hypoventilation (NH) as reflected by night-time hypercapnia in patients with amyotrophic lateral sclerosis (ALS). In addition, prevalence and clinical determinants of sleep apnoea in ALS were evaluated. In 250 patients with non-ventilated ALS, transcutaneous capnometry was performed along with polysomnography or polygraphy and early morning blood gases. 123 patients were female, and 84 patients had bulbar-onset ALS. 40.0% showed NH, and an apnoea-hypopnoea index (AHI) >5/hour was found in 45.6%. In 22.3%, sleep apnoea and NH coincided. The obstructive apnoea index was significantly higher than the central apnoea index (p<0.0001). Both NH and sleep apnoea were significantly more common in male than in female patients. Sleep apnoea and AHI were associated with better bulbar function. Desaturation time (t<90%) and transcutaneous CO2 were negatively correlated with upright vital capacity. Early morning base excess (EMBE), bicarbonate and t<90% were independent predictors of NH. However, among 100 patients with NH, 31 were missed by t<90% >5 min and 17 were not identified when EMBE >3 mmol/L and t<90% >5 min were combined. In ALS, sleep apnoea is common and often accompanies NH. It is mainly obstructive, and central apnoea appears to be clinically irrelevant. Polygraphy or oxymetry alone are not sufficient to uncover NH. Combination of EMBE and t<90% may increase sensitivity, but transcutaneous capnography is strongly recommended for reliable detection of NH in patients with ALS.


Acute type A aortic dissection surgery impeded by substernal colon interposition.
A 54-year old female patient presented with acute aortic dissection, Stanford type A, and a past history of oesophageal resection with substernal colon interposition. Preoperative computer tomography confirmed the aortic dissection and revealed a colonic graft that was adherent to the sternum. We report the first successful surgical treatment of aortic dissection in this challenging patient.


Associations between lying behavior and activity and hypocalcemia in grazing dairy cows during the transition period.
Hypocalcemia is a common metabolic disorder of transition dairy cows that is considered a gateway disease, increasing the risk of other health disorders and reducing cow performance. Clinical milk fever is associated with long periods of recumbency, and it is plausible that cows experiencing non-paretic hypocalcemia may spend more time lying; hence, lying behavior and activity measures may be useful in identifying at-risk cows. The objective of this study was to describe associations among blood calcium (Ca) status at calving and lying behavior and activity measures during the transition period in grazing dairy cows. Blood was sampled on the day of calving (d 0), and d 1, 2, 3, and 4 postcalving, and analyzed for total plasma Ca concentration. Twenty-four multiparous Holstein-Friesian and Holstein-Friesian × Jersey grazing dairy cows were classified, retrospectively, as clinically hypocalcemic (CLIN; blood Ca ≤ 1.4 mmol/L at 1 or more consecutive samplings within 48 h postcalving, but without parturient paresis). These cows were pair-matched (using milk production potential from their estimated breeding value for milk protein, mean body weight at wk -5 and -6 precalving, and, where possible, parity) with 24 cows classified as subclinically hypocalcemic (SUB; blood Ca > 1.4 and < 2.0 mmol/L at 2 consecutive samplings within 48 h postcalving), and 24 cows classified as normocalcemic (NORM; blood Ca ≥ 2.0 mmol/L at 3 consecutive samplings within 72 h postcalving). Lying behavior and activity were monitored using triaxial accelerometers from -21 to +35 d relative to calving. Data were summarized to calculate daily lying time (h/d), daily number of lying bouts (LB; no./d), mean LB duration (min/bout), and the number of steps taken (steps/d). On d 0, the CLIN group were less active and spent approximately 2.6 h longer lying than the SUB and NORM groups, particularly between 0200 and 1400 h. On d 0, the NORM group had fewer LB (16.3/d) than the SUB and CLIN groups (18.2 and 19.2/d, respectively). These differences in behavior were no longer detected 2 d postcalving, and no further differences were observed. The day before calving, the CLIN group spent 1.4 h longer lying down than did the SUB and NORM groups. Further, the relative change in steps from a precalving baseline period (d -14 to -7) until d 0 was positively, linearly associated with blood Ca concentration within 24 h postcalving. Future work should consider daily and temporal changes in behavior in individual cows to determine the potential for these measures to allow early detection of hypocalcemia.


Processing and presentation of hen egg-white lysozyme by macrophages.
The processing and presentation by macrophages of the well-defined protein hen egg-white lysozyme (HEL) was analyzed using two HEL-specific T cell hybridomas. The processing studies revealed that both clones required that native HEL be processed, while neither clone required any processing of a tryptic digest of lysozyme. A differential requirement for processing was found for the intact, denatured lysozyme (CM-HEL) with one clone (2A11) requiring processing, and a second clone (3A9) did not require any processing. The determinant on the HEL molecule that both clones recognized was localized to a tryptic fragment containing residues 46 to 61. By testing the immunogenicity of fragments of the 46-61 peptide, mouse lysozyme, and human lysozyme, we were able to localize the T cell determinant to either of two residues, Gly-49 or Leu-56.


Two Cases of Primary Rhinovirus Pneumonia with Multiple Pulmonary Nodules.
Two patients, a 60-year-old man and 43-year-old woman, presented to our hospital with symptoms of respiratory tract infection. These patients showed imaging findings of multiple small nodules, ground-glass opacities, and consolidations. In case 1, although antibiotics were started, bilateral shadows spread widely, which made us suspect interstitial pneumonia. The condition improved after steroid administration, and there has been no recurrence since completing this treatment. In case 2, the patient recovered rapidly with antibiotics only. In both cases, we performed bronchoalveolar lavage, in which only human rhinovirus infection was detected by multiplex polymerase chain reaction testing, and primary rhinovirus pneumonia was diagnosed.


Burning plasma achieved in inertial fusion.
Obtaining a burning plasma is a critical step towards self-sustaining fusion energy1. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule2,3 through two different implosion concepts4-7. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics3,8. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.


Endoscopic resection of the third ventricular epidermoid cysts: A case review and review of literature.
Epidermoid cysts are benign, congenital lesions that originate from ectodermal cells, they are most commonly found in the cerebellopontine angle, but rarely in the ventricular system. There is limited literature regarding the different microsurgical techniques utilized to approach these lesions. A 63-year-old female with a recurrent third ventricular epidermoid cyst underwent gross total resection utilizing an endoscopic technique. We also reviewed the various endoscopic/microsurgical approaches and outcomes reported in literature. We identified 15 cases, including our own. Nine of these were managed using microsurgical techniques, while six cases (including ours) were treated endoscopically; gross total resection was achieved in 10/15 cases (67%). Most commonly, surgeons utilized the interhemispheric transcallosal approach (five cases). Tumor recurrence was seen in two cases. Complications attributed to these resections included: disorders of the hypothalamic-pituitary axis (3) - diabetes insipidus, galactorrhea, and hypopituitarism; tumor recurrence (2); aseptic meningitis (1); and a transient Korsakoff syndrome (1). Epidermoid cysts of the third ventricle are exceedingly rare, and surgical resection is generally well tolerated. Microsurgical transcortical, transcallosal, and endoscopic approaches each have advantages and disadvantages, and are associated with unique procedure-specific complications. Continuing technological improvement would favor endoscopic approaches for resection of tumors of the third ventricle in the future.


The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology.
The profound influence of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) on T-cell immunity has been known for over a decade, yet the precise roles played by these molecules still continue to emerge. Initially viewed as molecules that provide cell-intrinsic costimulatory and inhibitory signals, recent evidence suggests that both CD28 and CTLA-4 are also important in the homeostasis and function of a population of suppressive cells, termed regulatory T cells (Tregs). Here we review the main features of the CD28 and CTLA-4 system and examine how these impact upon Treg biology.


Physical analysis of the process of cavitation in xylem sap.
Recent studies have confirmed that cavitation in xylem is caused by air bubbles. We analyzed expansion of a preexistent bubble adhering to a crack in a conduit wall and a bubble formed by the passage of air through a pore of a pit membrane, a process known as air seeding. We consider that there are two equilibrium states for a very small air bubble in the xylem: one is temporarily stable with a bubble radius r1 at point s1 on the curve P(r) relating pressure within the bubble (P) with bubble radius (r); the other is unstable with a bubble radius r2 at point s2 on Pr (where r1 < r2). In each equilibrium state, the bubble collapse pressure (2sigma/r, where sigma is surface tension of water) is balanced by the pressure difference across its surface. In the case of a bubble from a crack in a conduit wall, which is initially at point s1, expansion will occur steadily as water potential decreases. The bubble will burst only if the xylem pressure drops below a threshold value. A formula giving the threshold pressure for bubble bursting is proposed. In the case of an air seed entering a xylem conduit through a pore in a pit membrane, its initial radius may be r2 (i.e., the radius of the pore by which the air seed entered the vessel) at point s2 on Pr. Because the bubble is in an unstable equilibrium when entering the conduit, it can either expand or contract to point s1. As water vaporizes into the air bubble at s2, P rises until it exceeds the gas pressure that keeps the bubble in equilibrium, at which point the bubble will burst and induce a cavitation event in accordance with the air-seeding hypothesis. However, other possible perturbations could make the air-seeded bubble contract to s1, in which case the bubble will burst at a threshold pressure proposed for a bubble expanding from a crack in a conduit wall. For this reason some cavitation events may take place at a xylem threshold pressure (Pl'*) other than that determined by the formula, Plp'* = -2sigma/rp, proposed by Sperry and Tyree (1988), which is applicable only to air-seeded bubbles at s2. The more general formula we propose for calculating the threshold pressure for bubble breaking is consistent with the results of published experiments.


Aortic stiffness and left ventricular mass in a rat model of isolated systolic hypertension.
We tested whether cardiac mass can be related to decreased aortic stiffness in an original rat model of isolated systolic hypertension. Increased aortic stiffness was produced by calcium overload of elastic arteries after vitamin D3 plus nicotine treatment. Half of the animals were chronically treated with the angiotensin-converting enzyme inhibitor perindopril (1 mg/kg per day PO). Rats were pithed, and lower body vascular resistance was measured. Blood pressure was then increased by phenylephrine infusion, and carotidofemoral pulse wave velocity was measured. This value together with those for thoracic aorta internal diameter and medial thickness (determined after in situ fixation and histomorphometry) were used to calculate elastic modulus. Vitamin D3 plus nicotine treatment produced parallel increases in cardiac mass and elastic modulus, with a significant correlation between the two. There was no significant change in resistance. Treatment with perindopril reversed the changes in cardiac mass and elastic modulus but had no effect on resistance after calcium overload of the elastic arteries. In this model of isolated systolic hypertension, we showed that cardiac mass is related to arterial elasticity.


[Impaired calcium uptake by cardiac sarcoplasmic reticulum and its underlying mechanism during rat septic shock].
The underlying mechanism of Ca2+ uptake function of cardiac sarcoplasmic reticulum (SR) was investigated in the rat septic shock model produced by cecal ligation and puncture (CLP). The results are as follows. During the early phase of sepsis, the initial rate of ATP-dependent Ca2+ uptake by SR was decreased, while both the capacity of Ca2+ uptake and the activity of Ca(2+)-ATPase were unaffected. In the late sepsis, the impairment in SR function was even greater as the initial rate and the capacity of Ca2+ uptake by SR were significantly decreased, and this was paralleled by a reduction in Ca(2+)-ATPase activity. Although Ca2+ affinity (Km value) to calcium pump and the A0.5 values for Mg2+ and ATP activation on the Ca2+ uptake rate were unchanged, during sepsis the phosphorylation of SR vesicles by adding of catalytic subunit of the cAMP-dependent protein kinase (PKA), calmodulin, or the fragment of PKC into Ca2+ uptake buffer, failed to stimulate Ca2+ uptake activities of SR isolated from early or late septic rats. These data suggest that depression of cardiac SR function is aggravated as sepsis develops, the impairment of SR Ca2+ uptake is possibly based on a mechanism of defective phosphorylation of SR rather than the ionic and energic regulatory actions of Ca2+, Mg2+, ATP on cardiac SR.


Influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in children under 5 years old: A time-series study for the 2001-2013 period.
S treptococcus pneumoniae is the main agent in bacterial consolidated pneumonias. In 2012, the 13-valent pneumococcal conjugate vaccine was introduced in the Argentine national immunization schedule for immunocompetent children as of two months old with a two-dose schedule plus a booster. To analyze the influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in relation to the number of hospitalizations for radiologically-confirmed consolidated pneumonias (RCCP). Observational, analytical, time-series study. All children hospitalized with a diagnosis of RCCP as per the World Health Organization's criteria between March and November throughout the2001-2013period were included. Viral diagnosis (respiratory syncytial virus, adenovirus, influenza and parainfluenza) was performed by indirect immunofluorescence using nasopharyngeal aspirates or by reverse transcription polymerase chain reaction. Time-series were developed to compare preimmunization 2001-2011 and post-immunization 2012-2013 periods. Out of a total of 11,306 children under 5 years old with acute lower respiratory tract infections, 4974 with RCCP were included. Annual average number of hospitalizations for RCCP: 394.8 pre-immunization, 315.5 post-immunization (reduction of 20.1%, 95% confidence interval |-CI-|: 13.13-26.49%, p < 0.001). Annual average number of hospitalizations for non-viral RCCP: 255.5 pre-immunization, 183 post-immunization (reduction of 28.4%, 95% CI: 20.5-35.78%, p < 0.001). Annual average number of hospitalizations for viral RCCP: 139.2 pre-immunization, 132 post-immunization (reduction of 4.8%, 95% CI: 8.38-16.49%, p= 0.4758). The proportion of RCCP with positive viral diagnosis was 35.3 % pre-immunization and 42% post-immunization (p= 0.001). An overall significant reduction in the number of hospitalizations for RCCP was observed following the introduction of the 13-valent pneumococcal conjugate vaccine, especially in the case of non-viral pneumonias. It is critical to continue with the epidemiological surveillance to evaluate the impact of this intervention and viral behavior in relation to RCCP.


Coincidental renal cell and endometrial carcinoma: a case report.
A case of renal cell carcinoma and coexistent endometrial carcinoma is reported. The renal tumor in the lower pole of left kidney was detected by staging preoperative ultrasound scan and was confirmed to be a multilocular cystic renal cell carcinoma. There were two separate foci of moderately differentiated endometrial cancer in the endometrial cavity. Microscopic tumor deposits were also found in the left ovary and the right obturator pelvic lymph nodes. The multicentric involvement of endometrial cavity is uncommon and even rarer is the association with renal cell carcinoma. To the best of our knowledge, this is the first report of an association between renal cell carcinoma and endometrial cancer. This case demonstrates the importance of complete preoperative investigation before any definitive surgery for cancer. Without the abdominal ultrasound scanning, the asymptomatic renal cell carcinoma would probably have been undetected.


In vitro and in vivo antitumour effects of phenylboronic acid against mouse mammary adenocarcinoma 4T1 and squamous carcinoma SCCVII cells.
The cytotoxic activity of phenylboroxine acid was evaluated in vitro on mouse mammary adenocarcinoma 4T1, mouse squamous cell carcinoma SCCVII, hamster lung fibroblast V79 and mouse dermal fibroblasts L929 cell lines. The cytotoxic effects were dose dependent for all tested tumour and non-tumour cell lines. Under in vivo conditions, three application routes of phenylboronic acid were studied: intra-peritoneal (i.p.), intra-tumour (i.t.) and per-oral. After tumour transplantation in syngeneic mice, phenylboronic acid was shown to slow the growth of both tumour cell lines (4T1 and SCCVII) compared with the control. The inhibitory effects were pronounced during the application of phenylboronic acid. For both tested tumour cell lines, the most prominent antitumour effect was obtained by intraperitoneal administration, followed significantly by oral administration.


[Reoperations in retroperitoneal tumors of non-organic origin].
Great, solid and fixed tumors should not always be considered as a reason for refusal of an operative treatment of patients with retroperitoneal tumors of nonorganic origin. Resection of such tumors especially those of benign genesis results in a complete recovery of the patients and their rehabilitation. The appearance of a recurrent retroperitoneal tumor of nonorganic origin should not be regarded as an inoperable condition. The timely diagnosis and operative treatment of patients with recurrences give three times better remote results of the treatment.


Long-term survival of 'damaged' Nippostrongylus brasiliensis adult worms in the testosterone-treated Indian soft-furred rat, Millardia meltada.
When testosterone-treated female Millardia meltada were infected with Nippostrongylus brasiliensis, adult worms persisted for over seven weeks. The kinetics of faecal egg counts showed a biphasic pattern having a transient decline at around two weeks post infection (p.i.). Thus the status of N. brasiliensis adult worms surviving in the small intestines of testosterone-treated M. meltada was examined. The fecundity and maturity of eggs in the uteri of female adult worms were examined at one, two, three and seven weeks p.i. Both the fecundity and maturity of eggs transiently decreased at two and three weeks p.i. and then completely recovered by seven weeks. Adoptive transfer of N. brasiliensis adult worms into naive recipients can discriminate the status of worms. Those obtained from the stable phase of a primary infection ('normal' worm) can establish and survive in the recipients, whereas those obtained at the time of expulsion ('damaged' worm) are rapidly expelled. Therefore, 300 each of N. brasiliensis adult worms collected from the testosterone-treated female M. meltada at one, two and seven weeks p.i. were transferred intraduodenally into normal rats to determine their status. Those collected at one week p.i. persisted for eight days, indicating that they were still 'normal'. In contrast, worms collected at two and seven weeks p.i. were expelled within four days, indicating that they had already been 'damaged'. Moreover, when the 'damaged' worms obtained from rats were intraduodenally transferred into testosterone-treated female M. meltada, they were not expelled, suggesting that testosterone-treatment affected the final expulsive step, but not the damaging process, of the mucosal defence of M. meltada against N. brasiliensis adult worms.


Serological investigations on Babesia orientalis infection. Status of water buffaloes in Hubei Province.
A total of 230 water buffaloes were sampled for the determination of the epidemiological situation of Babesia orientalis infection in Hubei Province, using the latex agglutination test. This serological test revealed that 74.7% of the collected sera were positive for antibodies against B. orientalis in endemic areas. In contrast, only 1.79% of water buffaloes were positive in non-epidemic areas. The incidence of the infection was substantially higher in older than in younger animals. The results were analysed using mathematical model and indicated that these areas were in a stable situation.


Advances in drug discovery to assess cholinergic neurotransmission: a systematic review.
Neurotransmission is essential to physiological processes of cellular communication. The search for new molecules that may influence neurotransmission systems is an open field with possible impact on several pathophysiological conditions or diseases: Alzheimer's disease, Parkinsonism and myasthenia gravis, etc. The present review describes the most important aspects of cholinergic neurotransmission, as well as natural and synthetic compounds that, as clinical or experimental drugs, are able to influence this transmission. The pharmacological effects of substances that bind to muscarinic or nicotinic cholinergic receptors, along with their corresponding affinities will also be presented.


Physical connection decreases benefits of clonal integration in Alternanthera philoxeroides under three warming scenarios.
Physical connection between ramets usually allows clonal plants to perform better but can have the opposite effects in some cases. Clonal integration and the effects of climate warming have been extensively studied, but to date little is known about how climate warming affects the benefits of clonal integration. We conducted a field experiment in which Alternanthera philoxeroides segments with connected and severed stolons were subject to four climate regimes (ambient, day warming, night warming and daily warming), and measured final biomass, number of ramets and total length of stolons. Across the three warming treatments, temperature rise suppressed growth of clonal fragments with connected stolons but increased growth of fragments with severed stolons; temperature rise affected the biomass of distal ramets but not proximal ramets, and had similar effects on the numbers of proximal and distal ramets. When the three warming treatments were considered separately, they had contrasting consequences for the benefits of clonal integration. Specifically, when fragments were exposed to day and night warming, physical connection evened out the advantages of clonal integration that occur under ambient conditions; when fragments were exposed to daily warming, physical connection led to smaller clonal plants. These findings suggest that physical connection between ramets may be disadvantageous to overall performance of A. philoxeroides fragments under climate warming, and also indicate that the net consequences of daily warming outweigh those of day or night warming.


Differential Effects of Anxiety on Internet Gaming Disorder: A Large-Scale Cross-Sectional Survey.
Internet gaming disorder (IGD) has become a serious public health problem in East Asia, and studies have reported IGD to be significantly associated with anxiety, but no causal relationship between the two has yet been demonstrated. Children are at high risk of developing IGD, however, previous studies have principally focused on the condition in adults and adolescents and reported non-clinical samples. A large-scale survey is needed to research and evaluate IGD and anxiety in children and adolescents to understand the current situation of IGD in children and explore the impact of IGD on anxiety. A cross-sectional study using an online questionnaire was conducted between March 1 and July 31, 2021. A total of 10,479 school children and adolescents in the western provinces of China were selected by convenience sampling. A questionnaire was used to collect data anonymously. The questionnaire covered IGD and the Revised Children's Manifest Anxiety Scale (RCMAS). Welch's ANOVA Test and Games-Howell test were used to test for differences in anxiety levels between IGD groups. Poisson regression analysis was used to further investigate the key predictors of IGD. 3.2% of participants (n = 334) (95% CI: 2.9-3.2%) were classified as at high risk of presenting with IGD, 71.1% (n = 7,454) (95% CI: 70.3-72.0%) were classified as low-risk players, and 25.7% (n = 2,691) (95% CI: 24.9-26.5%) were classified as non-gaming. The average RCMAS score was (7.18 ± 7.534). The high-risk group had a higher total score RCMAS, as well as scoring higher in its three dimensions. Regression analysis using gender, age, and total RCMAS score as independent variables, and risk of IGD as a dependent variable showed that the odds ratio (OR) for gender was 2.864 (95% CI: 2.267-3.618), and the OR for total RCMAS score was 1.101 (95% CI: 1.087-1.114). The OR for age was not statistically significant. Anxiety was a predictor of IGD, with statistically significant group differences in total anxiety, as well as the dimensions of physiological anxiety, social correlation, and sensitivity. The timely assessment of anxiety in children and adolescents, training social skills, and facilitating effective integration into society could be effective ways of reducing the incidence and impact of IGD.


[Purulent pericarditis].
Purulent pericarditis is diagnosed when pus is drained from the pericardial space or when bacteria are cultured from the pericardial fluid. This rare disease is often diagnosed late, when severe hemodynamic compromise develops due to pericardial tamponade. It is usually a complication of pneumonia, especially if there is empyema as well, and often follows chest surgery or chest wall infections. It sometimes appears in patients with septicemia, especially when they are debilitated or immuno-compromised. Diagnosis is aided by echocardiography. Pericardiocentesis and drainage of the pus, as well as prolonged antibiotic treatment, are mandatory. Delay in diagnosis and treatment often results in death. Some surviving patients may develop constrictive pericarditis and require pericardiectomy. We report a 73-year-old man with pulmonary lymphoma who suffered from purulent pericarditis secondary to sepsis with methicillin-resistant Staphylococcus aureus. Pericardial drainage and appropriate antibiotic treatment eventually resulted in complete recovery.


The relationship between smoking status and serious psychological distress: findings from the 2007 Behavioral Risk Factor Surveillance System.
To examine the associations between smoking and quit attempts with psychological distress and also by socioeconomic groups. Using data on 172,938 adult respondents from the 2007 Behavioral Risk Factor Surveillance System we used the Kessler-6 scale to assess psychological distress among never, former, some-day, and everyday smokers and smokers attempting to quit. Everyday smokers and attempting quitters had higher mean levels of 30-day psychological distress than never smokers. Compared with never smokers, the odds of having serious psychological distress (SPD) were: former smokers, 1.3 (95 % CI: 1.1-1.6); some-day smokers, 2.5 (95 % CI: 2.0-3.1); and everyday smokers, 3.3 (95 % CI: 2.8-3.8). As for unsuccessful quit attempts, the odds were highest for current smokers (3.3 [95 % CI: 2.8-3.8]) versus never smokers. Among current smokers, persons with less than high school education, income less than $ 50,000, or who were unemployed or unable to work had the highest odds of reporting SPD. Given the association between current smoking behaviors and psychological distress, future tobacco prevention and control efforts may benefit by including components of mental health, especially for low SES populations.


Accidental exposure of children to polychlorinated biphenyls.
Children exposed to polychlorinated biphenyls (PCBs) while playing with parts of a capacitor had elevated serum concentrations of lower chlorinated PCBs, similar to Arochlor 1242. These levels declined over 11 months of followup to about half their initial values, from a mean of 12.9 to 6.3 ppb (parts per billion, ng/mL) among four children. In comparison, other persons in the same household and a reference group of persons seen in the same geographic area had serum levels of Aroclor 1242-like PCBs below the limit of detection (less than 5 ppb). All three groups--the children, household members, and geographic referents--also had higher chlorinated PCBs in their serum similar to Aroclor 1260 (HPCBs). HPCB concentrations were similar in these groups (approximately 2 ppb) and did not decline significantly.


Aneurysmal bone cyst of the scapula. A case report.
Aneurysmal bone cyst (ABC) is an uncommon, benign but locally destructive bone lesion of unknown origin. Differential diagnosis can be challenging as it shares common radiological and pathological features with other benign and malignant bone lesions. The degree of diagnostic difficulty grows even more when an unusual location has to be taken into account. We report a rare and challenging case of a large primary ABC located at the scapula of a young male, who was surgically treated with subtotal removal of the scapula.


Construct validity of the short inventory of problems among Spanish speaking Hispanics.
Research on ethnic health disparities requires the use of psychometrically sound instruments that are appropriate when applied to ethnically diverse populations. The Short Inventory of Problems (SIP) assesses alcohol-related consequences and is often used as a measure to evaluate intervention effectiveness in alcohol research; however, whether the psychometric properties of this instrument are comparable across language and ethnicity remains unclear. Multi-group confirmatory factor analysis (MGCFA) was used to test for the invariance of the measurement structure of the SIP across White Non-Hispanic English speaking (N=642), Hispanic English speaking (N=275), and Hispanic Spanish speaking (N=220) groups. The MGCFA model in which factor loadings, measurement intercepts, and item residuals were constrained to be equal between English speakers and Spanish speakers exhibited a reasonable fit to the data, χ(2)(221)=1089.612 p<.001, TLI=.926; CFI=.922, RMSEA=.059 (90% CI=.055-.062). The ΔCFI supported strict factorial invariance, ΔCFI=.01, across groups; no significant group differences were found between factor loadings, measurement intercepts, or item residuals between English speakers and Spanish speakers. This study extends the existing confirmatory factor analysis results of the SIP by providing additional data to inform the utility of the SIP among Hispanics. Strict factorial invariance between Spanish and English speakers is necessary to: conclude that the underlying constructs have the same meaning across groups; test for group differences in the latent variables across groups; and presume that group differences are attributable only to true differences between groups. Thus, the SIP is strongly supported for evaluating the effectiveness of alcohol treatment among Hispanics.


Metabolic Incorporation of Azide Functionality into Cellular RNA.
Real-time tracking of RNA expression can provide insight into the mechanisms used to generate cellular diversity, as well as help determine the underlying causes of disease. Here we present the exploration of azide-modified nucleoside analogues and their ability to be metabolically incorporated into cellular RNA. We report robust incorporation of adenosine analogues bearing azide handles at both the 2'- and N6-positions; 5-methylazidouridine was not incorporated into cellular RNA. We further demonstrate selectivity of our adenosine analogues for transcription and polyadenylation. We predict that azidonucleosides will find widespread utility in examining RNA functions inside living cells, as well as in more complex systems such as tissues and living animals.


Scapula-focused exercises with or without biofeedback increase corticospinal excitability in recreational overhead athletes with shoulder impingement.
Individuals with shoulder impingement syndrome (SIS) exhibit changed corticospinal excitability, scapular kinematics, and scapular muscle activation patterns. To restore the scapular kinematics and muscle activation patterns in individuals with SIS, treatment protocols usually include scapula-focused exercises, such as scapular orientation training and strength training. To investigate whether these two types of scapular exercise can reverse the changed corticospinal excitability of recreational overhead athletes with SIS. Randomized Controlled Clinical Trial. University laboratory. Forty-one recreational overhead athletes with SIS (n=20 in the scapular orientation group with age= 26.45±4.13 years; height= 171.85±7.88 cm; mass= 66.70±10.68 kg; n=21 in the strengthening group with age= 26.43±5.55 years; height= 171.62±5.87 cm; mass= 68.67±10.18 kg). Both groups performed a 30-minute training protocol consisting of three exercises to strengthen the lower trapezius and serratus anterior muscles without overactivating the upper trapezius. Participants in the scapular orientation group were instructed to consciously activate their scapular muscles with electromyographic biofeedback and cues, whereas the strengthening group did not have biofeedback or cues for scapular motion. Corticospinal excitability was assessed using transcranial magnetic stimulation. Scapular kinematics and muscle activation during arm elevation were also measured. After the training, both groups demonstrated a significant increase in motor evoked potentials in lower trapezius (P=0.004) and significant increases in scapular upward rotation (P=0.032), lower trapezius activation (P<0.001), and serratus anterior activation (P<0.001) during arm elevation. Moreover, the scapular orientation group showed higher lower trapezius activation levels during arm elevation following the training, compared with the strengthening group (P=0.028). With or without biofeedback and cues, scapula-focused exercises improved scapular control and increased corticospinal excitability. Adding biofeedback and cues for scapular control during exercise helped facilitate greater lower trapezius activation, and thus, feedback and cues are recommended during scapula-focused training.


Emerging and reemerging diseases of avian wildlife.
Of the many important avian wildlife diseases, aspergillosis, West Nile virus, avipoxvirus, Wellfleet Bay virus, avian influenza, and inclusion body disease of cranes are covered in this article. Wellfleet Bay virus, first identified in 2010, is considered an emerging disease. Avian influenza and West Nile virus have recently been in the public eye because of their zoonotic potential and links to wildlife. Several diseases labeled as reemerging are included because of recent outbreaks or, more importantly, recent research in areas such as genomics, which shed light on the mechanisms whereby these adaptable, persistent pathogens continue to spread and thrive.


Transdermal drug delivery: problems and possibilities.
Transdermal drug delivery has, in recent years, attracted considerable interest. However, despite the obvious advantages of this novel route of drug administration to achieve systemic therapeutic effect, there remain important, and sometimes severe, limitations on the physiochemical and pharmacological properties of the agent to be delivered. This article reviews the present status and accomplishments of transdermal drug delivery. The benefits, disadvantages, and, as yet, unresolved problems inherent to drug input via the skin are addressed. Deficiencies in our knowledge of the percutaneous absorption process in man are identified, and approaches to elucidate these unknowns are discussed. Finally, with respect to the future potential of transdermal drug delivery, experimental and modeling techniques, which can be employed to assess the feasibility and promise of a therapeutic candidate, are described and illustrated with pertinent examples.


Radotinib-induced lentiginosis: a report of an adverse cutaneous reaction associated with a tyrosine kinase inhibitor.
Tyrosine kinase inhibitors (TKIs) are associated with various adverse cutaneous reactions, including pigmentary changes. Radotinib is a novel and selective BCR-ABL1 TKI, which has shown activity and safety in the treatment of patients with chronic myeloid leukaemia resistant or intolerant to imatinib. A 69-year-old Korean man presented with lentiginosis after taking radotinib for 6 months. On histopathological examination, the numbers of melanocytes and melanin pigment were found to be increased due to c-KIT activation, consequently upregulating microphthalmia-associated transcription factor. This finding is in contrast to previous reports analysing the mechanisms of previously reported tyrosine kinase inhibitors inhibiting c-KIT.


Intravenous iron therapy in end-stage renal disease.
Intravenous iron therapy is instrumental in the management of anemia in patients with end-stage renal disease (ESRD). Iron is available in several different preparations, with slight differences in the pharmacology of each. Given the importance of intravenous iron in the management of these patients, clinicians should be aware of the potential risks associated with it. Intravenous iron has effects on host immunity that raise concerns about clinical infection risk. Iron preparations appear to increase oxidative stress in these patients, which has important implications for cardiovascular disease states. Lastly, the effects of intravenous iron on liver disease are largely unknown.


Telomere loss: mitotic clock or genetic time bomb?
The Holy Grail of gerontologists investigating cellular senescence is the mechanism responsible for the finite proliferative capacity of somatic cells. In 1973, Olovnikov proposed that cells lose a small amount of DNA following each round of replication due to the inability of DNA polymerase to fully replicate chromosome ends (telomeres) and that eventually a critical deletion causes cell death. Recent observations showing that telomeres of human somatic cells act as a mitotic clock, shortening with age both in vitro and in vivo in a replication dependent manner, support this theory's premise. In addition, since telomeres stabilize chromosome ends against recombination, their loss could explain the increased frequency of dicentric chromosomes observed in late passage (senescent) fibroblasts and provide a checkpoint for regulated cell cycle exit. Sperm telomeres are longer than somatic telomeres and are maintained with age, suggesting that germ line cells may express telomerase, the ribonucleoprotein enzyme known to maintain telomere length in immortal unicellular eukaryotes. As predicted, telomerase activity has been found in immortal, transformed human cells and tumour cell lines, but not in normal somatic cells. Telomerase activation may be a late, obligate event in immortalization since many transformed cells and tumour tissues have critically short telomeres. Thus, telomere length and telomerase activity appear to be markers of the replicative history and proliferative potential of cells; the intriguing possibility remains that telomere loss is a genetic time bomb and hence causally involved in cell senescence and immortalization.


Compatibility of dexamethasone sodium phosphate with hydromorphone hydrochloride or diphenhydramine hydrochloride.
The stability and compatibility of dexamethasone sodium phosphate and hydromorphone hydrochloride or diphenhydramine hydrochloride at various concentrations at room temperature was studied. Solutions containing equal volumes in the following ranges of concentrations were prepared: dexamethasone sodium phosphate 0-10 mg/mL, diphenhydramine hydrochloride 0-50 mg/mL, and hydromorphone hydrochloride 0-40 mg/mL. Samples of each combination were analyzed immediately after mixing and at 7 and 24 hours using a stability-indicating high-performance liquid chromatographic assay. The pH of each solution was measured, and each combination was visually inspected. Precipitation occurred in solutions containing dexamethasone and hydromorphone hydrochloride or diphenhydramine hydrochloride when equal volumes of the most concentrated solutions were mixed. Some of the combinations at lower concentrations were visually compatible, and more than 90% of the initial concentrations of both drugs (i.e., dexamethasone-hydromorphone and dexamethasone-diphenhydramine) remained in these compatible solutions. Dexamethasone is visually compatible with diphenhydramine or hydromorphone but only within specific concentration ranges. In visually compatible solutions, both drug combinations are stable for up to 24 hours at room temperature.


Putting Humpty together and pulling him apart: accessing and unbinding the hippocampal item-context engram.
A remarkable act of memory entails binding different forms of information. We focus on the timeless question of how the bound engram is accessed such that its component features-item and context-are extracted. To shed light on this question, we investigate the dynamics between brain structures that together mediate the binding and extraction of item and context. Converging evidence has implicated the Parahippocampal cortex (PHc) in contextual processing, the Perirhinal cortex (PRc) in item processing, and the hippocampus in item-context binding. Effective connectivity analysis was conducted on fMRI data gathered during retrieval on tests that differ with regard to the to-be-extracted information. Results revealed that recall is initiated by context-related PHc activity, followed by hippocampal item-context engram activation, and completed with retrieval of the study-item by the PRc. The reverse path was found for recognition. We thus provide novel evidence for dissociative patterns of item-context unbinding during retrieval.


A new species of Gamasiphis Berlese (Acari: Ologamasidae) from North Asia, with a key to the Eurasian species.
Gamasiphis angaridis sp. n. is described from females and males collected from litter and soil in the North Asian part of Russia-Siberia and the Far East. This is the first species of the large genus Gamasiphis to be described from the northern Palaearctic Region. A key for the separation of females of the 11 recognisable species of Gamasiphis described in Eurasia is provided.


Wave propagation in coupled left ventricle-arterial system. Implications for aortic pressure.
The objective of this study was to examine the effects of wave propagation properties (global reflection coefficient gamma IG; pulse wave velocity, c(ph); and characteristic impedance zeta(o) on the mechanical performance of the coupled left ventricle-arterial system. Specifically, we sought to quantify effects on aortic pressure (P(ao)) and flow Q(ao) while keeping constant other determinants of P(ao) and Q(ao) (left ventricular end-diastolic volume, V(ed), and contractility, heart rate, and peripheral resistance, R(s)). Isolated rabbit hearts were subjected to real-time, computer-controlled physiological loading. The arterial circulation was modeled with a lossless tube terminating in a complex load. The loading system allowed for precise and independent control of all arterial properties as evidenced by accurate reproduction of desired input impedances and computed left ventricular volume changes. While propagation phenomena affected P(ao) and Q(ao) morphologies as expected, their effects on absolute P(ao) values were often contrary to the current understanding. Diastolic (Pd) and mean (Pm) P(ao) and stroke volume decrease monotonically with increases in gamma G, c(ph), or zeta(o) over wide ranges. In contrast, these increase had variable effects on peak systolic P(ao) (Ps): decreasing with gamma G, biphasic with c(ph), and increasing with zeta(o). There was an interaction between gamma G and c(ph) such that gamma G effects on P(m) and P(d) were augmented a higher C(ph) and vice versa. Despite large changes in system parameters, effects on Pm and Ps were modest ( < 10% and < 5%, respectively); effects on Pd were always two to four times greater. Similar results were obtained when the single-tube model of the arterial system was replaced by an asymmetrical T-tube configuration. Our data do not support the prevailing hypothesis that P(s) (and therefore ventricular load) can be selectively and significantly altered by manipulating gamma G, c(ph), and/or zeta o.


Role of sp transcription factors in the regulation of cancer cell metabolism.
Cancer cells exhibit altered metabolism characterized by the generation of adenosine triphosphate by glycolysis and generation of fatty acids by de novo synthesis. The majority of genes involved in these pathways have binding sites for specificity protein (Sp) transcription factors in their promoters. Studies showing that Sp transcription factors, particularly Sp1, are involved in the regulation in cancer cells of hexokinase, pyruvate kinase, lactate dehydrogenase, fatty acid synthase, and hypoxia-inducible factor-1α are reviewed. Glycolysis and lipogenesis in cancers are also known to be stimulated by the constitutive activation of the PI3K/Akt signaling pathway. Evidence is presented for the notion that Sp transcription factors may act in concert with Akt to regulate the abnormal metabolism of cancer cells.


Increase of plasminogen activator inhibitor levels predicts outcome of leukocytopenic patients with sepsis.
Variables of the fibrinolytic system were prospectively studied in patients with haematologic malignancies in chemotherapy-induced leukocytopenia at onset and during the course of septicemia to evaluate their prognostic value. This group of patients was chosen because of their high risk of developing severe septic complications, thus allowing serial prospective testing of fibrinolytic variables prior to and during evolving sepsis or septic shock. 62 patients with febrile infectious events were accrued to the study. Of these, 13 patients progressed to severe sepsis and an additional 13 patients to septic shock as defined according to standard diagnostic criteria. At onset of fever, plasminogen activator inhibitor (PAI) activity and PAI-1 antigen levels increased from normal baseline levels and were significantly higher in the group of patients who developed septic shock compared to those with severe sepsis (medians: 10.6 versus 1.3 U/ml, p = 0.0001; 50.0 versus 5.0 ng/ml, p = 0.0002). The increase in PAI activity and antigen in septic shock was accompanied by an increase in tissue-type plasminogen activator antigen and total fibrin(ogen) degradation products and a decrease in alpha(2)-antiplasmin activity (p < 0.006). In contrast, in the group of patients that developed severe sepsis the variables of the fibrinolytic system remained unchanged at onset of fever. These differences between septic shock and severe sepsis were sustained throughout the septic episode for all variables (p < 0.0001). PAI activity of > 5 U/ml at onset of fever predicted a lethal outcome with a sensitivity of 92% and a specificity of 100%. Thus, septic shock in leukocytopenia is associated with significant activation of the fibrinolytic system presumably as a response of the vascular endothelium to inflammatory injury. Furthermore, PAI activity measurements are sensitive markers of an unfavourable prognosis.


Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by hamster, mouse and rat intestine: relevance of species differences.
We recently demonstrated the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in rat intestinal segments, as well as the inducibility of intestinal NNK metabolism by starvation or acetone treatment. To improve our understanding of intestinal NNK turnover we have additionally investigated NNK metabolism in isolated perfused jejunal segments from NMRI mice and Syrian golden hamsters. [14C]NNK (1 micromol/l) was metabolized extensively by jejunal segments from female NMRI mice (88.5%) and female Syrian hamsters (86.4%), whereas in male NMRI mouse segments a slightly lower metabolism (68.8%) was observed. Alpha-Hydroxylation was the predominant metabolic pathway in mice (58% of total metabolism), whereas in female Syrian hamsters N-oxidation accounted for >50% of the metabolites [4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol 27%, 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone 22% of total radioactivity]. Formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was low in both species. Total NNK metabolism in male NMRI mice was increased by starvation to 84.4% and by acetone treatment to 90.0% of the absorbed radioactivity. This increase was due to an increase in N-oxidation, whereas the amounts of alpha-hydroxides and NNAL remained unchanged. In female Syrian hamsters acetone treatment had only minimal effects upon the metabolite composition. Acetone-treated NMRI mice and Syrian hamsters were additionally gavaged with the chemopreventive agent phenethylisothiocyanate (PEITC). In mice this treatment slightly decreased keto acid formation (0.6-fold, P<0.05), whereas in hamsters PEITC had no effect. In summary, intestinal metabolism of NNK in rats, mice and hamsters differs in both the extent of total metabolism (hamsters > or = mice > rats) and the metabolite composition, indicating major species differences.


[Use of daily and weekly ferrous sulfate to treat anemic childbearing-age women].
A blind randomized trial was conducted in a low-income community in the city of Recife, Pernambuco, Brazil, with 193 anemic (Hb <12 mg/dl) and "menstruating" women (age range: 15-45 years) to compare daily and weekly doses of ferrous sulfate (60 mg elemental iron) and treatment compliance. Blood samples were taken from 484 women to determine hemoglobin levels before and after the trial and mean corpuscular volume (MCV) at end of treatment. After 12 weeks' follow-up, 150 women completed the trial, 79 on the alternative weekly regimen and 71 on the conventional daily regimen. Mean corpuscular hemoglobin concentrations (MCHC) prior to treatment were 10.52 g/dl (DP=1.13) and 10.72 g/dl (DP=0.92), respectively, for the alternative and conventional regimens. After the intervention they were 11.83 g/dl (DP=0.97) for the weekly regimen and 11.62 g/dl (DP=1.39) for the daily one. The alternative regimen was better accepted than the conventional one. There was no significant difference (p=0.22) between differences in the mean values of the two regimens, although the cure rate was higher after the alternative treatment. The study concluded that the weekly regimen was no less effective than daily treatment.


Psychometric qualities of the English Coping Scales of the Stress and Coping Inventory in a representative UK sample.
The Coping Scales of the Stress and Coping Inventory (SCI; Satow in Stress- und Coping-Inventar (SCI): Test- und Skalendokumentation. Stress and coping inventory. http://www.drsatow.de , 2012) are well-established German self-report scales measuring five coping styles: Positive Thinking, Active Coping, Social Support, Support in Faith, and Alcohol and Cigarette Consumption. The purpose of this study was to translate the scales into English and to psychometrically evaluate this English version of the SCI coping scales with a representative sample of the UK population. The coping scales of the SCI were forward-backward translated into English and administered to a representative sample according to age, gender, education, and region for the UK (N = 1006). Internal consistencies, factorial validity, and construct validity were assessed for both the original factor structure of the SCI, as well as a newly identified factor structure. The results for the original factor structure indicated good internal consistency and construct validity. The adaptive coping styles of this version were positively correlated with resilience and negatively with perceived stress. The maladaptive coping strategy, alcohol and cigarette consumption, showed the opposite correlations. The exploratory factor analysis (EFA) of the English version resulted in a five-factor structure, but some items loaded on different factors than in the German version. These new factors were Religious Coping, Social Support, Various Coping, Alcohol and Cigarette Consumption, and Reflective Coping. The novel factors showed similar correlations to resilience and perceived stress as the original factor structure. Only religious coping did not significantly correlate to perceived stress. Confirmatory factor analysis with the original factor structure of the German SCI coping scales revealed poor model fit for the English SCI coping scales. The English SCI coping scales consistently and accurately measure five different coping styles. Nevertheless, the original factor structure of the SCI coping scales, when applied to an English-speaking sample, did not fit the data well. The new factor structure established by EFA is only preliminary and needs further validation in future large samples using the English version of the SCI coping scales.


Training in bereavement communication - attitudes to guidance and training for clinical photographers.
Bereavement is one of the most emotionally intense situations healthcare staff can find themselves in and requires extensive communication training to work in. While other healthcare staff receive specific training in bereavement, clinical photographers do not receive much, if any, in the form of bereavement communication training. The lack of training can lead to clinical photographers feeling ill-prepared to communicate with bereaved parents. This paper aims to identify if clinical photographers feel there is a need for training or written guidance and what they would wish to see included within it. A questionnaire was distributed to clinical photographers via the Institute of Medical Illustrators to gather opinions, results indicate that the majority feel there is a need.


Acoustic Control of Mosquito Larvae In Artificial Drinking Water Containers.
Emerging technology designed to kill mosquito larvae with sound waves may present a nonchemical and nonbiological alternative to reduce larval populations of key medically important mosquito species such as Aedes aegypti in containers or catchments of water. These devices could benefit integrated vector management programs facing public resistance to the use of chemical or biological larvicides in stored drinking water. In this study we investigate the efficacy of a Larvasonic SD-Mini Acoustic Larvicide device in reducing larval populations of Ae. aegypti in 3 volumes of water across a range of acoustic exposure durations. We report lethal pulse duration times for 50% and 90% mortality and optimal exposure durations for the tested water volumes.


Identification of Salmonella enterica serovar Typhimurium genes regulated during biofilm formation on cholesterol gallstone surfaces.
Salmonella spp. are able to form biofilms on abiotic and biotic surfaces. In vivo studies in our laboratory have shown that Salmonella can form biofilms on the surfaces of cholesterol gallstones in the gallbladders of mice and human carriers. Biofilm formation on gallstones has been demonstrated to be a mechanism of persistence. The purpose of this work was to identify and evaluate Salmonella sp. cholesterol-dependent biofilm factors. Differential gene expression analysis between biofilms on glass or cholesterol-coated surfaces and subsequent quantitative real-time PCR (qRT-PCR) revealed that type 1 fimbria structural genes and a gene encoding a putative outer membrane protein (ycfR) were specifically upregulated in Salmonella enterica serovar Typhimurium biofilms grown on cholesterol-coated surfaces. Spatiotemporal expression of ycfR and FimA verified their regulation during biofilm development on cholesterol-coated surfaces. Surprisingly, confocal and scanning electron microscopy demonstrated that a mutant of type 1 fimbria structural genes (ΔfimAICDHF) and a ycfR mutant showed increased biofilm formation on cholesterol-coated surfaces. In vivo experiments using Nramp1(+/+) mice harboring gallstones showed that only the ΔycfR mutant formed extensive biofilms on mouse gallstones at 7 and 21 days postinfection; ΔfimAICDHF was not observed on gallstone surfaces after the 7-day-postinfection time point. These data suggest that in Salmonella spp., wild-type type 1 fimbriae are important for attachment to and/or persistence on gallstones at later points of chronic infection, whereas YcfR may represent a specific potential natural inhibitor of initial biofilm formation on gallstones.


Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity.
This study was undertaken to investigate the molecular mechanisms underlying the neuroprotective actions of lithium against glutamate excitotoxicity with a focus on the role of proapoptotic and antiapoptotic genes. Long term, but not acute, treatment of cultured cerebellar granule cells with LiCl induces a concentration-dependent decrease in mRNA and protein levels of proapoptotic p53 and Bax; conversely, mRNA and protein levels of cytoprotective Bcl-2 are remarkably increased. The ratios of Bcl-2/Bax protein levels increase by approximately 5-fold after lithium treatment for 5-7 days. Exposure of cerebellar granule cells to glutamate induces a rapid increase in p53 and Bax mRNA and protein levels with no apparent effect on Bcl-2 expression. Pretreatment with LiCl for 7 days prevents glutamate-induced increase in p53 and Bax expression and maintains Bcl-2 in an elevated state. Glutamate exposure also triggers the release of cytochrome c from the mitochondria into the cytosol. Lithium pretreatment blocks glutamate-induced cytochrome c release and cleavage of lamin B1, a nuclear substrate for caspase-3. These results strongly suggest that lithium-induced Bcl-2 up-regulation and p53 and Bax down-regulation play a prominent role in neuroprotection against excitotoxicity. Our results further suggest that lithium, in addition to its use in the treatment of bipolar depressive illness, may have an expanded use in the intervention of neurodegeneration.


The management of drug-induced gingival overgrowth.
This review critically evaluates the different therapies that are available to manage drug-induced overgrowth (DIGO). This review is based on literature identified using the online databases MEDLINE and PUB MED. It is not a systematic review, but a conventional review of the relevant literature. Patients benefit from a non-surgical approach if this can be delivered before commencement of medication although in many instances this may not be practicable. Systemic antibiotic usage has been evaluated in the management of ciclosporin-induced gingival overgrowth. Efficacy appears to be equivocal and long-term use is undesirable. Surgical excision remains the main treatment option especially for patients with severe overgrowth. Few studies have compared different techniques with respect to recurrence rate or post-operative sequelae. DIGO is a common clinical problem that often requires intervention. Non-surgical techniques can limit the occurrence of this unwanted affect, reduce the extent of plaque-induced gingival inflammation and reduce the rate of recurrence. Wherever possible this management strategy should be adopted first. Surgical treatment is often the most reliable option and scalpel gingivectomy remains the treatment of choice. Further investigations are required to develop appropriate management strategies to prevent recurrence of DIGO.


Color difference between the vita classical shade guide and composite veneers using the dual-layer technique.
The purpose of this in vitro study was to evaluate the color difference between the Vita Classical Shade Guide and composite veneers using the dual-layer technique. Thirty samples were fabricated using a custom-made mold (Easy Layering Shade Guide Kit, 3M) using two resin composites: Filtek Supreme Ultra (3M); and Estelite Omega (Tokuyama) (n=3). The composite veneers were made by layering the different enamel and body or dentin shades from each composite. The color measurements were taken using a spectrophotometer (Vita Easyshade V®, Vita Zahnfabrik). The ΔE00 between the Vita Classical Shade Guide (Vita Zahnfabrik) and the composite veneers were calculated using the CIEDE2000 formula. For the composite veneers using Filtek Supreme Ultra, the best match for A1 Vita shade was achieved layering either EA1 with DA2 or DA3; EA2 with DA1 or DA2 (ΔE00= 1.53 ~ 1.96 ± 0.4). For A2 Vita shade the best match would be EA3 with DA3 or EA3 with DA2 (ΔE00= 1.40 ~ 1.85 ± 0.1); or for A3 Vita shade the best match would be EA3 with DA2 2.50±(0.6). For the composite veneers using Estelite Omega, the were no best match for neither A1, A2 or A3 Vita shade (ΔE00> 2.5). The combination of enamel and dentin shades from Filtek Supreme Ultra provided acceptable color match for A1, A2 and A3 shades from the Vita Shade Guide, while Estelite Omega did not provide acceptable color match for any of the Vita Shade Guide standard shades tested. Key words:Color, color matching, optical properties, resin composite, layering.


Health analytics: the road not traveled.
Review of the development of health administration by chronological examination of textbooks reveals that the definition of health administration has changed. In the process of conversion to a business management model, health analytics have been undervalued by health administration programs. Health analytics can be defined as "techniques for the analysis of health services that require in-depth understanding of the workings of the health system and are grounded in a rational-comprehensive public health model of health administration." Health analytics are not simply the application of business techniques to health services. Quality assessment and planning methods are examples of two important aspects of health administration that are addressed by health analytics.