Posttraumatic Stress Disorder Upon Admission to Shelters Among Female Victims of Domestic Violence: An Ecological Model of Trauma.
The study used the ecological model of trauma and recovery (Harvey, 1996) to examine the rates of probable posttraumatic stress disorder (PTSD) among female victims of domestic violence. Five hundred and five participants completed questionnaires upon entering shelters in Israel. Analysis showed that 61% of the participants reported probable PTSD. Childhood exposure to violence, violence severity, and feeling helpless were all associated with high PTSD levels. By contrast, Ethiopian ethnicity, social support, and a stronger sense of control were associated with lower PTSD levels. However, the interaction between social support and violence duration showed that social support did not moderate PTSD when exposure to violence endured. The study emphasizes that resources deteriorate, and that policy-augmenting prevention programs would increase treatment potential to strengthen survivors' coping capacities.


Periconceptional Folate Supplementation in Women after Bariatric Surgery-A Narrative Review.
The prevalence of obesity is increasing globally, and along with it, there is a growing number of patients opting to undergo bariatric surgery to treat this condition. Whilst it has many advantages, bariatric surgery is known to induce micronutrient deficiency, with possible deleterious effects on overall health. This topic becomes even more relevant during pregnancy, where deficiencies can also affect the developing fetus, possibly being the cause of an increase in congenital anomalies. Most notably amongst these micronutrients is folate, or vitamin B9, which plays an essential role in development, gene expression and genomic stability. As insufficient levels of folate are associated with neural tube defects in the fetus, preventing and treating folate deficiencies during pregnancies after bariatric surgery is a relevant issue. Unfortunately, folate supplementation recommendations for bariatric patients who wish to become pregnant are not clear. In this narrative review, we discuss whether the recommendations for the general population are still valid for bariatric patients. Furthermore, we discuss the role of folate in the human body, folate status in both non-bariatric and bariatric patients, the various types of folate that are available for substitution and the risk associated with over-supplementation.


Immunotoxicity of monoclonal antibodies.
Monoclonal antibodies (mAbs) are large molecules intended to bind to specific targets often expressed on the immune system, and to treat various immunopathological conditions. Therefore, mAbs can be considered to have a high potential for immunotoxicity, which is reflected in the clinical experience accumulated on mAbs-induced adverse effects related to immunosuppression, immunostimulation and hypersensitivity (immunogenicity). So far, non clinical immunotoxicity studies have been inadequate to address all safety issues in relation to the possible immunotoxicity of mAbs, because they are fraught with limitations and pitfalls primarily related to the lack of relevant animal species. In addition, clinical studies rarely include validated end-points dedicated to the prediction of immunotoxicity. With the ongoing development of mAbs as novel therapeutic strategies for a wide variety of diseases, efforts should be paid to improve our understanding of mAbs-induced immunotoxic effects and design dedicated strategies to assess their immunological safety, both non clinically and clinically.


Genomic profiling identifies novel mutations and SNPs in ABCD1 gene: a molecular, biochemical and clinical analysis of X-ALD cases in India.
X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and adrenal cortex secondary to mutations in the ABCD1 gene that encode the peroxisomal membrane protein. We conducted a genomic and protein expression study of susceptibility gene with its clinical and biochemical analysis. To the best of our knowledge this is the first preliminary comprehensive study in Indian population that identified novel mutations and SNPs in a relatively large group. We screened 17 Indian indigenous X-linked adrenoleukodystrophy cases and 70 controls for mutations and SNPs in the exonic regions (including flanking regions) of ABCD1 gene by direct sequencing with ABI automated sequencer along with Western blot analysis of its endogenous protein, ALDP, levels in peripheral blood mononuclear cells. Single germ line mutation was identified in each index case in ABCD1 gene. We detected 4 novel mutations (2 missense and 2 deletion/insertion) and 3 novel single nucleotide polymorphisms. We observed a variable protein expression in different patients. These findings were further extended to biochemical and clinical observations as it occurs with great clinical expression variability. This is the first major study in this population that presents a different molecular genetic spectrum as compared to Caucasian population due to geographical distributions of ethnicity of patients. It enhances our knowledge of the causative mutations of X-ALD that grants holistic base to develop effective medicine against X-ALD.


Pediatric and adolescent injury in wilderness and extreme environments.
The participation of children and adolescents in wilderness and extreme environment sports is increasing. Engaging in these activities is not without risk of injury, illness, or death. To date, there is limited research investigating pediatric and adolescent injuries in wilderness and extreme environments. With the intent of creating awareness within the sports medicine field, this review begins by examining the growth in popularity of outdoor sports in wilderness and extreme environments and the injury impact they are registering. The review then examines reported pediatric and adolescent injuries in multiple wilderness and extreme environments. Close examination is paid to youth adventuring on global expeditions and entering high altitude environments. Future studies acquiring denominator data to help establish injury rates while keeping pace with the rapidly diversifying outdoor and extreme wilderness sport trends are necessary.


An analysis of the cellular localization of cytochrome oxidase in the lateral geniculate nucleus of the adult cat.
The distribution of cytochrome oxidase (C.O.) was examined in the normal adult cat lateral geniculate nucleus at the cellular and electron-microscopic levels. The darker reactivity of the X- and/or Y-receptive laminae (A, A1, magnocellular lamina C [Cm], and medial interlaminar nucleus [MIN]) compared with the lightly reactive W-receptive parvicellular lamina C (Cp) indicates that there are pathway-specific histochemical differences in the visual system of the cat. At the cellular level, darkly reactive large cells in the lateral geniculate nucleus (LGN) closely resemble class 1, Y-cells, in relative size and distribution, thus indicating that C.O. histochemistry may be used as a functional marker for these cells. Perigeniculate neurons are also darkly reactive. Neuronal classes 2, 4, and 3 (presumed X-cells, W-cells, and/or interneurons) have moderate to lightly reactive perikarya. The darkly reactive neuronal classes tend to receive relatively stronger proximal excitatory synaptic input than do the less reactive neuronal classes. Since all neuronal classes appeared to have darkly (or moderately) reactive dendrites, C.O. reactivity must differ between dendrite and soma of some neuronal classes. At the electron-microscopic level, distinct components of the neuropil tend to have specific levels of C.O. reactivity. The predominance of darkly reactive mitochondria in dendrites indicates that dendrites are metabolically very active. RLD and may F's, but few large axon terminals with round vesicles (RL) or small axon terminals with round vesicles (RS) profiles are darkly reactive, implying that specific classes of presynaptic structures are more active than others. Thus C.O. histochemistry may be useful for distinguishing not only functionally active neuronal classes such as Y-cells and perigeniculate (PG) neurons from less active neuronal classes, but also functionally more or less active parts of the same neuron including its dendrites, axons, and/or axon terminals.


[A double suicide gene system driven by KDR promoter selectively kills human colon adneocarcinoma SW480 cells].
To study the selective killing effect of adenovirus (Ad)-mediated double suicide gene system driven by the KDR promoter (KDR-CDglyTK) on human colon adneocarcinoma SW480 cells. KDR-expressing SW480 cells and LS174T cells that did not express KDR were infected by KDR-CDglyTK, and the infection efficiency and the expression of CDglyTK in the cells were detected by RT-PCR. The infected cells were treated with the prodrugs 5-FC and GCV at different concentrations, and the cell-killing effects and bystander effects were evaluated by MTT method. DNA content and the cell cycle changes in SW480 cells were detected by flow cytometry. The expression of green fluorescent protein (GFP) was observed in 95% of the infected SW480 and LS174T cells with a multiplicity of infection (MOI) of 100. RT- PCR demonstrated that the product of CD/TK gene existed in SW480 cells infected by Ad- KDR- CD/TK, but not in infected LS174 cells. The infected SW480 cells exhibited high sensitivity to the prodrugs, but the infected LS174T cells did not (P<0.01). Bystander effects of the double suicide gene system were observed in the coculture of the infected and non-infected SW480 cells. At the MOI of 100, treatment of the infected cells with the prodrugs resulted in increased cell percentage in G(0)-G(1) phase and decreased percentage in S phase and the prodrug-treated cells showed an apoptotic peak in flow cytometry. CDglyTK fusion gene system driven by the KDR promoter selectively kills and induces the apoptosis of the KDR-CDglyTK SW480 cells.


Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria.
This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria (PKU). The meta-analysis of PKU is challenging because high-quality evidence is lacking due to the limited number of affected individuals and few placebo-controlled, double-blind studies of adults with high and low blood Phe. Neuropsychiatric symptoms associated with PKU exceed general population estimates for inattention, hyperactivity, depression, and anxiety. High Phe is associated with an increased prevalence of neuropsychiatric symptoms and executive functioning deficits whereas low Phe is associated with improved neurological performance. Findings support lifelong maintenance of low blood Phe.


The type IV phosphodiesterase inhibitor rolipram induces expression of the cell cycle inhibitors p21(Cip1) and p27(Kip1), resulting in growth inhibition, increased differentiation, and subsequent apoptosis of malignant A-172 glioma cells.
Upregulation of the cAMP/protein kinase A (PKA) pathway has been shown to result in decreased proliferation, increased differentiation, and subsequent apoptosis of malignant glioma cells. Conventional cAMP analogs, however, are difficult to use in a clinical setting. Therefore, we investigated the effects of rolipram, a drug that has undergone clinical trials as an antidepressant and has also been proposed as a treatment for multiple sclerosis. Rolipram acts as a specific inhibitor of type IV phosphodiesterase (PDE4), leading to increased intracellular levels of cAMP. We report that the inhibition of PDE4 by rolipram results in the activation of the cAMP/PKA pathway, with potent stimulation of a reporter gene containing a cAMP-responsive element in its promoter region. Further, treatment of the human glioma cell line A-172 with rolipram results in increased expression of the cell cycle inhibitors p21(Cip1) and p27(KiP1), and decreased activity of cdk2, a cyclin-dependent kinase essential for cell cycle progression. As a result, the proliferation of A-172 cells is inhibited, with induction of a Gl block. Eventually, rolipram-treated A-172 cells undergo differentiation, which is followed by apoptotic cell death. As we observe this effect with other glioma cell cultures as well, our results suggest that rolipram could prove useful as a novel differentiating agent with both cytostatic and cytotoxic potential in the treatment of malignant gliomas.


Baseline neurocognitive profiles differentiate abstainers and non-abstainers in a cocaine clinical trial.
Previous studies have shown that cocaine users have higher levels of impulsivity and impaired decision making; however, few have examined these factors as predictors of treatment success. We obtained baseline neurocognitive measures from 75 cocaine-dependent individuals participating in a 12-week clinical trial targeting impulsivity with behavioral therapies and pharmacotherapy. Participants treated with citalopram had higher cocaine abstinence rates compared to placebo-treated participants. The aim of this secondary analysis study was to determine whether profiles of performance on neurocognitive measures administered at baseline discriminated among patients who achieved abstinence and those who did not. Participants completed the Immediate and Delayed Memory Task, Barratt Impulsiveness Scale-11, and Iowa Gambling Task. Profile analysis results showed different patterns of performance on these baseline measures as a function of outcome. Compared with non-abstinent participants, abstinent participants had higher scores on the Barratt Impulsiveness Scale-11 Non-Planning subscale and better performance on the Iowa Gambling Task. Profile differences for the two outcome groups did not vary as a function of treatment condition. Results suggest that cocaine-dependent patients entering treatment with higher impulsivity and less impaired decision-making abilities may respond favorably to targeted behavioral interventions. Neurocognitive profiles may be useful in understanding population heterogeneity and predicting differential outcomes in subgroups of cocaine abusers.


Innovative active packaging systems to prolong the shelf life of Mozzarella cheese.
In this work the effectiveness of different antimicrobial packaging systems on the microbial quality decay kinetics during storage of Mozzarella cheese was evaluated. Lemon extract, at 3 different concentrations, was used as active agent, in combination with brine and with a gel solution made of sodium alginate. Shelf life tests were run at 15 degrees C to simulate thermal abuse. The cell load of spoilage and dairy functional microorganisms were monitored at regular time intervals during storage. By fitting the experimental data through a modified version of the Gompertz equation, the shelf life of dairy products packaged in the different systems was calculated. Results show an increase in the shelf life of all active packaged Mozzarella cheeses, confirming that the investigated substance may exert an inhibitory effect on the microorganisms responsible for spoilage phenomena without affecting the functional microbiota of the product.


Overexpression of EC-SOD suppresses endothelial-cell-mediated LDL oxidation.
Reactive oxygen species have been proposed to play important roles in atherosclerosis. To investigate the protective role of extracellular superoxide dismutase (EC-SOD), its inhibition of endothelial-cell-mediated LDL oxidation was examined. We constructed the recombinant adenovirus AxCAEC-SOD expressing human EC-SOD by CAG promoter. Infection of endothelial cells with AxCAEC-SOD resulted in EC-SOD protein secretion in a dose-dependent manner and a decrease of endothelial-cell-derived superoxide production. Moreover, it was proven to coexist with heparan sulfate by immunohistochemical staining. Endothelial-cell-mediated LDL oxidation enhanced by ferric-sodium EDTA was inhibited by 47% in TBARS formation by AxCAEC-SOD infection. In agarose gel electrophoresis, AxCAEC-SOD decreased the negative charge of oxidized LDL by 50% and suppressed fragmentation of apolipoprotein B. These results suggested that human EC-SOD localized in the extracellular space and reduced endothelial-cell-mediated LDL oxidation. In subendothelial space, EC-SOD bound on heparan sulfate might suppress LDL oxidation through reduction of superoxide anion.


Effects of intravenous anesthesia with sevoflurane combined with propofol on intraoperative hemodynamics, postoperative stress disorder and cognitive function in elderly patients undergoing laparoscopic surgery.
To analyze the effects of intravenous anesthesia with sevoflurane combined with propofol on intraoperative hemodynamics, postoperative stress disorder and cognitive function in elderly patients undergoing laparoscopic surgery. Eighty elderly patients undergoing laparoscopic surgery in Xianning Central Hospital from September 2014 to February 2018. Enrolled patients were divided into observation group (n=40) and control group (n=40) according to the random regionalization method. Patients in the control group were given intravenous anesthesia with propofol, while those in the observation group were provided with a combined use of sevoflurane based on the method in the control group. The general surgical data, intraoperative hemodynamics, postoperative stress disorder and cognitive function were compared between the two groups. There were no blood transfusions and no complications during operation in the two groups, and the operation completed successfully. There was no significant difference in the time of unconsciousness, intubation time, and duration of pneumoperitoneum establishment (p>0.05). However, the spontaneous breathing time, eye opening time upon calling and extubation time in observation group were shorter than those in control group (p<0.05). The heart rate (HR) in the two groups at intubation and at exploration was significantly higher than that at the time of entering the room (p<0.05), which was lower in observation group than that in control group (p<0.05). While there was no significant difference in the index at the other time points compared with that before entering the room and control group (p>0.05). The systolic blood pressure (SBP) had different degrees of change before intubation, after 0 minutes, three minutes and six minutes of intubation, after 0 minutes and five minutes of pneumoperitoneum establishment and at exploration when compared with that before entering the room (p<0.05). But the SBP at intubation and at exploration was significantly lower in observation group than that in control group (p<0.05). MAP was only decreased significantly at intubation compared with that before entering the room (p<0.05). At exploration, there was no significant fluctuation in the MAP level in observation group (p>0.05), but the MAP was increased significantly in control group (p<0.05). In addition, the postoperative stress disorder in observation group was milder than that in control group (p<0.05), and the postoperative cognitive function was better than that in control group (p<0.05). Intravenous anesthesia with sevoflurane combined with propofol has little effects on intraoperative hemodynamics and postoperative cognitive function in elderly patients undergoing laparoscopic surgery. Besides, it can obtain better recovery quality and have milder postoperative stress disorder than single use of propofol.


The multidimensional nature of perceived barriers: global versus practical barriers to HPV vaccination.
Perceived barriers are one of the strongest determinants of health behavior. The current study presents a novel conceptualization of perceived barriers by testing the following hypotheses: (a) perceived barriers are multidimensional and thus should cluster into distinct factors; (b) practical barriers should be salient for individuals intending to engage in a particular health behavior, whereas global barriers should be salient for individuals not intending to enact the behavior; and (c) whereas global barriers should be negatively associated with behavioral intentions, practical barriers should be positively related to intentions. The context for this investigation was young adult women's perceived barriers to human papillomavirus (HPV) vaccination. Two months after viewing an educational video about HPV vaccination, women (aged 18-26) who had not received any doses of the HPV vaccine (n = 703) reported their perceived barriers to HPV vaccination and intentions to receive the vaccine. Relative to the conventional single-factor approach, a five-factor model provided a better fit to the data and accounted for a larger proportion of variance in vaccination intentions. The relative salience of different perceived barriers varied as a function of women's intentions. Participants who were not intending to get vaccinated cited global concerns about vaccine safety and low perceived need for the vaccine. In contrast, participants intending to get vaccinated cited practical concerns (cost, logistical barriers) related to carrying out their intentions. Moreover, whereas global perceived barriers were associated with lower intentions, practical barriers were associated with higher intentions. Perceived barriers are multidimensional and vary systematically as a function of people's behavioral intentions.


Sites and Functional Consequence of Alkylphenol Anesthetic Binding to Kv1.2 Channels.
Inhalational general anesthetics, such as sevoflurane and isoflurane, modulate a subset of brain Kv1 potassium channels. However, the Kv1.2 channel is resistant to propofol, a commonly used intravenous alkylphenol anesthetic. We hypothesize that propofol binds to a presumed pocket involving the channel's S4-S5 linker, but functional transduction is poor and, therefore, propofol efficacy is low. To test this hypothesis, we used a photoactive propofol analog (meta-aziPropofol = AziPm) to directly probe binding and electrophysiological and mutational analyses in Xenopus oocytes to probe function. We find that AziPm photolabels L321 in the S4-S5 linker of both the wild-type Kv1.2 and a mutant Kv1.2 (G329 T) with a novel gating phenotype. Furthermore, whereas propofol does not significantly modulate Kv1.2 WT but robustly potentiates Kv1.2 G329T, AziPm inhibits Kv1.2 WT and also potentiates Kv1.2 G329T. Kv1.2 modulation by AziPm was abolished by two mutations that decreased hydrophobicity at L321 (L321A and L321F), confirming the specific significance of the S4-S5 linker in the mechanism of general anesthetic modulation. Since AziPm binds to Kv1.2 G329T and shares the propofol ability to potentiate this mutant, the parent propofol likely also binds to the Kv1.2 channel. However, binding and alkylphenol-induced transduction are seemingly sensitive to the conformation of the S4-S5 linker site (altered by G329T) and subtle differences in the chemical structures of propofol and AziPm. Overall, the results are consistent with a mechanism of general anesthetic modulation that depends on the complementarity of necessary ligand binding and permissive ion channel conformations that dictate modulation and efficacy.


Histopathological features of malignant craniopharyngioma: Case report and literature review.
Malignant transformation in craniopharyngiomas is a very uncommon event and scarcely mentioned in the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS). So far, there are only 34 reported cases. We report an additional case in a 63-year-old woman who was diagnosed with craniopharyngioma 47 years ago. We reviewed the literature in order to define the histological features of malignant craniopharyngioma and its overlap with odontogenic tumors. Our case presented morphology of mixed odontogenic ghost cell/ameloblastic carcinoma. Analyzing all reported cases, 18 of them presented malignization as squamous cell carcinoma (SCC), 1 as odontogenic ghost cell carcinoma, 2 as ameloblastic carcinoma, and 10 cases were mentioned just as malignant craniopharyngiomas. We concluded that SCC represented only half of the malignant cases, while the morphology of ~ 11% of them was comparable with ameloblastic or odontogenic ghost cell carcinomas and 28% lacked a specific histological diagnosis. Most cases were fatal, which makes it necessary to include the entity of malignant craniopharyngioma in the WHO Classification of Tumors of the CNS as a high-grade tumor defining its histological variability.


The evolution of otolaryngic allergy practices.
We review the evolution of the allergy diagnosis and treatment techniques endorsed by the American Academy of Otolaryngic Allergy. These endorsements were made only after careful consideration of supporting data accumulated during their evolution.


Synthesis of Bare Iron Nanoparticles from Ferrocene Hexane Solution by Femtosecond Laser Pulses.
Iron-based nanoparticles (FeNPs) have unique and attractive properties such as superparamagnetism, biocompatibility, and catalytic activity. Although the synthesis of precious metal NPs from a metal in liquid and/or metal salt solution by a pulsed laser has been investigated, comparably little effort has been devoted to examine the production of FeNPs. Here we report the synthesis of carbon-shell free spherical NPs of iron oxide (magnetite) from ferrocene hexane solution by femtosecond near infrared laser pulses. Nanosecond UV laser pulses are used to compare the evolution of the particle size distribution as a function of laser irradiation time. The size of NPs remains constant even for extended exposure to femtosecond laser pulses, whereas it grows with exposure to nanosecond laser pulses. The primary particles are generated by photochemical reactions regardless of pulse duration; however, the fragmentation of NPs by successive femtosecond laser pulses regulates the particle size.


New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation.
Aseries of novel 1,4-disubstituted 1,2,3-triazoles were synthesized from an (R)-carvone terminal alkyne derivative via a Cu (I)-catalyzed azide-alkyne cycloaddition reaction using CuSO4,5H2O as the copper (II) source and sodium ascorbate as a reducing agent which reduces Cu (II) into Cu (I). All the newly synthesized 1,2,3-triazoles 9a-h were fully identified on the basis of their HRMS and NMR spectral data and then evaluated for their cell growth inhibition potential by MTS assay against HT-1080 fibrosarcoma, A-549 lung carcinoma, and two breast adenocarcinoma (MCF-7 and MDA-MB-231) cell lines. Compound 9d showed notable cytotoxic effects against the HT-1080 and MCF-7 cells with IC50 values of 25.77 and 27.89 µM, respectively, while compound 9c displayed significant activity against MCF-7 cells with an IC50 value of 25.03 µM. Density functional calculations at the B3LYP/6-31G* level of theory were used to confirm the high reactivity of the terminal alkyne as a dipolarophile. Quantum calculations were also used to investigate the mechanism of both the uncatalyzed and copper (I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC). The catalyzed reaction gives complete regioselectivity via a stepwise mechanism streamlining experimental observations. The calculated free-energy barriers 4.33 kcal/mol and 29.35 kcal/mol for the 1,4- and 1,5-regioisomers, respectively, explain the marked regioselectivity of the CuAAC reaction.


Comparison, synthesis and evaluation of anticancer drug-loaded polymeric nanoparticles on breast cancer cell lines.
Breast cancer is a major form of cancer, with a high mortality rate in women. It is crucial to achieve more efficient and safe anticancer drugs. Recent developments in medical nanotechnology have resulted in novel advances in cancer drug delivery. Cisplatin, doxorubicin, and 5-fluorouracil are three important anti-cancer drugs which have poor water-solubility. In this study, we used cisplatin, doxorubicin, and 5-fluorouracil-loaded polycaprolactone-polyethylene glycol (PCL-PEG) nanoparticles to improve the stability and solubility of molecules in drug delivery systems. The nanoparticles were prepared by a double emulsion method and characterized with Fourier Transform Infrared (FTIR) spectroscopy and Hydrogen-1 nuclear magnetic resonance ((1)HNMR). Cells were treated with equal concentrations of cisplatin, doxorubicin and 5-fluorouracil-loaded PCL-PEG nanoparticles, and free cisplatin, doxorubicin and 5-fluorouracil. The 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) assay confirmed that cisplatin, doxorubicin, and 5-fluorouracil-loaded PCL-PEG nanoparticles enhanced cytotoxicity and drug delivery in T47D and MCF7 breast cancer cells. However, the IC50 value of doxorubicin was lower than the IC50 values of both cisplatin and 5-fluorouracil, where the difference was statistically considered significant (p˂0.05). However, the IC50 value of all drugs on T47D were lower than those on MCF7.


Ameliorating effects and autonomic mechanisms of needle-less transcutaneous electrical stimulation at ST36 on stress-induced impairment in gastric slow waves.
Stress has long been documented to alter gastrointestinal motility. The effects of electroacupuncture (EA) on stress and gastric motility are relatively well known; however, whether EA has an ameliorating effect on stress-induced dysmotility remained unclear. This study aims to investigate the effects and mechanisms of needle-less transcutaneous electroacupuncture (TEA) on stress-induced impairment in gastric slow waves. A watch-size digital stimulator was developed. Ten healthy volunteers were involved in a four-session study (control, cold stress, TEA, and sham TEA). Electrogastrograpy was used to assess gastric slow waves, and electrocardiogram was recorded for the assessment of autonomic functions. The recordings were made in each session with/without stress and with TEA at ST36 or sham points. The results are as follows: (i) Cold stress-induced gastric dysrhythmia and impaired normal slow waves (P < 0.01). TEA showed a preventive effect on cold stress-induced impairment in gastric slow waves. TEA at ST36, but not sham TEA, normalized slow waves (P = 0.03 vs stress; P = 0.44 vs control), attributed to the suppression of gastric dysrhythmia; (ii) Postprandially, there was a decrease in vagal activity in both control (P = 0.004) and stress (P = 0.002) sessions; this decrease was prevented with TEA (P < 0.05). Similarly, there was a postprandial increase in sympathetic activity in both control (P = 0.01) and stress (P = 0.002) sessions, and this increase was suppressed with TEA. Needle-less TEA at ST36 using a watch-size stimulator is able to improve stress-induced impairment in gastric slow waves, possibly mediated via the autonomic mechanism. Home-based needle-less TEA may be a viable therapy for stress-induced impairment in gastric motility functions.


The Rapid Mood Screener (RMS): a novel and pragmatic screener for bipolar I disorder.
Depressive episodes and symptoms of bipolar I disorder are commonly misdiagnosed as major depressive disorder (MDD) in primary care. The novel and pragmatic Rapid Mood Screener (RMS) was developed to screen for manic symptoms and bipolar I disorder features (e.g. age of depression onset) to address this unmet clinical need. A targeted literature search was conducted to select concepts thought to differentiate bipolar I from MDD and screener tool items were drafted. Items were tested and refined in cognitive debriefing interviews with individuals with self-reported bipolar I or MDD (n = 12). An observational study was conducted to evaluate predictive validity. Participants with clinical interview-confirmed bipolar I or MDD diagnoses (n = 139) completed a draft 10-item screening tool and other questionnaires. Data were analyzed to identify the smallest possible subset of items with optimized sensitivity and specificity. Adults with confirmed bipolar I (n = 67) or MDD (n = 72) participated in the observational study. Ten draft screening tool items were reduced to 6 final RMS items based on the item-level analysis. When 4 or more items of the RMS were endorsed ("yes"), sensitivity was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. These properties were an improvement over the Mood Disorder Questionnaire in the same analysis sample while using 60% fewer items. The pragmatic 6-item RMS differentiates bipolar I disorder from MDD in patients with depressive symptoms, providing real-world guidance to primary care practitioners on whether a more comprehensive assessment for bipolar I disorder is warranted.


Chronopharmaceutics: a promising drug delivery finding of the last two decades.
Pulsatile drug delivery system capable of releasing the drug after a predetermined lag period in pulsed or controlled release manner recently has drawn the attention of both academic and industrial research. Depending on the effective therapeutic application of the drug, a variety of design strategies have been formulated in the pursuit of pulsatile release. Circadian (24 hr cycle) dependency of various physiological and pathological functions is well established, thus, it becomes imperative to develop a drug delivery system to achieve release of drug at specific site and time. Such systems are advantageous for drugs which have an extensive first pass metabolism, biological tolerance, needs targeting of locally absorbed / active drug to a specific site in intestine and are useful for the therapy for chronopharmacological needs. This manuscript portrays the important patents related to chronomodulated release system such as system with eroding, rupturing or soluble barrier coatings. In addition, recently developed chronotherapeutic dosage forms including tablets, capsules, pellets, beads implants, osmotic pump, liposome, thermoresponsive, inflammation stimuli sensitive, electrical stimuli sensitive, ultrasound stimuli responsive, magnetic stimuli responsive etc., are also conferred.


Stimulation of spontaneous transmitter release by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C.
Treatment of frog neuromuscular preparations with the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) (100 nM) resulted in a 40% rise in the frequency of miniature endplate potentials (MEPPs) (P less than 0.05). When these experiments were repeated on preparations bathed in saline containing 10 mM K+ (a procedure that raises MEPP frequency by approximately 10-fold due to the elevated level of [Ca2+]i), TPA caused a 70-75% increase in MEPP frequency (P less than 0.02), although the data did not differ significantly from those recorded in standard frog saline due to the variability between preparations. It is concluded that transmitter release mechanisms may be modulated by protein kinase C and that such modulation probably acts synergistically with [Ca2+]i.


Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment-resistant bipolar depression.
To construct a population pharmacokinetic (popPK) model for ketamine (Ket), norketamine (norKet), dehydronorketamine (DHNK), hydroxynorketamine (2S,6S;2R,6R)-HNK) and hydroxyketamine (HK) in patients with treatment-resistant bipolar depression. Plasma samples were collected at 40, 80, 110, 230 min on day 1, 2 and 3 in nine patients following a 40 min infusion of (R,S)-Ket (0.5 mg kg⁻¹) and analyzed for Ket, norKet and DHNK enantiomers and (2S,6S;2R,6R)-HNK, (2S,6S;2R,6R)-HK and (2S,6R;2R,6S)-HK. A compartmental popPK model was constructed that included all quantified analytes, and unknown parameters were estimated with an iterative two-stage algorithm in ADAPT5. Ket, norKet, DHNK and (2S,6S;2R,6R)-HNK were present during the first 230 min post infusion and significant concentrations (>5 ng ml⁻¹) were observed on day 1. Plasma concentrations of (2S,6S;2R,6R)-HK and (2S,6R;2R,6S)-HK were below the limit of quantification. The average (S) : (R) plasma concentrations for Ket and DHNK were <1.0 while no significant enantioselectivity was observed for norKet. There were large inter-patient variations in terminal half-lives and relative metabolite concentrations; at 230 min (R,S)-DHNK was the major metabolite in four out of nine patients, (R,S)-norKet in three out of nine patients and (2S,6S;2R,6R)-HNK in two out of nine patients. The final PK model included three compartments for (R,S)-Ket, two compartments for (R,S)-norKet and single compartments for DHNK and HNK. All PK profiles were well described, and parameters for (R,S)-Ket and (R,S)-norKet were in agreement with prior estimates. This represents the first PK analysis of (2S,6S;2R,6R)-HNK and (R,S)-DHNK. The results demonstrate that while norKet is the initial metabolite, it is not the main metabolite suggesting that future Ket studies should include the analysis of the major metabolites.


Endogenous Retroelements in Cellular Senescence and Related Pathogenic Processes: Promising Drug Targets in Age-Related Diseases.
Endogenous retroelements (ERs) represent nearly half of the human genome. Considered up to recent years as "functionless" DNA sequences, they are now known to be involved in important cellular functions such as stress response and generation of non coding regulatory RNAs. Moreover, an increasing amount of data supports the idea of ERs as key players in cellular senescence and in different senescence-related pathogenic cellular processes, including those leading to inflammation, cancer and major age-related multifactorial diseases. The involvement of ERs in these biological mechanisms can suggest new therapeutic strategies in neoplasms, inflammatory/autoimmune diseases and in different age-related pathologies, such as macular degeneration, diabetes, cardiovascular diseases and major age-related neurodegenerative disorders. The therapeutic approaches which can be suggested range from a set of well-known, common drugs that have been shown to modulate ERs activity, to immune therapy against ER-derived tumor antigens, to more challenging strategies such as those based on anti-ERs RNA interference.


Spatiotemporal distribution of schistosomiasis transmission risk in Jiangling County, Hubei Province, P.R. China.
This study aims to explore the spatiotemporal distribution of schistosomiasis in Jiangling County, and provide insights into the precise schistosomiasis control. The descriptive epidemiological method and Joinpoint regression model were used to analyze the changes in infection rates of humans, livestock, snails, average density of living snails and occurrence rate of frames with snails in Jiangling County from 2005 to 2021. Spatial epidemiology methods were used to detect the spatiotemporal clustering of schistosomiasis transmission risk in Jiangling county. The infection rates in humans, livestock, snails, average density of living snails and occurrence rate of frames with snails in Jiangling County decreased from 2005 to 2021 with statistically significant. The average density of living snails in Jiangling County was spatially clustered in each year, and the Moran's I varied from 0.10 to 0.26. The hot spots were mainly concentrated in some villages of Xionghe Town, Baimasi Town and Shagang Town. The mean center of the distribution of average density of living snails in Jiangling County first moved from northwest to southeast, and then returned from southeast to northwest after 2014. SDE azimuth fluctuated in the range of 111.68°-124.42°. Kernal density analysis showed that the high and medium-high risk areas of Jiangling County from 2005 to 2021 were mainly concentrated in the central and eastern of Jiangling County, and the medium-low and low risk areas were mainly distributed in the periphery of Jiangling County. The epidemic situation of schistosomiasis decreased significantly in Jiangling County from 2005 to 2021, but the schistosomiasis transmission risk still had spatial clustering in some areas. After transmission interruption, targeted transmission risk intervention strategies can be adopted according to different types of schistosomiasis risk areas.


Prognostic influence of PD-1/PD-L1 suppressors in combination with chemotherapeutic agents for non-small cell pulmonary carcinoma: system review and meta-analysis.
Lung cancer is a common malignant tumor, which is seriously harmful to human life and health. Nowadays, it has gradually become one of the best treatments for non-small cell lung cancer (NSCLC) to combine immunotherapy and chemotherapy, and its clinical efficacy is preliminary. Nevertheless, substantial differences exist between various studies and various indicators. Despite their unconvincing results, high-quality research evidence is needed to support them. In this case, further correlative studies are necessary to investigate the prognostic outcomes of PD-1/PD-L1 suppressors in combination with chemotherapeutic drugs in NSCLC. The online public databases were searchable for the clinical trials that consisted of NSCLC patients who had concluded their chemotherapy and who had accepted PD-1/PD-L1 suppressors. The time-span of the search spanned from the beginning to the end of the database. Two investigators retrieved the data independently. RevMan 5.3 statistical software was utilized for the assessment of bias risk. The software followed the Cochrane Handbook 5.3 guidelines. There were seven clinically controlled studies with 2781 NSCLC samples finally included in this study. A meta-analysis of the post-treatment overall response rate (ORR) was undertaken. A remarkably higher ORR rate was observed in the study group (p<0.05). Study participants had a noticeably longer PFS (HR=0.61, 95% CI=0.54-0.70, P<0.00001). Study participants had markedly longer overall survival (OS) (HR=0.651, 95% CI=0.52-0.82, P<0.05). The incidence of adverse events (AEs) of Grade 3 or above was not clinically clearly different (P>0.05), as demonstrated by the incidence of AEs. The funnel plots were separately charted in accordance with ORR rate, PFE, OS, and Grade 3 AEs. The majority of the funnel plots were symmetrical and a minority of funnel plots were asymmetrical, indicating the heterogeneity of research and the limited evidence available may lead to some publication bias in the contained literature. The combined PD-1/PD-L1 inhibitors with conventional chemotherapy can dramatically elevate the prognosis of NSCLC patients, obviously enhancing the ORR rate and prolonging their PFS and OS. Furthermore, it was found that adding PD-1/PD-L1 inhibitors to conventional chemotherapy did not result in any additional adverse effects.


[Professional burnout among university and high school teachers--comparative study].
Professional burnout is a set of negative emotional and behavioral symptoms, observed in workers of widely understood human service occupations, including teachers. In spite of the considerable number of studies of burnout in teachers, a few of them concern university teachers. The aim of the article was to estimate the degree of burning threat in this professional group and to analyze individual determinants and dynamics of burning out in academic teachers. Gender, age, personality traits and temperament traits were given the status of main factors in the study. The role of the perceived social support was also analyzed. 97 academic workers of three state universities (University, Medical University and Technical University) in Łódź took part in the study; 100 teachers of high schools formed a comparative group. MBI General Survey was applied to measure dependent variables (burnout and its three components: Emotional Exhaustion, Cinicism and Professional Efficacy). The level of factors was measured with standard psychological tests: NEO-FFI and FCZ-KT. The Scale of Perceived Social Support was also applied. The results show considerably lower threat of the burning out syndrome in university than in high school teachers. Among individual factors only two temperament traits (emotional reactivity and perseveration) and one personality trait (extroversion) seem to be important determinants of professional burnout. The perceived social support does not prevent the progress of burnout syndrome. Based on the obtained results several practical conclusions were formulated. They refer mainly to preventive training for beginners in teaching and changes in the organization of academic teachers' work.


Comorbidity of schizophrenia and galactosemia: effective clozapine treatment with weight gain.
Weight gain with atypical antipsychotics such as clozapine has been hypothesized to have a multifactorial genesis. Beside changes in neurotransmitter systems caused by antipsychotic-induced receptor blockade, hormonal changes and other neuroleptic side-effects (sedation, reduced activity, reduced basal metabolic rate, dry mouth) are also discussed. Our unique case report of a patient with comorbid galactosemia and schizophrenia is an interesting example of weight gain being a positive side-effect of clozapine, not necessarily associated with increased appetite and higher caloric intake.


A novel toolkit to improve percutaneous subxiphoid needle access to the healthy pericardial sac.
The current practice of percutaneous subxiphoid needle access to the "healthy" pericardial sac has significant limitations. We sought to examine the feasibility of a novel toolkit designed to improve this procedure. The toolkit included a pericardial access needle and a virtual imaging platform. The needle had a 0.036 inch outer diameter, abbreviated 25° bevel, and was electrically insulated except for two small surfaces recessed from the tip. Radiofrequency energy was delivered via these surfaces to facilitate pericardial perforation. The virtual imaging system demonstrated the needle in real time and in its entirety within the thoracic anatomy of the individual animal, which was reconstructed from computed tomographic images obtained preoperatively and registered to the operative field. In five large (40-60 kg) healthy pigs, percutaneous subxiphoid access to the sac using both anterior and posterior approaches was performed. Spatial inaccuracy was measured as the distance between the pericardial puncture site and the anterior or posterior descending coronary artery, the pericardium contiguous to which had been targeted by the needle. In each animal, pericardial access was gained at 4 discrete sites (2 anterior, 2 posterior). Inaccuracy was 4.2 ± 2.2 millimeters (range 0-8 millimeters) and did not differ significantly between anterior and posterior approaches. No damage to the epicardium or coronary arteries was observed. Percutaneous subxiphoid access to the pericardial sac utilizing this toolkit was feasible, including safety and reasonable accuracy.


Individual differences in hedonic capacity.
Hedonic capacity--an individuals ability to experience pleasurable affect--is important, not Only in accounting for the development of psychopathology but in understanding normal personality as well. In this article, the development and validation of three scales of hedonic capacity are described. One scale consists of MMPI items, a second consists of CPI items, and the third combines items from both inventories. These scales demonstrated acceptable internal consistency and test-retest reliability. Initial support for the construct validity of the scales was also obtained. Because they have been constructed from the MMPI and CPI, the scales described in this article can be used to address important questions in research on schizophrenia, depression, and normal personality with a wide variety of data that has already been collected.


[Pathophysiologic and clinical relevance of atrial natriuretic factor in patients with cirrhosis of the liver].
Defects of the ANF system in cirrhosis have not been demonstrated in terms of absolute deficiency of plasma levels or by evidence of major abnormalities of processing in patients with cirrhosis. In the present study, the responsiveness of the ANF system to acute volume stimulation by water immersion and the diuretic and natriuretic effects of ANF infusion were examined. Stimulation of ANF release by 1-h immersion was significantly blunted in ten cirrhotic patients with ascites (increase of plasma ANF by 46 +/- 18%), whereas 11 cirrhotics without ascites showed a 104 +/- 16% increase, similar to the 117 +/- 29% stimulation in 25 healthy controls. Immersion increased urinary volume by 3.6 +/- 0.6/2.0 +/- 0.8/0.7 +/- 0.4 ml/min and urinary sodium excretion by 146 +/- 38/75 +/- 43/43 +/- 19 mumol/min in controls/cirrhotics without/cirrhotics with ascites. Infusion of ANF for 30 min prompted an increase in diuresis and natriuresis in seven cirrhotic patients, which was less marked in patients with ascites, as compared to patients without ascites. Thus, the stimulus response coupling for ANF may be impaired in patients with cirrhosis and ascites.


Effect of oestrogen or cyproterone acetate treatment on adrenocortical function in prostate carcinoma patients.
The antiandrogen cyproterone acetate (CA), as well as oestrogens have been reported to influence pituitary-adrenal function in prostate cancer patients, but the clinical relevance of these findings is unknown. We therefore investigated serum cortisol (F), dehydro-epiandrosterone sulphate (DS), testosterone (T) and prolactin (Prl) levels in patients treated with CA or oestradiol undecylate for at least 6 months. Hypothalamic-pituitary-adrenal function was further assessed by analysis of diurnal hormone variation and by ACTH stimulation and dexamethasone suppression tests. To differentiate between direct CA or oestrogen effects and secondary effects resulting from therapy-induced hypogonadism, we performed similar tests in untreated normogonadal and hypogonadal patients. CA treatment effected a significant decrease in serum F (-40%), DS (-73%) and T (-58%) levels and an increase in serum Prl (+118%). Oestrogen treatment resulted in markedly lowered T levels (-89%), slightly elevated serum F (+24%) and significantly increased serum Prl (+192%). Corresponding changes of F, DS and Prl could not be found in the untreated hypogonadal controls, thus indicating a direct drug-related effect. Neither diurnal rhythmicity of serum F nor adrenal response to ACTH stimulation or sensitivity to dexamethasone suppression significantly changed under CA or oestrogen treatment. We conclude that, although serum F levels may decrease under CA or increase slightly under oestrogen therapy for prostate carcinoma, these findings do not justify specific treatment, since neither clinical side effects nor an impairment of hypothalamic-pituitary-adrenal feedback occurs.


Understanding Men's Perceptions of Human Papillomavirus and Cervical Cancer Screening in Kampala, Uganda.
This preliminary study explores Ugandan men's knowledge and attitudes about human papillomavirus (HPV), cervical cancer, and screening. A local physician led an education session about cervical cancer for 62 men in Kisenyi, Kampala in Uganda. Trained nurse midwives administered surveys to assess knowledge and attitudes before and after the education session. From the pre-education survey, only 24.6% of men had heard of HPV previously, and 59% of men had heard of cervical cancer. Posteducation, 54.5% of men believed only women could be infected with HPV and 32.7% of men believed antibiotics could cure HPV. Despite their limited knowledge, 98.2% of men stated they would support their partners to receive screening for cervical cancer, and 100% of men surveyed stated they would encourage their daughter to get the HPV vaccine if available. Knowledge of HPV and cervical cancer among Ugandan men is low. Even after targeted education, confusion remained about disease transmission and treatment. Ongoing education programs geared toward men and interventions to encourage spousal communication about reproductive health and shared decision making may improve awareness of cervical cancer prevention strategies.


Calcium chloride and tricalcium phosphate effects on the pink color defect in cooked ground and intact turkey breast.
Calcium chloride (250, 500ppm) was examined for its ability to reduce the pink color defect induced by sodium nitrite (10ppm) and nicotinamide (1.0%) in cooked ground turkey in the presence and absence of sodium tripolyphosphate (0.25, 0.5%) and sodium citrate (0.5, 1.0%). The ability of tricalcium phosphate (0.1-0.5%) to reduce pink cooked color also was evaluated in ground turkey and both calcium chloride and tricalcium phosphate were tested for their effects on pink cooked color in whole breast muscle. The combination of calcium chloride and sodium tripolyphosphate, not calcium chloride alone, was necessary for a reduction in pink cooked color induced by nicotinamide. Subsequently, in the presence of phosphate, both calcium chloride and sodium citrate reduced pink cooked color and were most effective in combination. Tricalcium phosphate also was capable of reducing pink cooked color in ground turkey, however substituting tricalcium phosphate for sodium tripolyphosphate resulted in lower pH and cooking yields. Neither calcium chloride nor tricalcium phosphate was capable of reducing pink cooked color in whole turkey breast. Currently, a combination of sodium tripolyphosphate, calcium chloride, and sodium citrate represents the most suitable means for reducing or preventing the pink color defect in uncured ground turkey.


Insensitive dependence of delay-induced oscillation death on complex networks.
Oscillation death (also called amplitude death), a phenomenon of coupling induced stabilization of an unstable equilibrium, is studied for an arbitrary symmetric complex network with delay-coupled oscillators, and the critical conditions for its linear stability are explicitly obtained. All cases including one oscillator, a pair of oscillators, regular oscillator networks, and complex oscillator networks with delay feedback coupling, can be treated in a unified form. For an arbitrary symmetric network, we find that the corresponding smallest eigenvalue of the Laplacian λ(N) (0 >λ(N) ≥ -1) completely determines the death island, and as λ(N) is located within the insensitive parameter region for nearly all complex networks, the death island keeps nearly the largest and does not sensitively depend on the complex network structures. This insensitivity effect has been tested for many typical complex networks including Watts-Strogatz (WS) and Newman-Watts (NW) small world networks, general scale-free (SF) networks, Erdos-Renyi (ER) random networks, geographical networks, and networks with community structures and is expected to be helpful for our understanding of dynamics on complex networks.


Dementia has a categorical, not dimensional, latent structure.
Recently, Walters ("Dementia: Continuum or distinct entity?", Psychology and Aging, 2010, 25, 534-544) published a taxometric study suggesting a dimensional latent structure for the construct of dementia. However, because that study did not conceptualize dementia according to accepted conventions (i.e., there were no measures of cognitive change or independent functioning), its results may represent a false negative error caused by insufficient content coverage. We replicated Walters, and we used the same taxometric methods and the same data source--but with indicators of cognitive change and functional independence. Our results support a categorical interpretation of dementia; whereas Walters' results suggest that cognitive ability, rather than dementia, is dimensional in nature.


Concentration-Dependent Solar Thermochemical CO2/H2O Splitting Performance by Vanadia-Ceria Multiphase Metal Oxide Systems.
The effects of V and Ce concentrations (each varying in the 0-100% range) in vanadia-ceria multiphase systems are investigated for synthesis gas production via thermochemical redox cycles of CO2 and H2O splitting coupled to methane partial oxidation reactions. The oxidation of prepared oxygen carriers is performed by separate and sequential CO2 and H2O splitting reactions. Structural and chemical analyses of the mixed-metal oxides revealed important information about the Ce and V interactions affecting their crystal phases and redox characteristics. Pure CeO2 and pure V2O5 are found to offer the lowest and highest oxygen exchange capacities and syngas production performance, respectively. The mixed-oxide systems provide a balanced performance: their oxygen exchange capacity is up to 5 times higher than that of pure CeO2 while decreasing the extent of methane cracking. The addition of 25% V to CeO2 results in an optimum mixture of CeO2 and CeVO4 for enhanced CO2 and H2O splitting. At higher V concentrations, cyclic carbide formation and oxidation result in a syngas yield higher than that for pure CeO2.


[A clinical study on different decompression methods in cervical spondylosis].
To analyze the different decompression methods to treat cervical spondylosis based on imageological evaluation. Two hundred and sixty three consecutive patients with cervical spondylosis between Nov. 2004 and Oct. 2007 were involved in this study. Patients were distributed to different operation groups based on the preoperative imageological evaluation, including anterior or posterior decompression methods. The Anterior method is to use the discectomy of one to three segments, autogenous iliac graft or titanium mesh or cage fusion and titanium plate fixation, or subtotal vertebrectomy of one to two segments autogenous iliac graft or titanium mesh fusion and titanium plate fixation, or discectomy plus subtotal vertebrectomy, The posterior expansive single open door laminoplasty and other operation types. All the patients were divided into different groups by the preoperative imageological evaluation, age, sex and course of diseases. Then we collected each group's preoperative and postoperative JOA scores and mean improvement rate to evaluate the postoperative effect by different decompression methods. Two hundred and thirty five patients were followed up with a mean period of 18 months (range, 4 to 36 months). JOA scores of all patients were improved by different degrees after operations. Anterior and posterior decompression methods both can achieve higher mean improvement rates. There were no significant differences in mean improvement rates between anterior groups, and so did male and female (P > 0.05). The effect will decrease as age increases or the course of disease prolongs. Statistical significance existed among the different age groups and between course groups (P < 0.05). Anterior and posterior decompression methods both can achieve good effect. The key point is to choose the surgical indication correctly, decompress thoroughly, and make the fusion reliable and fixation firm. In regard to the patients' imageological evaluation, the methods should be differentiated. The anterior operation type included discectomy of one to three segments, subtotal vertebrectomy of one to two segments and discectomy plus subtotal vertebra ectomy.


What are the potential benefits of clinical beta-cell imaging in diabetes mellitus?
Previously, studies of the endocrine pancreatic beta-cell were mainly performed ex vivo by morphological means. This data supported the analysis of pathophysiological changes in the pancreatic islet during insults such as diabetes mellitus. Metabolic testing of the pancreatic islet by assaying hormone parameters such als plasma insulin or C-peptide combined with more or less sophisticated calculations allowed conclusions about states of insulin resistance or secretory failure. It also allowed certain correlations of endocrine function with beta-cell mass. Today, with firmer pathophysiological concepts about beta-cell failure, modern protocols of islet transplantation, and drugs on the market coming with promises of preservation or even expansion of beta-cell mass in diabetes mellitus it has become very attractive to search for tools measuring beta-cell mass, if possible even repeatingly in the same organism in vivo. From a clinical point of view, the potential of pancreatic beta-cell mass imaging technologies is looked upon with high expectations. Methodologically, the decisive question is whether it is likely that future beta-cell imaging will provide significant advantages over the metabolic methods already in hand. With new in vivo tools, studies of beta-cell mass and function may offer even new approaches stratifying patients to anti-diabetic therapies.


Ocular complications related to breast cancer.
One in 10 women will be affected by breast cancer in their lifetime. The potential for loss of vision from breast cancer metastases to the eye will affect a small proportion of these women. Ocular complications related to these metastases and cancer treatments (drugs, irradiation) and the psychosocial support for the patient and family make the role of the ophthalmic nurse an extremely important one. This article will review these issues.


In vitro tendon engineering with avian tenocytes and polyglycolic acids: a preliminary report.
Although there are many reports of in vivo tendon engineering using different animal models, only a few studies involve the short-term investigation of in vitro tendon engineering. Our previous study demonstrated that functional tendon tissue could be engineered in vivo in a hen model using tenocytes and polyglycolic acid (PGA) fibers. This current study explored the feasibility of in vitro tendon engineering using the same type of cells and scaffold material. Tenocytes were extracted from the tendons of a hen's foot with enzyme digestion and cultured in DMEM plus 10% FBS. Unwoven PGA fibers were arranged into a cord-like construct and fixed on a U-shape spring, and tenocytes were then seeded on PGA fibers to generate a cell-PGA construct. In experimental group 1, 22 cell-scaffold constructs were fixed on the spring with no tension and collected at weeks 4 (n = 7), 6 (n = 7) and 10 (n = 8); in experimental group 2, five cell-scaffold constructs were fixed on the spring with a constant strain and collected after 6 weeks of culture. In the control group, three cell-free scaffolds were fixed on the spring without tension. The collected engineered tendons were subjected to gross and histological examinations and biomechanical analysis. The results showed that tendon tissue could be generated during in vitro culture. In addition, the tissue structure and mechanical property became more mature and stronger with the increase of culture time. Furthermore, application of constant strain could enhance tissue maturation and improve mechanical property of the in vitro engineered tendon (1.302 +/- 0.404 Mpa with tension vs 0.406 +/- 0.030 Mpa without tension at 6 weeks). Nevertheless, tendon engineered with constant strain appeared much thinner in its diameter than tendon engineered without mechanical loading. Additionally, its collagen fibers were highly compacted when compared to natural tendon structure, suggesting that constant strain may not be the optimal means of mechanical load. Thus, application of dynamic mechanical load with a bioreactor to the construction of tendon tissue will be our next goal in this series of in vitro tendon engineering study.


Free fatty acid receptors in the endocrine regulation of glucose metabolism: Insight from gastrointestinal-pancreatic-adipose interactions.
Glucose metabolism is primarily controlled by pancreatic hormones, with the coordinated assistance of the hormones from gastrointestine and adipose tissue. Studies have unfolded a sophisticated hormonal gastrointestinal-pancreatic-adipose interaction network, which essentially maintains glucose homeostasis in response to the changes in substrates and nutrients. Free fatty acids (FFAs) are the important substrates that are involved in glucose metabolism. FFAs are able to activate the G-protein coupled membrane receptors including GPR40, GPR120, GPR41 and GPR43, which are specifically expressed in pancreatic islet cells, enteroendocrine cells as well as adipocytes. The activation of FFA receptors regulates the secretion of hormones from pancreas, gastrointestine and adipose tissue to influence glucose metabolism. This review presents the effects of the FFA receptors on glucose metabolism via the hormonal gastrointestinal-pancreatic-adipose interactions and the underlying intracellular mechanisms. Furthermore, the development of therapeutic drugs targeting FFA receptors for the treatment of abnormal glucose metabolism such as type 2 diabetes mellitus is summarized.


High-Confidence Sequencing of Phosphopeptides by Electron Transfer Dissociation Mass Spectrometry Using Dinuclear Zinc(II) Complex.
Phosphorylation is the most abundant protein modification, and tandem mass spectrometry (MS2) with electron transfer dissociation (ETD) has proven to be a promising method for phosphoproteomic applications owing to its ability to determine phosphorylation sites on proteins. However, low precursor charge states hinder the ability to obtain useful information through peptide sequencing by ETD, and the presence of acidic phosphate groups contributes to a low charge state of peptide ions. In the present report, we used a dinuclear zinc complex, (Zn2L)3+ (L = alkoxide form of 1,3-bis[bis(pyridin-2-ylmethyl)amino]propan-2-ol) for electrospray ionization (ESI), followed by ETD-MS2 analysis. Since (Zn2L)3+ selectively bound to phosphopeptide with addition of a positive charge per phosphate group, the use of (Zn2L)3+ for ESI improved the ionization yield of phosphopeptides in phosphoprotein digest. Additionally, an increase in the charge state of phosphopeptides were observed by addition of (Zn2L)3+, facilitating phosphopeptide sequencing by ETD-MS2. Since the binding between (Zn2L)3+ and the phosphate group was retained during the ETD process, a comparison between the ETD mass spectra obtained using two dinuclear zinc complex derivatives containing different zinc isotopes, namely (64Zn2L)3+ and (68Zn2L)3+, provided information about the number of phosphate groups in each fragment ion, allowing the phosphorylation site to be unambiguously determined. The details of the fragmentation processes of the (Zn2L)3+-phosphopeptide complex were investigated using a density functional theory calculation. As in the case of protonated peptides, ETD induced peptide backbone dissociation in the (Zn2L)3+-phosphopeptide complex proceeded through an aminoketyl radical intermediate.


Medical management of diverticular disease.
Diverticular disease is a common disorder affecting 30-55% of the population in the developed world. It has been described as "a deficiency disease of Western civilization", a theory that has been proposed since it was observed that diverticular disease was uncommon in African and other developing countries where dietary fibre consumption was high. At the turn of the century the medical treatment of colonic diverticulosis involved the avoidance of "roughage", which was felt to exacerbate the problem. However, the use of high fibre diets in the prevention and treatment of the symptoms of diverticular disease has now become commonplace, and the development of this practice is discussed in this chapter.


Correlation of new bone metabolic markers with conventional biomarkers in hemodialysis patients.
New bone metabolic markers have become available clinically for evaluating chronic kidney disease mineral and bone disorders (CKD-MBD). The aim of this study was to correlate these new bone metabolic markers with conventional markers in regular hemodialysis (HD) patients. One hundred forty three HD patients underwent cross-sectional assessment. Two bone formation markers, bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and one bone resorption marker, amino-terminal telopeptides of type 1 collagen (NTx), were selected for study. Both circulating OC and NTx levels showed positive correlations with serum intact parathyroid hormone (iPTH) levels. The levels of NTx and OC showed a strongly positive correlation, although they are known to be markers of different aspects of bone metabolism: bone formation and resorption. Patients with high iPTH (≥300pg/mL) had significantly higher levels of all the three bone markers compared with patients with low or normal iPTH . Serum OC and NTx levels may be useful markers of serum iPTH levels for evaluating bone turnover in HD patients and may eventually prove useful in the management of patients with CKD-MBD.


[Association of type 1 neurofibromatosis and primary hyperparathyroidism].
The combination of neurofibromatosis type I with hyperparathyroidism is classical but rare. Our report is on the original observation of a patient affected with Von Recklinghausen's disease complicated by chronic restrictive breathing deficiency. After an intense breathing decompensation and a spreading convulsive attack, hyperparathyroidism was diagnosed. The similarity of the bone lesions seen in type I neurofibromatosis and in hyperparathyroidism strongly suggests a genetic link between these two pathologies. Hence, hyperparathyroidism should be searched for in all patients affected with Von Recklinghausen's disease, since the adjustment of hypercalcemia can lead to partial reversibility of the bone abnormalities.


Induced Membrane Technique Is Effective for the Management of Acute Traumatic Bone Loss in Both Diaphyseal and Metaphyseal Lower Extremity Fractures.
To compare outcomes of Masquelet-induced membrane technique (IMT) in metaphyseal and diaphyseal fractures with acute bone loss. Retrospective cohort study. Four Level 1 Academic Trauma Centers. Patients acutely treated with IMT for traumatic lower extremity bone loss at 4 Level 1 trauma centers between 2010 and 2020. Operative treatment with placement of cement spacer within 3 weeks of initial injury followed by staged removal and bone grafting to the defect. Fracture union, infection, revision grafting, time to union, and amputation. One hundred twenty fractures met inclusion criteria, including 43 diaphyseal fractures (DIM) and 77 metaphyseal fractures (MIM). Demographic characteristics were not significantly different, except for age (DIM 34 years vs. MIM 43 years, P < 0.001). Union after treatment with IMT was 89.2% overall. After controlling for age, this was not significantly different between DIM (41/43, 95.3%) and MIM (66/77, 85.7%) ( P = 0.13) nor was the rate of infection between groups. There was no difference in any secondary outcomes. The overall union rate in the current series of acute lower extremity fractures treated with the induced membrane technique was 89%. There was no difference in successful union between patients with diaphyseal bone loss or metaphyseal bone loss treated with IMT. Similarly, there was no difference in patients with tibial or femoral bone loss treated with induced membrane. Defect size after debridement may be more prognostic for secondary operations rather than the limb segment involved or the degree of soft-tissue injury. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


[Transcutaneous electrical acupoint stimulation based on electro-oculogram signal regulation for children with mental retardation: a randomized controlled trial].
To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) at Changqiang (GV 1) based on the modulation of electro-oculogram (EOG) signal for children with mental retardation, and explore the evaluation effect of the goal attainment scale (GAS) in children with mental retardation. Sixty children with mental retardation were randomly divided into a treatment group and a control group, with 30 cases in each one. The children in the control group were treated with conventional rehabilitation, 5 times a week. On the basis of the control group, TEAS at Changqiang (GV 1) under the modulation of EOG signal was adopted in the treatment group. When the similarity between the collected EOG signal and the template was within the range of EOG threshold, one electric stimulation was triggered at Changqiang (GV 1) for 20 s (continuous wave, 70-100 Hz in frequency, 0.1-0.2 ms in pulse width), lasting 30 min in each treatment, the intervention was given twice a week. One course of treatment was composed of 4 weeks, and 3 courses were required in total in the two groups. The infant-junior high school student's social living ability scale (S-M) and GAS were scored and compared before and after treatment in the two groups. After treatment, the scores of self-living ability in the treatment group and communication ability in the control group were higher than those before treatment (P<0.01, P<0.05). The scores of collective activity and motor ability in the treatment group were higher than those in the control group (P<0.05). After treatment, GAS scores were higher than before treatment in both groups (P<0.001), and the score in the treatment group was higher than the control group (P<0.05). TEAS under the modulation of EOG signal is conductive to improving the collective, motor and self-living abilities of the children with mental retardation and promoting children's individual goals. Compared with the standard score of S-M, the T value of GAS can better reflect the subtle progress of individual.


Fabry disease: clinical spectrum and evidence-based enzyme replacement therapy.
The clinical spectrum of Fabry disease, an X-linked lysosomal storage disorder due to alpha-galactosidase A (alpha-Gal A) deficiency, has been expanded beyond the classic phenotype to include the recently recognized later-onset "cardiac" and "renal" variants. The clinical manifestations in each of these disease subtypes are presented with particular emphasis on early recognition among pediatric patients as well as identification of unrecognized patients diagnosed as hypertrophic cardiomyopathy or in renal dialysis clinics. Previously, treatment of patients with Fabry disease was limited to palliative care of the excruciating pain, cardiac and cerebrovascular manifestations, and renal failure. Recently, Fabry-specific enzyme replacement therapy (ERT) with recombinant alpha-Gal A (Fabrazyme) has proven safe and effective. The preclinical, Phase 1/2 and multicenter, double-blind, randomized, placebo-controlled Phase 3 and 4 trials provided the evidence for the safety and efficacy of Fabrazyme treatment. The preclinical and Phase 1/2 studies demonstrated that enzyme delivery to various tissues and GL-3 clearance were dose-dependent. The Phase 3 clinical trial and 3-year extension study provided long-term data documenting the safety and effectiveness of 1 mg/kg of Fabrazyme for this disease. Finally, the "top-line" data from the Phase 4 trial indicates that in patients with mildly to moderately advanced renal disease, Fabrazyme can slow the progression of renal, cardiac, and cerebrovascular events taken together or individually. The Phase 4 trial results also emphasize the importance of early treatment. In sum, these clinical trials provide the evidence-based safety and efficacy of Fabrazyme replacement therapy for Fabry disease.


Shear bond strength of some sealants under saliva contamination.
The purpose of this in vitro study was to compare the shear bond strength of different types of sealant to non-contaminated and saliva-contaminated enamel. The buccal surfaces of 60 sound permanent third molars were individually embedded in self-curing acrylic resin and wet ground with 1,000-grit silicone carbide paper to obtain a flat enamel surface. The specimens were randomly assigned to one of three groups: 1) non-fluoride-releasing resin sealant (Concise), 2) fluoride-releasing resin sealant (Clinpro), 3) glass-ionomer sealant (Fuji VII). Each group was divided into 2 subgroups (n = 10): non-contaminated and saliva contaminated with 0.02 ml of fresh human saliva for 20 seconds and then blowed dried prior to sealant placement. All samples were thermocycled 2,000 cycles. The specimens were tested using an Instron running at a crosshead speed of 0.05 mm/min. Stereomicroscope examinations were carried out to evaluate failure sites of the sealants. Data were analyzed with one-way ANOVA and the Turkey test at a siginificance level of p < 0.05. Comparison of the different types of sealant revealed the shear bond strength of the glass-ionomer sealant was the same for the non-contaminated and saliva-contaminated subgroups. The shear bond strength was lower in both the fluoride and non-fluoride releasing resin-based sealant groups contaminated with saliva than in the fluoride and non-fluoride releasing resin-based sealant groups not contaminated with saliva. Comparison of the different types of sealant also revealed the shear bond strength of the glass-ionomer sealant had a significantly lower shear bond strength than the fluoride and non-fluoride releasing resin-based sealant groups for both the non-contaminated and saliva-contaminated subgroups. The fluoride and non-fluoride releasing resin-based sealant groups were not significantly different from each other. The modes of failure were mostly mixed with the glass-ionomer sealant in both the non-contaminated and saliva-contaminated subgroups of this sealant. The resin-based sealant groups (both fluoride and non-fluoride releasing) had cohesive/mixed failure in the non-contaminated and adhesive/mixed failure in the saliva-contaminated subgroups. In conclusion, saliva-contamiantion did not affect the shear bond strength of glass-ionomer sealant but the glass-ionomer sealant had the lowest shear bond strength.


Concomitant T-cell prolymphocytic leukemia and visceral leishmaniasis: A case report.
T-cell prolymphocytic leukaemia (T-PLL) is a rare aggressive lymphoid disease featured by a significant increased lymphocyte count and obvious hepatosplenomegaly with poor prognosis. The concomitant presentation of T-PLL and visceral leishmaniasis (VL) has not previously been reported. The patient initially suffered from anorexia, skin pigmentation, fever and hepatosplenomegaly. Bone marrow smear described leishmania and antibody test was positive. VL was diagnosed and he was given antimony gluconate therapy. His symptoms recurred. A combination of serological rk39 test, morphologic evaluation and immunophenotyping by flow cytometry finally supported the diagnosis of concomitant VL and T-PLL. Amphotericin B was used for the treatment of VL first and a referral for treating T-PLL after recovery from VL was suggested. Unfortunately, the patient requested to be discharged. Telephone follow-up indicated that he died a few days after leaving the hospital. Due to the rarity of the disease combination, the pathogenesis association of T-PLL and VL is unclear. However, a duly diagnosis is crucial for treatment. In immunosuppressed patients due to malignancies and treatment, VL should be considered as an opportunistic infection. In VL infections, the clinical manifestations mimicking hematological malignancies may cover up the underlying disease. Under such conditions, a complete work-up based on laboratory test is necessary to achieve a correct diagnosis.


Association of ADIPOQ genetic variants and plasma adiponectin isoforms with the risk of incident renal events in type 2 diabetes.
Adiponectin levels are high in cases of diabetic nephropathy, but it remains unclear whether these high levels are a cause or a consequence of the disease. We investigated the possible association of polymorphisms in the adiponectin gene and baseline adiponectin levels with the incidence of renal events in subjects with type 2 diabetes. We studied three adiponectin polymorphisms (-11391G > A, +45T > G and +276G > T) in 3086 subjects with type 2 diabetes and high levels of albumin excretion from the diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events and ramipril (DIABHYCAR) trial. Baseline concentrations of total adiponectin and of adiponectin isoforms were determined in cases with incident renal events and in controls matched for sex, age, body mass index (BMI) and adiponectin genotype. We used another cohort of type 2 diabetes patients-the survie, diabète de type 2 et génétique(SURDIAGENE) study (n = 1004)-for the replication of genetic data. In DIABHYCAR, the -11391A and +45G alleles were associated with a higher incidence of renal events [hazard ratio (HR) = 1.73; 95% confidence interval (CI), 1.10-2.71; and HR = 1.68; 95% CI, 1.14-2.47, respectively]. The haplotype containing susceptibility alleles, -11391A/+45G/+276G, was more frequent in cases with renal events (5.1% vs. 1.9% in those without, P = 0.005). In SURDIAGENE, the -11391A/+45G/+276G haplotype was also associated with renal events (5.6% vs. 1.9% in those without, P = 0.03). In DIABHYCAR, all isoforms were more abundant in subjects carrying the -11391A or +45G alleles. Medium- (MMW) and low-molecular weight (LMW) isoforms were more abundant in cases with renal events. In subjects with type 2 diabetes and early renal dysfunction, adiponectin gene variants are determinants of the renal risk. The -11391A and +45G alleles may affect renal risk by leading to high circulating adiponectin concentrations, at least those of MMW and LMW isoforms.


[Acute papillary necrosis in the transplanted kidney].
After a brief literature survey revealing the rarity of the papillary necrosis in transplanted kidneys, the authors report the case of one of their patients, aged 32, transplanted a corpse kidney of a 30-year old male with blood-group compatibility and with coincidence of the two antigens in locus A. Regardless of the increased diuresis of the patient to 3-4 1 within 24 hours, its nitrogen bodies persisted their elevation, necessitating two dialysis. After the second dialysis performed on the tenth day after the transplantation, the patient had very strong pains in the transplantation region, edema around it and a hypovolemic shock. The kidney was explanted and at the examination--necrosis of all papillae in it was established. Blood collection was found round the kidney. The same patient, after that incidence, suffered three successive severe gastrointestinal hemorrhages with shock that necessitated abundant blood transfusions. The cause was a small erosion, about the size of a millet, at the pyloric lumen, result from corticotherapy and favoured by the periodical heparinization during the following hemodialysis. The patient was reanimated and put again on a programmed chroniodialysis.


Promotion of evidence-based practice by professional nursing associations: literature review.
This paper reports a literature review examining the activities of professional nursing associations in the promotion of evidence-based practice. Professional nursing associations can play a role in the implementation and achievement of evidence-based practice as such associations aim to develop and further educate nurses professionally, build professional networks representing the interests of nurses and the nursing profession, influence the government and policymakers, and support and protect the basic values of nurses. The exact role of professional nursing associations in the promotion of evidence-based practice is as yet unclear, along with just how the role of such associations can be expanded and which strategies can be used to promote evidence-based practice among members. A literature and Internet search was undertaken using the PUBMED, CINAHL, SCIRUS, INVERT, and the Cochrane databases using the terms evidence-based practice(s)* or EBP*, which were then combined with Nursing Society*, Nursing Organization*, Nursing Organisation*, Nursing Association* or Nursing Council*. Other sources included a Google search of the Internet, and the sites of various members of the International Council of Nurses. Publications in English, French or German from 1993 to 2004 were used, and the Internet search was conducted on 17 July 2003. Sixty nursing associations described the dissemination of evidence-based practice using one or more types of activities (179 activities in total). All of these activities were of a voluntary nature, with a predominant focus (132/179 activities) on intrinsic motivation of nurses. More specifically, most of the activities were aimed at nurses' competences and attitudes in relation to evidence-based practice. Professional nurses' associations are active in promoting evidence-based practice among their nurse members, but only those focusing on changing competences and attitude by addressing intrinsic motivation are well used. Other types of activities deserve to be explored, including behaviour-oriented approaches, approaches using structural, social or financial influence measures and perhaps methods based on 'involuntary involvement'.


Anatomy of equine incisors: Pulp horns and subocclusal dentine thickness.
Equine incisors are often reduced in height during corrective dental procedures. Increased knowledge of subocclusal dentine thickness and pulp morphology may help prevent iatrogenic pulpar exposure. Although such data exist for equine cheek teeth, there are currently no reliable data for incisors. To measure the distances between pulp cavities and the occlusal as well as the labial surfaces of equine incisors and to test if these distances change with age. Furthermore, pulp morphology with regard to number and orientation of pulp horns was investigated. Observational study using cadaver material and high-resolution computed tomography. Upper and lower incisor arcades were removed from heads of 13 horses and scanned with high-resolution computed tomography. 3D Models were reconstructed and configuration as well as number of the pulp horns was evaluated. Anatomical marker points were set to measure distances between the pulp horn tips and the labial and occlusal surfaces. Subocclusal dentine thickness ranged between 1.5 and 11.7 mm in upper and 0.7 and 6.7 mm in lower incisors. It decreased with tooth age. Distance to labial aspect ranged between 3.5 and 9.0 mm in upper and 3.8 and 8.1 mm in lower incisors and increased with tooth age. Details of horse management, feeding and previous dental care were not available. Therefore, it remains unknown how these factors influenced the results. Although mean subocclusal dentine thickness of greater than 4.1 mm was found, equine incisors occasionally have less than 1 mm of thickness with potential for iatrogenic pulpar exposure during incisor reduction. Therefore, great care should be exercised by any practitioner during incisor reduction.


Valorization of Eggshell Biowaste for Sustainable Environmental Remediation.
The management of large amounts of eggshell waste annually produced in the world is problematic as generally this material is only disposed at landfills with odor production and microbial growth. On the contrary, significant environmental and economic advantages could be obtained transforming this biowaste into new value-added products. Eggshell biowaste was the starting material for the synthesis of hydroxyapatite by a simple and sustainable procedure and applied for the removal of Co2+ from aqueous solutions. The effects of contact time and initial metal concentration were investigated in batch experiments. Eggshell-based hydroxyapatite (ESHAP) before and after Co2+ removal was characterized by X-ray diffraction and scanning electron microscopy. The process was rapid and reached equilibrium within 80 min. The removal efficiency was in the range 70-80% which is generally higher than other waste-derived adsorbents. Adsorption of Co2+ on the surface of ESHAP particles and ion exchange with Ca2+ resulting in the formation of a Co-phosphate are the main mechanisms of the metal removal. The conversion of eggshell waste to a low-cost adsorbent for the treatment of metal contaminated waters could contribute to a more sustainable and effective management of this biowaste.


Cardiolipin Structure and Oxidation Are Affected by Ca2+ at the Interface of Lipid Bilayers.
Ca2+-overload contributes to the oxidation of mitochondrial membrane lipids and associated events such as the permeability transition pore (MPTP) opening. Numerous experimental studies about the Ca2+/cardiolipin (CL) interaction are reported in the literature, but there are few studies in conjunction with theoretical approaches based on ab initio calculations. In the present study, the lipid fraction of the inner mitochondrial membrane was modeled as POPC/CL large unilamellar vesicles (LUVs). POPC/CL and, comparatively, POPC, and CL LUVs were challenged by singlet molecular oxygen using the anionic porphyrin TPPS4 as a photosensitizer and by free radicals produced by Fe2+-citrate. Calcium ion favored both types of lipid oxidation in a lipid composition-dependent manner. In membranes containing predominantly or exclusively POPC, Ca2+ increased the oxidation at later reaction times while the oxidation of CL membranes was exacerbated at the early times of reaction. Considering that Ca2+ interaction affects the lipid structure and packing, density functional theory (DFT) calculations were applied to the Ca2+ association with totally and partially protonated and deprotonated CL, in the presence of water. The interaction of totally and partially protonated CL head groups with Ca2+ decreased the intramolecular P-P distance and increased the hydrophobic volume of the acyl chains. Consistently with the theoretically predicted effect of Ca2+ on CL, in the absence of pro-oxidants, giant unilamellar vesicles (GUVs) challenged by Ca2+ formed buds and many internal vesicles. Therefore, Ca2+ induces changes in CL packing and increases the susceptibility of CL to the oxidation promoted by free radicals and excited species.


Automated 16S Sequencing Using an R-Based Analysis Module for Bacterial Identification.
Sanger sequencing of the 16S rRNA gene is routinely used for the identification of bacterial isolates. However, this method is still performed mostly in more-specialized reference laboratories, and traditional protocols can be labor intensive. In this study, 99 clinical bacterial isolates were used to validate a fast, simplified, and largely automated protocol for 16S sequencing. The workflow combines real-time PCR of the first 500 bp of the bacterial 16S rRNA gene and amplicon sequencing on an automated, cartridge-based sequence analyzer. Sequence analysis, NCBI BLAST search, and result interpretation were performed using an automated R-based script. The automated workflow and R analysis described here produced results equal to those of manual sequence analysis. Of the 96 sequences with adequate quality, 90 were concordantly identified to the genus (n = 62) or species level (n = 28) compared with routine laboratory identification of the organism. One organism identification was discordant, and 5 resulted in an inconclusive identification. For sequences that gave a valid result, the overall accuracy of identification to at least the genus level was 98.9%. This simplified sequencing protocol provides a standardized approach to clinical 16S sequencing, analysis, and quality control that would be suited to frontline clinical microbiology laboratories with minimal experience. IMPORTANCE Sanger sequencing of the 16S rRNA gene is widely used as a diagnostic tool for bacterial identification, especially in cases where routine diagnostic methods fail to provide an identification, for organisms that are difficult to culture, or from specimens where cultures remain negative. Our simplified protocol is tailored toward use in frontline laboratories with little to no experience with sequencing. It provides a highly automated workflow that can deliver fast results with little hands-on time. Implementing 16S sequencing in-house saves additional time that is otherwise required to send out isolates/specimens for identification to reference laboratories. This makes results available much faster to physicians who can in turn initiate or adjust patient treatment accordingly.


The Magistrates Early Referral Into Treatment (MERIT) Pilot Program: a descriptive analysis of a court diversion program in rural Australia.
There has been a rapid expansion of drugs courts and diversion programs in Western countries, with the aim of diverting drug offenders into treatment. This study presents data from a rural pre-plea court-based diversion into treatment program for adult defendants appearing at a Local (Magistrate's) Court who have significant illicit drug problems. Unusual features include the intended duration of treatment (three months), and the emphasis on specialised caseworkers, who provide case management services, intensive individual counseling and group therapy sessions, and attend court, providing detailed legal reports. In the first two years, 238 participants were recruited to 266 program episodes. The participants were mostly recidivist offenders, with 61% having been previously imprisoned, and 85% having at least one prior conviction. Half the participants completed the program. Characteristics significantly associated with program completion were principal drug of concern (heroin/amphetamines vs. cannabis/other, OR = 0.4 [95% CI: 0.2, 0.7]), Aboriginality (Aboriginal vs. not, OR = 0.4 [95% CI: 0.2, 0.9]) and accommodation (privately owned vs. other, OR = 2.5 [95% CI: 1.3, 4.7]). Participants identified the caseworker support as the most important element of the program. We conclude that the program was successfully implemented, and that adequately supported skilled caseworkers were critical to its success.


An organized approach to the control of hazards to health at work.
Shell U.K. has an approach which facilitates the implementation of its occupational hygiene programme in its many locations. The main elements of the system are Company Policy, Standards, Methods and Management. The Policy sets the scene and is rigorous in its aims. The new COSHH legislation has emphasized particular duties which have influenced the approach. The Company Occupational Health Guidelines [Guidelines on Health at Work for Shell in the U.K. Shell U.K. Ltd, London (1989)] set the standards for control of exposure, among other things, and the Company adopts appropriate methods to achieve them. Of particular note is the Company's COSHH Programme [Implementation of the Shell U.K. Policy on the Control of Substances Hazardous to Health. Shell U.K. Ltd, London (1989)] which applies to all hazards to health (including physical and biological agents) in the workplace. Its introduction has been given full corporate support and is in the process of implementation. Appropriate procedures have been introduced for assessments of risk and for work histories. Guidance has been given on competence, reflecting a philosphy based on a team approach using local resources to the full, supported by corporate resources as required. The awards of the British Examining and Registration Board in Occupational Hygiene (1987) are used as the professional standard. Because of difficulties in obtaining basic hazard data, an internal core hazard data system (CHADS) [Core Hazard Data System. Shell U.K Ltd, London (1989)] has been introduced. The whole programme is managed through Occupational Hygiene Focal Points (OHFP) which represent local activities but also participate in corporate strategy. Through them the multidisciplinary approach is promoted, working in conjunction with local and sector Medical Advisers. Work done by the central Occupational Hygiene Unit is recorded and the reports are used for time management and recovery of costs. In its entirety, the approach is being used successfully to implement a comprehensive occupational hygiene programme in a diversified and dispersed industrial organization.


Functional analysis of the carboxy-terminal region of Bacillus subtilis TnrA, a MerR family protein.
The Bacillus subtilis TnrA transcription factor belongs to the MerR family of proteins and regulates gene expression during nitrogen-limited growth. When B. subtilis cells are grown with excess nitrogen, feedback-inhibited glutamine synthetase forms a protein-protein complex with TnrA that prevents TnrA from binding to DNA. The C-terminal region of TnrA is required for the interaction with glutamine synthetase. Alanine scanning mutagenesis of the C-terminal region of TnrA identified three classes of mutants that altered the regulation by glutamine synthetase. While expression of the TnrA-regulated amtB gene was expressed constitutively in the class I (M96A, Q100A, and A103G) and class II (L97A, L101A, and F105A) mutants, the class II mutants were unable to grow on minimal medium unless a complex mixture of amino acids was present. The class III tnrA mutants (R93A, G99A, N102A, H104A, and Y107A mutants) were partially defective in the regulation of TnrA activity. In vitro experiments showed that feedback-inhibited glutamine synthetase had a significantly reduced ability to inhibit the DNA-binding activity of several class I and class II mutant TnrA proteins. A coiled-coil homology model of the C-terminal region of TnrA is used to explain the properties of the class I and II mutant proteins. The C-terminal region of TnrA corresponds to a dimerization domain in other MerR family proteins. Surprisingly, gel filtration and cross-linking analysis showed that a truncated TnrA protein which contained only the N-terminal DNA binding domain was dimeric. The implications of these results for the structure of TnrA are discussed.