Emergency caesarean delivery in prolonged obstructed labour as risk factor for obstetric fractures--a case series.
Birth fractures predominantly affect the clavicle, humerus or femur. Brachial plexus injury may co-exist with humeral or clavicular fractures. From January 2002 to December 2010, 8 neonates with fractures after caesarean section were treated under the supervision of the first author following obstructed labour and caesarean delivery. The most classical of the cases is a vertex-presenting neonate who was delivered by caesarean section for obstructed labour in a primipara in whom ipsilateral klumpke's palsy and fractures of the clavicle and humerus were confirmed. Literature review did not consider emergency caesarean delivery as one of the predisposing factors for such birth injuries. This case series, in addition to presenting emergency caesarean section as a predisposing factor for birth injuries, offers to suggest a manoeuvre that may reduce severity and rate of birth injuries in caesarean section for obstructed labour in our environment where obstructed labour is still rife.


A Sargassum fluitans Borgesen Ethanol Extract Exhibits a Hepatoprotective Effect In Vivo in Acute and Chronic Liver Damage Models.
One of the leading causes of death worldwide, cirrhosis, is a liver condition characterized by chronic necrosis, inflammation, and fibrosis. Hepatoprotective compounds, such as antioxidants, can prevent fibrosis. Macroalgae (seaweed) contain high amounts of antioxidant compounds and are plentiful; indeed, species such as Sargassum fluitans Borgesen (Phaeophyceae) carpet many beaches in the Caribbean Basin. An in vivo assay was done evaluating the possible hepatoprotective effect of a Sargassum fluitans ethanol extract. Two murine liver damage models were employed: acetaminophen (APAP) in Balb/c mice to induce acute damage; carbon tetrachloride (CCl4) in Wistar rats to induce chronic damage. Serum liver enzyme levels and relative liver weight were measured, and histopathological and immunohistochemical analyses of liver tissue sections were done. Both APAP and CCl4 significantly raised serum enzyme marker enzymes. Administration of 50 mg/kg S. Fluitans ethanol extract reduced this APAP- and CCl4-induced elevation to normal levels. This effect was corroborated by the extract's inhibition of inflammation and fibrosis in liver tissue observed in the histopathological analysis. The analyzed S. fluitans ethanol extract exhibited an in vivo hepatoprotective effect in acute and chronic liver injury models.


[Compliance of asylum seekers with an expanded border health screening program in the Basel-Stadt canton 1992-1993].
In 1992, the Swiss Public Health Office introduced an expanded tuberculosis screening program for refugees. In addition to routine chest X-rays, it includes tuberculosis skin testing and prophylactic treatment with isoniazid of skin test positive individuals. In addition, a vaccine program has been established which, besides routine hepatitis B vaccination of anti-HBc negative individuals, includes vaccination of all refugees against tetanus, diphtheria, polio, measles, mumps and rubella. The two-year experience of this expanded program is reported from Canton Basel-Stadt, Switzerland. During the two-year period (1992 to 1993), 289 adults and 53 children were screened. In 3.1% (n = 9) of 289 refugees who were examined by X-ray, smear positive tuberculosis was found. These 9 cases contributed 12% of all tuberculosis cases identified in Canton Basel-Stadt during the observation period. In 4.4% of all refugees prophylactic treatment with isoniazid was initiated, but 7 of the 15 cases (46.6%) did not complete the prophylaxis. In contrast, compliance with the vaccine program was better and complete vaccination was achieved in 90% of all refugees. The prevalence of anti-HBc antibodies was 28.7% and highest among refugees from Turkey (48.6%) and Africa (34.2%). X-ray screening for tuberculosis in high risk populations such as refugees is effective. However, compliance with 6 months' prophylactic treatment with isoniazid for skin test positives was only moderate.


Stimulation of the human CTP:phosphoethanolamine cytidylyltransferase gene by early growth response protein 1.
Change in phosphoethanolamine pool size in tumor tissues is an important indicator of tumor prognosis and drug therapy efficacy. Phosphoethanolamine is the substrate of the regulatory enzyme CTP:phosphoethanolamine cytidylyltransferase (ECT) in the de novo biosynthesis of phosphatidylethanolamine (PE). Metabolic labeling with [14C]ethanolamine revealed a reduced ECT activity in MCF-7 breast cancer cells, which led to an accumulation of phosphoethanolamine and a decrease in PE synthesis in comparison with MCF-10A mammary epithelial cells. The enhanced ECT activity in MCF-10A cells was due to significantly elevated CTP:phosphoethanolamine cytidylyltransferase gene (PCYT2) expression, at the level of promoter activity, mRNA, and protein content. The early growth response protein 1 (EGR1) could account for most of the elevated ECT activity in MCF-10A cells relative to MCF-7 cells, as evidenced by promoter-luciferase reporter assays, gel-shift analyses, and by alterations in the EGR1 gene expression. In MCF-7 cells, EGR1 is present at lower levels and the basal PCYT2 promoter activity is maintained by proximal CAAT and GC regions and by elevated nuclear NFkappaB activity. Together, these data demonstrate that EGR1 is an important transcriptional stimulator of the human PCYT2 and that conditions that modify EGR1 also affect the function of ECT and consequently PE synthesis.


Long non-coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability.
Long non-coding RNAs (lncRNAs), a recently characterized class of non-coding RNAs, have been shown to have important regulatory roles and are de-regulated in a variety of tumors. However, the contributions of lncRNAs to gastric carcinoma and their functional mechanisms remain largely unknown. In this study, we found that lncRNA gastric carcinoma high expressed transcript 1 (lncRNA-GHET1) was up-regulated in gastric carcinoma. The over-expression of this lncRNA correlates with tumor size, tumor invasion and poor survival. Gain-of-function and loss-of-function analyses demonstrated that GHET1 over-expression promotes the proliferation of gastric carcinoma cells in vitro and in vivo. Knockdown of GHET1 inhibits the proliferation of gastric carcinoma cells. RNA pull-down and immunoprecipitation assays confirmed that GHET1 physically associates with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) and enhances the physical interaction between c-Myc mRNA and IGF2BP1, consequently increasing the stability of c-Myc mRNA and expression. The expression of GHET1 and c-Myc is strongly correlated in gastric carcinoma tissues. Depletion of c-Myc abolishes the effects of GHET1 on proliferation of gastric carcinoma cells. Taken together, these findings indicate that GHET1 plays a pivotal role in gastric carcinoma cell proliferation via increasing c-Myc mRNA stability and expression, which suggests potential use of GHET1 for the prognosis and treatment of gastric carcinoma.


Nutritional consequences of inflammatory bowel disease on growth.
This review summarizes much of the current information concerning the problem of growth failure in children and adolescents with inflammatory bowel disease. Growth impairment is discussed as a dynamic process and ways of recognizing and monitoring subtle changes in growth velocity are presented. Factors which contribute to growth delay are described, with special attention to prolonged insufficient nutrient intake. Studies using different methods of nutritional intervention to reverse growth failure are presented as a guide to the management of this challenging group of patients.


cDNA sequence and in vitro folding of GsMTx4, a specific peptide inhibitor of mechanosensitive channels.
The peptide GsMTx4 from the tarantula venom (Grammostola spatulata) inhibits mechanosensitive ion channels. In this work, we report the cDNA sequence encoding GsMTx4. The gene is translated as a precursor protein of 80 amino acids. The first 21 amino acids are a predicted signal sequence and the C-terminal residues are a signal for amidation. An arginine residue adjacent to the N-terminal glycine of GsMTx4 is the cleavage site for release. The resulting peptide is 34 amino acids in length with a C-terminal phenylalanine and not a serine-alanine previously identified [J. Gen. Physiol. 115 (2000) 583]. We chemically synthesized this peptide and folded it in 0.1 M Tris, pH 7.9 with oxidized/reduced glutathione (1/10). Properties of the synthetic peptide were identical to the wild type for high performance liquid chromatography (HPLC), mass spectrometry, CD, and NMR. We also cloned GsMTx4 in a thioredoxin fusion protein system containing six histidines. Nickel affinity columns allowed rapid purification and folding occurred in conditions described above with 0.5 M guanidiniumHCl present. Thrombin cleavage liberated GsMTx4 with three extra amino acids at the N-terminus. The retention time in HPLC analysis and the CD spectrum was similar to wild type. Both the synthetic and cloned peptides were active in the patch clamp assay.


Measurement of the differential cross section and charge asymmetry for inclusive [Formula: see text] production at [Formula: see text] TeV.
The differential cross section and charge asymmetry for inclusive [Formula: see text] production at [Formula: see text] are measured as a function of muon pseudorapidity. The data sample corresponds to an integrated luminosity of 18.8[Formula: see text] recorded with the CMS detector at the LHC. These results provide important constraints on the parton distribution functions of the proton in the range of the Bjorken scaling variable x from [Formula: see text] to [Formula: see text].


Does the z-score value of the abdominal aorta predict recoarctation in an infant?
We evaluated left ventricular dimensions and aortic arch z-scores in infants who underwent balloon angioplasty (BAP) or surgery for coarctation of aorta (CoA). We searched for risk factors predicting recoarctation. Between 2007-2011, 27 male and 17 female infants (mean age 2.93 ± 4.78 months, range 2 days-24 months) with CoA were evaluated. Left ventricular dimensions, systolic functions, mitral and aortic annuli, transverse aortic arch, isthmus, coarctation site, and diaphragmatic aorta measurements were done and z-scores were determined before intervention. Six patients underwent primary operation, 38 patients had BAP (86.4%). Associated cardiac pathologies in operated patients were double outlet right ventricle (n = 2), atrioventricular septal defect (n = 1), Ebstein's anomaly (n = 1), arch hypoplasia (n = 2). Twelve patients (27.2%) had simple coarctation. Ventricular septal defect was the most frequent associated cardiac pathology (n = 20, 45.4%). The patients were followed for 10.22 ± 8.21 months. Among 33 primary successful BAP's, 14 had recoarctation (42%). Eleven patients were primarily operated (including 5 with unsuccessful BAP), two had recoarctation (18%). Abdominal and transverse aorta values and z-scores were significantly lower in the recoarctation group (7.15 ± 2.12 mm and 6.07 ± 1.86 mm respectively in the "no-recoarctation group"; vs. 5.53 ± 0.75 mm and 4.94 ± 1.53 mm in the "recoarctation group" P <.05). Abdominal aorta z-score of 0.42 was 88.9% sensitive and 53.8% specific to predict recoarctation (area under ROC curve: 0.618-0.902, P <.05). Although BAP for native coarctation is still a controversial treatment option due to frequent restenosis rates, abdominal aorta z-score of 0.42 could correctly eliminate recoarctation in 89% of these cases. This cutoff value might help us choose patients for primary BAP and decrease the recoarctation rate after BAP.


Challenges and complexity of functionality evaluation of flavan-3-ol derivatives.
Flavan-3-ol derivatives are common plant-derived bioactive compounds. In particular, (-)-epigallocatechin-3-O-gallate shows various moderate biological activities without severe toxicity, and its health-promoting effects have been widely studied because it is a main ingredient in green tea and is commercially available at low cost. Although various biologically active flavan-3-ol derivatives are present as minor constituents in plants as well as in green tea, their biological activities have yet to be revealed, mainly due to their relative unavailability. Here, I outline the major factors contributing to the complexity of functionality studies of flavan-3-ol derivatives, including proanthocyanidins and oligomeric flavan-3-ols. I emphasize the importance of conducting structure-activity relationship studies using synthesized flavan-3-ol derivatives that are difficult to obtain from plant extracts in pure form to overcome this challenge. Further discovery of these minor constituents showing strong biological activities is expected to produce useful information for the development of functional health foods.


Lyme neuroborreliosis in the rhesus monkey.
Although there are several animal models of Lyme disease, only the rhesus monkey model exhibits all of the key manifestations of the disease. After infection with Borrelia burgdorferi, rhesus monkeys develop signs of early localized, early disseminated, and chronic Lyme disease. Specific features include erythema migrans, uveitis, myocarditis, arthritis, and disease of the peripheral and central nervous system. One of the unique features of the rhesus monkey model is the development of Lyme neuroborreliosis. Peripheral nervous system (PNS) involvement is usually in the form of a mononeuropathy multiplex with primarily axonal-loss features. Evidence of central nervous system (CNS) disease has included CSF pleocytosis, meningeal inflammation, spinal cord lesions, and polymerase chain reaction (PCR) data consistent with chronic CNS infection. The pathogenesis of Lyme neuroborreliosis is not well understood, but it is likely to involve complex interactions between B. burgdorferi and host immune mechanisms.


Taxonomic revisions within Embiotocidae (Teleostei, Perciformes) based on molecular phylogenetics.
Embiotocidae, a unique family within the Perciformes that has evolved a complex viviparous natural history, has lacked full resolution and strong support in several interspecific relationships until recently. Here we propose three taxonomic revisions within embiotocid surfperches based on recent molecular phylogenetic analyses that robustly resolve all interspecific relationship in the Eastern Pacific species: Hypsurus caryi (Agassiz, 1853) resurrected to its original name Embiotoca caryi Agassiz, 1853, Rhacochilus vacca (Girard, 1855) shifted into the genus Phanerodon Girard, 1854, and Hyperprosopon anale Agassiz, 1861 separated into the available genus Hypocritichthys Gill, 1862. The proposed changes would leave three previously paraphyletic groups monophyletic (Embiotoca, Hyperprosopon, and Phanerodon) and would maintain the current number of genera at 13.


Risk factors for proximal junctional kyphosis in a multicenter study of Lenke type 5 and 6 adolescent idiopathic scoliosis patients.
In Lenke type 5 and 6 curves, a major thoracolumbar or lumbar curve, the rates of PJK are reported as high as 50%. The purpose of this study was to confirm the rate of PJK, investigate possible risk factors, and evaluate surgical complications and the long-term effects of PJK on patient outcomes. A retrospective review of multicenter data identified 192 with patients with 2 year and 94 with 5-year follow-up. Included patients had a Lenke type 5 or 6 curve and underwent a selective thoracolumbar or lumbar curve fusion. All radiographs preoperatively and postoperatively (1 year, 2 years, and 5 years) were evaluated. Demographic and radiographic data was analyzed as risk factors for PJK using a multi-variate regression. Outcomes scores and complications were compared between groups. 17 patients (8.9%) developed radiographic PJK; 1 at 1 year, 7 at 2 years, and another 9 at 5 years. All 17 patients had an upper instrumented vertebra (UIV) within 3 levels or less caudal of the thoracic kyphosis apex (the most horizontal vertebra on the sagittal); no patient with a UIV 4 or more levels from the thoracic apex (n = 96) developed PJK (X2 = 13.03, p < 0.001). In addition, PJA > 8° was found to significantly increase the risk of PJK (p = 0.039). SRS scores were significantly worse for PJK patients at 5 years in the self-image and function (p < 0.01). In Lenke 5/6 curves, no patient with a UIV 4 or more levels caudal to the thoracic kyphosis apex had PJK up to 5 years postoperatively. PJA greater than 8° was identified as a risk factor for PJK. Patients with radiographic PJK had worse SRS scores 5 years postoperatively.


Human Contrast Acuity Variability.
Army vision standards have varied little from Aviation's nominal birth. On the basis of classic Snellen acuity, we simply cannot predict threshold skill levels of any one individual(s). A growing number of Army Flight Surgeons, clinicians, and vision scientists have argued for the inclusion of contrast acuity metrics within flight physical standards. Previous monitoring of operational contact lens utility in 223 Apache pilots, visual acuity data were gathered under two conditions: high illuminance; low illuminance combined with low contrast. Spectacle, contact lens, and aging influences were evaluated. The high-contrast Snellen acuities clustered at 20/15 and 20/20. Low-contrast acuities stretched from 20/25 to 20/125. LogMAR analysis highlighted statistical significance between the two acuity sets (p < 0.001) to an unanticipated data spread. The known underlying mechanisms possibly related to this effect are poorly documented; all such variables collectively explain <30% of the known variation in low-illuminance vision. Some pilots possessed the capacity to resolve 20/25 lettering under obfuscating conditions; others were adversely influenced by those same conditions. Snellen acuity involves target recognition; contrast acuity detects threshold differences; both aspects can be important. Prescreening under both vision assessment conditions will help identify and select superior vision performers. The validity and predictability of documenting this effect is targeted within planned future research efforts.


Determination of gate-on and -off timing in respiration-gated radiotherapy.
The purpose of this study was to develop an efficient method of determining gate-on and -off timing in respiration-gated radiotherapy. Gate-on and -off timing in a breathing cycle were defined as the respiratory signal level for the start of irradiation (Ls) in the expiration phase and that for the end of irradiation (Le) in the inspiration phase, respectively. Thirty subjects participated in this study. The diaphragm was used as the tracking target, and time-dependent changes in the position of the target were measured together with those in the respiratory signal level. For each subject, the following maps were created by varying the combination of Ls and Le: absolute target displacement (ATD) map, relative target displacement (RTD) map, and gate-on duty cycle (GDC) map. By classifying respiratory signal waveforms, three respiratory types were derived (A: the length of end-expiration level >40% of a breathing cycle, B: the length of end-expiration level <or=40% and that of end-inspiration level >20% of a breathing cycle, and C: the length of end-expiration level <or=40% and that of end-inspiration level <or=20% of a breathing cycle). For each respiratory type, average RTD and GDC maps were created. We presented an algorithm to obtain the optimal Ls and Le using the RTD (or ATD) and GDC maps, and this algorithm was verified by demonstrating that, in determining Ls and Le for a subject, the average RTD and GDC maps corresponding to the subject's respiratory type could be used effectively.


An assessment of the novel antihistamine BW 825C in the treatment of chronic idiopathic urticaria. A placebo-controlled study.
20 patients with a diagnosis of chronic idiopathic urticaria were entered into a double-blind placebo-controlled cross-over study. All patients completed the trial and during the assessment period they were treated with placebo, BW 825C (4 mg) and BW 825C (8 mg) according to a fully randomised and balanced treatment plan. Both doses of BW 825C were found to be highly effective and significantly better than placebo in controlling signs and symptoms of urticaria. Few adverse reactions were reported and in this small group of patients there was no significant difference from placebo in reports of drowsiness or any other side-effects.


Threshold dose of liver tumor promoting effect of β-naphthoflavone in rats.
To determine the threshold dose of β-Naphthoflavone (BNF) that induces hepatocellular tumor promoting effects, reactive oxygen species (ROS) generation and thiobarbituric acid-reactive substance (TBARS) formation, and drug-metabolizing enzymes that protect against ROS generation, two-stage liver carcinogenesis model was used. Partial hepatectomized rats (n = 11 to 12) were fed diets containing 0, 0.03, 0.06, 0.125 or 0.25% BNF for 6 weeks after an intraperitoneal injection of N-diethylnitrosamine (DEN) to initiate hepatocarcinogenesis. Histopathologically, glutathione S-transferase placental form (GST-P)-positive foci significantly increased in rats given 0.25% BNF. No marked changes in ROS production and TBARS contents were observed between the BNF treated and DEN alone groups. Real-time RT-PCR showed that the expression of Cyp1a1, Cyp1a2, Cyp1b1 and Nqo1 significantly increased in the groups given 0.03% BNF or more, but Ugt1a6, Akr7a3 and Gstm1 significantly increased in the groups given 0.125% BNF or more. Gpx2 and Yc2 significantly increased in the groups given 0.06% BNF or more and 0.25% BNF, respectively. Inflammation-related genes such as Ccl2, Mmp12, Serpine1 and Cox-2 significantly increased in the 0.25% BNF group. In immunohistochemistry, the number of cyclooxygenase-2 (COX-2)-positive cells increased in rats given 0.25% BNF. These results suggest that 0.25% BNF is the threshold dose for liver tumor promotion, and the fact that inflammation-related genes and COX-2 protein increased in the 0.25% BNF group strongly suggests that inflammation is involved in the liver tumor promoting effect of BNF in rats.


The effect of lead on immune and viral interferon production.
Female BDF1 mice were exposed to lead acetate in the drinking water at concentrations ranging form 0 to 1000 micrograms/mL lead for three weeks. The mice tolerated these levels of lead exposure without exhibiting signs of clinical toxicity. Weight gains were not affected by lead exposure. The production of viral interferon induced by the oral administration of tilorone was not altered by lead exposure. The T-lymphocyte mitogens concanavalin A, phytohemagglutinin and staphylococcal enterotoxin A induced immune interferon to varying degrees, with concanavalin A and staphylococcal enterotoxin A exhibiting the most potent induction capabilities. The production of immune interferon induced by T-lymphocyte mitogens was not suppressed by lead exposure.


Y-SNP Haplogroup Hierarchy Finder: a web tool for Y-SNP haplogroup assignment.
The application of massively parallel sequencing (MPS) data from whole genomes has allowed very many more Y-SNP loci to be genotyped simultaneously than previously possible. Although this greatly increases the resolution of Y-SNP haplogroups to link common ancestors, it remains a great challenge to provide a phylogenetic tree to clearly display the relationship of varying haplogroups. Y-SNP Haplogroup Hierarchy Finder is a web tool to generate hierarchical haplogroups based on Y-SNP data with the derived allele at the terminal of a haplogroup tree. The input data can include that from whole-genome sequencing. Confidence in assignment using Y-SNP Haplogroup Hierarchy Finder was demonstrated using Y-SNP genotypes of 1233 samples, sourced from the 1000 genomes project phase 3, used to generate the expected haplogroups. The outcome includes 2 reports: a 'Haplogroup Report' lists mutation types from the submitted Y-SNPs and their corresponding haplogroups, and a 'Haplogroup Hierarchy Report' lists all possible hierarchical haplogroups and ranks the three most supported haplogroups. Each layer of the descending haplogroups from one step to the next is shown and the supporting numbers of Y-SNPs are also included in these reports. All haplogroups that exhibited a clear relationship between the ancestral through to the derived SNPs can be clustered into a hierarchy of haplogroups. The assigned 1233 haplogroups were compared with 2 other software programs designed to assemble haplogroups, which resulted in one where there were many differences and the other one where there was only minor difference. The advantage of this web-based tool is that it provides an easy way to assign Y-SNP haplogroup based on the visualized hierarchical pattern.


Sex hormones and the thymus in relation to thymocyte proliferation and maturation.
This paper reviews the mechanism of sex hormone actions on the thymus, presenting mainly our data obtained at the cellular and molecular levels. First, data supporting the "genomic" action via the nuclear sex hormone receptor complexes are as follows: 1) sex hormone receptors and the thymic factor (thymulin) are co-localized in thymic epithelial cells, but not in T cells; 2) production/expression of thymic factors (thymulin, thymosin alpha 1) are remarkably inhibited by sex hormone treatment; 3) sex hormones cause changes in T cell subpopulations in the thymus; and 4) sex hormones strongly influence the development of thymus tumors in spontaneous thymoma BUF/Mna rats through their receptor within the tumor cells. Secondly, data indicating the "non-genomic" action of sex hormones via a membrane signal-generating mechanism are as follows: 1) the proliferation/maturation of thymic epithelial cells is mediated through protein kinase C activity introduced by sex hormones; 2) sex hormones directly influence DNA synthesis and cdc2 kinase (cell cycle-promoting factor) activity.


Reconstituting middle turbinate anatomy after pituitary surgery.
Pituitary surgery is now increasingly performed as a joint procedure combining the expertise of a neurosurgeon and an otorhinolaryngologist. As endoscopic sinus surgery is currently one of the commonest surgical procedures performed by ear, nose and throat surgeons, familiarity of sphenoid sinus anatomy over several years of training becomes second nature to those with this interest. The endoscopic approach to the pituitary fossa via the sphenoid sinus allows a minimally invasive approach, thus reducing postsurgical morbidity and duration of hospital stay. The surgical approach involves lateralization of the middle turbinate followed by burring away of the face of the sphenoid air cell. Those without experience of sinus surgery may neglect to reconstitute the position of the middle turbinate at completion of surgery. Further mucosal contraction, scarring and synechiae formation will cause spontaneous lateralization of the middle turbinate during the healing period. This may predispose the patient to chronic sinusitis as a consequence of occlusion at the critical osteomeatal complex. The most satisfactory postoperative results are achieved by maintaining patency of the middle meatus. This will allow sinus aeration and drainage, and the delivery of topical medication should this be required. This paper describes a conchopexy suture placed at completion of pituitary fossa surgery. A carefully placed suture will maintain a widely patent middle meatus during the phase of postoperative healing, thus reducing the risk of chronic sinusitis.


Novel Drugs Implicated in Pigmented Purpuric Dermatoses.
We describe two cases of cutaneous eruptions of pigmented purpuric dermatoses (PPDs) arising after exposure to medications not previously reported in the literature as causing these reactions. Specifically, two women had biopsy-proven PPDs, one after exposure to an over-the-counter iodine supplement marketed as an extract from "Norwegian kelp," and the other after intraocular injections of pegaptanib, a vascular endothelial growth factor inhibitor. The eruption occurred shortly after beginning the medication and resolved upon discontinuation. This highlights the importance of considering over-the-counter and intraocular medications when assessing cutaneous eruptions that may be medication related, such as PPDs.


Pulse laser deposited nanocrystalline cobalt ferrite thin films.
Cobalt ferrite thin films were pulsed laser deposited on fused quartz substrates at different substrate temperatures and ex-situ annealed at 750 degrees C in air. Grain size of these films was found to be 6-44 nm. Magnetization of these nanocrystalline thin films was found to be dependent on the substrate temperature. Magnetization higher than the cobalt ferrite bulk value was observed in the room temperature deposited film after post deposition annealing at 750 degrees C. This could be explained on the basis of a changed cation distribution in the film caused by quenching during deposition.


Triggering vacuum capillaries for pneumatic pumping and metering liquids in point-of-care immunoassays.
An innovative vacuum capillary pneumatic actuation concept that can be used for point-of-care testing has been investigated. The vacuum glass capillaries are encapsulated within a laminated pouch and incorporated into the fluidic card. Vacuum glass capillaries broken by external force such as finger pressure, generate the pneumatic forces to induce liquid flow in the fluidic system. The sizes of vacuum capillary play a vital role in the pumping and metering functions of the system. The luteinizing hormone (LH) chromatographic immunoassay performances in the fluidic cards show consistency comparable to that obtained by manual micropipetting. The vacuum capillary pneumatic actuation will be applied in other complex handling step bioassays and lab-on-a-chip devices.


Inhibition of cellular protein secretion by poliovirus proteins 2B and 3A.
Poliovirus RNA replication occurs on the surface of membranous vesicles that proliferate throughout the cytoplasm of the infected cell. Since at least some of these vesicles are thought to originate within the secretory pathway of the host cell, we examined the effect of poliovirus infection on protein transport through the secretory pathway. We found that transport of both plasma membrane and secretory proteins was inhibited by poliovirus infection early in the infectious cycle. Transport inhibition did not require viral RNA replication or the inhibition of host cell translation by poliovirus. The viral proteins 2B and 3A were each sufficient to inhibit transport in the absence of viral infection. The intracellular localization of a secreted protein in the presence of 3A with the endoplasmic reticulum suggested that 3A directly blocks transport from the endoplasmic reticulum to the Golgi apparatus.


Cardiac-specific and ligand-inducible target gene expression in transgenic mice.
Conditional transgene expression in the heart is a useful approach to explore the physiological basis of the cardiac phenotype. The present study describes the development of a binary transgenic system in which transgene expression in the mouse heart can be turned on/off by administration/withdrawal of an exogenous compound. We generated a transgenic line (alphaMHC-Glp 65) harboring a mifepristone (RU486)-controlled chimeric transcription factor (Glp 65) under the regulatory control of the cardiac-specific alpha-myosin heavy chain (alphaMHC) promoter. In the presence of RU486, Glp 65 expressed in the heart is able to bind to a target gene promoter containing four copies of the 17-mer GAL4 binding site, resulting in ligand-inducible transactivation of the target gene. We tested this system by crossing the transgenic mice, alphaMHC-Glp 65, with a transgenic line harboring human growth hormone (hGH) target gene. We observed that expression of hGH could be induced in adults as well as in the embryonic hearts of bigenic mice by RU486. The basal hGH expression was very low and the inducible level in the heart was estimated over 800-fold higher versus the basal level after 4 days of administration of RU486 at 500 microg/kg body weight per day at 2-5 months of age. The level of the transgene returned to the basal level within 7 days after withdrawal of RU486. This system can be used to control cardiac-specific expression of transgene in a time- and dose-dependent manner.


Ambient particulate matter, ozone, and neurologic symptoms in U.S. Gulf states adults.
Research on neurologic effects of air pollution has focused on neurodevelopment or later-life neurodegeneration; other effects throughout adulthood have received less attention. We examined air pollution levels and neurologic symptoms among 21,467 adults in US Gulf Coast states. We assigned exposure using Environmental Protection Agency estimates of daily ambient particulate matter 2.5 (PM2.5) and ozone. Gulf Long-term Follow-up Study participants reported neurologic symptoms at enrollment (2011-2013). We estimated cross-sectional associations between each air pollutant and prevalence of "any" neurologic, central nervous system (CNS), or peripheral nervous system (PNS) symptoms. Ambient PM2.5 was consistently associated with prevalence of neurologic symptoms. The highest quartile of 30-day PM2.5 was associated with any neurologic symptom (prevalence ratio [PR] = 1.16; 95% confidence interval [CI] = 1.09, 1.23) and there were increasing monotonic relationships between 30-day PM2.5 and each symptom category (P-trend ≤ 0.01). Associations with PM2.5 were slightly stronger among nonsmokers and during colder seasons. The highest quartile of 7-day ozone was associated with increased prevalence of PNS symptoms (PR = 1.09; 95% CI = 1.00, 1.19; P-trend = 0.03), but not with other outcomes. Ozone concentrations above regulatory levels were suggestively associated with neurologic symptoms (PR = 1.06; 95% CI = 0.99, 1.14). Mutual adjustment in co-pollutant models suggests that PM2.5 is more relevant than ozone in relation to prevalence of neurologic symptoms.


Characteristics of Panfacial Fractures in the Elderly: Etiology, Fracture Patterns, Concomitant Injuries, and Postoperative Complication Risk.
Facial trauma, including panfacial fractures caused by high-impact trauma, is increasingly frequent in elderly patients. The purpose of this study was to investigate the effects of the particularly serious and challenging panfacial fractures on elderly adults. The authors retrospectively reviewed the files of all patients who were operated for panfacial fractures at our institution from December 2006 to December 2018. The definition of a panfacial fracture was a concurrent fracture in 2 or more locations, including nasoethmoid, frontozygomaticomaxillary, Le Fort I and II, and mandibular fractures. The authors reviewed in-hospital medical records to collect data on the medical history, cause of injury, fracture location, accompanying surgery, postoperative complications, duration of hospital stay, laboratory results, radiographic studies, and computed tomography scans. A total of 454 patients were enrolled. Among them, 57 (13%) were <19 years old, 304 (72%) were 19 to 60 years old, and 62 (15%) were >60 years old. Compared with younger patients, those aged older than 60 years were more likely to have underlying diseases including diabetes, hypertension, and antiplatelet, and showed a significantly higher proportion of brain hemorrhage, internal organ contusion, surgical site infection, and hematoma after surgery. The authors have analyzed the largest number of panfacial fractures in an elderly population so far. The pattern of injury and sequelae of severe facial trauma in elderly patients may be more serious, and the postoperative course more prone to complications than in younger patients. Therefore, more delicate treatment and a high degree of suspicion are needed.


Oxidative Stress and Cardiovascular Complications in Chronic Kidney Disease, the Impact of Anaemia.
Patients with chronic kidney disease (CKD) have significant cardiovascular morbidity and mortality as a result of risk factors such as left ventricular hypertrophy (LVH), oxidative stress, and inflammation. The presence of anaemia in CKD further increases the risk of LVH and oxidative stress, thereby magnifying the deleterious consequence in uraemic cardiomyopathy (UCM), and aggravating progression to failure and increasing the risk of sudden cardiac death. This short review highlights the specific cardio-renal oxidative stress in CKD and provides an understanding of the pathophysiology and impact of uraemic toxins, inflammation, and anaemia on oxidative stress.


GNOSIS: guidelines for neuro-oncology: standards for investigational studies-reporting of phase 1 and phase 2 clinical trials.
We present guidelines to standardize the reporting of phase 1 and phase 2 neuro-oncology trials. The guidelines are also intended to assist with accurate interpretation of results from these trials, to facilitate the peer-review process, and to expedite the publication of important and accurate manuscripts. Our guidelines are summarized in a checklist format that can be used as a framework from which to construct a phase 1 or 2 clinical trial.


Compulsory notification at skilled nursing facilities.
Notifiable diseases (NDs) encompass conditions of high clinical severity and/or contagious. Being closed communities, long-term care facilities (LTCF) are places that deserve attention on their own, but one might be left wondering: what is the reality of NDs at Brazilian LTCFs? To determine the prevalence and type of NDs at large LTCF. Active search for NDs conducted by the Hospital Infection Control Committee (HICC) in 459 beds. Due to the low turnover of patients, the monthly list kept by the HICC on NDs was analyzed. Data were grouped into males and females, and into elderly (age ≥ 60 years) and non-elderly (age ≤ 59 years). 31 diseases in 29 patients (6.9% of all inpatients - 19 males and 10 females): 23 cases of hepatitis C, five of hepatitis B, two of human immunodeficiency virus (HIV), and one case of renal tuberculosis. One patient with hepatitis B and another HIV-positive also had hepatitis C. There was no statistical significance in the comparison of the two groups with the total number of other institutionalized patients - by age and gender - for total number of NDs and cases of hepatitis C (p>0.05). Chronic NDs and those requiring chronic treatment observed in this study suggest that Brazil needs more studies to define the dynamics of these diseases at LTCFs.


Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats.
Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P < 0.05) than that of the contralateral TA muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P < 0.05). As a result of these coordinated changes, the DNA-to-protein ratio of the hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.


[LEFT VENTRICULAR MYOCARDIAL REMODELING IN PATIENTS WITH ARTERIAL HYPERTENSION ASSOCIATED WITH ACID-DEPENDENT DISEASES].
Comorbid pathologies remain a serious challenge for researchers and practitioners. According to different authors, from 11.6 to 50% therapeutic patients suffer arterial hypertension (AH) concomitant with acid-dependent diseases (ADD). Peculiarities of such combination are poorly known. The aim of this work was to evaluate the structural and functional status of left ventricular (LV) myocardium in patients with AH and ADD. It included 127 patients of mean age 42.44:2.78 years. Control group consisted of 25 age-matched patients with isolated AH. The ultrasound study of structural and functional parameters of LV myocardium was followed by the analysis of various types of its remodeling. It was shown that patients with isolated AH are characterized by significantly higher structural and functional parameters of LV myocardium remodeling compared with the patients having AH and concomitant ADD. It suggests a specific type of remodeling in the former group that can be used as a predictor of higher cardiovascular risk in these patients.


Anatomical Considerations for Gallbladder Sonography: A Cross-Sectional Study of CT Imaging by BMI Group.
Objective The purpose of this study was to establish an association between the body mass index (BMI) group and anatomical gallbladder position to aid novices in gallbladder sonography. Methods This was a cross-sectional, Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-compliant study that examined the association between gender and the BMI group with quantitative gallbladder position measurements from computed tomography (CT) scans. Results A quantitative analysis determined that the gallbladder was positioned relatively higher and oriented more horizontally within the abdomen of individuals with obese BMI than those with normal BMI (p < 0.001), irrespective of gender. Additionally, the gallbladder was more obstructed by the rib cage in individuals with obese BMI than those with normal BMI (p = 0.007 for females and p < 0.001 for males). The gallbladder was significantly more horizontal in overweight males than females (p < 0.001) and more obstructed by the rib cage in obese males than females (p = 0.013). Conclusion This association provides ultrasound novices knowledge for a more targeted approach in localizing the gallbladder and evidence to recommend an intercostal approach for gallbladder sonography in obese patients.


Mobile Apps as Audience-Centered Health Communication Platforms.
Health communication campaigns often suffer from the shortcomings of a limited budget and limited reach, resulting in a limited impact. This paper suggests a shift of these campaigns to audience-centered communication platforms-particularly, apps on mobile phones. By using a common platform, multiple interventions and campaigns can combine resources and increase user engagement, resulting in a larger impact on health behavior. Given the widespread use of mobile phones, mobile apps can be an effective and efficient tool to provide health interventions. One such platform is Father's Playbook, a mobile app designed to encourage men to be more involved during their partner's pregnancy. Health campaigns and interventions looking to reach expectant fathers can use Father's Playbook as a vehicle for their messages.


Nonretentive solid-phase extraction of phosphorylated peptides from complex peptide mixtures for detection by matrix-assisted laser desorption/ionization mass spectrometry.
Widespread interest in protein phosphorylation has led to the development of a variety of methods for the analysis of phosphoproteomes of different types of organisms. Many applications involve pretreatment of the sample before mass spectrometric measurement and can crucially improve the detection efficiency of individual phosphopeptides. Despite intense research efforts, separation and extraction of phosphorylated peptides, especially multiphosphorylated ones, remain challenging tasks and need to be further explored and expanded with unconventional approaches. In this study, we describe the application of nonretentive solid-phase extraction (SPE) to the analysis of phosphopeptides using the highly cross-linked polystyrene-divinylbenzene material Strata-X. This study indicates that the procedure allows for the preferential extraction of phosphopeptides regardless of their extent of phosphorylation. The Strata-X material primarily retains nonphosphorylated peptides by hydrophobic interaction, whereas the inherent hydrophilicity of phosphorylated peptides leads to their partitioning into the aqueous phase. Phosphopeptides that were rapidly segregated out of tryptic digest mixtures and collected in the early aqueous fractions generated intense signals in mass spectra. The method was developed using SPE Strata-X columns, then suited for detection and sequencing of phosphopeptides by miniaturizing the system to the scale of custom-made microcolumns. This provided fast isolation of phosphopeptides from protein digests along with direct MALDI on-target deposition. The possibility of on-target washing during sample preparation is also presented.


Did Princess Charlotte die of pulmonary embolism?
The cause of death of the Princess Charlotte of Wales in 1817 has been attributed to postpartum haemorrhage. Although an autopsy was performed, pulmonary embolism was not diagnosed because this condition was not recognized until 1846, but the clinical description of her last hours clearly points to pulmonary embolization as the most likely cause of death.


Electrophysiologic monitoring of facial nerve during temporal bone surgery.
Monitoring of peripheral nerves during surgical procedures decreases trauma to the nerve, which may preserve function. During 1984, electrophysiologic monitoring of the facial nerve was used during 32 operative procedures in and around the temporal bone. The largest group were for cerebellopontine angle tumors. Clinically, monitoring appeared to be helpful by providing objective evidence of trauma to the facial nerve and a method of demonstrating integrity of the nerve. However, review of this series did not reveal objective evidence of improved facial nerve preservation compared to results in a similar group of patients operated on without monitoring. We think that the monitoring is best done by personnel experienced with the technique.


Mechanical factors in experimental spinal cord injury.
Reliable animal models of spinal cord injury are essential for studying pathological mechanisms and for laboratory testing of experimental treatments. The normal unpredictability of neurological outcome following experimental injury results partly from variations in the mechanics of both apparatus and tissue. Weight drop contusion models have been used extensively, and often effectively within a given study, but direct comparison between studies is usually made impossible by differences in the experimental parameters. The most important differences include the weight-height combination, the mass of the interface between weight and cord, and the support given to the cord from below. There are also important dimensional and physiological variables intrinsic to the biological material, which are usually ignored. A morphometric study of contusion injuries of the cat thoracic cord indicates that the major determinant of axon disruption is the extrusion of tissue from the impact site, due to viscoelastic distortion of the parenchyma within the meningeal tube. Direct compression and shear do not appear to play an important role in this kind of injury, where a brief compression of the cord occurs at an initial velocity of about 1.5 m/sec. The pathology produced by slower compression rates may vary, but the pattern of central necrosis, expected to be produced by extrusion, is common to most types of experimental lesion and to a large proportion of human injuries.


Cardiopressor effects of short-term treatment with cabergoline in L-dopa stable responder parkinsonian patients: relevance of postprandial hypotension.
The hemodynamic and biochemical effects of cabergoline, a new ergoline derivative with selective, potent, and long-lasting dopamine (DA) agonistic properties, were evaluated in 19 parkinsonian patients, all previously identified as stable responders to levodopa plus L-Dopa decarboxylase inhibitor. The purpose of the study was to find markers capable of predicting the development of cardiopressor side effects during DA-agonistic therapy. Blood pressure (BP), heart rate, and plasma catecholamine responses to a standard meal and a tilt table test were evaluated before and during cabergoline therapy. Cabergoline (1.0 mg/day x os) in this open study significantly reduced the BP response to standing exclusively in the subgroup of patients who exhibited marked postprandial hypotension in baseline conditions. The patients subsequently experienced a partial recovery at day 7 of treatment. This finding indicates that postprandial hypotension is an early marker of autonomic failure in patients with Parkinson's disease (PD) and suggests the usefulness of evaluating cardiopressor response to a standard meal before starting new DA-agonist therapy in PD.


Sequence and expression of two regulated transcription units during Drosophila melanogaster development: Deb-A and Deb-B.
Two transcription units, Deb-A and Deb-B (developmental embryonic), are present in a recombinant bacteriophage clone containing a DNA insert from Drosophila melanogaster. The insert maps cytologically to chromosome 2R at 48EF. Sequence analysis of the open reading frames indicates that both are putative membrane proteins with similar hydropathy profiles. The expression of the encoded poly(A)+ RNAs is regulated during oocyte embryonic and larval development. The 600 base Deb-A RNA is present in oocytes and increases in abundance until 15 h of embryogenesis. Its abundance level drops dramatically between 15 and 19 h and is modulated at a low level in the three larval instars and pupae. The 525 base Deb-B RNA is present in oocytes at a 10-fold lower level than the Deb-A transcript. Its abundance increases until a maximum level is reached at 9-12 h. After this time the transcript is undetectable on Northern transfers. Both RNAs are present in greater than 95% polyadenylated form in the cytoplasm. Deb-B RNA is found on polysomes in proportions similar to the bulk of poly(A)+ RNA populations. Deb-A RNA, on the other hand is mostly nonpolysomal during embryogenesis. The RNAs from both Deb-A and Deb-B are found uniformly distributed throughout the embryo during development.


Fatty liver and its fibrous changes found in simple obesity of children.
Of 299 obese children who visited our obesity clinics, 36 were found to have elevated levels of serum transaminases by routine laboratory examination. Liver biopsy was carried out in 11 children. Based on the criteria of Adler and Schaffner (1979), the biopsy specimens were studied histologically. As a result, fatty liver (Group I) was observed in three patients, fatty hepatitis (Group II) in two, fatty fibrosis (Group III) in five, and fatty cirrhosis (Group IV) in one. The duration of obesity, but not its degree, was considered to be related to the extent of fibrosis. Accordingly, we concluded that the fatty liver of simple obesity in children may progress to liver cirrhosis and that childhood obesity should be treated as early as possible.


Global knowledge and attitudes towards mpox (monkeypox) among healthcare workers: a systematic review and meta-analysis.
The recent increase in human mpox (monkeypox) cases emphasizes the importance of early detection, prompt response and preventive management to control the spread of the disease. Healthcare workers (HCWs) play a crucial role in this process. This study aimed to determine the global knowledge and attitudes towards mpox among HCWs. This study searched multiple databases, including Google Scholar, Scopus, PubMed/MEDLINE, Science Direct, Web of Science, Embase, Springer and ProQuest, to locate various publications. The search was limited to English-language articles published between May 2022 (when the increase in mpox incidence was reported) and August 2023. The Joanna Briggs Institute (JBI) quality checklist was utilized to evaluate the quality of the included studies. Data were obtained using a Microsoft Excel spreadsheet and subsequently scrutinized through STATA software, version 14. The heterogeneity of the studies was assessed using the inverse variance and Cochran Q statistics based on the I2 test statistics. The Dersimonian and Liard random effects models were used where heterogeneity existed. Subgroup analysis and univariate and multivariable metaregression techniques were used to examine the causes of heterogeneity. A total of 22 studies, including 22 studies for knowledge (27 731 HCWs) and 6 studies for attitudes (14 388 HCWs), were included in the meta-analysis. The pooled estimates for good knowledge and positive attitudes among HCWs were 26.0% (95% confidence interval [CI] 17.8 to 34.2) and 34.6% (95% CI 19.0 to 50.2), respectively. Moreover, the knowledge was 34.8% (95% CI 24.1 to 45.6) among HCWs with <5 y of work experience and 41.6% (95% CI 33.1 to 50) among individuals possessing >5 y of professional background. Good knowledge of HCWs is at a low level. It is suggested that training sessions should be tailored towards younger HCWs with less healthcare experience. Additionally, it is essential to identify strategies on how to improve the knowledge and attitudes for better practice about the disease in HCWs worldwide.


Role of toll-like receptors in myocardial infarction.
Toll-like receptors (TLRs) play a pivotal role in both innate and adaptive immunity, and TLRs recognize invading pathogens through molecular pattern recognition, and ultimately lead to the activation of transcription factors and inflammatory responses. Myocardial infarction leads to changes in the remodeling of the left ventricle of the heart, and the degree and type of remodeling provides important diagnostic information for the therapeutic management of ischemic heart disease. Innate immune takes a most important role in myocardial infarction. There are some studies reporting that TLRs play an important role in the myocardial infarction. The literatures were searched extensively and this review was performed to review the role of TLRs in myocardial infarction.


Methods for sampling and determining chlorotrifluoroethylene (CTFE) in air.
Two new methods for sampling and analysis of chlorotrifluoroethylene (CTFE) exceeding 1 ppm (4.8 mg/m3) time-weighted-average concentrations were developed and compared. The first involved collecting air in bags followed by gas chromatographic (GC) analysis of sample aliquots using flame ionization detection (FID). Using specified procedural details, analyte recoveries of greater than 90% were demonstrated even for samples stored for five days. A second method used charcoal to adsorb and concentrate analyte from 10-L air samples. Toluene was used to desorb CTFE which was quantitated by GC/FID. Desorption efficiencies were greater than 90%. Analyte recoveries of greater than 90% were obtained from charcoal tubes which had been used to sample air containing 10 ppm of CTFE and were stored for two weeks at 4 degrees C. Recoveries from five field spikes (3 to 20 ppm) averaged 94%. Using dry air containing 800 ppm CTFE, no significant breakthrough of a 400 mg sorbent bed was observed. After comparing the advantages and disadvantages of each method, the charcoal procedure was recommended.


The distribution of income is worse than you think: Including pollution impacts into measures of income inequality.
This paper calculates the distribution of an adjusted measure of income that deducts damages due to exposure to air pollution from reported market income in the United States from 2011 to 2014. The Gini coefficient for this measure of adjusted income is 0.682 in 2011, as compared to 0.482 for market income. By 2014, we estimate that the Gini for adjusted income fell to 0.646, while the market income Gini did not appreciably change. The inclusion of air pollution damage acts like a regressive tax: with air pollution, the bottom 20% of households lose roughly 10% of the share of income, while the top 20% of households gain 10%. We find that, unlike the case for market income, New England is not the most unequal division with respect to adjusted income. Further, the difference between adjusted income for white and Hispanics is smaller than expected. However, the gap in augmented income between whites and African-Americans is widening.


Pivotal role of phosphodiesterase 10A in the integration of dopamine signals in mice striatal D1 and D2 medium-sized spiny neurones.
Dopamine in the striatum plays a crucial role in reward processes and action selection. Dopamine signals are transduced by D1 and D2 dopamine receptors which trigger mirror effects through the cAMP/PKA signalling cascade in D1 and D2 medium-sized spiny neurons (MSNs). Phosphodiesterases (PDEs), which determine the profile of cAMP signals, are highly expressed in MSNs, but their respective roles in dopamine signal integration remain poorly understood. We used genetically encoded FRET biosensors to monitor at the single cell level the functional contribution of PDE2A, PDE4 and PDE10A in the changes of the cAMP/PKA response to transient and continuous dopamine in mouse striatal brain slices. We found that PDE2A, PDE4 and PDE10A operate on the moderate to high cAMP levels elicited by D1 or A2A receptor stimulation. In contrast, only PDE10A is able to reduce cAMP down to baseline in both type of neurones, leading to the dephosphorylation of PKA substrates. In both MSN types, PDE10A inhibition blunts the responsiveness to dopamine, whereas PDE2A or PDE4 inhibition reinforces dopamine action.


HPV 6-associated HSIL/Squamous Carcinoma in the Anogenital Tract.
Human papillomavirus (HPV) type 6 is historically classified as low-risk HPV type and associates with low-grade squamous intraepithelial lesions of the anogenital tract. Rare squamous carcinomas have been reported in association with these HPV types but the mechanism(s) behind this carcinogenic sequence have been unclear. We report 4 cases of low risk anogenital HPV infections-3 cervical (immature low-grade squamous intraepithelial lesion with metaplastic phenotype) and one anal (exophytic condyloma) lesion-that manifested with high-grade squamous intraepithelial lesion/squamous cell carcinoma. Two were associated with invasion one of which metastasized to a regional node. Two cases exhibited strong p53 positivity in the high-grade squamous intraepithelial lesion/squamous cell carcinoma component analogous to that seen in HPV-negative differentiated intraepithelial lesions of the external genitalia. This series of cases adds to the literature on low risk HPV-associated cervical squamous carcinomas. It underscores the similarities between the baseline cyto-morphology and benign mimics (low-grade squamous intraepithelial lesions), the subtle cytologic and immunohistochemical (MIB1) features heralding biologic aggressiveness, and in some potential pathways (p53) not usually involved in HPV-related anogenital neoplasia.


Progress in Nurturing Human Well-Being.
Substantial evidence in the behavioral and social sciences has accrued in support of numerous intervention programs and policies bearing on improving the lives of children and families. To this end, Clinical Child and Family Psychology Review features a special journal issue on "Evolving Toward a More Nurturing Society." The field has achieved numerous advances regarding how to create and promote nurturing environments that foster successful development and prevent psychological and behavioral problems in children and youth. Such advances cut across multiple strategies (e.g., programs and interventions, practices, and public policies), settings (e.g., family, school including preschool and K-12, service sectors, community), domains (e.g., behavioral health, parenting, cognitive and academic functioning, nutrition, physical activity, obesity, safety, and many other domains), and developmental periods of childhood. The special journal issue showcases a sampling of strategies and domains relevant to producing optimal conditions of nurturance for children and families.


[Clinicopathological and molecular genetic characteristics of adult IDH wild-type diffuse gliomas].
Objective: To analyze the clinicopathological and molecular features and prognostic implications of adult isocitrate dehydrogenase wild type (IDH-wt) diffuse gliomas. Methods: A total of 87 cases of adult IDH-wt diffuse gliomas from 2016 to 2020 in Xuanwu Hospital of Capital Medical University were retrospectively collected. The clinicopathological characteristics and prognosis were analyzed. Molecular characteristics were also analyzed using Sanger sequencing and next generation sequencing. Results: There were 53 males and 34 females, aged from 19 to 78 years (mean 53 years). Histopathologically, there were 63 (72.4%) glioblastomas, 16 (18.4%) anaplastic astrocytomas, six (6.9%) diffuse astrocytomas, and one (1.1%) each of anaplastic oligodendrocytoma, and anaplastic oligodendroglioma. Common molecular genetic changes in IDH-wt gliomas included TERT promoter mutation which was found in 60 cases (69.0%); MGMT promoter methylation in 43 cases (49.4%); EGFR mutation in 38 cases (43.7%); PTEN mutation in 35 cases (40.2%) and TP53 mutation in 32 cases (36.8%). In addition, PDGFRA mutation was detected in 17 cases (19.5%), CDK4 amplification in 15 cases (17.2%) and MDM2 amplification in 11 cases (12.6%). In IDH-wt diffuse gliomas, there was no significant difference in the overall survival between TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4, MDM2 mutations and the wild-type, since these gene mutations could co-occur in any case (P>0.05). Also there was no significant difference in the overall survival between the WHO grade Ⅱ/Ⅲ gliomas and glioblastoma patients with these gene mutations (P>0.05). Conclusions: TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4 and MDM2 gene mutations are common molecular genetic changes in adult IDH-wt gliomas, and are associated with poor prognosis. It is suggested that these genes are potentially useful for predicting the prognosis and should be tested in adult IDH-wt gliomas.


Aberrant proliferation of lumen-forming cells in stratified epithelium of porokeratosis skin.
The present investigation was based on the postulate, first proposed by Reed and Leone in 1970, that porokeratosis lesions represent clonal growth of epidermal cells. Comparative studies using immunocytochemical staining, epidermal cell culture, and non-equilibrium pH gradient (NEpHG) gel electrophoresis analysis of the keratins extracted were carried out on five patients with various types of porokeratosis. Positive type IV collagen staining on the stratum corneum was found in lesional skin specimens of all patients, but not in normal controls. A search for connections between type IV collagen in the basement membrane of epidermis and the skin surface disclosed infrequent intra-epidermal streaking of type IV collagen and one positively stained trans-epidermal acrosyringium. Positive intra-epidermal laminin staining in porokeratosis lesions confirmed the trans-epidermal passage of basement-membrane materials. Epidermal cells cultured from lesional skin showed low plating efficiency, and all colonies exhibited intracytoplasmic vacuole formation and excessive top cell shedding. NEpHG gel electrophoresis of keratins extracted showed that lesional profiles not only contained keratins normally present in glabrous skin, but also possibly K9 and some additional proteins. K9 had been immunolocalized to periductal cells in previous studies. Our findings, taken together, strongly suggest that porokeratosis epidermis consists of epithelial cells with lumen-forming ability.


Lipid abnormalities and changes in plasma proteins in glomerular diseases and chronic renal failure.
Lipid abnormalities are almost a constant feature of kidney disease. However, the contribution of deranged lipid metabolism to the increased incidence of cardiovascular disease among renal patients has not been definitely established. Conversely, the role of lipid abnormalities in the progression of renal disease has gained considerable experimental support. Both dietary and pharmacologic interventions, which reduce circulating lipid levels, have been proven to decrease the incidence of glomerulosclerosis in various animal models. Whether similar results can be achieved in renal patients is, at present, unknown. If the new lipid-lowering drugs prove useful in preventing the progression of both glomerulosclerosis and atherosclerosis, a major advance in the therapy for renal patients will be achieved.


Cyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies.
Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperazine ([(18)F]MPPF) for binding to hydroxytryptamine(1A) (5-HT(1A)) receptors. Those increases were quantified in rat brain with in vivo microPET and ex vivo tissue studies. Each Sprague-Dawley rat (n = 4) received a baseline [(18)F]MPPF microPET scan followed by second scan 2-3 weeks later that included cyclosporine pretreatment (50 mg/kg, i.p.). Maximum a posteriori reconstructed images and volumetric ROIs were used to generate dynamic radioactivity concentration measurements for hippocampus, striatum, and cerebellum, with simplified reference tissue method (SRTM) analysis. Western blots were used to semiquantify P-gp regional distribution in brain. MicroPET studies showed that hippocampus uptake of [(18)F]MPPF was increased after cyclosporine; ex vivo studies showed similar increases in hippocampus and frontal cortex at 30 min, and for heart and kidney at 2.5 and 5 min, without concomitant increases in [(18)F]MPPF plasma concentration. P-gp content in cerebellum was twofold higher than in hippocampus or frontal cortex. These studies confirm and extend prior ex vivo results (J. Passchier, et al., Eur J Pharmacol, 2000) that showed [(18)F]MPPF as a substrate for P-gp. Our microPET results showed that P-gp modulation of [(18)F]MPPF binding to 5-HT(1A) receptors can be imaged in rat hippocampus. The heterogeneous brain distribution of P-gp appeared to invalidate the use of cerebellum as a nonspecific reference region for SRTM modeling. Regional quantitation of P-gp may be necessary for accurate PET assessment of 5-HT(1A) receptor density when based on tracer uptake sensitive to P-gp modulation.


fMRI bold signal analysis using a novel nonparametric statistical method.
We present in this article a novel analytical method that enables the application of nonparametric rank-order statistics to fMRI data analysis, since it takes the omnipresent serial correlations (temporal autocorrelations) properly into account. Comparative simulations, using the common General Linear Model and the permutation test, confirm the validity and usefulness of our approach. Our simulations, which are performed with both synthetic and real fMRI data, show that our method requires significantly less computation time than permutation-based methods, while offering the same order of robustness and returning more information about the evoked response when combined with/compared to the results obtained with the common General Lineal Model approach.


Postsplenectomy vaccination guideline adherence: Opportunities for improvement.
Patients undergoing splenectomy for trauma are at life-long risk for rapidly progressive septicemia. The purpose of this study was to investigate long-term patient understanding and follow-up with recommendations regarding their asplenia. Patients undergoing splenectomy for trauma January 2010-December 2014 were analyzed. Medical records were reviewed and telephone follow-up interviews were conducted in October-December 2015. Patients were asked a standard set of questions that included hospitalizations, awareness of infectious risks associated with asplenia, need for revaccination, and vaccines they had received since their index hospitalization. Two hundred forty-four patients underwent splenectomy during the study period. A total of 95 patients (39%) were included in the study. Thirty (32%) had been hospitalized since their trauma admission. Only 46% were aware of the risks for sepsis and the need to revaccinate. Only 7% reported having rapid access to antibiotics. Despite uniform education prior to discharge, most patients undergoing splenectomy for trauma were unaware of the risks for sepsis and did not follow recommended guidelines for risk reduction. Improvements that have direct implications for advanced practice included the need to refer for vaccination, educate regarding infection risks, and facilitate rapid access to antibiotic treatment.


Detection of distinct α-helical rearrangements of cyclobutane pyrimidine dimer photolyase upon substrate binding by Fourier transform infrared spectroscopy.
Photolyases (PHRs) utilize near-ultraviolet (UV)-blue light to specifically repair the major photoproducts (PPs) of UV-induced damaged DNA. The cyclobutane pyrimidine dimer PHR (CPD-PHR) from Escherichia coli binds flavin adenine dinucleotide (FAD) as a cofactor and 5,10-methenyltetrahydrofolate as a light-harvesting pigment and specifically repairs CPD lesions. By comparison, a second photolyase known as (6-4) PHR, present in a range of higher organisms, uniquely repairs (6-4) PPs. To understand the repair mechanism and the substrate specificity that distinguish CPD-PHR from (6-4) PHR, we applied Fourier transform infrared (FTIR) spectroscopy to bacterial CPD-PHR in the presence or absence of a well-defined DNA substrate, as we have studied previously for vertebrate (6-4) PHR. PHRs show light-induced reduction of FAD, and photorepair by CPD-PHR involves the transfer of an electron from the photoexcited reduced FAD to the damaged DNA for cleaving the dimers to maintain the DNA's integrity. Here, we measured and analyzed difference FTIR spectra for the photoactivation and DNA photorepair processes of CPD-PHR. We identified light-dependent signals only in the presence of substrate. The signals, presumably arising from a protonated carboxylic acid or the DNA substrate, implicate conformational rearrangements of the protein and substrate during the repair process. Deuterium exchange FTIR measurements of CPD-PHR highlight potential differences in the photoactivation and photorepair mechanisms in comparison to those of (6-4) PHR. Although CPD-PHR and (6-4) PHR appear to exhibit similar overall structures, our studies indicate that distinct conformational rearrangements, especially in the α-helices, are initiated within these enzymes upon binding of their respective DNA substrates.


Regular-Fat Dairy and Human Health: A Synopsis of Symposia Presented in Europe and North America (2014-2015).
In recent history, some dietary recommendations have treated dairy fat as an unnecessary source of calories and saturated fat in the human diet. These assumptions, however, have recently been brought into question by current research on regular fat dairy products and human health. In an effort to disseminate, explore and discuss the state of the science on the relationship between regular fat dairy products and health, symposia were programmed by dairy industry organizations in Europe and North America at The Eurofed Lipids Congress (2014) in France, The Dairy Nutrition Annual Symposium (2014) in Canada, The American Society for Nutrition Annual Meeting held in conjunction with Experimental Biology (2015) in the United States, and The Federation of European Nutrition Societies (2015) in Germany. This synopsis of these symposia describes the complexity of dairy fat and the effects regular-fat dairy foods have on human health. The emerging scientific evidence indicates that the consumption of regular fat dairy foods is not associated with an increased risk of cardiovascular disease and inversely associated with weight gain and the risk of obesity. Dairy foods, including regular-fat milk, cheese and yogurt, can be important components of an overall healthy dietary pattern. Systematic examination of the effects of dietary patterns that include regular-fat milk, cheese and yogurt on human health is warranted.


Untrained acquisition of /s/ in a phonologically disordered child.
The untrained /s/ productions of a phonologically disordered child were followed over a period of several months as she produced /s/ in imitated words and in spontaneous connected speech. For this child, as has been reported in the literature for children acquiring phonology normally, /s/ occurred earliest in the word-final position, appearing in word-initial position only several weeks later. Two word-medial, or intervocalic, contexts were compared: (a) monomorphemic words in which /s/ is word- and morpheme-medial (e.g., lasso); and (b) bimorphemic words in which /s/ is word-medial but morpheme-final (e.g., missing). In this latter group, a grammatical inflection or morpheme was added to a morpheme that ends with /s/. Correct responses to the intervocalic position where /s/ occurred at a morpheme boundary (i.e., in inflected morphemes) occurred earlier and more frequently than responses to single-morpheme intervocalic position. The variability of the child's productions over time is examined and discussed.


Successful Late Treatment of Orbital Infantile Haemangiomas in Two Teenagers with Topical Transcutaneous Timolol Maleate 0.5% Alone.
We previously described the first successful treatment of deep periocular and, subsequently, orbital infantile haemangiomas (IH) with topical transcutaneous timolol maleate 0.5% (TM 0.5%) alone as the first-line treatment in the acute proliferative phase in infancy. It is not known whether orbital IH with persistent proptosis in later years, untreated in infancy, would still respond to TM 0.5% treatment as well. To our best knowledge, we here present the first reports of the successful late treatment of persistent orbital IH with topical timolol maleate 0.5% applied to the skin overlying the orbital IH in two teenagers. Case 1 was an 11-year-old girl with proptosis measuring 4 mm before and 7 mm after Valsalva manoeuvre that diminished to 1 mm after topical treatment. Case 2 was a 10-year-old girl with 2 mm (before) and 4 mm proptosis (after Valsalva) that decreased to 0 mm proptosis with topical treatment. The time to resolution was 19 months (case 1) and 13 months (case 2). The treatment dose was 3 drops of TM 0.5% applied an average of 1.94 (case 1) and two times daily (case 2). In comparison to proptosis, resolution of periorbital swelling required less treatment time. There was no recurrence of either proptosis or periorbital swelling 1 year after stopping treatment in either case. The findings indicate that beta-blockers are effective not just in the proliferative but also in the late involutional phase in older children. No adverse clinical effects were noted throughout treatment in either case. The presence of increased proptosis with a Valsalva manoeuvre predicts a significant persistent vascular compartment in the orbital IH and may thus serve as a simple predictive clinical sign of likely treatment success. We recommend that a trial with this well-tolerated treatment form is considered in persistent cases of orbital IH, especially in the presence of enhanced proptosis with a Valsalva manoeuvre.


Multiple spontaneous cerebrospinal fluid leaks: a rare case report and review of literature.
While a spontaneous cerebrospinal fluid leak (sCSFL) is a rare phenomenon, patients who present with multiple cerebrospinal fluid leaks (mCSFLs) are an even rarer entity. There have been documented cases reported over the last decades, but many with only limited descriptions of each patient. We present a mCSFL patient as a case report and demonstrate the need for future prospective studies to improve further understanding and management of the condition. This is explored through summarizing the literature on mCSFLs to the present time. A 45-year-old obese female presented with a 5-week history of bilateral clear nasal discharge with no previous surgery or trauma. Initially misdiagnosed as allergic rhinitis, nasal discharge was later confirmed positive for beta-2-transferrin and a CT scan revealed multiple bony areas of skull base erosion. The patient underwent image guided endoscopic sinus surgery with multilayer skull base defect repair of three active CSFLs. Three months post-operatively the patient had no evidence of a recurrence. As mCSFL tend to be sporadic and asymptomatic in nature, it is likely they are underreported. Future prospective studies in the area of mCSFLs that take into consideration demographic and geographical information are needed for more accurate interpretation and better recruitment. Additionally, studies need to ensure longer follow-up time due to the underlying chronicity of increased intracranial pressure (ICP) and investigate whether or not a non-active leak site should be repaired or left alone.


The hybrid progress note: semiautomating daily progress notes to achieve high-quality documentation and improve provider efficiency.
Health care institutions are moving toward fully functional electronic medical records (EMRs) that promise improved documentation, safety, and quality of care. However, many hospitals do not yet use electronic documentation. Paper charting, including writing daily progress notes, is time-consuming and error prone. To improve the quality of documentation at their hospital, the authors introduced a highly formatted paper note template (hybrid note) that is prepopulated with data from the EMR. Inclusion of vital signs and active medications improved from 75.5% and 60% to 100% (P < .001), respectively. The use of unapproved abbreviations in the medication list decreased from 13.3% to 0% (P < .001). Prepopulating data enhances provider efficiency. Interviews of key clinician leaders also suggest that the initiative is well accepted and that documentation quality is enhanced. The hybrid progress note improves documentation and provider efficiency, promotes quality care, and initiates the development of the forthcoming electronic progress note.


Unusual presentation of severe dengue: Dengue maculopathy.
Dengue infection is epidemic but ocular complications of dengue are less reported. We report a case of dengueinfected patient with disturbing ocular symptoms. He was admitted for severe dengue. Subsequently, he presented with symptoms of bilateral central scotoma with metamorphosia. Fundus examination revealed cotton wool spots and flame-shaped haemorrhages at the macula, with dull foveal light reflex. He was diagnosed with bilateral dengue maculopathy. The patient was managed conservatively with surveillance. One week later, his eye symptoms improved and were resolved six months later. Early recognition and close monitoring remains the key to successful management and interventions are rarely needed.


[Validity and reliability of Turkish version of St. George's respiratory questionnaire].
The importance of the evaluation of health status in chronic obstructive pulmonary disease (COPD) is recently highlighted in many studies. In this study, we aimed to test the validity and reliability of the Turkish version of St. George Respiratory Questionnaire (SGRQ). The study was conducted in seven centers in Turkey. Three hundred and twenty one COPD patients (40-75 years) were included to the study. Turkish versions of breathlessness, Cough, and Sputum Scale (BCSS), mMRC (Modified Medical Research Council) dyspnea scale, SGRQ, COPD assessment test (CAT) and Short Form Health Survey (SF-36) were carried out to the patients. The statistical analysis of SGRQ was performed by using the coefficient of internal consistency, discriminative analysis for different stages and the correlation with the other scales. The mean age was 62.4 ± 8.9 years and the mean FEV1 was 51.9 ± 19.2% pred. The coefficient of internal consistency (Cronbach alpha) was 0.8815. The correlation between the total score measured initially and that obtained two weeks later was found to be highly significant (r= 0.90, p< 0.0001). According the results of validation of both total score and the components of SGRQ, the correlation between the total score of SGRQ and CAT was 0.782 (p< 0.0001), SGRQ and SF-36 was between -0.481 ile -0.819 (p< 0.0001). The total and component scores were able to discriminate different disease stages and a significant correlation was found to be with pulmonary function tests. SGRQ Turkish version is a reliable and valid assessment tool for COPD patients in clinical practice.


Fermi-Pasta-Ulam-Tsingou recurrence and cascading mechanism for resonant three-wave interactions.
Evolution of resonant three-wave interaction is governed by quadratic nonlinearities. While propagating localized modes and inverse scattering mechanisms have been studied, transient states such as rogue waves and breathers are not fully understood. Modulation instability modes can trigger growth of disturbances and the eventual development of breathers. Here we study computationally the dynamics beyond the first formation of breathers, and demonstrate repeating patterns of breathers as a manifestation of the Fermi-Pasta-Ulam-Tsingou recurrence (FPUT). While nonlinearity governs the actual dynamics, the range of wave numbers for modulation instability remains a useful indicator. Depending on the stability characteristics of the fundamental mode and the higher-order harmonics ("sidebands"), "regular" and "staggered" FPUT patterns can arise. A "cascading mechanism" provides analytical verification, as the fundamental and sideband modes attain the same magnitude at one particular instant, signifying the first occurrence of a breather. A triangular spectrum is also computed, similar to experimental observations of optical pulses. Such spectra can elucidate the spreading of energy among the sidebands and components of the triad resonance. The concept of "effective energy" is examined and the eigenvalues of the inverse scattering mechanism are computed. Both approaches are utilized to correlate with the occurrence of regular or staggered FPUT. These numerical and analytical studies can enhance our understanding of wave interactions in fluid mechanics and optics.


Cathepsin L regulates CD4+ T cell selection independently of its effect on invariant chain: a role in the generation of positively selecting peptide ligands.
CD4+ T cells are positively selected in the thymus on peptides presented in the context of major histocompatibility complex class II molecules expressed on cortical thymic epithelial cells. Molecules regulating this peptide presentation play a role in determining the outcome of positive selection. Cathepsin L mediates invariant chain processing in cortical thymic epithelial cells, and animals of the I-A(b) haplotype deficient in this enzyme exhibit impaired CD4+ T cell selection. To determine whether the selection defect is due solely to the block in invariant chain cleavage we analyzed cathepsin L-deficient mice expressing the I-A(q) haplotype which has little dependence upon invariant chain processing for peptide presentation. Our data indicate the cathepsin L defect in CD4+ T cell selection is haplotype independent, and thus imply it is independent of invariant chain degradation. This was confirmed by analysis of I-A(b) mice deficient in both cathepsin L and invariant chain. We show that the defect in positive selection in the cathepsin L-/- thymus is specific for CD4+ T cells that can be selected in a wild-type and provide evidence that the repertoire of T cells selected differs from that in wild-type mice, suggesting cortical thymic epithelial cells in cathepsin L knockout mice express an altered peptide repertoire. Thus, we propose a novel role for cathepsin L in regulating positive selection by generating the major histocompatibility complex class II bound peptide ligands presented by cortical thymic epithelial cells.


The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies.
In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull-brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin "phantom," displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull-brain interface will be valuable in the parameterization and validation of computer models of TBI.


Treatment of occupational cramp with botulinum toxin: diffusion of toxin to adjacent noninjected muscles.
Over a 5-year period, 40 patients, 11 with musician's and 29 with writer's cramp, were treated with botulinum toxin A using a precise injection technique in which the hollow-bore electromyography (EMG) needle was positioned by both standard EMG and by muscle twitch evoked by stimulating current passed through it. Moderate to complete improvement in dystonia occurred in 28 patients (70%) after the first injection and in 34 patients (85%) after the second injection with better outcome in nonmusicians than in musicians. Of note, weakness of uninjected muscles, immediately adjacent to those injected, was found in 25/40 patients (63%). The most common patterns of toxin spread were from flexor digitorum sublimis to profundus, extensor carpi radialis to extensor digitorum communis, and extensor indicis proprius to extensor pollicis brevis. Spread to, and weakness of, adjacent uninjected muscles was a major factor contributing to suboptimal outcome in 6/39 (15%) such patients.


Serious mental illness in Florida nursing homes: need for training.
This study examined how the mental health needs of nursing home (NH) residents with serious mental illness (SMI) are addressed. Data were collected from three sources: interviews with 84 SMI stakeholders; surveys of 206 NH staff members; and focus groups at two psychiatry specialty NHs. Four common themes emerged: placement of older adults with SMI was a significant problem for discharge planners and NH admission coordinators; NH staff reported being uneasy with SMI residents and were concerned over aggressive behavior; staff in NHs with psychiatry specialty units appeared more comfortable serving SMI residents; and SMI training was a consistent recommendation of all SMI stakeholders and NH staff. Implications for training are discussed.


ATP-binding Cassette (ABC) Transport System Solute-binding Protein-guided Identification of Novel d-Altritol and Galactitol Catabolic Pathways in Agrobacterium tumefaciens C58.
Innovations in the discovery of the functions of uncharacterized proteins/enzymes have become increasingly important as advances in sequencing technology flood protein databases with an exponentially growing number of open reading frames. This study documents one such innovation developed by the Enzyme Function Initiative (EFI; U54GM093342), the use of solute-binding proteins for transport systems to identify novel metabolic pathways. In a previous study, this strategy was applied to the tripartite ATP-independent periplasmic transporters. Here, we apply this strategy to the ATP-binding cassette transporters and report the discovery of novel catabolic pathways for d-altritol and galactitol in Agrobacterium tumefaciens C58. These efforts resulted in the description of three novel enzymatic reactions as follows: 1) oxidation of d-altritol to d-tagatose via a dehydrogenase in Pfam family PF00107, a previously unknown reaction; 2) phosphorylation of d-tagatose to d-tagatose 6-phosphate via a kinase in Pfam family PF00294, a previously orphan EC number; and 3) epimerization of d-tagatose 6-phosphate C-4 to d-fructose 6-phosphate via a member of Pfam family PF08013, another previously unknown reaction. The epimerization reaction catalyzed by a member of PF08013 is especially noteworthy, because the functions of members of PF08013 have been unknown. These discoveries were assisted by the following two synergistic bioinformatics web tools made available by the Enzyme Function Initiative: the EFI-Enzyme Similarity Tool and the EFI-Genome Neighborhood Tool.


Telomere attrition and accumulation of senescent cells in cultured human endothelial cells.
The human umbilical vein endothelial cell (HUVEC) is an important model of the human endothelium that is widely used in vascular research. HUVECs and the adult endothelium share many characteristics including progression into senescence as the cells age. Despite this, the shortening of telomeres and its relationship to the progression into senescence are poorly defined in HUVECs. In this study of several HUVEC lines we show notable consistency in their growth curves. There is a steady decline in the growth rate of HUVECs grown continually in culture and we estimate complete cessation of growth after approximately 70 population doublings. The HUVECs lose telomeric DNA at a consistent rate of 90 base pairs/population doubling and show a progressive accumulation of shortened telomeres (below 5 kilobases). This telomeric loss correlates with the accumulation of senescent HUVECs in culture as assessed by staining for beta-galactosidase activity at pH 6. Although the telomere length of a large population of cells is a relatively crude measure, we suggest that in HUVECs a mean telomere length (as measured by terminal restriction fragment length) of 5 kilobases is associated with entry into senescence. These data demonstrate the strong relationship between telomere attrition and cell senescence in HUVECs. They suggest that DNA damage and subsequent telomere attrition are likely to be key mechanisms driving the development of endothelial senescence in the pathogenesis of vascular disease.


Irreducible indirect inguinal hernia containing uterus and bilateral adnexa in a premature female infant: report of an exceptional case and review of the literature.
Indirect inguinal hernia is the most common congenital anomaly in the pediatric age group. About 15-20% of hernias in infant girls contain ovary, sometimes with a Fallopian tube. The presence of the uterus incarcerated with the adnexa is a very unusual occurrence in female infants with normal kariotype and phenotype, being commonly associated with several disorders of sex development. The surgical repair of this form of hernia is more difficult than a common herniorrhaphy because of the adhesions between the organs and the wall of the sac and the risk of damage during their freeing. We present a rare case of irreducible indirect inguinal hernia containing uterus and bilateral adnexa (fallopian tubes and ovaries) in a premature female infant, discussing the etiopathogenesis and the surgical features of this disorder.


Pyridoxine (vitamin B6) neurotoxicity: enhancement by protein-deficient diet.
Large doses of pyridoxine cause injury to the primary sensory neurons in trigeminal and dorsal root ganglia of animals and patients subjected to megavitamin therapy. The increased hazard to subjects with reduced renal excretory function has been explored previously. In the present work, the neurotoxicity of pyridoxine for rats was found to be increased by dietary protein deficiency. A mere 3 or 7 days of pretreatment with either of two protein-deficient diets were sufficient to accelerate and intensify the clinical neurological signs and histological lesions from pyridoxine injections. These results are caused, at least in part, by loss of body weight, decreased protein binding in serum and decreased consumption of water and decreased volume of urine, which reduce the urinary losses of the toxicant. The vitamers related to pyridoxine (pyridoxal, pyridoxamine) and the coenzyme (pyridoxal 5-phosphate) did not cause clinical signs or lesions similar to those produced by pyridoxine even when injected in maximum tolerated doses. Neither a protein-deficient diet nor bilateral nephrectomy changed the results with the vitamers.


Nurses' attitudes regarding the importance of families in pediatric nursing care.
Affective, cognitive and behavioral components affect nurses´ attitudes to include families in the care processes. The purpose of this study was to investigate the attitudes of nurses about the importance of including families in nursing care. Data collection was performed in pediatric and maternal-child unit of a Brazilian university hospital. A sample of 50 nurses completed the Portuguese version of the instrument Families'Importance in Nursing Care-Nurses' Attitudes (FINC-NA). The results indicated that nurses have supportive attitudes regarding families participation in nursing care. Attitudes of lower support for involving families in nursing care were found among nurses with older age, more time in the profession and who had no previous contact with contents related to Family Nursing. The application of the instrument in other contexts of assistance may help to illuminate important aspects of the challenges to implementing a family-centered approach in clinical practice.


High Mobility Group Protein B1 (HMGB1) and Interleukin-1β as Prognostic Biomarkers of Epilepsy in Children.
The present study examined whether serum biomarkers can predict the prognosis of childhood epilepsy, including seizure frequency, electroencephalographic (EEG) changes, and cognitive impairment. We measured serum concentrations of high mobility group protein B1 (HMGB1), interleukin-1β (IL-1β), S100 calcium-binding protein B (S-100B), glial fibrillary acidic protein (GFAP), and α1-antichymotrypsin (AACT) in 180 children with new-onset epilepsy and 40 healthy children. Cognitive evaluations were performed 18 months after the initial seizure episodes at diagnosis (ie, baseline visit). The relationship between serum biomarkers and epilepsy prognosis was investigated using Pearson correlation coefficients, logistic regression analyses, and receiver operating characteristic curves. Sixty-seven patients had generalized tonic-clonic seizures, 92 had focal motor seizures, and 21 had epileptic spasms. Serum concentrations of HMGB1, IL-1β, S-100B, and GFAP were significantly higher in the epilepsy group within 24 hours of a seizure episode than in the control group. Furthermore, HMGB1 and IL-1β were significant predictors of epilepsy prognosis. Receiver operating characteristic curve analysis revealed that HMGB1 could more accurately predict seizure frequency than IL-1β; when the serum concentration of HMGB1 was >9.625 ng/mL, there was 80.6% sensitivity and 92.5% specificity for predicting seizure frequency reduction. In conclusion, HMGB1 and IL-1β have a predictive value for epilepsy prognosis in children.


Regional specialization and market integration: agroecosystem energy transitions in Upper Austria.
We investigate agroecosystem energy flows in two Upper Austrian regions, the lowland region Sankt Florian and the prealpine region Grünburg, at five time points between 1830 and 2000. Energetic agroecosystem productivity (energy contents of crops, livestock products, and wood per unit area) is compared to different types of energy inputs, i.e., external inputs from society (labor, industrial inputs, and external biomass inputs) and biomass reused from the local agroecosystem (feed, litter, and seeds). Energy transfers between different compartments of the agroecosystem (agricultural land, forest, and livestock) are also quantified. This allows for delineating an agroecosystem energy transition: In the first stage of this transition, i.e., in the nineteenth century, agroecosystem productivity was low (final produce ranged between 14 and 27 GJ/ha/yr), and local biomass reused made up 97% of total energy inputs in both regions (25-61 GJ/ha/yr). In this period, agroecosystem productivity increase was achieved primarily through more recycling of energy flows within the agroecosystems. In the second stage of the agroecosystem energy transition, i.e., after World War II, external energy inputs increased by factors 2.5 (Sankt Florian) and 5.0 (Grünburg), partly replacing local energy transfers. Final produce per area increased by factors 6.1 (Sankt Florian) and 2.9 (Grünburg). The difference in the resulting energy returns on investment (EROI) owes to regional specialization on cropping versus livestock rearing and to increasing market integration. Our results suggest that sustainable land-use intensification may benefit from some regional specialization harnessing local production potentials based on a mix of local and external inputs.