Pluronic F127-g-poly(acrylic acid) copolymers as in situ gelling vehicle for ophthalmic drug delivery system.
To prolong the precorneal resident time and improve ocular bioavailability of the drug, Pluronic F127-g-poly(acrylic acid) copolymers were studied as in situ gelling vehicle for ophthalmic drug delivery system. The rheological properties and in vitro drug release of Pluronic-g-PAA copolymer gels were investigated. The rheogram and in vitro drug release studies indicated that the drug release rates decreased as acrylic acid/Pluronic molar ratio and copolymer solution concentration increased. But the drug concentration had no obvious effect on drug release. The release rates of the drug from such copolymer gels were mainly dependent on the gel dissolution. In vivo resident experiments showed the drug resident time and the total resident amount in rabbit's conjunctiveal sac increased by 5.0 and 2.6 folds for in situ gel, compared with eye drops. The decreased loss angle at body temperature and prolonged precorneal resident time also indicated that the copolymer gels had bioadhesive properties. These in vivo experimental results, along with the rheological properties and in vitro drug release studies, demonstrated that in situ gels containing Pluronic-g-PAA copolymer may significantly prolong the drug resident time and thus improve bioavailability. Pluronic-g-PAA copolymer can be a promising in situ gelling vehicle for ophthalmic drug delivery system.


Crouch gait or flexed-knee gait in cerebral palsy: Is there a difference? A systematic review.
Crouch or flexed-knee gait is one of the most common pathological gait patterns in cerebral palsy (CP). Differences exist in definitions used; the degree of knee flexion, inclusion of hip or ankle position, and timing in the gait cycle. This ambiguity may be responsible for variations in prevalence rates and difficulty comparing data across studies. What are the kinematic parameters used to define crouch or flexed-knee gait in CP gait? A secondary aim was to examine the quality of data reporting, focusing on the sample characteristics, inclusion/exclusion criteria and the choice of limb included for analysis. Articles included in this review reported on a specified cohort of adults or children with crouch or flexed-knee gait assessed with 3-dimensional gait analysis. A customised data extraction and quality assessment table was designed specific to the research question. The majority (75 %) of included studies used the term crouch gait. Where the pattern was defined, 80 % of crouch papers and 94 % of flexed-knee gait papers based this solely on knee position. Kinematic parameters were clearly defined when they provided objective values of knee flexion, supported this with rationale and provided a reference point in the gait cycle. Only 22 % of crouch papers and 19 % of flexed-knee gait papers provided this information. The majority of studies (67 % crouch; 90 % flexed-knee) specified which limb(s) were included for analysis with the majority including both limbs. Objective values of knee flexion ranged from 8 o to 30 o. This review highlights that crouch and flexed knee are synonymous and ambiguity exists in the kinematic definition making it difficult to make compare data amongst study cohorts. Future research should provide detailed definitions including the threshold value of knee flexion, how it was derived, the timing in the gait cycle and the limb(s) included in analysis.


Erythropoietin therapy improves graft patency with no increased incidence of thrombosis or thrombophlebitis.
Recombinant human erythropoietin (rHuEPO) for the treatment of severe anemia in patients with end-stage renal disease (ESRD) is suggested to improve rehabilitation and cognitive function. The criticism is the alleged increase in the failure rate of arteriovenous (AV) access grafts and in the incidence of lower-extremity deep venous thrombophlebitis (DVT). This study addressed the longevity of AV grafts and the incidence of DVT. We reviewed 481 consecutive patients with ESRD on dialysis with PTFE access grafts, including 173 consecutive patients who were receiving rHuEPO and 308 who were not. rHuEPO was administered during dialysis titrated against the hematocrit to achieve a level of 33% to 38%. The rHuEPO-ESRD group included 173 patients with a mean age of 58 years, including 54% women; 84% of the grafts were in the upper extremity. In the control group of 308 patients, 57% were women. Diabetes and hypertension were controlled in both groups. Forty-five of 173 rHuEPO patients (26%) experienced graft thrombosis within 1 year. Among 88 episodes of thrombosis, 14 patients experienced multiple episodes. Primary patency was 8.9 months; secondary patency was 11.2 months. In the control population, 95 of 308 patients (31%) experienced graft thrombosis; 27 patients had multiple episodes. Primary patency was 7.8 months and secondary patencywas 9.8 months. The hematocrit improved from a mean of 23% in the control group to 34% in the treated rHuEPO group. Two patients in the control group and one patient receiving rHuEPO experienced DVT in the lower extremity. Primary and secondary AV fistula patency rates were improved by 10% with rHuEPO. rHuEPO did not increase DVT.


Decompressive hemicraniectomy for malignant middle cerebral artery infarction including patients with additional involvement of the anterior and/or posterior cerebral artery territory-outcome analysis and definition of prognostic factors.
According to current evidence, adding decompressive craniectomy (DC) to best medical therapy reduces case fatality rate of malignant middle cerebral artery infarction by 50-75%. There is currently little information available regarding the outcome of subgroups, in particular of patients with extensive infarctions exceeding the territory of the middle cerebral artery. The records of 101 patients with large hemispheric infarctions undergoing DC were retrospectively reviewed. Twenty-seven patients had additional ACA and/or PCA infarcts. Sequential CTs were used for postoperative follow-up. Intracranial pressure (ICP) was monitored via a ventricular catheter in comatose patients. The main aim of treatment was to keep midline shift below 10 mm and ICP below 20 mmHg. If midline shift increased despite preceding DC, repeat surgery with removal of clearly necrotic tissue was considered. For the current analysis, Glasgow Coma Scale (GCS) at 14 days and modified Rankin Scale (mRS) at 3 months were used as outcome parameters. mRS 2 and 3 were defined as "moderate disability", mRS 4 as "severe disability", and mRS 5 and 6 as "poor outcome". These outcome parameters were correlated to age, gender, side, vascular territory, and time delay after stroke, GCS at the time of decompression, maximum ICP, maximum midline shift, and delay of maximum shift. The median age of the 39 female and 62 male patients was 56 years (range, 5-79 years). Overall, 12 patients died in the acute stage (11.9%). Twenty-three (22.8%) patients recovered to moderate disability at 3 months (mRS ≤ 3), 45 (44.6%) to severe disability and 33 (32.6%) suffered a poor outcome (mRS 5 or 6). Twenty patients (19.8%) required additional necrosectomy due to secondary increasing midline shift and/or intracranial hypertension. Patients recovering to moderate disability at 3 months were in the median 10 years younger than patients with less favorable outcome (P < 0.001) and had a higher GCS prior to surgery (P < 0.001). Eleven of the 27 patients with infarctions exceeding the MCA territory needed secondary surgery, indicating a higher necrosectomy rate as for isolated MCA infarction. At 3 months, the distribution of the outcomes in terms of mRS was comparable between the patients suffering from extended infarctions and patients having isolated MCA stroke. Infarctions exceeding the territory of the middle cerebral artery were seen in 30% of the group recovering to moderate disability and thus as frequent as in the groups suffering a less favorable outcome. Intensified postoperative management including possible secondary decompression with necrosectomy may further reduce case fatality rate of patients with large hemispheric infarction. Age above 60 years and severely reduced level of consciousness are the most significant factors heralding unfavorable recovery. Patients suffering infarctions exceeding the MCA territory have a comparable chance of favorable recovery as patients with isolated MCA infarction.


Brief report: patient cognitive status and the identification and management of depression by primary care physicians.
No known study has examined the role of patients' cognitive impairment in the identification and management of depression by primary care physicians. A cross-sectional survey conducted between 2001 and 2003. A sample of 330 adults aged 65 and older from Maryland primary care practices with complete information on cognitive and psychological status, and physician assessments. Primary care physicians were asked to rate cognition and depression on a Likert scale, as well as report management of depression within 6 months of the index visit. Patient interviews included standardized measures of psychological and cognitive status. Older adults identified as depressed by their physician were more likely to be identified as cognitively impaired (unadjusted odds ratio [OR] = 3.71, [95% confidence interval] [CI] [1.93, 7.16]). Older adults identified as cognitively impaired had a tendency to be managed for depression (unadjusted OR = 2.62, 95% CI [0.96, 7.19]). In adjusted multivariate models, these associations remained unchanged. When physicians identified a patient as cognitively impaired, they were more likely to identify the patient as depressed and to report treatment of the depression. An understanding of how physicians think about depression in the context of cognitive impairment is important for designing depression interventions for older adults.


Reduction of absorption of digoxin, phenytoin and aspirin by activated charcoal in man.
The inhibitory effect of activated charcoal 50 g suspended in water on the absorption of digoxin, phenytoin and aspirin was studied in six healthy volunteers in a cross-over manner. The absorption of digoxin and phenytoin were almost completely prevented (about 98%) when activated charcoal was ingested immediately after the drug. The total absorption of aspirin was inhibited by 70%; with clear postponement of absorption and partial release of aspirin from the charcoal in the gut: The peak serum concentration of aspirin was reduced by 95% by charcoal. When activated charcoal was ingested 1 hour after the drugs the inhibition of absorption was considerably less. However, since the absorption of larger doses of the drugs is often slow, the administration of an adequate dose of activated charcoal will be of definite value in the treatment of acute intoxication, even if delayed for several hours.


A review on nanomaterial-based field effect transistor technology for biomarker detection.
Field effect transistor (FET) based sensors have attractive features such as small size, ease of mass production, high versatility and comparably low costs. Over the last decade, many FET type biosensors based on various nanomaterials (e.g. silicon nanowires, graphene, and transition metal dichalcogenides) have been developed to detect various classes of biomolecular targets due to their integration into portable and rapid test systems, both for use in the clinical lab and in point-of-care testing. This review (with 197 refs.) starts with an introduction into the specific features of FET biosensor technology. This is followed by a description of the essentials of methods for immobilization of recognition elements. The next section discusses the progress that has been made in FET based biosensors using semiconducting nanostructures composed of silicon, graphene, metal oxides, and transition metal dichalcogenides. A further section is devoted to microfluidic systems combined with FET biosensors. We then emphasize the biosensing applications of these diagnostic devices for analysis of clinically relevant biomarkers, specifically to sensing of neurotransmitters, metabolites, nucleic acids, proteins, cancer and cardiac biomarkers. Two tables are presented which summarize advances in applications of 1D and 2D nanomaterial-based FETs for biomarker sensing. A concluding section summarizes the current status, addresses current challenges, and gives perspective trends for the field. Graphical abstract Field effect transistor devices based on the use of 1D and 2D semiconductor nanostructures (so called nano-FETs) are making use of materials including silicon nanowires, graphene, zinc oxide, indium oxide, titanium oxide, and molybdenum disulfide that are further modified with recognition elements for biosensing application.


Alterations in in vivo knee joint kinematics following a femoral nerve branch block of the vastus medialis: Implications for patellofemoral pain syndrome.
A potential source of patellofemoral pain, one of the most common problems of the knee, is believed to be altered patellofemoral kinematics due to a force imbalance around the knee. Although no definitive etiology for this imbalance has been found, a weak vastus medialis is considered a primary factor. Therefore, this study's purpose was to determine how the loss of vastus medialis obliquus force alters three-dimensional in vivo knee joint kinematics during a volitional extension task. Eighteen asymptomatic female subjects with no history of knee pain or pathology participated in this IRB approved study. Patellofemoral and tibiofemoral kinematics were derived from velocity data acquired using dynamic cine-phase contrast MRI. The same kinematics were then acquired immediately after administering a motor branch block to the vastus medialis obliquus using 3-5ml of 1% lidocaine. A repeated measures analysis of variance was used to test the null hypothesis that the post- and pre-injection kinematics were no different. The null hypothesis was rejected for patellofemoral lateral shift (P=0.003, max change=1.8mm, standard deviation=1.7mm), tibiofemoral lateral shift (P<0.001, max change=2.1mm, standard deviation=2.9mm), and tibiofemoral external rotation (P<0.001, max change=3.7°, standard deviation=4.4°). The loss of vastus medialis obliquus function produced kinematic changes that mirrored the axial plane kinematics seen in individuals with patellofemoral pain, but could not account for the full extent of these changes. Thus, vastus medialis weakness is likely a major factor in, but not the sole source of, altered patellofemoral kinematics in such individuals.


Central giant cell lesion.
A classic case of central giant cell lesion (CGCL) is presented with emphasis on clinical, radiologic, and histologic features. The differential is discussed including peripheral giant cell granuloma, brown tumor of hyperparathyroidism, and giant cell tumor of bone. The molecular pathway of osteoclastogenesis is selectively reviewed and applied to suggest possible etiologies of the giant cell lesions. CGCL syndromes and treatment are also discussed.


Male predominance of pneumonia and hospitalization in pandemic influenza A (H1N1) 2009 infection.
Pandemic influenza A (H1N1) disproportionately affects different age groups. The purpose of the current study was to describe the age and gender difference of pandemic influenza A (H1N1) cases that lead to pneumonia, hospitalization or ICU admission. Data were collected retrospectively between May 2009 and December 2009. All of the diagnoses of H1N1 were confirmed by real-time reverse-transcription polymerase chain reaction (RT-PCR). During the study period there were 3402 cases of RT-PCR positive H1N1, among which 1812 were males and 1626 were adults (> 15 years of age). 6% (206/3402) of patients required hospitalization, 3.6% (122/3402) had infiltrates on chest radiographs, and 0.70% (24/3402) were admitted to intensive care unit (ICU). The overall fatality rate was 0.1% (4/3402). The rate of hospitalization was sharply increased in patients ≥ 50 years of age especially in male. Out of 122 pneumonia patients, 68.8% (84 patients) were male. Among the patients admitted to the ICU, 70.8% (17 patients) were male. Approximately 1 of 10 H1N1-infected patients admitted to the ICU were ≥ 70 years of age. Among the confirmed cases of H1N1, the ICU admission rate was < 1% and the case fatality rate was 0.1%. Male had a significantly higher rate of pneumonia and hospital admission. These findings should be taken into consideration when developing vaccination and treatment strategies.


Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements.
Maternal perception of reduced fetal movements (RFM) is associated with increased risk of fetal growth restriction (FGR) and stillbirth, mediated by placental insufficiency. The maternally expressed imprinted gene PHLDA2 controls fetal growth, placental development and placental lactogen production in a mouse model. A number of studies have also demonstrated abnormally elevated placental PHLDA2 expression in human growth restricted pregnancies. This study examined whether PHLDA2 was aberrantly expressed in placentas of RFM pregnancies resulting in delivery of an FGR infant and explored a possible relationship between PHLDA2 expression and placental lactogen release from the human placenta. Villous trophoblast samples were obtained from a cohort of women reporting RFM (N = 109) and PHLDA2 gene expression analysed. hPL levels were assayed in the maternal serum (N = 74). Placental PHLDA2 expression was significantly 2.3 fold higher in RFM pregnancies resulting in delivery of an infant with FGR (p < 0.01), with highest levels of PHLDA2 expression in the most severe cases. Placental PHLDA2 expression was associated with maternal serum hPL levels (r = -0.30, p = 0.008, n = 74) although this failed to reach statistical significance in multiple linear regression analysis controlling for birth weight (p = 0.07). These results further highlight a role for placental PHLDA2 in poor perinatal outcomes, specifically FGR associated with RFM. Furthermore, this study suggests a potential relationship between placental PHLDA2 expression and hPL production by the placenta, an association that requires further investigation in a larger cohort.


[Application of percutaneous trans esophageal gastro-tubing (PTEG) in to home care for a patient with terminal stage of gastric cancer].
Since 1994, we devised and have continued to develop a percutaneous trans esophageal gastro-tubing (PTEG) as an effective technique to drain gastrointestinal contents of critical patients suffering from gastric carcinoma. Here we report our satisfactory experience with a critical gastric cancer patient for whom we improved QOL by the application of the PTEG technique. The patient suffered from severe stenosis or obstruction of the digestive tract. This method was found to be effective enough to enable the patient to receive further medical care at home. The patient was a 36-year-old female who had far-advanced, inoperable gastric carcinoma. It was therefore decided to use the PTEG method. The PTEG method was performed using a rupture-free balloon (RFB) catheter to drain the gastrointestinal contents. A reservoir-port for IVH use was embedded to control the patient's nutrition. A morphine hydrochloride suppository was then given for the pain. PTEG was found to be effective, safe and simple; moreover, it is a less-invasive, intestine-maintaining method, which enabled the patient to continue receiving further medical treatment at home.


The mystery of the COVID toes - turning evidence-based medicine on its head.
The recent and rapid emergence of COVID-19 infection has led to a flood of publications describing all aspects of the disease and its presentation. The appearance of chilblain-like lesions, in children and young adults has particularly caught the attention of healthcare professionals with an interest in the foot. With such a novel infection, demand for information is high at a time when evidence is scarce. Consequently, there has been a renaissance in the publication of case studies. This type of research, previously relegated from many mainstream journals, as a low level source of evidence, has permitted the rapid reporting, publication and dissemination of much needed clinical data which can be used as a foundation to inform further research and investigations about a new global infection.


[Computerized management of the Chemico-Clinical and Microbiological Analysis Laboratory of U.S.S.L. No. 47 in Biella].
The current degree of computerisation in the chemical, clinical and microbiological analysis laboratory in USL 47, Biella, is reported with a description of the system employed. Future plans for further computerisation are described with particular reference to the random acceptance of samples and the direct link-up of analysts that will further improve a situation that is already highly satisfactory.


Designer broad-spectrum polyimidazolium antibiotics.
For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a membrane electric potential is required for PIM1 activity. In laboratory evolution experiments with the gram-positive Staphylococcus aureus we obtained PIM1-resistant isolates most of which had menaquinone mutations, and we found that a site-directed menaquinone mutation also conferred PIM1 resistance. In similar experiments with the gram-negative pathogen Pseudomonas aeruginosa, PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.


The fungicide tebuconazole modulates the sodium current of human NaV1.5 channels expressed in HEK293 cells.
The fungicide Tebuconazole is a widely used pesticide in agriculture and may cause cardiotoxicity. In our present investigation the effect of Tebuconazole on the sodium current (INa) of human cardiac sodium channels (NaV1.5) was studied using a heterologous expression system and whole-cell patch-clamp techniques. Tebuconazole reduced the amplitude of the peak INa in a concentration- and voltage-dependent manner. At the holding potential of -120 mV the IC50 was estimated at 204.1 ± 34.3 μM, while at -80 mV the IC50 was 0.3 ± 0.1 μM. The effect of the fungicide is more pronounced at more depolarized potentials, indicating a state-dependent interaction. Tebuconazole caused a negative shift in the half-maximal inactivation voltage and delayed recovery from fast inactivation of INa. Also, it enhanced closed-state inactivation, exhibited use-dependent block in a voltage-dependent manner. Furthermore, Tebuconazole reduced the increase in late sodium current induced by the pyrethroid insecticide β-Cyfluthrin. These results suggest that Tebuconazole can interact with NaV1.5 channels and modulate INa. The observed effects may lead to decreased cardiac excitability through reduced INa availability, which could be a new mechanism of cardiotoxicity to be attributed to the fungicide.


Piloting a classroom-based intervention in after-school programmes: a case study in science migration.
Policy-makers are looking to after-school programs to improve family and child well-being and are searching for evidence-based ways to improve the quality of after-school programs. This study examines whether the Good Behavior Game, a behavior management curriculum designed for school classrooms, can be easily migrated to academically-focused after-school programs. Our results are based on program observations, qualitative interviews, and ratings of implementation fidelity. We provide a description of the structure and activities in these after-school programs, then identify challenges to implementing and evaluating classroom-based interventions in the after-school setting.


Expression of constitutively active Gs alpha-subunits in GH3 pituitary cells stimulates prolactin promoter activity.
Although G protein alpha subunits are known to regulate such cellular functions as growth and enzymatic activity, the ability of these proteins to regulate target gene expression has not yet been directly investigated. Transient expression in GH3 pituitary cells of a target rat prolactin promoter-chloramphenicol acetyltransferase construct, (-1957)PRL-CAT, was increased by coexpressed constitutively active alpha s mutant Q227L-alpha s but not by wild-type alpha s. Thus activated alpha s but not basal state alpha s can stimulate prolactin promoter activity. Q227L-alpha s also stimulated expression of construct (-187)PRL-CAT, showing that only the proximal prolactin promoter region is required for a response to activated alpha s. The promoter specificity of the transcriptional influence of activated alpha s was demonstrated by the inability of either Q227L-alpha s or wild-type alpha s to stimulate expression of control target constructs containing either the rat growth hormone promoter or the thymidine kinase promoter. Previous studies have shown that the most proximal prolactin promoter binding site for the pituitary-specific transcription factor pit-1, site 1P, can act as an independent response element for either thyrotropin-releasing hormone or Ca2+. Two copies of site 1P conferred upon a heterologous metallothionein promoter a response to Q227L-alpha s. This implies that site 1P can also serve as an independent response element for alpha s and suggests that pit-1 may be a mediator of the cellular regulation by alpha s of the prolactin promoter.


Two-stage revision for periprosthetic joint infection in cemented total hip arthroplasty: an increased risk for failure?
The impact of the prior fixation mode on the treatment outcome of chronic periprosthetic joint infection (PJI) of the hip is unclear. Removal of cemented total hip arthroplasty (THA) is particularly challenging and residual cement might be associated with reinfection. This study seeks to compare the results of two-stage revision for PJI in cemented and cementless THA. We reviewed 143 consecutive patients undergoing two-stage revision THA for PJI between 2013 and 2018. Thirty-six patients with a fully cemented (n = 6), hybrid femur (n = 26) or hybrid acetabulum (n = 4) THA (cemented group) were matched 1:2 with a cohort of 72 patients who underwent removal of a cementless THA (cementless group). Groups were matched by sex, age, number of prior surgeries and history of infection treatment. Outcomes included microbiological results, interim re-debridement, reinfection, all-cause revision, and modified Harris hip scores (mHHS). Minimum follow-up was 2 years. Compared with PJI in cementless THA, patients undergoing removal of cemented THA had increasingly severe femoral bone loss (p = 0.004). Patients in the cemented group had an increased risk for positive cultures during second-stage reimplantation (22% compared to 8%, p = 0.043), higher rates of reinfection (22% compared to 7%, p = 0.021) and all-cause revision (31% compared to 14%, p = 0.039) compared to patients undergoing two-stage revision of cementless THA. Periprosthetic femoral fractures were more frequent in the group of patients with prior cementation (p = .004). Mean mHHS had been 37.5 in the cemented group and 39.1 in the cementless group, and these scores improved significantly in both groups (p < 0.01). This study shows that chronic infection in cemented THA might be associated with increased bone loss, higher rates of reinfection and all-cause revision following two-stage revision. This should be useful to clinicians counselling patients with hip PJI and can guide treatment and estimated outcomes.


A LONELY GUY protein of Bordetella pertussis with unique features is related to oxidative stress.
The Gram-negative bacterium B. pertussis is the causative agent of whooping cough. This infection is re-emerging and new features related to Bordetella pathogenesis and microbiology could be relevant to defeat it. Therefore, we focused our attention on BP1253, a predicted exported protein from B. pertussis erroneously classified as lysine decarboxylase. We showed that BP1253 shares the highly conserved motif PGGxGTxxE and the key catalytic amino-acid residues with newly structurally characterized "LONELY GUY" (LOG) proteins. Biochemical studies have confirmed that this protein functions as a cytokinin-activating enzyme since it cleaves the N-glycosidic linkage between the base and the ribose, leading to the formation of free bases, which are the active form of plant hormones called cytokinins. Remarkably, BP1253 selectively binds monophosphate nucleotides such as AMP, GMP and CMP, showing a wider variety in binding capacity compared to other LOGs. Cytokinin production studies performed with B. pertussis have revealed 6-O-methylguanine to be the physiological product of BP1253 in agreement with the higher activity of the enzyme towards GMP. 6-O-methylguanine is likely to be responsible for the increased sensitivity of B. pertussis to oxidative stress. Although BP1253 has a primary sequence resembling the hexameric type-II LOGs, the dimeric state and the presence of specific amino-acids suggests that BP1253 can be classified as a novel type-II LOG. The discovery of a LOG along with its product 6-O-methylguanine in the human pathogen B. pertussis may lead to the discovery of unexplored functions of LOGs, broadening their role beyond plants.


Soluble P-selectin and thrombomodulin-protein C-Protein S pathway in cyanotic congenital heart disease with secondary erythrocytosis.
The aim of the study was to elucidate the roles of soluble P-selectin and thrombomodulin (TM)-protein C-protein S pathway in the pathogenesis of coagulopathy or thrombosis in cyanotic congenital heart disease (CCHD) with secondary erythrocytosis, and their correlations with hematocrit (Hct) value. We studied 27 patients (age: 4.8 to 34.9, median 15) with cyanotic congenital heart disease complicated by secondary erythrocytosis (hematocrit >45%) and 26 patients with acyanotic congenital heart disease (ACHD). Plasma levels of P-selectin, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), thrombomodulin, protein S and activity of protein C were compared between the two groups, and the relationships between these indices and hematocrit value were evaluated. Plasma levels of P-selectin, beta-thromboglobulin and platelet factor 4 [mean (S.D.)] were significantly high in cyanotic patients comparing with acyanotic patients [138 (70.1) vs. 82.5 (28.7), p<0.001; 94.4 (74.0) vs. 54.9 (19.7), p<0.01; 45.4 (48.7) vs. 22.7 (11.9), p=0.020, respectively]. Those of thrombomodulin and protein S and activity of protein C were significantly low in cyanotic patients comparing with acyanotic patients [22.1 (9.69) vs. 34.3 (27.4), p=0.029; 90.7 (15.1) vs. 112 (21.4D), p<0.0001; 88.8 (19.7) vs. 106 (27.7), p<0.01, respectively]. P-selectin (r=0.445, p=0.001) and beta-thromboglobulin (r=0.311, p=0.025) correlated positively, and platelet count (r=-0.418, p=0.0015), protein C (r=-0.322, p=0.018) and protein S (r=-0.368, p=0.007) correlated negatively with hematocrit. Chronic platelet activation and suppression of the thrombomodulin-protein C-protein S pathway might play an important role in coagulopathies identified in patients with erythrocytosis. Hematocrit is an important determinant of such abnormalities.


The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins.
We present the cDNA and amino acid sequences of a cytoskeletal keratin from human epidermis (Mr = 56K) that belongs to one of the two classes of keratins (Type I and Type II) present in all vertebrates. In these two types of keratins the central approximately 300 residue long regions share approximately 30% homology both with one another and with the sequences of other IF proteins. Within this region, all IF proteins are predicted to contain four helical domains demarcated from one another by three regions of beta-turns. The amino and carboxy termini of the Type II keratin are very different from those of microfibrillar keratins and other nonkeratin IF proteins. However, they contain unusual glycine-rich tandem repeats similar to the amino terminus of the Type I keratin. Thus the size heterogeneity among keratins appears to be a result of differences in the length of the terminal ends rather than the structurally conserved central region.


Prevalence of repeat pregnancies and associated factors among teenagers in KwaZulu-Natal, South Africa.
To determine the prevalence of repeat teenage pregnancy and the interval between first/most recent and repeat pregnancies, as well as to evaluate the sexual/reproductive health characteristics of teenagers with repeat pregnancies. A prospective observational study was undertaken at a hospital in KwaZulu-Natal, South Africa, between May and September 2013. Teenagers aged 13-19years who were pregnant, had recently delivered, or had terminated a pregnancy were enrolled. A questionnaire was used to obtain data. Among 341 participants, 281 (82.4%) were seen for a first pregnancy and 60 (17.6%) for a repeat pregnancy. The interval between first/most recent and repeat pregnancies was 24months or lower in 45 (75.0%) of repeat pregnancy participants. Only 58 (17.0%) participants had previously used contraception (54 [93.1%] of whom stopped within 12months) and 28 (8.2%) had used emergency contraception. More participants with repeat pregnancy than with first pregnancy had a positive HIV status (18 [30.0%] vs 26 [9.3%]; P<0.001), more than one sexual partner in the past 12months (21 [35.0%] vs 35 [12.5%]; P<0.001), and a partner at least 5years older (38 [63.3%] vs 128 [45.6%]; P<0.001). High repeat pregnancy rates, low contraception use, and high HIV prevalence among teenagers in South Africa is worrying. Focused interventions targeting teenagers following their first pregnancy need to be urgently implemented.


Interaction of palytoxin with red cells: structure-function studies.
Palytoxin (PTX), a potent toxin isolated from the marine soft coral Palythoa tuberculosa increases the cationic permeability of red cell membranes and inhibits the (Na+,K+)-activated ATPase, effects that are completely reversed by ouabain. It has also been shown to compete with ouabain for a binding site and it has been suggested that it binds to the Na+,K(+)-pump molecule in cells. In a search for analogues of PTX that would bind covalently and could thus be used to identify and characterize the binding site, we have used compounds which differed from PTX at one end or at both ends simultaneously. In order to determine whether these derivatives could be used to replace palytoxin, we tested their potency to induce an increased cation flux, complete with ouabain for its binding site, and inhibit the isolated, purified (Na+,K(+)-ATPase). The results obtained indicate that departures from the PTX structure at one end or at both ends simultaneously substantially decrease the ability of the compounds to increase the cationic permeability of red blood cells and to inhibit the (Na+,K(+)-ATPase). These actions were found to be completely reversed by ouabain, but the analogues are two to three orders of magnitude less potent than PTX in competing with ouabain for its binding site. These results suggest that both ends of the palytoxin molecule participate in the interactions of the toxin with its receptor and that modifications in these regions of the molecule produce significant alterations in its binding and subsequent action on red cell membranes.


Lipoxygenase inhibitors from natural plant sources. Part 2: medicinal plants with inhibitory activity on arachidonate 12-lipoxygenase, 15-lipoxygenase and leukotriene receptor antagonists.
The metabolism of arachidonic acid can be catalysed by either one of two enzyme families: the cyclooxygenases or the lipoxygenases. The lipoxygenase enzymes are classed into several subcategories including 5-, 12- and 15-lipoxygenases. The 5-lipoxygenase pathway has been the major focus of study due to the pronounced pro-inflammatory role of leukotrienes and the approval of 5-lipoxygenase inhibitors and leukotriene receptor antagonists for the clinical treatment of asthma. Although less well characterized, the 12-lipoxygenase as well as the 15-lipoxygenase pathway may also play an important role in the progression of human diseases such as cancer, psoriasis and atherosclerosis. The present review article summarizes the findings from an extensive literature search on plants that have been assessed for 12- and 15-lipoxygenase inhibitory activity as well as for leukotriene receptor antagonistic properties. The results are presented in a tabular format, and a discussion about promising plant species and natural compounds as well as relevant in vitro assays are included in this article.


A case of undifferentiated pleomorphic sarcoma in esophagus after multiple cancer treatments of surgery and chemoradiotherapy.
Undifferentiated pleomorphic sarcoma (UPS) in the esophagus is extremely rare. Therefore, there are few reports of UPS in the esophagus (UPSE). We present a case of UPSE after multiple cancer treatments. A 73-year-old man with a history of cancer treatment, including distal gastrectomy, transverse colectomy, and chemoradiotherapy, was diagnosed with an elevated lesion such as a submucosal tumor in the lower esophagus by regular endoscopy. A boring biopsy was performed, and the specimen showed features of sarcoma. The patient underwent a partial esophagectomy without lymph node dissection. Histopathological findings confirmed an undifferentiated pleomorphic sarcoma. Adjuvant therapy was not administered, and the patient survived without recurrence 1 year after surgery. Currently, complete resection is the only treatment option for UPSE. An optimal treatment strategy using chemotherapy or radiotherapy should be established.


Segregation in a model system for tapped wet disks in two dimensions.
The problem of segregation of mixtures in a column of wet disks subjected to tapping is studied through a simple model that simulates, through a pseudo-dynamics algorithm, the formation of the packing and the successive tapping of it. The particles consist in a binary mixture of disks with two different sizes and the capillary forces are simulated stochastically by a sticking probability between the particles. We have recently shown that arch formation is one of the chief mechanisms determining size segregation in a non-convecting ensemble of dry disks (R.O. Uñac et al., Eur. Phys. J. E 37, 117 (2014)). In the present paper, we focus on the special role that capillary bridges can have on this type of segregation process, besides the proven effect of the presence of arches. We find that humidity between grains can enhance the segregation process in a binary mixture. In particular, for the case of the segregation of an intruder, humidity can promote the rise of the big particle even in cases where the number or the size of the arches would not normally favor the climb.


Effects of different carbon sources on the removal of ciprofloxacin and pollutants by activated sludge: Mechanism and biodegradation.
This research investigated the effects of ciprofloxacin (CIP) (0.5, 5, and 20 mg/L) on SBR systems under different carbon source conditions. Microbial community abundance and structure were determined by quantitative PCR and high-throughput sequencing, respectively. The biodegradation production of CIP and possible degradation mechanism were also studied. Results showed that CIP had adverse effects on the nutrient removal from wastewater. Compared with sodium acetate, glucose could be more effectively used by microorganisms, thus eliminating the negative effects of CIP. Glucose stimulated the microbial abundance and increased the removal rate of CIP by 18%-24%. The mechanism research indicated that Proteobacteria and Acidobacteria had a high tolerance for CIP. With sodium acetate as a carbon source, the abundance of nitrite-oxidizing bacterial communities decreased under CIP, resulting in the accumulation of nitrite and nitrate. Rhodanobacter and Microbacterium played a major role in nitrification and denitrification when using sodium acetate and glucose as carbon sources. Dyella and Microbacterium played positive roles in the degradation process of CIP and eliminated the negative effect of CIP on SBR, which was consistent with the improved removal efficiency of pollutants.


Biventricular assist device placement and immunosuppression as therapy for necrotizing eosinophilic myocarditis.
A previously healthy 47-year-old woman presented reporting nausea, anorexia and light-headedness of 2 weeks' duration, and three episodes of syncope. She also had pleuritic chest pain and rapidly declining cardiac function. The only reported medical history was urinary tract infection and an ankle fracture sustained 5 months before presentation. She was receiving no medication other than estrogen patches for menopause and did not smoke or use illicit drugs. Electrocardiography, chest radiography, echocardiography, measurement of creatinine phosphokinase and troponin T, coronary angiography and endomyocardial biopsy. Necrotizing eosinophilic myocarditis. Biventricular assist device implantation, methylprednisolone, prednisolone and mycophenolate mofetil.


Prioritizing patients for elective surgery: a systematic review.
Priority scoring tools are moot as means for dealing with burgeoning elective surgical waiting lists. There is ongoing development work in New Zealand, Canada and the UK. This emerging international perspective is invaluable in determining the application of these tools and addressing any pitfalls. A systematic electronic literature review was performed. Information was also retrieved using a search of reference lists of all papers included in the review and contact with those who were involved in the development of such criteria. The ethical basis of prioritization differed among priority scoring tools and in a number was not stated. The majority of tools covered criteria for specific procedures. Delphi consensus methods and regression were the predominant methods for -deter-mining -specific criteria. Authors' opinions were the main source of generic criteria. Linear and non-linear models or matrices sum-mated criteria. There is debate over the ethical basis for prioritization. It is a concern that it is not addressed in many studies. The development of generic criteria showed a dearth of consensus approaches that represents a significant gap in our knowledge. On the aspects of summation and weighting, the impact of assumptions on the prioritization of patients may not have been fully explored.


Differences between the endogenous and exogenous DNA sequences of Rous-associated virus-O.
DNA sequences related to the endogenous retrovirus of chickens, Rous-associated virus-O (RAV-O), have been examined using site-specific DNA endonuclease analysis of cellular DNA derived from line 15 and line 100 chickens. Individual embryos from both inbred lines were used as a source of embryonic fibroblasts from which cellular DNA was isolated. Analysis of DNA containing either endogenous RAV-O sequences alone or both endogenous and exogenous RAV-O sequences produced identical patterns of RAV-O-specific DNA fragments after digestion with the endonucleases Eco RI, Hind III, BgI II, Bam HI or Xho I. Similar analysis with endonucleases Hinc II or Hha I, however, produced several RAV-O-specific DNA fragments which were derived from cellular DNA containing both endogenous and exogenous RAV-O sequences but not from cellular DNA containing only endogenous sequences. Although some differences exist between the DNA fragments specific for the endogenous viral sequences of line 15 and line 100 cellular DNA, the DNA fragments specific for the exogenous viral sequences were identical between the two inbred lines. Cleavage of an unintegrated linear RAV-O DNA molecule with Hinc II or Hha I produced DNA fragments identical to those specific for the exogenously acquired RAV-O provirus. This suggests that these characteristic fragments contain no cellular DNA. The potential DNA junction fragments containing both viral and cellular DNA, identified after analysis of DNA that contains both endogenous and exogenous viral sequences, were identical to those observed after analysis of DNA containing only endogenous viral sequences. These results support the following conclusions. First, exogenous proviral sequences are integrated into chicken cell DNA following an interaction between viral and cellular DNA that is specific with respect to the virus and nonspecific with respect to the cell. Second, both the free linear RAV-O DNA intermediate and the newly integrated exogenous provirus contain specific endonuclease sites that are not found in endogenous RAV-O DNA sequences. These results suggest that the formation of the exogenous DNA provirus involves specific alteration of the endogenous viral DNA sequences before reinsertion of the sequences as the exogenous RAV-O DNA provirus. It is possible that newly integrated exogenous RAV-O sequences are characterized by specific differences in the pattern of base methylation and a limited sequence arrangement.


[Dot1 and Set2 Histone Methylases Control the Spontaneous and UV-Induced Mutagenesis Levels in the Saccharomyces cerevisiae Yeasts].
In the Saccharomyces cerevisiae yeasts, the DOT1 gene product provides methylation of lysine 79 (K79) of hi- stone H3 and the SET2 gene product provides the methylation of lysine 36 (K36) of the same histone. We determined that the dot1 and set2 mutants suppress the UV-induced mutagenesis to an equally high degree. The dot1 mutation demonstrated statistically higher sensitivity to the low doses of MMC than the wild type strain. The analysis of the interaction between the dot1 and rad52 mutations revealed a considerable level of spontaneous cell death in the double dot1 rad52 mutant. We observed strong suppression of the gamma-in- duced mutagenesis in the set2 mutant. We determined that the dot1 and set2 mutations decrease the sponta- neous mutagenesis rate in both single and d ouble mutants. The epistatic interaction between the dot1 and set2 mutations and almost similar sensitivity of the corresponding mutants to the different types of DNA damage allow one to conclude that both genes are involved in the control of the same DNA repair pathways, the ho- mologous-recombination-based and the postreplicative DNA repair.


Evaluation of the Risk of Grade 3 Oral and Pharyngeal Dysphagia Using Atlas-Based Method and Multivariate Analyses of Individual Patient Dose Distributions.
The study aimed to apply the atlas of complication incidence (ACI) method to patients receiving radical treatment for head and neck squamous cell carcinomas (HNSCC), to generate constraints based on dose-volume histograms (DVHs), and to identify clinical and dosimetric parameters that predict the risk of grade 3 oral mucositis (g3OM) and pharyngeal dysphagia (g3PD). Oral and pharyngeal mucosal DVHs were generated for 253 patients who received radiation (RT) or chemoradiation (CRT). They were used to produce ACI for g3OM and g3PD. Multivariate analysis (MVA) of the effect of dosimetry, clinical, and patient-related variables was performed using logistic regression and bootstrapping. Receiver operating curve (ROC) analysis was also performed, and the Youden index was used to find volume constraints that discriminated between volumes that predicted for toxicity. We derived statistically significant dose-volume constraints for g3OM over the range v28 to v70. Only 3 statistically significant constraints were derived for g3PD v67, v68, and v69. On MVA, mean dose to the oral mucosa predicted for g3OM and concomitant chemotherapy and mean dose to the inferior constrictor (IC) predicted for g3PD. We have used the ACI method to evaluate incidences of g3OM and g3PD and ROC analysis to generate constraints to predict g3OM and g3PD derived from entire individual patient DVHs. On MVA, the strongest predictors were radiation dose (for g3OM) and concomitant chemotherapy (for g3PD).


Crystallization and preliminary X-ray analysis of family 39 beta-D-xylosidase from Geobacillus stearothermophilus T-6.
beta-D-Xylosidases (EC 188.8.131.52) are hemicellulases that hydrolyze short xylooligosaccharides into single xylose units. In this study, the crystallization and preliminary X-ray analysis of the beta-D-xylosidase (XynB1) from Geobacillus stearothermophilus T-6, a family 39 glycoside hydrolase, are described. XynB1 is a tetrameric protein consisting of four identical subunits of 503 amino acids and with a calculated molecular weight of 58 001 Da. Both the native and the selenomethionine-containing XynB1 were crystallized by the hanging-drop vapour-diffusion method and the crystals were found to belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 92.7, b = 165.7, c = 311.0 A. The native crystals diffracted X-rays to a resolution of 2.1 A.


Cilioretinal artery occlusions following embolization of an artery to an intracranial meningioma.
To report a case in which a prophylactic embolization of a feeder artery to an intarcranial meningioma led to an occlusion of a cilioretinal artery. A case report. A 48-year-old man with an intracranial meningioma presented with ocular pain and visual loss in his right eye following embolization of a feeder artery to the meningioma with polyvinyl alcohol. Ophthalmoscopy 1 month later showed a cilioretinal artery occlusion which was confirmed by fluorescein angiography. His visual acuity was 0.01 in the right eye. The patient was not treated for his ocular symptoms, and his visual acuity 9 month postoperatively improved slightly to 0.1. Our case demonstrated that an occlusion of a retinal artery can be a complication of preoperative embolization of an artery to an intracranial tumor and can lead to severe visual loss.


[From stroke to reperfusion : How can we be faster?]
During the last two decades major efforts in clinical research have led to the establishment of intravenous thrombolysis as the first line acute therapy for ischemic stroke. More recently, data from successful phase III trials have provided proof of the efficiency of mechanical recanalization in acute stroke. The fact that the efficiency of the available therapies can be increased through faster delivery is well documented; however, many institutions dealing with the emergency care of stroke patients lack organizational or infrastructural arrangements to optimize time efficiency in the diagnostic and therapeutic workup. Many of these arrangements have been well evaluated, can be implemented at reasonable costs and have been proven to increase the beneficial effects of thrombolytic therapy.


Effect of enterotoxigenic Escherichia coli heat stable toxin on intestinal lysosomal enzymes in the suckling rat.
A preliminary study on 9 suckling Wistar rats, which received E. coli stable toxin, and on 12 sham-operated controls showed that acid phosphatase, the marker enzyme for lysosome, was significantly increased in the infected group whereas alkaline phosphatase, glucose 6-phosphatase, succinic dehydrogenase, and proteinase, the marker enzymes for brush border, microsome, mitochondria, and the soluble fraction, respectively, remained unaffected. The results suggest that lysosome, the subcellular organelle responsible for intracellular digestion could be modified by E. coli stable toxin. In another set of experiments, where 7 infected suckling rats and 7 sham-operated controls were used, the maximal activities of lysosomal enzymes (released by Triton X-100) were found to be increased in the infected group confirming the results obtained in the preliminary experiment. The values of the ratio between maximal and basal activity (an expression of the degree of retention of enzymes to lysosome) of acid phosphatase and cathepsin D were also significantly increased, indicating that lysosomal membrane may also be stabilized during the infection. The increased activities of lysosomal enzymes and the increased lysosomal membrane stability suggest that intracellular digestion by lysosome could be increased during E. coli stable toxin infection.


Possible parthenogenesis with in vitro fertilization subsequent to ovarian cystic teratomas.
A possible two-cell parthenogenetic embryo aspirated at oocyte retrieval for in vitro fertilization in a woman with a history of bilateral cystic teratomas is reported.


Life-threatening hemorrhage associated with dental implant surgery: a review of the literature.
Life-threatening bleeding may occur during implant placement. The present review was conducted to evaluate the localization, the symptoms, and therapies of life-threatening bleedings associated with implant placement. A literature review including 590 articles was performed in PubMed, Medline, and Cochrane database. Any article reporting on life-threatening bleeding was included which additionally reported on the site of implant surgery. Twenty-seven cases were extracted. In the majority of the cases, bleeding occurred in the anterior interforaminal region. Aside local management stopping the bleedings, most cases required intubation or tracheotomy. Surgeons must be aware of the risk of severe bleedings during implant surgery and should immediately refer patients to a specialized clinic in suspicious or proved cases.


Routine screening of abnormal vaginal flora during pregnancy reduces the odds of preterm birth: a systematic review and meta-analysis.
Prematurity is the leading cause of perinatal mortality and the morbidity among children under the age of 5. The prevalence of preterm birth is between 5 and 18% worldwide. Approximately 30% of preterm deliveries occur as a consequence of fetal or maternal infections. Bacterial vaginosis can increase the risk of ascending infections. However, there is no recommendation or protocol for screening of abnormal vaginal flora. The aim of this systematic review was to investigate the effectiveness of routine screening of abnormal vaginal flora during pregnancy care. We conducted our systematic search in the following databases: MEDLINE via PubMed, Embase, and Cochrane Library. Studies reporting on pregnant women with no symptoms of bacterial vaginosis were included in our analysis if they provided data on the outcome of their pregnancy. The intervention group went through screening of abnormal vaginal flora in addition to routine pregnancy care. Odds ratio (OR) with 95% confidence intervals (CIs) was used as effect size measure. From each study the total number of patients and number of events was extracted in both the intervention and control arm to calculate OR. Altogether we included 13 trials with 143,534 patients. The screening methods were Gram stain, pH screening, pH self-screening and pH screening combined with Gram stain. Regular screening of vaginal flora compared to no screening significantly reduces the odds of preterm birth before 37 weeks (8.98% vs 9.42%; OR 0.71, CI 0.57-0.87), birthweight under 2500 g (6.53% vs 7.24%; OR 0.64, CI 0.50-0.81), preterm birth before 32 weeks (1.35% vs 2.03%; OR 0.51, CI 0.31-0.85) and birthweight under 1000 g (0.86% vs 2.2%; OR 0.33, CI 0.19-0.57). In conclusion, the routine screening of abnormal vaginal flora might prevent preterm birth, extreme preterm birth, low birthweight deliveries and very low birthweight deliveries. Further research is needed to assess the problem more accurately.


[Professional profile of the established oromaxillofacial surgeon].
To qualify for further specialist training as a maxillofacial surgeon, a licence to practice in general medicine as well as a licence to practice in dentistry must be obtained beforehand. In addition to the 4-year course to qualify, maxillofacial surgeons can gain the additional qualification in the field of "plastic surgery" in a further course lasting 3 years. By the end of 1998, there were 698 maxillofacial surgeons in private practices in Germany in comparison to 322 hospital-employed maxillofacial surgeons. Of the work done by maxillofacial surgeons (in private practices), 28% is in contracted hospitals; this percentage is relatively high in comparison to other disciplines in which private specialists use contracted hospitals. It is impossible these days for an individual specialist to completely cover all areas of maxillofacial surgery. In our field, joint practices with an internal specialization will increase the spectrum and quality of treatment in the future and will counteract competition from hospital-employed specialists now that day-case surgery has been introduced in these hospitals. Further training by the individual will remain an indispensable necessity as well as personal involvement by every maxillofacial surgeon in the postgraduate medical training of doctors and dentists. This can only be achieved if the economic situation of specialists is maintained in health-politics.


Bereavement and anxiety.
Bereavement, one of life's most difficult experiences, usually triggers acute grief with yearning and longing for the deceased person that is often intense and preoccupying, along with frequent thoughts and memories of the person who died and relatively little interest in anything unrelated to the deceased loved one. Anxiety is a very common feature of grief that is often neglected. Anxiety is a natural response of the attachment system to separation from a loved one, seen in adults as well as children. Confrontation with one's own death is also a natural trigger of anxiety, though we usually protect ourselves from mortality salience using terror management strategies related to cultural values and self-esteem. In addition, loss of a loved one can trigger the onset of a DSM-IV anxiety disorder that, when present, can derail the mourning process and prolong acute grief. Bereavement-related anxiety disorders need to be recognized and treated.


Does thiamine protect the brain from iron overload and alcohol-related dementia?
Alcohol-related dementia (ARD) is a common and severe co-morbidity in alcohol use disorder (AUD). We propose brain iron overload (BIO) to be an important and previously neglected pathogenic process, accelerating cognitive decline in AUD. Furthermore, we suggest thiamine, which is frequently depleted in AUD, to be a key modulator in this process: Thiamine deficiency impairs the integrity of the blood-brain barrier, thereby enabling iron to pass through and accumulate in the brain. This hypothesis is based on findings from animal, translational, and neuroimaging studies, discussed in this article. To validate this hypothesis, translational studies focusing on brain iron homeostasis in AUD, as well as prospective clinical studies investigating prevalence and clinical impact of BIO in AUD, should be conducted. If proven right, this would change the understanding of ARD and may lead to novel therapeutic interventions in prevention and treatment of ARD.


Electric membrane properties of human DRG neurons in cell culture and the effect of high K medium.
Cell cultures were prepared from human fetal and newborn dorsal root ganglia (DRG) and maintained in culture medium with normal (4 mM) and elevated (20 mM) potassium (K). Both types of cultures were transferred to 4 mM K, and the electrical membrane properties of the DRG neurons characterized by an extensive investigation of resting membrane potential, specific membrane resistance (Rm) and capacitance, time constant (tau), rheobasic current, and various aspects of the action potential, including overshoot, duration (DT), afterhyperpolarization and absolute refractory period (ARP). No previous quantitative determinations of these membrane properties for human neurons could be found. However, our values were in good agreement with those reported for the DRG neurons of other mammalian species both in vitro and in situ. Significant correlations occurred between membrane properties and the developmental age of each specimen used for culturing. However, the data must be interpreted cautiously due to the limited number of specimens used (4) and the possibility of differential responses of the specimens to the experimental situation. Precultivation in high K medium had profound effects on both passive and active membrane properties: the primary effect being to reduce Rm, and as a result tau, DT, and ARP were also reduced. These observations add further support to the hypothesis that high K in vitro can substitute to some extent for trophic factors normally present in situ.


Downregulation of Cancer-Associated lncRNAs in Peripheral Blood of Multiple Sclerosis Patients.
Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of immune-related disorders including multiple sclerosis (MS). Based on the role of these transcripts in the regulation of immune response, peripheral levels of lncRNAs can reflect the level of immune activation. In the present study, we quantified expression of four lncRNAs namely SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 in venous blood of MS patients and controls using quantitative real-time PCR method. Relative expressions of SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 were significantly lower in female MS patients compared with female healthy subjects. For MEG3, this pattern of expression was also observed in male subjects. However, for other lncRNAs, no significant difference was detected between male patients and male controls. Expression of HOXA-AS2 was correlated with progression index (r = 0.36, P < 0.001). Besides, there was a significant correlation between expression of this lncRNA and expression of LINC-ROR in MS patients (r = 0.44, P < 0.0001). There was no other correlation between expression of lncRNAs and clinical data in MS patients. In control group, expressions of none of lncRNAs were correlated with age of persons. Notably, significant correlations were demonstrated between expression levels of all lncRNAs in healthy subjects with r values ranging from 0.23 to 0.42. The current investigation shows dysregulation of lncRNAs in MS patients in a sex-specific manner and warrants further studies to unravel the clinical and therapeutic implications of such dysregulation.


AlCl3-Catalyzed Cascade Reactions of 1,2,3-Trimethoxybenzene and Adipoyl Chloride: Spectroscopic Investigations and Density Functional Theory Studies.
The reaction of 1,2,3-trimethoxybenzene with adipoyl chloride in the presence of AlCl3 gave two isomeric cyclopentene derivatives, 1,6-bis(2,3,4-trimethoxyphenyl)hexane-1,6-dione, and two demethylation products of aryl methyl ethers. The cyclopentene derivatives including unconjugated or conjugated enones are products formed in a cascade reaction resulting from first the Friedel-Crafts acylation reaction and then aldol condensation. All compounds were optimized by density functional theory calculated using two functional levels, B3LYP and M06-2X, with the 6-311+G(d,p) basis set. The structural properties were established, natural bond orbital analysis of donor-acceptor interactions was carried out, and charges on the atoms and quantum chemical reactivity identifiers were determined to compare the strength of the intramolecular hydrogen bonds formed and their stabilities. To compare the experimental 1H and 13C NMR chemical shifts with the calculated values, NMR chemical shift calculations were carried out using the gauge-invariant atomic orbital method.


Melatonin and rhythmic photoreceptor metabolism: melatonin-induced cone elongation is blocked at high light intensity.
We have proposed a model for circadian regulation of cone position in Xenopus laevis that involves interaction of melatonin and dopamine as signals for darkness and light respectively. One problem, however, is that the effects of melatonin have not been detected in eye cups prepared from animals maintained on a cyclic light schedule. Since melatonin's effect would be expected to occur in low light intensity at night, we have investigated the relationship among melatonin, light intensity, and cone length. We report that melatonin mimics the effects of darkness and stimulates cone elongation in eye cups from cyclic light animals incubated at low but not at high light intensities.


Commensal-driven immune zonation of the liver promotes host defence.
The liver connects the intestinal portal vasculature with the general circulation, using a diverse array of immune cells to protect from pathogens that translocate from the gut1. In liver lobules, blood flows from portal triads that are situated in periportal lobular regions to the central vein via a polarized sinusoidal network. Despite this asymmetry, resident immune cells in the liver are considered to be broadly dispersed across the lobule. This differs from lymphoid organs, in which immune cells adopt spatially biased positions to promote effective host defence2,3. Here we used quantitative multiplex imaging, genetic perturbations, transcriptomics, infection-based assays and mathematical modelling to reassess the relationship between the localization of immune cells in the liver and host protection. We found that myeloid and lymphoid resident immune cells concentrate around periportal regions. This asymmetric localization was not developmentally controlled, but resulted from sustained MYD88-dependent signalling induced by commensal bacteria in liver sinusoidal endothelial cells, which in turn regulated the composition of the pericellular matrix involved in the formation of chemokine gradients. In vivo experiments and modelling showed that this immune spatial polarization was more efficient than a uniform distribution in protecting against systemic bacterial dissemination. Together, these data reveal that liver sinusoidal endothelial cells sense the microbiome, actively orchestrating the localization of immune cells, to optimize host defence.


Localization of the gene for human 11 beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) to chromosome band 16q22.
The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) is an NAD-dependent, high-affinity isoform that potently inactivates glucocorticoids. In the present study we have used fluorescence in situ hybridization and an 11 beta HSD2 cDNA isolated from human kidney as probe to localize the gene encoding 11 beta HSD2. The gene, which has been given the symbol HSD11B2, maps to human chromosome band 16q22.


Structure of the polymerase ε holoenzyme and atomic model of the leading strand replisome.
The eukaryotic leading strand DNA polymerase (Pol) ε contains 4 subunits, Pol2, Dpb2, Dpb3 and Dpb4. Pol2 is a fusion of two B-family Pols; the N-terminal Pol module is catalytic and the C-terminal Pol module is non-catalytic. Despite extensive efforts, there is no atomic structure for Pol ε holoenzyme, critical to understanding how DNA synthesis is coordinated with unwinding and the DNA path through the CMG helicase-Pol ε-PCNA clamp. We show here a 3.5-Å cryo-EM structure of yeast Pol ε revealing that the Dpb3-Dpb4 subunits bridge the two DNA Pol modules of Pol2, holding them rigid. This information enabled an atomic model of the leading strand replisome. Interestingly, the model suggests that an OB fold in Dbp2 directs leading ssDNA from CMG to the Pol ε active site. These results complete the DNA path from entry of parental DNA into CMG to exit of daughter DNA from PCNA.


Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia.
Using a sensitive immunohistochemical technique and a specific monoclonal antibody (RFD-3), follicular dendritic cells (FDC) have been demonstrated in a significant proportion (6/12) of bone marrow samples from patients with nodular marrow involvement of B-cell chronic lymphocytic leukemia (B-CLL). In all cases with "packed marrow" involvement and advanced stages of disease the FDC were absent. As these accessory cells are normally present only in the lymph nodes, their presence in the bone marrow is in accord with the view that B-CLL might be the malignancy of an immature subpopulation of lymph node lymphocytes that invade the bone marrow.


Chemical Characterization and Biological Evaluation of New Cobalt(II) Complexes with Bioactive Ligands, 2-Picolinehydroxamic Acid and Reduced Schiff Base N-(2-Hydroxybenzyl)alanine, in Terms of DNA Binding and Antimicrobial Activity.
Five new heteroligand cobalt(II) complexes with 2-picolinehydroxamic acid and reduced Schiff base, N-(2-hydroxybenzyl)alanine, were formed in an aqueous solution over a wide pH range. The coordination properties of ligands towards the metal ion were determined using a pH-metric method, and then the speciation model was confirmed by UV-Vis studies. A stacking interaction between the Schiff base phenol ring and the 2-picolinehydroxamic acid pyridine ring was found to improve the stability of the heteroligand species, indicating more effective coordination in mixed-ligand complexes than in their respective binary systems. The antimicrobial properties of heteroligand complexes were determined against Gram-negative and Gram-positive bacteria, as well as fungal strains. The formulation demonstrated the highest bacteriostatic and bactericidal activity (3.65 mM) against two strains of Gram-negative Helicobacter pylori bacteria and towards Candida albicans and Candida glabrata; this is important due to the potential co-existence of these microorganisms in the gastric milieu and their role in the development of gastritis. The binary complexes in the cobalt(II)-2-picolinehydroxamic acid system and 2-picolinehydroxamic acid were not cytotoxic against L929 mouse fibroblasts, neither freshly prepared solutions or after two weeks' storage. By comparison, the heteroligand complexes within the range 0.91-3.65 mM diminished the metabolic activity of L929 cells, which was correlated with increased damage to cell nuclei. The concentration of the heteroligand species increased over time; therefore, the complexes stored for two weeks exhibited stronger anticellular toxicity than the freshly prepared samples. The complexes formed in an aqueous solution under physiological pH effectively bound to calf thymus DNA in an intercalative manner. This DNA-binding ability may underpin the antimicrobial/antifungal activity of the heteroligand complexes and their ability to downregulate the growth of eukaryotic cells.


Transcriptomes reveal the genetic mechanisms underlying ionic regulatory adaptations to salt in the crab-eating frog.
The crab-eating frog, Fejervarya cancrivora, is the only frog that lives near seas. It tolerates increased environmental concentrations of sodium, chloride and potassium partly by raising ion and urea levels in its blood plasma. The molecular mechanism of the adaptation remains rarely documented. Herein, we analyze transcriptomes of the crab-eating frog and its closely related saline-intolerant species, F. limnocharis, to explore the molecular basis of adaptations to such extreme environmental conditions. Analyses reveal the potential genetic mechanism underlying the adaptation to salinity for the crab-eating frog. Genes in categories associated with ion transport appear to have evolved rapidly in F. cancrivora. Both positively selected and differentially expressed genes exhibit enrichment in the GO category regulation of renal sodium excretion. In this category, the positively selected sites of ANPEP and AVPR2 encode CD13 and V2 receptors, respectively; they fall precisely on conserved domains. More differentially expressed rapidly evolved genes occur in the kidney of F. cancrivora than in F. limnocharis. Four genes involved in the regulation of body fluid levels show signs of positive selection and increased expression. Significant up-regulation occurs in several genes of F. cancrivora associated with renin-angiotensin system and aldosterone-regulated sodium reabsorption pathways, which relate to osmotic regulation.


Ionic Diffusion-Driven Ionovoltaic Transducer for Probing Ion-Molecular Interactions at Solid-Liquid Interface.
Ion-solid surface interactions are one of the fundamental principles in liquid-interfacing devices ranging from various electrochemical systems to electrolyte-driven energy conversion devices. The interplays between these two phases, especially containing charge carriers in the solid layer, work as a pivotal role in the operation of these devices, but corresponding details of those effects remain as unrevealed issues in academic fields. Herein, an ion-charge carrier interaction at an electrolyte-semiconductor interface is interrogated with an ion-dynamics-induced (ionovoltaic) energy transducer, controlled by interfacial self-assembled molecules. An electricity generating mechanism from interfacial ionic diffusion is elucidated in terms of the ion-charge carrier interaction, originated from a dipole potential effect of the self-assembled molecular layer (SAM). In addition, this effect is found to be modulated via chemical functionalization of the interfacial molecular layer and transition metal ion complexation therein. With the aiding of surface analytic techniques and a liquid-interfacing Hall measurement, electrical behaviors of the device depending on the magnitude of the ion-ligand complexation are interrogated, thereby demonstrating the ion-charge carrier interplays spanning at electrolyte-SAM-semiconductor interface. Hence, this system can be applied to study molecular interactions, including chemical and physical influences, occurring at the solid-liquid interfacial region.


Omega-3 fatty acid intake and decreased risk of skin cancer in organ transplant recipients.
Organ transplant recipients have over 100-fold higher risk of developing skin cancer than the general population and are in need of further preventive strategies. We assessed the possible preventive effects of omega-3 polyunsaturated fatty acid (PUFA) intake from food on the two main skin cancers, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in kidney and liver transplant recipients. Adult kidney or liver transplant recipients transplanted for at least 1 year and at high risk of skin cancer were recruited from the main transplant hospital in Queensland, 2012-2014 and followed until mid-2016. We estimated their dietary total long-chain omega-3 PUFAs and α-linolenic acid intakes at baseline using a food frequency questionnaire and ranked PUFA intakes as low, medium, or high. Relative risks (RRsadj) of skin cancer adjusted for confounding factors with 95% confidence intervals (CIs) were calculated. There were 449 transplant recipients (mean age, 55 years; 286 (64%) male). During follow-up, 149 (33%) patients developed SCC (median 2/person; range 1-40) and 134 (30%), BCC. Transplant recipients with high total long-chain omega-3 PUFA compared with low intakes showed substantially reduced SCC tumour risk (RRadj 0.33, 95% CI 0.18-0.60), and those with high α-linolenic acid intakes experienced significantly fewer BCCs (RRadj 0.40, 95% CI 0.22-0.74). No other significant associations were seen. Among organ transplant recipients, relatively high intakes of long-chain omega-3 PUFAs and of α-linolenic acid may reduce risks of SCC and BCC, respectively.


Insights into homonuclear decoupling from efficient numerical simulation: techniques and examples.
A combination of techniques, including rational number synchronisation and pre-diagonalisation of the time-dependent periodic Hamiltonian, are described which allow the efficient simulation of NMR experiments involving both magic-angle spinning (MAS) and RF irradiation, particularly in the important special case of phase-modulated decoupling sequences. Chebyshev and conventional diagonalisation approaches to calculating propagators under MAS are also compared, with Chebyshev methods offering significant advantages in cases where the Hamiltonian is large and time-dependent but not block-diagonal (as is the case for problems involving combined MAS and RF). The ability to simulate extended coupled spin systems efficiently allows 1H spectra under homonuclear decoupling to be calculated directly and compared to experimental results. Reasonable agreement is found for the conditions under which homonuclear decoupling is typically applied for rigid solids (although the increasing deviation of experimental results from the predictions of theory and simulation at higher RF powers is still unexplained). Numerical simulations are used to explore three features of these experiments: the interaction between the magic-angle spinning and RF decoupling, the effects of tilt pulses in acquisition windows and the effects of "phase propagation delays" on tilted axis precession. In each case, the results reveal features that are not readily anticipated by previous analytical studies and shed light on previous empirical observations.


Clinical and neuroimaging predictors of seizure recurrence in solitary calcified neurocysticercosis: A prospective observational study.
Solitary calcified neurocysticercosis is a common cause of seizures in the developing countries. Factors responsible for seizure recurrence in patients with solitary calcified neurocysticercosis are not known. We evaluated the clinical, neuroimaging and biochemical predictors of seizure recurrence. This was a prospective observational study. Patients with new-onset seizures and a solitary calcified neurocysticercosis were included. Patients were evaluated clinically; baseline electroencephalography and magnetic resonance imaging of brain were done for all patients.. The patients were followed for 1year. Seizure recurrence was defined as the recurrence of an episode of seizure at least 1 week after the initiation of the anti-epileptic drugs. Fifty-four patients with a mean age of 20.43±7.34years were included. Thirteen patients developed seizure recurrence during the follow-up period. On univariate analysis, status epilepticus at presentation (p=0.025), size of the lesion >10mm (p=0.015), presence of perilesional edema (p<0.001) and scolex (p=0.033) were significantly associated with seizure recurrence. On multivariate analysis, only presence of perilesional edema (p=0.018, odds ratio=12.122, 95% confidence interval 1.521-96.639) was an independent predictor of seizure recurrence. Status epilepticus at presentation is associated with an increased risk of seizure recurrence. Neuroimaging features like presence of perilesional edema and scolex can similarly predict seizure recurrence. These neuroimaging features can serve as potential surrogate markers to define therapy in these patients. The findings of our study might be helpful in stratifying patients with a higher risk of seizure recurrence, especially those who may require a more aggressive management.


COVID-19 vaccine acceptance rates and predictors among the Egyptian general population and Healthcare workers, the intersectionality of age and other factors.
The promise of COVID-19 vaccines in ending the pandemic can only be achieved by overcoming the challenge of vaccine refusal. Healthcare workers (HCWs) are the trusted advisors of vaccination decisions. Recommendations for vaccinating children against COVID-19 are recently gaining more public health attention due to the role of children in disease transmission and associated morbidities. Vaccination is one of the first medical decisions parents or guardians make on behalf of their children. To investigate the determinants associated with vaccine acceptability among the general population through a direct interview questionnaire and assess guardians' views towards childhood COVID-19 vaccinations. This cross-sectional study included 2919 participants A pre-designed structured questionnaire about COVID-19 vaccination acceptability was completed by trained interviewers and interviewing the participants or their guardians (for those below 18 years old). Nearly two-thirds of participants (66.5%) accepted vaccination, 20.2% were refusing and 13.3% were hesitant. Most participants who were guardians of children below 12 years and from 13 to 17 years reported that they would accept vaccination of their children (72.5% and 70.5%, respectively). The acceptance rate among HCWs was 58.2%. The main reasons beyond vaccine refusal were mistrust of vaccine efficacy (39.5%) and having concerns regarding vaccine safety (38.8%). In a multivariable regression model, being male (OR 1.362, 95% CI 1.082-1.714, p = 0.008) resident in rural area (OR 1.796, 95% CI 1.435-2.247, p = 0.000), and lower education (OR 1.245, 95% CI 1.018-1.523, p = 0.033) were associated with an increased acceptance to be vaccinated. The acceptance rate for vaccinating children reported among their guardians was higher than adults for themselves. Extremes of age showed higher vaccine acceptance compared to young adults. Upper Egypt governorates (Faiyum and Giza) were outpacing Lower Egypt governorates in vaccination acceptance rates.


Assessment of novel antiviral filter using pseudo-type SARS-CoV-2 virus in fast air velocity vertical-type wind tunnel.
Current evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can remain suspended spread in aerosols for longer period of time under poorly ventilated indoor setting. To minimize spreading, application of antiviral filter to capture infectious aerosols and to inactivate SARS-CoV-2 can be a promising solution. This study aimed to develop a method to assess simultaneously the filtration and removal efficiency of aerosolized pseudo-type SARS-CoV-2 using a vertical-type wind tunnel with relatively high face velocity (1.3 m/s). Comparing with the untreated spunlace non-woven filter, the C-POLAR™ treated filter increased the filtration efficiency from 74.2 ± 11.5% to 97.2 ± 1.7%, with the removal efficiency of 99.4 ± 0.051%. The results provided not only solid evidence to support the effectiveness of the cationic polymeric coated filter in fighting against the SARS-CoV-2 pandemic, but also a method to test viral filtration and removal efficiency under relative fast air velocity and with a safer environment to the operators.


Lifetime accumulation of (137)Cs and (40)K in the ribs and sternum of an Austrian "mountain pasture" cow.
The accumulation of natural and artificial radionuclides in humans and domestic animals is of interest in estimating effective doses of exposed humans and to decide whether animal products can be used for nutrition of the population. In this paper we present an investigation of the (137)Cs- and (40)K-activity levels of the ribs and sternum of a "mountain pasture" cow, born in a highly contaminated region of Styria, Austria, at the time of the radioactive fallout following the Chernobyl accident. This is the first systematic investigation of the variation in activity levels of a contaminated animal. The International Commission on Radiological Protection (ICRP) assumes that cesium and potassium are homogenously distributed throughout the whole body of an organism. However, the presented results show that there is a non-uniform distribution of (137)Cs and (40)K in different skeletal bones and their adherent tissues of a dairy cattle. We found that activity concentrations of (137)Cs and (40)K varied up to a factor 2.5 in different components of the ribs. The minimum values of (137)Cs and (40)K in the ribs were 29.9 and 21Bqkg(-1) fresh mass for trabecular bone in the vertebral half of asternal ribs, and the maximum values 332 and 132Bqkg(-1) fresh mass for a mixed sample composed of a cartilaginous tissue layer and parts of the perichondrium, both originating from asternal costal cartilages, respectively.


Hepatosplenic T cell lymphoma with no expression of cytotoxic molecules.
Hepatosplenic T cell lymphoma is defined as an extranodal and systemic neoplasm derived from cytotoxic T cells. This report describes a postmortem case of T cell lymphoma that showed histological features of hepatosplenic T cell lymphoma but did not express cytotoxic molecules. The patient was a 57 year old man who presented with severe icterus and hepatosplenomegaly, followed by an aggressive clinical course. The liver and spleen were enlarged, weighing 2000 g and 360 g, respectively. Histologically, the liver, spleen, and bone marrow were entirely affected by lymphoma, comprising pleomorphic small and large cells, which displayed sinusoidal infiltration in the liver, diffuse infiltration in the splenic cord, and interstitial/diffuse infiltration with fibrosis in the bone marrow. Lymphoma cells showed positivity for CD3 epsilon, CD8, and CD45RO and clonal rearrangement of the TCRgamma gene by the polymerase chain reaction on paraffin wax embedded sections. However, they were negative for TIA-1 and granzyme B, in addition to betaF1, CD4, and CD56. Few neoplastic cells were stained for Epstein-Barr virus encoded mRNA 1. These findings indicate that this case might represent a variant of hepatosplenic T cell lymphoma despite the absence of cytotoxic molecules.


Thymic tumors: relevant molecular data in the clinic.
Thymic malignancies are rare intrathoracic tumors that may be aggressive and difficult to treat in advanced stage. Over the past years, significant efforts have been conducted to dissect the molecular pathways involved in the carcinogenesis of these tumors. Insights have been made following anecdotal clinical responses to targeted therapies, and large-scale genomic analyses have been conducted. Review of the literature, 1990-2010. The Epidermal Growth Factor Receptor (EGFR) is frequently overexpressed in thymomas and thymic carcinomas, but EGFR mutations are exceptional, and this does not support the use of EGFR tyrosine kinase inhibitors. On the contrary, single observations of responses create a basis for further evaluation of cetuximab in thymomas. KIT-mutant thymic carcinomas represent a small molecular subset of thymic tumors. The clinical relevance of KIT mutations is more limited in thymic carcinoma than in GIST as KIT mutations are far less frequent (7% of thymic carcinomas) and are not correlated with KIT expression; furthermore, KIT mutants are not uniformly sensitive to imatinib. Beyond EGFR and KIT signaling pathways, other molecular alterations with potential prognostic or predictive relevance are emerging in thymic malignancies. Given the rarity of these tumors, translation of preclinical findings to the clinic may be quick and represents one of the most promising therapeutic approaches for advanced-stage thymic malignancies.


Thiolation of preformed liposomes with iminothiolane.
Preformed phosphatidylethanolamine-containing liposomes were thiolated with 2-iminothiolane (Traut's reagent) and subsequently activated by mixed disulfide formation with 5,5'-dithiobis(2-nitrobenzoic acid). Up to 65% of amino groups of the outer liposomal lamella, corresponding to 230 SH-groups per vesicle, were modified. Covalent attachment of thiolated alpha-chymotrypsin to these thiol-liposomes via S-S bridges yielded a protein/lipid ratio of 3.6 X 10(-4) mol enzyme/mol lipid.


A prospective study of adjustment to hemodialysis.
To examine (a) changes in subjects' self-care self-efficacy over time and (b) the relationship of subjects' self-care self-efficacy with adjustment to hemodialysis. A longitudinal design was used to study changes in self-care self-efficacy and associations between self-care self-efficacy and measures of adjustment: health status, mood distress, symptom distress, dialysis stress, and perceived adherence to fluid restriction. Subjects were recruited from 8 settings in the Northeast where outpatient hemodialysis treatment was administered. Sixty-four subjects were recruited to the study. Twenty-eight subjects completed 3 occasions of data collection. Data were collected on three occasions: (a) baseline-within 100 days of beginning treatment; (b) 4 months after beginning treatment; and (c) 8 months after beginning treatment. Eta-squared, a measure of practical significance, is reported for four factors of the self-care self-efficacy measure on each of the three occasions. Associations between self-care self-efficacy and measures of adjustment were examined by means of Pearson correlations. Eta-squared estimates showed generally positive changes occurring over time in subjects' self-care self-efficacy, health status, mood distress, symptom distress, dialysis stress, and perceived adherence to fluid restriction. Changes were more positive at 4-months than at 8-months after enrollment. Significant correlations (p < .05) occurred between self-care self-efficacy and mood states, health status, symptom distress, and perceived adherence to fluid restrictions. Correlations occurred more frequently between self-care self-efficacy and mood states than between self-care self-efficacy and other measures of adjustment. The study provided pilot data suggesting that hemodialysis patients' self-care self-efficacy and measures of adjustment change over time. Patients who had increased confidence in self-care strategies (self-efficacy) were associated with having more positive mood states, health status, and perceived adherence to fluid restrictions and less symptom distress. Interventions designed to increase patients' self-care self-efficacy may yield positive results. Nurses are in an excellent position to give efficacy enhancing feedback that may promote patients' adjustment.


Research Note: Retinal cryptochrome gene expression is not altered by presence of light in incubators.
Cryptochromes are blue-, or ultraviolet-, light-absorbing proteins involved in the circadian clock, blue/ultraviolet light perception and potentially magnetoreception. At least 4 separate cryptochrome genes have been identified in avian species. The purpose of this study was to first determine if cryptochrome genes are expressed in the developing duck retina, and second to determine if the presence of lights in incubators affects the expression of cryptochrome genes. To accomplish these goals, duck eggs were placed in one of 2 commercial incubators (Buckeye, Single Stage Incubator, Model, SS-112) at Maple Leaf Farms, Inc., one with "poultry" LEDs obtained from a commercial source (Once Innovation, Agrishift) and the other in the absence of light (dark). Eggs in the incubators were placed on a reciprocating tray, tilting to 45° to simulate the rotation of eggs; thus all eggs spent 50% facing the light source and the other 50% of time facing 45° away from light source. Temperature gradients and humidity were maintained at industry standards. Retinal tissue samples from light and dark incubators were collected on days 3, 7, 11, 16, and 21 of incubation (extraction day, ED) known to be anatomical hallmarks of visual system development (n = 9-18 treatment group/ED timepoint). Samples were prepped and assayed for Cry2 and GAPDH gene transcription using qRT-PCR. Data were analyzed by using 2-ddCt method and a 2-way ANOVA was performed. No significant differences in Cry2 gene expression were observed between the lighted or dark incubator (P > 0.10). When combining light and dark treatment groups there is a significant 9 P < 0.05) increase in retinal Cry2 at ED 21, compared to ED 3 and 7. The presence of cryptochrome does not necessitate a migratory drive as evidenced by the fact that the Cry2 expression has been shown in non-migratory birds. However, since blue/ultraviolet wavelengths also activate the Cry2 photoreceptor, its presence could explain reports that suggest duck welfare can be improved if housed under lights that include ultraviolet wavelengths.


Thioxothiazolo[3,4-a]quinazoline derivatives inhibit the human cytomegalovirus alkaline nuclease.
Human cytomegalovirus (HCMV, human herpesvirus 5) is an opportunistic pathogen responsible for serious disease in immunocompromised patients. Current antiviral therapies rely predominantly on drugs interfering with viral DNA replication and packaging. However, the serious side effects of existing drugs and the emergence of drug resistance indicate the need for new targets for anti-HCMV therapy. One such target is the viral alkaline nuclease (AN), an enzyme highly conserved among the Herpesviridae. In this study, we validated the HCMV AN, encoded by the viral UL98 open reading frame, as a drug target by demonstrating that a UL98-deficient HCMV mutant is severely attenuated and shows a reduced ability to spread in cell culture. We established a fluorescence-based enzyme assay suitable for high-throughput screening and used it on a small-molecule compound library. The most promising hit, a thioxothiazolo[3,4-a]quinazoline derivative, blocked AN activity in vitro and inhibited HCMV replication in plaque reduction (PRA) and fluorescence reduction assays (FRA). Several derivatives of the hit compound were tested, some of which had similar or better inhibitory activities. The most potent derivative of hit scaffold A, compound AD-51, inhibited HCMV replication with a 50% effective concentrations (EC50) of 0.9 μM in the FRA and 1.1 μM in the PRA. AD-51 was also active against ganciclovir, foscarnet, and letermovir-resistant HCMVs. Moreover, it inhibited herpes simplex virus, Kaposi's sarcoma-associated herpesvirus, and murine CMV, a mouse virus serving as a model for HCMV. These results suggest that thioxothiazolo[3,4-a]quinazoline derivatives are a new class of herpesvirus inhibitors targeting the viral AN.


Duality of Antidepressants and Neuroprotectants.
The co-morbidity of neuropsychiatric disorders, particularly major depressive disorder (MDD) with neurodegenerative diseases, in particular Parkinson's disease (PD) is now well recognized. Indeed, it is suggested that depressive disorders, especially in late life, may be an indication of latent neurodegeneration. Thus, it is not unreasonable to expect that deterrents of MDD may also deter the onset and/or progression of the neurodegenerative diseases including PD. In this review, examples of neuroprotective efficacy of established as well as prospective antidepressants are provided. Conversely, mood-regulating effects of some neuroprotective drugs are also presented. Thus, in addition to currently used antidepressants, ketamine, nicotine, curcumin, and resveratrol are discussed for their dual efficacy. In addition, potential neurobiological substrates for their actions are presented. It is concluded that pharmacological developments of mood-regulating or neuroprotective drugs can have cross benefit in co-morbid conditions of neuropsychiatric and neurodegenerative disorders and that inflammatory and neurotrophic factors play important roles in both conditions.


Periodontitis regulates renal impairment in obese mice via TGF-β/Smad pathway.
To determine the impact of periodontitis on renal impairment induced by obesity. Periodontitis and obesity models were induced using silk ligatures with bacteria and high-fat diet, respectively. Indicators of renal function were compared. Renal tubular epithelial cells (RTECs) were treated with lipopolysaccharides from periodontal pathogens in a high-fat environment to induce cell models of periodontitis and obesity. The transforming growth factor-β/mothers against decapentaplegic homolog (Smad) (TGF-β/Smad) pathway was evaluated both in vivo and in vitro. The indicators of renal function, renal pathological changes, and serum inflammatory cytokines were measured. The viability/apoptosis of RTECs and the expression of inflammatory cytokines were determined. Periodontitis resulted in an increase in TGF-β/Smad activity in the kidney of obese mice. Moreover, the activity of RTECs was also increased in vitro. Downregulation of TGF-β led to reduced TGF-β, p-Smad2, p-Smad3, and Smad7 levels in kidney tissue and RTECs, ameliorated renal function indicators and renal pathological changes, increased viability and apoptosis of RTECs, and decreased levels of inflammatory cytokines. Periodontitis regulates renal impairment via the TGF-β/Smad pathway in obese mice.


Unequal burden of sleep-related obesity among black and white Americans.
This study ascertained whether individuals of the black race/ethnicity are unequally burdened by sleep-related overweight/obesity. Analysis was based on data obtained from Americans (ages, 18-85 years) in the National Health Interview Survey (1977-2009). Sleep duration was coded as either very short sleep (VSS) (≤5 hours), short sleep (SS) (5-6 hours), or long sleep (>8 hours), referenced to 7-8-hour sleepers. Overweight was defined as body mass index (BMI) ≥25.0 and ≤29.9 kg/m2 and obesity, BMI ≥30 kg/m2, referenced to normal weight (BMI = 18.5-24.9 kg/m2). Multivariate-adjusted regression analyses indicated that, among whites, VSS was associated with a 10% increased likelihood of being overweight and 51% increased likelihood of being obese, relative to 7-8-hour sleepers. Short sleep was associated with a 13% increased likelihood of being overweight and 45% increased likelihood of being obese. Long sleep was associated with 21% increased likelihood of being obese. Among blacks, VSS was associated with a 76% increased likelihood of being overweight and 81% increased likelihood of being obese. Short sleep was associated with a 16% increased likelihood of being overweight and 32% increased likelihood of being obese. As for the white stratum, long sleep was associated with a 25% increased likelihood of being obese. Our investigation demonstrates strong linkages between inadequate sleep and overweight/ obesity among black and white Americans. Although it cannot be said that insufficient sleep causes overweight/obesity, individuals of the black race/ethnicity sleeping ≤5 hours may be unequally burdened by sleep-related overweight/obesity.