Regulation of atrial contraction by PKA and PKC during development and regression of eccentric cardiac hypertrophy.
ANG II plays a major role in development of cardiac hypertrophy through its AT1 receptor subtype, whereas angiotensin-converting enzyme (ACE) inhibitors are effective in reversing effects of ANG II on the heart. The objective of this study was to investigate the role of PKA and PKC in the contractile response of atrial tissue during development and ACE inhibitor-induced regression of eccentric hypertrophy induced by aortocaval shunt. At 1 wk after surgery, sham and shunt rats were divided into captopril-treated and untreated groups for 2 wk. Then isometric contraction was assessed by electrical stimulation of isolated rat left atrial preparations superfused with Tyrode solution in the presence or absence of specific inhibitors KT-5720 (for PKA) and Ro-32-0432 (for PKC) and high Ca2+. Peak tension developed was greater in shunt than in sham hearts. However, when expressed relative to tissue mass, hypertrophied muscle showed weaker contraction than muscle from sham rats. In sham rats, peak tension developed was more affected by PKC than by PKA inhibition, whereas this differential effect was reduced in the hypertrophied heart. Treatment of shunt rats with captopril regressed left atrial hypertrophy by 67% and restored PKC-PKA differential responsiveness toward sham levels. In the hypertrophied left atria, there was an increase in the velocity of contraction and relaxation that was not evident when expressed in specific relative terms. Treatment with ACE inhibitor increased the specific velocity of contraction, as well as its PKC sensitivity, in shunt rats. We conclude that ACE inhibition during eccentric cardiac hypertrophy produces a negative trophic and a positive inotropic effect, mainly through a PKC-dependent mechanism.


Novel Allele Detection Tool Benchmark and Application With Antibody Repertoire Sequencing Dataset.
Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing (Rep-seq or Ig-seq) data via multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an antibody repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-quality datasets. We then systematically evaluated these NADTs using both simulated and genuine Ig-seq datasets. Finally, we applied these NADTs to 687 Ig-seq datasets and identified 43 novel allele candidates (NACs) using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the NACs detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies via Ig-seq.


Impact of sex steroids and their suppression on skeletal growth and maturation.
Forty girls with central precocious puberty (CPP) were studied before and during 1-3 yr of luteinizing hormone-releasing factor (LHRH) agonist (LHRHa) administration to examine the impact of gonadal steroid secretion and its suppression on skeletal growth and maturation. Pubertal growth velocity (GV) was 10.1 +/- 0.7 (SE) cm/yr and, when normalized for chronological age (CA) and bone age (BA), demonstrated that the effects of sex steroids were most profound in patients with the youngest CA and BA. GV decreased significantly to 5.8 +/- 0.3 (n = 40), 4.6 +/- 0.3 (n = 30), and 3.2 +/- 0.6 cm/yr (n = 12) during 3 yr of gonadal suppression and correlated negatively with starting BA. Skeletal maturation was markedly accelerated by premature sex steroid secretion (BA/CA = 1.8 +/- 0.1), was slowed significantly with gonadal suppression (mean delta BA/delta CA less than 1), and also was negatively correlated with the starting BA. Cumulative increases in predicted adult height were observed regardless of starting BA and averaged +2.0 +/- 0.4, +5.2 +/- 0.5, and +6.7 +/- 1.2 cm after 1, 2, and 3 yr of gonadal suppression. The comparable changes in height predictions across all BAs despite highly variable GVs underscore the need for use of developmental (i.e., BA-based) rather than CA-based standards in the analysis of growth during gonadal steroid exposure and suppression in childhood.


The Therapeutic Effects of Magnesium in Insulin Secretion and Insulin Resistance.
Insulin resistance (IR) is a chronic pathological condition that is related to reduce the rates of glucose uptake, especially in the liver, muscle, and adipose tissue as target tissues. Metabolic syndrome and type 2 diabetes mellitus can occur following progression of the disease. The majority of prior research has applied that some cations such as magnesium (Mg2+) have important physiological role in insulin metabolism. Mg2+ is the fourth most abundant mineral in the human body that gets involved as a cofactor of various enzymes in several metabolic events, such as carbohydrate oxidation, and it has a fundamental role in glucose transporting mechanism of the cell membrane. This cation has numerous duties in the human body such as regulation of insulin secretion in pancreatic beta-cells and phosphorylation of the insulin receptors in target cells and also gets involved in other downstream signal kinases as intracellular cation. On this basis, intracellular Mg2+ balancing is vital for adequate carbohydrate metabolism. This paper summarizes the present knowledge about the therapeutic effects of Mg2+ in reducing IR in liver, muscle, and pancreases with different mechanisms. For this, the search was performed in Google Scholar, PubMed, Scopus, and Web of Science by insulin resistance, skeletal muscle, liver, pancreases, magnesium, Mg2+, and inflammation keywords.


A multiple-layer finite-element model of the surface EMG signal.
The effect of skin, muscle, fat, and bone tissue on simulated surface electromyographic (EMG) signals was examined using a finite-element model. The amplitude and frequency content of the surface potential were observed to increase when the outer layer of a homogeneous muscle model was replaced with highly resistive skin or fat tissue. The rate at which the surface potential decreased as the fiber was moved deeper within the muscle also increased. Similarly, the rate at which the surface potential decayed around the surface of the model, for a constant fiber depth, increased. When layers of subcutaneous fat of increasing thickness were then added to the model, EMG amplitude, frequency content, and the rate of decay of the surface EMG signal around the limb decreased, due to the increased distance between the electrodes and the active fiber. The influence of bone on the surface potential was observed to vary considerably, depending on its location. When located close to the surface of the volume conductor, the surface EMG signal between the bone and the source and directly over the bone increased, accompanied by a slight decrease on the side of the bone distal to the active fiber. The results emphasize the importance of distinguishing between the effects of material properties and the distance between source and electrode when considering the influence of subcutaneous tissue, and suggest possible distortions in the surface EMG signal in regions where a bone is located close to the skin surface.


Assessing the risk-benefit profile of classical psychedelics: a clinical review of second-wave psychedelic research.
A broad reassessment of the potential benefits of psychedelic drugs has led to the initiation of multiple major clinical trials in an effort to advance their status to become FDA-approved medications, as well as local legislative efforts to legalize or decriminalize their use. To use recently published data to assess potential risks and benefits of psychedelic drugs as therapeutics, as well as to synthesize what is currently known in order to generate fruitful future research directions. A review of studies conducted since 1991 identified 14 clinical trials of classical psychedelics, including 11 of psilocybin (N = 257 participants), 1 of lysergic acid diethylamide (N = 12 participants), and 2 of ayahuasca (N = 46 participants). Other published studies (e.g., of healthy volunteers, survey studies, case reports, neuroimaging) were also considered for review. Published studies since 1991 largely support the hypothesis that small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation to symptoms of multiple psychiatric conditions. No serious adverse events attributed to psychedelic therapy have been reported. Existing studies have several limitations, including small sample sizes, inherent difficulty in blinding, relatively limited follow-up, and highly screened treatment populations. Substantial data have been gathered in the past 30 years suggesting that psychedelics are a potent treatment for a variety of common psychiatric conditions, though the ideal means of employing these substances to minimize adverse events and maximize therapeutic effects remains controversial. Unique factors related to study design are vital for clinical researchers in the field to address.


Management of surgical hemostasis: systemic agents.
Despite improvements in surgical techniques, the risk for perioperative bleeding remains significant. Transfusion of allogeneic red blood cells, platelets, and hemostatic factors remains the mainstay of current therapy strategy for management of perioperative bleeding. Transfusions significantly contribute to perioperative adverse events. Pharmacologic strategies to prevent or decrease perioperative bleeding are also important therapeutic approaches to reduce the need for allogeneic transfusions. This article discusses systemic pharmacologic prohemostatic agents (aprotinin, lysine analogues, protamine, desmopressin, and recombinant factor VIIa).


Toxicological and Safety Pharmacological Profiling of the Anti-Infective and Anti-Inflammatory Peptide Pep19-2.5.
Aspidasept (Pep19-2.5) and its derivative Pep19-4LF ("Aspidasept II") are anti-infective and anti-inflammatory synthetic polypeptides currently in development for application against a variety of moderate to severe bacterial infections that could lead to systemic inflammation, as in the case of severe sepsis and septic shock, as well as application to non-systemic diseases in the case of skin and soft tissue infections (SSTI). In the present study, Aspidasept and Aspidasept II and their part structures were analysed with respect to their toxic behavior in different established models against a variety of relevant cells, and in electrophysiological experiments targeting the hERG channel according to ICH S7B. Furthermore, the effects in mouse models of neurobiological behavior and the local lymph node according to OECD test guideline 429 were investigated, as well as a rat model of repeated dose toxicology according to ICH M3. The data provide conclusive information about potential toxic effects, thus specifying a therapeutic window for the application of the peptides. Therefore, these data allow us to define Aspidasept concentrations for their use in clinical studies as parenteral application.


Craniomandibular dysfunction in children with clefts and noncleft children with and without unpleasant life events: a comparative study.
An epidemiologic study was conducted to investigate any difference in the prevalence of signs and symptoms of craniomandibular dysfunction on children with clefts and noncleft children with and without unpleasant life events. The experimental group consisted of thirty white children six to ten years of age with unilateral cleft lip and cleft lip and palate. On the basis of the sex and age distribution of the experimental group 30 out of 25 white children without unpleasant life events and 30 out of 105 white children with unpleasant life events were selected as control group I and control group II, respectively. The results showed statistically significant difference in the prevalence of temporomandibular joint tenderness between experimental and control group I, while the difference between experimental and control group II was not significant. Statistically significant difference in the frequency of temporomandibular joint tenderness was also revealed between the control groups. With respect to the severity of the symptoms, the only statistically significant difference was that of the anamnestic dysfunction index with severe symptoms (AiII) between the experimental and control group I. The other differences were not significant. The present study suggests that children with clefts and those with unpleasant life events run a greater risk of developing temporomandibular joint tenderness.


[Comparative evaluation of healthy preschool children blink].
To evaluate spontaneous blink activity in the primary eye position in normal preschool children. Two hundred normal children aged 4 to 6 years were prospectively evaluated. They were digitally videotaped in a standard setting, taking the images on frontal and lateral plans, during the vigil state, in the primary eye position. The object of observation was located at the same level of the pupil. A Sony Lithium camera was used. The images were recorded on 8 mm tapes and transferred to a personal computer (MacIntosh G4) and processed with the iMovie software. Opening, closure and total blink times were measured using frame scale. The eyelid movement rhythm per minute was also evaluated, during three minutes. The data were submitted to statistical analysis. The complete eye blink was more frequently observed than the incomplete eye blink. The blink rate increased with age. The incomplete blink rate was the same for all the evaluated ages. The eyelid opening and closing times and the complete blink time were similar for both sexes, during all evaluation moments. There were no differences between genders regarding eye blink. The closing eyelid time was slower than the opening eyelid time. The complete blink rate increases with age. The closing and the opening eyelid times and the complete blink were similar for both sexes in all evaluated ages and the opening time is faster than the closing time.


Bacterial Osteomyelitis or Nonbacterial Osteitis in Children: A Study Involving the German Surveillance Unit for Rare Diseases in Childhood.
Although bacterial osteomyelitis (BO) is a commonly recognized diagnosis in pediatrics, it is often difficult to distinguish from nonbacterial osteitis (NBO). The goal of our study was to distinguish between the 2 disease entities and better define NBO. Using the German Surveillance Unit for Rare Diseases in Childhood (Erhebungseinheit für Seltene Paediatrische Erkrankungen in Deutschland), this prospective study during a 5-year period captured 657 patients at first diagnosis of either BO (n = 378) or NBO (n = 279) while analyzing epidemiologic, clinical and radiologic data. BO was reported in 1.2 per 100,000 children with a higher prevalence in younger male patients (58%), and NBO was reported in 0.45 per 100,000 children. BO patients tended to present with fevers (68%), elevated inflammation markers (82%) and local swelling (62%) but a shorter course of symptoms than NBO patients. NBO patients presented in good general health (86%) and were more likely to have multifocal lesions (66%). Staphylococcus aureus was the most prominent pathogen (83%), with only one methicillin-resistant S. aureus reported. Complications ranged from arthritis adjacent to the lesion to hyperostosis and vertebral fractures. BO and NBO can be distinguished based on symptoms, associated diseases and inflammation markers. NBO should always be considered in pediatric patients presenting with bone lesions and pain, especially in young female patients presenting with good general health, minimal inflammation markers and multifocal lesions in the vertebrae, clavicle and sternum.


Astaxanthin, a carotenoid with potential in human health and nutrition.
Astaxanthin (1), a red-orange carotenoid pigment, is a powerful biological antioxidant that occurs naturally in a wide variety of living organisms. The potent antioxidant property of 1 has been implicated in its various biological activities demonstrated in both experimental animals and clinical studies. Compound 1 has considerable potential and promising applications in human health and nutrition. In this review, the recent scientific literature (from 2002 to 2005) is covered on the most significant activities of 1, including its antioxidative and anti-inflammatory properties, its effects on cancer, diabetes, the immune system, and ocular health, and other related aspects. We also discuss the green microalga Haematococcus pluvialis, the richest source of natural 1, and its utilization in the promotion of human health, including the antihypertensive and neuroprotective potentials of 1, emphasizing our experimental data on the effects of dietary astaxanthin on blood pressure, stroke, and vascular dementia in animal models, is described.


Radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation.
Radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) is widely utilized as a bridge to liver transplant with limited evidence to support efficacy. The purpose of the present study was to measure the effect of RFA on time to drop-off in HCC-listed patients. Patients with Milan criteria tumours listed between January 1999 and June 2007 were stratified into RFA (n= 77) and No Treatment groups (n= 93). The primary effectiveness of RFA was 83% (complete radiographic response). RFA was associated with a longer median wait time to transplant (9.5 vs. 5 months). Tumour-specific drop-off events were equivalent between RFA (21%) and No Treatment (12%) groups (P= 0.11). Controlling for wait time, there was no difference in overall (P= 0.56) or tumour-specific drop-off (P= 0.94). Furthermore, there were no differences in 5-year overall or tumour-free survivals from list date or transplant. Using multivariate analysis, the likelihood of receiving a transplant and patient survivals were associated with tumour characteristics (AFP, tumour number and size) and not with bridge therapy or waiting time. RFA allows patients to be maintained longer on the waiting list without negative consequences on drop-off or survival compared with no treatment. Post-transplant outcomes are affected more by tumour characteristics than RFA or wait time.


Norharmane Matrix Enhances Detection of Endotoxin by MALDI-MS for Simultaneous Profiling of Pathogen, Host, and Vector Systems.
The discovery of novel pathogenic mechanisms engaged during bacterial infections requires the evolution of advanced techniques. Here, we evaluate the dual polarity matrix norharmane (NRM) to improve detection of bacterial lipid A (endotoxin), from host and vector tissues infected with Francisella novicida (Fn). We evaluated NRM for improved detection and characterization of a wide range of lipids in both positive and negative polarities, including lipid A and phospholipids across a range of matrix assisted laser desorption-ionization (MALDI)-coupled applications. NRM matrix improved the limit of detection (LOD) for monophosphoryl lipid A (MPLA) down to picogram-level representing a ten-fold improvement of LOD versus 2,5-dihydroxybenzoic acid (DHB) and 100-fold improvement of LOD versus 9-aminoacridine (9-AA). Improved LOD for lipid A subsequently facilitated detection of the Fn lipid A major ion (m/z 1665) from extracts of infected mouse spleen and the temperature-modified Fn lipid A at m/z 1637 from infected D. variabilis ticks. Finally, we simultaneously mapped bacterial phospholipid signatures within an Fn infected spleen along with exclusively host-derived inositol-based phospholipid (m/z 933) demonstrating co-profiling for the host-pathogen interaction. Expanded use of NRM matrix in other infection models and endotoxin-targeting imaging experiments will improve our understanding of the lipid interactions at the host-pathogen interface.


Pain referral and regional deep tissue hyperalgesia in experimental human hip pain models.
Hip disorder patients typically present with extensive pain referral and hyperalgesia. To better understand underlying mechanisms, an experimental hip pain model was established in which pain referrals and hyperalgesia could be studied under standardized conditions. In 16 healthy subjects, pain was induced by hypertonic saline injection into the gluteus medius tendon (GMT), adductor longus tendon (ALT), or gluteus medius muscle (GMM). Isotonic saline was injected contralaterally as control. Pain intensity was assessed on a visual analogue scale (VAS), and subjects mapped the pain distribution. Before, during, and after injections, passive hip joint pain provocation tests were completed, together with quantitative sensory testing as follows: pressure pain thresholds (PPTs), cuff algometry pain thresholds (cuff PPTs), cutaneous pin-prick sensitivity, and thermal pain thresholds. Hypertonic saline injected into the GMT resulted in higher VAS scores than hypertonic injections into the ALT and GMM (P<.05). Referred pain areas spread to larger parts of the leg after GMT and GMM injections compared with more regionalized pain pattern after ALT injections (P<.05). PPTs at the injection site were decreased after hypertonic saline injections into GMT and GMM compared with baseline, ALT injections, and isotonic saline. Cuff PPTs from the thigh were decreased after hypertonic saline injections into the ALT compared with baseline, GMT injections, and isotonic saline (P<.05). More subjects had positive joint pain provocation tests after hypertonic compared with isotonic saline injections (P<.05), indicating that this provocation test also assessed hyperalgesia in extra-articular soft tissues. The experimental models may open for better understanding of pain mechanisms associated with painful hip disorders.


Benchmarking London dispersion corrected density functional theory for noncovalent ion-π interactions.
The strongly attractive noncovalent interactions of charged atoms or molecules with π-systems are important binding motifs in many chemical and biological systems. These so-called ion-π interactions play a major role in enzymes, molecular recognition, and for the structure of proteins. In this work, a molecular test set termed IONPI19 is compiled for inter- and intramolecular ion-π interactions, which is well balanced between anionic and cationic systems. The IONPI19 set includes interaction energies of significantly larger molecules (up to 133 atoms) than in other ion-π test sets and covers a broad range of binding motifs. Accurate (local) coupled cluster values are provided as reference. Overall, 19 density functional approximations, including seven (meta-)GGAs, eight hybrid functionals, and four double-hybrid functionals combined with three different London dispersion corrections, are benchmarked for interaction energies. DFT results are further compared to wave function based methods such as MP2 and dispersion corrected Hartree-Fock. Also, the performance of semiempirical QM methods such as the GFNn-xTB and PMx family of methods is tested. It is shown that dispersion-uncorrected DFT underestimates ion-π interactions significantly, even though electrostatic interactions dominate the overall binding. Accordingly, the new charge dependent D4 dispersion model is found to be consistently better than the standard D3 correction. Furthermore, the functional performance trend along Jacob's ladder is generally obeyed and the reduction of the self-interaction error leads to an improvement of (double) hybrid functionals over (meta-)GGAs, even though the effect of the SIE is smaller than expected. Overall, the double-hybrids PWPB95-D4/QZ and revDSD-PBEP86-D4/QZ turned out to be the most reliable among all assessed methods for the description of ion-π interactions, which opens up new perspectives for systems where coupled cluster calculations are no longer computationally feasible.


Fostering Flu Vaccination in Healthcare Workers: Forum Theatre in a University Hospital.
The World Health Organization recommends flu vaccination as the most effective way to prevent the disease and its severe outcomes and has established the minimum vaccination coverage for people at risk at 75%. Even though healthcare workers (HCWs) represent a strongly recommended target group for flu vaccination campaigns, the average coverage among them is still inadequate. In flu season 2015/2016, our University Hospital tested Forum Theatre (FT) as a new participative strategy to foster HCWs engagement regarding flu vaccination. The aim of this study was to evaluate HCWs' satisfaction with and perceived utility of FT. In 2015, five FT sessions were organized in hospital units which were considered at risk for flu based on the type of admitted patients. After each session, participants were asked to complete an assessment questionnaire. The χ² test or the t-test was used to compare the proportion of participants who were satisfied with the FT and considered it useful (utility score). Data was analyzed according to gender, profession, and age. In all, 16.5% of HCWs who worked in four out of five of the units identified, participated in the FT sessions. Questionnaire results indicated that 74% of spectators were satisfied with their experience and 70% considered this methodology a useful approach for other health issues. Gender, age, and profession did not influence satisfaction or utility scores. Participative strategies such as FT represent an innovative solution to increasing HCWs' awareness of the importance of flu vaccination and could positively impact their adherence to vaccination recommendations. FT can also be a meaningful HCW teaching tool for learning about and changing attitudes toward other clinic and public health issues.


Evaluation of mitigation measures to reduce hydropeaking impacts on river ecosystems - a case study from the Swiss Alps.
New Swiss legislation obligates hydropower plant owners to reduce detrimental impacts on rivers ecosystems caused by hydropeaking. We used a case study in the Swiss Alps (hydropower company Kraftwerke Oberhasli AG) to develop an efficient and successful procedure for the ecological evaluation of such impacts, and to predict the effects of possible mitigation measures. We evaluated the following scenarios using 12 biotic and abiotic indicators: the pre-mitigation scenario (i.e. current state), the future scenario with increased turbine capacity but without mitigation measures, and future scenarios with increased turbine capacity and four alternative mitigation measures. The evaluation was based on representative hydrographs and quantitative or qualitative prediction of the indicators. Despite uncertainties in the ecological responses and the future operation mode of the hydropower plant, the procedure allowed the most appropriate mitigation measure to be identified. This measure combines a basin and a cavern at a total retention volume of 80,000m3, allowing for substantial dampening in the flow falling and ramping rates and in turn considerable reduction in stranding risk for juvenile trout and in macroinvertebrate drift. In general, this retention volume had the greatest predicted ecological benefit and can also, to some extent, compensate for possible modifications in the hydropower operation regime in the future, e.g. due to climate change, changes in the energy market, and changes in river morphology. Furthermore, it also allows for more specific seasonal regulations of retention volume during ecologically sensitive periods (e.g. fish spawning seasons). Overall experience gained from our case study is expected to support other hydropeaking mitigation projects.


No evidence of chromosome damage in chronic obstructive pulmonary disease (COPD).
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. It is characterized by a progressive airflow limitation resulting from an abnormal inflammatory response of the lungs to inhaled gases and particles. Since oxidative stress is thought to play a role in COPD, and since increased oxidative stress is associated with chromosomal instability in several diseases, we investigated whether such relationship also exists in COPD. Whole blood lymphocytes from 49 COPD patients and 48 age- and sex-matched controls were cultivated in vitro and cytogenetic damage was evaluated by micronucleus (MN) and sister-chromatid-exchange (SCE) assays. In patients with COPD, MN frequency was not significantly different from that of controls. Similarly, SCE frequency did not differ in the two groups suggesting no disturbance in DNA replication. Unlike other diseases characterized by oxidative stress, COPD does not appear to be associated with DNA damage.


Toll-like receptors and inflammation in metabolic neuropathy; a role in early versus late disease?
Neuropathy is a common, morbid complication of the metabolic syndrome, prediabetes, and diabetes. Recent studies have indicated a potential role for the immune system in the development of neuropathy. In particular, toll-like receptors (TLR) 2 and 4 have been linked to metabolic dysfunction, and blocking TLR4 is proposed as a treatment for neuropathic pain. In the current study, we investigated the role of the immune system, particularly TLRs 2 and 4, in the pathogenesis and progression of neuropathy. Sural or sciatic nerve gene expression arrays from humans and murine neuropathy models of prediabetes and diabetes were first analyzed to identify differentially expressed TLR2- and TLR4-associated genes within the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. We observed that genes associated with TLRs 2 and 4, particularly lipopolysaccharide binding protein (LPB) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB), were dysregulated across species and across multiple murine models of prediabetic and diabetic neuropathy. To further understand the role of these pathways in vivo, TLR 2 and 4 global knockout mice placed on a 60% high fat diet (HFD-TLR2/4-/-) were compared with wild type (WT) mice on a high fat diet (HFD-WT) and WT controls on a standard diet (CON). Mice then underwent metabolic, neuropathic, and immunological phenotyping at two time points to assess the impact of TLR signaling on neuropathy and immunity during metabolic dysfunction over time. We found that HFD-TLR2/4-/- and HFD-WT mice weighed more than CON mice but did not have increased fasting blood glucose levels. Despite normal blood glucose levels, HFD-TLR2/4-/- mice eventually developed neuropathy at the later time point (28 wks of age) but were somewhat protected from neuropathy at the early time point (16 wks of age) as measured by shorter hind paw withdraw latencies. This is in contrast to HFD-WT mice which developed neuropathy within 11 wks of being placed on a high fat diet and were neuropathic by all measures at both the early and late time points. Finally, we immunophenotyped all three mouse groups at the later time point and found differences in the number of peripheral blood Ly6C-myeloid cells as well as F4/80+ expression. These results indicate that TLR signaling influences early development of neuropathy in sensory neurons, potentially via immune modulation and recruitment.


Penetration of C8 and C9 in the C5b-9 complex across the erythrocyte membrane into the cytoplasmic space.
We have developed a technique in which transglutaminase is used to measure the penetration of terminal complement proteins across the erythrocyte membrane into the cytoplasmic space. Penetration of a given terminal complement protein into the cytoplasmic space was assessed by labeling the protein of interest with radioactive iodine, forming the complement channel using the labeled protein, adding transglutaminase to only one side of the membrane, and allowing the enzyme to cross-link the susceptible proteins on that side of the membrane. Cross-linking was assessed by measuring the increase in molecular weight of the appropriate molecule on sodium dodecyl sulfate gels under reducing conditions. The results of these experiments indicate that C8 and C9 are rapidly cross-linked to high molecular weight from either the interior or the exterior of the membrane. In order to determine whether the cross-linking mediated by enzyme on the interior was occurring from within the ghosts and not via enzyme that had leaked into the extracellular medium, experiments were performed with dimethylcasein in the extracellular medium. In the presence of this protein, cross-linking of C8 and C9 from outside was negligible. Hence, if cross-linking occurs when transglutaminase is trapped inside the ghosts, it cannot be due to leakage of enzyme, but must be attributable to cross-linking from the inside. The results show that C9 definitely penetrated across the membrane into the intracellular space. With respect to C8, statistical evaluation indicates that C8 probably penetrated into the intracellular space.


SCOUT: A Fast Monte-Carlo Modeling Tool of Scintillation Camera Output.
We have developed a Monte-Carlo photon-tracking and readout simulator called SCOUT to study the stochastic behavior of signals output from a simplified rectangular scintillation-camera design. SCOUT models the salient processes affecting signal generation, transport, and readout. Presently, we compare output signal statistics from SCOUT to experimental results for both a discrete and a monolithic camera. We also benchmark the speed of this simulation tool and compare it to existing simulation tools. We find this modeling tool to be relatively fast and predictive of experimental results. Depending on the modeled camera geometry, we found SCOUT to be 4 to 140 times faster than other modeling tools.


Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.
OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient-months of remission and treatment failure showed that the remission rate in the study sample statistically exceeds the rate in historical controls (71.9%; p = 0.0007, Fisher's exact test). Long-term unexpected hormonal deficiencies were statistically similar between study patients (29%) and those in a meta-analysis (25%; p = 0.7596, Fisher's exact test). CONCLUSIONS These preliminary findings reflect the promising potential of tissue-based ACTH-antibody-guided assay for improving the cure rates of Cushing disease patients undergoing TSR. Further studies with larger sample sizes, further refinements of assay interpretation, and longer-term follow-ups are needed.


Understanding the roles of genome and envirome: methods in genetic epidemiology.
In order to understand studies of psychiatric epidemiology focusing on the 'genome' and 'envirome', basic knowledge of the logic and methods is necessary. To provide a review of typical methods used in genetic epidemiology. Reviews of the research designs usually employed in quantitative and molecular genetic studies. Genotype-environment correlation and interaction are also discussed. Quantitative genetic studies indicate that genetic influences are important for both psychiatric disorders and behavioural traits. Specific gene loci can be tested for associations with both psychiatric risk and behavioural traits by means of molecular genetic techniques. There has been little examination of genotype-environment correlation and interaction, although the few reports that have appeared suggest that these complex relationships are important. Advances in quantitative and molecular genetics now permit more careful examination of genotype-environment interaction and correlation. Studies combining molecular genetic strategies with measurement of the environment are still at an early stage, however, and their results must be awaited.


[Effect of pro- and antioxidant food factors on macrophage oxidative metabolism].
The effects of vitamin E deficiency and excess polyunsaturated acids in the diet on luminol-dependent chemiluminescence were studied in Aug-Lac rats. It was chown that experimental prooxidant regiments led to the increase of oxidative metabolism in macrophages stimulated by opsonized zymozan. Vitamin E deficient regimens decreased superoxide dismutase activity of macrophages. In vitro DL-alpha-tocopherol and the synthetic antioxidants BHT and BHA inhibited chemiluminescence of macrophages. Arachidonic acid activated macrophages and induced the formation of oxygen radicals.


Decline of the calcium response on successive stimulation of a rat brain endothelial cell P2U purinoceptor.
A microfluorimetric method using Fura-2 as calcium indicator was used to study the mechanism of desensitization of the calcium response evoked by activation of a brain endothelial cell P2U receptor. The study was mainly carried out on an immortalized rat brain endothelial cell line (RBE4), with some additional experiments on primary cultured rat brain microvascular endothelial cells. As previously described (Nobles et al. 1995), ATP (100 microM, 20 s) caused a transient increase in intracellular calcium levels ([Ca2+]i). This effect was dependent on the rate of filling of intracellular calcium stores, since a large inhibition of the ATP-mediated response was seen in the presence of cyclopiazonic acid, an inhibitor of the store Ca(2+)-ATPase. Application of repeated pulses of extracellular ATP led to a desensitization of the response, as measured by a decline in the release of intracellular calcium (Nobles et al. 1995). This desensitization was partially reversed after 300 s of incubation in agonist-free medium. Extracellular phosphorylation of the purinergic receptor appeared not to be involved in the desensitization process, since a similar rate of desensitization was obtained with the non-hydrolysable ATP analogue ATP gammaS. Oxidation of the purinergic receptor cannot account for the desensitization, since the decline of the ATP-mediated response was unchanged in the presence of 3 mM dithiothreitol. In the presence of ATP together with UTP, two equally potent activators of the P2U receptor, the desensitization was less than in the presence of only one of the agonists. The desensitization was greater when ATP was applied for longer (150 s) periods. Although these results do not exclude the participation of post-receptor events in the desensitization process, they suggest that desensitization is governed at least in part by agonist-receptor interaction.


Inactıve hepatitis B surface antigen carriers and intrafamilial tramsmission: results of a 10-year study.
The aims of the present study were to determine the outcomes of inactive hepatitis B virus (HBV) surface antigen (HBsAg) carriers over a 10-year study period and to elucidate the HBV serological profile of their family members. We retrospectively analyzed the medical files of inactive HBsAg carriers followed up at the Department of Infectious Diseases of Kocatepe University Medical Faculty Hospital between March 2001 and January 2011. In total, 438 inactive HBsAg carriers were enrolled in this trial. The follow-up period was 33.7 ± 22.5 months (mean ± SD). Anti-hepatitis-B surface antibody seroconversion occurred in 0.7% of cases, while chronic hepatitis B was found in 0.5%. The anti-hepatitis-D virus (HDV) status was evaluated in 400 patients and anti-hepatitis C virus (HCV) in 430. It was found that 1% and 0.2% were positive for anti-HDV and anti-HCV, respectively. HBV serology was investigated in at least 1 family member of 334/438 (76.3%) patients. The HBsAg positivity rate was 34.6% in 625 family members of 334 patients. A comparison of the HBsAg positivity rates in terms of HBV DNA levels in index cases revealed that HBsAg seropositivity rates were higher in family members of HBV DNA-negative patients than in family members of HBV DNA-positive cases (P=0.0001). The HBsAg positivity rate was higher in family members of inactive HBsAg carriers than in the general population; these family members therefore have a higher risk of HBV transmission. Furthermore, despite negative HBV DNA levels, transmission risk was not reduced in these patients, and horizontal transmission seems to be independent of the HBV DNA value.


Intrathoracic Pressure Regulation Improves Cerebral Perfusion and Cerebral Blood Flow in a Porcine Model of Brain Injury.
Brain injury is a leading cause of death and disability in children and adults in their most productive years. Use of intrathoracic pressure regulation (IPR) to generate negative intrathoracic pressure during the expiratory phase of positive pressure ventilation improves mean arterial pressure and 24-h survival in porcine models of hemorrhagic shock and cardiac arrest and has been demonstrated to decrease intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these models. Application of IPR for 240 min in a porcine model of intracranial hypertension (ICH) will increase CPP when compared with controls. Twenty-three female pigs were subjected to focal brain injury by insertion of an epidural Foley catheter inflated with 3 mL of saline. Animals were randomized to treatment for 240 min with IPR set to a negative expiratory phase pressure of -12 cmH2O or no IPR therapy. Intracranial pressure, mean arterial pressure, CPP, and cerebral blood flow (CBF) were evaluated. Intrathoracic pressure regulation significantly improved mean CPP and CBF. Specifically, mean CPP after 90, 120, 180, and 240 min of IPR use was 43.7 ± 2.8 mmHg, 44.0 ± 2.7 mmHg, 44.5 ± 2.8 mmHg, and 43.1 ± 1.9 mmHg, respectively; a significant increase from ICH study baseline (39.5 ± 1.7 mmHg) compared with control animals in which mean CPP was 36.7 ± 1.4 mmHg (ICH study baseline) and then 35.9 ± 2.1 mmHg, 33.7 ± 2.8 mmHg, 33.9 ± 3.0 mmHg, and 36.0 ± 2.7 mmHg at 90, 120, 180, and 240 min, respectively (P < 0.05 for all time points). Cerebral blood flow, as measured by an invasive CBF probe, increased in the IPR group (34 ± 4 mL/100 g-min to 49 ± 7 mL/100 g-min at 90 min) but not in controls (27 ± 1 mL/100 g-min to 25 ± 5 mL/100 g-min at 90 min) (P = 0.01). Arterial pH remained unchanged during the entire period of IPR compared with baseline values and control values. In this anesthetized pig model of ICH, treatment with IPR significantly improved CPP and CBF. This therapy may be of clinical value by noninvasively improving cerebral perfusion in states of compromised cerebral perfusion.


Reversed development and cellular aging in an insect.
Larvae of the beetle Trogoderma glabrum undergo partially reversed development when deprived of food and water. Retrogressive larval ecdyses occur, and the larvae become diminished in size and weight. Given food, the larvae regrow, ecdyze, and regain their previous degree of maturity. Repeated cycles of retrogression and regrowth are possible. Although larval in form and organ differentiation, repeatedly retrogressed insects display a physiological deterioration suggestive of aging. A deterioration of the ability to regrow is accompanied by increasing fat body polyploidy.


Molluscan shell colour.
The phylum Mollusca is highly speciose, and is the largest phylum in the marine realm. The great majority of molluscs are shelled, including nearly all bivalves, most gastropods and some cephalopods. The fabulous and diverse colours and patterns of molluscan shells are widely recognised and have been appreciated for hundreds of years by collectors and scientists alike. They serve taxonomists as characters that can be used to recognise and distinguish species, however their function for the animal is sometimes less clear and has been the focus of many ecological and evolutionary studies. Despite these studies, almost nothing is known about the evolution of colour in molluscan shells. This review summarises for the first time major findings of disparate studies relevant to the evolution of shell colour in Mollusca and discusses the importance of colour, including the effects of visual and non-visual selection, diet and abiotic factors. I also summarise the evidence for the heritability of shell colour in some taxa and recent efforts to understand the molecular mechanisms underpinning synthesis of shell colours. I describe some of the main shell pigments found in Mollusca (carotenoids, melanin and tetrapyrroles, including porphyrins and bile pigments), and their durability in the fossil record. Finally I suggest that pigments appear to be distributed in a phylogenetically relevant manner and that the synthesis of colour is likely to be energetically costly.


Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus.
Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The precursor activity of serum Gc protein was reduced in all influenza virus-infected patients. These patient sera contained alpha-N-acetylgalactosaminidase (Nagalase) that deglycosylates Gc protein. Deglycosylated Gc protein cannot be converted to MAF, thus it loses the MAF precursor activity, leading to immunosuppression. An influenza virus stock contained a large amount of Nagalase activity. A sucrose gradient centrifugation analysis of the virus stock showed that the profile of Nagalase activity corresponds to that of hemagglutinating activity. When these gradient fractions were treated with 0.01% trypsin for 30 min, the Nagalase activity of each fraction increased significantly, suggesting that the Nagalase activity resides on an outer envelope protein of the influenza virion and is enhanced by the proteolytic process. After disruption of influenza virions with sodium deoxycholate, fractionation of the envelope proteins with mannose-specific lectin affinity column along with electrophoretic analysis of the Nagalase peak fraction revealed that Nagalase is the intrinsic component of the hemagglutinin (HA). Cloned HA protein exhibited Nagalase activity only if treated with trypsin. Since both fusion capacity and Nagalase activity of HA protein are expressed by proteolytic cleavage, Nagalase activity appears to be an enzymatic basis for the fusion process. Thus, Nagalase plays dual roles in regulating both infectivity and immunosuppression.


Prevalence of disorders in preweaned dairy calves from 731 dairies in Germany: A cross-sectional study.
The objective of this cross-sectional study was to determine the prevalence of disorders in preweaned calves in 3 regions in Germany, exemplary for structural diversity in dairy farming. A farm visit was performed on a single occasion on 731 dairy farms in the northern, eastern, and southern regions of Germany between December 2016 and July 2019. Farms differed in herd size, geographical location, and management. In the northern region, the farms had a median of 90 milking cows and were often run as full-time family businesses, partly with external workers. The eastern region tended to have larger farms (a median of 251 milking cows), which were often large-scale agricultural enterprises with employees. In the southern region, the farms had a median of 39 milking cows and were often traditional family businesses, some of these being part-time businesses. Clinical examinations were performed on 14,164 preweaned dairy calves (median 12 calves per farm) by trained veterinarians. A complete data set was available for 13,656 calves. Almost half (42.0%) of the evaluated calves were classified as being affected by at least 1 of the common calf disorders. Omphalitis (O, 20.9%; n = 2,876) and diarrhea (D, 18.5%; n = 2,670) were the most frequently recorded diagnoses, whereas respiratory diseases (RD) were observed to a lesser extent (8.7%; n = 1,100). A striking feature was the fact that 7.1% (n = 987) of the calves were affected by more than 1 disorder at the same time (multimorbidity, M). The following combinations of disorders were frequently observed: O and D (n = 596), O and RD (n = 164), and D and RD (n = 140). Disorders such as O and D, as well as M, were predominantly observed in calves aged 2 wk. A gradual increase in the frequency of RD was observed with age. For all disorders except RD, male calves were more often affected than females. Omphalitis was predominantly diagnosed in the summer months, whereas RD, D, and M were more common in the fall. We detected several statistically significant differences in the prevalence of clinical signs and disorders in preweaned dairy calves between the 3 exemplary regions. The prevalence of RD was higher in the south (10.8%) than in the north (8.2%) and east (7.4%). In the north (33.2%), O was observed more frequently than in the other regions (east: 18.9%; south: 10.5%), whereas D was found less frequently in the north (13.8%) than in the east (21.6%) and south (20.0%).


Rapid high performance liquid chromatographic method for determination of clarithromycin in human plasma using amperometric detection: application in pharmacokinetic and bioequivalence studies.
A rapid, sensitive and reproducible HPLC method using amperometric detector was developed and validated for the analysis of clarithromycin in human plasma. The separation was achieved on a monolithic silica column (MZ- C8 125×4.0 mm) using acetonitrile-methanol-potassium dihydrogen phosphate buffer (40:6:54,v/v), with pH of 7.5, as the mobile phase at a flow rate of 1.5 mL/min. The assay enables the measurement of clarithromycin for therapeutic drug monitoring with a minimum quantification limit of 20 ng/mL. The method involves simple, protein precipitation procedure and analytical recovery was complete. The calibration curve was linear over the concentration range of 0.1-6 μg/mL. The coefficients of variation for inter-day and intra-day assay were found to be less than 6%. This method was used in bioequivalency and pharmacokinetic studies of the test (generic) product 2 × 500 mg clarithromycin tablets, with respect to the reference product.


[Dacryoendoscopy and laser dacryoplasty: technique and results].
In a bicentrical study in the eye clinic of Darmstadt and the eye clinic of the St. Josef Hospital Hagen 261 dacryoendoscopies were performed until February 1997. In 261 dacryoendoscopies (143 women, 93 men and 25 children, the average age was 46.6 years). In dependence of the assessment of the mucosa conditions intraoperatively in all 261 cases the planed operative strategy was checked and if needed changed. After surgical interventions of the lacrimal system 70 cases of dacryocystorhinostomia externa were seen 138 cases of intubation of the lacrimal drainage system and 53 cases of laserdacryoplastic. Intubation of the lacrimal system was always performed after laserdacryoplastic and after a patency was produced (average age 58.3 years). Suitable indications for a laserdacryoplastic are: circumscribed stenosis of the distal saccus, point-sized stenosis of the canaliculus, membranous restenosis after dacryocystorhinostomia externa. The method shows no important rate of intraoperative complications, only in one case there was intraoperatively a protrusion bulbi and a haematoma of the eyelid, which postoperatively eased fastly away. The postoperative convalescence is in comparence to conventional surgical interventions of the lacrimal drainage system enormously shortened. The follow-up after 3 months showed a subjective improvement of epiphora in more than 75% of the patients, the success of this intervention therefore could be compared with conventional surgical methods of the lacrimal drainage system. The dacryoendoscopy is a new important diagnostic development, which shows with help of better developed endoscopy-systems compared to previous systems a much better quality of the image and is therefore a valuable diagnostic help. Due to the check of the preoperative indication it is intraoperatively possible to confirm or, if needed, to change the indication after dacryoendoscopy. The laserdacryoplastic is an important new therapeutical development of the dacryoendoscopy and shows in suitable indications a comparable success-rate of conventional surgical interventions of the lacrimal drainage system. Therefore the possibility exists to carry out minimal invasive interventions of the lacrimal drainage.


Health-related quality of life in asthma studies. Can we combine data from different countries?
The aim was to compare health-related quality of life (HRQL) in patients with asthma from 4 countries, and to investigate the correlations between HRQL and clinical indices.341 patients; 140 (Sweden), 54 (Norway), 65 (the Netherlands) and 82 (Greece) were treated with formoterol fumarate 4.5 microg or with terbutaline sulphate 0.5mg for 12 weeks inhaled 'on demand' via Turbuhaler. The Asthma Quality of Life Questionnaire (AQLQ) and clinical indices were assessed. The mean baseline AQLQ overall scores in Sweden (4.97), in the Netherlands (5.04), in Norway (4.68) and in Greece (4.68) were in the same range, however, with a significant difference between the four countries (p=0.038). When comparing AQLQ, activity limitation and symptoms domains, the differences between the countries were not statistically significant. The cross-sectional correlations between AQLQ overall score and the clinical indices were similar in all four countries. The magnitude of change in AQLQ was consistent with the other clinical variables. The correlations between change in AQLQ overall score and change in clinical indices were low to medium in all countries. In conclusion, the consistency of cross-sectional correlations between the AQLQ overall and clinical indices across countries supports the validity of translations of the AQLQ used in this study. There were differences in baseline values between the countries. The treatment response in AQLQ differed to the same extent as other clinical indices. When combining HRQL data from different countries, there might be cultural, gender and socio-economic differences, explaining different responses to treatment.


Concentration and detection of hepatitis A virus and rotavirus from shellfish by hybridization tests.
A modified polyethylene glycol precipitation method for concentration of virus followed by a new method to recover nucleic acid was used to detect hepatitis A virus (HAV) and rotavirus (SA11) in shellfish (oysters and hard-shell clams) by hybridization tests. Infectious virus, seeded into relatively large quantities of shellfish, was recovered consistently, with greater than 90% efficiency as measured by either in situ hybridization (HAV) or plaque assay (rotavirus SA11). Viral nucleic acid for dot blot hybridization assays was extracted and purified from virus-containing polyethylene glycol concentrates. Separation of shellfish polysaccharides from nucleic acid was necessary before viral RNA could be detected by dot blot hybridization. Removal of shellfish polysaccharides was accomplished by using the cationic detergent cetyltrimethylammonium bromide (CTAB). Use of CTAB reduced background interference with hybridization signals, which resulted in increased hybridization test sensitivity. After polysaccharide removal, dot blot hybridization assays could detect approximately 10(6) physical particles (corresponding to approximately 10(3) infectious particles) of HAV and 10(4) PFU of SA11 rotavirus present in 20-g samples of oyster and clam meats. These studies show continuing promise for the development of uniform methods to directly detect human viral pathogens in different types of shellfish. However, practical applications of such methods to detect noncultivatable human viral pathogens of public health interest will require additional improvements in test sensitivity.


Proteomics in nephrology: current status and future directions.
Proteomics is one among various 'OMICS' fields that have been growing rapidly in the postgenomic era. During the past few years, proteomics has been extensively applied to several fields of medicine to better understand normal physiology, to define the pathophysiology of diseases, and to identify novel biomarkers and new therapeutic targets. This review focuses on current status and future directions of proteomics in the nephrology field. Recent studies of renal proteome, proteomes of individual intrarenal structures (i.e., glomerular, vascular, tubular, brush border membrane, mesangial, and podocyte proteomes), urinary proteome, and protein profiles in dialysate or ultrafiltrate removed by renal replacement therapy are summarized.


Depth-resolving THz imaging with tomosynthesis.
We demonstrated a depth-resolved 3D imaging technique based on absorption contrast using tomosynthesis. Tomosynthesis is similar to computed tomography except that the number of projections is much smaller. We constructed a tomosynthesis imaging system, which detects a transmitted continuous THz wave. We applied a backprojection method that was suitable for the constructed detection configuration, to reconstruct an image. Using this system, we imaged a test sample made from paper and reproduced characters written by pencil.


How Does Homelessness Affect Parenting Behaviour? A Systematic Critical Review and Thematic Synthesis of Qualitative Research.
The adverse social and physical conditions of homelessness pose significant developmental risks for children, which may be compounded or buffered by the quality of parenting behaviour they are exposed to. There is currently a limited understanding of how parents approach their care-giving role and responsibilities while adjusting to the experience of homelessness. Advancing knowledge in this area is essential for developing acceptable, appropriate and effective interventions to support highly marginalised and vulnerable homeless families. This review explored homeless parents' perceptions of how homelessness affects their parenting behaviour and identified adaptive strategies that parents may use to mitigate the potentially negative impacts of homelessness on the quality of care-giving. A systematic search of four electronic databases (ASSIA, PsycINFO, Web of Science and MEDLINE) identified 13 published qualitative studies, all originating from the USA, which explored parenting behaviour in homeless contexts. The studies were critically appraised using the CASP qualitative assessment tool. Thematic synthesis identified the following determinants of parenting behaviour; negative self-concept in the parental role, parental mental health, material resources, challenges to autonomy and self-efficacy, daily hassles, physical environment and service context, stigma, child characteristics and lack of support. These were synthesised thematically using existing models of parenting determinants and positive parenting. Findings indicate substantive impacts of homelessness on parental mental health, parenting authority, material resources, parenting environments and social support. Parents developed a number of adaptive methods to negotiate the challenges of homeless parenting such as maintaining a positive mindset, cherishing the parental role and developing practical strategies. We conclude with recommendations that service providers should tailor parenting support to resource-constrained circumstances and that further research is required in order to better understand experiences of homeless parents in other international contexts.


Cost effectiveness analysis of duration of nonoperative management for adhesive bowel obstruction in a developing country.
Adhesive bowel obstruction (ABO) costs billions of dollars in developed countries. Cost is unknown in developing countries. This depends on the type of management and duration of hospital stay. Nonoperative management (NOM) of uncomplicated obstruction is safe for up to 10 days. While it remains cost effective, the most efficient duration of nonoperative management must retain its advantages over operative management. To describe cost effectiveness of various durations of nonoperative management of adhesive obstruction in a developing country. Over 2 year period, Patients who had uncomplicated adhesive obstruction were observed on trial of nonoperative management. Length of hospital stay and success rate were combined as surrogates for Cost effectiveness analysis of 2 to 5 days and ≥7 days nonoperative management. 41 patients (24(58.5%) females) were eligible. Mean age 38.4 ± 14.7 (range 18-80) years. 31 (75.6%) were first time admissions. The most common previous abdominal operations were for appendix and obstetrics and gynecologic pathologies. Median duration of nonoperative management (dNOM) was 4 days, median LOS was 9 days. Nonoperative management was successful in 53.7% (22 patients). Total estimated direct hospital cost of 41 adhesive bowel obstructions was $133,279. Total personnel charges were $112,142. Mean operative and nonoperative management was $4,914 and $1,814 respectively (p <0.0001). Most of successful nonoperative management was within 5 days. 4 days nonoperative management had the highest cost utility. From this study, without indications for immediate surgical intervention, 4 days nonoperative management is the most cost effective course, after which surgical intervention may be considered if there is no improvement.


Effects of epidermal growth factor and follicle-stimulating hormone during in vitro maturation on cytoplasmic maturation of porcine oocytes.
The present study was undertaken to investigate the influence of epidermal growth factor (EGF) and follicle-stimulating hormone (FSH) during in vitro maturation on cytoplasmic maturation of porcine oocytes as revealed by the success of fertilization and by the changes in the pattern of protein synthesis in oocytes and cumulus cells. For fertilization studies, oocyte-cumulus cell complexes (OCC) were cultured in media containing human recombinant EGF (1 ng/ml) or FSH (1.5 microg/ml) or both for 44 hr prior to fertilization with fresh sperm for 6-8 hr. The oocytes were then fixed, stained, and examined as whole mounts following an additional 14 hr of culture. Addition of EGF, FSH, and EGF + FSH significantly increased the proportion of oocytes reaching MII stage. The addition of EGF alone significantly decreased the percentage of polyspermic oocytes and increased the proportion of monospermic oocytes forming 2 normal pronuclei. FSH abolished these effects of EGF and significantly increased the percentage of polyspermic oocytes forming more than 2 pronuclei when added alone or with EGF. For protein analysis, OCC were cultured in media containing the above hormones for 6, 24, and 44 hr and exposed to 0.5 mCi/ml L-[35S]methionine during the last 3 hr of cultures. The oocytes and cumulus cells were separated prior to lysis in SDS sample buffer, and denatured polypeptides were separated by 1-dimensional SDS-PAGE. In the oocyte, addition of EGF and FSH alone stimulated the synthesis of 34, 45, and 97 kDa proteins after 6 hr of culture; however, the addition of EGF and FSH together was without any effect. After 24 hr, EGF alone inhibited the synthesis of these peptides, whereas FSH alone and with EGF maintained the stimulation of synthesis of 34 and 45 kDa proteins. Two additional peptides corresponding to 66 and 200 kDa appeared at this time as a result of exposure to FSH alone or with EGF. After 44 hr of culture, these 2 new peptides were observed in all groups and the stimulatory effect of FSH and FSH + EGF was still evident. An additional peptide of 26 kDa appeared at this time as a result of FSH and EGF + FSH treatments. In the cumulus cells, EGF and FSH each alone induced the synthesis of a new peptide of 26 kDa after 6 hr of culture. FSH when added alone or with EGF induced the synthesis of an additional peptide of 29 kDa, the synthesis of which remained unchanged at 24 and 44 hr. After 24 hr, FSH alone and in combination with EGF induced the synthesis of an additional 38 kDa peptide and its synthesis was still maintained at 44 hr. EGF alone had no effect on protein synthesis in cumulus cells at 24 and 44 hr. These studies indicate that EGF may have a physiological role in the regulation of cytoplasmic maturation of porcine oocytes.


Intimate Partner Violence Perpetration Among Sexual Minority Young Adults: Associations With Alcohol Use, PTSD Symptoms, Internalized Homophobia, and Heterosexist Discrimination.
Lesbian, gay, bisexual, queer, and other sexual minority (LGBQ+) young adults report similar or higher rates of intimate partner violence (IPV) perpetration than their heterosexual peers. Elevated IPV risk among LGBQ+ young adults may be attributable to experiencing heterosexist discrimination and internalized homophobia. In addition, LGBQ+ people report disproportionate posttraumatic stress disorder (PTSD) symptoms, alcohol use, and IPV perpetration in dating relationships. Thus, this study explored which combinations of IPV risk factors (i.e., experiencing heterosexist discrimination, internalized homophobia, PTSD symptoms, alcohol use) related to forms of IPV perpetration, inclusive of psychological, physical, and sexual forms, in a sample of 342 LGBQ+ young adults. Internalized homophobia was related to psychological IPV perpetration at high and medium levels of PTSD symptoms and only high levels of alcohol use. PTSD symptoms and alcohol use interacted to predict psychological IPV perpetration; and PTSD symptoms related to increased psychological IPV perpetration at high and medium, but not low, alcohol use levels. Alcohol use was positively related to physical IPV perpetration. No other risk factors or interactions were significantly related to physical or sexual IPV perpetration. Results were consistent with prior findings that linked internalized homophobia, alcohol use, and PTSD symptoms to IPV perpetration and highlight the interacting nature of these IPV perpetration risk factors. Comprehensive IPV interventions with LGBQ+ young adults should evaluate the impact of simultaneously targeting these multiple IPV risk factors considering their interacting contributions to IPV perpetration risk. More research is needed to examine the temporal relations between minority stress, PTSD symptoms, alcohol use, and IPV perpetration.


Entanglement between light and an optical atomic excitation.
The generation, distribution and control of entanglement across quantum networks is one of the main goals of quantum information science. In previous studies, hyperfine ground states of single atoms or atomic ensembles have been entangled with spontaneously emitted light. The probabilistic character of the spontaneous emission process leads to long entanglement generation times, limiting realized network implementations to just two nodes. The success probability for atom-photon entanglement protocols can be increased by confining a single atom in a high-finesse optical cavity. Alternatively, quantum networks with superior scaling properties could be achieved using entanglement between light fields and atoms in quantum superpositions of the ground and highly excited (Rydberg) electronic states. Here we report the generation of such entanglement. The dephasing of the optical atomic coherence is inhibited by state-insensitive confinement of both the ground and Rydberg states of an ultracold atomic gas in an optical lattice. Our results pave the way for functional, many-node quantum networks capable of deterministic quantum logic operations between long-lived atomic memories.


Geographic variation in the prevalence of common mental disorders in Britain: a multilevel investigation.
It is still not known whether the places that people live affect their mental health. The principal aim of this 1991 study was to quantify simultaneously variance in the prevalence of the most common mental disorders, anxiety and depression, in Britain at the individual, household, and electoral ward levels. Data from a cross-sectional, nationally representative survey of 8,979 adults aged 16-74 years living in private households nested within 642 electoral wards in England, Wales, and Scotland were analyzed by using multilevel logistic and linear regression. Common mental disorders were assessed by using the General Health Questionnaire. Less than 1% of the total variance in General Health Questionnaire scores occurred at the ward level. This variance was further reduced and was no longer statistically significant after adjustment for characteristics of persons. By contrast, the proportion of total variance at the household level (14.4%, 95% confidence interval: 11.4, 17.5 in the null model) (p < 0.001) was statistically significant and remained so after adjustment for individual- and household-level exposures. While these findings suggest that future interventions should target persons and households rather than places, further research is first required to establish whether other (particularly smaller) areas lead to similar results.


Cardiac sympathetic impairment parallels nigrostriatal degeneration in Probable Dementia with Lewy Bodies.
Dementia with Lewy Bodies (DLB) must be distinguished from other types of dementia because of important differences in patient management and outcome. Both reduction in cardiac 123I-metaiodobenzilguanidine (MIBG) uptake and decreased 123I-FP-CIT binding in basal ganglia have been described in DLB. The aim of this study was to assess the relationship between cardiac sympathetic activity and nigrostriatal degeneration in patients with probable DLB. Twenty-eight patients (15 males; mean age 77 years, range 64-88 years) with clinical international criteria of probable DLB were included in the study. All patients underwent a cardiac MIBG scintigraphy and a FP-CIT SPECT. Global cardiac MIBG uptake was semiquantified by means of heart-to-mediastinum ratio (HMR) (normal >1.56). FP-CIT binding in basal ganglia was calculated and compared with an age-matched control group. The relation between cardiac MIBG uptake and FP-CIT uptake in basal ganglia, and the relationship of these two techniques with distinctive symptoms of DLB, features of past medical history and data from the neuropsychological examination were assessed. Cardiac MIBG uptake was decreased in 23 of 28 patients (HMR=1.32, range 0.95-1.85). The FP-CIT binding in basal ganglia was significantly lower than in control group (2.01±0.5 vs 2.62±0.2, P<0.05). All patients with reduced cardiac HMR showed decreased FP-CIT binding in basal ganglia. There was a positive correlation between the HMR and specific binding ratio of striatum (P<0.01). A high correlation between FP-CIT SPECT and the presence of parkinsonism also was found. No correlation between cardiac MIBG uptake and demographic, clinical or neuropsychological data was found. In probable DLB cardiac MIBG uptake and FP-CIT binding in basal ganglia are reduced. The positive correlation between both measures suggests that cardiac sympathetic degeneration and nigrostriatal degeneration parallel similarly in patients with probable DLB.


The effect of dexamethasone on L-alpha-lysophosphatidyl choline (lysolecithin)-induced demyelination of the rat spinal cord.
Adult male Sprague-Dawley rats were injected intraspinally with 2 microL of 1% lysolecithin to induce demyelination. This was followed by systemic treatment with dexamethasone acetate for two weeks. Control groups were injected with lysolecithin but not treated. The animals were perfused at 8, 12, 28, and 60 days postoperatively, and the spinal cords were processed and examined histopathologically. The intraspinal injection of lysolecithin produced a focal area of primary demyelination followed by remyelination. In the steroid-treated groups, there was a suppression of the mononuclear phagocytic response, accompanied by slow clearance of the disrupted myelin sheaths and an apparent reduction in lesion size. Remyelination was substantially retarded in comparison with the controls. The findings suggest that steroids interfere with the process of remyelination, as they are known to do with myelination during development. Thus, dexamethasone appears to have a dual effect, decreasing demyelination but delaying remyelination.


Significant increase in 1-year posttransplant renal arterial index predicts graft loss.
Conflicting data have been reported concerning the use of kidney graft arterial resistance index (RI) measured by Doppler to predict death-censored graft loss. We hypothesized that changes in RI values could carry better information than a single measure of RI. Four hundred twenty-five renal transplant recipients were included in the study. We tested whether changes in renal arterial resistance index between 4 and 12 months after transplant (ΔRI(4→12)) were predictive of graft loss. Neither 4-month nor 1-year RI predicted graft loss. The area under the receiver operating characteristics curve of ΔRI(4→12) for graft loss was 0.75. A ΔRI(4→12) ≥10% had the best sensitivity and specificity. One year after transplant, 22% of the study population had ΔRI(4→12) ≥10%. Fifty-five patients (12.9%) experienced graft loss during follow-up. The annual incidence of graft loss was higher in patients with ΔRI(4→12) ≥10% (3.5 versus 1.3%; P = 0.009). In multivariate analysis, patients with ΔRI(4→12) ≥10% had an increased risk of graft loss (hazard ratio, 6.21; 95% confidence interval, 1.99 to 22.15; P = 0.002). A variation in RI ≥10% in the first year after transplant is an independent risk factor for death-censored graft loss in renal transplant recipients.


The use of rotational fluoroscopy and 3-D reconstruction in the diagnosis and surgical planning for complex cloacal malformations.
Cloacal malformations, a confluence of the urinary tract, vagina and rectum into a single common channel, has a broad and complex anatomic spectrum requiring an imaging tool for visualization, measurement, and surgical planning for the reconstruction of these structures. We evaluated the role of 3-D fluoroscopy for this purpose, as it offers a combination of spatial correlation with precise anatomic measurements. We examined our imaging protocol for patients with a cloacal malformation and report our experience with rotational fluoroscopy and 3-D reconstruction in 16 consecutive patients referred for cloacal reconstruction. The length of the common channel (CC), the length of the urethra from the bladder neck to the common channel, and the height (and existence or absence) of a vagina or vaginas were determinants of the surgical procedures used for the repair. We performed 16 consecutive 3-D cloacagrams (age range 4 months to 9 years) using a new protocol (Figure 1) that provided the following data which helped with surgical planning: Gynecologic: 3 cases with a single vagina, 5 cases with a duplicated Mullerian system (3 of which were asymmetric) and 2 cases with high vaginas requiring vaginal replacement. Colorectal: Four had a high rectum requiring an abdominal approach, and 6 had a rectum reachable via a posterior sagittal approach. Urologic: Two ectopic ureters requiring reimplantation, 3 patients had vesicoureteral reflux (1 bilateral, 2 unilateral), 1 patient had no bladder, and 7 had a normal sized bladder. Common channel length and urethral length were demonstrated in all cases and used to decide between a total urogenital mobilization or a separation of vagina(s) from the common channel, urogenital separation. The 3-D cloacagram can help predict the surgical plan for urologic, gynecologic, and colorectal components of the cloacal repair. It can predict the CC length as well as the length of the urethra. It helps with predicting the need for vaginal replacement and whether an abdominal approach is needed for the rectum. Its effectiveness is based on the ability to adequately distend structures and see their distal most extent, an advantage over other modalities such as MRI. Added benefits (particularly from the 3D view) include a better spatial understanding of the defect and the diagnosis of concomitant urological abnormalities such as vesicoureteral reflux and ectopic ureters. Disadvantages to this procedure include the need for general anesthesia and a higher exposure to radiation. 3.


Targeting the S and G2 checkpoint to treat cancer.
Cell survival following DNA damage depends on activating checkpoints to arrest proliferation. Most cancer cells have dysregulated G1 checkpoints making them dependent on their S and G2 checkpoints, which are activated by ATR/Chk1 signalling. Thus, inhibiting ATR or Chk1 should selectively sensitise cancer cells to DNA damage. Genetic inactivation of ATR and Chk1 abrogates cell cycle arrest and enhances cytotoxicity following exposure to DNA-damaging agents. Similar effects were seen with small-molecule Chk1 inhibitors in preclinical studies, and clinical trial data are starting to emerge. Recently, potent ATR inhibitors have been identified that also sensitise cancer cells in vitro. ATR and Chk1 inhibitors might also cause 'synthetic lethality' in tumour cells defective in defined DNA repair pathways.


Astrocyte Hypertrophy and Microglia Activation in the Rat Auditory Midbrain Is Induced by Electrical Intracochlear Stimulation.
Neuron-glia interactions contribute to tissue homeostasis and functional plasticity in the mammalian brain, but it remains unclear how this is achieved. The potential of central auditory brain tissue for stimulation-dependent cellular remodeling was studied in hearing-experienced and neonatally deafened rats. At adulthood, both groups received an intracochlear electrode into the left cochlea and were continuously stimulated for 1 or 7 days after waking up from anesthesia. Normal hearing and deafness were assessed by auditory brainstem responses (ABRs). The effectiveness of stimulation was verified by electrically evoked ABRs as well as immunocytochemistry and in situ hybridization for the immediate early gene product Fos on sections through the auditory midbrain containing the inferior colliculus (IC). Whereas hearing-experienced animals showed a tonotopically restricted Fos response in the IC contralateral to electrical intracochlear stimulation, Fos-positive neurons were found almost throughout the contralateral IC in deaf animals. In deaf rats, the Fos response was accompanied by a massive increase of GFAP indicating astrocytic hypertrophy, and a local activation of microglial cells identified by IBA1. These glia responses led to a noticeable increase of neuron-glia approximations. Moreover, staining for the GABA synthetizing enzymes GAD65 and GAD67 rose significantly in neuronal cell bodies and presynaptic boutons in the contralateral IC of deaf rats. Activation of neurons and glial cells and tissue re-composition were in no case accompanied by cell death as would have been apparent by a Tunel reaction. These findings suggest that growth and activity of glial cells is crucial for the local adjustment of neuronal inhibition to neuronal excitation.


[The value of peripheral quantitative computed tomography (pQCT) in the diagnosis of osteoporosis].
To evaluate the accuracy of distal radial pQCT in discriminating between osteoporotic fracture and non fracture cases and its efficiency to predict fractures. Densitometric data determined with an XCT 900 Stratec pQCT device at the distal radius of women who had suffered distal radius (57), spinal (87) or femoral neck fractures (21) before or after measurement were compared with densitometric data of age-matched healthy women (265) and were analyzed in regression tests. Women whose fractures occurred before measuring were selectively analyzed. More significant differences between fracture and non fracture groups were obtained by trabecular bone density (TBD) (r2radius = 0.531, r2spine = 0.528, r2femur = 0.711, p < 0.001) than by total bone density (BD) (r2radius = 0.468, r2spine = 0.495, r2femur = 0.605, p < 0.001). In the radius and spine group TBD data determined before fracture showed less significant differences than those determined afterwards, whereas in the femur group TBD data were almost equal. All femur fractures could be predicted. As TBD decreased, the relative risk of fracture increased by gradients of m radius = 0.017, m spine = 0.013, and m femur = 0.027 in the linear regions of the risk curves. Selective measuring of TBD at the distal radius enables one to detect bone loss at an early stage and to estimate the risk of future fractures not only at the point of measurement.


Structures of regenerated cellulose films revealed by grazing incidence small-angle x-ray scattering.
The characteristic in-plane length scales of ultrathin films of regenerated cellulose are measured using noncontact atomic force microscopy (NC-AFM) and grazing incidence small-angle x-ray scattering (GISAXS) in ambient atmosphere and under various humidity conditions. The aim is to elucidate the structural basis for the excellent compatibility of cellulose supports to planar lipid membranes. Films are deposited on silicon wafers by Langmuir-Blodgett (LB) transfer and spin coating. NC-AFM height profiles and the resulting calculated power spectral density functions indicate that both kinds of cellulose films have almost identical root-mean-square roughness values (0.7-0.8 nm) and very similar characteristic length scales (32 nm), respectively. GISAXS measurements, both above and below the critical angle of total external reflection, show that the dominant length scales in the bulk and near the surface of the films are comparable ( approximately 50 nm). The origin of these length scales can be attributed to the bundle of rodlike molecules of cellulose that result during the regeneration process (i.e., as a consequence of the cleavage of the silyl side chains of trimethylsilylcellulose). Exposure of the cellulose samples to various humidities shows that above a relative humidity of 97% a significant swelling of the films occurs, which is consistent with our previous findings. The swelling of films with more than 30 LB monolayers of cellulose induces a remarkable out-of-plane rearrangement of the cellulose bundles, due to a reduced influence of the solid substrate compared to thinner films with only eight to ten LB monolayers.


Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic testing, and targeted therapy.
CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was approved by the US Food and Drug Administration for use in Hodgkin lymphoma and anaplastic large cell lymphoma based on clinical trial data showing high response rates in these indications. Ongoing trials are examining brentuximab vedotin after autologous stem cell transplantation, as part of chemotherapy combination regimens, and in other CD30-expressing malignancies, including primary mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise specified, and cutaneous anaplastic large cell lymphoma.


Severe vitamin D deficiency is a risk factor for renal hyperfiltration.
Vitamin D deficiency is associated with renal progression in chronic kidney disease. Moreover, improvement of clinical outcomes after vitamin D supplementation has been reported in the diabetic and chronic kidney disease population. We investigated the association between renal hyperfiltration (RHF) and vitamin D status in a relatively healthy population. Data were retrieved from the Korean NHANES, a nationwide population-based cross-sectional study from 2008 to 2015. Overall, 33,210 subjects with normal renal function were included in the final analysis. Severe vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentration <10 ng/mL. RHF was defined as estimated glomerular filtration rate with residual in the >95th percentile after adjustment for age, sex, height, weight, and history of hypertension or diabetes. The mean ± SD age of subjects was 48.1 ± 15.9 y, and the number of women was 18,779 (56.5%). Estimated glomerular filtration rate was negatively associated with serum 25-hydroxyvitamin D concentrations in multivariable linear regression analysis (β: -0.02; 95% CI: -0.02, -0.01; P < 0.001). Furthermore, 1637 (4.9%) subjects were categorized into the RHF group, and the prevalence of RHF was significantly higher in the severe vitamin D deficiency group than in the sufficiency group (5.8% compared with 5.0%, P < 0.001). In a multivariable logistic regression model, severe vitamin D deficiency was a significant risk factor for RHF (OR: 2.41; 95% CI, 1.72, 3.43; P < 0.001). Severe vitamin D deficiency is significantly associated with increasing prevalence of RHF in a relatively healthy adult population.


Comparison of semi-automated commercial rep-PCR fingerprinting, spoligotyping, 12-locus MIRU-VNTR typing and single nucleotide polymorphism analysis of the embB gene as molecular typing tools for Mycobacterium bovis.
Purpose. Highly discriminatory genotyping strategies are essential in molecular epidemiological studies of tuberculosis. In this study we evaluated, for the first time, the efficacy of the repetitive sequence-based PCR (rep-PCR) DiversiLab Mycobacterium typing kit over spoligotyping, 12-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and embB single nucleotide polymorphism (SNP) analysis for Mycobacterium bovis typing.Methodology. A total of 49 M. bovis animal isolates were used. DNA was extracted and genomic DNA was amplified using the DiversiLab Mycobacterium typing kit. The amplified fragments were separated and detected using a microfluidics chip with Agilent 2100. The resulting rep-PCR-based DNA fingerprints were uploaded to and analysed using web-based DiversiLab software through Pearson's correlation coefficient.Results. Rep-PCR DiversiLab grouped M. bovis isolates into ten different clusters. Most isolates sharing identical spoligotype, MIRU-VNTR profile or embB gene polymorphism were grouped into different rep-PCR clusters. Rep-PCR DiversiLab displayed greater discriminatory power than spoligotyping and embB SNP analysis but a lower resolution power than the 12-locus MIRU-VNTR analysis. MIRU-VNTR confirmed that it is superior to the other PCR-based methods tested here.Conclusion. In combination with spoligotyping and 12-locus MIRU-VNTR analysis, rep-PCR improved the discriminatory power for M. bovis typing.


Primary breast aspergillosis mimicking breast malignancy - a rare case report.
Aspergillus is a group of saprophytic fungi which is widely present in our environment. It can be a cause of opportunistic infections of different organs, especially the lungs. Fungal mastitis is a rare infection in healthy subjects. It is seen in breastfeeding females and immunodeficient patients. We herein report a rare presentation of aspergilloma in a 73-year-old female who presented with a palpable mass in the breast. She was under medical control due to plasmocytoma. In ultrasound examination the lesion was classified as BI-RADS 4b and subsequently biopsy (fine needle and core needle aspiration) was performed. Biopsy provided immediate results and excluded breast cancer. In this rare case report of breast aspergillosis, we emphasize the role of pathology in medical diagnosis.


Effect of simultaneous isoniazid administration on pharmacokinetic parameters of pyrazinamide.
Pyrazinamide (PZN) was administered to 10 patients of pulmonary tuberculosis (for 7 consecutive days) each day after an overnight fast. On 8th day serum levels and urinary elimination were measured at 2,4,6 and 8 hours. Simultaneous administration of isoniazid to same patients significantly decreased the peak serum concentration (Cmax). Although, time to peak serum concentration (Tmax) remained unaffected, serum half life (t1/2) prolonged, the elimination rate constant (Kel) and area under serum concentration time curve (AUC) decreased and apparent volume of distribution (Vd) and plasma clearance (Clp) of PZN increased significantly. However, the cumulative per cent dose of PZN excreted in urine was not changed significantly. Although, serum levels of PZN were decreased at 2, 4, 6, and 8 hours, PZN levels remained above minimum effective concentration thereby not affecting the therapeutic status of PZN administered in combination with isoniazid, if PZN is administered in moderate doses.


Endophthalmitis caused by Bacillus species.
To investigate clinical settings, management, and visual outcomes of endophthalmitis caused by Bacillus species and to review in vitro effectiveness of antibiotics commonly used against Bacillus species. Retrospective, consecutive case series. Record review of all patients with endophthalmitis caused by Bacillus species treated at Bascom Palmer Eye Institute between January 1, 1990 and July 1, 2007. Antibiotic sensitivities were conducted on 21 of 22 isolates. Twenty-two eyes of 22 patients met study inclusion criteria. Median follow-up was 18 months. Clinical settings included open globe injury (18 eyes), endogenous (two eyes), delayed-onset bleb-associated (one eye), and acute-onset postoperative (one eye). Twelve (67%) of 18 patients with open globe injuries had intraocular foreign bodies. Presenting visual acuity (VA) was hand movements or better in 13 (59%) patients. Initial treatment included pars plana vitrectomy and injection of antibiotics in 14 eyes (64%), vitreous tap and injection of antibiotics in seven eyes (32%), and evisceration in one eye (5%). Four (18%) patients received additional doses of intravitreal antibiotics; 16 (73%) underwent secondary surgical procedures. Eight (36%) patients achieved a final VA of 20/400 or better and four (18%) achieved a final VA of 20/60 or better. All patients received intraocular vancomycin and a cephalosporin or aminoglycoside. Systemic antibiotics were used in 18 (82%) patients. Fifteen (68%) isolates were Bacillus cereus. All isolates tested were sensitive to vancomycin, gentamicin, and five fluoroquinolones. Only three of 21 isolates were susceptible to penicillin and cephalosporins. Endophthalmitis caused by Bacillus species often results in poor visual outcomes. In vitro antibiotic sensitivities indicate that vancomycin, aminoglycosides, and fluoroquinolones were effective against Bacillus isolates, whereas cephalosporins were relatively ineffective.


Commercial soft drinks: pH and in vitro dissolution of enamel.
Most soft drinks are acidic in nature and exposure to these drinks may result in enamel erosion. This study sought to measure the pH of 20 commercial brands of soft drinks, the dissolution of enamel resulting from immersion in these drinks, and the influence of pH on enamel loss. Comparison of the erosive potential of cola versus non-cola drinks as well as regular sugared and diet versions of the same brands was undertaken. The pH was measured immediately after opening the soft drink can. Enamel slices obtained from freshly extracted teeth were immersed in the soft drinks and weighed at baseline and after 6, 24, and 48 hours of immersion. Non-cola drinks had significantly higher pH values than cola drinks but showed higher mean percent weight loss. By contrast, sugared versions of the cola and non-cola drinks showed significantly lower pH values and higher mean percent weight loss than their diet counterparts. The pH value of the soft drink did not have a significant influence on the mean percent weight loss (r = -0.28). Prolonged exposure to soft drinks can lead to significant enamel loss. Non-cola drinks are more erosive than cola drinks. Sugared versions of cola and non-cola drinks proved to be more erosive than their diet counterparts. The erosive potential of the soft drinks was not related to their pH value.


Combination injectable contraceptives for contraception.
Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. We searched computerized databases for randomized controlled trials of combination injectable contraceptives. Randomized controlled trials reported in any language were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. The primary reviewer evaluated all titles and abstracts from the literature searches to determine their eligibility. Two reviewers independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan 4.2. Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These combination injectable contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems, but had higher rates of discontinuation due to other reasons than the progestin-only comparison contraceptives. Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall early discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials making this comparison. The NET-EN plus E(2)V group also had more cyclical (regular) bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation rates are dependent on many other factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinical sites, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.