Increased inflammatory cytokine expression in the vastus lateralis of patients with knee osteoarthritis.
Increased inflammation and pain are inseparable parts of knee osteoarthritis (OA) that may lead to disuse of the affected limb. The aim of this study was to examine the effects of knee OA on inflammation- and atrophy-related genes and proteins in the vastus lateralis muscle of patients with knee OA. Nineteen patients with knee OA and 14 asymptomatic control subjects matched for age and body mass index underwent strength measurements and a muscle biopsy. Muscle was analyzed for the total cellular protein of inflammatory kinases (p65 NF-κB, JNK1/2, STAT-3, and suppressor of cytokine signaling 3 [SOCS-3]) and inflammatory intracellular molecules (interleukin-6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1], tumor necrosis factor α [TNFα], IL-1β, and atrogin-1). Knee OA resulted in greater levels of IL-6 protein (34%; P = 0.002). The levels of inflammatory kinases, including STAT-3 (187%; P = 0.002), p65 NF-κB (156%; P = 0.002), and JNK1 (179%; P = 0.027), were also elevated. Furthermore, elevated expression of gene transcripts encoding MCP-1 (28%; P = 0.023), TNFα (85%; P < 0.001), and SOCS-3 (38%; P = 0.055) was observed in patients with knee OA compared with control subjects. Patients with knee OA had reduced muscle strength compared with control subjects (mean ± SEM 84.7 ± 8.7 versus 143.1 ± 20.8 Nm; P = 0.005). Negative correlations were observed between muscle strength and MCP-1 protein abundance (r = -0.37 [P = 0.042]) and the gene expression of TNFα and atrogin-1 messenger RNA (r = -0.46 [P = 0.012] and r = -0.36 [P = 0.040], respectively). Gene expression and the protein abundance of numerous muscle markers of inflammation and atrophy were elevated in patients with knee OA, and the increase in muscle inflammation was associated with a reduction in muscle strength. Given the role inflammation markers may play in muscle strength and atrophy, further studies are needed to investigate the effect of exercise intervention on skeletal muscle inflammation.


High serum levels of inflammatory markers are associated with early recurrence in patients with high-grade serous ovarian cancer after platinum therapy.
To determine if inflammatory biomarkers can predict the long-term outcome of platinum therapy in patients with high-grade serous ovarian cancer. Women diagnosed with high-grade serous epithelial ovarian cancer (n = 70) at a single institution were enrolled in a prospective serum collection study between 2005 and 2020. Seventeen markers of inflammation and oxidative stress were measured in serum samples on a chemistry analyzer. Association was tested for serum levels with progression-free survival (PFS), time to recurrence (TTR), overall survival (OS), and time to death (TTD) using Cox proportional hazards and Kaplan-Meier curves. Patient survival was censored at 10 years. Higher serum levels of LDH were associated with worse PFS (HR 2.57, p = 0.028). High serum levels of BAP (HR 0.38, p = 0.025), GSP (HR 0.40, p = 0.040), HDL-c (HR 0.27, p = 0.002), and MG (HR 0.36, p = 0.017) were associated with improved PFS. Higher expression of LDH was associated with worse OS (HR 2.16, p = 0.023). Higher levels of CK.nac (HR 0.39, p = 0.033) and HDL-c (HR 0.35, p = 0.029) were associated with improved OS. Similar outcomes were found with TTR and TTD analyses. General inflammatory biomarkers may serve as a guide for prognosis and treatment benefit. Future studies needed to further define their role in predicting prognosis or how these markers may affect response to therapy.


Response of fission yeast to toxic cations involves cooperative action of the stress-activated protein kinase Spc1/Sty1 and the Hal4 protein kinase.
Stress-activated protein kinases (SAPKs), members of a mitogen-activated protein kinase (MAPK) subfamily, are highly conserved among eukaryotes. Studies of yeasts demonstrated that SAPKs play pivotal roles in survival responses to high osmolarity, oxidative stress, and heat shock. Here we report a novel physiological role of the fission yeast Spc1 SAPK in cellular resistance to certain cations, such as Na(+), Li(+), and Ca(2+). Strains lacking Spc1 or its activator, Wis1 MAPK kinase, are hypersensitive to these cations. Spc1 positively regulates expression of sod2(+) encoding a Na(+)/H(+) antiporter through Atf1 and other transcription factors. In addition, we have identified a novel Spc1-interacting protein, Hal4, which is highly homologous to the budding yeast Sat4/Hal4 protein kinase. Like its budding yeast counterpart, the fission yeast Hal4 kinase is essential for cellular resistance to Na(+), Li(+), and Ca(2+). The hal4-null phenotype is complemented by overexpression of the Trk1 potassium transporter or increased K(+) in the growth medium, suggesting that Hal4 promotes K(+) uptake, which consequently increases cellular resistance to other cations. Interestingly, the Spc1-Hal4 interaction appears to be required for cellular resistance to Ca(2+) but not Na(+) and Li(+). We propose that Spc1 SAPK and Hal4 kinase cooperatively function to protect cells from the toxic cations.


Epigenetic regulation of aging in honeybee workers.
Aging and longevity are complex life history traits that are influenced by both genes and environment and exhibit significant phenotypic plasticity in a broad range of organisms. A striking example of this plasticity is seen in social insects, such as ants and bees, where different castes can have very different life spans. In particular, the honeybee worker offers an intriguing example of environmental control on aging rate, because workers are conditionally sterile and display very different aging patterns depending on which temporal caste they belong to (hive bee, forager, or a long-lived caste capable of surviving for several months on honey alone). The ubiquitous yolk protein vitellogenin appears to play a key role in the regulatory circuitry that controls this variation. Here we outline the current understanding of the relation between vitellogenin and somatic maintenance in honeybee workers, and how this relation can be understood in a life history context.


Projection of HIV infection in Calcutta.
Starting with the base year of 1991, the HIV infection projection for 1992-99 for the total, as well as various high-risk sub-populations of Calcutta, the first of its kind is provided. These projections are based on statistical methodology developed in this paper. Our methodology for spread of HIV infection takes into account various social interactions and practices and also uses available data. Rates of these interactions and practices and estimates of demographic parameters used in making projections were obtained primarily from surveys and census data. Since one of these estimated rates, that of HIV transmission rate through heterosexual encounters between an infected and an uninfected had a large range, we have provided two sets of projections based on the largest of these rates (worst-case scenario) and another that is consistent with the available data. The total projection of the number of HIV infected cases in Calcutta for 1999 is between 49,000 and 1,26,000. Separate projections are also provided for high-risk sub-groups. Among these, the sex workers expectedly will continue to manifest the highest numbers of newly infected cases. The temporal rate of increase in prevalence is projected to be alarmingly higher in the general population than even among sex workers, although the actual prevalence will continue to be the lowest in the general population compared to all other sub-groups of the population.


Gamow-Teller transition strengths from 56Ni.
A new technique to measure (p,n) charge-exchange reactions in inverse kinematics at intermediate energies on unstable isotopes was successfully developed and used to study the (56)Ni(p,n) reaction at 110 MeV/u. Gamow-Teller transition strengths from (56)Ni leading to (56)Cu were obtained and compared with shell-model predictions in the pf shell using the KB3G and GXPF1A interactions. The calculations with the GXPF1A interaction reproduce the experimental strength distribution much better than the calculations that employed the KB3G interaction, indicating deficiencies in the spin-orbit and proton-neutron residual potentials for the latter. The results are important for improving the description of electron-capture rates on nuclei in the iron region, which are important for modeling the late evolution of core-collapse and thermonuclear supernovae.


Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity.
Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI). Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed. There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity. These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress.


Soybean CALCIUM-DEPENDENT PROTEIN KINASE17 Positively Regulates Plant Resistance to Common Cutworm (Spodoptera litura Fabricius).
Soybean is frequently attacked by herbivorous pests throughout the growth period. Exploring anti-insect genes to improve insect resistance in soybean is an important soybean breeding goal. Here, we cloned and characterized the gene for a quantitative trait locus (QTL) related to insect resistance, Glyma.06g189600, which encodes CALCIUM-DEPENDENT PROTEIN KINASE17 (GmCDPK17) in soybean. The pairwise sequence alignment analysis revealed that the presumed protein of GmCDPK17 shares 52.06% similarity with that of GmCDPK38, a known negative regulatory gene of insect resistance in soybean. Ectopic expression of GmCDPK17 and GmCDPK38 restored the phenotypes of the Arabidopsis insect-susceptible mutant cpk10 and insect-resistant mutant cpk28, respectively. Moreover, transgenic hairy roots of the soybean cultivar Jack were generated by Agrobacterium-mediated transformation. Overexpression of GmCDPK17 increased soybean hairy root resistance to common cutworm (CCW), while RNA interference of the gene decreased soybean hairy root resistance to CCW. Sequencing data from the cultivated and wild soybeans were used to analyze the genetic diversity of GmCDPK17. This gene was subjected to domestication selection. Six and seven haplotypes (Haps) were identified in cultivated and wild soybeans, respectively. The resistance Hap1 is not widely used in cultivated soybeans and is mainly distributed at low latitudes. Accessions with resistance haplotypes of the GmCDPK17 and GmCDPK38 genes showed high resistance to CCW. Altogether, we revealed a novel positive regulatory insect resistance gene, GmCDPK17, which may further improve insect resistance in soybean.


Actein activates stress- and statin-associated responses and is bioavailable in Sprague-Dawley rats.
The purpose of this study was to assess in rats the pharmacological parameters and effects on gene expression in the liver of the triterpene glycoside actein. Actein, an active component from the herb black cohosh, has been shown to inhibit the proliferation of human breast cancer cells. To conduct our assessment, we determined the molecular effects of actein on livers from Sprague-Dawley rats treated with actein at 35.7 mg/kg for 6 and 24 h. Chemogenomic analyses indicated that actein elicited stress and statin-associated responses in the liver; actein altered expression of cholesterol and fatty acid biosynthetic genes, p53 pathway genes, CCND1 and ID3. Real-time RT-PCR validated that actein induced three time-dependent patterns of gene expression in the liver: (i) a decrease followed by a significant increase of HMGCS1, HMGCR, HSD17B7, NQO1, S100A9; (ii) a progressive increase of BZRP and CYP7A1 and (iii) a significant increase followed by a decrease of CCND1 and ID3. Consistent with actein's statin- and stress-associated responses, actein reduced free fatty acid and cholesterol content in the liver by 0.6-fold at 24 h and inhibited the growth of human HepG2 liver cancer cells. To determine the bioavailability of actein, we collected serum samples for pharmacokinetic analysis at various times up to 24 h. The serum level of actein peaked at 2.4 microg/mL at 6 h. Actein's ability to alter pathways involved in lipid disorders and carcinogenesis may make it a new agent for preventing and treating these major disorders.


What pretreatment prostate-specific antigen level warrants long-term androgen deprivation?
Several large randomized prospective studies have demonstrated a survival benefit with the addition of long-term androgen deprivation to definitive radiotherapy for patients with Gleason score 8-10 or T3-T4 prostate cancer. However, these studies were performed before the routine use of prostate-specific antigen (PSA) measurement. The purpose of this study was to determine what pretreatment (initial) PSA (iPSA) level, if any, warrants the addition of long-term androgen deprivation in the PSA era. The data set evaluated consisted of 1003 prostate cancer patients treated definitively with three-dimensional conformal radiotherapy between May 1, 1989 and November 30, 1999 (median follow-up, 61 months). Specifically excluded were patients with T3-T4 disease or Gleason score greater than 7 or those who had undergone androgen deprivation as a part of their initial therapy. The median radiation dose was 76 Gy. Patients were randomly split into two data sets, with the first (n = 487) used to evaluate the optimal iPSA cutpoint for which a statistically significant difference in outcome was noted. The second data set (n = 516) served as a validation data set for the initial modeling. The analysis of the optimal iPSA cutpoint was based on a recursive partitioning approach for censored data using the log-rank test for nodal separation of freedom from biochemical failure (FFBF) as defined by the American Society for Therapeutic Radiology and Oncology definition. Cox multivariate regression analysis was used to confirm independent predictors of outcome among the clinical and treatment-related factors: iPSA (grouped as defined by the recursive partitioning analysis), Gleason score (2-6 vs. 7), T stage (T1c-T2a vs. T2b-T2c), and total radiation dose (continuous). The recursive partitioning analysis data set resulted in an optimal iPSA cutpoint of 35 ng/mL, such that the 5-year Kaplan-Meier estimate of FFBF was 80%, 69%, and 19% for iPSA groups of 0-9.9, 10-35, and >35 ng/mL, respectively. The validation data set demonstrated the optimal iPSA cutpoint to be 30 ng/mL. Conservatively choosing 30 ng/mL as the optimal cutpoint, the 5-year FFBF estimate for the entire 1003 patients was 82%, 69%, and 20% for iPSA groups 0-9.9 (n = 630), 10-30 (n = 329), and >30 (n = 44) ng/mL, respectively. On multivariate regression analysis, with the iPSA grouped as above, the Gleason score and radiation dose were independent predictors of outcome in this patient group (all p < 0.001). On univariate analysis, a higher radiation dose improved FFBF when the iPSA level was between 10 and 30 ng/mL (p = 0.001) but not when the iPSA level was >30 or <10 ng/mL. Recursive partitioning techniques defined an iPSA cutpoint of 30 ng/mL for delineating intermediate vs. high risk. Patients with a PSA level >30 ng/mL in the absence of Gleason score >7 or T3 disease do poorly when treated with radiotherapy alone and should be considered for long-term androgen deprivation or other aggressive systemic therapy.


Projected changes in distributions of Australian tropical savanna birds under climate change using three dispersal scenarios.
Identifying the species most vulnerable to extinction as a result of climate change is a necessary first step in mitigating biodiversity decline. Species distribution modeling (SDM) is a commonly used tool to assess potential climate change impacts on distributions of species. We use SDMs to predict geographic ranges for 243 birds of Australian tropical savannas, and to project changes in species richness and ranges under a future climate scenario between 1990 and 2080. Realistic predictions require recognition of the variability in species capacity to track climatically suitable environments. Here we assess the effect of dispersal on model results by using three approaches: full dispersal, no dispersal and a partial-dispersal scenario permitting species to track climate change at a rate of 30 km per decade. As expected, the projected distributions and richness patterns are highly sensitive to the dispersal scenario. Projected future range sizes decreased for 66% of species if full dispersal was assumed, but for 89% of species when no dispersal was assumed. However, realistic future predictions should not assume a single dispersal scenario for all species and as such, we assigned each species to the most appropriate dispersal category based on individual mobility and habitat specificity; this permitted the best estimates of where species will be in the future. Under this "realistic" dispersal scenario, projected ranges sizes decreased for 67% of species but showed that migratory and tropical-endemic birds are predicted to benefit from climate change with increasing distributional area. Richness hotspots of tropical savanna birds are expected to move, increasing in southern savannas and southward along the east coast of Australia, but decreasing in the arid zone. Understanding the complexity of effects of climate change on species' range sizes by incorporating dispersal capacities is a crucial step toward developing adaptation policies for the conservation of vulnerable species.


Simian immunodeficiency virus utilizes human and sooty mangabey but not rhesus macaque STRL33 for efficient entry.
It has been established that many simian immunodeficiency virus (SIV) isolates utilize the orphan receptors GPR15 and STRL33 about as efficiently as the chemokine receptor CCR5 for entry into target cells. Most studies were performed, however, with coreceptors of human origin. We found that SIV from captive rhesus macaques (SIVmac) can utilize both human and simian CCR5 and GPR15 with comparable efficiencies. Strikingly, however, only human STRL33 (huSTRL33), not rhesus macaque STRL33 (rhSTRL33), functioned efficiently as an entry cofactor for a variety of isolates of SIVmac and SIV from sooty mangabeys. A single amino acid substitution of S30R in huSTRL33 impaired coreceptor activity, and the reverse change in rhSTRL33 greatly increased coreceptor activity. In comparison, species-specific sequence variations in N-terminal tyrosines in STRL33 had only moderate effects on SIV entry. These results show that a serine residue located just outside of the cellular membrane in the N terminus of STRL33 is critical for SIV coreceptor function. Interestingly, STRL33 derived from sooty mangabeys, a natural host of SIV, also contained a serine at the corresponding position and was used efficiently as an entry cofactor. These results suggest that STRL33 is not a relevant coreceptor in the SIV/macaque model but may play a role in SIV replication and transmission in naturally infected sooty mangabeys.


Phaclofen-reversible effects of GABA in the spinal cord of the rat.
Our earlier observation that intrathecal administration of L- and D-baclofen had different effects on sympathetic output regulating arterial pressure and heart rate in the rat prompted the present study which was designed to determine whether intrathecal administration of GABA elicits a phaclofen-reversible effect on arterial pressure and/or heart rate and whether this effect mimics that of L-baclofen or that of D-baclofen. Following intrathecal administration of the GABAA antagonist, bicuculline (10 nmol), at the T9 level, administration of GABA at a dose of 5 mumol (n = 8) decreased arterial pressure and heart rate by about 25 mm Hg and 45 bpm, respectively. The responses started at 1-2 min and lasted 3-20 min; comparison was made with rats given NaCl (5 mumol; n = 5), which was without effect on arterial pressure and heart rate. In rats pretreated with both bicuculline and the GABAB antagonist, phaclofen (5 mumol intrathecally; n = 9), the effect of GABA on arterial pressure was attenuated and the effect of GABA on heart rate was absent; comparisons were made with rats given bicuculline, phaclofen and NaCl (n = 5) and with rats given bicuculline, NaCl and GABA (n = 6). These data suggest that there is a phaclofen-reversible effect of GABA in spinal pathways regulating sympathetic output and that this effect of GABA resembles that L-baclofen reported in our earlier study.(ABSTRACT TRUNCATED AT 250 WORDS)


Systematic review of the research evidence examining the effectiveness of interventions using a sensory integrative approach for children.
Twenty-seven studies were systematically reviewed to identify, evaluate, and synthesize the research literature on the effectiveness of sensory integration (SI) intervention on the ability of children with difficulty processing and integrating sensory information to engage in desired occupations and to apply these findings to occupational therapy practice. Results suggest the SI approach may result in positive outcomes in sensorimotor skills and motor planning; socialization, attention, and behavioral regulation; reading-related skills; participation in active play; and achievement of individualized goals. Gross motor skills, self-esteem, and reading gains may be sustained from 3 mo to 2 yr. Findings may be limited by Type II error because of small sample sizes, variable intervention dosage, lack of fidelity to intervention, and selection of outcomes that may not be meaningful to clients and families or may not change with amount of treatment provided. Replication of findings with methodologically and theoretically sound studies is needed to support current findings.


Helping, spirituality and Alcoholics Anonymous in recovery.
The purpose of this study is to examine how helping activities and spirituality--perhaps key influences on sobriety--change over recovery. The study also explores interrelations among Alcoholics Anonymous (AA), helping and spirituality. Questionnaires were administered to recovering alcoholics (118 men, 80 women) recruited at AA and Women for Sobriety meetings, treatment programs and through personal connections. A helping scale measured Recovery Helping (8-item alpha = 0.78), Life Helping (12-item alpha = 0.62), and Community Helping (6-item alpha = 0.60). The Daily Spiritual Experiences scale assessed two components of spirituality identified by factor analysis: Theism and Self-Transcendence. Two components of an AA scale, Involvement and Achievement, were also treated separately on the basis of factor analysis. Structural equation modeling revealed that longer sobriety predicted significantly more time spent on Community Helping, less time spent on Recovery Helping and higher levels of Theism, Self-Transcendence and AA Achievement. Model covariances revealed that both AA components were related to more Recovery Helping and higher Theism. Both spirituality components related to all forms of helping, with one exception. The findings highlight important changes in helping with length of sobriety. As their sobriety accumulates, recovering alcoholics seem to devote less time to informal helping and more time to organized community projects--perhaps indicating evolving needs and abilities. The results also suggest roles for AA and spirituality in encouraging helping, and they indicate that some forms of spirituality relate to AA affiliation. Future work might establish whether and when helping in different domains contributes to the maintenance of abstinence and to other drinking-related outcomes.


Expression of autocrine motility factor receptor (AMFR) in human breast and lung invasive micropapillary carcinomas.
The aim of this study was to evaluate the clinicopathological significance of autocrine motility factor receptor (AMFR) expression in a variety of human invasive micropapillary carcinomas (IMPC). AMFR expression was compared in 111 samples of a variety of human IMPCs which had intrinsic non-micropapillary components and with 26 cases of control pulmonary adenocarcinoma (CPA, carcinoma without an IMPC component) by immunohistochemistry (IHC). In the 137 cases analysed, AMFR expression was significantly elevated in the IMPC components compared to the non-IMPC components (p = .005) and normal tissues (p < .001). AMFR expression was also higher in the IMPC samples compared to their intrinsic non-IMPC components (p = .0234). Between the 69 cases of lung IMPC and 26 cases of CPA, AMFR expression was notably higher in the IMPC components than in the CPA components (p = .0455). However, there was no significant difference between the non-IMPC components in the lung and the CPA components (p = .4584). Moreover, in breast cancer, elevated AMFR expression was not significantly correlated with mixed type or pure type IMPC (p = .5969) or with age, gender, T stage, or lymph node metastasis (LNM). Between IMPC and CPA of the lung, there was no statistical significance in age, T stage, and LNM, where AMFR expression was higher in IMPC (p = .0071). Thus this study demonstrated that AMFR was overexpressed in a variety of human IMPC components compared with non-micropapillary components. This suggests that AMFR expression is a potential new prognostic indicator for different types of human IMPC, which might thus be a new therapeutic target.


Human punishment is motivated by inequity aversion, not a desire for reciprocity.
Humans involved in cooperative interactions willingly pay a cost to punish cheats. However, the proximate motives underpinning punitive behaviour are currently debated. Individuals who interact with cheats experience losses, but they also experience lower payoffs than the cheating partner. Thus, the negative emotions that trigger punishment may stem from a desire to reciprocate losses or from inequity aversion. Previous studies have not disentangled these possibilities. Here, we use an experimental approach to ask whether punishment is motivated by inequity aversion or by a desire for reciprocity. We show that humans punish cheats only when cheating produces disadvantageous inequity, while there is no evidence for reciprocity. This finding challenges the notion that punishment is motivated by a simple desire to reciprocally harm cheats and shows that victims compare their own payoffs with those of partners when making punishment decisions.


Manganese exposure: cognitive, motor and behavioral effects on children: a review of recent findings.
Manganese (Mn) is an essential element, but can be neurotoxic when exceeding the homeostatic range. We reviewed the most recent human studies (from January 2011 to July 2012) regarding the association between Mn exposure and cognitive, motor and behavioral effects on children. A total of 10 articles were located; data were collected from five different countries. Six studies showed adverse effect of Mn on cognitive function. The most adopted cognitive test was the Wechsler Intelligence Scale for Children (WISC) or some subtests from it and results suggest an inverse association of higher Mn exposure with lower intellligence quotient. Three studies focused on motor effects of Mn; two of them found a direct association of higher Mn exposure with increased motor impairment. Two studies assessed Mn impact on behavior; one of them showed a correlation between higher Mn in water and both internalizing and externalizing behavioral scores. Potential limitations of these studies included the lack of validated biomarkers and the lack of consideration of mixed co-exposure with other neurotoxic agents. Despite some potential limitations of the reviewed studies, the adverse effects of manganese exposure on the developing brain is well demonstrated and preventive strategies should be promoted.


Malleability of the motor system: training for maximizing power output.
The training programmes used to improve the strength and/or endurance capacities of athletes are described. Specific stimuli are either high tension in contracting myofibrils or high turnover rates in the oxidative metabolism of the muscle cell. Structural adaptations consist of the synthesis of additional myofibrillar material or increased volume density of both interfibrillar and subsarcolemmal mitochondria. Transformation of fibre types at the level of the molecular structure of myosin seems possible with high-intensity training of long duration. Functional adaptations consist of higher activities of important enzymes in either anaerobic or aerobic energy metabolism and of larger intracellular stores of the respective substrates. All adaptations are highly specific and reversible through detraining or immobilization of the muscle.


Strong and electrically conductive graphene-based composite fibers and laminates.
Graphene is an ideal candidate for lightweight, high-strength composite materials given its superior mechanical properties (specific strength of 130 GPa and stiffness of 1 TPa). To date, easily scalable graphene-like materials in a form of separated flakes (exfoliated graphene, graphene oxide, and reduced graphene oxide) have been investigated as candidates for large-scale applications such as material reinforcement. These graphene-like materials do not fully exhibit all the capabilities of graphene in composite materials. In the current study, we show that macro (2 inch × 2 inch) graphene laminates and fibers can be produced using large continuous sheets of single-layer graphene grown by chemical vapor deposition. The resulting composite structures have potential to outperform the current state-of-the-art composite materials in both mechanical properties and electrical conductivities (>8 S/cm with only 0.13% volumetric graphene loading and 5 × 10(3) S/cm for pure graphene fibers) with estimated graphene contributions of >10 GPa in strength and 1 TPa in stiffness.


Whole-body doses of occupationally exposed female workers in Nigeria (1999-2001).
The work described in this note is based on the national dose registry of radiation workers in Nigeria kept by the Federal Radiation Protection Service. In each of the three years (1999-2001) used for this analysis, the number of male radiation workers was more than that of female radiation workers in both medicine and industry. The ratio of the number of female radiation workers to that of their male counterparts, however, is smaller in industry. The mean of the annual doses of all radiation workers increased from 3.6 mSv in 1999 to 4.7 mSv in 2000 and to 7.7 mSv in 2001. This increase was a result of the yearly increase in mean annual doses to radiation workers in industry. In the industrial category, the mean annual doses of female radiation workers were higher than those of their male counterparts in 1999 and 2001 in both occupation categories. In 2000, while the mean annual doses were the same for both male and female radiation workers in the medical category, the mean annual dose of male radiation workers was higher than that of female radiation workers in industry. Female radiation workers received the highest annual doses in 1999 and 2001. These results indicate the need for the regulatory authority to pay more careful attention to the control of female radiation workers' exposures.


Identification of probabilistic cellular automata.
The identification of probabilistic cellular automata (PCA) is studied using a new two stage neighborhood detection algorithm. It is shown that a binary probabilistic cellular automaton (BPCA) can be described by an integer-parameterized polynomial corrupted by noise. Searching for the correct neighborhood of a BPCA is then equivalent to selecting the correct terms which constitute the polynomial model of the BPCA, from a large initial term set. It is proved that the contribution values for the correct terms can be calculated independently of the contribution values for the noise terms. This allows the neighborhood detection technique developed for deterministic rules in to be applied with a larger cutoff value to discard the majority of spurious terms and to produce an initial presearch for the BPCA neighborhood. A multiobjective genetic algorithm (GA) search with integer constraints is then evolved to refine the reduced neighborhood and to identify the polynomial rule which is equivalent to the probabilistic rule with the largest probability. A probability table representing the BPCA can then be determined based on the identified neighborhood and the deterministic rule. The new algorithm is tested over a large set of one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) BPCA rules. Simulation results demonstrate the efficiency of the new method.


The anatomy of job polarisation in the UK.
This paper studies the contribution of different skill groups to the polarisation of the UK labour market. We show that the large increase in graduate numbers contributed to the substantial reallocation of employment from middling to top occupations which is the main feature of the polarisation process in the UK over the past three decades. The increase in the number of immigrants, on the other hand, does not account for any particular aspect of the polarisation in the UK. Changes in the skill mix of the workforce account for most of the decline in routine employment across the occupational distribution, but within-group changes account for most of the decline in routine occupations in middling occupations. In addition, there is no clear indication of polarisation within all skill groups-a fact that previous literature has cited as evidence that technology drives the decline of middling occupations. These findings differ substantially from previous evidence on the US and cast doubts on the role of technology as the main driver of polarisation in the UK.


Toxic effects of the administration of Mikania glomerata Sprengel during the gestational period of hypertensive rats.
Herbal medicine is an ancient practice that has been gaining acceptance of the medical class through scientific studies that prove its effectiveness. However, its use should still be cautious. Medicinal plants have potential toxic effects not yet discovered, and may have unproven interactions with other medications. The use of drugs during pregnancy is still very dangerous and vigorously studied; however, there are few studies of herbal medicines in pregnant women. Existing studies prioritize on teratogenic or abortifacient effects. The aim of this study was to analyze the toxic effects of Mikania glomerata Sprengel administration, popularly known as "guaco" during the gestational period of hypertensive rats. For this experimental groups consisting of pregnant Wistar rats received treatments with guaco extract (1 to 2 mL). In order to analyze the possible toxic effects of guaco during pregnancy, weight gain of rats was assessed during pregnancy; reproductive performance of rats, morphological parameters, and fetal placental histology were compared. Although some parameters presented significant differences, we can conclude that changes prioritized by literature, such as toxicity, vasodilation and hypotension, have not been caused by guaco. The only fetal changes observed were due to the maternal hypertension. Some studies have reported vasodilator and hypotensive effects of guaco. However, only a few studies exist, and its actual effects remain unknown. Specific studies should be developed with higher doses of guaco for a definitive conclusion of its toxic and non-toxic effects.


Topical treatment of psoriasis with fludarabine.
Fludarabine is not used as a topical medication for the treatment of psoriasis. In this study we evaluated the efficacy of fludarabine for this purpose. Four male patients with two bilaterally symmetrical psoriatic plaques were treated with 0.2 percent topical fludarabine in aquaphor (fludarabine site) or aquaphor alone (control site). The fludarabine and control sites were compared before and during the study on a weekly basis for three weeks by degree of redness, scaliness, and thickness on a scale of 0 to 4 (0, not apparent; 4, very apparent). The results of our study showed no significant difference between topical fludarabine and aquaphor in the treatment of psoriatic plaques.


Chronic Lymphocytic Thyroiditis May Lower Accuracy of AUS/FLUS Cytopathology in Surgical Patients.
Chronic lymphocytic thyroiditis (CLT) increases cytologic atypia on fine-needle aspiration of thyroid nodules, and its effect on rate of malignancy in atypia of undetermined significance (AUS)/follicular lesions of undetermined significance (FLUS) thyroid nodules remains unclear. This study evaluates the effect of concomitant CLT on malignancy rates of AUS/FLUS thyroid nodules in surgical patients. Retrospective review of 1061 patients who underwent thyroidectomy for a dominant thyroid nodule from a single institution was performed. Fine-needle aspiration was classified according to the Bethesda System for Reporting Thyroid Cytopathology. Patients with AUS/FLUS cytopathology were classified into two cohorts: AUS/FLUS with CLT and AUS/FLUS without CLT. Final pathology was reviewed, and the cohorts were further stratified into benign and malignant subgroups. When applicable, patients with gene expression classifier (GEC) testing were reviewed and the positive predictive value (PPV) was calculated. Of the entire surgical series, 293 (28%) patients had AUS/FLUS cytopathology with a rate of malignancy of 56% (163/293) on final pathology. Seventy-three (25%) patients had AUS/FLUS with CLT, of which 44% (n = 32) were malignant by final pathology. The remaining 75% (n = 220) had AUS/FLUS without CLT, 60% (n = 131) of which were malignant. GEC testing was performed in 36 of the AUS/FLUS with CLT patients, where of the 33 suspicious results, 17 were malignant on final pathology, yielding a PPV of 52%. The rate of malignancy for AUS/FLUS thyroid nodules is lower with coexisting CLT, and similar to previous studies, the PPV of GEC testing is approximately 50%. Cytologic atypia due to CLT may increase more AUS/FLUS results in thyroid nodules, which may lead to overestimation of malignancy rates in this patient population.


Preoperative CT histogram analysis to predict the expression of Ki-67 in solid pseudopapillary tumours of the pancreas.
To explore the value of preoperative computed tomography (CT) histogram features in predicting the expression status of Ki-67 in patients with solid pseudopapillary pancreatic tumours (SPTP). This retrospective study analysed venous phase CT images of 39 patients with SPTP confirmed at surgery and histopathology and measured using the Ki-67 proliferation index from November 2015 to February 2022. According to the Ki-67 proliferation index, they were divided into high expression (Ki-67 ≥ 4%) and low expression (Ki-67 < 4%) groups. The histogram features of quantitative parameters were extracted using MaZda software, and the quantitative parameters of CT histograms were compared between groups. The receiver operating characteristic (ROC) curves of the patients were plotted according to the parameters, with statistically significant differences. The area under the curve (AUC), sensitivity, and specificity were calculated, and the effectiveness of the histogram parameters in predicting Ki-67 expression was analysed and evaluated. In total, 27 SPTP patients were enrolled, including 11 with high expression of Ki-67 and 16 with low expression. Comparative analysis of the Ki-67 high- and low-expression groups revealed a statistically significant in necrosis and variance (p<0.05). ROC curve analysis showed that the AUC of necrosis and variance predicting Ki-67 expression status were 0.753 and 0.841, the sensitivities were 81.8% and 81.3%, and the specificities were 68.7% and 81.8%, respectively. Preoperative CT histogram features help predict Ki-67 expression status in patients with SPTP.


Dopamine activity in the nucleus accumbens during consummatory phases of oral ethanol self-administration.
BACKGROUND This present study was designed to clarify the role of dopamine in the nucleus accumbens during operant ethanol self-administration by separating bar pressing (ethanol seeking) from ethanol consumption. Furthermore, we sought to define the relationship between ethanol in the brain and the accumbal dopamine response after oral self-administration of ethanol. Two separate groups of male Long-Evans rats were trained to bar press with 10% ethanol or water. Rats were trained to elicit an escalating number of bar presses across daily sessions before gaining access to the drinking solution for 20 min. Microdialysis was performed before (during a waiting period), during, and after bar pressing and drinking. A handling control group was included, but did not receive training. A significant increase in dopamine occurred during placement of the rats into the operant chamber in trained rats and handling controls. The lever-pressing period did not produce an increase in dialysate dopamine. Accumbal dopamine was increased in the first 5 min of ethanol, but not water, consumption. Ethanol appeared in the dialysate sample following ethanol availability, and peak concentrations were reached at 10 min. Most of the ethanol and water consumption occurred within 5 min of fluid access. The probes were distributed in the core (32%), shell (32%), and core plus shell (36%) regions of the nucleus accumbens. The enhancement of dopamine during transfer into the operant chamber does not depend on anticipation or operant training with ethanol or water reinforcement. Furthermore, the difference between the time course of accumbal dopamine and ethanol in dialysates suggests that the dopamine response is not solely due to pharmacological effects of ethanol. The dopamine response may be associated with the stimulus properties of ethanol presentation, which would be strongest during consumption.


[The role of the hypothalamus in the mechanism of positional nystagmus].
The typical positional nystagmus was induced in 30 intact rabbits with injection of 0.1-0.4 ml of 0.03-0.05% dicaine solution into the cerebral cisterna magna. The positional nystagmus resulted, supposedly, from the effect of the anesthetic upon the basal structures of the 3rd ventricle of the brain, upon the hypothalamus in particular. The trigger mechanism of the phenomenon is the displacement of the membraneous ampullae of semicircular canals at the tilting of the head. To prove this, 0.01-0.03 ml of 4% dicaine solution were injected directly into the anterior and posterior hypothalamus through a metallic cannula. When introduced into the anterior hypothalamus the dose of the anesthetic necessary for occurrence of the positional nystagmus is two or three times lesser than when it is injected into the posterior nypothalamus. In two delabyrinthed rabbits we failed to induce the nystagmus in this way.


The relative impact of chronic food restriction and acute food deprivation on plasma hormone levels and hypothalamic neuropeptide expression.
Our understanding of the central regulation of food intake and body weight has increased tremendously through implication of a high number of neuropeptides. However, lack of all-embracing studies have made comparison difficult in the past. The objective of this study was to demonstrate the relative importance of the different neuropeptides in terms of involvement in appetite regulatory mechanisms. We quantified expression levels of 21 hypothalamic neuropeptides and circulating levels of leptin, insulin, corticosterone, adrenocorticotropic hormone, ghrelin and adiponectin in rats after acute food deprivation and chronic food restriction using validated quantitative real-time PCR and hormone measurements. Body weight, insulin and leptin were reduced whereas corticosterone was increased by both acute food deprivation and chronic food restriction. Our results confirmed the relative importance in body weight homeostasis of neuropeptide Y and proopiomelanocortin, which were increased and decreased as predicted. The expression of other neuropeptides previously attributed central roles in body weight homeostasis, e.g. melanin-concentrating hormone and orexin, appeared to be less affected by the treatments. Moreover, the expression of dynorphin, galanin-like peptide and neuropeptide B was dramatically reduced after both treatments. This suggests that the latter neuropeptides--although previously known to be involved in body weight homeostasis--may be of unexpected importance in states of negative energy balance.


Mutational decay and age of chloroplast and mitochondrial genomes transferred recently to angiosperm nuclear chromosomes.
Transfers of organelle DNA to the nucleus established several thousand functional genes in eukaryotic chromosomes over evolutionary time. Recent transfers have also contributed nonfunctional plastid (pt)- and mitochondrion (mt)-derived DNA (termed nupts and numts, respectively) to plant nuclear genomes. The two largest transferred organelle genome copies are 131-kb nuptDNA in rice (Oryza sativa) and 262-kb numtDNA in Arabidopsis (Arabidopsis thaliana). These transferred copies were compared in detail with their bona fide organelle counterparts, to which they are 99.77% and 99.91% identical, respectively. No evidence for purifying selection was found in either nuclear integrant, indicating that they are nonfunctional. Mutations attributable to 5-methylcytosine hypermutation have occurred at a 6- to 10-fold higher rate than other point mutations in Arabidopsis numtDNA and rice nuptDNA, respectively, revealing this as a major mechanism of mutational decay for these transferred organelle sequences. Short indels occurred preferentially within homopolymeric stretches but were less frequent than point mutations. The 131-kb nuptDNA is absent in the O. sativa subsp. indica or Oryza rufipogon nuclear genome, suggesting that it was transferred within the O. sativa subsp. japonica lineage and, as revealed by sequence comparisons, after its divergence from the indica chloroplast lineage. The time of the transfer for the rice nupt was estimated as 148,000 (74,000--296,000) years ago and that for the Arabidopsis numtDNA as 88,000 (44,000--176,000) years ago. The results reveal transfer and integration of entire organelle genomes into the nucleus as an ongoing evolutionary process and uncover mutational mechanisms affecting organelle genomes recently transferred into a new mutational environment.


Vaccine implementation factors affecting maternal tetanus immunization in low- and middle-income countries: Results of the Maternal Immunization and Antenatal Care Situational Analysis (MIACSA) project.
To examine the characteristics of existing maternal tetanus immunization programmes for pregnant women in low- and middle-income countries (LMICs) and to identify and understand the challenges, barriers and facilitators associated with maternal vaccine service delivery that may impact the introduction and implementation of new maternal vaccines in the future. A mixed methods, cross sectional study with four data collection phases including a desk review, online survey, telephone and face-to-face interviews and in country visits. LMICs. The majority of countries (84/95; 88%) had a maternal tetanus immunization policy. Countries with high protection at birth (PAB) were more likely to report tetanus toxoid-containing vaccine (TTCV) coverage targets > 90%. Less than half the countries included in this study had a TTCV coverage target of > 90%. Procurement and distribution of TTCV was nearly always the responsibility of the Expanded Programme on Immunization (EPI), however planning and management of maternal immunization was often shared between EPI and Maternal, Newborn and Child Health (MNCH) programmes. Receipt of TTCV at the same time as the antenatal care visit correlated with high PAB. Most countries (81/95; 85%) had an immunization safety surveillance system in place although only 11% could differentiate an adverse event following immunization (AEFI) in pregnant and non-pregnant women. Recommendations arising from the MIACSA project to strengthen existing services currently delivering maternal tetanus immunization in LMICs include establishing and maintaining vaccination targets, clearly defining responsibilities and fostering collaborations between EPI and MNCH, investing in strengthening the health workforce, improving the design and use of existing record keeping for immunization, adjusting current AEFI reporting to differentiate pregnant women and endeavoring to integrate the provision of TTCV within ANC services where appropriate.


Artificial Intelligence in Predicting Cardiac Arrest: Scoping Review.
Cardiac arrest is a life-threatening cessation of activity in the heart. Early prediction of cardiac arrest is important, as it allows for the necessary measures to be taken to prevent or intervene during the onset. Artificial intelligence (AI) technologies and big data have been increasingly used to enhance the ability to predict and prepare for the patients at risk. This study aims to explore the use of AI technology in predicting cardiac arrest as reported in the literature. A scoping review was conducted in line with the guidelines of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping reviews. Scopus, ScienceDirect, Embase, the Institute of Electrical and Electronics Engineers, and Google Scholar were searched to identify relevant studies. Backward reference list checks of the included studies were also conducted. Study selection and data extraction were independently conducted by 2 reviewers. Data extracted from the included studies were synthesized narratively. Out of 697 citations retrieved, 41 studies were included in the review, and 6 were added after backward citation checking. The included studies reported the use of AI in the prediction of cardiac arrest. Of the 47 studies, we were able to classify the approaches taken by the studies into 3 different categories: 26 (55%) studies predicted cardiac arrest by analyzing specific parameters or variables of the patients, whereas 16 (34%) studies developed an AI-based warning system. The remaining 11% (5/47) of studies focused on distinguishing patients at high risk of cardiac arrest from patients who were not at risk. Two studies focused on the pediatric population, and the rest focused on adults (45/47, 96%). Most of the studies used data sets with a size of <10,000 samples (32/47, 68%). Machine learning models were the most prominent branch of AI used in the prediction of cardiac arrest in the studies (38/47, 81%), and the most used algorithm was the neural network (23/47, 49%). K-fold cross-validation was the most used algorithm evaluation tool reported in the studies (24/47, 51%). AI is extensively used to predict cardiac arrest in different patient settings. Technology is expected to play an integral role in improving cardiac medicine. There is a need for more reviews to learn the obstacles to the implementation of AI technologies in clinical settings. Moreover, research focusing on how to best provide clinicians with support to understand, adapt, and implement this technology in their practice is also necessary.


Diagnosis and Treatment of Myogenous Temporomandibular Disorders: A Clinical Update.
Myogenous temporomandibular disorders (M-TMDs) are the most common chronic orofacial pain, affecting the masticatory muscles and, thus, jaw movement. While a concise diagnosis is crucial to formulate a rational treatment plan, the similarities in clinical presentations that M-TMDs share with other neuromuscular disorders affecting the temporomandibular joint (TMJ) could easily confuse physicians. In addition to the basics, such as thorough history taking and meticulous clinical examinations, different imaging techniques are useful adjuncts to facilitate the diagnostic process. This review presents an overview of the current understanding on a variety of diagnostic and treatment modalities for M-TMD patients. It is essential to highlight that there is not a single treatment for all, and the benefits of multidisciplinary strategies have been noted for the effective management of myogenous TMD pain. Treatment modalities ranging from conservative to minimally invasive options are discussed in this review.


Genetic blueprint of the zoonotic pathogen Toxocara canis.
Toxocara canis is a zoonotic parasite of major socioeconomic importance worldwide. In humans, this nematode causes disease (toxocariasis) mainly in the under-privileged communities in developed and developing countries. Although relatively well studied from clinical and epidemiological perspectives, to date, there has been no global investigation of the molecular biology of this parasite. Here we use next-generation sequencing to produce a draft genome and transcriptome of T. canis to support future biological and biotechnological investigations. This genome is 317 Mb in size, has a repeat content of 13.5% and encodes at least 18,596 protein-coding genes. We study transcription in a larval, as well as adult female and male stages, characterize the parasite's gene-silencing machinery, explore molecules involved in development or host-parasite interactions and predict intervention targets. The draft genome of T. canis should provide a useful resource for future molecular studies of this and other, related parasites.


Screening the methanol extracts of some Iranian plants for acetylcholinesterase inhibitory activity.
Acetylcholinesterase (AChE) is the main enzyme for the breakdown of acetylcholine. Nowadays, usage of the inhibitors of this enzyme is one of the most important types of treatment of mild to moderate neurodegenerative diseases such as Alzheimer's disease. Herbal medicines can be a new source of inhibitors of this enzyme. In this study we examined around 100 different plants to evaluate their inhibitory properties for AChE enzyme. Plants were scientifically identified and their extracts were prepared by methanol percolation. Acetylcholinesterase activity was measured using a colorimetric method in the presence or absence of the extracts. Eserine was used as a positive control. Methanol extracts of the Levisticum officinale, Bergeris integrima and Rheum ribes showed more than 50% AChE inhibitory activity. The inhibition kinetics were studied in the presence of the most effective extracts. L. officinale and B. integrima inhibited AChE activity in a non-competitive manner, while R. ribes competitively inhibitied the enzyme as revealed by double-reciprocal Linweaver-Burk plot analysis. Under controlled condition, K(m) and V(max) values of the enzyme were found to be 9.4 mM and 0.238 mM/min, respectively. However, in the presence of L. officinale, B. integrima, and R. ribes extracts, V(max) values were 0.192, 0.074 and 0.238 mM/min, respectively. Due to the competitive inhibition of the enzyme by R. ribes extract, the K(m) value of 21.2 mM was obtained. The concentration required for 50% enzyme inhibition (IC50 value) was 0.5, 0.9, and 0.95 mg/ml for the L. officinale, B. integrima and R. ribes extracts, respectively. The IC50 of the eserine was determined to be 0.8 mg/ml.


"None of us are lying": an interpretive description of the search for legitimacy and the journey to access quality health services by individuals living with Long COVID.
Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs. Our study was informed by the Levesque et al.'s (2013) "conceptual framework of access to health care." We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed. Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants' Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants' attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and 'normal' results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants. With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately.


A sensitive specific hemolytic assay for proenzyme C1.
The traditional hemolytic assay of the functional activity of C1, the first component of the classical complement pathway, was modified to permit differentiation between proenzyme (unactivated) C1 and the activated state of the enzyme (C1). A two-step assay was developed to quantitate proenzyme C1. The C1 sample to be assayed was first preincubated with C1 inhibitor, a process that specifically inhibits the enzymatic activity of C1 without affecting the subsequent activation of proenzyme C1 by EAC4, a model immune complex. Since the rate of reaction between C1 inhibitor, a serum regulatory protein, and C1 is concentration-dependent, this step is performed at high C1 and C1 inhibitor concentrations. Subsequent dilutions of the sample prevents C1 inhibitor-mediated inactivation of the C1 that is activated during the C1 hemolytic assay. Thus, in the presence of C1 inhibitor, the level of C1 hemolytic activity specifically reflects the activity of proenzyme C1, while in the absence of C1 inhibitor, the hemolytic activity reflects the total activity of C1. Both the absolute and the relative amounts of the proenzyme (unactivated) and activated C1 can thereby be quantitated in most samples. Furthermore, a partially purified C1 inhibitor reagent, easily prepared from serum, was shown to function identically to the purified C1 inhibitor, obviating the need for a multistep isolation procedure for this protein. Using this simple yet sensitive assay to investigate the efficiency of reconstitution of C1 activity from the purified components C1q, C1r, and C1s, we also find evidence for temperature- and concentration-dependent reaction steps in the formation of functional C1.


A curious case of cololithiasis.
Gallstone ileus is an uncommon cause of bowel obstruction that involves cholecystoenteric fistulation and resultant passage of gallstones into the bowel. In the vast majority of cases, the fistula forms between the gallbladder and duodenum leading to small bowel obstruction. We report a case of cholecystocolic fistulation and subsequent large-bowel obstruction in a 75-year-old woman who presented acutely after taking a bowel preparation for an outpatient colonoscopy during the course of an investigation of anaemia and nonspecific abdominal pain. Preintervention imaging revealed a giant gallstone at the rectosigmoid junction, in the presence of a cholecystocolic fistula, and subsequent large bowel obstruction. After a failed period of expectant management, laparotomy and Hartmann's procedure were performed and the patient made an uneventful recovery.


Use of superparamagnetic microbeads in tracking subretinal injections.
The purpose of these studies was to develop a method to track intraocular injections. Retinal pigment epithelial (RPE) cells, purified from adult mouse eyes, were incubated with superparamagnetic microbeads (Dynabeads, 4.5 microm) coated with bovine serum albumin to verify that they could phagocytose the microbeads. For in vivo tracking studies, mice were anesthetized and a small incision was made at the pars plana and 2 mul of microbeads (around 10(5) microbeads) or RPE that had taken up the microbeads were injected into the subretinal space (SRS). Mice were sacrificed at various times after injection. The eyes were enucleated, fixed in formalin, and embedded in paraffin. Sections were stained with H&E, visualized by light microscopy. Some eyes were digested with collagenase and inflammatory cells determined by flow cytometry. Cultured adult RPE phagocytosed the magnetic microbeads. One day after injection into the SRS, a retinal detachment was observed at the injection point and free microbeads were easily detected at this site. One week later, the host RPE cells had phagocytized the microbeads and the retina had reattached. No inflammatory response was detected in the eyes that were injected with microbeads in the SRS at any time examined. Histology showed normal morphology of all retinal layers around the injection site. The microbeads remained in situ throughout the study. Protein coated magnetic microbeads are non-inflammatory after injection into the SRS. Host RPE cells phagocytized the microbeads and the retina maintained a healthy morphology after reattachment. This technique proved not only to be a good training tool to determine the precise location of injection, but also provided a noninflammatory method for long term marking of delivery into the SRS. However, the microbeads can not be used as a tracer of injected RPE because the microbeads were readily transferred to the endogenous RPE.


Sleep Disorders and Their Management in Children With Ehlers-Danlos Syndrome Referred to Sleep Clinics.
The nature of sleep disorders in children with Ehlers-Danlos syndrome (EDS) is unknown. We aimed to describe the type, the management, and the short-term outcome of sleep disorders in children with EDS referred to sleep clinics. This is a retrospective review of medical records and polysomnography tests of children with EDS younger than 18 years who were referred to the sleep clinic. Demographic information and medical history were collected, and polysomnography tests were reviewed. Questionnaires completed during previous clinic visits, including the Pediatrics Sleep Questionnaire (PSQ), Epworth Sleepiness Scale (ESS), and Pediatric Quality of Life Inventory (PedsQL), were also evaluated. Sixty-five patients with EDS-hypermobility type were included. The mean age was 13.15 ± 3.9 years. There were 68% of patients who were female, and 91% of patients were Caucasian. The mean follow-up period was 1.14 ± 1.55 years. Common sleep diagnoses included insomnia (n = 14, 22%), obstructive sleep apnea (OSA) (n = 17, 26%), periodic limb movement disorder (PLMD) (n = 11, 17%), and hypersomnia (n = 10, 15%). In addition, 65% required pharmacologic treatment and 29% were referred to behavioral sleep medicine. For OSA, two patients required continuous positive airway pressure. A significant improvement was observed in the PSQ, ESS, and PedsQL scores during follow-up visits after treatment (n = 34; P = .0004, 0.03, and 0.01, respectively). There is a high prevalence of sleep disorders, including OSA, insomnia, PLMD, and hypersomnia in children with EDS referred to sleep clinics. Specific management can improve quality of life and questionnaire scores of this patient population. Our study emphasizes the importance of screening for sleep disorders in children with EDS.


Predictors of mortality in patients with Acute Coronary Syndrome (ACS) undergoing Percutaneous Coronary Intervention (PCI): Insights from National Cardiovascular Disease Database (NCVD), Malaysia.
The aim of this study is to determine risks factor of mortality among patient with post percutaneous coronary intervention. Estimation of post operative mortality risk factor is essential for planning prevention modalities. This is retrospective cohort study based on secondary data extracted from the National Cardiovascular Disease Database (NCVD-ACS and NCVD PCI). Both these registries were interlinked and was further matched to JPN (Jabatan Pendaftaran Negara/National registration Department) to assess mortality among the patients who underwent PCI and all death which occurred in between 2007, 2008 and 2009. There were 630 patients in this studied. Age, history of diabetes mellitus, peripheral vascular, renal failure and previous percutaneous coronary intervention were univariately associated with mortality. However based on logistics stepwise method, only age and history of renal failure had showed statistically significant and sizeable odds ratio in predicting the patient died of coronary death. Older age and renal failure are the predicting factors for mortality among patients with post percutaneous coronary intervention.


Carotid artery stenting.
Atherosclerotic narrowing (stenosis) of the internal carotid artery accounts for about 10-15% of ischaemic strokes. Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic stenosis and - to a lesser degree - with asymptomatic carotid stenosis. Endovascular treatment including balloon angioplasty and carotid artery stenting (CAS) has emerged as an alternative to CEA to treat carotid stenosis. The present review summarises the existing evidence on risks and benefits of CAS in comparison with CEA, with a focus on evidence from randomised clinical trials. Across all randomised trials, CEA was associated with a lower risk of peri-procedural stroke or death than CAS, while CAS had lower risks of myocardial infarction, cranial nerve palsy and access site haematoma. The increased stroke risk with CAS is mainly observed in elderly patients; therefore, CAS appears to be a safe option to CEA in younger patients. In the first few years following treatment, both procedures are equally effective in preventing ipsilateral recurrent strokes. Nevertheless, long-term follow-up of ongoing trials must be awaited to investigate whether a potential increase in recurrent stenosis following CAS might limit the long-term effectiveness in stroke prevention. The optimal treatment for asymptomatic carotid stenosis remains to be determined in ongoing clinical trials.


Mapping fluorophore distributions in three dimensions by quantitative multiple angle-total internal reflection fluorescence microscopy.
The decay of evanescent field intensity beyond a dielectric interface depends upon beam incident angle, enabling the 3-d distribution of fluorophores to be deduced from total internal reflection fluorescence microscopy (TIRFM) images obtained at multiple incident angles. Instrumentation was constructed for computer-automated multiple angle-TIRFM (MA-TIRFM) using a right angle F2 glass prism (n(r) 1.632) to create the dielectric interface. A laser beam (488 nm) was attenuated by an acoustooptic modulator and directed onto a specified spot on the prism surface. Beam incident angle was set using three microstepper motors controlling two rotatable mirrors and a rotatable optical flat. TIRFM images were acquired by a cooled CCD camera in approximately 0.5 degree steps for >15 incident angles starting from the critical angle. For cell studies, cells were grown directly on the glass prisms (without refractive index-matching fluid) and positioned in the optical path. Images of the samples were acquired at multiple angles, and corrected for angle-dependent evanescent field intensity using "reference" images acquired with a fluorophore solution replacing the sample. A theory was developed to compute fluorophore z-distribution by inverse Laplace transform of angle-resolved intensity functions. The theory included analysis of multiple layers of different refractive index for cell studies, and the anisotropic emission from fluorophores near a dielectric interface. Instrument performance was validated by mapping the thickness of a film of dihexyloxacarbocyanine in DMSO/water (n(r) 1.463) between the F2 glass prism and a plano-convex silica lens (458 mm radius, n(r) 1.463); the MA-TIRFM map accurately reproduced the lens spherical surface. MA-TIRFM was used to compare with nanometer z-resolution the geometry of cell-substrate contact for BCECF-labeled 3T3 fibroblasts versus MDCK epithelial cells. These studies establish MA-TIRFM for measurement of submicroscopic distances between fluorescent probes and cell membranes.


Intractable temporal lobe epilepsy: comparison of positron emission tomography with qualitative and quantitative MR.
To compare the ability of qualitative fludeoxyglucose F 18 positron emission tomography (QPET), qualitative MR imaging (QMR), and quantitative MR imaging with hippocampal formation volumetric assessment (HV MR) to lateralize the seizure focus in patients with temporal lobe epilepsy. Sixteen consecutive patients undergoing presurgical examination for temporal lobe seizures had QPET, QMR, and HV MR. The presence of temporal lobe epilepsy was confirmed by Engel class I or II outcomes at 1-year postoperative follow-up examinations. A QPET, QMR, or HV MR study was considered to be lateralizing if it matched the side of the seizure focus, nonlateralizing if it did not lateralize the seizure focus to either temporal lobe, or incorrectly lateralizing if it lateralized the seizure focus to the incorrect side. Of 16 patients with proved temporal lobe seizures, QPET was correctly lateralizing in nine (56%), nonlateralizing in six (37.5%), and incorrectly lateralizing in one (6%). QMR was correctly lateralizing in six (37.5%), nonlateralizing in six (37.5%), and incorrectly lateralizing in four (25%). HV MR was correctly lateralizing in all 16 patients (100%). Age at onset, seizure duration, and total number of seizures did not correlate with QPET, QMR, and HV MR lateralization. Our results show that each imaging technique yields useful information for seizure lateralization in temporal lobe epilepsy and that HV MR yields considerably more information that QPET or QMR.


Mucosal impedance for esophageal disease: evaluating the evidence.
Impedance has traditionally been employed in esophageal disease as a means to assess bolus flow and reflux episodes. Recent and ongoing research has provided new and novel applications for this technology. Measurement of esophageal mucosal impedance, via either multichannel intraluminal impedance catheters or specially designed endoscopically deployed impedance catheters, provides a marker of mucosal integrity. Mucosal impedance has been shown to segregate gastroesophageal reflux disease (GERD) and eosinophilic esophagitis from non-GERD controls and may play a role in predicting response to reflux intervention. More data are needed with regard to other esophageal subgroups, outcome studies, and functional disease. Our paper reviews the history of impedance in esophageal disease, the means of assessing baseline and mucosal impedance, data with regard to the newly developed mucosal impedance probes, the clinical utility of mucosal impedance in specific clinical conditions, and limitations in our existing knowledge, along with suggestions for future studies.


A Random Dot E stereogram for the vision screening of children.
The purpose of school vision screenings is to detect those children with vision problems that may impede normal development (eg, amblyopia, refractive error, strabismus, suppression). In a double-blind investigation, 483 schoolchildren, ranging in age from 5 to 13 years, had their vision screened using both the Random Dot E (RDE) stereogram and the Modified Clinical Technique (MCT). The validity of each technique was determined using the phi coefficient and was compared with results of similar reports in the literature for the Modified Clinical Technique, Snellen letter acuity, and vision-screening kits. Our data show that the RDE is more effective than five of six other techniques in identifying those children who need further visual examination. In addition, screening with the RDE can be taught to nonprofessionals in ten minutes or less, can be completed on each child within two minutes, and is inexpensive.


I-kappa B kinases alpha and beta have distinct roles in regulating murine T cell function.
NF-kappaB is a transcription factor that regulates a variety of genes involved in the control of the immune and inflammatory responses. Activation of NF-kappaB is mediated by an inducible I-kappaB kinase (IKK) complex comprised of two catalytic subunits, IKKalpha and IKKbeta. In this study, the role of these kinases in the development and function of T lymphocytes was explored using transgenic mice expressing the dominant-negative forms of one or both kinases under the control of a T cell-specific promoter. Activation of the NF-kappaB pathway in thymocytes isolated from these transgenic mice following treatment with either PMA and ionomycin or anti-CD3 was markedly inhibited. Although inhibition of IKKalpha and/or IKKbeta function did not alter T cell development in these transgenic mice, the proliferative response to anti-CD3 was reduced in thymocytes isolated from mice expressing dominant-negative IKKbeta. However, inhibition of both IKKalpha and IKKbeta was required to markedly reduce cytokine production in thymocytes isolated from these transgenic mice. Finally, we demonstrated that IKKalpha and IKKbeta have opposite roles on the regulation of anti-CD3-induced apoptosis of double-positive thymocytes. These results suggest that IKKalpha and IKKbeta have distinct roles in regulating thymocyte function.


Impacted morsellised allograft and cemented cup in acetabular revision surgery. A five to nine year follow-up study.
Seventy cemented cups associated with impacted morsellised allograft in revision surgery in hips with an acetabular bone defect greater than 30% (Paprosky Grades 3A and 3B) were analyzed. The mean follow-up was 6.8 years. One hip showed cup migration and was re-revised; this represents a total cumulative probability of re-revision of the cup of 1.4 2.8%. Radiolucent lines were uncommon: six cups showed radiolucent lines in DeLee and Charnley zone 1, five in zones 1 and 2, one in all three zones, while one hip showed migration.Although the frequent use of a metallic mesh makes graft remodeling difficult to evaluate, six hips showed minor and one major bone resorption. The mid-term results with impacted allograft and cemented all-polyethylene cups are favourable in acetabular revision surgery. (Hip International 2002; 12: 281-8).


The hair growth promoting effect of Asiasari radix extract and its molecular regulation.
Hair loss is a distressing condition for an increasing number of men and women. It is of great importance; therefore, to develop new therapies for the treatment of hair loss. We examined the effects of 45 plant extracts that have been traditionally used for treating hair loss in oriental medicine in order to identify potential stimulants of hair growth. Six-week-old female C57BL/6 and C3H mice were used for evaluating the hair growth-promoting effects of the plant extracts. Topical application onto the backs of the C57BL/6 and C3H mice was performed daily for 30 days and 45 days, respectively. Protein synthesis was measured by the cysteine uptake assay, using cultured murine vibrissae follicles. Proliferation of the immortalized human keratinocyte cell line (HaCaT) and human dermal papilla (DP) cells was evaluated by the MTT and thymidine incorporation assays. The mRNA levels of several growth factors that have been implicated in hair growth control were measured by reverse transcription-polymerase chain reaction (RT-PCR). Among the tested plant extracts, the extract of Asiasari radix showed the most potent hair growth stimulation in C57BL/6 and C3H mice experiments. In addition, this extract markedly increased the protein synthesis in vibrissae follicle cultures and the proliferation of both HaCaT and human DP cells in vitro. Moreover, the A. radix extract induced the expression of VEGF in human DP cells that were cultured in vitro. These results suggest that the A. radix extract has hair growth-promoting potential, and that this effect may be due to its regulatory effects on both cell growth and growth factor gene expression.


Auditory aversive learning increases discrimination thresholds.
Animal studies of discriminative fear conditioning traditionally use stimuli that are distant in physical features and thus easily distinguished perceptually. Independently, human studies have shown that training mostly improves discrimination thresholds. We found that aversive learning actually induced an increase in discrimination thresholds in humans and that subjective aversion during conditioning predicted the individual threshold change. This counterintuitive performance deterioration occurred when using odors or sounds as aversive reinforcers and was not a result of attentional distraction or decision bias. In contrast, positive reinforcement or mere exposure induced the typically reported decrease in thresholds. Our findings indicate that aversive outcomes induce wider stimulus generalization by modulating perceptual thresholds, suggesting the engagement of low-level mechanisms. We suggest that for risk- or loss-related stimuli, less specificity could be a benefit, as it invokes the same mechanisms that respond quickly and efficiently in the face of danger.


Osteoid osteoma of the hallux.
A case involving a 29-year-old female with aspirin allergy who exhibited osteoid osteoma at the distal phalanx of the hallux is presented. Osteoid osteoma is a relatively rare occurrence in the foot (1). It is a benign bone tumor usually consisting of an oval osteolytic area with a central nidus (2). Pathologic, clinical, and radiographic findings are included.


On biodiversity conservation and poverty traps.
This paper introduces a special feature on biodiversity conservation and poverty traps. We define and explain the core concepts and then identify four distinct classes of mechanisms that define important interlinkages between biodiversity and poverty. The multiplicity of candidate mechanisms underscores a major challenge in designing policy appropriate across settings. This framework is then used to introduce the ensuing set of papers, which empirically explore these various mechanisms linking poverty traps and biodiversity conservation.


Toxic effects of zinc from trout farm sediments on ATP, protein, and hemoglobin concentrations of Limnodrilus hoffmeisteri.
Zinc (Zn) is a nutritionally essential metal, and deficiency results in severe health consequences to aquatic organisms. In this study toxicity data for Limnodrilus hoffmeisteri produced by Zn in systems using three natural sediments (trout farms: El Oyamel, El Truchón, and El Potrero) are presented. Hemoglobin, adenosine triphosphate (ATP), and protein concentrations were measured in L. hoffmeisteri exposed to spiked sediments, as indicators of exposure. Physicochemical characteristics of water and sediments were also considered. Zn concentrations were measured in water and sediment. El Oyamel, El Truchón, and El Potrero pond sediments did not have similar physicochemical characteristics. Zn concentrations of water obtained from the rustic ponds were near 0.4575 mg/L; however, this metal was always found to be higher in the sediments (0.0271-0.9754 mg/kg). The bioassay with worms demonstrated that pond sediments from El Oyamel, El Potrero, and El Truchón produced toxicity since ATP and protein concentrations were low compared to controls (organisms without metal). All spiked sediments had a significant reduction effect on ATP, protein, and hemoglobin concentrations. This investigation clearly shows that sediments of El Truchón, El Oyamel, and El Potrero possess toxicity potential. These results suggest the usefulness of these bioassays to evaluate the toxicity of sediments polluted with heavy metals.


Use of RapidChek® SELECT™ Salmonella to detect shedding of live attenuated Salmonella enterica serovar Typhi vaccine strains.
Identification of individuals shedding Salmonella enterica serovar Typhi in stool is imperative during clinical trial safety evaluations. Recovery of live attenuated S. Typhi vaccine strains can be difficult because the mutations necessary for safety in humans often compromise survival in stringent selective enrichment media. RapidChek® SELECT™ Salmonella is a highly sensitive detection method for S. enterica species which utilizes a bacteriophage cocktail designed to reduce the growth of competitor microbes in mildly selective enrichment medium. Detection of Salmonella is enhanced by means of a Salmonella-specific antibody strip targeted to lipopolysaccharide. The RapidChek® SELECT™ Salmonella method was compared to conventional enrichment and plating methods to determine the most sensitive method for detecting attenuated S. Typhi strains in human stool samples. Although traditional enrichment strategies were more sensitive to the presence of wild-type S. Typhi, RapidChek® SELECT™ Salmonella was superior at detecting attenuated strains of S. Typhi. Strains containing a wide variety of attenuating mutations were detected with equal sensitivity as the wild type by RapidChek® SELECT™ Salmonella. The presence of Vi capsule or mutations which affected O-antigen synthesis (Δpmi, ΔgalE) did not decrease the sensitivity of the RapidChek® SELECT™ Salmonella assay.


Effect of rocker-soled shoes on parameters of knee joint load in knee osteoarthritis.
This study evaluated the immediate effects of rocker-soled shoes on parameters of the knee adduction moment (KAM) and pain in individuals with knee osteoarthritis (OA). Three-dimensional gait analysis was performed on 30 individuals (mean (SD): age, 61 (7) yr; 15 (50%) male) with radiographic and symptomatic knee OA under three walking conditions in a randomized order: i) wearing rocker-soled shoes (Skechers Shape-ups), ii) wearing non-rocker-soled shoes (ASICS walking shoes), and iii) barefoot. Peak KAM and KAM angular impulse were measured as primary indicators of knee load distribution. Secondary measures included the knee flexion moment (KFM) and knee pain during walking. Peak KAM was significantly lower when wearing the rocker-soled shoes compared with that when wearing the non-rocker-soled shoes (mean difference (95% confidence interval), -0.27 (-0.42 to -0.12) N·m/BW × Ht%; P < 0.001). Post hoc tests revealed no significant difference in KAM impulse between rocker-soled and non-rocker-soled shoe conditions (P = 0.13). Both peak KAM and KAM impulse were significantly higher during both shoe conditions compared with those during the barefoot condition (P < 0.001). There were no significant differences in KFM (P = 0.36) or knee pain (P = 0.89) between conditions. Rocker-soled shoes significantly reduced peak KAM when compared with non-rocker-soled shoes, without a concomitant change in KFM, and thus may potentially reduce medial knee joint loading. However, KAM parameters in the rocker-soled shoes remained significantly higher than those during barefoot walking. Wearing rocker-soled shoes did not have a significant immediate effect on walking pain. Further research is required to evaluate whether rocker-soled shoes can influence symptoms and progression of knee OA with prolonged wear.


[Seasonal dynamics of oviposition in non-autogenous population of Culex pipiens pipiens (Diptera: Culicidae) in the Leningrad province].
Seasonal patterns of oviposition in a synanthropic unautogenous population of Culex pipiens pipiens mosquitoes from 69 suburban settlements (60 degrees 30' N, 30 degrees E') of the Leningrad province were studied during the period 1998-2002 years. The numbers of egg rafts laid in six artificial pools (barrels) were counted every day; altogether 692 rafts were collected. The general patterns of oviposition activity were similar for all studied years, in spite of their differences in the summer temperature regimes. The first peak of oviposition was observed during the second decade of July, the second peak--during the third decade of July--the first decade of August. The first and second summer generations of mosquitoes were responsible for these oviposition peaks, whereas the third generation completely entered the reproductive diapause. Thus, the oviposition activity was successfully used for populational monitoring of C. p. pipiens, that was for the first time recommended by Madder and co-authors (1980), taking into consideration the simplicity and economy of this technique. The differences in the attractiveness of distinct reservoirs for oviposition were recorded. The females preferred the barrels located on open sun-lit space and waters with organic pollution settled by mosquito larvae. Windly and rainy weather and also low (below 10 degrees C) night temperatures suppressed mosquito oviposition.


[Current status of implantable cardioverter defibrillator].
Clinical trials have established the superiority of the implantable cardioverter defibrillator (ICD) over antiarrhythmic drug therapy in survivors of sudden cardiac arrest and in high risk patients with coronary artery disease. The ICD has evolved to overcome the limitation of earlier devices that required thoracotomy for implantation and inadequate therapies. At present, it is implanted in a similar manner to cardiac pacemakers and incorporates discrimination algorithms to prevent inappropriate therapy. Managing the patients with an ICD requires an understanding of the multiprogrammable features of modern devices. The cost-effectiveness of ICD therapy appears favorable, given the marked survival benefit seen in randomized trials relative to antiarrhythmic drug treatment. A goal of newer-generation ICD devices is to avoid intervention. Such programmable therapies may include pacing to avoid long short coupling, intermittent antiarrhythmic drug infusion, or multisite pacing to improve hemodynamics. Further advances in device technology will undoubtedly expand the role of the ICD in the primary and secondary prevention of sudden cardiac arrest.


[White-Bland-Garland syndrome: the maximum natural development of the coronary anastomosis(II)].
The anomalous origin of the left coronary artery from pulmonary artery (White-Bland-Garland syndrome) is a very rare coronary malformation, having despite the great mortality in the early childhood, an adult form, characterized by minor symptoms and long course. This paradoxical situation is totally dependent to the complete development of the coronary anastomosis, allowing the right coronary flow to perfuse the left myocardium. The theory of the "terminal arterial perfusion" of the heart, still persistent in some monographs is meeting in this natural situation its strongest opponent argumentation. The coronary anastomosis, clearly visible by coronarography are large enough (in late stages) to inverse the flow in left coronary artery, filling the pulmonary artery. Is the coronary-pulmonary shunt, responsible for the majority of symptoms, in the 5th or 6th decades. The adult form of the White-Bland-Garland syndrome is indicative for the maximum result we may hope to reach using the new revascularisation method for ischemic heart disease: new vessels formation and enhancing the coronary anastomosis by growth factors administration therapy.


Healthcare continuity from hospital to territory in Lombardy: TELEMACO project.
To verify implementation and use of TELEMACO (TELEMedicina Ai piccoli COmunilombardi; http://www.telemaco.regione.lombardia.it/), which provides specialized continuity of care with innovative healthcare services in remote areas of the Lombardy region of Italy; to design a network in the territory for sharing of continuityof- care programs; and to allow the relevant health authorities to collect cost data to establish a model for sustainable pricing for implementing these services. TELEMACO provides home-based telemanagement services for patients with chronic heart failure and chronic obstructive pulmonary disease (COPD), as well as second-opinion teleconsultations in cardiology, dermatology, diabetology, and pulmonology for general practitioners and second-opinion teleconsultations on digital images in cases of traumatic brain injury and stroke. A total of 2 service centers, 10 cardiology and pneumology departments, 30 specialists, 176 general practitioners, 40 nurses, 2 emergency departments, and 2 consultant hospitals were involved. A total of 166 patients with chronic heart failure and 474 patients with COPD were enrolled. There were 4830, 51, and 44 second-opinion teleconsultations for cardiologic, dermatologic, and diabetic conditions, respectively. There were 147 second-opinion teleconsultations on digital images, 68 for stroke, and 79 for traumatic brain injury. Implementation of TELEMACO introduced innovations in working methods and provided evidence to the health authorities for allocating funds for such services. TELEMACO provided evidence that there is a growing need for home management of patients using telemedicine, a common and efficacious approach that can ensure care continuity, especially in chronic diseases.


Metabolic syndrome in patients undergoing coronary angiography.
Metabolic Syndrome (MetS) is basically a cluster of cardiovascular risks that involve changes in metabolic and hemodynamic indicators; various organizations have defined it with small differences. Metabolic syndrome is a lethal endocrinopathy starting with insulin resistance and inviting a chain of systemic disorders such as abdominal obesity, glucose intolerance or diabetes mellitus (DM), dyslipidemia, hypertension (HT) and coronary artery disease (CAD). This prospective and descriptive study was conducted at the Cardiology Clinic of a Private Hospital in Osmaniye between January 2014 and May 2014. The study population included all patients who were administered a CA procedure at the Cardiology Clinic of Private New Life Hospital in Osmaniye in 2014. The majority of the patients were male (63.3%), the mean age was 59.09±10.98, vast majority of them had social security (98.5%), 32.8% of them smoked, 7.2% had peripheral arterial disease (PAD), 52.5% were diagnosed with DM, 24.8% with HT, percutaneous transluminal coronary angioplasty (PTCA) or stent was administered to 40.3% of the patients who underwent CA and coronary artery bypass grafting (CABG) was decided for 15.5% of them. 41.8% of the patients met the MetS diagnosis criteria. The mean BMI was found to be 28.61±4.68, the mean FBS to be 143.20±74.83, the mean triglyceride value to be 168.73±96.94 and the mean HDL value to be 37.04±9.20. Although male gender came first among the patients who underwent CA, the prevalence of MetS did not show a statistically significant correlation with gender, mean age or smoking. The prevalence of HT, PAD and DM was significantly higher in the patients who met the MetS criteria. The mean values of FBS, HDL, CK-MB, triglyceride and cholesterol were also significantly higher in the patients who met the MetS criteria. As BMI increased, the rate at which MetS criteria are met also increased. The objective is to prevent diabetes and cardiovascular diseases. Weight loss achieved with proper nutrition and an exercise program will have a reversing effect on all the disorders seen in metabolic syndrome.


Next generation of ALDH substrates and their potential to study maturational lineage biology in stem and progenitor cells.
High aldehyde dehydrogenase (ALDH) activity is a feature of stem cells from normal and cancerous tissues and a reliable universal marker used to isolate them. There are numerous ALDH isoforms with preferred substrate specificity variably expressed depending on tissue, cell type, and organelle and cell status. On the other hand, a given substrate may be metabolized by several enzyme isoforms. Currently ALDH activity is evidenced by using Aldefluor, a fluorescent substrate likely to be metabolized by numerous ALDH isoforms. Therefore, isolation techniques based on ALDH activity detection select a heterogeneous population of stem or progenitor cells. Despite active research in the field, the precise role(s) of different ALDH isoforms in stem cells remains enigmatic. Understanding the metabolic role of different ALDH isoform in the control of stem cell phenotype and cell fate during development, tissue homeostasis, or repair, as well as carcinogenesis, should open perspectives to significant discoveries in tissue biology. In this perspective, novel ALDH substrates are being developed. Here we describe how new substrates could be instrumental for better isolation of cell population with stemness potential and for defining hierarchy of cell populations in tissue. Finally, we speculate on other potential applications.


Deeply coded aperture for lensless imaging.
In this Letter, we present a method for jointly designing a coded aperture and a convolutional neural network for reconstructing an object from a single-shot lensless measurement. The coded aperture and the reconstruction network are connected with a deep learning framework in which the coded aperture is placed as a first convolutional layer. Our co-optimization method was experimentally demonstrated with a fully convolutional network, and its performance was compared to a coded aperture with a modified uniformly redundant array.


The upregulation of p27Kip1 by rapamycin results in G1 arrest in exponentially growing T-cell lines.
An immunosuppressant Rapamycin (Rap) has been reported to cause G1 arrest by inhibiting p70 S6 kinase and G1 cyclin/cdks kinase activities when added to quiescent cells with mitogens. However, antiproliferative effects of Rap on exponentially growing cells have been poorly investigated. We examined the intracellular events after the treatment of Rap in exponentially growing T cells and found that Rap upregulated a cdks inhibitor, p27Kip1 at both mRNA and protein levels in Rap-sensitive cells. Antiproliferative effect of Rap was mainly ascribed to the inhibition of cyclin E/cdk2 kinase activity through the formation of cyclin E/cdk2-p27Kip1 complex rather than inhibition of p70 S6 kinase activity. Furthermore, we showed that Rap-sensitive cells with elevated p27Kip1 expression lost sensitivity to Rap when antisense p27Kip1 was introduced, which indicates that the basal level of p27Kip1 is one of the limiting factors that determine the sensitivity to Rap in already cycling cells. These data suggest the presence of a putative threshold level of p27Kip1 at late G1 phase in already cycling cells. Rap may cause G1 arrest by upregulating the amount of p27Kip1 beyond the threshold in some Rap-sensitive cells that are exponentially growing.


Characterization and clinical association of antibody inhibitory to HIV reverse transcriptase activity.
Reverse transcriptase activity of the human immunodeficiency virus (HIV) was blocked in vitro by immunoglobulin G (IgG) derived from certain individuals infected with this retrovirus. A heterogeneous immune response for inhibition of enzyme function was noted. Catalytic activity was depressed by 50% or more with the use of 10 micrograms of IgG from 11 of 16 HIV-seropositive asymptomatic carriers, but from 0 of 8 seronegative controls and 2 of 12 patients with acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The inhibitor was confined to the F(ab')2 fragment. It was not directed against the poly(rA) X oligo(dT) template, nor against major envelope or structural viral antigens, and did not cross-react with bacterial, avian, or other mammalian DNA polymerases. It did not correlate with recognition of polymerase antigens by radioimmunoprecipitation. Loss of this inhibitor may be associated with development of clinical disease. Ten asymptomatic HIV-seropositive carriers with high titers of IgG antibodies to reverse transcriptase were followed for a mean of 3 years. All of four lost inhibitory capability prior to development of AIDS or ARC, while titers persist in the six who remain clinically healthy.