Calorimetric and spectroscopic studies of the effects of cholesterol on the thermotropic phase behavior and organization of a homologous series of linear saturated phosphatidylethanolamine bilayers.
Aqueous dispersions of cholesterol-containing phosphatidylethanolamine (PE) bilayers were examined by a combination of high-sensitivity differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) and 31P-nuclear magnetic resonance spectroscopy. Regardless of hydrocarbon chain length, the incorporation of low levels of cholesterol into these bilayers causes progressive reductions in the temperature, enthalpy and overall cooperativity of the lipid hydrocarbon chain-melting phase transition. Moreover, at low cholesterol levels, the heating and cooling thermograms observed for the cholesterol/PE binary mixtures are similar, indicating comparable levels of lateral miscibility of cholesterol with PE bilayers in the gel and liquid-crystalline states. However, at higher levels of cholesterol incorporation, marked differences between the heating and cooling thermograms are noted. Upon heating, complex multicomponent thermograms are observed in PE bilayers containing large amounts of cholesterol, and the temperature and overall enthalpy values increase discontinuously from the pattern of monotonic decrease observed at lower cholesterol levels. Moreover, these discontinuities begin to emerge at progressively lower cholesterol concentrations as PE hydrocarbon chain length increases. Upon cooling, a simpler pattern of thermotropic behavior is observed, and the measured temperature and enthalpy values continue to decrease monotonically with increases in cholesterol content. These results suggest that at higher concentrations cholesterol exhibits a decreased degree of lateral miscibility in the gel or crystalline as compared to the liquid-crystalline states of PE bilayers, particularly in the case of the longer-chain PEs. Our FTIR and 31P-nuclear magnetic resonance spectroscopic studies also show that the thermotropic events observed with mixtures of low cholesterol content are analogous to the gel/liquid-crystalline phase transitions exhibited by the pure PEs. However, lamellar crystalline phases readily form when mixtures of high cholesterol content are cooled to low temperatures. Moreover, these crystalline phases are spectroscopically indistinguishable from those formed by the pure PEs, indicating that cholesterol is excluded from such phases. Upon subsequent heating, the melting of these crystalline phases gives rise to the complex thermograms detected by DSC and to the discontinuities in the phase transition temperature and enthalpy noted above. This pattern of behavior differs markedly from that observed with the corresponding phosphatidylcholines (PCs), where comparable degrees of cholesterol miscibility are observed in the gel and liquid-crystalline states even at high cholesterol concentrations, and where cholesterol inhibits rather than facilitates the formation of lamellar crystalline phases. We also find that the presence of cholesterol does not result in the hydrophobic mismatch-dependent shifts in the phase transition temperature in PE bilayers previously observed in PC bilayers of varying thickness. We attribute these differences in the effects of cholesterol on phospholipid thermotropic phase behavior to stronger electrostatic and hydrogen bonding interactions at the surfaces of PE and compared to PC bilayers.


Early events in murine erythroleukemia cells induced to differentiate. Accumulation and gene expression of the transformation-associated cellular protein p53.
Oncogenes may play a crucial role in the genetic program of cellular differentiation; even, probably, at a very early stage in this program, which can be described as pre-commitment. We have investigated the variation in, and the control level of, the accumulation of the transformation-associated cellular protein p53 in murine erythroleukemia cells induced to differentiate by hexamethylene bisacetamide. Using flow cytofluorimetry after double staining of the cells, we have found that p53 decreased from two hours after the input of the inducer, to reach a basal level of about 30% of the starting value. The stability of the protein was found to be affected neither by the inducer nor by the position of the cells in the cell cycle. Looking for the regulation mechanism of the p53 decay, we found that the mRNA started to decrease as early as half an hour after the hexamethylene bisacetamide was put in the culture medium, and that the transcription rate of the gene itself could not account for the observed down-regulation of the mRNA, suggesting a post-transcriptional control for the mRNA accumulation. This control did not require the de-novo synthesis of a protein component, as shown by cycloheximide experiments, but seemed to be governed by the induced synthesis of an RNA molecule. Hypothetical models for such a regulation process are discussed in the light of recent reports on the metabolism of mRNA.


Potential preventive effects of a new visual intervention for accommodative insufficiency and asthenopia due to sustained near task.
The objective of this study was to experimentally investigate whether a new visual intervention with optical and binocular vergence demands prevents accommodative insufficiency and asthenopia after sustained periods of visual task. Fourteen female students were given the intervention with optical and binocular vergence demands for 1.5 min immediately after 20 min of a sustained task on a three-dimensional display. Before and after the trial, their ocular functions were measured and their symptoms assessed. A new type of intervention was developed that can vary optical and binocular vergence demands. For control, the subjects rested with eyes closed for 1.5 min after the task instead of the intervention. In the control group, accommodative contraction time (from far to near) and accommodative relaxation time (from near to far) was delayed from 1.13 to 1.68 s and from 1.36 to 1.60 s, respectively, and the symptom of asthenopia increased after rest. In the intervention group, however, changes in those functions were smaller than those in the control group. These results suggest that the new intervention with optical and binocular vergence demands is effective for the treatment of accommodative insufficiency that follows sustained periods of visual task, and consequently, the symptom of asthenopia induced by accommodative insufficiency may decrease.


Sex-specific risk profiles for substance use among college students.
Growing evidence indicates sex and gender differences exist in substance use. Framed by a lifecourse perspective, we explored prospectively by sex the effects of distal and proximal factors on the initiation of drug use in college. College students without prior drug use (n = 5,120 females; n = 2,951 males) were followed longitudinally across 4 years. Analyses were estimated as a multigroup survival analysis separately by sex within a latent variable SEM framework with illicit drug use (6 or more times in past year) as the latent factor. More males initiated drug use (8.5%) than females (6.4%, χ2 (1) = 10.351, p = .001), but less so for Black males (AOR 0.33, 95% CI [0.18, 0.60]) and females (0.35 [0.23, 0.54]). Students initiating drug use more likely included students smoking cigarettes at baseline (males 1.40 [1.23, 1.59]; females 1.43 [1.24, 1.64]), using alcohol (males 1.04 [1.02, 1.06]; females 1.04 [1.02, 1.06]), or having cannabis using peers (males 1.79 [1.52, 2.11]; females 1.70 [1.49, 1.93]). Impulsivity domain associations differed by sex [negative urgency: females (1.23 [1.02, 1.49) and sensation seeking: males (1.33 [1.01, 1.75])]. History of unwanted/uncomfortable sexual experience predicted drug use for males (1.60 [1.09, 2.35]) and females (1.95 [1.45, 2.62]) but physical assault only for females (1.45 [1.08, 1.94]). Mood symptoms predicted drug use only for males [depression (0.73 [0.56, 0.95]); anxiety (1.40 [1.04, 1.89])]. Risk factors for initiating drug use during college differ by sex. As substance use during early age predisposes one for addiction, sex- and gender-informed interventions for young adults are needed.


Distribution of exudated FITC-dextrans in experimental vasogenic brain edema produced by a focal cryogenic injury.
Mice were subjected to cortical cryogenic brain injury, and FITC-dextrans (mol. wt. 20,000 or 150,000) were injected intravenously (i.v.). After a survival period of 4 h the distribution of the FITC-dextrans was determined by a histotechnical procedure described recently ( Hultstr öm et al. 1982a ). This technique is based on freeze-drying and vapor fixation to immobilize the tracer and to provide tissue fixation. In and around the cryogenic injury both tracers leaked out of the cortical and the leptomeningeal vessels and spread into the brain parenchyma. They were seen as multiple, closely apposed droplets of fluorescent material best recognized by fluorescence microscopy under high magnification. The tracers were also taken up by neuronal perikarya and in glial cell nuclei of, presumably, astrocytic origin. Our study shows that the FITC-dextran technique can be used for experimental studies on the vasogenic form of brain edema. The patterns formed by the extravasated tracers have qualitative similarities to those produced by other more commonly used tracers, such as fluorochrome-labeled serum proteins and peroxidase.


Monoclonal Antibodies for the Treatment of Nasal Polyps.
Biologics are novel therapeutic medications developed for the targeted therapy for a variety of inflammatory conditions. The biologics currently investigated for the treatment of chronic rhinosinusitis (CRS) with nasal polyps modulate specific inflammatory pathways involved in the pathogenesis of disease. Investigations have focused on the most severe form of the disease, namely, CRS with nasal polyps. It is hoped that specific targeted therapies using these biologics can significantly modulate the immune system, offering both disease control and symptomatic relief. This review summarizes those therapies that have been used to treat nasal polyps.


Can drug screening lead to candidate therapies for testing in diabetic neuropathy?
A key mechanism of dorsal root ganglia (DRG) neuron injury in high glucose is mitochondrial overload leading to oxidative stress. We screened selected compounds for the ability to prevent hyperglycemia-induced mitochondrial superoxide in primary sensory DRG neurons. Twenty five out of 1,040 compounds decreased both mitochondrial superoxide and subsequent neuronal injury. These data both validate our screening strategy and indicate further mechanistic evaluation of drug hits and related compounds. Such studies may lead to the design of rational therapeutic approaches for this severe complication of diabetes.


Long non-coding RNAs: Emerging regulators for chemo/immunotherapy resistance in cancer stem cells.
Cancer stem cells (CSCs) are a small subpopulation of tumor cells critical for tumor development. Their unique abilities, such as self-renewal, have resulted in tumor resistance to various cancer treatments, including traditional chemotherapy and latest immunotherapy. CSCs-targeting therapy is a promising treatment to overcome the therapeutic resistances to different tumors. However, despite their significance, the regulatory mechanism generating therapy-resistant CSCs is still obscure. Long non-coding RNAs (lncRNAs) are key regulators in various biological processes, including cell proliferation, apoptosis, migration, and invasion. Recent studies have revealed that lncRNAs play an important role in the therapeutic resistance of CSCs. Here we summarize the latest studies on the regulatory role of lncRNAs in sustaining the stemness of CSCs, and discuss the associated mechanisms behind these behavior changes in CSCs-related chemo- and immune-resistance. Future research implications are also discussed, shedding light on the potential CSCs-targeted strategies to break through the resistance of current therapies.


XRCC1 genetic polymorphisms and bladder cancer susceptibility: a meta-analysis.
To examine the association between three x-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms (Arg(194)Trp, Arg(280)His, and Arg(399)Gln) and bladder cancer susceptibility. A comprehensive search was conducted to identify all case-control studies of XRCC1 polymorphisms and bladder cancer risk. Statistical analysis was performed with the software program Review Manage, version 4.2. A total of 10 eligible reports, including 3749 cases and 3947 controls, were identified. For Arg(194)Trp (six studies, 3091 cases, 3219 controls), no evidence indicated that individuals carrying the variant genotypes (Trp/Trp + Arg/Trp), relative to those carrying the wild homozygote Arg/Arg genotype, had a decreased risk of bladder cancer (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.77 to 1.05; P = 0.17). For Arg(280)His (three studies, 2547 cases, 1784 controls), individuals with His/His+Arg/His genotypes had no significant risk of bladder cancer, compared with those with the Arg/Arg genotype (OR 0.99, 95% CI 0.55 to 1.77; P = 0.97). For Arg(399)Gln (10 studies, 3729 cases, 3927 controls), the Gln/Gln genotype carriers did not have a decreased cancer risk compared with those individuals with the Arg/Arg genotype (OR 0.95, 95% CI 0.82 to 1.10; P = 0.48). Similarly, no associations were found in the recessive and dominant modeling (Gln/Gln versus Arg/Gln+Arg/Arg: OR 0.92, 95% CI 0.80 to 1.05; P = 0.23; Arg/Gln+Gln/Gln versus Arg/Arg: OR 1.04, 95% CI 0.95 to 1.14; P = 0.36). No association was found between the polymorphisms in XRCC1 (Arg(194)Trp, Arg(280)His, Arg(399)Gln) and bladder cancer susceptibility.


[Wenyang Huoxue Recipe up-regulates the expression of angiopoietin-1 mRNA in rats with chronic aristolochic acid nephropathy].
To investigate the effects of Wenyang Huoxue Recipe (WRHXR), a compound traditional Chinese herbal medicine for warming yang and promoting blood flow, on the expression of angiopoietin mRNA in rats with chronic aristolochic acid nephropathy induced by Caulis Aristolochia Manshuriensis (CAM) decoction, and to explore the protection mechanism of WYHXR against kidney damage. Twenty-eight male SD rats were randomly divided into normal control group, CAM group and WYHXR-treated group. Rats in the normal control group (n=8) and CAM group (n=10) were intragastrically administered with normal saline 10 ml/(kg.d) or CAM decoction 10 ml/(kg.d) respectively. Rats in the WYHXR-treated group (n=10) were intragastrically administered with WYHXR 30 g/(kg.d) and CAM decoction 10 ml/(kg.d). The expressions of Ang-l and Ang-2 mRNAs were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) after 20-week treatment. Compared with the normal control group, the expression of Ang-l mRNA was significantly decreased, and the expression of Ang-2 mRNA was significantly increased in the CAM group (P<0.01). Compared with the CAM group, the expression of Ang-l mRNA was increased in the WYHXR-treated group (P<0.01). The expression of Ang-2 mRNA had no significant difference between the CAM group and the WYHXR-treated group (P>0.05). Renal pathology showed that renal damage in WYHXR-treated group was significantly reduced as compared with the CAM group. WYHXR can up-regulate the expression of Ang-l mRNA, which may be its action mechanism in protecting the kidneys.


Impaired cognitive control moderates the relation between the attribution of incentive salience and severity of consumption in patients with methamphetamine dependence.
Cognitive control and the attribution of incentive salience are two key neuropsychological processes proposed to explain substance use disorder (SUD). However, little is known about how they interact to influence the severity of drug use in people with SUD. To determine if cognitive control exerts a moderating effect on the relation between the attribution of salience to drug/reward-related cues and the severity of drug use in SUD cases. Sixty-nine SUD cases with methamphetamine as the main drug of consumption were selected and evaluated. Participants performed the Stroop, Go/No-Go, and Flanker tasks to identify a latent cognitive control factor, and the Effort-Expenditure for Reward task, as well as answering the Methamphetamine Incentive Salience Questionnaire to measure the attribution of incentive salience. Severity of drug use was determined by the KMSK scale and an exploratory clinical interview. As expected, higher incentive salience attribution predicted greater severity of methamphetamine use. Unexpectedly, however, we found a moderating effect of impaired cognitive control on the relations between higher incentive salience scores and higher monthly drug use, and between younger age at onset of systematic drug use and higher incentive salience scores. Results show the moderating role of cognitive control on the relation between incentive salience attribution and severity of drug use in SUD cases, and help explain the chronic, relapsing nature of addiction, knowledge necessary to develop more precise prevention and treatment strategies.


Association between social vulnerability profiles, prenatal care use and pregnancy outcomes.
Evaluating social vulnerability is a challenging task. Indeed, former studies demonstrated an association between geographical social deprivation indicators, administrative indicators, and poor pregnancy outcomes. To evaluate the association between social vulnerability profiles, prenatal care use (PCU) and poor pregnancy outcomes (Preterm birth (PTB: <37 gestational weeks (GW)), small for gestational age (SGA), stillbirth, medical abortion, and late miscarriage). Retrospective single center study between January 2020 and December 2021. A total of 7643 women who delivered a singleton after 14 GW in a tertiary care maternity unit were included. Multiple component analysis (MCA) was used to assess the associations between the following social vulnerabilities: social isolation, poor or insecure housing conditions, not work-related household income, absence of standard health insurance, recent immigration, linguistic barrier, history of violence, severe dependency, psychologic vulnerability, addictions, and psychiatric disease. Hierarchical clustering on principal component (HCPC) from the MCA was used to classify patients into similar social vulnerability profiles. Associations between social vulnerability profiles and poor pregnancy outcomes were tested using multiple logistic regression or Poisson regression when appropriate. The HCPC analysis revealed 5 different social vulnerability profiles. Profile 1 included the lowest rates of vulnerability and was used as a reference. After adjustment for maternal characteristics and medical factors, profiles 2 to 5 were independently associated with inadequate PCU (highest risk for profile 5, aOR = 3.14, 95%CI[2.33-4.18]), PTB (highest risk for profile 2, aOR = 4.64, 95%CI[3.80-5.66]) and SGA status (highest risk for profile 5, aOR = 1.60, 95%CI[1.20-2.10]). Profile 2 was the only profile associated with late miscarriage (adjusted incidence rate ratio (aIRR) = 7.39, 95%CI[4.17-13.19]). Profiles 2 and 4 were independently associated with stillbirth (highest association for profile 2 (aIRR = 10.9, 95%CI[6.11-19.99]) and medical abortion (highest association for profile 2 (aIRR = 12.65, 95%CI[5.96-28.49]). This study unveiled 5 clinically relevant social vulnerability profiles with different risk levels of inadequate PCU and poor pregnancy outcomes. A personalized patient management according to their profile could offer better pregnancy management and reduce adverse outcomes.


Relationship between imidazoline and alpha2-adrenoceptors involved in the sympatho-inhibitory actions of centrally acting antihypertensive agents.
Since the first suggestion of the existence of imidazoline receptors, there has been a continuing and yet unresolved debate as to their contribution to the antihypertensive actions of clonidine-like agents. In this review we bring together a number of studies from our laboratory which have examined the importance and interdependence of imidazoline receptors and alpha2-adrenoceptors in the mechanism of action of centrally acting antihypertensive drugs. Using conscious rabbits and a range of imidazoline and specific alpha2-adrenoceptor antagonists we have consistently found that second generation agents rilmenidine and moxonidine preferentially act via imidazoline receptors but that alpha2-adrenoceptors are important for the hypotension produced by clonidine and alpha-methyldopa. Despite this difference in receptor mechanism, the hypotension produced by all these drugs is dependent on central noradrenergic pathways. In other studies using anaesthetised rabbits and direct measures of sympathetic nerve activity we confirmed the generally held view that the major site of sympatho-inhibitory actions and sympathetic baroreflex effects of centrally acting antihypertensive agents is the rostral ventrolateral medulla (RVLM). We also found, using microinjection of specific antagonists, that alpha2-adrenoceptors in this nucleus appear to be activated as a consequence of imidazoline receptor activation. Thus, there appears to be a close relationship between imidazoline receptors and alpha2-adrenoceptors located in the RVLM in mediating the hypotension and inhibition of renal sympathetic nerve activity. Furthermore in recent studies using a noradrenergic neurotoxin microinjected into the RVLM we found that this treatment selectively blocked the actions of moxonidine but not clonidine, suggesting that I1-imidazoline receptors may be located on adrenergic terminals in situ. By contrast, clonidine acts predominantly via alpha2-adrenoceptors, perhaps located on cell bodies in the nucleus. We conclude that there is indeed a close nexus between 'presynaptic' imidazoline receptors on noradrenergic terminals and 'downstream' alpha2-adrenoceptors within the RVLM. Our hypothesis brings together opposing points of view that the mechanism for hypotension must involve either the imidazoline receptor or the alpha2-adrenoceptor. Clearly both are important.


Epigenetic basis and targeting of cancer metastasis.
Despite the development of novel therapeutic approaches and improved clinical management, survival from metastatic disease remains poor. Indeed, metastasis accounts for the vast majority of cancer-related deaths. The metastatic cascade comprises a complex range of molecular events that cannot be explained by genetic aberrations alone; dynamic, epigenetic regulatory mechanisms are now being implicated as key drivers of successful metastasis. With the emergence of CRISPR-based epigenomic editing, it is now possible to investigate the direct role of locus-specific epigenetic alterations in metastatic progression. Here, we review the role of epigenetic mechanisms in cancer metastasis, explore recent developments in technologies for epigenomic investigation, and highlight the emerging applications of epigenomic editing technologies in the clinical management of cancer.


The impact of cerebrovascular risk factors on postoperative memory decline in patients with left temporal lobe epilepsy.
Cerebrovascular risk factors (CVRFs) and comorbid cardiovascular and metabolic disease have been linked to accelerated cognitive aging and dementia in the general population; however, the contribution of these comorbidities to the risk of post anterior temporal lobectomy (ATL) memory decline has been unexamined. We explored the effects of CVRFs on postoperative verbal memory decline in a cohort of 22 patients with left temporal lobe epilepsy (LTLE) who completed pre- and one-year postsurgical neuropsychological testing. Diagnoses of interest included preoperative cardiovascular and metabolic disorders, as well as CVRFs [pulse pressure proxy, body mass index (BMI), and fasting glucose]. Twenty-three percent of patients had a history of cardiovascular disease, 9% of metabolic disorders, and 38% had a BMI indicating overweight or obese status. Higher preoperative BMI and glucose were associated with greater decline in verbal memory. The association between BMI and memory decline remained significant after controlling for age and left hippocampal volume. These findings suggest that modifiable health-related risk factors, including CVRFs, may impact the risk of postoperative cognitive decline, and that BMI in particular could be an important factor to consider and/or target for intervention early in clinical care to protect cognitive health.


Monitoring and spatial traceability of river water quality using Sentinel-2 satellite images.
Due to limited monitoring stations along rivers, it is difficult to trace the specific locations of high pollution areas along the whole river by traditionally in situ measurement. High-spatiotemporal-resolution Sentinel-2 satellite images make it possible to routinely monitor and trace the spatial distributions of river water quality if reliable retrieval algorithms are available. This study took seven major rivers (Qiantang River (QTR), Cao'e River (CEJ), Yongjiang River (YJ), Jiaojiang River (JJ), Oujiang River (OJ), Feiyun River (FYR), and Aojiang River (AJ)) in Zhejiang Province, China, as examples to illustrate the spatial traceability of river water quality parameters (permanganate index (CODMn), total phosphorus (TP), and total nitrogen (TN)) from Sentinel-2 satellite images. The regional retrieval models established for these parameters (CODMn, TP and TN) provided correlation coefficients (R) of 0.68, 0.82, and 0.7, respectively. Based on these models, time-series CODMn, TP, and TN products were obtained for the seven rivers from 2016 to 2021 from Sentinel-2 satellite images, and the results show that the CODMn, TP and TN were high downstream and low upstream; exceptions the CEJ, which was slightly higher in the middle reach than other reaches, and the TN in YJ, which was higher upstream than downstream. The downstream reaches were the main areas suffering from relatively high values in most seasons. Except for the springtime TN level in CEJ, the high value areas were located along the middle reaches. In summer and autumn, the high TN areas in JJ, OJ, and AJ were located along the middle and lower reaches, and the TN in YJ was highest in the upstream. More importantly, this study revealed that the specific locations of high pollution areas along rivers can be effectively traced using Sentinel-2 satellite images, which would be helpful for precise water quality control of rivers.


Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4.
Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders.


Relationship of clinical and aerobiological pollen data in the north-west of Spain.
few studies report clinical and aerobiological pollen data in the north-west of Spain, a region similar to northern and central Europe. Moreover, it is difficult to obtain patients' collaboration in filling out symptom cards. The aim of this study was to establish a relationship between pollen types and clinical data obtained through questionnaire and telephone calls. from January to December 2000, 24 patients aged 28 10.6 years and allergic to pollens were studied. The seasonal and hourly rhythm of symptoms and their intensity were obtained monthly by telephone calls. Atmospheric pollen was collected over the same period using a Hirst-type volumetric pollen sampler. the most important pollen types recorded were Poaceae, Betula, Parietaria and Plantago. Most patients (83 %) showed symptoms during March and in the period between May and July (99 %), which coincided with the greatest quantity of atmospheric pollen. Fifty-six percent of the patients complained of symptoms during the first hours of the morning, 63 % during the central hours of the day and 22 % at nightfall. In specific sensitizations, symptoms were more evident during the hours of maximum atmospheric levels of their taxa. the method employed in the present study to obtain information on patients' symptomatology (telephoning their homes once a month) proved useful and revealed a clear relationship between the presence of certain pollens in the atmosphere and the development of symptoms.


Metal induction of haem oxygenase without concurrent degradation of cytochrome P-450. Protective effects of compound SKF 525A on the haem protein.
The induction of hepatic haem oxygenase (EC 22.214.171.124) by a series of metals, organometals and metalloporphyrins was examined in vivo in the presence of compound SKF 525A, which is known to complex with the prosthetic group of cytochrome P-450. Concurrent administration of SKF 525A and an inducing metal did not affect the extent and time course of haem oxygenase induction. The decrease in cytochrome P-450 content normally associated with metal administration was, however, prevented, indicating that haem oxygenase induction by metals can proceed without the significant labilization of the haem moiety of cytochrome P-450. In addition, the integrity of this haem protein can be maintained by chemical means in the presence of sustained high activities of haem oxygenase.


Differential impact of statin on new-onset diabetes in different age groups: a population-based case-control study in women from an asian country.
Statins reduce cardiovascular risks but increase the risk of new-onset diabetes (NOD). The aim of this study is to determine what effect, if any, statins have on the risk of NOD events in a population-based case-control study. An evaluation of the relationship between age and statin-exposure on NOD risks was further examined in a female Asian population. In a nationwide case-controlled study, the authors assessed 1065 female NOD patients and 10650 controls with matching ages, genders and physician visit dates. The impact of statin-exposure on NOD was examined through multiple logistic regression models. Subgroup analysis for exploring the risk of NOD and statin-exposure in different age groups was performed. Statin-exposure was statistically significantly associated with increased new-onset diabetes risks using multivariate analysis. Interaction effect between age and statin-exposure on NOD risk was noted. For atorvastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted odds ratio [OR], 8.0; 95% confidence interval [CI], 2.57-24.90). For rosuvastatin, the risk of cDDDs>60 was highest among the 40-54 year-olds (adjusted OR, 14.8; 95% CI, 2.27-96.15). For simvastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted OR, 15.8; 95% CI, 5.77-43.26). For pravastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted OR, 14.0; 95% CI, 1.56-125.18). This population-based study found that statin use is associated with an increased risk of NOD in women. The risk of statin-related NOD was more evident for women aged 40-64 years compared to women aged 65 or more, and was cumulative-dose dependent. The use of statins should always be determined by weighing the clinical benefits and potential risks for NOD, and the patients should be continuously monitored for adverse effects.


Atomic structure of a thin silica film on a Mo(112) substrate: a two-dimensional network of SiO4 tetrahedra.
The structure of a thin single crystalline SiO(2) film grown on Mo(112) has been studied by scanning tunneling microscopy, infrared reflection absorption spectroscopy, and x-ray photoelectron spectroscopy. In excellent agreement with the experimental results, density functional theory calculations show that the film consists of a two-dimensional network of corner sharing [SiO(4)] tetrahedra, with one oxygen of each tetrahedron binding to the protruding Mo atoms of the Mo(112) surface.


Trans-epithelial fluid flow and mechanics of epithelial morphogenesis.
Active fluid transport across epithelial monolayers is emerging as a major driving force of tissue morphogenesis in a variety of healthy and diseased systems, as well as during embryonic development. Cells use directional transport of ions and osmotic gradients to drive fluid flow across the cell surface, in the process also building up fluid pressure. The basic physics of this process is described by the osmotic engine model, which also underlies actin-independent cell migration. Recently, the trans-epithelial fluid flux and the hydraulic pressure gradient have been explicitly measured for a variety of cellular and tissue model systems across various species. For the kidney, it was shown that tubular epithelial cells behave as active mechanical fluid pumps: the trans-epithelial fluid flux depends on the hydraulic pressure difference across the epithelial layer. When a stall pressure is reached, the fluid flux vanishes. Hydraulic forces generated from active fluid pumping are important in tissue morphogenesis and homeostasis, and could also underlie multiple morphogenic events seen in other developmental contexts. In this review, we highlight findings that examined the role of trans-epithelial fluid flux and hydraulic pressure gradient in driving tissue-scale morphogenesis. We also review organ pathophysiology due to impaired fluid pumping and the loss of hydraulic pressure sensing at the cellular scale. Finally, we draw an analogy between cellular fluidic pumps and a connected network of water pumps in a city. The dynamics of fluid transport in an active and adaptive network is determined globally at the systemic level, and transport in such a network is best when each pump is operating at its optimal efficiency.


The effects of fenclozic acid on fertility of male rats.
Fenclozic acid, a prostaglandin synthesis inhibitor, was administered to male rats by stomach intubation. A second group of rats received the vehicle (1% methylcellulose) alone. The dose schedule used was 75 mg/kg on day 1, 50 mg/kg on day 2 and 25 mg/kg on days 3, 4 and 5. The dose was progressively reduced to eliminate the toxic effects seen in the initial stages of the treatment. All the animals had normal fertility and libido before treatment and during administration of the vehicle. However, sterility or subfertility was seen in 4 of the 6 animals treated with fenclozic acid. Sperm were always present in the vaginal smears. It was concluded that the reduction in fertility was probably caused by an effect of the drug on maturation or metabolism of the sperm.


Description of two new HLA alleles: HLA-DRB1*09:01:12 and HLA-DRB1*09:49.
Compared to HLA-DRB1*09:01:02:01, the alleles HLA-DRB1*09:01:12 and HLA-DRB1*09:49 each show one nucleotide substitution, respectively.


PGC-1α prevents apoptosis in adipose-derived stem cells by reducing reactive oxygen species production in a diabetic microenvironment.
To examine whether overexpression of peroxisome proliferator activated receptor-gamma coactivator-1 alpha (PGC-1α) can prevent apoptosis in adipose-derived stem cells (ASCs) by reducing reactive oxygen species (ROS) production and enhancing mitochondrial function in a diabetic environment. After the isolation, expansion and characterisation of rat ASCs, we overexpressed PGC-1α in ASCs using an adenoviral vector encoding green fluorescent protein (GFP) or PGC-1α and tested the apoptotic effect under conditions of high glucose, hypoxia and serum deprivation. The production of intracellular ROS and mitochondrial ROS was evaluated using dihydroethidium and CM-H2XRos fluorescent probes. Under conditions of high glucose, hypoxia and serum deprivation, the overexpression of PGC-1α in ASCs decreased apoptosis and led to an increased survival rate. The ASCs modified with PGC-1α produced lower intracellular and mitochondrial ROS. The mitochondrial morphology and structure in the PGC-1α-ASC group remained relatively complete compared with the control group. These results reveal a crucial protective role for PGC-1α in the treatment of diabetes mellitus and its complications using stem cells therapy.


Changes in computed tomography values of mandibular condyle and temporomandibular joint disc position after sagittal split ramus osteotomy.
The purpose of this study was to evaluate change in computed tomography (CT) value of condyle and temporomandibular joint (TMJ) disc position after sagittal split ramus osteotomy (SSRO) setback surgery, retrospectively. The subjects were 76 patients (152 condyles) who underwent bilateral SSRO setback surgery. They were divided into 2 groups (43 symmetric patients and 33 asymmetric patients). CT values (pixel values) of 5 sites of the condyle and condylar width, length, horizontal angle were measured pre-operatively and 1 year post-operatively. Disc position was classified as anterior disc displacement, anterior type, fully covered type and posterior type, preoperatively and postoperatively using magnetic resonance imaging (MRI). In maximum CT value at the center of the condyle, post-operative value was significantly lower than pre-operative value bilaterally (Deviation side: P = 0.0003, Non-deviation side: P = 0.0003) in asymmetry group. In minimum CT value at the center of the condyle, the post-operative value was significantly lower than the pre-operative value bilaterally (Deviation side: P = 0.0309, Non-deviation side: P = 0.0004) in the symmetry group. With regard to maximum CT value at the lateral site of the condyle in the deviation side, the value for the anterior disc displacement group was significantly larger than that of the posterior type pre-operatively (P = 0.0123). CT value of the anterior disc displacement group was significantly larger than those of some other areas pre- and post-operatively (P < 0.05). This study suggested that CT value of condylar bone changes after 1 year in SSRO and anterior disc displacement may partially affect the CT value of the condyle in the TMJ in mandibular prognathism patients.


Predictive information processing in music cognition. A critical review.
Expectation and prediction constitute central mechanisms in the perception and cognition of music, which have been explored in theoretical and empirical accounts. We review the scope and limits of theoretical accounts of musical prediction with respect to feature-based and temporal prediction. While the concept of prediction is unproblematic for basic single-stream features such as melody, it is not straight-forward for polyphonic structures or higher-order features such as formal predictions. Behavioural results based on explicit and implicit (priming) paradigms provide evidence of priming in various domains that may reflect predictive behaviour. Computational learning models, including symbolic (fragment-based), probabilistic/graphical, or connectionist approaches, provide well-specified predictive models of specific features and feature combinations. While models match some experimental results, full-fledged music prediction cannot yet be modelled. Neuroscientific results regarding the early right-anterior negativity (ERAN) and mismatch negativity (MMN) reflect expectancy violations on different levels of processing complexity, and provide some neural evidence for different predictive mechanisms. At present, the combinations of neural and computational modelling methodologies are at early stages and require further research.


Inhibitory effect of cyanide on wastewater nitrification determined using SOUR and RNA-based gene-specific assays.
The effect of cyanide (CN(-) ) on nitrification was examined with samples from nitrifying bacterial enrichments using two different approaches: by measuring substrate (ammonia) specific oxygen uptake rates (SOUR), and by using RT-qPCR to quantify the transcripts of functional genes involved in nitrification. The nitrifying bioreactor was operated as a continuous reactor with a 24 h hydraulic retention time. The samples were exposed in batch vessels to cyanide for a period of 12 h. The concentrations of CN(-) used in the batch assays were 0·03, 0·06, 0·1 and 1·0 mg l(-1) . There was considerable decrease in SOUR with increasing dosages of CN(-) . A decrease of more than 50% in nitrification activity was observed at 0·1 mg l(-1) CN(-) . Based on the RT-qPCR data, there was notable reduction in the transcript levels of amoA and hao for increasing CN(-) dosage, which corresponded well with the ammonia oxidation activity measured via SOUR. The inhibitory effect of cyanide may be attributed to the affinity of cyanide to bind ferric haeme proteins, which disrupt protein structure and function. The correspondence between the relative expression of functional genes and SOUR shown in this study demonstrates the efficacy of RNA-based function-specific assays for better understanding of the effect of toxic compounds on nitrification activity in wastewater. The effect of cyanide on nitrifying bacteria was characterized by measuring physiological and transcriptional response. Cyanide was inhibitory to nitrification at concentrations that may be found in industrial waste. The RNA-based function-specific assays represent a mechanistic approach for better understanding the effect of toxic compounds on nitrification activity in wastewater. Moreover, the relative abundance of RNA transcripts can be used to closely track in situ nitrifying bacterial activity which can be used to predict inhibition events, thereby providing a metric to potentially improve performance of wastewater nitrifying systems.


Comparing sports vision among three groups of soft tennis adolescent athletes: Normal vision, refractive errors with and without correction.
The effect of correcting static vision on sports vision is still not clear. To examine whether sports vision (depth perception [DP], dynamic visual acuity [DVA], eye movement [EM], peripheral vision [PV], and momentary vision [MV],) were different among soft tennis adolescent athletes with normal vision (Group A), with refractive error and corrected with (Group B) and without eyeglasses (Group C). A cross-section study was conducted. Soft tennis athletes aged 10-13 who played softball tennis for 2-5 years, and who were without any ocular diseases and without visual training for the past 3 months were recruited. DPs were measured in an absolute deviation (mm) between a moving rod and fixing rod (approaching at 25 mm/s, receding at 25 mm/s, approaching at 50 mm/s, receding at 50 mm/s) using electric DP tester. A smaller deviation represented better DP. DVA, EM, PV, and MV were measured on a scale from 1 (worse) to 10 (best) using ATHLEVISION software. Chi-square test and Kruskal-Wallis test was used to compare the data among the three study groups. A total of 73 athletes (37 in Group A, 8 in Group B, 28 in Group C) were enrolled in this study. All four items of DP showed significant difference among the three study groups (P = 0.0051, 0.0004, 0.0095, 0.0021). PV displayed significant difference among the three study groups (P = 0.0044). There was no significant difference in DVA, EM, and MV among the three study groups. Significant better DP and PV were seen among soft tennis adolescent athletes with normal vision than those with refractive error regardless whether they had eyeglasses corrected. On the other hand, DVA, EM, and MV were similar among the three study groups.


Simultaneous determination of Ciprofloxacin and the active metabolite of Prulifloxacin in aqueous human humor by high-performance liquid chromatography.
A rapid and simple method for determining two fluoroquinolones (FQNs), namely Ciprofloxacin and Ulifloxacin, this being the last active metabolite of Prulifloxacin, in aqueous human humor (AHH) has been developed and validated. The calibration data resulted linearly correlated in the 4-500 ng/mL concentration range with 8 ng/mL lower limit of quantification (LLOQ) for Ciprofloxacin, and 5-600 ng/mL concentration range with 6 ng/mL LOD for Ulifloxacin. The proposed analytic procedure has been validated by testing quality control sample (QCS) of AHH probed with the two FQNs at 10, 50, 500, and 1000 ng/mL concentration values. Validation of the method has been checked by accuracy and precision data of intra-day and long-term experiments. The two FQN concentrations have been measured by HPLC technique with UV detection at 278-nm wavelength for the AHH of patients to whom were supplied oral doses of FQNs (500 mg) twice in a day, within 1-24h before the surgery intervention of cataract. The average concentration of Ciprofloxacin resulted 186 ng/mL and that of Ulifloxacin 78 ng/mL. The nice quality of the proposed analytic procedure means that it may be suitable for in vivo studies of pharmacokinetics regarding these substances in the AHH medium.


Psychiatric screening in the emergency department: its effect on physician behavior.
The purpose of our prospective, controlled study was to determine whether providing the results of a psychiatric screening instrument, the General Health Questionnaire (GHQ), to emergency physicians would result in a change in the detection and management of patients with psychosocial problems. Five hundred ninety-nine emergency department patients were enrolled, 242 in the control and 357 in the intervention group. Noncritical patients, selected by presenting complaint, were given the GHQ to complete before physician evaluation; those whose GHQ scores were high (10 or higher) were identified as having a greater likelihood of having psychosocial problems. During the intervention phase, physicians were provided the patient's GHQ score before beginning their evaluation, as well as a specific mechanism for psychosocial referral. A significantly greater proportion of patients with high GHQ scores in both study groups were judged by physicians to have a psychiatric problem (P less than .0001). During the intervention phase, patients with high scores more frequently were assigned a psychiatric diagnosis (14.1% vs 7.7%) and received psychosocial referral (36.1% vs 5.7%). However, only the latter difference was statistically significant (P less than .0001). The majority (85.7%) of patients offered psychosocial referral accepted their referral. There was no difference in the number of laboratory tests ordered or medical/surgical referrals requested between patients in the control or intervention groups with high scores. Therefore, providing GHQ results to emergency physicians led to more frequent psychiatric diagnoses and psychosocial referrals of patients with high GHQ scores but did not alter their medical management.


DLL3 expression in large cell neuroendocrine carcinoma (LCNEC) and association with molecular subtypes and neuroendocrine profile.
For stage IV pulmonary large cell neuroendocrine carcinoma (LCNEC), the only therapeutic option is palliative chemotherapy. DLL3 is a new therapeutic target, which seems to be often expressed in SCLC and LCNEC. It has recently been reported that DLL3 mRNA expression is particularly upregulated in the LCNEC subgroup with STK11/KEAP1 and TP53 co-mutations, in contrast to lower expression levels in RB1 and TP53 co-mutated LCNEC. Our aim was to investigate DLL3 protein expression in stage IV LCNEC and correlate data with mutational profiles (i.e.STK11/KEAP1/RB1), immunostaining results (pRb, NE markers) and clinical characteristics. Immunohistochemical analysis for DLL3 (SC16.65) and ASCL1 (SC72.201) was performed on 94 and 51 FFPE tissue sections, respectively, of pathologically reviewed stage IV LCNEC. DLL3 and ASCL1 were scored positive if ≥1% of the tumor cells showed cytoplasmic/membranous or dotlike (DLL3) or nuclear (ASCL1) immunostaining. Data were correlated with available sequencing (TP53, RB1, STK11, KEAP1), immunostaining (pRb, NE markers) and clinical data. DLL3 was expressed in 70/94 (74%) LCNEC, 56 (80%) of which showed cytoplasmic/membranous staining. Median H-score was 55 (interquartile range 0-160). DLL3 staining was not different in pRb immunohistochemistry negative and positive patients (DLL3+ in 53/70 (76%) vs. 14/21 (67%), p = 0.409) or RB1 mutated and wildtype patients (DLL3+ in 27/34 (79%) vs. 23/33 (70%), p = 0.361). Nevertheless, 6/6 (100%) STK11 mutated, 10/11 (91%) KEAP1 mutated and 9/9 (100%) TP53 wildtype tumors were DLL3+ . Furthermore, DLL3 expression was associated with expression of ASCL1 and at least 2 out of 3 neuroendocrine markers. The high percentage (74%) of DLL3 expression in stage IV LCNEC denotes the potential of DLL3 targeted therapy in this patient group.


Irony as a game of implicitness: acoustic profiles of ironic communication.
Irony, as "quotation" and "fencing game," consists of an interactive script, grounded on a focal event "trigger," in which the dialogic comment shows the ironist's intention through an antiphrastic process and syncoding to "hit" the victim of the irony (blame by praise or praise by blame). Through acoustic analysis of the suprasegmental profiles of standard phrases inserted into inductors expressly composed and read by 50 naive subjects, the presence and nature of significant differences between sarcastic and kind irony in low- and high-context utterances (contextualization effect--Experiments 1 and 2) have been verified. It has also been observed that, where more "specific weight" is given to the linguistic stream (corrective irony hypothesis), a markedness of suprasegmental features emerges (correctivity effect--Experiment 3). Finally, comparison between sarcastic irony and blame and between kind irony and praise shows that there exists a precise manner of contrastive syncoding, whereby the voices of irony do not coincide with those of direct blame or praise, but assume a specific caricature and emphatic profile (contrastivity effect--Experiment 4).


Transport of 14C-prosulfocarb through soil columns under different amendment, herbicide incubation and irrigation regimes.
This study sets out to evaluate the effect on the leaching of prosulfocarb through packed soil columns of applying green compost (GC) as an organic amendment (20% w/w), herbicide ageing over 28 days in the soil (incubation vs. no incubation), and two different irrigation regimes (saturated or saturated-unsaturated flows). Peak concentrations decreased after herbicide incubation in the columns for both unamended (S) and amended (S + GC) soils under both flow regimes. The leached amounts decreased when the herbicide was incubated for 28 days in S (2.1 and 1.9 times) and S + GC (2.9 and 1.6 times), under saturated or saturated-unsaturated flow, respectively. In the S columns, the total amounts retained (43.3%-60.8%) were lower than the ones obtained for the S + GC columns under saturated flow (77.4%-85.2%), suggesting a stronger interaction between the herbicide and the GC-amended soil. This behaviour was not observed under saturated-unsaturated flow, as the total amounts retained were similar in both the S and S + GC columns. Prosulfocarb was primarily retained in the first segment of the S (>28%) and S + GC (>43%) columns under all conditions. Incubation time did not greatly affect the herbicide retention, but it significantly increased the mineralized amount under saturated flow. The total balances of 14C-prosulfocarb were >73% and >80% in the S and S + GC columns, respectively, indicating that amendment decreased prosulfocarb loss by volatilization. Several factors, such as amendment, herbicide ageing and water flow, proved to be important for controlling the leaching of this herbicide through the soil profile.


Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch-Schönlein Purpura Nephritis.
Henoch-Schönlein purpura nephritis (HSPN) is considered a major cause of chronic renal failure and is the most common secondary glomerular disease in children. Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects against HSPN in clinical practice. However, the potential molecular targets and mechanisms underlying HSPN treatment remain unclear. By constructing a protein-protein interaction (PPI) network, core targets related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways related to HSPN based on the core targets. To screen the main active ingredients of HQH against HSPN, an ingredient-target-pathway network was constructed using the top 10 main pathways associated with HSPN. Then, molecular docking was performed to explore the interactions and binding patterns between molecules and proteins. Clinical data showed that HQH combined with conventional medicine significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15 potential core targets were identified. The top 10 main pathways showed higher enrichment ratios, including the cytokine-cytokine receptor interaction and signaling pathways related to NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and molecular docking, we revealed that five active ingredients of HQH had good affinities with three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. The study preliminarily explored the active ingredients, targets, and pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be attributed to the modulation of inflammatory response, immune response, and oxidative stress. Combined with clinical data, our results indicate that HQH is highly effective in treating HSPN.


Philosophy, psychology, physics and practice of ki.
Ki (in Japanese) or Qi (in Chinese) is the key concept in Eastern medicine, Eastern philosophy, as well as in martial arts. We explain the philosophical and psychological background of Ki. We emphasize that the unique aspects of Eastern philosophy are 'non-linearity' and 'holistic' approach. We then present physics aspect of Ki. Our experiments demonstrated that a 'Ki-beam' carries 'entropy' (or information), which is different from 'energy'. We introduce our experience of having taught Ki to 37 beginners in the United States through the Nishino Breathing Method. If beginners had martial arts training or a strong background in music or dance, about half of them could sense Ki within 10 weeks (1 h class per week) of practice.


Impaired binding of insulin to erythrocyte membrane receptor and the activation of nitric oxide synthase by the hormone in human breast cancer.
Nitric oxide, a messenger molecule has been reported as having various antineoplastic properties. The activation of insulin-activated nitric oxide synthase (IANOS) was found to be related to the production of NO as a result of the binding of insulin to its receptor through the activation of tyrosine kinase in erythrocyte membrane. As nitric oxide is reported to be a systemic anticancer agent, studies were carried out to determine the role of insulin receptor binding that lead to the activation of tyrosine kinase and IANOS in erythrocytes in breast cancer. Blood samples were collected from female breast cancer patients who, at the time of participation in the study, had not undergone any therapeutic intervention but had opted for surgery. The binding of insulin to its receptor in erythrocyte membrane and the activation of both receptor tyrosine kinase and IANOS due to the hormone binding were determined and compared with the appropriate control. It was found that the impaired NO synthesis in erythrocyte membrane in breast cancer was related to the marked decrease of insulin binding sites of the high-affinity hormone receptor population. This impaired insulin binding to high-affinity receptors resulted in the impairment of both reaction velocity (Vmax) of the IANOS and receptor tyrosine kinase activation. These results indicated that the impairment of interaction between insulin and its high-affinity receptors in erythrocyte membrane might be a critical pathophysiological event in the development of breast cancer.


Visualization of pig sperm chromosomes by in-vitro penetration of zona-free hamster ova.
Zona-free hamster eggs were penetrated by pig spermatozoa capacitated using bovine follicular fluid and Percoll gradients. A mean penetration rate of 80.1% was obtained from 5 ejaculates from 2 boars. Penetrated eggs were cultured and analysable metaphase chromosome spreads were obtained from 16.8%. The analysis of 20 pig sperm complements indicated that 9 were 19, Y, 10 were 19, X and 1 appeared to have an XY sex chromosome constitution.


[A new approach to the isolation of genomic DNA samples from yeast and fungi: preparation of DNA-containing cell envelopes and their use in PCR].
A simple and rapid procedure for the preparation of yeast and fungal DNA samples useful in PCR amplification was developed. The DNA was purified from proteins, lipids, polysaccharides, and other impurities by their high-temperature extraction (in a boiling water bath) with buffer solutions containing chaotropic salts. Under these conditions, yeast and fungal cell envelopes remain unbroken and retain the original DNA and RNA that could be used for direct PCR amplification. We called the proposed PCR technique as the PCR using DNA-containing cell envelopes.


The heart in polymyositis: a prospective evaluation of 26 patients.
Although cardiac abnormalities have been reported in patients with idiopathic polymyositis-dermatomyositis (PM), the nature and extent of these abnormalities have varied. The purpose of this study was to determine the prevalence and to obtain a better description of the spectrum of cardiac abnormalities in a cohort of patients with PM by use of a thorough noninvasive cardiac evaluation. Accordingly, we studied 26 patients with a history of PM and clinically inactive myositis (22 polymyositis, 4 dermatomyositis) between June 1984 and June 1991. Examination included history, physical examination, 12-lead electrocardiography, 24-h ambulatory electrocardiographic monitoring, chest radiography, transthoracic echocardiography, and radionuclide ventriculography. Of the patients studied, 77% were taking corticosteroid medications at a mean dose of 39 +/- 27 mg at the time of their evaluation. All 26 patients were identified as having two or more cardiac abnormalities. Cardiac symptoms and signs were common (62 and 81%, respectively), but were generally nonspecific. Electrocardiographic findings were most common (in 85% of cases), followed by findings on ambulatory monitoring (77%), echocardiography (42%), and radionuclide ventriculography (15%). The prevalence of mitral valve prolapse (8%) and hyperkinetic left ventricular contraction (12%) was significantly lower than previously reported. A secondary aim of this study was to determine associations between demographic variables including age, disease duration, cardiovascular symptoms, immunosuppressive therapy, autoantibody status, and creatinine phosphokinase level, and the presence of cardiac abnormalities. Of these patient variables, only increasing patient age was associated with an increased likelihood of cardiac abnormalities on noninvasive testing.(ABSTRACT TRUNCATED AT 250 WORDS)


The evaluation of sexual abuse in children.
This clinical report serves to update the statement titled "Guidelines for the Evaluation of Sexual Abuse of Children," which was first published in 1991 and revised in 1999. The medical assessment of suspected sexual abuse is outlined with respect to obtaining a history, physical examination, and appropriate laboratory data. The role of the physician may include determining the need to report sexual abuse; assessment of the physical, emotional, and behavioral consequences of sexual abuse; and coordination with other professionals to provide comprehensive treatment and follow-up of victims.


Factors that influence the efficacy of bereavement life review therapy for spiritual well-being: a qualitative analysis.
We have previously shown that bereavement life review therapy improves the spiritual well-being of a bereaved family, but the factors that influence the efficacy of this therapy have not been determined. Therefore, this study was performed to identify factors associated with improvement of spiritual well-being of bereaved families. The participants were 21 bereaved family members who lost a relative who had been treated in a palliative care unit in Japan. The family members received the Bereavement Life Review over two sessions of about 60 min each. In the first session, the bereaved family member reviewed their memories of the deceased relative with a clinical psychologist and answered several questions. After the first session, the psychologist made an album. In the second session, the family member and the psychologist confirmed the accuracy of the contents of the album. Assessment was performed using the Functional Assessment Chronic Illness Therapy-Spiritual score, based on which the participants were separated into effective and non-effective groups. Factors were extracted from the narrative of the therapy using a text-mining software. Factors such as "good memories of family," "loss and reconstruction," and "pleasant memories of last days" were commonly found in the effective group, whereas factors such as "suffering with memories," "regret and sense of guilt," and "disagreement on funeral arrangements" were more common in the non-effective group. Factors like "good memories of families," "loss and reconstruction," and "pleasant memories of last days" were associated with the improvement of spiritual well-being of bereaved families.


Antispermatogenic effect of embelin, a plant benzoquinone, on male albino rats in vivo and in vitro.
Embelin, the active principle of the seeds of Embelia ribes Burm, has been isolated and the purity established. Daily subcutaneous administration of the compound at a dose of 20 mg/kg body weight to male albino rats for 15 or 30 days revealed an inhibition of: a) epididymal motile sperm count, b) fertility parameters such as pregnancy attainment and litter size, and c) the activities of the enzymes of glycolysis and energy metabolism. These changes were reversible, as seen after 15 and 30 days of recovery. Addition of embelin to epididymal sperm suspensions caused a dose- and duration-dependent inhibition of spermatozoal motility and the activities of the enzymes of carbohydrate metabolism. Light and scanning electron microscopy showed that both in vivo and in vitro treatment with the drug causes profound morphological changes in spermatozoa such as: a) decapitation of the spermatozoal head, b) discontinuity of the outer membranous sheath in the mid-piece and the tail region, and c) alteration in the shape of the cytoplasmic droplet in the tail.


Kupffer phase image of Sonazoid-enhanced US is useful in predicting a hypervascularization of non-hypervascular hypointense hepatic lesions detected on Gd-EOB-DTPA-enhanced MRI: a multicenter retrospective study.
It remains unknown whether Kupffer-phase images in Sonazoid-enhanced ultrasonography (US) can be used to predict hypervascularization of borderline lesions. Therefore, we aimed to clarify whether Kupffer-phase images in Sonazoid-enhanced ultrasonography can predict subsequent hypervascularization in hypovascular borderline lesions detected on hepatobiliary-phase gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging. From January 2008 to March 2012, 616 low-intensity hypovascular nodules were detected in hepatobiliary-phase images of Gd-EOB-DTPA-enhanced MRI at nine institutions. Among these, 167 nodules, which were confirmed as hypovascular by Gd-EOB-DTPA-enhanced MRI and Sonazoid-enhanced US, were evaluated in this study. Potential hypervascularization factors were selected based on their clinical significance and the results of previous reports. The Kaplan-Meier model and log-rank test were used for univariate analysis and the Cox regression model was used for multivariate analysis. The cumulative incidence of hypervascularization of borderline lesions was 18, 37, and 43 % at 1, 2, and 3 years, respectively. Univariate analyses showed that tumor size (p = 0.0012) and hypoperfusion on Kupffer-phase images in Sonazoid-enhanced US (p = 0.004) were associated with hypervascularization of the tumor. Multivariate analysis showed that tumor size [HR: 1.086, 95 % confidence interval = 1.027-1.148, p = 0.004] and hypo perfusion on Kupffer-phase images [HR: 3.684, 95 % confidence interval = 1.798-7.546, p = 0.0004] were significantly different. Kupffer-phase images in Sonazoid-enhanced US and tumor diameter can predict hypervascularization of hypointense borderline lesions detected on hepatobiliary-phase Gd-EOB-DTPA-enhanced MRI.


Trends in Prostate Cancer Incidence Rates and Prevalence of Prostate Specific Antigen Screening by Socioeconomic Status and Regions in the United States, 2004 to 2013.
To our knowledge it is unknown whether decreases in the prevalence of prostate specific antigen screening and prostate cancer incidence rates following the USPSTF (United States Preventive Services Task Force) recommendations against routine prostate specific antigen screening are similar across socioeconomic groups and United States census regions. We analyzed incidence rates and prostate specific antigen screening prevalence by age, race/ethnicity, disease stage, United States region and area level socioeconomic status. Annual percent changes were examined for changes in rates with time. The predicted marginal probability and 95% CIs were calculated to estimate changes in prostate specific antigen screening. Incidence rates in men 50 years old or older decreased in all race/ethnic, regional and socioeconomic status groups. From 2007 to 2013 the overall incidence rates for localized cancer significantly decreased 7.5% per year (95% CI -10.5--4.4) at ages 50 to 74 years and 11.1% per year (95% CI -14.1--8.1) at ages 75 years or greater. In contrast, the incidence of distant stage cancer significantly increased 1.4% per year (95% CI 0.3-2.5) from 2008 to 2013 at ages 50 to 74 years but stabilized from 2011 to 2013 at ages 75 years or greater at 5.1% per year (95% CI -3.4-14.4). Distant stage disease rates increased with increasing poverty level at ages 50 to 74 years but not at 75 years or greater. The prostate cancer incidence of early stage disease decreased in men 50 years old or older while the rate of distant stage disease slightly increased in men 50 to 74 years old following USPSTF recommendations against routine prostate specific antigen screening. Further studies with additional years of data are needed to substantiate our findings and monitor the effects of the late stage disease increase on prostate cancer mortality rates.


Real-time PCR detection of the nontoxic nonhemagglutinin gene as a rapid screening method for bacterial isolates harboring the botulinum neurotoxin (A-G) gene complex.
Botulinum neurotoxin (BoNT) producing clostridia contain genes encoding a specific neurotoxin serotype (A-G) and nontoxic associated proteins that form the toxin complex. The nontoxic nonhemagglutinin (NTNH) is a conserved component of the toxin complex in all seven toxin types. A real-time PCR assay that utilizes a locked nucleic acid hydrolysis probe to target the NTNH gene was developed to detect bacterial strains harboring the botulinum neurotoxin gene cluster. The specificity of the assay for Clostridium botulinum types A-G, Clostridium butyricum type E and Clostridium baratii type F was demonstrated using a panel of 73 BoNT producing clostridia representing all seven toxin serotypes. In addition, exclusivity of the assay was demonstrated using non-botulinum toxin producing clostridia (7 strains) and various enteric bacterial strains (n=27). Using purified DNA, the assay had a sensitivity of 4-95 genome equivalents. C. botulinum type A was detected directly in spiked stool samples at 10(2)-10(3) CFU/ml. Stool spiked with 1 CFU/ml was detected when the sample was inoculated into enrichment broth and incubated for 24 h. These results indicate that the NTNH real-time PCR assay can be used to screen enrichment cultures of primary specimens at earlier time points (24 h) than by toxin detection of unknown culture supernatants (up to 5 days).


Fluorescence from pilosebaceous follicles.
Fluorescence studies were performed on the extrusions from pilosebaceous follicles. Pressure extractions produced follicle samples which showed fluorescence under Wood's light. The samples were then analysed in a fluorometer giving corrected excitation spectra. The structured emission spectra achieved were interpreted as being due to porphyrins produced by Propionibacterium acnes (P. acnes). Details in the spectra showed close resemblance to spectra from cultured P. acnes cells. The emission spectra showed distinct features in all the four subjects investigated (who were different with respect to age, sex, follicle sampling area, and tendency to acne) and dominant peaks due to at least three porphyrins were found. The concentrations of these porphyrins vary from case to case. Excitation spectra were recorded and supported the assumption that the fluorescent emission was partly due to coproporphyrins and metalloporphyrins in the samples. Free protoporphyrins did not seem to be present in the extrusions. The excitation spectra, in particular, vary from person to person but seem to be constant over time in one and the same subject.


Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration.
Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol). The authors studied 38 non-obese volunteers (58±12 years; Low-Density Lipoprotein Cholesterol ‒ LDL-C ≥ 130 mg/dL) randomly assigned to consume 400 mL/day of soy milk (Control phase) or soy milk + PS (1.6 g/day) for four weeks in a double-blind, cross-over study. PS and lathosterol were measured in plasma by gas chromatography coupled to mass spectrophotometry. PS treatment reduced plasma total cholesterol concentration (-5.5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration), but plasma lathosterol, campesterol and sitosterol expressed per plasma cholesterol increased. The lathosterol-to-cholesterol plasma ratio predicted the plasma cholesterol response to PS feeding. The highest plasma lathosterol concentration during the control phase was associated with a lack of response of plasma cholesterol during the PS treatment period. Consequently, cholesterol synthesis in non-responders to dietary PS being elevated in the control phase indicates these cases resist to further synthesis rise, whereas responders to dietary PS, having in the control phase synthesis values lower than non-responders, expand synthesis on alimentary PS. Responders absorb more PS than non-responders, likely resulting from responders delivering into the intestinal lumen less endogenous cholesterol than non-responders do, thus facilitating greater intestinal absorption of PS shown as increased plasma PS concentration.


Similarity as a Window on the Dimensions of Object Representation.
Hebart et al. recently analysed 1.5 million human similarity judgments and found that natural objects are described by a small set of interpretable dimensions. Such large-scale analyses offer new opportunities to characterise how people represent their knowledge, but also challenges, including scaling to even larger data sets and integrating accounts of semantic representation.


Factors of patient satisfaction in adult outpatient departments of private wing and regular services in public hospitals of Addis Ababa, Ethiopia: a comparative cross-sectional study.
Knowing the factors for patient satisfaction is an important and direct indicator of quality of health care which is essential for providers to fill their gaps. Although few studies have been conducted on patient satisfaction in Ethiopia; but there is limited evidence for comparing patient satisfaction and associated factors in the public and private wing of the health services. Thus, this study aimed to investigate factors of patient satisfaction in adult outpatient departments in the private wing and regular services at public hospitals of Addis Ababa, Ethiopia. A comparative institution based cross-sectional study was conducted from March to April 2018. A total of 955 systematically selected patients were interviewed by using an interviewer-administered structured questionnaire. Binary logistic regression analysis was performed. In the multivariable logistic regression analysis p value < 0.05 and adjusted odd ratio (AOR) with 95% confidence interval (CI) were used to identify the associated factors. The overall patient satisfaction was 89.3% (95% CI: 87.2-91.2). At the regular and private wings of outpatient departments it was 88.3% (95% CI: 85.4-91.2) and 90.4% (95% CI: 87.6-93), respectively. At regular service OPD, patient satisfaction was affected by female sex (AOR: 7.78; 95% CI: 2.89-20.93), long waiting time (AOR: 0.22; 95% CI: 0.07-0.73), information on the prevention of recurrent illnesses (AOR: 14.16; 95% CI: 4.58-43.83), and information on drug use and side effects (AOR: 0.22; 95% CI: 0.08-0.63). In private wing, it was affected by being in the age group of 38 to 47 years (AOR: 22.1; 95% CI: 2.39-203.6), attended elementary school (AOR: 4.69; 95% CI: 1.04-21.26), availability of drugs (AOR: 0.14; 95% CI: 0.04-0.58), and the accessibility of latrines (AOR: 6.56; 95% CI: 1.16-37.11). Patient satisfaction at the private wing and regular adult OPDs' of public hospitals had no statistically significant difference. Female sex and information on the prevention of recurrent illnesses were factors positively affected patient satisfaction at regular services, whereas at private wing OPDs' age, attended elementary school, and accessibility of latrines were factors that positively affected patient satisfaction.


Clinical course of incidental syringomyelia without predisposing pathologies.
Although the widespread use of MRI has facilitated the diagnosis of subclinical syringomyelia, little information has been established regarding its natural course. To elucidate the clinical course and treatment strategy of incidental syringomyelia without predisposing pathologies, we retrospectively reviewed the clinical course of 12 adult patients with incidental syringomyelia. No patients had any predisposing pathology, including Chiari malformation or spinal cord tumor. Using the medical records and MRI, we analyzed the neurological and radiological features of each patient. After a mean of 39.9 months follow-up, no patient developed neurological deterioration. Although one patient had radiological progression without neurological deterioration, 11 patients (91.7%) had no change on MRI. Additionally, all patients experienced a favorable clinical course without surgery. These results indicate that, for patients with incidental syringomyelia without predisposing pathology, close observation rather than surgery can be recommended.


Operative hysteroscopy intravascular absorption syndrome is more than just the gynecological transurethral resection of the prostate syndrome: A case series and literature review.
Operative hysteroscopy intravascular absorption (OHIA) syndrome refers to fluid overload complications from operative hysteroscopies. Despite guidelines for safe operative hysteroscopies, instances of OHIA syndrome have been reported. We reported three cases of OHIA syndrome. A 48-year-old female patient presented net irrigation fluid of 11,900 mL and developed severe metabolic acidosis, conscious disturbance, acute pulmonary edema, and unexpected intensive care unit admission. A 49-year-old female patient presented net irrigation fluid of 4500 mL and developed desaturation and acute pulmonary edema. A 45-year-old female patient presented net irrigation fluid of 2400 mL and developed hyponatremia, increased hilum lung marking, and prolonged postanesthesia care unit observation. For safety, clinicians should use isotonic electrolyte-containing distension media and bipolar electrosurgical instruments in operative hysteroscopies, and fluid status should be monitored closely, particularly at net and total irrigation amounts >3000 and > 8000 mL, respectively. Intrauterine pressure should also be minimized to reduce intravascular and intraperitoneal absorption.


Sex differences in cocaine-induced behavioral responses, pharmacokinetics, and monoamine levels.
Female rats display a more robust behavioral response to acute cocaine administration than do male rats. However, a clear understanding of the biological mechanisms underlying these differences remains elusive. The present study investigated whether sexual dimorphisms in cocaine-induced motor behavior might be based on monoaminergic levels and/or cocaine pharmacokinetics. An acute injection of cocaine (5, 15, 20 or 30 mg/kg) or saline was administered to male and female rats, and behavioral activity was monitored for 3 h. Following acute cocaine or saline administration motor behavior varied according to dose and sex; overall, female rats displayed greater rearing counts and stereotypic scores, greater total locomotor counts at 15, 20, and 30 mg/kg of cocaine, and greater ambulatory counts at 20 and 30 mg/kg of cocaine than did male rats. Neurochemical determinations in post-mortem tissue showed that both male and female rats had increases in total dopamine (DA) in the caudate putamen (CPu) 15 min following cocaine administration. Additionally, male rats had a decrease in dihydroxyphenylacetic acid (DOPAC)/DA turnover. Female rats showed significant reductions in total levels of DA, DOPAC, HVA, serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and DOPAC/DA turnover in the nucleus accumbens (NAc). Male rats displayed a reduction only in DOPAC/DA turnover and increases in 5-HT in the NAc following cocaine administration. Furthermore, sex differences in cocaine metabolism were observed where females had greater brain/blood levels of norcocaine and ecgonine methyl ester while male rats had higher blood levels of benzoylecgonine. These results suggest that sex differences in the behavioral responses to cocaine administration could be explained in part by intrinsic differences in both monoaminergic levels and metabolic processes.


Night and day variations of sleep in patients with disorders of consciousness.
Brain injuries substantially change the entire landscape of oscillatory dynamics and render detection of typical sleep patterns difficult. Yet, sleep is characterized not only by specific EEG waveforms, but also by its circadian organization. In the present study we investigated whether brain dynamics of patients with disorders of consciousness systematically change between day and night. We recorded ~24 h EEG at the bedside of 18 patients diagnosed to be vigilant but unaware (Unresponsive Wakefulness Syndrome) and 17 patients revealing signs of fluctuating consciousness (Minimally Conscious State). The day-to-night changes in (i) spectral power, (ii) sleep-specific oscillatory patterns and (iii) signal complexity were analyzed and compared to 26 healthy control subjects. Surprisingly, the prevalence of sleep spindles and slow waves did not systematically vary between day and night in patients, whereas day-night changes in EEG power spectra and signal complexity were revealed in minimally conscious but not unaware patients.


Destruction of cultured vascular endothelial cells and red blood cells by immune-activated polymorphonuclear leukocytes.
The cytotoxicity of human polymorphonuclear leukocytes (PMNs) against autologous red blood cells (RBC) and cultured vascular endothelial cells (EC) was investigated. PMNs were activated by phorbol myristate acetate (PMA) together with immune stimuli such as immune complexes and aggregated IgG. In the standard 51Cr-release assay, in which PMA concentration was 5 ng/ml and effector versus target ratio was 5, 76.7% and 34.2% specific 51Cr release was observed from RBC and EC, respectively. Significant levels of 51Cr were released, albeit to a lesser degree, when PMNs were stimulated by immune stimuli. Further experiments which employed various scavengers of oxygen radicals suggested that hydrogen peroxide was the most potent mediator of this cytotoxicity; the implications of these in vitro observations with the pathogenesis of immune vasculitis are of clinical interest.


Heat stress related dairy cow mortality during heat waves and control periods in rural Southern Ontario from 2010-2012.
Heat stress is a physiological response to extreme environmental heat such as heat waves. Heat stress can result in mortality in dairy cows when extreme heat is both rapidly changing and has a long duration. As a result of climate change, heat waves, which are defined as 3 days of temperatures of 32 °C or above, are an increasingly frequent extreme weather phenomenon in Southern Ontario. Heat waves are increasing the risk for on-farm dairy cow mortality in Southern Ontario. Heat stress indices (HSIs) are generally based on temperature and humidity and provide a relative measure of discomfort which can be used to predict increased risk of on-farm dairy cow mortality. In what follows, the heat stress distribution was described over space and presented with maps. Similarly, on-farm mortality was described and mapped. The goal of this study was to demonstrate that heat waves and related HSI increases during 2010-2012 were associated with increased on-farm dairy cow mortality in Southern Ontario. Mortality records and farm locations for all farms registered in the CanWest Dairy Herd Improvement Program in Southern Ontario were retrieved for 3 heat waves and 6 three-day control periods from 2010 to 2012. A random sample of controls (2:1) was taken from the data set to create a risk-based hybrid design. On-farm heat stress was estimated using data from 37 weather stations and subsequently interpolated across Southern Ontario by geostatistical kriging. A Poisson regression model was applied to assess the on-farm mortality in relation to varying levels of the HSI. For every one unit increase in HSI the on-farm mortality rate across Southern Ontario increases by 1.03 times (CI95% (IRR) = (1.025,1.035); p = ≤ 0.001). With a typical 8.6 unit increase in HSI from a control period to a heat wave, mortality rates are predicted to increase by 1.27 times. Southern Ontario was affected by heat waves, as demonstrated by high levels of heat stress and increased on-farm mortality. Farmers should be aware of these risks, and informed of appropriate methods to mitigate such risks.


Skin immunosenescence: decreased receptor for activated C kinase-1 expression correlates with defective tumour necrosis factor-alpha production in epidermal cells.
Skin immunosenescence accounts for increased susceptibility in the elderly to cutaneous infections and malignancies, and decreased contact hypersensitivity and response to vaccination. We have recently shown in immune cells that decreased expression of the receptor for activated C kinase (RACK)-1 underlies defective protein kinase C (PKC) activation and functional immune impairment with ageing. This study was designed to determine if an age-related decline in skin RACK-1 expression was present and whether it correlated with defective tumour necrosis factor (TNF)-alpha production. PKC isoforms and RACK-1 expression were evaluated by Western blot analysis and by immunofluorescence in skin obtained from Sprague-Dawley rats of different ages. TNF-alpha release by epidermal cells induced by lipopolysaccharide, 12-O-tetradecanoyl-phorbol-13-acetate and the contact allergen dinitrochlorobenzene was assessed by the L929 biological assay. Skin obtained from old rats (> 18 months) showed decreased RACK-1 immunoreactivity if compared with young rats (< 3 months). RACK-1 preferentially interacts with PKC beta. Despite a similar total skin content of this isoform, the reduced expression of RACK-1 was associated with a decreased translocation of PKC beta in the membrane compartment. The defective PKC beta translocation associated with ageing correlated with decreased TNF-alpha release from epidermal cells following treatment with different inflammatory stimuli. Overall, we demonstrated for the first time a decrease in RACK-1 expression, defective PKC beta translocation and reduced TNF-alpha release in epidermal cells with ageing. These alterations might be mechanistically significant, and provide a new understanding of the consequences of ageing on skin immunology.


A game-theoretic approach to donor kidney sharing.
Graft survival in renal transplantation is a function, amongst other things, of the degree of histocompatibility lymphocyte-A (HLA) tissue matching achieved between donor and recipient. Yet a donor procured at centre A might match a transplant candidate at centre B and vice versa. This raises the question of whether, and under what circumstances, surgeons will offer and exchange donor kidneys and gain from such trade in terms of graft survival. We analyse the problem in a game-theoretic framework where the choice of strategy 'to offer or not?' is evaluated in the context of the uncertainty of reciprocation by the other player(s) in the game. The equilibrium solution to a number of variations of the game is predicted to be non-cooperation resulting in collectively sub-optimal graft survival rates. Some policy options for improving cooperation are considered including exchange incentives and coercive measures.


Oxidative stress in chronic pancreatitis: pathophysiological relevance and management.
Chronic pancreatitis (CP) is a progressive, inflammatory disease of the pancreas leading to slow destruction of pancreatic parenchyma and progressive fibrosis. The pathophysiological mechanism of CP is not well understood. A pathophysiologic role of oxidative stress in CP has, however, been suggested in recent years. Pancreatic acinar cells contain phase I cytochrome P450 (CYP 450) biotransforming enzymes and phase II conjugation reactions for the metabolism of xenobiotics. The oxidative stress in the acinar cell may result from generation of free radicals through CYP induction, concurrent exposure to a chemical that undergoes bioactivation, and insufficiency of micronutrients that are required to sustain antioxidant (AO) capacity. Studies have shown that there is indeed a state of oxidative stress as evidenced by increased levels of products of oxidative stress and reduced AO capacity in patients with CP. A recent randomized, controlled trial has shown beneficial effect of AO therapy in CP; a combination of AOs (0.54 g ascorbic acid, 9000 IU β-carotene, 270 IU α-tocopherol, 600 μg organic selenium, and 2 g methionine per day in divided doses) led to significant reductions in pain and oxidative stress in patients with CP. Similar studies from other centers and multicenter studies should confirm that oxidative stress plays an important role in the pathophysiology of CP and supplementation with AOs leads to significant pain relief in patients with this disease.


LncRNA ZNF667-AS1 Targets miR-523-3p/KIF5C Axis to Hinder Colon Cancer Progression.
LncRNA ZNF667-AS1 plays an important role in the carcinogenesis and progression of various cancers. However, their role in colon cancer (CC) remains unclear. The expression of ZNF667-AS1, KIF5C, and miR-523-3p in CC cells and tissues was analyzed using RT-qPCR and western blotting. CCK-8 scratch-wound assay, western blotting, and flow cytometry were conducted to investigate the malignant activity of CC in vitro. Luciferase reporter, RNA pull-down, and Ago2 immunoprecipitation (RIP) experiments were conducted to ascertain the association of miR-523-3p with ZNF667-AS1 and KIF5C 3'UTR. Xenograft tumor experiments were also performed. CC cells and tissues showed low expression of NF667-AS1 and KIF5C and elevated expression of miR-523-3p. ZNF667-AS1 overexpression attenuates proliferation and migration of CC cells, restores inactivated apoptosis in vitro, and inhibits tumor growth in vivo. MiR-523-3p targets both ZNF667-AS1 and the KIF5C 3'UTR. ZNF667-AS1 overexpression in SW480 and SW620 cells attenuated the oncogenic effect of miR-523-3p in CC. However, this attenuating effect was counteracted by KIF5C overexpression. ZNF667-AS1 sequestered miR-523-3, reducing miR-523-3p-mediated inhibition of KIF5C expression, thereby repressing colon carcinogenesis in vitro. Our findings shed light on a novel anticancer strategy that could potentially combat CC.


Heart rate variability metrics for fine-grained stress level assessment.
In spite of the existence of a multitude of techniques that allow the estimation of stress from physiological indexes, its fine-grained assessment is still a challenge for biomedical engineering. The short-term assessment of stress condition overcomes the limits to stress characterization with long blocks of time and allows to evaluate the behaviour change in real-world settings and also the stress level dynamics. The aim of the present study was to evaluate time and frequency domain and nonlinear heart rate variability (HRV) metrics for stress level assessment using a short-time window. The electrocardiogram (ECG) signal from 14 volunteers was monitored using the Vital JacketTM while they performed the Trier Social Stress Test (TSST) which is a standardized stress-inducing protocol. Window lengths from 220 s to 50 s for HRV analysis were tested in order to evaluate which metrics could be used to monitor stress levels in an almost continuous way. A sub-set of HRV metrics (AVNN, rMSSD, SDNN and pNN20) showed consistent differences between stress and non-stress phases, and showed to be reliable parameters for the assessment of stress levels in short-term analysis. The AVNN metric, using 50 s of window length analysis, showed that it is the most reliable metric to recognize stress level across the four phases of TSST and allows a fine-grained analysis of stress effect as an index of psychological stress and provides an insight into the reaction of the autonomic nervous system to stress.


Antioxidant Role in Critically Ill Patients with Vasodilatory Shock: Does Glutathione Peroxidase Correlate to Severity of Tissue Hypoxia and Organ Failure.
We aimed to evaluate the antioxidant role in critically ill patients with vasodilatory shock as it relates to severity of tissue hypoxia and organ failure. An observational and prospective study was conducted in critically ill patients with vasodilatory shock. Glutathione peroxidase (GPx) levels as antioxidants were measured based on their levels in the patient's serum. Tissue hypoxia as micro-hemodynamic status was represented by lactate levels, the macro-hemodynamic status was represented by vasoactive inotropic score (VIS) and mean arterial pressure (MAP), while organ dysfunction severity was represented by the shock index (SI), the sequential organ failure assessment (SOFA) score, and the acute physiology and chronic health evaluation (APACHE) II score. Thirty-four critically ill patients with vasodilatory shock met the eligibility criteria. The mortality rate was 41.2%. Glutathione peroxidase levels did not show a significant difference between survivors and non-survivors at baseline or after 24 hours. At the initial measurement, there was a correlation between GPx and lactate levels, GPx and SOFA scores. The macrohemodynamic status was represented by VIS and MAP, which were correlated with SI. Glutathione peroxidase as antioxidant is related to severity of tissue hypoxia and organ failure in critically ill patients with vasodilatory shock.


Massive rotator cuff tears: definition and treatment.
The aim of this review is to summarise tear pattern classification and management options for massive rotator cuff tears (MRCT), as well as to propose a treatment paradigm for patients with a MRCT. Data from 70 significant papers were reviewed in order to define the character of reparability and the possibility of alternative techniques in the management of MRCT. Massive rotator cuff tears (MRCT) include a wide panoply of lesions in terms of tear pattern, functional impairment, and reparability. Pre-operative evaluation is critical to successful treatment. With the advancement of medical technology, arthroscopy has become a frequently used method of treatment, even in cases of pseudoparalytic shoulders. Tendon transfer is limited to young patients with an irreparable MRCT and loss of active rotation. Arthroplasty can be considered for the treatment of a MRCT with associated arthritis. There is insufficient evidence to establish an evidence-based treatment algorithm for MRCTs. Treatment is based on patient factors and associated pathology, and includes personal experience and data from case series.


A simple and selective method for visualizing the kinetoplast of trypanosomes by means of phosphomolybdic acid and a photographic developer.
Trypanosoma cruzi epimastigotes treated with phosphomolybdic acid and the photographic developer Rodinal display bright kinetoplasts when unmounted smears are observed using low-magnification phase-contrast objectives. This simple method enables the rapid and accurate identification of kinetoplasts in trypanosomes.


COVID-19 Pandemic Recession and Recovery.
This review draws pragmatic lessons for developing countries to address COVID-19-induced recessions and to sustain a developmental recovery. These recessions are unique, caused initially by supply disruptions, largely due to government-imposed 'stay-in-shelter lockdowns'. These have interacted with falling incomes and demand, declining exports (and imports), collapsing commodity prices, shrinking travel and tourism, decreasing remittances and foreign exchange shortages. Highlighting implications for employment, wellbeing and development, it argues that governments need to design comprehensive relief measures and recovery policies to address short-term problems. These should prevent cash-flow predicaments from becoming full-blown solvency crises. Instead of returning to the status quo ante, developing countries' capacities and capabilities need to be enhanced to address long-term sustainable development challenges. Multilateral financial institutions should intermediate with financial sources at low cost to supplement the International Monetary Fund's Special Drawing Rights to lower borrowing costs for relief and recovery.


Long-term validity and reliability of a patient survey instrument designed for general dental practice.
To consider the extent to which the validity and reliability of the Denplan Excel Patient Survey (DEPS) has been confirmed during its development and by its use in general dental practice and to explore methods by which any survey instrument used in general dental practice might be validated and tested for reliability. DEPS seeks to measure perceived practice performance on those issues considered to be of greatest importance to patients. Content validity was developed by a literature review and tested in a pilot study. Criterion validity was tested by comparing patient retention in a payment plan for practices achieving the highest DEPS scores with those attaining the lowest scores over a two year period (surveys completed between 2010 and 2012). Reliability was assessed using the test/re-test method for 23 practices with approximately a three year time interval between tests. Internal consistency was tested by comparing Net Promoter Scores (NPS - which is measured in DEPS) attained by practices with their Patient Perception Index (PPI) as measured by the ten core questions in DEPS. Practices in the pilot study strongly endorsed the content validity of DEPS. The 12 practices with the highest scores in the DEPS slightly increased their number of patients registered in Denplan payment plans during a two year period. The 12 lowest scoring practices saw 7% of their patients de-register during the same period. The 23 practices selected for the test/re-test study averaged more than 250 responses for both the test and re-test phases. The magnitude and pattern of their results were similar in both phases, while, on average, a modest improvement in results was observed. Internal consistency was confirmed as NPS results in DEPS closely mapped PPI results. The higher the measurement of perceived quality (PPI) the more likely patients were to recommend the practice (NPS). Both through its development and use over the last four years The DEPS has demonstrated good validity and reliability. The authors conclude that this level of validity and reliability is adequate for the clinical/general care audit purpose of DEPS and that it is therefore likely to reliably inform practices where further development are indicated. It is important and quite straightforward to both validate and check the reliability of patient surveys used in general dental practice so that dental teams can be confident in the instrument they are using.