Calcium-dependent neutrophil secretion: characterization and regulation by annexins.
To gain direct access to the secretory machinery and study the regulation, mechanisms, and effectors of Ca2+-dependent neutrophil secretion, we developed an efficient and reproducible method of plasma membrane permeabilization using streptolysin O. We confirmed previous studies that permeabilized neutrophils secrete in response to calcium alone, but we also found that the Ca2+ dose-response is biphasic. Secretion is detectable at <1.0 microM Ca2+ and reaches a plateau between 1.0 and 60 to 80 microM. When stimulated with >80 microM Ca2+, secretion is two- to threefold greater than at lower [Ca2+], suggesting that two distinct mechanisms of Ca2+-dependent secretion that differ in their affinity for Ca2+ exist in neutrophils. Although permeabilization allows 100% leak of lactate dehydrogenase, maximum secretion from permeabilized cells is 80% that of f-met-leu-phe-stimulated intact cells, indicating that the essential components of the Ca2+-dependent secretory apparatus are predominantly, if not entirely, membrane bound. Permeabilization causes leakage of 100% of annexins V and VI, but 41% of annexin I and 12% of annexin III are retained. Immunofluorescence microscopy revealed that retained annexins I and III are associated with granule membranes. Addition of soluble annexins I and III to permeabilized cells increased Ca2+-induced secretion up to 15% and 90%, respectively, implying that both annexins participate in this secretory pathway. While annexin V is not required for secretion, it inhibits the low Ca2+-affinity mechanism of secretion.


Infections After Renal Transplant in Recipients With Familial Mediterranean Fever: A Life-Threatening Issue.
We evaluated long-term results and infections requiring hospitalization in kidney transplant patients with Familial Mediterranean Fever (associated amyloidosis-type). We retrospectively reviewed medical records of patients with familial Mediterranean fever with at least 1-year posttransplant follow-up. Kidney transplant recipients with primary glomerulonephritis and equivalent demography, immunity status, and follow-up comprised the control group. In 32 patients with familial Mediterranean fever versus 25 control patients (mean follow-up 82 ± 57 vs 79 ± 54 mo; P = .82), average serum creatinine values were 1.7 ± 0.9 versus 1.5 ± 1.0 mg/dL (P = .41) at discharge, 1.4 ± 0.4 versus 1.3 ± 0.5 mg/dL (P = .44) at 1 year, 1.4 ± 0.6 versus 1.3 ± 0.5 mg/dL (P = .63) at 3 years, and 2.0 ± 1.5 versus 2.1 ± 1.5 mg/dL (P = .92) at last follow-up. Groups were not statistically different regarding average inpatient and number of hospitalizations due to infections at 1 year; however, at last follow-up, 26 patients with familial Mediterranean fever (81%) had 8.6 average admissions and 13 control patients (52%) had 2.8 average admissions (P = .02, P < .01). Early posttransplant, both groups were taking a triple drug immunosuppression regimen. However, at 1 and 3 years posttransplant, withdrawal and/or minimization occurred in 40.6% and 83.3% of patients with familial Mediterranean fever and 28% and 55.5% of control patients (P < .05, P < .05). During follow-up, 6 familial Mediterranean fever patients (18.7%) and 2 control patients (8%) died (P = .23). Although renal transplant patients with associated amyloidosis-type familial Mediterranean fever and those with glomerulonephritis have similar rejection and/or graft loss rates, hospital admissions due to infection and increased mortality are more common in the familial Mediterranean fever group, with immunosuppression drug withdrawal.


[From simple past to future tense. The essential role of medical history, an example: saturnism].
Too frequently seen as an underknowledge, History of Sciences and Medicine may be quite on the contrary see understood as anmatter exemplary matter of instruction for students and practicians. This paper shows how it is possible to interpret difficult cases by a good knowledge of very old medical and historical stories, and the example of past diseases owing to saturnism (lead poisoning) may be very eloquent.


Carbon-centered radicals add reversibly to histidine--implications.
Carbon-centered radicals of alcohols commonly used as hydroxyl radical scavengers (MeOH, EtOH, i-PrOH and t-BuOH) add reversibly to histidine with equilibrium constants up to 3 × 10(3) M(-1) and rate constants on the order of 10(9) M(-1) s(-1). Similar equilibria may compromise determinations of one-electron (radical) electrode potentials.


Improving On-Time Starts for Pediatric Cardiac MRI.
Delayed start times for cardiac MRI examinations have resulted in longer patient fasts, extended wait times, and poor synchronization of anesthesia induction and contrast administration. The aim of this work was to improve on-time start rates from an initial baseline of 10%. A multidisciplinary team comprising members of the cardiac and radiology services used the Realizing Improvement Through Team Empowerment methodology to target the root causes of the delays and enhance workflow. The main factors identified as contributing to examination delays were late patient arrival, variations in patient preparation time, unavailability of equipment, and inefficient scheduling processes. The implementation of various interventions, such as the use of standardized equipment scripts, ensuring timely patient preparation, and ensuring the availability of equipment when required, resulted in an increase in on-time start rates for cardiac MRI examinations to 34%. The study's systematic approach proved to be valuable in both understanding and resolving the identified problems. Through the continuous application of plan-do-study-act cycles, the authors effectively pinpointed obstacles and tested multiple potential measures to overcome them. This approach made it possible to comprehend the issue and to implement targeted interventions to address it.


Photoconductive Core-Shell Liquid-Crystals of a Perylene Bisimide J-Aggregate Donor-Acceptor Dyad.
A novel core-shell structured columnar liquid crystal composed of a donor-acceptor dyad of tetraphenoxy perylene bisimide (PBI), decorated with four bithiophene units on the periphery, was synthesized. This molecule self-assembles in solution into helical J-aggregates guided by π-π interactions and hydrogen bonds which organize into a liquid-crystalline (LC) columnar hexagonal domain in the solid state. Donor and acceptor moieties exhibit contrasting exciton coupling behavior with the PBIs' (J-type) transition dipole moment parallel and the bithiophene side arms' (H-type) perpendicular to the columnar axis. The dyad shows efficient energy and electron transfer in solution as well as in the solid state. The synergy of photoinduced electron transfer (PET) and charge transport along the narcissistically self-assembled core-shell structure enables the implementation of the dye in two-contact photoconductivity devices giving rise to a 20-fold increased photoresponse compared to a reference dye without bithiophene donor moieties.


Effects of an antiseptic mouthwash on odorigenic microbes in the human gingival crevice.
Odorigenic gram-negative anaerobes in human gingival crevices were significantly decreased for up to 120 minutes after rinsing with an antiseptic mouthwash. This observation parallels clinical measurements of the antiseptic effect on oral malodor and suggests that its odor-decreasing properties are related to its antimicrobial action in the mouth.


Pathogenesis of pre-eclampsia: marinobufagenin and angiogenic imbalance as biomarkers of the syndrome.
Pre-eclampsia (preE), a pregnancy disorder with the de novo onset of hypertension and proteinuria after 20 weeks of gestation, has multiple triggers that initiate pathophysiologic mechanisms. This review addresses translational aspects of preE by synthesizing information on preE pathogenesis, describing diagnostic biomarkers that predict disease, and suggesting strategies to lessen adverse outcomes. Key to this understanding is the role of cardiotonic bufodienolides, with marinobufagenin (MBG) as the prototype, and angiogenic factors in preE pathogenesis. Data from a rat model believed to mimic human preE show that urinary excretion of MBG increases before the onset of hypertension and proteinuria and that affected animals have an increased vascular leakage and blood brain barrier permeability. Angiogenic imbalance occurs with the onset of the syndrome in this model. Also, we report that MBG levels in preE patients exceed those in normal pregnancy and that angiogenic factors are altered in patients showing signs and symptoms of overt disease. In vitro administration of MBG inhibits cytotrophoblast function and triggers hyperpermeability in endothelial cell monolayers. We advance the hypotheses that MBG precedes preE; MBG causes disruption of tight junction proteins leading to vascular leak via activation of MAPK which triggers apoptotic mechanisms resulting in further endothelial dysfunction leading to edema with the release of angiogenic factors. This review provides new evidence about the role of MBG and vasoactive intermediates in preE pathogenesis including the neurologic sequela and may reveal new therapeutic targets for the prevention of preE complications.


Enhanced negative feedback responses in remitted depression.
Major depressive disorder (MDD) is characterized by hypersensitivity to negative feedback that might involve frontocingulate dysfunction. MDD patients exhibit enhanced electrophysiological responses to negative internal (errors) and external (feedback) cues. Whether this dysfunction extends to remitted depressed (RD) individuals with a history of MDD is currently unknown. To address this issue, we examined the feedback-related negativity in RD and control participants using a probabilistic punishment learning task. Despite equivalent behavioral performance, RD participants showed larger feedback-related negativities to negative feedback relative to controls; group differences remained after accounting for residual anxiety and depressive symptoms. The present findings suggest that abnormal responses to negative feedback extend to samples at increased risk for depressive episodes in the absence of current symptoms.


[Simultaneous determination of eight derivatives of propranolol in cornea perfusate in vitro by high performance liquid chromatography].
A high performance liquid chromatographic method was developed for the simultaneous determination of eight derivatives of propranolol. Cassette dosing method was used in the epithelium side of cornea in vitro to get the effect of penetrant, and the perfusate was collected in the side of endothelium. The protein in the sample was precipitated and discarded by high speed centrifugation before injection. An Agilent Zorbax Extend column (150 mm x 3 mm, 5 microm) was used at 30 degrees C. The mobile phase system contained acetonitrile and 0.03% (v/v) phosphoric acid aqueous solution and the percentage of acetonitrile changed between 3% and 20% (v/v) in a linear gradient elution. The samples were detected by an ultraviolet (UV) detector at 205 nm. The results showed that the eight derivatives of propranolol were completely separated and determined in 31 min. The correlation coefficients were above 0.9970 and good linear relationships were obtained in the range of 0.2 (0.1)-40.0 micromol/L. Under the optimized conditions, the recoveries of the derivatives were in the range of 91.12%-105.73%. The intra-day relative standard deviations (RSDs) were in the range of 1.00%-11.63%, and the inter-day RSDs were in the range of 1.18%-18.58%. The sample showed stability under room temperature, freeze and three cycles of freeze-thaw conditions. This method is fast and accurate for the quantitative analysis of the derivatives of propranolol in transmembrane absorption such as cornea perfusion in vitro or transwell cell system.


Integration of Circadian and Metabolic Control of Reproductive Function.
Optimal fertility in humans and animals relies on the availability of sufficient metabolic fuels, information about which is communicated to the brain via levels of the hormones leptin and insulin. The circadian clock system is also critical; this input is especially evident in the precise timing of the female-specific surge of GnRH and LH secretion that triggers ovulation the next day. Chronodisruption and metabolic imbalance can both impair reproductive activity, and these two disruptions exacerbate each other, such that they often occur simultaneously. Kisspeptin neurons located in the anteroventral periventricular nucleus of the hypothalamus are able to integrate both circadian and metabolic afferent inputs and use this information to modulate the timing and magnitude of the preovulatory GnRH/LH surge. In an environment in which exposure to high caloric diets and chronodisruptors such as artificial night lighting, shift work, and transmeridian travel have become the norm, the implications of these factors for couples struggling to conceive deserve closer attention and more public education.


Nursing interventions for adult patients undergoing cancer cardiotoxic therapy: Scoping review.
To identify nursing interventions for the management of adult patients undergoing cardiotoxic oncologic therapy. This scoping review was performed in accordance with the JBI guidelines. The literature search took place between July and August 2022. Studies examining interventions for the management of adult cancer patients undergoing cardiotoxic therapy were included. The characteristics and results of the studies were synthesized and analyzed in a narrative way. In the nine included studies, it was verified that the interventions were implemented to guide the actions of the health team in general rather than specifically nursing staff. Nine nursing interventions related to the Classification of Nursing Interventions were included. The nursing interventions identified focused on rigorous cardiovascular surveillance, risk assessment, and actions to identify and mitigate cardiotoxicity. It is believed that the implementation of the identified nursing interventions will lead to evidence-based nursing practice and will contribute to the development of care products and processes that assess the cardiological risks and cardiotoxicity.


Characterization of Tetraploid Somatic Cell Nuclear Transfer-Derived Human Embryonic Stem Cells.
Polyploidy is occurred by the process of endomitosis or cell fusion and usually represent terminally differentiated stage. Their effects on the developmental process were mainly investigated in the amphibian and fishes, and only observed in some rodents as mammalian model. Recently, we have established tetraploidy somatic cell nuclear transfer-derived human embryonic stem cells (SCNT-hESCs) and examined whether it could be available as a research model for the polyploidy cells existed in the human tissues. Two tetraploid hESC lines were artificially acquired by reintroduction of remained 1st polar body during the establishment of SCNT-hESC using MII oocytes obtained from female donors and dermal fibroblasts (DFB) from a 35-year-old adult male. These tetraploid SCNT-hESC lines (CHA-NT1 and CHA-NT3) were identified by the cytogenetic genotyping (91, XXXY,-6, t[2:6] / 92,XXXY,-12,+20) and have shown of indefinite proliferation, but slow speed when compared to euploid SCNT-hESCs. Using the eight Short Tendem Repeat (STR) markers, it was confirmed that both CHA-NT1 and CHA-NT3 lines contain both nuclear and oocyte donor genotypes. These hESCs expressed pluripotency markers and their embryoid bodies (EB) also expressed markers of the three embryonic germ layers and formed teratoma after transplantation into immune deficient mice. This study showed that tetraploidy does not affect the activities of proliferation and differentiation in SCNT-hESC. Therefore, tetraploid hESC lines established after SCNT procedure could be differentiated into various types of cells and could be an useful model for the study of the polyploidy cells in the tissues.


Rising incidence of small renal masses: a need to reassess treatment effect.
The incidence of kidney cancer has been rising over the last two decades, especially in cases where the disease is localized. Although rates of renal surgery parallel this trend, mortality rates have continued to rise. To investigate the basis of this "treatment disconnect" (i.e., increased rates of treatment accompanied by increased mortality rates), we analyzed patient data from nine registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. We assembled a cohort of 34,503 kidney cancer patients and derived incidence, treatment, and mortality trends for kidney cancer, overall and as a function of tumor size. From 1983 to 2002, the overall age-adjusted incidence rate for kidney cancer rose from 7.1 to 10.8 cases per 100,000 US population; tumors < or = 4 cm in size accounted for most of the increase. Adjusted rates of renal surgery increased concurrently, most notably for tumors < or = 4 cm (0.9-3.6 surgeries per 100,000 US population). However, among kidney cancer patients, all-cause mortality per 100,000 US population increased from 1.5 deaths in 1983 to 6.5 deaths in 2002, with the greatest absolute increase noted for patients with lesions > 7 cm. Our results demonstrate that the rising incidence of kidney cancer is largely attributable to an increase in small renal masses that are presumably curable. The fact that increased detection and treatment of small tumors is not reducing mortality argues for a reassessment of the current treatment paradigm.


Surface Assay for Specific Detection of Soluble Amyloid Oligomers Utilizing Pronucleon Peptides Instead of Antibodies.
Immunoassays such as enzyme-linked immunosorbent assays (ELISAs) are widely used for diagnostics; however, antibodies as detection reagents may be insufficiently selective and have other shortcomings. We present a novel non-antibody-based detection method based on binding target molecules to peptides (used as recognition molecules): a surface assay for A-β oligomers employing a peptide comprising amino acid residues of the human β-amyloid protein (Pronucleon peptide) as the capture agent. For the sake of convenience, we term this the "Pronucleon peptide-linked immunosorbent assay", or PLISA. Pronucleon peptides are amino acid sequences matched to target amyloids of interest, in particular soluble Aβ-1-42 amyloid protein oligomers, which are widely considered as an early biomarker for Alzheimer's disease in body fluids. The Pronucleon peptide in a PLISA is immobilized on the surface and substitutes for the capture antibody used in an ELISA for binding the Aβ-1-42 oligomers present in the sample. We present data comparing synthetic oligomer PLISAs in spiked buffer and body fluids (such as cerebrospinal fluid, brain extracts, or whole blood) to those from an ELISA and demonstrate better selectivity of the PLISA for amyloid β-42 oligomers versus monomers and fibrils. The detection limit, calculated as the mean (blank) plus three standard deviations, was in the range of 0.35-1.5 pM (32-135 ng/L) (oligomers contained approximately 20 monomers on average).


Interaction of parenting experiences and brain structure in the prediction of depressive symptoms in adolescents.
Although some evidence suggests that neuroanatomic abnormalities may confer risk for major depressive disorder, findings are inconsistent. One potential explanation for this is the moderating role of environmental context, with individuals differing in their biological sensitivity to context. To examine the influence of adverse parenting as an environmental moderator of the association between brain structure and depressive symptoms. Cross-sectional measurement of brain structure, adverse parenting, and depressive symptoms in early adolescents. General community. A total of 106 students aged 11 to 13 years (55 males [51%]), recruited from primary schools in Melbourne, Australia, and their mothers. Selection was based on affective temperament, aimed at producing a sample representing a broad range of risk for major depressive disorder. No participant evidenced current or past case-level depressive, substance use, or eating disorder. (1) Volumetric measures of adolescents' amygdala, hippocampus, and anterior cingulate cortex (ACC); (2) frequency of observed maternal aggressive behavior during a mother-adolescent conflict-resolution interaction; and (3) adolescent depressive symptoms. Boys with smaller right amygdalas reported more depressive symptoms. However, neither hippocampal volume nor asymmetry measures of limbic or paralimbic ACC were directly related to level of depressive symptoms. Importantly, frequency of maternal aggressive behaviors moderated the associations between both the amygdala and ACC, and adolescent symptoms. Particularly, in conditions of low levels of maternal aggressiveness, boys with larger right amygdalas, girls with smaller bilateral amygdalas, and both boys and girls with smaller left paralimbic ACC reported fewer symptoms. These findings help elucidate the complex relationships between brain structure, environmental factors, and depressive symptoms. Further longitudinal research is required to examine how these factors contribute to the onset of case-level disorder, but given that family context risk factors are modifiable, our findings do suggest the potential utility of targeted early parenting interventions.


Simultaneous Detection of Methane, Ethane, and Propane by QEPAS Sensors for On-Site Hydrocarbon Characterization and Production Monitoring.
Natural gas is sampled and produced throughout the lifespan of a petroleum field. Gas composition and isotope data are critical inputs in the exploration and field development, such as gas show identification, petroleum system analysis, fluid characterization, and production monitoring. On-site gas analysis is usually conducted within a mud gas unit, which is operationally unavailable after drilling. Gas samples need to be taken from the field and shipped back to the laboratory for gas chromatography and isotope-ratio mass spectrometry analyses. Results are usually without sufficient resolution to fully characterize the heterogeneity and dynamics of fluids within the reservoir and the production system. In addition, it often takes a considerable time to obtain the results using the traditional method. A novel QEPAS (quartz-enhanced photoacoustic spectroscopy) sensor system was developed to move gas composition analyses to field for quasi-real-time characterization and monitoring. With respect to previously reported QEPAS prototypes for trace gas detection, the new system realized measuring concentrations of methane (C1), ethane (C2), and propane (C3) in gas phase within the percentage range that is typically encountered in natural gas samples from oil and gas fields. A gas mixing enclosure was used to dilute the natural gas-like mixtures in nitrogen gas (N2) to avoid the saturation of QEPAS signals. An iterative analysis based on multilinear regression of QEPAS spectra was developed to filter out the influence of gas matrix variation from multiple hydrocarbon components. The advance in simultaneous measuring hydrocarbon gases and expanded linearity range of QEPAS, with previously reported detection of H2S, CO2, and gas isotopes (12CO2/13CO2, 13CH4/12CH4), opens a way to use the advanced sensing technology for in situ and real-time gas detection and chemical analysis in the oil industry.


XK aprosencephaly.
We report a baby with aprosencephaly, preaxial limb defect and ambiguous genitalia. This combination of abnormalities have been reported previously and constitute the XK aprosencephaly syndrome.


Regeneration of condyle with a functional appliance.
Condylar regeneration with the use of functional appliances after condylectomy has been validated. However, the process during treatment remains unclear. In this study, we evaluated the condylar regeneration process and then examined mandibular growth and masticatory muscle activity after regeneration in growing rats. Seventy-five male Wistar rats aged 4 weeks were equally divided into 3 groups: unilateral condylectomy group, unilateral condylectomy + appliance group, or control group. The use of a functional appliance following condylectomy promoted mandibular growth and regeneration of the condyle 1 week after condylectomy. Condyle regeneration showing normal morphology was finally achieved 8 weeks after condylectomy. Asymmetrical masticatory muscle activity was observed after condylectomy. However, the use of a functional appliance produced symmetrical masticatory muscle activity. These results indicate a favorable regeneration process in the condylectomized area due to the use of a functional appliance. In addition, due to condylar regeneration, symmetrical masticatory muscle activity was achieved.


[Stress response mechanism in hematopoietic stem cells.]
At steady state, hematopoietic stem cells(HSCs), the most undifferentiated cells in the hematological system, are kept quiescent in the cell cycle. Upon hematological stresses, including radiation, anti-cancer medication, infection, and transplantation, bone marrow HSCs enter the cell cycle and robustly repopulate the entire hematopoietic system via multi-lineage differentiation and self-renewal, partly due to the alteration of their surrounding microenvironment or niche. Such hematological repopulation activity is termed "stress hematopoiesis," an activity essential for homeostatic maintenance of blood production. Understanding stress hematopoiesis is also critical to establish efficient methods enabling expansion in vitro of HSCs, since forced activation of the cell cycle by cytokine supplementation induces a stress-like cellular state.


Optimizing compliant, model-based robotic assistance to promote neurorehabilitation.
Based on evidence from recent experiments in motor learning and neurorehabilitation, we hypothesize that three desirable features for a controller for robot-aided movement training following stroke are high mechanical compliance, the ability to assist patients in completing desired movements, and the ability to provide only the minimum assistance necessary. This paper presents a novel controller that successfully exhibits these characteristics. The controller uses a standard model-based, adaptive control approach in order to learn the patient's abilities and assist in completing movements while remaining compliant. Assistance-as-needed is achieved by adding a novel force reducing term to the adaptive control law, which decays the force output from the robot when errors in task execution are small. Several tests are presented using the upper extremity robotic therapy device named Pneu-WREX to evaluate the performance of the adaptive, "assist-as-needed" controller with people who have suffered a stroke. The results of these experiments illustrate the "slacking" behavior of human motor control: given the opportunity, the human patient will reduce his or her output, letting the robotic device do the work for it. The experiments also demonstrate how including the "assist-as-needed" modification in the controller increases participation from the motor system.


Effects of glycine on motor performance in rats after traumatic spinal cord injury.
It has been reported that glycine improves some functions lost after spinal cord injury (SCI). In order to assess the effects of glycine administration on motor performance after SCI, we used fifteen male Wistar rats distributed into three groups: sham (n = 3), spinal-cord injury (n = 6,) and spinal cord injury + glycine (n = 6). Motor performance was assessed using the beam-walking paradigm and footprint analysis. Results showed that for all animals with spinal-cord injury, scores in the beam-walking increased, which is an indication of increased motor deficit. In addition, footprint analysis showed a decrease in stride length and an increase in stride angle, additional indicators of motor deficit. These effects trended towards recovery after 8 weeks of recording and trended toward improvement by glycine administration; the effect was not significant. These results suggest that glycine replacement alone is not sufficient to improve the motor deficits that occur after SCI.


Using Corticomuscular and Intermuscular Coherence to Assess Cortical Contribution to Ankle Plantar Flexor Activity During Gait.
The present study used coherence and directionality analyses to explore whether the motor cortex contributes to plantar flexor muscle activity during the stance phase and push-off phase during gait. Subjects walked on a treadmill, while EEG over the leg motorcortex area and EMG from the medial gastrocnemius and soleus muscles was recorded. Corticomuscular and intermuscular coherence were calculated from pair-wise recordings. Significant EEG-EMG and EMG-EMG coherence in the beta and gamma frequency bands was found throughout the stance phase with the largest coherence towards push-off. Analysis of directionality revealed that EEG activity preceded EMG activity throughout the stance phase until the time of push-off. These findings suggest that the motor cortex contributes to ankle plantar flexor muscle activity and forward propulsion during gait.


iNOS expression in CD4+ T cells limits Treg induction by repressing TGFβ1: combined iNOS inhibition and Treg depletion unmask endogenous antitumor immunity.
Expression of inducible nitric oxide synthase (iNOS) in different cellular compartments may have divergent effects on immune function. We used a syngeneic tumor model to functionally characterize the role of iNOS in regulation of CD4(+)FOXP3(+) regulatory T cells (Treg), and optimize the beneficial effects of iNOS inhibition on antitumor immunity. Wild-type (WT) or iNOS knockout mice bearing established MT-RET-1 melanoma were treated with the small-molecule iNOS inhibitor L-NIL and/or cyclophosphamide alone or in combination. The effect of iNOS inhibition or knockout on induction of Treg from mouse and human CD4(+) T cells in ex vivo culture was determined in parallel in the presence or absence of TGFβ1-depleting antibodies, and TGFβ1 levels were assessed by ELISA. Whereas intratumoral myeloid-derived suppressor cells (MDSC) were suppressed by iNOS inhibition or knockout, systemic and intratumoral FOXP3(+) Treg levels increased in tumor-bearing mice. iNOS inhibition or knockout similarly enhanced induction of Treg from activated cultured mouse splenocytes or purified human or mouse CD4(+) T cells in a TGFβ1-dependent manner. Although either iNOS inhibition or Treg depletion with low-dose cyclophosphamide alone had little effect on growth of established MT-RET1 melanoma, combination treatment potently inhibited MDSC and Treg, boosted tumor-infiltrating CD8(+) T-cell levels, and arrested tumor growth in an immune-dependent fashion. iNOS expression in CD4(+) T cells suppresses Treg induction by inhibiting TGFβ1 production. Our data suggest that iNOS expression has divergent effects on induction of myeloid and lymphoid-derived regulatory populations, and strongly support development of combinatorial treatment approaches that target these populations simultaneously.


Concordance--An alternative term to 'compliance' in the Aboriginal population.
'Compliance' is an important issue for the health of the Aboriginal people. The word implies that patients are not following the doctor's 'rules'. Concordance may be a better concept to describe both doctor and patient working together in 'harmony and agreement'. This article describes some of the parameters that affect consultations with Aboriginal patients and how they might be better addressed. The broader socio-political issues, the 'ethnocentrism' of the doctor, the health literacy of the patient, a more 'patient centred' model of the doctor-patient interaction, and the support of organisations are some of the variables that can be improved. It is important for general practitioners not to have a pessimistic attitude toward these issues, to identify ways in which the best possible results can be achieved, and to work hard to accomplish them.


Network Analysis of Anxiety in the Autism Realm.
The anxiety and autism realms are each complicated and heterogeneous, and relationships between the two areas are especially complex. Network analysis offers a promising approach to the phenotypic complexities of typical and atypical human behavior. The Revised Children's Anxiety and Depression Scale (RCADS) was used to assess anxiety in 126 high-functioning 9-13 year-olds with ASDs. Network graphs of Autism Diagnostic Observation Schedule items and RCADS anxiety total score, social, generalized, panic and separation anxiety subscores consistently found the anxiety node (score) to be highly peripheral. Also, the networks of RCADS anxiety items themselves were similar for the ASDs group and a general population comparison group (n = 2017). The results suggest anxiety is not a central part of autism and that anxiety is dynamically similar (aspects of anxiety relate to one another in a similar manner) in high-functioning autism and the general population.


On-treatment HBV DNA dynamics predict virological breakthrough in entecavir-treated HBeAg-positive chronic hepatitis B.
Virological breakthrough (VBT) could be a manifestation of chronic hepatitis B (CHB) in patients treated with long-term nucleot(s)ide analogues. We aimed to determine the association of on-treatment serum hepatitis B virus (HBV) DNA with VBT in HBeAg-positive CHB patients receiving entecavir (ETV) treatment. A retrospective cohort study, including 162 consecutive patients (95 men and 67 women; mean age, 43.1±13.4 years) with HBeAg-positive CHB treated with ETV for at least 48 weeks between August 2008 and May 2015, was conducted. Univariate and multivariate cox regression analysis were used to identify associations with VBT and clinical factors, including HBV DNA and HBeAg serum status. Among the 162 ETV-treated HBeAg-positive CHB patients, eighteen patients (11.1%) experienced VBT (VBT group), whereas the other 144 patients were without VBT (non-VBT group). The cumulative rate of HBV DNA < 100 IU/mL in the VBT group and the non-VBT group at week 48 were 44.44% and 70.14%, and at week 96 were 58.33% and 92.56%, respectively (p = 0.015). The cumulative rate of HBeAg seroclearance in the VBT group and non-VBT group at week 48 and week 96 were statistically significant (p = 0.014). Multivariate analysis disclosed that failure to achieve HBeAg seroclearance were the factors significantly associated with VBT. Our results demonstrated that on-treatment HBV DNA could probably predict VBT in ETV-treated HBeAg-positive chronic hepatitis B patients. Failure to achieve HBeAg seroclearance was associated with VBT in ETV-treated HBeAg-positive CHB patients. HBV DNA >100IU/mL at 48 weeks is potentially a predictor for VBT.


Social adaptation after cardiothoracic transplantation: a review of the literature.
From the earliest days of transplantation, research has contributed to our knowledge of the psychosocial sequelae associated with the outcomes of the procedure. The purpose of this review is to describe the social adaptation literature for heart, lung, and heart-lung recipients. Social adaptation refers to employment and performance of social roles and responsibilities. Employment research focused on vocational rehabilitation, physical health restoration, and return to work. Social roles and responsibilities research focused on social roles, family relationships, social support, and psychosocial adjustment. Predictors, interventions, and their associations with outcomes are discussed.


Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer.
The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are lacking in normal colorectal crypt epithelium and are aberrantly expressed in a subset of colorectal cancer. The aim of the present study was to evaluate the expression of CK7 and CD117 in morphologically normal transitional mucosa adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was performed in the mucosa adjacent to five groups of surgically resected colorectal tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small-sized invasive adenocarcinoma (≤2 cm) and large-sized invasive adenocarcinoma (>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal tumors, and the positivity ratio increased according to tumor grade from low-grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive adenocarcinoma (25.0%) was significantly lower compared with that of the next lower grade. CD117 was also expressed in the mucosa adjacent to a subset of colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased according to tumor grade from low-grade adenoma all the way through to the large-sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer may be different, and analysis of their individual expression may provide novel insights into the development and progression of colorectal cancer.


Immunoglobulin structure: partial amino acid sequence of a Bence Jones protein.
Sequence analysis and ordering of the soluble tryptic peptides of one Bence Jones protein and comparison with partial sequence data for another have revealed many structural differences in the half of the molecule with the terminal amino group, but only one structural difference in the half of the molecule having the terminal carboxyl group. Somatic chromosomal rearrangements may effect such changes and account for variability in antibody structure.


Trends in conservative procedures and peripartum hysterectomy rates in severe postpartum haemorrhage.
The objective of this study is to explore whether increase in use of second-line conservative surgical procedures will alter the rate of peripartum hysterectomies in management of severe postpartum haemorrhage (PPH). This is a retrospective cohort. All pregnant patients with gestation > = 28 weeks with severe PPH (> = 1.5 L) within 72 h of delivery from year 2000 to 2015 (16-year period) in an obstetric training unit was recruited. Basic patient anthropometric characteristics and the main causes for PPH were calculated. The incidence of any second-line conservative surgical procedures and peripartum hysterectomies were evaluated. The total number of patients in each category was then stratified into four 4 years-intervals (4 quadrennium) to compare trends. The incidence of severe PPH gradually increased over the study period (lowest 0.21% in 2002 to 0.76% in 2015) (p < .001). There is an obvious increasing trend in the overall use of second-line surgical procedures from nil to 82% (p < .001), with balloon tamponade constituting up to 48%. The incidence of successful second-line procedures increased gradually from 72.2% in the second quadrennium to 89% in the fourth quadrennium. The total peripartum hysterectomy rate among cases of severe PPH could be seen to drop from 40.2% in the first to 10.9% in the fourth quadrennium (p = .04). Despite the increasing trends in PPH, the increasing utilisation of second-line conservative surgical procedures in severe PPH should be able to reduce the need for peripartum hysterectomy.


Dysphagia in Parkinson's disease.
Although dysphagia is an important symptom associated with prognosis in patients with Parkinson's disease (PD), dysphagia tends to be overlooked until swallowing difficulties reach an advanced phase. We assessed dysphagia with videofluoroscopic examination of swallowing in 31 patients with mainly mild or moderate PD. Swallowing problems were observed in the pharyngeal phase in 28 patients, oral phase in 19 patients, esophageal phase in 15 patients, and oral preparatory phase in 1 patient. Therefore, dysphagia in the pharyngeal phase was observed in almost all patients with mild or moderate PD. In contrast, no dysfunction was detected in most patients when screening was conducted via questionnaire or other methods. Assessment of clinical parameters in the present study suggests that latent swallowing dysfunction may be present even in the early disease stage in PD. A future prospective study to follow swallowing functions in a pre-symptomatic phase in PD would be fruitful to find whether swallowing dysfunction is one of the prodromal symptoms.


Prediabetes and older age increase the risk of post-transplantation diabetes mellitus: Qatar experience.
Post-transplantation diabetes mellitus (PTDM) is a major complication in kidney transplant recipients leading to reduced allograft and patient survival. Given the high prevalence of diabetes in Qatar, which is twice the global average, we were interested in determining the incidence of PTDM, identifying risk factors, and comparing clinical outcomes in kidney transplant recipients with and without diabetes. We retrospectively followed up 191 adult kidney allograft recipients transplanted between January 1, 2012, and December 31, 2016, for a median of 41 months. A total of 76 patients (40%) had pre-existing diabetes. A total of 39 patients developed PTDM during follow-up; they represent 34% of patients who did not have diabetes prior to transplantation. Two thirds of PTDM occurred within 3-6 months post-transplantation. Prediabetes before transplant [OR = 6.07 (1.24-29.74), P = .026] older recipient's age at the time of transplantation [OR = 1.10 (1.00-1.20), P = .039] and average fasting blood sugar during 3-6 months post-transplant [OR = 1.06 (1.01-1.11), P = .010] were independently associated with PTDM. Patient and kidney allograft survival rates exceeded 97% in all groups. The incidence of PTDM in kidney transplant recipients living in Qatar is high. Older age and prediabetes are independent risk factors for developing PTDM.


Development of cell-penetrating peptide-based drug leads to inhibit MDMX:p53 and MDM2:p53 interactions.
The transcription factor p53 has a tumor suppressor role in leading damaged cells to apoptosis. Its activity is regulated/inhibited in healthy cells by the proteins MDM2 and MDMX. Overexpression of MDM2 and/or MDMX in cancer cells inactivates p53, facilitating tumor development. A 12-mer dual inhibitor peptide (pDI) was previously reported to be able to target and inhibit MDMX:p53 and MDM2:p53 interactions with nanomolar potency in vitro. With the aim of improving its cellular inhibitory activity, we produced a series of constrained pDI analogs featuring lactam staples that stabilize the bioactive helical conformation and fused them with a cell-penetrating peptide to increase cytosol delivery. We compared pDI and its analogs on their inhibitory potency, toxicity, and ability to enter cancer cells. Overall, the results show that these analogs keep their nanomolar affinity for MDM2 and MDMX and are highly active against cancer cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 853-863, 2016.


American Society for Enhanced Recovery (ASER) and Perioperative Quality Initiative (POQI) joint consensus statement on prevention of postoperative infection within an enhanced recovery pathway for elective colorectal surgery.
Colorectal surgery (CRS) patients are an at-risk population who are particularly vulnerable to postoperative infectious complications. Infectious complications range from minor infections including simple cystitis and superficial wound infections to life-threatening situations such as lobar pneumonia or anastomotic leak with fecal peritonitis. Within an enhanced recovery pathway (ERP), there are multiple approaches that can be used to reduce the risk of postoperative infections. With input from a multidisciplinary, international group of experts and through a focused (non-systematic) review of the literature, and use of a modified Delphi method, we achieved consensus surrounding the topic of prevention of postoperative infection in the perioperative period for CRS patients. As a part of the first Perioperative Quality Initiative (POQI-1) workgroup meeting, we sought to develop a consensus statement describing a comprehensive, yet practical, approach for reducing postoperative infections, specifically for CRS within an ERP. Surgical site infection (SSI) is the most common postoperative infection. To reduce SSI, we recommend routine use of a combined isosmotic mechanical bowel preparation with oral antibiotics before elective CRS and that infection prevention strategies (also called bundles) be routinely implemented as part of colorectal ERPs. We recommend against routine use of abdominal drains. We also give consensus guidelines for reducing pneumonia, urinary tract infection, and central line-associated bloodstream infection (CLABSI).


Responsiveness and clinically important differences for the WOMAC and SF-36 after hip joint replacement.
To study responsiveness and establish the minimal clinically important differences (MCID) and minimal detectable change (MDC) in patients undergoing total hip replacement (THR) using the Short Form 36 (SF-36) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We conducted a prospective observational study in three public hospitals of all consecutive patients with a diagnosis of hip osteoarthritis (OA) on waiting lists to undergo THR. Patients completed the SF-36 and the WOMAC (subscales transformed to 0 to 100), which measured the health-related quality of life (HRQoL), before intervention and 6 months and 2 years later, and additional transitional questions, which measured the changes in the joint 6 months postoperatively. Improvements at 6 months after a THR were between 37 (stiffness) and 39 points (pain), depending on the WOMAC domain. The SF-36 domains also showed improvements: physical function (31.91), physical role (33.71), and bodily pain (29.77). From 6 months to 2 years, improvements ranged from 2 to 5 points, except for role physical (13.25). A ceiling effect was detected on some WOMAC domains as well as a floor effect on the SF-36. The MCID ranged from 25.91 (stiffness) to 29.26 (pain) on the WOMAC and from 10.78 (physical role) to 20.40 (physical function) on the SF-36. The MDC ranged from 21.38 (pain) to 27.98 (stiffness) on the WOMAC and from 18.99 (physical function) to 42.05 (social function) on the SF-36. These values indicate expected gains after THR. However, the MCID and MDC values must be viewed cautiously due to the uncertainty of these estimators and should not be considered as absolute thresholds.


[DNA amplification on chemically structured chips in forensic STR analysis].
The present study deals with low-volume amplification of short tandem repeats (STRs) for forensic DNA analysis. A chemically structured chip in microscopic slide format was used to amplify standard forensic casework samples in a 1-microL reaction volume primarily with the well-known and widely used PowerPlex kit and with other commercially available STR kits. Tests regarding sensitivity, mixture analysis, robustness, reproducibility, buffer composition and technical performance were carried out to check the usefulness of this amplification strategy. The results obtained show that low-volume amplification is a promising option in the forensic DNA typing toolbox. Restrictions to this method, which are strictly related to the kit and the respective buffer used, were found in low copy number (LCN) DNA typing, mixture analysis and technical performance. Problematic typing results included artefact alleles, increase in locus and heterozygote imbalance, allelic and locus dropout as well as increase of stutters, especially when amplifying less than 200-300 pg of DNA. In contrast, convincing advantages are a higher sensitivity, better amplification efficiency and the low cost factor of this method.


P53 and cancer-associated sialylated glycans are surrogate markers of cancerization of the bladder associated with Schistosoma haematobium infection.
Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers. Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%), cell-surface cancer-associated glycan sialyl-Tn (sTn) and sialyl-Lewisa/x (sLea/sLex), involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLex that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLea. However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLea was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLea and sLex. Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium. This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLea and sLex antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests.


Linking microscopy and high content screening in large-scale biomedical research.
Microscopy has been a cornerstone of discovery in the academic life sciences for more than 100 yr. This comes from a unique ability to provide extremely rich information of biological structure and dynamics. The advent of digital imaging and machine vision has brought within itself the ability to collect images more easily and critically, the ability to measure objects and intensities within images. Although many continue to use microscopy in a qualitative manner, the analytical capabilities afforded by machine vision are increasingly being applied to basic cell biology and biomedical research. Scalable quantitative imaging technology might enable scientists and engineers to determine structure, dynamics, and function of entire biological systems rather than individual molecules or pathways. This chapter will provide an overview of early efforts in the academic community to apply high content screening to the study of biological systems.


Prognostic value of blood glucose in Hodgkin's disease.
Subjects with Hodgkin's disease and an initial blood glucose greater than 115 mg/dL had an impressively shorter survival than those with a glucose below that level. The same is true if the groups are formed from those having glucose above or below 100. The correlation between glucose and survival persisted after allowing for the survival effects of histology, stage, symptom class, and age.


Causal mediation analyses with rank preserving models.
We present a linear rank preserving model (RPM) approach for analyzing mediation of a randomized baseline intervention's effect on a univariate follow-up outcome. Unlike standard mediation analyses, our approach does not assume that the mediating factor is also randomly assigned to individuals in addition to the randomized baseline intervention (i.e., sequential ignorability), but does make several structural interaction assumptions that currently are untestable. The G-estimation procedure for the proposed RPM represents an extension of the work on direct effects of randomized intervention effects for survival outcomes by Robins and Greenland (1994, Journal of the American Statistical Association 89, 737-749) and on intervention non-adherence by Ten Have et al. (2004, Journal of the American Statistical Association 99, 8-16). Simulations show good estimation and confidence interval performance by the proposed RPM approach under unmeasured confounding relative to the standard mediation approach, but poor performance under departures from the structural interaction assumptions. The trade-off between these assumptions is evaluated in the context of two suicide/depression intervention studies.


Thickness of the palatal masticatory mucosa with reference to autogenous grafting: a cadaveric and histologic study.
The aims of this study were to measure the thickness of the palatal masticatory mucosa and determine its histologic characteristics with reference to autogenous grafting. Thirty-two fully dentate, cadaver hemimaxillae were examined (from 13 men and 3 women; mean age, 57.1 years). The thickness of the palatal masticatory mucosa was assessed at 24 standard measurement points on the sectioned specimens after decalcification, and then the specimens were processed for embedding in paraffin, sectioned, and stained with hematoxylin and eosin. The thickness of the palatal masticatory mucosa varied by tooth site as follows: 3.55 ± 1.09 mm (mean ± SD; distal canine), 3.51 ± 0.99 mm (distal first premolar), 3.28 ± 1.07 mm (distal second premolar), 2.83 ± 1.00 mm (midline first molar), 2.92 ± 1.03 mm (distal first molar), and 3.15 ± 1.66 mm (distal second molar). The thickness also varied according to distance from the cementoenamel junction (CEJ): 2.35 ± 0.79 mm at 3 mm below the CEJ, 2.65 ± 0.77 mm at 6 mm, 3.52 ± 0.94 mm at 9 mm, and 4.29 ± 1.14 mm at 12 mm. Histologic analysis showed that the thickness of the lamina propria decreased toward the posterior palatal area and midpalatal suture, while that of the submucosa increased. These results suggest that the most appropriate donor site for gingival autogenous grafting is the region 3 to 9 mm below the CEJ between the distal surface of the canine and the midline surface of the first molar.


Reactive oxygen species mediated bacterial biofilm inhibition via zinc oxide nanoparticles and their statistical determination.
The formation of bacterial biofilm is a major challenge in clinical applications. The main aim of this study is to describe the synthesis, characterization and biocidal potential of zinc oxide nanoparticles (NPs) against bacterial strain Pseudomonas aeruginosa. These nanoparticles were synthesized via soft chemical solution process in a very short time and their structural properties have been investigated in detail by using X-ray diffraction and transmission electron microscopy measurements. In this work, the potential of synthesized ZnO-NPs (∼ 10-15 nm) has been assessed in-vitro inhibition of bacteria and the formation of their biofilms was observed using the tissue culture plate assays. The crystal violet staining on biofilm formation and its optical density revealed the effect on biofilm inhibition. The NPs at a concentration of 100 µg/mL significantly inhibited the growth of bacteria and biofilm formation. The biofilm inhibition by ZnO-NPs was also confirmed via bio-transmission electron microscopy (Bio-TEM). The Bio-TEM analysis of ZnO-NPs treated bacteria confirmed the deformation and damage of cells. The bacterial growth in presence of NPs concluded the bactericidal ability of NPs in a concentration dependent manner. It has been speculated that the antibacterial activity of NPs as a surface coating material, could be a feasible approach for controlling the pathogens. Additionally, the obtained bacterial solution data is also in agreement with the results from statistical analytical methods.


Spontaneous coronary artery dissection in a healthy postmenopausal woman.
Spontaneous coronary artery dissection (SCAD) is rare and when it occurs is most commonly seen in young females following childbirth. We report a case of a 55-year-old female who was found dead at her home. She had no history of cardiovascular disease. She smoked approximately 10 cigarettes per day. She complained of mild chest discomfort the night before her death, lasting for 10 minutes, for which no medical attention was sought. She had been seen and appeared well 15 minutes before death. At autopsy, the only abnormality was in the left anterior descending coronary artery, which showed a two cm segment with periluminal blood in the wall of the vessel compressing the lumen. Histologically, a dissection was seen between the media and the external elastic lamina of the affected artery. There was a mixed inflammatory infiltrate including eosinophils and very occasional giant cells. Alcian blue staining was negative. The appearances were those of a localised dissection. The remaining coronary arteries were free of atheroma. SCAD should be suspected in young females in their postpartum period presenting with chest pain since emergency treatment can greatly increase survival.


Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1.
A novel mouse macrophage galactose-type C-type lectin 2 (mMGL2) was identified by BLAST analysis of expressed sequence tags. The sequence of mMGL2 is highly homologous to the mMGL, which should now be called mMGL1. The open reading frame of mMGL2 contains a sequence corresponding to a type II transmembrane protein with 332 amino acids having a single extracellular C-type lectin domain. The 3'-untranslated region included long terminal repeats of mouse early transposon. The Mgl2 gene was cloned from a 129/SvJ mouse genomic library and sequenced. The gene spans 7,136 base pairs and consists of 10 exons, which is similar to the genomic organization of mMGL1. The reverse transcriptase-PCR analysis indicates that mMGL2 is expressed in cell lines and normal mouse tissues in a macrophage-restricted manner, also very similar to that of mMGL1. The mMGL2 mRNA was also detected in mMGL1-positive cells, which were sorted from thioglycollate-induced peritoneal cells with a mMGL1-specific monoclonal antibody, LOM-8.7. The soluble recombinant proteins of mMGL2 exhibited carbohydrate specificity for alpha- and beta-GalNAc-conjugated soluble polyacrylamides, whereas mMGL1 preferentially bound Lewis X-conjugated soluble polyacrylamides in solid phase assays. These two lectins may function cooperatively as recognition and endocytic molecules on macrophages and related cells.


[Trials using drugs in diseases of the silkworm (Bombyx mori L.)].
Studied was the pharmacokinetic of chloramphenicol, tylosine, ampicillin, and penicillin in silkworm moths. The antibiotics were applied only once in the form of water solutions in concentrations of 0.062 to 1 per cent for chloramphenicol, 50 to 1500 IU/cm3 for tylosine, 0.03 to 0.5 per cent for ampicillin, and 300 to 2500 IU/cm3 for benzilpenicillin at the rate of 25 cm3/cm2 of a mulberry tree leaf. It was found that chloramphenicol in conc. 0.25 to 0.5 per cent was absorbed in the alimentary canal of the silkworm and was found in the haemolymph in bacteriostatic levels up to the 96th hour following treatment. Tylosine was also absorbed, and in concentrations of 500 to 1500 IU/cm3 was shown to maintain bacteriostatic levels in the haemolymph of the moths for a period of 24-32 hours. Ampicillin and penicillin were absorbed to a slight extent, and were eliminated from the haemolymph up to the eighth hour. It is suggested to use chloramphenicol and tylosine in the concentrations referred to for the control of the spontaneous nuclear polyhedria and flasheria in silkworm moths.


Selenistasis: epistatic effects of selenium on cardiovascular phenotype.
Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease.


Relationship of fertility to ovarian follicular waves before breeding in dairy cows.
Cows with two waves of follicular growth during the estrous cycle yield follicles that are older and larger at ovulation compared with cows having three waves. The objectives of the current research were 1) to compare fertility in cows with two or three follicular waves and 2) to examine associations between luteal function, follicular development, and fertility after breeding. Follicular waves were monitored by ultrasonography during the estrous cycle before insemination in 106 dairy cows. Fewer cows had three follicular waves before next estrus and ovulation than two waves (P < 0.01; 30% vs 68%, respectively), but pregnancy rate was higher (P = 0.058; 81 vs 63%, respectively). Cows with two waves had shorter estrous cycles (P < 0.01), with the ovulatory follicle being both larger (P < 0.05) and older (P < 0.01). In cows with three waves, luteal function was extended (P < 0.05) and the peak in plasma progesterone occurred later (P < 0.05) in the estrous cycle compared to two wave cows. Considering cows that became pregnant, luteal phase length was shorter (P < 0.05) during the estrous cycle preceding insemination than for nonpregnant cows. In conclusion, fertility was greater in lactating cows inseminated after ovulation of the third-wave follicle that had developed for fewer days of the estrous cycle as compared with two-wave cows.


A6V polymorphism of the human μ-opioid receptor decreases signalling of morphine and endogenous opioids in vitro.
Polymorphisms of the μ opioid receptor (MOPr) may contribute to the variation in responses to opioid drugs in clinical and unregulated situations. The A6V variant of MOPr (MOPr-A6V) is present in up to 20% of individuals in some populations, and may be associated with heightened susceptibility to drug abuse. There are no functional studies examining the acute signalling of MOPr-A6V in vitro, so we investigated potential functional differences between MOPr and MOPr-A6V at several signalling pathways using structurally distinct opioid ligands. CHO and AtT-20 cells stably expressing MOPr and MOPr-A6V were used. AC inhibition and ERK1/2 phosphorylation were assayed in CHO cells; K channel activation was assayed in AtT-20 cells. Buprenorphine did not inhibit AC or stimulate ERK1/2 phosphorylation in CHO cells expressing MOPr-A6V, but buprenorphine activation of K channels in AtT-20 cells was preserved. [D-Ala2, N-MePhe4, Gly-ol]-enkephalin, morphine and β-endorphin inhibition of AC was significantly reduced via MOPr-A6V, as was signalling of all opioids to ERK1/2. However, there was little effect of the A6V variant on K channel activation. Signalling to AC and ERK via the mutant MOPr-A6V was decreased for many opioids, including the clinically significant drugs morphine, buprenorphine and fentanyl, as well endogenous opioids. The MOPr-A6V variant is common and this compromised signalling may affect individual responses to opioid therapy, while the possible disruption of the endogenous opioid system may contribute to susceptibility to substance abuse.


Asymmetric catalysis of the transannular Diels-Alder reaction.
Transannular chemical reactions are unparalleled in their ability to generate high degrees of stereochemical and architectural complexity in a single transformation. However, the successful application of this approach in synthesis depends on the ability to predict and control the outcome of the transannular reaction. Use of a chiral catalyst in this context represents an attractive, yet unused, strategy. This report describes a catalytic, asymmetric transannnular Diels-Alder (TADA) reaction that affords polycyclic products in high enantiomeric excess. This catalyst system can also alter the inherent diastereoselectivity of cyclizations with substrates containing chiral centers. Additionally, the catalytic enantioselective TADA has been used as the key step in a total synthesis of the sesquiterpene 11,12-diacetoxydrimane; this route may provide a general approach to the polycyclic carbon framework shared by many terpene natural products.


Septicaemia secondary to Vibrio vulnificus cellulitis.
Vibrio vulnificus is a naturally occurring, salt-water bacteria found in estuarine and coastal waters worldwide. It prefers low salinity and warm water temperatures for optimum growth. Infection from Vibrio vulnificus is uncommon, although it has been reported from many locations (e.g. southern United States of America, Israel, Republic of Korea, Japan, Taiwan, Spain, Turkey). It can be serious and life threatening, causing septicaemia and wound infections. This paper reports a case of septicaemia secondary to Vibrio vulnificus cellulitis in an elderly woman. The infection was acquired after wading in a coastal lagoon with a pre-existing superficial leg wound.


The weekly measurement deviations of indoor radon concentration from the annual arithmetic mean.
The difference between weekly measurements and the annual arithmetic mean of radon indoor concentration CRn,Indoor was studied in the Czech Republic. The deviations were analysed for 1537 weekly measurements which were consecutively obtained in 29 rooms over a period of 1 year and the annual arithmetic mean was calculated for each particular room. The relationship of the deviations to three meteorological parameters (i.e. outside temperature, atmospheric pressure, and weekly rainfall) and to the sequential number of a calendar week was studied. The effect of atmospheric pressure and weekly rainfall was not significant. The deviation between a weekly measurement and the annual arithmetic mean depended significantly on outside weekly average temperatures. If the average outside weekly temperature was below 10 degrees C, the radon concentration was systematically higher than that of the annual arithmetic mean. The deviation variability was lower up to a temperature of 10 degrees C. If the weekly average outdoor temperature was higher than 10 degrees C, the uncertainty of a weekly measurement of radon concentration was also higher.


Oroxylin A inhibited autoimmune hepatitis-induced liver injury and shifted Treg/Th17 balance to Treg differentiation.
Autoimmune hepatitis (AIH) is a kind of autoimmune disease mediated by T cells, and its incidence is gradually increasing in the world. Oroxylin A (OA) is one of the major bioactive flavonoids that has been reported to inhibit inflammatory. Here, an AIH model of mouse was induced by Concanavalin A (Con A). It found that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were decreased in mice with the treatment of OA. Hematoxylin-eosin staining showed that the liver injury was attenuated by OA, and TUNEL staining indicated that the cells apoptosis of liver was weakened in mice with OA treatment. ELISA analysis of cytokines and chemokines suggested that OA reduced the expression of IL-6, IL-17A, chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 1 (CXCL1) and CXCL10, but promoted the expression of IL-10 and TGF-β in mice. The mRNA levels of Il-17a in liver and spleen tissues were also significantly decreased, on the contrary, the mRNA levels of Il-10 in liver and spleen tissues were increased. The proportion of Treg/Th17 detected by flow cytometry revealed that OA promoted the differentiation of Treg and inhibited the differentiation of Th17 both in the liver and spleen. The results of this study demonstrated the inhibitory effects of OA on AIH-induced liver injury and the inflammatory response of AIH, and revealed that OA affected the balance of Treg/Th17 and shifted the balance toward Treg differentiation. It provided new potential drugs for the prevention of AIH.


Fungal Hyphosphere Microbiomes Are Distinct from Surrounding Substrates and Show Consistent Association Patterns.
Mat-forming fungi are common in forest and grassland soils across the world, where their activity contributes to important soil ecological processes. These fungi maintain dominance through aggressive and abundant hyphae that modify their internal physical and chemical environments and through these modifications select for what appears to be a suite of mycophilic bacteria. Here, the bacteria associated with the fungal mats of Leucopaxillus gentianeus and Leucopaxillus albissimus from western North America are compared to adjacent nonmat substrates. Within the mats, the bacterial richness and diversity were significantly reduced, and the community composition was significantly different. The bacterial community structure between the two fungal hosts was marginally significant and indicated a shared set of bacterial associates. The genera Burkholderia, Streptomyces, Bacillus, Paenibacillus, and Mycobacterium were significantly abundant within the fungal mats and represent core members of these hypha-rich environments. Comparison with the literature from fungal mat studies worldwide showed that these genera are common and often significantly found within fungal mats, further reinforcing the concept of a mycophilic bacterial guild. These genera are incorporated into a synthesis discussion in the context of our current understanding of the nature of fungal-bacterial interactions and the potential outcomes of these interactions in soil nutrient cycling, plant productivity, and human health. IMPORTANCE Fungi and bacteria are the most abundant and diverse organisms in soils (perhaps more so than any other habitat on earth), and together these microorganisms contribute to broad soil ecosystem processes. There is a suite of bacteria that appears consistently within the physical space called the hyphosphere, the area of influence surrounding fungal hyphae. How these bacteria are selected for, how they are maintained, and what broader ecological functions they perform are subjects of interest in this relatively new field-the cross-kingdom interactions between fungi and bacteria. Understanding their cooccurrence and their interactions can open new realms of understanding in soil ecological processes with global consequences.


New ocular therapeutics: a view from the patenting perspective.
This feature article provides an overview of the newest therapeutic developments for ocular diseases, based on patents and patent applications that were published in the 12-month period from November 2005 to October 2006. In contrast to peer-reviewed literature covering breakthroughs in basic science research, the patenting perspective discloses the intentions of the pharmaceutical industry for imminent drug development. Selected documents describing drug delivery, dry eye syndrome, ocular infections and lesions, glaucoma and age-related macular degeneration are discussed. The role of RNA interference, which is of particular interest in ophthalmology research, is also highlighted.


Studying human respiratory disease in animals--role of induced and naturally occurring models.
Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance.


Antimelanogenic Effect of Urolithin A and Urolithin B, the Colonic Metabolites of Ellagic Acid, in B16 Melanoma Cells.
Antimelanogenic agents from natural sources have been widely investigated. Urolithin A (UA) and B (UB), the main gut microflora metabolites of dietary ellagic acid derivatives, have various bioactivities such as anti-inflammatory and antiaging effects. In this study, the metabolites were found to possess depigmentation efficacy by suppressing tyrosinase activity. Both UA and UB could attenuate melanogenesis in B16 melanoma cells to 55.1 ± 3.8 and 76.4 ± 17.4% of control at noncytotoxic dosage, 10 μM, respectively. UA showed comparable efficacy to positive control, 5 μM of kojic acid treatment (51.2 ± 7.8). RT-PCR results revealed that UA and UB inhibited melanin formation by affecting the catalytic activity of tyrosinase rather than its mRNA expression. Kinetics for UA and UB on tyrosinase activity revealed that their inhibition behavior toward cellular tyrosinase involved competitive inhibition. UA and UB may be potent tyrosinase inhibitors and they possess significant antimelanogenesis ability as novel skin-whitening ingredients.


An explosive course of squamous cell penile cancer in an AIDS patient.
We report the case of a 37-year-old man in whom penile cancer was discovered while he was treated for AIDS 4 years after a human papillomavirus (HSV) infection. Despite initially localised disease with T1 N0 staging, he died of metastasis within 3 years. A brief review of the literature regarding HPV-related cancer in HIV-infected patients is presented and therapeutic options are discussed.


Presentation of Leishmania donovani promastigotes occurs via a brefeldin A-sensitive pathway.
For the presentation of Leishmania promastigotes to polyclonal CD4+ T cells, a processing period within activated macrophages of 3-4 h is required. Presentation can be inhibited by both chloroquine and brefeldin A (BFA), the latter implicating a requirement for newly synthesized MHC class II molecules. This inhibition is both reversible and specific, in that BFA did not inhibit mixed lymphocyte reaction stimulation by these infected macrophages. Immunogold labeling demonstrated that class II was associated with the parasite-containing phagolysosome. The level of class II was not significantly altered in BFA-treated cells in the time period studied, suggesting that antigen may exist the phagolysosome and interact with class II in another cellular compartment.


The IL-20 subfamily of cytokines--from host defence to tissue homeostasis.
The interleukin-20 (IL-20) subfamily of cytokines comprises IL-19, IL-20, IL-22, IL-24 and IL-26. These cytokines are all members of the larger IL-10 family, but have been grouped together to form the IL-20 subfamily based on their usage of common receptor subunits and similarities in their target-cell profiles and biological functions. Members of the IL-20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. In this Review, we describe the cellular sources and targets of the IL-20 subfamily cytokines, and we detail how their expression is regulated. Much of our understanding of the unique biology of this group of cytokines is still based on IL-22, which is the most studied member of the IL-20 subfamily. Nevertheless, we attempt a broader discussion of the emerging functions of IL-20 subfamily cytokines in host defence, inflammatory diseases, cancer and metabolism.


[Determination of patulin in fruits and jam by solid phase extraction-ultra performance liquid chromatography].
With magnesium silicate, silica gel, diatomite and calcium sulfate as raw materials, a new solid phase extraction column was prepared through a series of processes of grinding to ethanol homogenate, drying and packing into polypropylene tube. The sample was hydrolyzed by pectinase, extracted by acetonitrile and purified by solid phase extraction. The target compounds were separated on a C18 column (100 mm×2.1 mm, 1.8 μm), using 0.8% (v/v) tetrahydrofuran solution as mobile phase with a flow rate of 0.5 mL/min. The detection wavelength was 276 nm. The effect of pectinase on extraction yield and purification effect of solid-phase extraction column were investigated. The optimum chromatographic conditions were selected. There was a good linear relationship between the peak heights and the mass concentrations of patulin in the range of 0.1 to 10 mg/L with the correlation coefficient (R2) of 1. The limit of detection for this method was 10.22 μg/kg. The spiked recoveries of samples were 86.58%-94.84% with the relative standard deviations (RSDs) of 1.45%-2.28%. The results indicated that the self-made solid phase extraction column had a good purification efficiency, and the UPLC had a high separation efficiency. The method is simple, accurate and of great significance for the quality and safety control of fruit products.


Clinicopathological features of primary thyroid leiomyosarcoma without Epstein-Barr virus infection: A case report.
Primary thyroid leiomyosarcoma (LMS) is a rare tumor type with an unusual location, the diagnosis is based entirely on histological and immunohistochemical evaluations. In the present study, a rare case of a 74-year-old female patient who exhibited a right anterior neck mass for 12 months, which rapidly enlarged for the last 3 months. Ultrasound of the thyroid revealed a 55×42 mm hypoechoic mass with clear margins in the right lobe. Histological examination of the tumor demonstrated malignant spindle cells in interlacing fascicles and whorls. Additionally, nuclear pleomorphism, tumor giant cells, necrosis and abnormal mitotic figures were observed. The immunohistochemistry indicated that the tumor cells were strongly positive for smooth muscle actin, desmin, p53 and vimentin expression, but negative for cytokeratin, epithelial membrane antigen, thyroid transcription factor-1, paired box-8, 34βE12, cytokeratin 5/6, cluster of differentiation (CD)117, myoglobin, S100, p16. The final histopathological diagnosis was primary thyroid LMS.


Unemployed and poor in New York: the impact of mentalization and Axis II psychopathology on job outcome.
This study examined the relationships between the capacity for reflective functioning (RF) and the presence of Axis II psychopathology and their respective and combined impact on the ability of unemployed, low-income individuals to complete work-readiness training and to obtain and retain employment. Forty-one adult clients selected randomly from individuals participating in The HOPE Program, a work-readiness program in Brooklyn, New York, participated in the current study. Results indicated that RF and Axis II pathology were not only found to be related to each other, but were also found to significantly predict job outcomes. Moreover, it was determined that while the presence of an Axis II diagnosis impeded participants' ability to obtain jobs, the impact of such a diagnosis on job acquisition was attributable to having lower levels of RF ability. These results are discussed in relation to implications for the design of programs and interventions to assist unemployed and underserved populations.


Human T cell leukemia virus type I (HTLV-I) and human diseases.
HTLV-I infection is causally associated with a variety of human diseases including leukemia/lymphoma, myelopathy, uveitis, and arthropathy. Tax protein of HTLV-I, which is considered oncogenic, binds to transcription factors or other cytoplasmic cellular molecules involved in the fundamental cell function and thereby induces cellular changes. The interaction between HTLV-I-infected cells with dysregulated function and different kinds of cells in the host, such as lymphocytes and vascular endothelial cells through viral peptides, antigen receptors cell adhesion molecules, and cytokines, appears to be one of the basic mechanisms underlying the development of HTLV-I-associated diseases. This interaction may play a major role in determining tumorigenicity and in forming clinical features of the diseases. The in vivo cell proliferation model of HTLV-I-infected cells using severe combined immunodeficient (SCID) mice can differentiate tumorigenicity from cell immortalization in vitro. The OX40 and its ligand gp34, which are induced by HTLV-I infection and directly mediate the adhesion between HTLV-I-infected T cells and vascular endothelial cells, may be critically involved in the localization and proliferation of HTLV-I-infected cells in vivo.


MR fistulography with percutaneous instillation of aqueous jelly: A cost effective technique innovation.
Perianal fistula is a commonly encountered condition in routine surgical practice. Accurate presurgical mapping of these tracts is vital to prevent recurrence. We have assessed the effectiveness of percutaneous instillation of aqueous jelly prior to magnetic resonance (MR) fistulography. To study the role of percutaneous instillation of aqueous jelly in fistulous tracts prior to MR fistulography. All patients with active discharge, referred for MR fistulography between January 2014 and April 2016, were included in this study. Approximately 3-5 ml of sterile aqueous jelly was percutaneously instilled into the external openings prior to MR fistulography. Post MR fistulography, patients were monitored till surgery for pain, fever, or bleeding. The type of fistulae, location of internal openings, lateral ramifications, and presence of abscess were compared with per operative findings for diagnostic accuracy. Sixty-four patients enrolled in our study had undergone preoperative MR fistulography with aqueous jelly instillation. MR fistulography revealed a total of 77 tracts and showed a sensitivity and specificity of 100% in delineation of type of tract. Forty-nine internal openings were identified with 94.2% sensitivity, 100% specificity, and 95.3% accuracy. 90.5% sensitivity, 100% specificity, and accuracy of 97% were observed in delineation of lateral ramifications. None of the patients reported pain, fever, or bleeding post procedure till surgery. Percutaneous instillation of aqueous jelly prior to MR fistulography is a safe, cost effective, and accurate technique to provide a comprehensive delineation of the complex anatomy of perianal fistulae.


Bronchoscopic interventions for severe emphysema: Where are we now?
Patients with severe emphysema have limited treatment options and only derive a small benefit from optimal medical treatment. The only other therapy to have significant clinical beneficial effect in emphysema is LVRS but the perceived risk and invasiveness of surgery has fuelled bronchoscopic approaches to induce lung volume reduction. There are multiple bronchoscopic methods for achieving volume reduction in severe emphysema: EBV, airway bypass procedure, endobronchial coils, thermal (vapour) sclerosis and chemical sclerosis (sealants). Optimal patient selection is key to successful patient outcomes. This review discusses bronchoscopic approaches for emphysema treatment which has progressed through clinical trials to clinical practice.


[Economic aspects of ambulatory and inpatient treatment of HIV positive patients].
Highly active antiretroviral therapy (HAART) was introduced in the midst of the 1990s. The sustained declin of morbidity and mortality by HAART has been proven to be cost effective despite high expenditures for regular administration of cost intensive antiretroviral drugs. Yearly direct treatment costs are estimated as high as [symbol: see text] 20,000 to [symbol: see text] 30,000 per case in Germany. Approximately two third of all direct costs are caused by the use of antiretrovirals. Despite rising use of HAART and increasing drug prices, general costs for treatment decreased in the last years. This is explained by declining costs for hospitalisation and by increasing use of less expensive drug combinations. In addition deferment of initiation of HAART to slightly more advanced stages of immunodeficiency is recommended in recent treatment guidelines and leads to further reduction of direct costs. Modified treatment concepts with presumed cost saving effects, like periods of antiretroviral treatment interruption, are currently under investigation.


Aspartame: effects on learning, behavior, and mood.
The effect of aspartame on the learning, behavior, and mood of children was evaluated in two experiments. After an overnight fast and a standard breakfast, 20 healthy 9- to 10-year-old children were given the treatments in a double-blind crossover design at 10:30 AM. Lunch was served at 12:00 noon. In experiment 1, the treatment consisted of an ice slurry of strawberry Kool-Aid containing 1.75 g/kg of carbohydrate (polycose) plus either aspartame (34 mg/kg) or the equivalent sweetness as sodium cyclamate and amino acids as alanine. In experiment 2, the treatment consisted of a drink of cold unsweetened strawberry Kool-Aid, containing either 1.75 g/kg of sucrose or 9.7 mg/kg of aspartame. Measures of associative learning, arithmetic calculation, activity level, social interaction, and mood were unaffected by treatment in experiment 1. In experiment 2, the only significant treatment effect was that on the frequency of minor and gross motor behaviors, which were less frequent after the consumption of sucrose than after aspartame. Thus, the effect of aspartame on the short-term behavior of healthy 9- to 10-year-old children appears to be related to its absence of metabolic consequences rather than to its amino acid composition and putative neurochemical impact.


Orange juice-induced hyperkalemia in schizophrenia.
Some fruit juices have very high potassium content. However, only several cases of juice-induced hyperkalemia have been reported that involved non-psychiatric, diabetic outpatients with renal compromise. We present a highly unusual case of a 66-year-old non-diabetic, schizophrenic woman with psychogenic polydipsia and normal renal function who developed hyperkalemia secondary to excessive orange juice consumption while an inpatient. In addition to demonstrating this previously undescribed medical comorbidity of schizophrenia, this case highlights the need for careful attention when communicating with both nursing and patients when managing psychogenic polydipsia.


GPS & GLONASS mass-market receivers: positioning performances and peculiarities.
Over the last twenty years, positioning with low cost Global Navigation Satellite System (GNSS) sensors have rapidly developed around the world at both a commercial and academic research level. For many years these instruments have only acquired the GPS constellation but are now able to track the Global'naja Navigacionnaja Sputnikovaja Sistema (GLONASS) constellation. This characteristic is very interesting, especially if used in hard-urban environments or in hard conditions where satellite visibility is low. The goal of this research is to investigate the contribution of the GLONASS constellation for mass-market receivers in order to analyse the performance in real time (Network Real Time Kinematic-NRTK positioning) with post-processing approaches. Under these conditions, it is possible to confirm that mass-market sensors could be a valid alternative to a more expensive receiver for a large number of surveying applications, but with low cost hardware the contribution of the GLONASS constellation for fixing ambiguities is useless, if not dangerous.


Fibrin functionalization with synthetic adhesive ligands interacting with α6β1 integrin receptor enhance neurite outgrowth of embryonic stem cell-derived neural stem/progenitors.
To enhance fibrin hydrogel affinity towards pluripotent stem cell-derived neural stem/progenitor cells (NSPCs) and its capacity to support NSPC migration and neurite extension, we explored the tethering of synthetic peptides engaging integrin α6β1, a cell receptor enriched in NSPCs. Six α6β1 integrin ligands were tested for their ability to support integrin α6β1-mediated adhesion of embryonic stem cell-derived NSPCs (ES-NSPs) and sustain ES-NSPC viability, migration, and neuronal differentiation. Due to their better performance, peptides T1, HYD1, and A5G81 were immobilized into fibrin and functionalized gels characterized in terms of peptide binding efficiency, structure and viscoelastic properties. Tethering of T1 or HYD1 successfully enhanced cell outgrowth from ES-NSPC neurospheres (up to 2.4-fold increase), which exhibited a biphasic response to peptide concentration. Inhibition assays evidenced the involvement of α6β1 and α3β1 integrins in mediating radial outgrowth on T1-/HYD1-functionalized gels. Fibrin functionalization also promoted neurite extension of single ES-NSPCs in fibrin, without affecting cell proliferation and neuronal differentiation. Finally, HYD1-functionalized gels were found to provide a permissive environment for axonal regeneration, leading up to a 2.0-fold increase in neurite extension from rat dorsal root ganglia explants as compared to unmodified fibrin, and to significant improved locomotor function after spinal cord injury (complete transection), along with a trend toward a higher area positive for growth associated protein 43 (marker for axonal growth cone formation). Our results suggest that conjugation of α6β1 integrin-binding motifs is of interest to increase the biofunctionality of hydrogels used in 3D platforms for ES-NSPC culture and potentially, in matrix-assisted ES-NSPC transplantation. Impact statement: The transplantation of NSPCs derived from pluripotent stem cells holds much promise for the treatment of central nervous system disorders. Moreover, the combinatorial use of biodegradable hydrogels with NSPCs was shown to contribute to the establishment of a more permissive environment for survival and integration of transplanted cells. In this study, fibrin hydrogels functionalized with a synthetic peptide engaging integrin α6β1 (HYD1) were shown to promote neurite extension of ES-NSPCs, which is fundamental for the formation of functional neuronal relay circuits after NSPC transplantation. Notably, HYD1-functionalized fibrin per se led to enhanced axonal growth ex vivo and to an improvement in locomotor function after implantation in a rat model of spinal cord injury. Conjugation of α6β1 integrin-binding motifs may therefore be of interest to confer bioactivity to NSPC hydrogel vehicles.


Altered error-related brain activity in youth with major depression.
Depression is associated with impairments in cognitive control including action monitoring processes, which involve the detection and processing of erroneous responses in order to adjust behavior. Although numerous studies have reported altered error-related brain activity in depressed adults, relatively little is known about age-related changes in error-related brain activity in depressed youth. This study focuses on the error-related negativity (ERN), a negative deflection in the event-related potential (ERP) that is maximal approximately 50ms following errors. High-density ERPs were examined following responses on a flanker task in 24 youth diagnosed with MDD and 14 low-risk healthy controls (HC). Results indicate that compared to HC, MDD youth had significantly smaller ERN amplitudes and did not exhibit the normative increases in ERN amplitudes as a function of age. Also, ERN amplitudes were similar in depressed youth with and without comorbid anxiety. These results suggest that depressed youth exhibit different age-related changes in brain activity associated with action monitoring processes. Findings are discussed in terms of existing work on the neural correlates of action monitoring and depression and the need for longitudinal research studies investigating the development of neural systems underlying action monitoring in youth diagnosed with and at risk for depression.


Deep Anterior Lamellar Keratoplasty with Large Descemet's Membrane Perforation: Should We Stop Conversion to Penetrating Keratoplasty?
To evaluate the outcome of eyes with large Descemet's membrane (DM) perforation during deep anterior lamellar keratoplasty (DALK). A retrospective, interventional case series of 12 eyes with completed DALK, despite DM perforation larger than 4 mm in its widest dimension. The main outcome measures included graft clarity, endothelial cell density (ECD), corrected distance visual acuity (CDVA), and DM detachment. The mean age of patients was 26.8 ± 11.4 years. Preoperative pathology included keratoconus (n = 10), macular dystrophy (n = 1), and postmicrobial keratitis corneal scar (n = 1). The average size of DM perforation was 6.5 mm ± 1.3 mm. At the end of the follow-up period (median 15 months, range 6-53 months), the mean CDVA was 0.32 ± 0.09 logMAR and the mean ECD was 1830.8 ± 299.7 cells/mm2. Nine patients (75%) developed DM detachments postoperatively and was managed by intracameral air injection once in six eyes, and twice in three eyes. Other complications included persistent localized stromal edema at the site of DM defect in one eye and Urrets Zavalia syndrome in one eye. Completing DALK in eyes with large DM perforation provides good visual acuity, endothelial cell count and may be superior to penetrating keratoplasty regarding long-term graft survival if confirmed in future comparative studies.


Behavioural Problems in Children with 46XY Disorders of Sex Development.
The aim of this study is to determine the behavioural problems of children with 46XY disorders of sex development (DSD) with genital ambiguity and to identify the risk factors that may influence behaviour. The 27 participants (aged 6-18 years) consisted of 21 patients raised as boys and 6 patients raised as girls. Control data were obtained from a representative sibling of each patient who was matched for age and gender. The study tool used was the Child Behaviour Checklist (CBCL), which is a parent-administered questionnaire. The analysis of the behavioural scores revealed that the patient group had poorer scores in the total, externalizing, and internalizing realms. This group also had poorer scores in the anxious-depressed, social, and rule-breaking realms as compared to the control group. In addition, the XY-F group had higher scores (more pathological) than the XY-M group, although the difference in the scores was not statistically significant. A comparison of the prevalence of patients with scores in the clinical range with that of the control group was not statistically significant. These findings support the current recommendations that psychological counselling should be an integral part of the professional support offered to patients with DSD.