Renal myolipoosteoma: A distinctive lesion in a child.
We describe a distinctive renal tumor, a myolipoosteoma (MLO), in an 11-year-old boy who presented with a 6-month history of slight right flank intermittent pain. A gross examination revealed a well-defined, 5.5 cm mass with bone-like consistency. The lesion histologically featured an admixture of mature adipose tissue, spindle cells, and bony components. No atypia, mitotic activity, or pleomorphisms were observed in the tumor. The spindle cells were smooth muscle actin (SMA) and desmin positive but HMB45 and Melan-A negative, indicating that they were of a muscular nature and differed from that of angiomyolipoma (AML). The patient had no evidence of recurrence or metastasis 56 months postoperatively. We speculate that the present tumor, which to the best of our knowledge differs from all previously described tumors, is of nephrogenic rest (NR) origin and has a favorable prognosis.


Double nerve transfer for restoration of hand grasp and release in C7 tetraplegia following complete cervical spinal cord injury.
Cervical spinal cord injury (SCI) can cause tetraplegia. Nerve transfer has been routinely utilized for reconstruction of hand in brachial plexus injuries. Here, we report reconstruction of finger flexion (hand grasp) and extension (hand release) in a victim of cervical spinal cord injury with tetraplegia. We also focus on importance of extension phase in restoration of hand function in the tetraplegic case, in addition to provision of a detailed description of both operations including text, photographs, and a video. We used double nerve transfer, namely brachialis branches of musculocutaneous nerve to anterior interosseous nerve (AIN) and supinator branch of radial nerve to posterior interosseous nerve (PIN). We found that brachialis nerve transfer to AIN (for finger flexion) and supinator branch nerve transfer to PIN (for finger extension) can provide finger flexion and extension simultaneously. Brachialis nerve transfer to AIN and supinator branch nerve transfer to PIN may be an acceptable surgical technique to restore hand grasp and release in tetraplegia after SCI.


Ultrasound diagnosis of recurring Jeune's syndrome: a case report.
Jeune's Syndrome or asphyxiating thoracic dystrophy (ATD) is a rare autosomal recessive skeletal dysplasia syndrome characterized by a small and narrow chest, short extremities, and often polydactyly associated with multiple organ manifestations. The severity of complications ranges from mild to lethal. This is a report of two cases of ATD diagnosed in successive pregnancies of a nonconsanguineous couple. The contribution of sonography in prenatal diagnosis of the syndrome is highlighted.


Extracellular signal-regulated kinase involved in NGF/VEGF-induced neuroprotective effect.
Compelling evidence has shown that extracellular signal-regulated kinase (ERK) is widely expressed in many tissues, including the brain. In the present work, we investigated the temporospatial alterations of ERK1 immunoreactivity in hippocampus and perifocal cortex, and the expression involved in NGF/VEGF-induced neuroprotective effect. We demonstrated that ERK1 expression was first increased in hippocampal CA3/DG 1 h after reperfusion, then it was also increased 6 h after reperfusion in other brain regions, with a peak at day 1-3, and then gradually decreased to basal level at day 14. The expression of caspase-3 was strongly increased 1 h after reperfusion, with peak demonstrated at 3d. NGF/VEGF significantly inhibited the expression of ERK1 and caspase-3. These results suggest that ERK1 signaling pathway may be involved in neuronal cell death and NGF/VEGF-induced neuroprotective effect and there appeared an association between ERK and caspase-3. Inhibition of the ERK signaling pathway might therefore provide an efficient way to prevent neuronal cell death after ischemic cerebral injuries.


Humanizing Pedophilia as Stigma Reduction: A Large-Scale Intervention Study.
The stigmatization of people with pedophilic sexual interests is a topic of growing academic and professional consideration, owing to its potential role in moderating pedophiles' emotional well-being, and motivation and engagement in child abuse prevention schemes. Thus, improving attitudes and reducing stigmatization toward this group is of paramount importance. Prior research has suggested that narrative humanization-presenting personal stories of self-identified non-offending pedophiles-could be one route to doing this. However, this work has only been conducted with students or trainee psychotherapists, meaning the public generalizability of this method is still unknown. In this study, we compared two stigma interventions to test whether narratives reduce stigma toward people with pedophilic interests more effectively than an informative alternative (scientific information about pedophilia). Using a longitudinal experimental design with a lack of non-intervention control (initial N = 950; final N = 539), we found that narratives had consistently positive effects on all measured aspects of stigmatization (dangerousness, intentionality), whereas an informative alternative had mixed results, and actually increased perceptions of pedophiles' levels of deviance. These effects were still present four months after the initial presentation. We discuss these data in relation to ongoing debates about treating pedophilia as a public health issue requiring a broad societal approach to well-being and child abuse prevention.


Nitric oxide synthase-2 modulates chemokine production by Trypanosoma cruzi-infected cardiac myocytes.
An intense inflammatory process is associated with Trypanosoma cruzi infection. We investigated the mediators that trigger leukocyte activation and migration to the heart of infected mice. It is known that nitric oxide (NO) modulates the inflammatory response. During T. cruzi infection, increased concentrations of NO are produced by cardiac myocytes (CMs) in response to IFN-gamma and TNF. Here, we investigated whether NO, IFN-gamma and TNF regulate chemokine production by T. cruzi-infected CMs. In addition, we examined the effects of the NOS2 deficiency on chemokine expression both in cultured CMs and in hearts obtained from infected mice. After infection of cultured WT CMs with T. cruzi, the addition of IFN-gamma and TNF increased both mRNA and protein levels of the chemokines CXCL1, CXCL2, CCL2, CCL3, CCL4 and CCL5. Interestingly, T. cruzi-infected NOS2-deficient CMs produced significantly higher levels of CCL2, CCL4, CCL5 and CXL2 in the presence of IFN-gamma and TNF. Infection of NOS2-null mice resulted in a significant increase in the expression of both chemokine mRNA and protein levels in the heart of, compared with hearts obtained from, infected WT mice. Our data indicate that NOS2 is a potent modulator of chemokine expression which is critical to triggering the generation of the inflammatory infiltrate in the heart during T. cruzi infection.


Anti-inflammatory effects of C-peptide on kidney of type 1 diabetes mellitus animal model.
Type 1 diabetes mellitus (T1DM) is characterized by C-peptide deficiency and elevated levels of pro-inflammatory cytokines. The aim of this study was to investigate the role of C-peptide in renal and inflammatory complications in streptozotocin (STZ)-diabetic mice model of T1DM with kidney disease. The study was performed in 8-week old male C57BL/6 mice. Two streptozotocin-diabetic groups (a T1DM animal model), after 4 weeks of diabetes, were treated with subcutaneous infusion of either vehicle (n = 12) or C-peptide (n = 11). Two non-diabetic groups (vehicle, n = 10; C-peptide, n = 9) were treated using the same protocol as described for the diabetic mice. The treatment with C-peptide in the diabetic group reduced the urinary levels of IL17 and TNFα, as well as IL4 and IL10 (p < 0.05). Contrary, the diabetic + C-peptide group presented higher IL10 gene expression in kidney. Besides, it displayed a reduction of TNFα gene expression. The data suggest that C-peptide may modulate pro- and anti-inflammatory signalling pathways, resulting in attenuation of kidney inflammation in T1DM animal model.


Update of REACH-1 and MERIT-HF clinical trials in heart failure. Cardio.net Editorial Team.
This article reviews the design and results of REACH-1 (Research on Endothelin Antagonism in Chronic Heart Failure) and MERIT (Metoprolol controlled and Extended release, Randomised Intervention Trial in congestive Heart Failure), two recently reported clinical trials that investigated, respectively, the role of a non-selective endothelin antagonist (bosentan) and of a beta-selective blocker for the treatment of heart failure. The REACH-1 trial demonstrated that initiation of bosentan therapy is associated with an increased risk of worsening heart failure. However, long-term therapy with bosentan may have improved symptoms and favourably altered the progression of heart failure. The MERIT-HF clinical trial indicated that beta-blockade using metoprolol confers a significant beneficial effect on total mortality in patients with stable chronic heart failure.


Hypothesis-Based Weight of Evidence: An Approach to Assessing Causation and its Application to Regulatory Toxicology.
Other papers in this symposium focus on combining direct observations or measurements of a phenomenon of interest. Here, I consider the distinct problem of integrating diverse kinds of data to address the scientific case for toxicological causation in view of information that usually contains gaps and outright contradictions. Existing weight-of-evidence approaches have been criticized as either too formulaic or too vague, simply calling for professional judgment that is hard to trace to its scientific basis. I discuss an approach-hypothesis-based weight of evidence-that emphasizes articulation of the hypothesized generalizations, their basis, and span of applicability. Hypothesized common processes should be expected to act elsewhere as well-in different species or different tissues-and so outcomes that ought to be affected become part of the evidence evaluation. A compelling hypothesis is one that provides a common unified explanation for observed results. Any apparent exceptions and failures to account for some data must be plausibly explained. Ad hoc additions to the explanations introduced to "save" hypotheses from apparent contradiction weaken the degree to which available data test causal propositions. In the end, we need an "account" of all the results at hand, specifying what is ascribed to hypothesized common causal processes and what to special exceptions, chance, or other factors. Evidence is weighed by considering comparative plausibility of an account including the proposed causal effect versus an alternative that explains all of the results at hand otherwise.


Occurrence and immunogenicity of proteinases from Legionella species.
Proteinases produced by various Legionella species were studied by means of caseinate precipitation. Proteinase production was particularly high in strains of Legionella pneumophila (serogroups 1-6), much lower in other Legionella species, and absent in Legionella micdadei strain Tatlock. Immunoglobulins against proteinases of Legionella pneumophila (serogroup 1, strain Philadelphia 1) inhibited the proteinase activity of all strains of Legionella pneumophila, Legionella bozemanii, Legionella dumoffi and Legionella gormanii. There was no cross-reactivity between these antibodies and proteinases from bacteria belonging to other genera. Antibodies against Legionella pneumophila proteinases were not found in human convalescent sera. The proteinases of Legionella species could possibly be associated with pathogenicity factors.


DNA methylation and methylcytosine oxidation in cell fate decisions.
Changes in cellular phenotypes and identities are fundamentally regulated by epigenetic mechanisms including DNA methylation, post-translational histone modifications and chromatin remodeling. Recent genome-wide profiles of the mammalian DNA 'methylome' suggest that hotspots of dynamic DNA methylation changes during cell fate transitions occur at distal regulatory regions with low or intermediate CpG densities. These changes are most prevalent early during the course of cellular differentiation and can be locally influenced by binding of cell-type specific transcription factors. With the advent of next-generation quantitative base-resolution maps of 5-methylcytosine and its oxidized derivatives and better coverage of the genome, we expect to learn more about the true significance of these DNA modifications in the regulation of cell fate choices.


Mucoepidermoid carcinoma of the parotid infiltrating the chorda tympani nerve.
We present here the first case report of a mucoepidermoid carcinoma of the parotid infiltrating the chorda tympani nerve and also discuss why an initial diagnosis of Bell palsy may be misleading.


A flexible assay strategy for non-glucose targets based on sulfhydryl-terminated liposomes combined with personal glucometer.
The personal glucose meter (PGM) is one of the most successful point-of-care (POC) testing devices. It is simple, robust and inexpensive, but cannot be easily adapted to analytes other than glucose. We report a novel chemical conjugation-based assay strategy, using rational design of chemically-derivatized glucose-encapsulating liposomes, to repurpose a PGM, taking an important mycotoxin patulin as the model analyte. Sulfhydryl (-SH) was proposed for the first time as a specific functional group for efficient recognition of patulin. Multifunctional sulfhydryl-terminated glucose-encapsulating liposomes (G-LIP-SH) were synthesized in a simple, single step, which efficiently captured patulin by covalent bonding, and interacted strongly with NH2-Au@Fe3O4 nanoparticles. Magnetic removal of nanoparticles efficiently and selectively separated patulin-derivatized from un-derivatized G-LIP-SH, permitting the latter to be lysed and the released glucose measured by PGM. The PGM signal was inversely proportional to the patulin concentration, over the range of 0.1-50 ng mL-1 (R2 = 0.995) with a detection limit of 0.05 ng mL-1 (S/N = 3). This approach overcame interference from endogenous glucose, other mycotoxins and metal ions, allowing the analysis of a wide range of sample matrices and showed high specificity, acceptable reproducibility, good accuracy and optimal applicability. Other derivatization chemistries will enable this approach to be adapted to analytes with a wide range of chemical structures, to facilitate development of rapid, portable, user-friendly and cost-effective assays applicable to diverse analytes and sample matrices.


Insect-based agri-food waste valorization: Agricultural applications and roles of insect gut microbiota.
Meeting the demands of the growing population requires increased food and feed production, leading to higher levels of agri-food waste. As this type of waste seriously threatens public health and the environment, novel approaches to waste management should be developed. Insects have been proposed as efficient agents for biorefining waste, producing biomass that can be used for commercial products. However, challenges in achieving optimal outcomes and maximizing beneficial results remain. Microbial symbionts associated with insects are known to have a critical role in the development, fitness, and versatility of insects, and as such, they can be utilized as targets for the optimization of agri-food waste insect-based biorefinery systems. This review discusses insect-based biorefineries, focusing on the agricultural applications of edible insects, mainly as animal feed and organic fertilizers. We also describe the interplay between agri-food waste-utilizing insects and associated microbiota and the microbial contribution in enhancing insect growth, development, and involvement in organic waste bioconversion processes. The potential contribution of insect gut microbiota in eliminating pathogens, toxins, and pollutants and microbe-mediated approaches for enhancing insect growth and the bioconversion of organic waste are also discussed. The present review outlines the benefits of using insects in agri-food and organic waste biorefinery systems, describes the roles of insect-associated microbial symbionts in waste bioconversion processes, and highlights the potential of such biorefinery systems in addressing the current agri-food waste-related challenges.


A cross-sectional study assessing determinants of the attitude to the introduction of eHealth services among patients suffering from chronic conditions.
Provision of care to patients with chronic diseases remains a great challenge for modern health care systems. eHealth is indicated as one of the strategies which could improve care delivery to this group of patients. The main objective of this study was to assess determinants of the acceptance of the Internet use for provision of chosen health care services remaining in the scope of current nationwide eHealth initiative in Poland. The survey was carried out among patients with diagnosed chronic conditions who were treated in three health care facilities in Krakow, Poland. Survey data was used to develop univariate and multivariate logistic regression models for six outcome variables originating from the items assessing the acceptance of specific types of eHealth applications. The variables used as predictors were related to the sociodemographic characteristics of respondents, burden related to chronic disease, and the use of the Internet and its perceived usefulness in making personal health-related decisions. Among 395 respondents, there were 60.3% of Internet users. Univariate logistic regression models developed for six types of eHealth solutions demonstrated their higher acceptance among younger respondents, living in urban areas, who have attained a higher level of education, used the Internet on their own, and were more confident about its usefulness in making health-related decisions. Furthermore, the duration of chronic disease and hospitalization due to chronic disease predicted the acceptance of some of eHealth applications. However, when combined in multivariate models, only the belief in the usefulness of the Internet (five of six models), level of education (four of six models), and previous hospitalization due to chronic disease (three of six models) maintained the effect on the independent variables. The perception of the usefulness of the Internet in making health-related decision is a key determinant of the acceptance of provision of health care services online among patients with chronic diseases. Among sociodemographic factors, only the level of education demonstrates a consistent impact on the level of acceptance. Interestingly, a greater burden of chronic disease related to previous hospitalizations leads to lower acceptance of eHealth solutions.


Mutation in Eth A protein of Mycobacterium tuberculosis conferred drug tolerance against enthinoamide in Mycobacterium smegmatis mc2155.
EthA is an NADPH-specific flavin adenine dinucleotide (FAD) containing monooxygenase that activates the -second-line drug ethionamide (ETH). ETH gets converted to an active form after interaction with the EthA (monooxygenase) protein. Upon activation, ETH interacts with NAD+ to form an ETH-NAD adduct, which hampers the activity of InhA (Enoyl-[(acyl-carrier-protein) reductase (NADH)]. This, in turn, inhibits the cell wall synthesis, thus killing the Mycobacterium tuberculosis (Mtb). Mutations in the EthA gene can modulate ETH activation. The mutation at 202 position (Val202-Leu) of EthA protein has been reported frequently in ETH resistance. In this study, the effect of this mutation on the function of the EthA protein was examined through structural and functional analysis. Molecular docking of wild type and mutated EthA protein with ETH were compared to inspect the effect of mutation on molecular mechanism of drug resistant. Docking results corroborated that the lower docking score of the mutant protein, larger binding cavity, and lower affinity towards ETH resulted in a less compact and energetically less stable structure than the wild type protein. The computational outcome was authenticated by in-vitro experiments. The wild type and mutated genes were cloned and expressed in M. smegmatis, a surrogate host. Antibiotic susceptibility testing demonstrated that the mutant showed high growth and survival in the presence of the ETH drug. Overall, the results indicated that a mutation in the intergenic region of EthA protein could result in the altered conversion of ETH to the active form, resulting in differential ETH sensitivity for M. smegmatis carrying the wild type and mutant gene.


Genetic organization of the unc-22 IV gene and the adjacent region in Caenorhabditis elegans.
The genetic organization of the region immediately adjacent to the unc-22 IV gene in Caenorhabditis elegans has been studied. We have identified twenty essential genes in this interval of approximately 1.5-map units on Linkage Group IV. The mutations that define these genes were positioned by recombination mapping and complementation with several deficiencies. With few exceptions, the positions obtained by these two methods agreed. Eight of the twenty essential genes identified are represented by more than one allele. Three possible internal deletions of the unc-22 gene have been located by intra-genic mapping. In addition, the right end point of a deficiency or an inversion affecting the adjacent genes let-56 and unc-22 has been positioned inside the unc-22 gene.


[Role of interferon alpha in the management of severe acute pancreatitis].
To investigate the efficacy of IFN-alpha on severe acute pancreatitis (SAP) of IFN-alpha. A SAP model was developed in adult male rats by retrograde injection of 5% sodium taurocholate in the pancreatic duct. Serum amylase was measured by the blue-starch method and serum cytokines were determined by ELISA. Compared with to the control group, less pancreatic injury and lower amylase level were observed treat in the rats with IFN-alpha. In contrast, the concentration of IL-10 was higher. IFN-alpha has significant curative effect on SAP.


Physical Breast Examination in Pregnancy and Lactation.
Physical exam of the breast is a very important part of breast assessment both for breast cancer screening, and when approaching breast lesions. Examination during pregnancy and breastfeeding follows exactly the same method as non-pregnancy periods. However, physical changes that occur in the breast during these times due to hormonal effects cause alterations that can on one hand conceal some pathologic disorders, and may on the other hand appear as pathologic findings while being purely physiologic. This chapter focuses first on some key points for an accurate breast examination, and then reviews some challenging controversial findings that may be noticed during breast exam in a pregnant or lactating woman.


Reirradiation Using 198Au Grain Brachytherapy for Recurrent Oral Cancer Cases Previously Treated by Definitive Radiotherapy.
We investigated treatment outcomes and complications during reirradiation of patients with oral cancers. Six patients who received definitive radiotherapy for oral cancer as the initial treatment and brachytherapy for recurrence were included. Local control and overall survival rates, soft tissue and mandibular complications, and tooth extraction were investigated. The five-year local control and overall survival rates were 83.3% and 100%, respectively. The occurrence rate of grade 2 soft tissue and mandible complications was 33.3%, and the primary sites were the buccal mucosa and the floor of mouth. The positions of the extracted tooth in the two cases were adjacent to the tumor, and one case developed grade 2 complication of the mandible. During recurrence of the buccal mucosa and the floor of mouth cancers, reirradiation should be avoided considering mandibular complications. To avoid reirradiation-related complications, tooth extraction near the radiation field should be avoided.


Nursing home status is an independent risk factor for adverse 30-day postoperative outcomes after common, nonemergent inpatient procedures.
Nursing home residents undergoing surgery have a higher rate of postoperative adverse outcomes than nonnursing home patients. This study seeks to determine what contribution nursing home status makes to theses occurrences, independent of comorbid conditions. Using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database, the 30-day postoperative outcomes of the 5 commonest nonemergent inpatient procedures performed on nursing home residents were compared with those in nonnursing home residents using logistic regression analysis. Nursing home status was found to be an independent risk factor for septic complications in all procedures, for blood transfusion requirement after lower leg amputation, for pneumonia and stroke/cerebrovascular accident after thromboendarterectomy, and for mortality after partial colectomy with primary anastomosis. These data suggest that, in addition to serving as a surrogate indicator of health status and current morbidity, residence in a nursing home makes an independent contribution to adverse postoperative outcomes.


Evidence of a sex-dependent restrictive epigenome in schizophrenia.
When compared to women, men have a higher incidence of schizophrenia, with increases in negative and cognitive symptoms, and an overall poorer disease course. Schizophrenia is conceptualized as a disorder of aberrant gene transcription and regulation. Thus, epigenetics, the study of environmentally induced changes in gene regulation, could advance our understanding of the molecular underpinnings of schizophrenia. Peripheral histone methyltransferase (HMT) mRNA levels have been previously shown to be significantly increased in patients with schizophrenia and correlate with symptomology. In this independent study, peripheral lymphocytes were extracted and clinical symptoms were measured on 74 participants, (40 patients with schizophrenia (19 women, 21 men) and 34 healthy individuals (19 women, 15 men)). HMT (G9α, SETDB1 and GLP) mRNA levels and their resulting histone modification H3K9me2 were measured with RT-PCR and ELISA respectively. Plasma estradiol levels were also measured via ELISA and correlated with HMT mRNA. Clinical symptoms were measured utilizing the Positive and Negative Syndrome Scale (PANSS) and the Heinrichs Carpenter Quality of Life Scale (QLS). The results indicate that men with schizophrenia expressed the highest levels of G9α, SETDB1 mRNA and H3K9me2 protein levels. Additionally, higher levels of symptom presentation and an overall poorer quality of life were correlated with higher HMT mRNA and H3K9me2 protein levels in a sex-dependent pattern. These data support the hypothesis of a sex-dependent restrictive epigenome contributing towards the etiology of schizophrenia. The histone methyltransferases measured here could be potential future therapeutic targets for small molecule pharmacology.


A basic phospholipase A from the venom of the Australian king brown snake (Pseudechis australis) showing diverse activities against membranes.
1. A basic phospholipase A (MSPA) was isolated from the venom of the Australian king brown snake, Pseudechis australis. 2. MSPA had an approximate Mr of 13,000 and consisted of a single polypeptide chain of 119 amino acid residues cross-linked by seven disulphide bridges. 3. MSPA exhibited direct haemolytic, anticoagulant and myotoxic activities. 4. Treatment of MSPA with p-bromophenacyl bromide modified a single histidine residue, resulting in complete loss of enzyme activity.


Fast atom bombardment mass spectrometry and its application to the analysis of some peptides and proteins.
The techniques of fast atom bombardment mass spectrometry has overtaken (but not entirely replaced) field desorption mass spectrometry as the method of choice for the analysis of nonvolatile, thermally labile polar compounds. The ease with which information may be obtained on a wide variety of molecules is a result of the relative simplicity of the technique. A brief history of bioorganic mass spectrometry leading to the development of fast atom bombardment is presented, as well as a description of the method and ancillary techniques. Selected examples of its application to peptide and protein structural problems attest to the power and utility of fast atom bombardment mass spectrometry.


Many hands make light work: CNV of GSTM1 effect on the oral carcinoma risk.
Genetic alterations of oral squamous cell carcinoma (OSCC) allow the understanding of the oral carcinogenesis and the identification of molecular biomarkers that aid the early diagnosis of the disease. The copy number variation (CNV) of GSTM1 and GSTT1 are promising targets because these two genes codify enzymes that perform the inactivation of tobacco carcinogens, which are the main risk factor of OSCC. However, the different levels of - detoxification mechanism in relation to each copy of the genes are unknown. Therefore, this study aimed to investigate the possible association of the CNV of GSTM1 and GSTT1 with the risk of development of OSCC. A total of 234 OSCC patients and 422 patients without any cancer diagnoses were recruited from Heliópolis Hospital from 2000 to 2011. The CNV was determined by TaqMan real-time PCR and the CopyCaller software. Odds ratio (OR) and 95% confidence interval (95% CI) values were calculated by Multiple Logistic Regression. Most OSCC patients reported they continued smoking high amounts of cigarettes despite the tumor diagnosis. The CNV of GSTM1 varied from zero to two copies and the analysis revealed that two copies of GSTM1 decreased by 53% the OSCC risk (OR 0.47; 95% CI 0.24-0.92) and the risk of the tumor was modified according to the interaction of the CNV of GSTM1 and the cigarette smoking consumption, which for the amount of 40 packs-year of cigarettes the OSCC risk diminished progressively according to the increase of copies of GSTM1. Although the GSTT1 gene varied from zero to three copies, none of them were associated with the tumor risk. The findings suggest that the CNV of GSTM1 might be applied as a tool for the surveillance of patients and the early detection of OSCC.


Cultured T cells from patients with T cell chronic lymphocytic leukemia demonstrate a normal phenotype.
Peripheral blood mononuclear cells from eight patients with the rare T-cell form of chronic lymphocytic leukemia were isolated and cultured with Interleukin-2 (IL-2). In all but one case, cultured T-cells (CTC) were established. Various culture conditions were tested for their effectiveness; feeder layers proved valuable for expanding the cultures to large volumes. The CTC remained IL-2 dependent. Analysis of surface determinants on these CTC showed a polyclonal proliferation of T-cells. The distribution of subset markers in the patients' CTC population had completely changed in comparison to the "fresh" peripheral blood cell population but was similar to CTC initiated from healthy donors. Our data suggest that the patients' few contaminating normal T-lymphocytes expanded in culture, while the malignant cells were unresponsive to IL-2. This conclusion is supported by growth characteristics and morphology of the CTC.


Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier.
Here, we report that diesel exhaust particles (DEPs), a major constituent of urban air pollution, affect blood-brain barrier function at the tissue, cellular, and molecular levels. Isolated rat brain capillaries exposed to DEPs showed increased expression and transport activity of the key drug efflux transporter, P-glycoprotein (6 h EC(50) was approximately 5 microg/ml). Up-regulation of P-glycoprotein was abolished by blocking transcription or protein synthesis. Inhibition of NADPH oxidase or pretreatment of capillaries with radical scavengers ameliorated DEP-induced P-glycoprotein up-regulation, indicating a role for reactive oxygen species in signaling. DEP exposure also increased brain capillary tumor necrosis factor-alpha (TNF-alpha) levels. DEP-induced P-glycoprotein up-regulation was abolished when TNF-receptor 1 (TNF-R1) was blocked and was not evident in experiments with capillaries from TNF-R1 knockout mice. Inhibition of JNK, but not NF-kappaB, blocked DEP-induced P-glycoprotein up-regulation, indicating a role for AP-1 in the signaling pathway. Consistent with this, DEPs increased phosphorylation of c-jun. Together, our results show for the first time that a component of air pollution, DEPs, alters blood-brain barrier function through oxidative stress and proinflammatory cytokine production. These experiments disclose a novel blood-brain barrier signaling pathway, with clear implications for environmental toxicology, CNS pathology, and the pharmacotherapy of CNS disorders.


Fludarabine monophosphate as salvage for refractory chronic lymphocytic leukaemia.
To assess the efficacy of the purine analogue fludarabine monophosphate (FAMP) as salvage therapy in patients at Groote Schuur Hospital with chronic lymphocytic leukaemia (CLL) refractory to standard therapy. Non-randomised trial. Tertiary care, referral academic hospital. Seven patients with B-lineage CLL, 4 in Rai stage IV and 1 each in stages A(I), A(II) and A(III), refractory to treatment with chlorambucil or cyclophosphamide, with or without whole-body irradiation. Intravenous FAMP at a dose of 25 mg/m2 daily for 5 days every 28 days. Partial remission, complete remission, stable disease or progressive disease. Two patients entered CR and 4 PR after a median of 8 courses of treatment (range 2 - 12). One patient died of Pneumocystis carinii pneumonia after 3 courses of therapy. The most common adverse effect of the treatment was myelosuppression, with the nadir of neutrophil counts being less than 0.5 x 10(9)/1 in 5 patients. Three developed infections and required hospitalisation while on therapy. FAMP is effective as a cytoreductive agent in patients with CLL refractory to alkylating agents, with or without whole-body irradiation.


Monitoring of respiratory variations of aortic blood flow velocity using esophageal Doppler.
The purpose of this study was to determine whether monitoring of respiratory changes in aortic blood flow velocity, recorded by esophageal Doppler, could be used to detect changes in volume depletion. Animal study. After general anesthesia and tracheotomy, ten New Zealand female rabbits, weighing 4-4.5 kg were studied under mechanical ventilation at a fixed tidal volume; during this time 5-ml blood samples were withdrawn (in increments up to a total of 30 ml) and then retransfused. At each step, systolic (SBP), diastolic (DBP), pulse (PP) pressures and maximum descending aortic blood flow (V) were recorded. Respiratory changes of V (DeltaV), SBP (DeltaSBP) and PP (DeltaPP) were calculated as the difference of maximal and minimal values divided by their respective means and expressed as a percentage. The amount of blood withdrawn correlated negatively with SBP, DBP, PP and V and positively with DeltaSBP, DeltaPP and DeltaV. Among these parameters, DeltaV correlated best with the amount of blood withdrawn ( r=0.89, p<0.001) and it was the most accurate index of volume depletion. Monitoring of the respiratory variation in V, calculated by esophageal Doppler technique, seems to be a highly accurate index of blood volume depletion and restitution.


Long term sequelae from childhood pneumonia; systematic review and meta-analysis.
The risks of long term sequelae from childhood pneumonia have not been systematically assessed. The aims of this study were to: (i) estimate the risks of respiratory sequelae after pneumonia in children under five years; (ii) estimate the distribution of the different types of respiratory sequelae; and (iii) compare sequelae risk by hospitalisation status and pathogen. We systematically reviewed published papers from 1970 to 2011. Standard global burden of disease categories (restrictive lung disease, obstructive lung disease, bronchiectasis) were labelled as major sequelae. 'Minor' sequelae (chronic bronchitis, asthma, other abnormal pulmonary function, other respiratory disease), and multiple impairments were also included. Thirteen papers were selected for inclusion. Synthesis was by random effects meta-analysis and meta-regression. Risk of at least one major sequelae was 5.5% (95% confidence interval [95% CI] 2.8-8.3%) in non hospitalised children and 13.6% [6.2-21.1%]) in hospitalised children. Adenovirus pneumonia was associated with the highest sequelae risk (54.8% [39.2-70.5%]) but children hospitalised with no pathogen isolated also had high risk (17.6% [10.9-24.3%]). The most common type of major sequela was restrictive lung disease (5.4% [2.5-10.2%]) . Potential confounders such as loss to follow up and median age at infection were not associated with sequelae risk in the final models. All children with pneumonia diagnosed by a health professional should be considered at risk of long term sequelae. Evaluation of childhood pneumonia interventions should include potential impact on long term respiratory sequelae.


Individual differences in children's private speech: the role of imaginary companions.
Relations between children's imaginary companion status and their engagement in private speech during free play were investigated in a socially diverse sample of 5-year-olds (N=148). Controlling for socioeconomic status, receptive verbal ability, total number of utterances, and duration of observation, there was a main effect of imaginary companion status on type of private speech. Children who had imaginary companions were more likely to engage in covert private speech compared with their peers who did not have imaginary companions. These results suggest that the private speech of children with imaginary companions is more internalized than that of their peers who do not have imaginary companions and that social engagement with imaginary beings may fulfill a similar role to social engagement with real-life partners in the developmental progression of private speech.


An alternative to the magic bullet paradigm for specific cancer therapy.
To improve on current cancer therapies, which attack cells on the basis of their proliferative tendencies, much effort has been devoted to a search for properties of tumor cells that are tumor-specific rather than proliferation specific. Evidence from molecular genetic studies suggests, however, that most tumors may lack such properties. An alternative approach to therapy is described that is based on a property known to characterize the majority of human tumors; viz., a monoclonal origin. The strategy requires the prophylactic induction in tissues of mosaicism for genes dictating sensitivity or resistance to chemotherapeutic agents, and exploits the observation that any clone of cells arising in a mosaic tissue must inevitably differ from some other cells in the mosaic. Recent advances in genetic technology imply that the strategy is likely to be testable soon in animals, and that it may significantly improve the results of cancer therapy when a technology safe and efficient enough for its human implementation becomes available.


Malfunctioned inflammatory response and serotonin metabolism at the microbiota-gut-brain axis drive feather pecking behavior in laying hens.
Feather pecking (FP) is a multifactorial abnormal behavior in laying hens where they display harmful pecks in conspecifics. FP has been associated with the altered functioning of the microbiome-gut-brain axis affecting host emotions and social behavior. The altered levels of serotonin (5-HT), a key monoaminergic neurotransmitter at both terminals of the gut-brain axis, affect the development of abnormal behavior, such as FP in laying hens. However, the underlying mechanism involving reciprocal interactions along the microbiota-gut-brain axis, particularly about the metabolism of 5-HT, remains unclear in FP phenotypes. This study examined the microbiota diversity, intestinal microbial metabolites, inflammatory responses, and 5-HT metabolism in divergently selected high (HFP; n = 8) and low (LFP; n = 8) FP hens to investigate the possible interconnections between FP behavior and the examined parameters. The 16S rRNA analysis revealed that compared to LFP birds, the gut microbiota of HFP birds exhibited a decrease in the abundance of phylum Firmicutes and genera Lactobacillus, while an increase in the abundance of phylum Proteobacteria and genera Escherichia Shigella and Desulfovibrio. Furthermore, the intestinal differential metabolites associated with FP phenotypes were mainly enriched in the tryptophan metabolic pathway. HFP birds had higher tryptophan metabolites and possibly a more responsive immune system compared to the LFP birds. This was indirectly supported by altered TNF-α levels in the serum and expression of inflammatory factor in the gut and brain. Moreover, HFP birds had lower serum levels of tryptophan and 5-HT compared to LFP birds, which was consistent with the downregulation of 5-HT metabolism-related genes in the brain of HFP birds. The correlation analysis revealed that genera Lactobacillus and Desulfovibrio were associated with differences in intestinal metabolites, 5-HT metabolism, and inflammatory response between the LFP and HFP birds. In conclusion, differences in the cecal microbiota profile, immune response and 5-HT metabolism drive FP phenotypes, which could be associated with the gut abundance of genera Lactobacillus and Desulfovibrio.


A meta-analysis for neurobehavioural results due to occupational mercury exposure.
A meta-analysis for neurobehavioural test results of subjects occupationally exposed to mercury was carried out in order to find general tendencies and express possible deficits numerically. Out of 44 studies investigating neurobehavioural functions of occupationally exposed individuals, 12 studies provided the data required and were included in the analysis. In all, 14 neuropsychological tests with 20 different tasks were analysed. The results related to 686 exposed and 579 control subjects. Nine significant performance effects were shown for mean urinary concentrations between 18 and 34 microg Hg/g creatinine. The effects sizes (D(W+)) referred to attention (D(W+)=-0.40 and -0.46), memory (D(W+)=-0.38 and -0.40), construction (D(W+)=-0.20) and motor performance (D(W+)=-0.24, -0.40, -0.44 and -0.47). Additionally there was evidence for a dose-response relationship of effect sizes, if all test results were taken into account. Whether the effect sizes could be subject to overestimation was discussed, but there were no reasons for such an assumption. The results can be used as suggestions for new discussions about threshold limit values.


Interaction of purple membrane with solvents. II. Mode of interaction.
Using the solubility parameter mapping technique (Eisenbach, M., Caplan, S.R. and Tanny, G (1979) Biochim. Biophys. Acta 554, 269-280) we studied spectroscopically the mode of interaction between the purple membrane of Halobacterium halobium and pure organic solvents or solvent mixtures. Although the interacting solvents formed a well-defined closed region in the interaction maps, mapping the modes of interaction did not reveal a closed region for each spectrally classifiable type. A suggested interpretation for this is that interaction with the purple membrane chromophore requires that a solvent (or solvent mixture) possess apolar groups in order to obtain access to the chromophore, together with a polar character and hydrogen-bonding capacity. The mode of interaction, however, is dependent on the specificity of the reactive group of the solvent for retinal, and this has nothing to do with membrane properties. We also examined the influence of the duration of the interaction and of illumination. Some solvents appeared to react more sluggishly than others, but no generalization in terms of the solubility parameter mapping was found, probably because the map describes thermodynamic rather than kinetic phenomena. The only effect of illumination was to enhance the reaction of some of these solvents. It did not change the solubility parameters of purple membrane.


Exogenous BDNF facilitates strategy set-shifting by modulating glutamate dynamics in the dorsal striatum.
Brain-derived neurotrophic factor (BDNF) signaling via tropomyosin-related kinase B (trkB) receptors exerts modulatory effects on glutamatergic transmission, learning, memory and reward processing. Although the role of BDNF in the regulation of mnemonic and affective/motivational processes is well studied, whether this neurotrophin could also regulate executive functions is not known. In the present study, we assessed the effects of intrastriatal infusions on BDNF (1-100 ng/hemisphere) in mice performing an operant strategy set-shifting task that required the animals to eliminate a visual cue-based strategy and adopt a new egocentric spatial response strategy to achieve rewards. Exogenous BDNF administration facilitated the acquisition of strategy shifting by minimizing response perseveration to the previously acquired strategy and this effect resemble an inverted-U shaped dose-response pattern. Faster acquisition of strategy switching in BDNF-infused animals was dependent upon the activation of striatal trkB receptors. Moreover, activation of mGluR2/3 receptors by the selective group II metabotropic receptor agonist LY379268 abolished BDNF-induced cognitive enhancement suggesting the involvement of presynaptic glutamatergic activity. Assessment of striatal glutamate dynamics using electrochemical recordings indicated that local application of BDNF directly induces glutamate release by activating presynaptic trkB receptors on glutamatergic terminals, and this effect followed a bell-shaped dose-response pattern similar to strategy shifting performance. These data suggest that activation of BDNF-trkB signaling in the dorsal striatum improves strategy switching by effectively minimizing response conflicts, and this effect primarily involves facilitation of glutamatergic transmission.


Elevated expression of astrocyte elevated gene-1 (AEG-1) is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III-IV serous ovarian carcinoma.
To correlate astrocyte elevated gene-1 (AEG-1) expression with the clinicopathological features and outcome of patients with stages III-IV ovarian serous carcinoma, and to clinically assess the involvement of AEG-1 in acquired cisplatin resistance. The frequency and intensity of immunohistochemical AEG-1 expression increased in a step-wise fashion from normal to chemosensitive to chemoresistant tissues. These observations were confirmed by Western blot analysis. AEG-1 expression level was correlated with lymph nodal metastasis, histological differentiation, residual tumour size and response to primary chemotherapy. Five-year progression-free survival (PFS) and overall survival (OS) rates were lower in the high-expression group than that in the low-expression group. AEG-1 overexpression was an independent but poor prognostic factor in the OS and PFS of these patients, as determined by multivariate Cox regression analysis. Multivariate logistic regression analysis revealed that the presence of cisplatin-based chemoresistance was significantly associated with expression level of AEG-1 and the degree of residual disease (P = 0.0001 and P = 0.0027, respectively). Our findings indicate that tumour AEG-1 overexpression is associated with poor prognosis and cisplatin resistance in advanced serous ovarian cancer.


Hepatoprotective effect of ganoderma triterpenoids against oxidative damage induced by tert-butyl hydroperoxide in human hepatic HepG2 cells.
Ganoderma triterpenoids (GTs) have been recognised as an important bioactive ingredient in Ganoderma Lucidum (Leyss. ex Fr.) Karst. (Polyporaceae), widely used for treating and preventing chronic hepatopathy of various etiologies. The objective of this study is to better understand the hepatoprotective effect of GTs and to enhance their use in food supplement pharmaceutical and medical industries. HepG2 cells were pretreated in the presence or absence of GTs (50, 100 and 200 μg/ml) for 4 h, then exposed with 60 μmol/L of t-BHP for an additional 4 h. The cell viability was evaluated by MTT method. ALT, AST and LDH production in culture medium and intracellular MDA, GSH and SOD levels were determined. Moreover, the total triterpenoid content and chemical constituents in GTs were detected by ultraviolet spectrophotometry and HPLC/Q-TOF-MS, respectively. GTs (50, 100 and 200 μg/ml) significantly increased the relative cell viability by 4.66, 7.78 and 13.46%, respectively, and reduced the level of ALT by 11.44%, 33.41% and 51.24%, AST by 10.05%, 15.63% and 33.64%, and LDH by 16.03%, 23.4% and 24.07% in culture medium, respectively. GTs could also remarkably decrease the level of MDA and increase the content of GSH and SOD in HepG2 cells. Furthermore, the total triterpenoid content in GTs was 438 mg GAAEs/g GTs. And 16 triterpenoids in GTs were identified or tentatively characterised. Our results showed that GTs had potent cytoprotective effect against oxidative damage induced by t-BHP in HepG2 cells, thus suggesting their potential use as liver protectant.


Synthesis and characterizations of amphiphilic poly(L-lactide)-grafted chondroitin sulfate copolymer and its application as drug carrier.
In this investigation, new biodegradable brush-like amphiphilic copolymers were synthesized by ring opening polymerization. Poly(L-lactide) (PLLA) was grafted onto chondroitin sulfate (CS), which is one of the physiologically significant specific glycosaminoglycans (GAGs), using a tin octanoate [Sn(Oct)2] catalyst in DMSO. The hydroxyl groups of the chondroitin sulfate were used as initiating groups. These functional groups enable specific mucoadhesion or receptor recognition. The degree of substitution (DS), the degree of polymerization (DP) and the chondroitin sulfate content (from 1.1 to 15.4%) were analyzed by 1H NMR. The characteristics of these grafted copolymers, including the structure, the thermal properties and biodegradability, etc., were examined with respect to CS content. Meanwhile, the amphiphilic core (PLLA)-corona (CS) nanoparticles, with size smaller than 200 nm, was examined by dynamic light scattering (DLS). Zeta potential analysis exhibited the value in the range -18.3 to -49.4 mV. The morphologies of the nanoparticles were observed by field-emission scanning electron microscopy (FE-SEM). The nanoparticles with lower cytotoxicity were examined by MTT assay. Furthermore, the in vitro BSA release kinetics of those CSn-PLLA nanoparticles was also determined in this study.


Antigenic relationships between plasma membrane ATPases of two different yeasts, Candida tropicalis and Schizosaccharomyces pombe.
Antibodies raised against purified plasma membrane ATPase from the yeast S. pombe inhibit the plasma membrane-bound ATPase of another yeast, C. tropicalis. The kinetic constants, Vm and Km, of the ATPases are both modified by the antibodies. These results show antigenic relationships between the plasma membrane ATPases belonging to the two yeast genera.


Mode of ventilation during cardiopulmonary bypass does not affect immediate postbypass oxygenation in pediatric cardiac patients.
To investigate the impact of different modes of ventilation during cardiopulmonary bypass (CPB) on immediate postbypass oxygenation in pediatric cardiac surgery. Prospective, randomized clinical trial. University hospital. 50 pediatric patients (18 girls, 32 boys), aged 4 months to 15 years, undergoing elective repair of congenital heart disease. Patients were randomized to receive one of 5 modes of ventilation during bypass. Groups 1 and 2 received high-frequency/low-volume ventilation with 100% (group 1) or 21% oxygen (group 2). Groups 3 and 4 received continuous positive airway pressure of 5 cm H(2)O with 100% (group 3) or 21% oxygen (group 4); and in group 5, each patient's airway was disconnected from the ventilator (passive deflation). Blood gas analysis and spirometry data were recorded 5 minutes before chest opening, 5 minutes before inducing bypass, 5 minutes after weaning from bypass, and 5 minutes after chest closure. There were no differences in Pao(2) values among the 5 groups studied and at the different time points. Lung compliance was higher 5 minutes before bypass in group 1 versus group 5 (34 +/- 13 mL/cm H(2)O vs 20 +/- 9 mL/cm H(2)O; P = 0.048). Mode of ventilation during CPB did not affect immediate postbypass oxygenation.


TDP1 and TOP1 as targets in anticancer treatment of NSCLC: Activity and protein level in normal and tumor tissue from 150 NSCLC patients correlated to clinical data.
Topoisomerase 1 (TOP1) is a drug target used in anticancer treatment of various cancer types. The effect of the TOP1 drugs can be counteracted by the enzymatic activity of tyrosyl-DNA phosphodiesterase 1 (TDP1). Thus, to elucidate the relevance of combining TDP1 and TOP1 as drug targets for anticancer treatment in NSCLC, TDP1 and TOP1 was for the first time quantified in a large cohort of paired normal and tumor tissue from NSCLC patients, and data were correlated between the two enzymes and to clinical data. TDP1 and TOP1 activity and protein concentration were measured in paired normal and tumor tissue from 150 NSCLC patients using TDP1 and TOP1 specific biosensors and ELISA. TDP1 and TOP1 activity and protein concentration were correlated to clinical data. TDP1 and TOP1 activity and protein concentration were significantly upregulated from normal to tumor tissue for the individual patients, but did not correlate to any of the clinical data. TDP1 and TOP1 activity were upregulated in 89.3% and 82.7% of the patients, respectively, and correlated in both normal and tumor tissue. The same tendency was observed for protein concentration with an upregulation of TDP1 and TOP1 in 73.0% and 84.4% of the patients, respectively. The activity and protein concentration correlated in normal and tumor tissue for both TDP1 and TOP1. The upregulations of TDP1 and TOP1 from normal to tumor tissue combined with the observation that TDP1 and TOP1 did not correlate to any of the clinical data indicate that both proteins are important for development or maintenance of the tumor cells in NSCLC. Correlations between TDP1 and TOP1 indicate a biological dependency and potential co-regulation of the enzymes. These observations is encouraging in relation to using TOP1 and TDP1 as targets in anticancer treatment of NSCLC.


Malignancy risk for solitary and multiple nodules in Hürthle cell-predominant thyroid fine-needle aspirations: A multi-institutional study.
Hürthle cell metaplasia is common in hyperplastic nodules, particularly within the setting of lymphocytic thyroiditis (LT). The Bethesda System for Reporting Thyroid Cytopathology indicates that it is acceptable to classify Hürthle cell-predominant fine-needle aspiration (HC FNA) specimens as atypia of undetermined significance (AUS) rather than suspicious for a Hürthle cell neoplasm (HUR) within the setting of multiple nodules or known LT. The goal of the current study was to address whether this approach is justified. HC FNA specimens were identified and correlated with ultrasound and surgical pathology reports if available. Multinodularity was determined based on findings on macroscopic examination if imaging results were unavailable. A total of 698 HC FNA specimens were identified, including 576 resected nodules, 455 of which (79%) were benign. The overall risk of malignancy for HUR was 27%, whereas the risk of malignancy for AUS was 10%. The mean size of the benign nodules was 2.1 cm on surgical resection specimens, with multiple nodules noted in 293 cases (64%) and histologic LT noted in 116 cases (25%). The mean size of the malignant nodules was 2.8 cm, with multiple nodules and histologic LT noted in 74 cases (61%) and 22 cases (18%), respectively. The malignancy rate did not differ between solitary or multiple nodules (P = .52) or in the presence or absence of LT (P = .12). However, size did significantly differ between malignant and benign nodules (P < 0.01). The malignancy rate did not differ significantly in the presence of multiple nodules or LT, although the latter demonstrated a statistical trend. A diagnosis of AUS over HUR based solely on the presence of multinodularity is not warranted.


Is There a Relationship Between Mating and Pathogenesis in Two Human Fungal Pathogens, Candida albicans and Candida glabrata?
Human fungal pathogens are rapidly increasing in incidence and readily able to evade the host immune responses. Our ability to study the genetic behind this has been limited due to the apparent lack of a sexual cycle and forward genetic tools. In this review, we discuss the evolution of mating, meiosis, and pathogenesis and if these processes are advantageous to pathogens. This review summarises what is currently known about the sexual cycles of two important human fungal pathogens, Candida albicans and Candida glabrata. This includes the identification of parasexual cycle in C. albicans and the observed low levels of recombination in C. glabrata populations. In this review, we present what is currently known about the mating types and mating/sexual cycles of two clinically important human fungal pathogens, Candida albicans and Candida glabrata. We discuss the evolution of meiosis using the knowledge that has been amassed from the decades of studying Saccharomyces cerevisiae and how this can be applied to fungal pathogens. We further discuss how the evolution of pathogenesis has played a role in influencing mating processes in human fungal pathogens and compare sexual cycles between C. albicans and C. glabrata, highlighting knowledge gaps and suggesting how these two fungi have evolved distinct mating niches to allow the development of disease in a human host.


Plasma cells producing lambda light chains are predominant in human gut and tonsils. An immunohistomorphometric study.
An immunohistomorphometric study was performed on human samples of duodenum (10) and tonsil (25) to assess the numbers of plasma cells producing kappa or lambda chains. Different reagents were used and carefully assayed for specificity and absence of cross-reactivity. Kappa chains were found predominantly with these antibodies in 46 bone marrow-derived B-cell proliferations used as reagents' control samples. In contrast, plasma cells producing lambda chains were found to be more numerous in the samples of mucosal tissues. The kappa/lambda ratio observed was 0.53. This finding could be another feature reflecting the autonomy of the immune system of mucosae (MALT) in humans.


Synchronized Cardiac Impulses Emerge From Heterogeneous Local Calcium Signals Within and Among Cells of Pacemaker Tissue.
This study sought to identify subcellular Ca2+ signals within and among cells comprising the sinoatrial node (SAN) tissue. The current paradigm of SAN impulse generation: 1) is that full-scale action potentials (APs) of a common frequency are initiated at 1 site and are conducted within the SAN along smooth isochrones; and 2) does not feature fine details of Ca2+ signaling present in isolated SAN cells, in which small subcellular, subthreshold local Ca2+ releases (LCRs) self-organize to generate cell-wide APs. Immunolabeling was combined with a novel technique to detect the occurrence of LCRs and AP-induced Ca2+ transients (APCTs) in individual pixels (chronopix) across the entire mouse SAN images. At high magnification, Ca2+ signals appeared markedly heterogeneous in space, amplitude, frequency, and phase among cells comprising an HCN4+/CX43- cell meshwork. The signaling exhibited several distinguishable patterns of LCR/APCT interactions within and among cells. Rhythmic APCTs that were apparently conducted within the meshwork were transferred to a truly conducting HCN4-/CX43+ network of striated cells via narrow functional interfaces where different cell types intertwine, that is, the SAN anatomic/functional unit. At low magnification, the earliest APCT of each cycle occurred within a small area of the HCN4 meshwork, and subsequent APCT appearance throughout SAN pixels was discontinuous and asynchronous. The study has discovered a novel, microscopic Ca2+ signaling paradigm of SAN operation that has escaped detection using low-resolution, macroscopic tissue isochrones employed in prior studies: synchronized APs emerge from heterogeneous subcellular subthreshold Ca2+ signals, resembling multiscale complex processes of impulse generation within clusters of neurons in neuronal networks.


Complete genomic characterization of bovine papillomavirus type 1 and 2 strains infers ongoing cross-species transmission between cattle and horses.
Infection with bovine papillomavirus (BPV) types 1 and 2 results in the most common skin tumor of horses, termed equine sarcoid. The persistent and recurrent nature of this tumor stands in contrast to the regressive nature of BPV-1/- 2 induced cutaneous papillomas in cattle. The circulation of horse-specific BPV-1/- 2 variants within equine populations has been suggested as a possible explanation for the difference in clinical presentation of BPV-1/- 2 infection between horses and cattle. In order to investigate this hypothesis, we identified 98 complete BPV-1/- 2 genomes using a Nanopore sequencing approach. Separate BPV-1/- 2 alignments were used to infer Bayesian phylogenetic trees. Phylogeny-trait association concerning host species was investigated using Bayesian Tip-association Significance software (BaTS) Overall, 179 unique BPV-1 and 128 BPV-2 substitutions were found. The E2 coding region in the viral genome exhibited an exceptionally high rate of non-synonymous mutations (81 %, n = 13/16). Interestingly, extensive deletions in the L1/L2 region (up to 1.5 kb) were found exclusively in horse-derived samples. Nevertheless, the most frequently detected single nucleotide polymorphisms were shared between equine and bovine hosts, which is in agreement with BaTS results indicating no phylogeny-host correlation. We found indications that horse-specific mutations might exist in subpopulations of equine derived BPV-1/- 2, but these did not result in horse-adapted genetic variants. Based on these observations, cross-species transmission from cattle to horses seems to be an ongoing process, rather than an ancient occurrence that has been followed by the circulation of horse-adapted BPV variants in the horse population..


Towards a collective biology of the gene.
Two features of heterochromatin: heteropycnosis (high values of chromatin condensation), and repressed genetic expression, force upon us the use of cooperative variables, rather than molecular ones. In particular a "repressor" hypothesis is formulated, in which a useful parameter is clearly identified. This enables us to discuss the synchronized repression of a large number, n, of genes (as in the case of the Barr body, in which n is larger than 100). The hypothesis is documented with phenomena known to occur in active chromatin. Possible tests are suggested.


Novel keratin 14 gene mutations in patients from Hungary with epidermolysis bullosa simplex.
Mutations in genes keratin 5 (KRT5) and 14 (KRT14) encoding the basal type keratin intermediate filaments have been identified in epidermolysis bullosa simplex (EBS) families and are likely to cause skin fragility. Three novel keratin 14 mutations in cases from the Hungarian Epidermolysis Bullosa Centre are reported. In a 7-year-old boy with Dowling-Meara type EBS (DM-EBS), who had severe skin symptoms with extended herpetiform blisters, a novel amino acid substitution N123K in keratin 14 had been detected. A 26-year-old woman with mild DM-EBS with prominent palmoplantar hyperkeratosis and without active blister formation had a novel R125G mutation in keratin 14. In a 6-year-old girl, with Weber-Cockayne type EBS (WC-EBS) with palmoplantar blisters and moderate mental retardation, a novel V133L substitution was detected. Her pedigree showed autosomal dominant mode of inheritance; in the two other families, only the index patients were affected. The N123K and R125G mutations causing DM-EBS phenotypes are located within the helix initiation motif of the rod domain, whereas the very close V133L mutation underlying the WC-EBS phenotype is outside of this region. These novel amino acid substitutions provide further information for genotype-phenotype correlation in KRT14 mutations, and demonstrate the first molecular genetic data in EBS patients from Hungary.


Cytogenetic and histologic analyses of spontaneous abortions.
In a study of spontaneous abortions the correlations between karyotype (166 cases), anamnestic data, and macroscopic and histologic findings in placentas (107 cases) and embryos (73 cases) were analyzed. The main results were: 1. The rate of chromosomal aberrations was 39%. Trisomies predominated (60%), followed by monosomy X (20%), triploidies (14%), and structural aberrations (6%). 2. In trisomies a clear prevalence of female sex constitution (2:1) was observed. In normal karyotypes a slight prevalence of females was seen (1.2:1). 3. With increasing maternal age, more trisomies were found in the abortions. 4. Women whose index abortion had a normal karyotype had a history of fewer births but more abortions. 5. Trisomies of acrocentric chromosomes were mainly chorionic sacs with an embryo, while trisomies of the other autosomes resulted in intact empty sacs. 6. The average developmental stage of the embryos was 5 weeks, with a mean gestational age of 14 weeks. Gross malformations were found in 58% of the embryos.


Inappropriate growth-hormone (GH) response to thyrotropin-releasing hormone (TRH) occurs infrequently in well-regulated diabetes mellitus.
We randomly administered thyrotropin-releasing hormone (200 micrograms, as an i.v. bolus) or control saline (in isovolumic amount) to 30 male diabetic subjects (23 IDDM, 7 NIDDM) in fair metabolic control (HbA1 9.7 +/- 0.3%, means +/- SEM) and to 12 healthy male controls on two different mornings. While GH in the basal state was similar in IDDM, NIDDM and normal subjects, TRH administration evoked a significant GH release only in a single IDDM individual. The only GH-responder to TRH was a newly-diagnosed (two weeks) IDDM patient, still with a high glycated hemoglobin level (HbA1 11.1%), despite normal plasma glucose levels. Saline infusion did not affect GH concentrations either in normals or in diabetics. Exaggerated GH responses to TRH are uncommon in diabetic patients in good metabolic conditions.


Successful treatment of psoriasis of the nails.
Psoriasis of fingernails and toenails presents a challenge that has not been met by the available therapeutic modalities. Three cases of treatment with x-ray therapy of varying intensities are presented herein. Cure was acheived in all three cases with no x-ray sequelae.


Genetic Instruction of Megakaryocytes and Platelets Derived from Human Induced Pluripotent Stem Cells for Studies of Integrin Regulation.
Platelets are small, anucleate cells that play oversized roles in hemostasis, immunity, and inflammation. An important mediator of platelet function is integrin αIIbβ3, which is required for fibrinogen-dependent platelet aggregation during hemostasis. This platelet response is dependent on conformational changes in the integrin induced by "inside-out" biochemical signals that are triggered by platelet agonists. In turn, fibrinogen binding to αIIbβ3 initiates "outside-in" biochemical and mechanical signals that regulate the platelet cytoskeleton and help to promote full platelet aggregation and secretory responses. Without a nucleus, there is a limited range of experimental manipulations that are possible with human platelets to study the molecular basis of integrin signaling in these primary cells. Consequently, many studies of αIIbβ3 function use genetic approaches that rely on heterologous expression systems or platelets from gene-targeted mice, sometimes with uncertain applicability to human platelets. This chapter will detail a method for genetic manipulation of megakaryocytes and platelets derived from human induced pluripotent stem cells for molecular studies of αIIbβ3 signaling and for modeling of human platelet functions potentially relevant to hemostasis, immunity, and inflammation.


Quantification of iodiconazole by LC-MS/MS, a new topical transdermal cream, in dermatophytosis patients' plasma.
A rapid and sensitive LC-MS/MS method was established to measure iodiconazole (ADKZ) in dermatophytosis patients treated topically with 2% ADKZ cream. ADKZ was extracted by liquid-liquid extraction (LLE) and separated by an Agilent Zorbax SB-C18 column (2.1 × 150 mm, 3.5 μm) using methanol - 0.01% formic acid (70:30, v/v) as the mobile phase. All the validation assays met the acceptable criteria and the linearity ranged from 10 to 1000 pg/ml. The method has been validated to be simple, sensitive and successfully applied to the study. The average amount of ADKZ absorbed into blood was approximately 0.51 μg daily, and ADKZ blood concentrations were consistent during the four-week treatment course. The cumulation of ADKZ in vivo was almost negligible.


Effect of pazufloxacin mesilate on the serum concentration of theophylline.
We studied the effect of pazufloxacin mesilate (T-3762), a new fluoroquinolone for intravenous administration, on the serum concentration of theophylline. Evaluation consisted of comparisons of serum levels of theophylline (when it was given alone, as a control), with serum levels of theophylline when T-3762 was given concomitantly. We measured the serum concentrations and the urinary excretion rates of theophylline in healthy adult male volunteers who were given theophylline for 5 days, followed by an i.v. infusion of T-3762. Blood and urine samples were investigated on the third and fifth days after the concomitant dosing with T-3762, to compare the serum levels and urinary concentrations of theophylline with the control values. We found that the serum concentration and the urinary excretion rates of theophylline on the fifth day after concomitant dosing with T-3762 were significantly increased compared with the levels when the volunteers had been given theophylline alone.


[The time-related risk for knee osteoarthritis after ACL injury. Results from a systematic review].
The aim of this review was to evaluate the time-related risk for knee osteoarthritis in patients after ACL injury. The primary search was carried out in different medical databases with the deadline 12.01.2014. The search strategy for the evaluation was [ACL] AND [osteoarthritis] including "all fields". All 1656 title/abstracts were reviewed by two independent researchers who selected 140 papers for full text review. Finally, a total of 21 relevant publications were identified for inclusion in this current paper. The incidence of knee osteoarthritis rises significantly over time. Two years after injury it was 6.9%, after 5 years 32.2%, after 7 years 36.3%, and after 10 years 79.6%. At the same time, the crude relative risk of OA rises as the time interval since injury increases. The relative risk of OA has already doubled by 2 years after ACL injury). By 7 years it has increased fivefold and compared with OA status at the time of injury it is still increasing significantly after 10 years. The ACL injury is a significant risk factor for the development of early-onset secondary knee osteoarthritis. Within 5 years of the injury the knee shows clear signs of osteoarthritis on MRI. However, these lesions are often not associated with any clinical signs. Knee osteoarthritis as a severe disease starts 8 years or later after the injury, when it requires treatment.


Molecular genotyping of Blastocystis spp. in wild mammals from Mexico.
Blastocystis spp. are common intestinal parasites found worldwide in humans and a wide range of animals. They exhibit extensive genetic diversity; currently, 17 subtypes (STs) and some groups called non-mammalian and avian STs (NMASTs) have been proposed. In addition, a large variety of animals have been reported as hosts of the parasite, and new hosts and STs are still being described. In this study, Blastocystis infection of wild animals in two sylvatic areas of Mexico was surveyed. Of one hundred twenty-four fecal samples, six were positive for Blastocystis: specifically, one sample from an opossum, one sample from a bat, and four samples from different species of rodents. ST4, ST17, and nucleotide sequences similar to Blastocystis lapemi were identified based on SSU rDNA sequences. To our knowledge, this is the first report to investigate species poorly or not previously evaluated for Blastocystis infection. Mammals having different niches and geographical distribution were infected with similar genetic type of Blastocystis, so that we suggest that local water or food sources could play an important role in Blastocystis transmission and ST maintenance in wild animals. Additionally, there are STs with scarce genetic variation, suggesting that they could be highly adapted to their hosts. These data contribute to our understanding of the host range and genetic diversity of Blastocystis.


Mobile phone effects on children's event-related oscillatory EEG during an auditory memory task.
To assess the effects of electromagnetic fields (EMF) emitted by mobile phones (MP) on the 1 - 20 Hz event-related brain oscillatory EEG (electroencephalogram) responses in children performing an auditory memory task (encoding and recognition). EEG data were gathered while 15 subjects (age 10 - 14 years) performed an auditory memory task both with and without exposure to a digital 902 MHz MP in counterbalanced order. During memory encoding, the active MP modulated the event-related desynchronization/synchronization (ERD/ERS) responses in the approximately 4 - 8 Hz EEG frequencies. During recognition, the active MP transformed these brain oscillatory responses in the approximately 4 - 8 Hz and approximately 15 Hz frequencies. The current findings suggest that EMF emitted by mobile phones has effects on brain oscillatory responses during cognitive processing in children.


Nuclear envelope formation in vitro: a sea urchin egg cell-free system.
The formation of the nuclear envelope (NE) typically occurs once during every mitotic cycle in somatic cells, and also around the sperm nucleus following fertilization. Much of our understanding of NE assembly has been derived from systems modeling the latter event in vitro. In these systems, demembranated sperm nuclei are combined with fertilized egg cytoplasmic extracts and an ATP-regenerating system and in a multistep process they form the functional double bilayer of the NE. Using a system that we developed from sea urchin gametes, we have demonstrated that NE assembly is regulated by membrane vesicles in a spatial and temporal fashion, emphasizing the roles of phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)), diacylglycerols (DAG), and lipid-modifying enzymes in NE assembly.


Effects of inhaled chromium dioxide dust on rats exposed for two years.
Rats were exposed by inhalation to chromium dioxide (CrO2) dust at design concentrations of 0, 0.5 mg/m3 (stabilized and unstabilized, respectively), or 25 mg/m3 (stabilized) for 6 hr/day, 5 days/week for 2 years. No dust-exposure-related pathological changes other than lung lesions were observed in all exposed rats. There were no significant differences in pulmonary responses between unstabilized and stabilized CrO2 at the 0.5 mg/m3 exposure level. The lungs showed minute dust deposition in the alveoli adjacent to the alveolar ducts, but maintained an intact general architecture. The pulmonary responses satisfied the biological criteria for a nuisance dust. At 25 mg/m3, dust deposition was sharply confined to the alveoli in the alveolar duct region. Alveolar walls enclosing dust-laden macrophage (dust cell) aggregates were thickened with hyperplastic Type II pneumocytes and slightly collagenized fibrosis. Alveoli adjacent to the terminal bronchioles were lined with bronchiolar epithelium (alveolar bronchiolarization). In addition, lungs showed foamy macrophage response, cholesterol granulomas, alveolar proteinosis, and minute fibrotic pleurisy. These pulmonary lesions occurred predominantly in female rats. Of 108 female rats, 6 developed keratin cysts and 2 had cystic keratinizing squamous cell carcinoma (CKSCC). None of 106 male rats had either a keratin cyst or a CKSCC. The lung tumors developed from metaplastic squamous cells in the areas of alveolar bronchiolarization at the alveolar duct region. The lung tumors were well differentiated and devoid of characteristics of true malignancy. The CKSCC is an experimentally induced, unique tumor type and is different from the type of spontaneous lung tumor seen in man or animals. The relevance to man of this type of lung tumor appears to be negligible.


Tumor-stroma TGF-β1-THBS2 feedback circuit drives pancreatic ductal adenocarcinoma progression via integrin αvβ3/CD36-mediated activation of the MAPK pathway.
The pancreatic ductal adenocarcinoma (PDAC) microenvironment contains dense desmoplastic stroma dominated by cancer-associated fibroblasts (CAFs) and is crucial to cancer development and progression. Several studies have revealed that thrombospondin 2 (THBS2) is a valuable serological-marker in PDAC. However, the detailed mechanism of the cancer-stroma interactome remains unclear. Here we showed that elevated THBS2 expression in PDAC was predominantly restricted to stroma and correlated with tumor progression and poor prognosis by quantitative proteomics and immunohistochemistry analyses. RNA in situ hybridization confirmed that CAFs but not neoplastic cells expressed THBS2 in precancerous lesions and its levels gradually increased with disease progression in genetically engineered mouse models. Mechanistically, cancer cell-secreted TGF-β1 activated CAFs to induce THBS2 expression via the p-Smad2/3 pathway. Consequently, CAF-derived THBS2 bound to the membrane receptors integrin αvβ3/CD36 and activated the MAPK pathway in PDAC cells to promote tumor growth and adhesion in vitro and in vivo. Inhibition of integrin αvβ3, CD36, MEK and JNK rescued THBS2-induced malignant phenotypes. In conclusion, the TGF-β1-THBS2-integrin αvβ3/CD36-MAPK cascade forms a complex feedback circuit to mediate reciprocal interactions of pancreatic cancer cells-CAFs. THBS2 may act as a novel therapeutic-target to block the cancer-stroma communication.


Effects of cadmium on lipid metabolism in female estuarine crab, Chiromantes dehaani.
Due to the nature of their habitat, which contains a high level of pollutants, estuarine crabs are at great risk of exposure to contaminants such as cadmium. Thus, in this study, the effects of cadmium on lipid metabolism were investigated in estuarine crab Chiromantes dehaani. Adult female estuarine crabs were randomly exposed to 0.05, 0.1, 0.5, and 1mg/L of CdCl2 for 7, 14 and 21days, after which the lipid contents of the hepatopancreas and ovary were measured. Also, the substance contents and the activities of the enzyme in lipid digestion, lipid synthesis and lipid transport metabolism were analyzed. The results showed that the lipid contents in the hepatopancreas and ovary of the exposed crabs decreased after prolonged exposure to cadmium compared to the control. The lipase activity decreased while the activities of fatty acid synthase and acetyl coenzyme A in the hepatopancreas increased on day 7 but decreased on days 14 and 21. Moreover, the change in non-esterified fatty acid level was similar to fatty acid synthase. The level of low-density lipoprotein increased in the exposed crabs compared to the control group while the level of high-density lipoprotein and the activity of lipoprotein lipase decreased at a higher concentration of cadmium and longer exposure time. These observations suggest that cadmium decreases the lipid content by weakening the ability of digestion, transportation and synthase of lipid, thus affecting hepatopancreas and ovary indices.


Canonical correlation analysis of abiotic and biotic variates in insect-infested grain bulks.
The impact of insect infestation on several biotic and abiotic variates in 3 small bulk-wheat ecosystems was studied by measuring these variates at monthly intervals during 1969-1970. One ecosystem was insect-free, the second was artificially infested with Cryptolestes ferrugineus and Oryzaephilus surinamensis, and the third with Sitophilus granarius and Tribolium castaneum. The relationships between 8 environmental and 8 entomological and microbial variates were examined by canonical correlation analyses. The degree of predictability (R c2 ) of the first pair of canonical variates in the 3 ecosystems ranged from 80% to 95%. The first 2 pairs of canonical variates were highly significant in all 3 analyses (P<0.01). In the insect-free ecosystems the canonical variates revealed that temperature and the period of storage were the primary environmental antecedents involved and the criterion was composed primarily of the field fungus Alternaria and the storage fungus Aspergillus. In the second ecosystem uric acid level in the grain bulk was an additional environmental factor that affected the population of both species of insects and 3 kinds of fungi Altrnaria, Aspergillus, and Penicillium. In the third ecosystem temperature, time, uric acid and moisture interacted collectively, with density of insect populations, reduction of Alternaria, and increase of Aspergillus.


Caffeinated coffee blunts the myocardial protective effects of statins against ischemia-reperfusion injury in the rat.
We asked whether caffeinated coffee (CC) blunts the infarct size (IS)-limiting effects of atorvastatin (ATV). Adenosine receptor activation is essential for mediating the IS-limiting effects of statins. Caffeine is a nonspecific adenosine receptor blocker, and thus drinking CC may block the myocardial protective effects of statins. Rat received 3-day ATV (10 mg/kg/day) or water by oral gavage once daily. Drinking water was replaced by water + sugar (7.5 g/100 ml), CC with sugar, or decaffeinated coffee (DC) with sugar. On the 4th day, rats were anesthetized and underwent 30 min of coronary artery occlusion and 4 h reperfusion. Area at risk was assessed by blue dye and infarct size by TTC. Body weight and area at risk was comparable among groups. IS was 25.1 +/- 3.9% of the area at risk in the control group. In rats not receiving ATV, CC (25.5 +/- 3.1%) and DC (34.0 +/- 2.8%) did not affect IS. IS was significantly reduced by ATV in the water + sugar (11.7 +/- 0.7%, p = 0.015) and DC (11.5 +/- 1.0%; p < 0.001) groups, but not in the CC group (32.3 +/- 3.0%; p = 0.719). ATV increased myocardial levels of Ser-473 phosphorylated Akt in the water + sugar and DC groups, but not in the CC group. CC, but not DC, abrogated the IS-limiting effects of ATV by blocking the adenosine receptors and preventing the phosphorylation of Akt. CC did not affect IS in rats not receiving ATV.


An immunohistochemical study of hepatoblastoma producing human chorionic gonadotropin.
High tissue concentrations of human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) were revealed by radioimmunoassay in a hepatic tumor which was surgically removed from a two-year, eight-month-old boy manifesting sexual precocity. Histologically the tumor showed an embryonal type hepatoblastoma admixed with multinucleated tumor giant cells. The localization of native hCG and hCG-beta subunit was immunohistochemically demonstrated in some of the above giant cells, while that of alpha-fetoprotein was diffusely in the tumor cells of hepatoblastoma of embryonal type. Ultrastructural features of the giant cells were also presented.


Hyponatremic hypertensive syndrome in pediatric patients: is it really so rare?
Hyponatremic hypertensive syndrome (HHS) is characterized by unilateral renal artery stenosis with secondary hypertension and glomerular and tubular dysfunction due to hyperfiltration and activation of the renin-angiotensin system (RAS). We describe four children with HHS. All presented with polyuria and polydipsia, electrolyte disturbances, metabolic alkalosis, variable tubular dysfunction, and nephrotic range proteinuria along with hypertension. Interestingly, in one patient, glomerular and tubular abnormalities preceded the development of hypertension. All symptoms resolved after the underlying renal ischemia was corrected by percutaneous angioplasty. Hyponatremic hypertensive syndrome may be more common in children than previously thought. Clinicians should be alert of the signs and symptoms because cure is possible with timely diagnosis and treatment.


Camptothecins and two new monoterpene glucosides from Ophiorrhiza liukiuensis.
Two new monoterpene glucosides, demethylsecologanol and 3'''-O-glucosylsenburiside II, were isolated from Ophiorrhiza liukiuensis (Rubiaceae) together with 23 known compounds, including camptothecins and beta-carboline-type alkaloids. Their structures were determined by spectroscopic analysis.


Evaluation of the relationship between clinical variables and thromboelastographic findings in dogs with protein-losing nephropathy.
To determine whether hypercoagulability in proteinuric dogs, defined by thromboelastography (TEG), is related to the degree of proteinuria, presence of systemic arterial hypertension, presence of hypoalbuminemia, or reduced antithrombin activity. Prospective study of client-owned dogs. Data collected from each patient included signalment, body weight, urine protein-to-creatinine ratio (UPC), serum albumin concentration, TEG values, noninvasive arterial blood pressure, and AT activity. Hypercoagulability was diagnosed by TEG and odds ratios for other measurements were assessed by univariate logistic regression. Urban referral center and teaching hospital. Seventy-six dogs with protein-losing nephropathy (PLN) based on UPC, diagnosed between Oct 2009 and Oct 2012. None. The prevalence of hypercoagulability was 89%. No statistically significant associations were detected between hypercoagulability and UPC, serum albumin, noninvasive blood pressure, or AT activity (all P > 0.05). The prevalence of thromboembolism was 6.6%. Hypercoagulability was prevalent in dogs with PLN but could not be predicted based upon the presence or degree of proteinuria, systemic arterial hypertension, hypoalbuminemia, or low AT activity. The prevalance of thromboembolism was low in this population with PLN.


Renal insufficiency and magnesium deficiency correlate with a decreased formation of biologically active cholecalciferol: a retrospective observational study.
Vitamin D is synthesized in the skin or supplied. Cholecalciferol is hydroxylated in the liver to 25(OH) vitamin D [25D]. 25D is further hydroxylated in the kidney to 1,25(OH) vitamin D [1,25D]. Catabolism occurs by further hydroxylation. Magnesium is a cofactor of all involved hydroxylases. To investigate the association between renal function and serum magnesium levels, and the biologically active hormone 1,25D. Anonymised serum values of 25D, 1,25D, magnesium and creatinine measured in an outpatient cohort over 2 years were analysed. Renal function and magnesium level did not influence 25D values (r = - 0.144 and 0.030, respectively). Mean serum 1,25D values decreased from 106.5 ± 44.3 pmol/l in individuals with normal renal function to 51.7 ± 18.9 pmol/l in those with severe renal insufficiency (p < 0.01). A weak positive correlation was observed between 1,25D and eGFR (r = 0.317), and between 1,25D and serum magnesium (r = 0.217). Impaired renal function and low magnesium serum levels are slightly associated with low 1,25D concentrations. Measuring 25D, but not 1,25D, may overestimate the patient's vitamin D status. In patients with renal insufficiency adequate magnesium supply should be ensured.


Human Immunodeficiency Virus Treatment and Prevention for Pregnant and Postpartum Women in Global Settings.
Efforts to prevent mother-to-child transmission of human immunodeficiency virus (HIV) have led to dramatic reductions in pediatric HIV worldwide. New advances in HIV treatment and prevention, focused on pregnant and breastfeeding women living with HIV, have improved maternal health while decreasing vertical and horizontal HIV transmission. In this article, we describe how such interventions-including antiretroviral therapy and HIV pre-exposure prophylaxis-can be incorporated into antepartum and postpartum care in global settings.


"The best of a bad situation?" A mixed methods survey exploring patients' perspectives on physiotherapy-led online group exercise programmes.
The COVID-19 pandemic saw the migration of many physiotherapy-led group exercise programmes towards online platforms. This online survey aimed to ascertain the patients' views of online group exercise programmes (OGEP), including their satisfaction with various aspects of these programmes, the advantages and disadvantages and usefulness beyond the pandemic. A mixed-methods design was utilised with a cross-sectional national online survey of patients who had previously attended a physiotherapy-led OGEP in Ireland. The survey collected both qualitative and quantitative data. Descriptive statistics were used to summarise the ordinal and continuous data and conventional content analysis was used to analyse the free-text responses. In total, 94 patients completed the surveys. Fifty percent of patients questioned would prefer in-person classes. Despite only a quarter of patient respondents preferring online classes going forward, satisfaction with the OGEPs was high with nearly 95% of respondents somewhat or extremely satisfied. Decreased travel and convenience were cited as the main benefits of OGEPs. Decreased social interaction and decreased direct observation by the physiotherapist were the main disadvantages cited. Patients expressed high satisfaction rates overall with online classes, but would value more opportunities for social interaction. Although 50% of respondents would choose in-person classes in the future, offering both online and in-person classes beyond the pandemic may help to suit the needs of all patients and improve attendance and adherence.


Intermediate lymphocytic lymphoma: an immunophenotypic study with comparison to small lymphocytic lymphoma and diffuse small cleaved cell lymphoma.
Sixteen cases of intermediate lymphocytic lymphoma (ILL), including eight cases with mantle zone architecture, were studied using cryostat sections, a biotin-avidin immunoperoxidase technique, and a large panel of monoclonal antibodies. The neoplastic cells invariably expressed IgM, most B lineage antigens (B1, TO15, Leu-12, 6A4, 41H, BA-1, and LN-2), and Ia. IgD was expressed in 12 cases. Leu-1 and Leu-8 were weakly expressed by the tumor cells in 12 and 11 cases, respectively. The neoplastic cells did not express common acute lymphoblastic leukemia antigen (CALLA) or the T10 antigen in any case. Because ILL is difficult to differentiate from small lymphocytic lymphoma (SLL) and diffuse small cleaved cell lymphoma (DSCCL) on the basis of light microscopic criteria, the immunologic findings of ILL were compared to 31 cases of B cell SLL and 11 cases of B cell DSCCL previously studied in the laboratory to determine if immunologic findings might aid in the distinction. No absolute, and five statistically significant, differences were found; IgD in combination with IgM was seen more commonly in cases of ILL and DSCCL than in SLL (P less than .01), IgG was found more often in SLL than in ILL and DSCCL (P less than .05), Leu-8 was more commonly expressed in ILL and SLL than in DSCCL (P less than .05), T9 expression was less frequent in ILL as compared with SLL (P less than .05) and more proliferating cells were seen in ILL and DSCCL than in SLL (P less than .01). The investigators conclude that these three classes of lymphoma are remarkable much more for their immunologic similarities than for their differences and that immunologic studies are of limited usefulness in differentiating the three neoplasms. Their results also support the concept that these lymphomas are closely related to each other. In particular, DSCCL immunologically appears to be more closely related to SLL and ILL than to follicular small cleaved cell lymphoma.


Prostaglandin E2 and cyclic AMP levels in human breast tumors.
Prostaglandin E2 (PGE2) and cyclic adenosine-3', 5'-monophosphate (cAMP) concentrations were measured in human benign and malignant breast tumors by radioimmunoassay. Two groups were found among the malignant tissues, one with high PGE2 (M = 65.89 pg/mg) and high cAMP (M = 0.704 pmole/mg) concentrations and one with low concentrations (M = 9.24 pg/mg and M = 0.299 pmole/mg, respectively). The low PGE2 levels in the malignant tumors did not differ significantly from the levels found in benign tumors (M = 8.06 pg/mg). cAMP levels were positively and highly correlated (r = +0.81) with PGE2 levels. No bone osteolysis could be discovered in any of the patients a few weeks after mastectomy operation, but PGE2 analysis of breast tumors may have prognostic value for the future.


Ischemic stroke caused by giant cell arteritis associated with pulmonary adenocarcinoma.
Giant cell arteritis (GCA) is the most common vasculitis in patients older than 50 years, and it is occasionally a cause of ischemic stroke. GCA as a paraneoplastic manifestation has been rarely described. We describe a 77-year-old man with a sudden onset of dizziness, vomiting, and gait disturbances. Following imaging studies, a diagnosis of bulbar ischemic stroke with left vertebral artery stenosis was made. Based on a history of polymyalgia rheumatica, on laboratory tests, and brain digital subtraction angiography, a diagnosis of GCA was advanced and the patient underwent high-dose steroidal therapy. After a total body 18-FGD PET imaging, a pulmonary adenocarcinoma was found. Vertebral artery involvement is a rare but important occurrence in GCA as it carries a high mortality rate, and may require a vigorous therapeutic approach. The association of lung cancer and GCA is infrequent, and the relationship between malignancy and GCA remains unclear. Whereas the search for a malignancy in the setting of a GCA is not routinely performed, the use of total body PET when a large vessel vasculitis is suspected may provide useful information on disease and help recognize occult neoplasms.


Intraoperative functional mapping of calculation in parietal surgery. New insights and clinical implications.
Parietal areas play a crucial role in calculation processing. The purpose of this study is to report our experience in the assessment of calculation processing during awake surgery in parietal areas, focusing on clinical implications and new insights provided by this approach. We retrospectively reviewed clinical and surgical data of 13 patients who underwent parietal surgery with calculation mapping. Cortical and sub-cortical areas (in 13 and five patients, respectively) involved in single-digit multiplications and additions were identified using bipolar electro-stimulation. Cortical stimulation data showed that the inferior parietal lobule and the intraparietal sulcus were specifically related to calculation in all cases, regardless of the side (100% of cases, in both sides). Conversely, the superior parietal lobule was inconstantly involved in calculation processing (40% of cases in the left and 75% in the right side), whereas the somatosensory area was never involved. Sub-cortical stimulation was able to detect functional areas for calculation in all patients: in 90% of cases the sub-cortical sites positive for calculation were in close anatomical connection with the cortical sites mapping for the same function. The intraoperative preservation (-or damaging-) of functional sites correlated with the absence (- or occurrence-) of post-operative calculation processing impairment. Our findings support the specificity of the reported technique in the intraoperative identification of sites functional for calculation. Our data show the bilateral involvement of parietal cortex, especially of the inferior lobule, in calculation processing. Furthermore, our study suggests the existence of a sub-cortical pathway specific for calculation, whose better understanding might be crucial for the clinical outcome of patients.


Spatial distribution of ectoparasites on the gills of the mullet, Liza macrolepis: the effects of pollution.
Spatial distribution of ectoparasites on the gills of the mullet Liza macrolepis collected from two sites, the unpolluted reference site (Site I) and the heavily polluted North western arm of Visakhapatnam harbour (Site II), was analysed. Of the various ectoparasite species found on the gills of the mullet, only Ancyrocephalus vanbenedeni (Monogenea) and Dermergasilus varicoleus (Copepoda), occurred commonly at both the sites with more or less high prevalence and mean intensity. A. vanbenedeni at site I preferred gill arch 1 and posterior most and central sections, whereas at site II, it showed preference for gill arch 3, and posterior and proximal sections of the gill. D. varicoleus is highly specific in site selection. It preferred gill arch 1 and the anterior and distal parts at both the sites. Ergasilus rostralis favoured gill arch 3 and anterior and proximal sectors, a safe place providing absolute protection from the environmental pollution. It is concluded that the distribution of various ectoparasites on the gills of L. macrolepis is determined by the force of ventilation water current, the behavioral response of the parasite to the stress induced by pollution and the surface area of gill arches.


Probiotics in health and disease in the pediatric patient.
Probiotics are truly a timeless concept. Initially standard components of the human diet, potentially beneficial bacteria and yeast have been eliminated systematically through modern methods of preparing and preserving foods. Although the concept of probiotics is not new, the science of probiotics is in its infancy. Only recently have techniques been developed to identify, culture, and produce the probiotics that are suitable for medical use consistently. Furthermore, the potential uses for these organisms may extend far beyond what originally was thought. In no way should probiotics be thought of as a panacea for the diseases described earlier; however, when used appropriately, they represent a potentially beneficial adjunct to other proved therapies and have the added benefit of providing a stabilizing influence on the delicate balance between the ecosystem that consists of the human and its flora.