MMP-9 microsatellite polymorphism: association with the progression of intima-media thickening and constrictive remodeling of carotid atherosclerotic plaques.
Intima-media thickening (IMT) of carotid arteries and constrictive remodeling (CR) of atherosclerotic plaques are vascular pathologic characteristics that precede the onset of vascular events. SMC migration and proliferation are linked both to IMT and CR and are matrix metalloproteinase 9 (MMP-9) dependent. A genetic polymorphism (PM) of MMP-9, a CA (13-27) microsatellite in the promoter region, which accounts for differential expression of MMP-9, could be linked to progression of IMT and CR. Progression of IMT and CR of plaques in carotid arteries were studied in 55 consecutive patients with a 12-18 months follow-up. All patients were genotyped for MMP-9 PM. A positive linear relationship between the number of repeats and the progression of IMT (P=0.028) as well as of CR (P=0.018) was found. The analogous relationship was obtained when only the allele with longer microsatellite was considered. Carriers of more than 20 repeats in one allele showed faster both IMT growth (P=0.045) and stenosis progressions of plaques (P=0.019). In multivariate analysis, age, dyslipidemia, and MMP-9 PM were determinants of IMT progression, while MMP-9 PM was the only one of CR. In conclusion, the high number of CA repeats in MMP-9 promoter is positively correlated with faster IMT and CR progression.


The bouba-kiki effect and its relation to the Autism Quotient (AQ) in autistic adolescents.
The bouba-kiki effect refers to the correspondence between arbitrary visual and auditory stimuli. Previous studies indicate ASD persons' reduced bouba-kiki effect compared to controls. This study examines the relation between ASD symptomology and performance on the bouba-kiki task. Twenty ASD participants and 20 matched controls were presented the bouba-kiki task. Autism-Quotient (AQ) scores and several cognitive measures were obtained for all participants. Results demonstrate that among all measures, only AQ scores were significantly correlated to the performance on the bouba-kiki task in the ASD group. Results thus support the existence of a relation between autism symptoms and performance on the bouba-kiki task, and are discussed in light of current theories.


Comparable search efficiency for human and animal targets in the context of natural scenes.
In a previous series of studies, we have shown that search for human targets in the context of natural scenes is more efficient than search for mechanical targets. Here we asked whether this search advantage extends to other categories of biological objects. We used videos of natural scenes to directly contrast search efficiency for animal and human targets among biological or nonbiological distractors. In visual search arrays consisting of two, four, six, or eight videos, observers searched for animal targets among machine distractors, and vice versa (Exp. 1). Another group searched for animal targets among human distractors, and vice versa (Exp. 2). We measured search slope as a proxy for search efficiency, and complemented the slope with eye movement measurements (fixation duration on the target, as well as the proportion of first fixations landing on the target). In both experiments, we observed no differences in search slopes or proportions of first fixations between any of the target-distractor category pairs. With respect to fixation durations, we found shorter on-target fixations only for animal targets as compared to machine targets (Exp. 1). In summary, we did not find that the search advantage for human targets over mechanical targets extends to other biological objects. We also found no search advantage for detecting humans as compared to other biological objects. Overall, our pattern of findings suggests that search efficiency in natural scenes, as elsewhere, depends crucially on the specific target-distractor categories.


Multi-scale structural characteristics of black Tartary buckwheat resistant starch by autoclaving combined with debranching modification.
The impact of autoclaving or autoclave-debranching treatments on the multi-scale structure of resistant starch (RS) and the relationship with starch digestion remains unclear, despite their widespread use in its preparation. This work investigated the relationship between RS structure in black Tartary buckwheat and its digestibility by analyzing the effects of autoclaving and autoclave-debranching combined treatments on the multi-scale structure of RS. The results showed that black Tartary buckwheat RS exhibited a more extensive honeycomb-like network structure and enhanced thermal stability than either black Tartary buckwheat native starch (BTBNS) or common buckwheat native starch (CBNS). Autoclaving and autoclaving-debranching converted A-type native starch to V-type and possibly the formation of flavonoid-starch complexes. Autoclaving treatment significantly increased the proportion of short A chain (DP 6-12) and the amylose (AM) content, reduced the viscosity and the total crystallinity. Notably, the autoclave-debranching co-treatment significantly enhanced the resistance of starch to digestion, promoted the formation of perfect microcrystallines, and increased the AM content, short-range ordered degree, and the proportion of long B2 chain (DP 25-36). This study reveals the relationship between the multi-scale structure and digestibility of black Tartary buckwheat RS by autoclaving combined with debranching modification.


A step toward inclusive green growth: can digital finance be the main engine?
Inclusive green growth (IGG) has become a worldwide consensus to achieve the target of sustainable development goals. Although the prominent role of digital finance (DF) against the pandemic has drawn considerable attention from policymakers, its plausible effect on IGG and underlying mechanisms have not been distinctly explored in academia. The aim of the study is to explore the causal effect of DF on IGG based on prefecture city-level data from 2011 to 2019 in China. To this end, we employed the non-radial direction distance function approach within the global production technology to evaluate the aggregate IGG performance and its three sub-dimensions. The empirical results demonstrate that DF exerts a significant promotional effect on urban IGG. This finding continues to survive in an extensive set of robustness checks using an alternative dependent variable, model specifications, instrumental variable, and difference-in-difference approaches to address the endogeneity concerns. Meanwhile, sub-dimensional regressions show that this positive effect is driven predominantly by the scale economy of DF, while the depth of usage and digitalization playing a minor role. Moreover, we uncover that DF enhances IGG by leveraging greater marginal product of labor rather than capital, improving environmental externalities, increasing fuller employment, and reducing rural-urban income inequality. However, we also reveal the dark side of DF on imbalanced regional development. The promotional effect of DF on IGG is only prominent for cities with better inherent comparative advantages, and we are thus likely to see a widening digital divide resulting from the "Matthew effect" on regional disparity without timely policy interventions.


Do prenatal depressive symptoms developed by hospitalized women with high-risk pregnancy persist to post-partum?
This study aims to explore the level of depressive symptoms during pregnancy and after childbirth comparing women hospitalized due to high-risk pregnancy (clinical group) and women with low-risk pregnancy (control group). Seventy pregnant women (26 clinical group and 44 control group) filled in the Edinburgh Postnatal Depression Scale both during pregnancy and three months after childbirth. Results showed that the clinical group reported significant higher levels of prenatal depression than the control group, while no differences were found on postnatal depression. Data highlighted that hospitalization could represents a significant stressor that can exacerbate depression in women with high-risk pregnancy.


Endothelin antagonism reduces hemoglobin A1c in patients with pulmonary hypertension.
Our lab recently reported that the blockade of endothelin-1 (ET-1) receptors attenuates insulin resistance in obese mice; therefore, we hypothesized that patients taking ET-1 receptor antagonists (ERAs) will have improved glycemic control. University of Mississippi Medical Center (2013-2020) electronic health record (EPIC) data were extracted from patients ≥18 years old with a clinical diagnosis of pulmonary hypertension (Food and Drug Administration indication for ERA use) and at least two clinical visits within 2 years. Patients prescribed ERAs (n = 11) were similar in age (61 ± 14 years vs. 60 ± 14 years), body mass index (BMI) (34 ± 8 kg/m 2 vs. 35 ± 11 kg/m2), diabetes prevalence (73% vs. 80%, p = 0.59), and follow-up time (209 ± 74 days vs. 283 ± 180 days) compared with patients not taking ERAs (n = 137). There was a small but similar decrease in BMI at follow-up in the ERA (-1.9 ± 3 kg/m2) and control patients (-1.6 ± 5 kg/m2). At follow-up, hemoglobin A1c (HbA1c) significantly decreased -12% ± 11% of baseline in patients taking ERAs, while this did not occur in the control patients (2% ± 20% increase in HbA1c). In the whole population, baseline HbA1c and ERA prescription predicted the fall in HbA1c, while there was no significant association with demographics, diabetes prevalence, and diabetic treatment. These data suggest a potential role of ET-1 in promoting insulin resistance and warrant further investigation into using these drugs for glycemic control.


Electrostatic mechanism of V600E mutation-induced B-Raf constitutive activation in colorectal cancer: molecular implications for the selectivity difference between type-I and type-II inhibitors.
The oncogenic mutation V600E in B-Raf activation loop (A-loop) has been frequently observed to cause drug resistance in colorectal cancer chemotherapy. Here, the molecular mechanism of V600E-induced conformational flipping of B-Raf activation loop (A-loop) is investigated systematically via continuum electrostatic analysis. It is found that substitution of the electroneutral Val600 residue with negatively charged glutamic acid Glu600 electrostatically destabilizes the inactive DFG-out conformation of B-Raf kinase and promotes its shifting to active DFG-in conformation. This is analogous with natural phosphorylation of Thr598 and/or Ser601 residues in A-loop to activate the kinase, that is, both the mutation and phosphorylation can introduce negative charge to B-Raf A-loop and then trigger the loop flipping. Energetic analysis reveals that the V600E mutation can affect inhibitor binding indirectly via regulation of kinase conformation. Type-I and type-II inhibitors respond distinctly to V600E mutation; the former is sensitized by the mutation, while the latter generally shows a low sensitivity to the mutation. Based on this guideline, the sophisticated type-I pan-kinase inhibitor Staurosporine as well as its analogs Midostaurin and Lestaurtinib are identified as potent mutant-selective inhibitors by modeling analysis and kinase assay, which exhibit a moderate or high selectivity for B-RafV600E over B-RafWT (3.7-fold, 6.1-fold and > 3.1-fold, respectively).


Controlling the quantum dynamics of a mesoscopic spin bath in diamond.
Understanding and mitigating decoherence is a key challenge for quantum science and technology. The main source of decoherence for solid-state spin systems is the uncontrolled spin bath environment. Here, we demonstrate quantum control of a mesoscopic spin bath in diamond at room temperature that is composed of electron spins of substitutional nitrogen impurities. The resulting spin bath dynamics are probed using a single nitrogen-vacancy (NV) centre electron spin as a magnetic field sensor. We exploit the spin bath control to dynamically suppress dephasing of the NV spin by the spin bath. Furthermore, by combining spin bath control with dynamical decoupling, we directly measure the coherence and temporal correlations of different groups of bath spins. These results uncover a new arena for fundamental studies on decoherence and enable novel avenues for spin-based magnetometry and quantum information processing.


Effects of visible and near-infrared lasers on cell cultures.
The effect of 360, 632 and 780 nm light on NIH fibroblast cells was examined. Mitosis counts of irradiated cells at various energy doses were taken. Scanning electron micrographs of these cells were studied. It is suggested that low-level laser therapy in the visible and in the near-infrared region is due to cell respiration stimulation by either the endogenous porphyrins in the cell, or by the cytochromes.


Effects of Deep Cooling and Re-Warming on Ionotropic Glutamatergic Receptors In Vitro.
We studied the effects of cooling to -10°C and re-warming to 37°C on slices of rat olfactory cortex. The amplitudes of action potential in the lateral olfactory tract and excitatory postsynaptic potential activated by AMPA recovered during slow cooling/re-warming (0.1°C/min), while during rapid cooling/re-warming (9°C/min), they surpassed the control values. NMDA receptor-dependent mechanism was blocked in both cooling/re-warming modes. Swelling of the brain slices was observed during re-warming, especially during rapid cooling/re-warming. Nerve fibers of the lateral olfactory tract and AMPA-related processes survived deep cooling/re-warming, while NMDA-related processes were irreversibly blocked.


Quality of Life and Resilience of Patients With Juvenile Stroke: A Systematic Review.
The incidence of juvenile stroke is increasing. Considering younger age of patients and the potential long-lasting disability, the consequences of juvenile stroke may have a greater societal impact than those of stroke in elder population. A systematic review was performed in order to evaluate quality of life in juvenile stroke. All studies on quality of life in juvenile stroke published in PUBMED before March 1st, 2020. The search terms were "stroke", "juvenile", "young", "adult", "quality of life" and "resilience" were considered. After the abstract evaluation of 748 hits only six studies we identified as appropriate for the review. The age criterion for juvenile stroke was set as 55 years and younger. The studies have shown a decline of quality of life in at least 46% of patients with juvenile stroke. On average, quality of life was reduced by 37%. The following domains as measured on SF-36 were particularly impaired: physical role, physical functioning and emotional role. The factors influencing the quality of life in juvenile stroke were ability to return to work, post-stroke depression, functional outcome, level of education and age of stroke onset. This systematic review shows a decline of quality of life in patients with juvenile stroke. Rehabilitation programs should consider the factors influencing quality of life in these patients in order to improve outcome of juvenile stroke. Patients who are unable to return to work should receive necessary social support. In addition, our data underline the importance of screening procedures for post-stroke depression in this population.


An emerging direction in glucagon-based therapy.
Glucagon receptor (GCGR) is an essential regulator of hepatic metabolism. In this issue of Cell Metabolism, Sekar et al. report that the endosomal protein Vps37a uncouples hepatic glucose production from lipid metabolism by altering the intracellular localization of GCGR, thereby providing a new potential therapeutic direction for type 2 diabetes.


Efficacy, safety, and tolerability of mirabegron in patients aged ≥65yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR).
The majority of patients with overactive bladder (OAB) are aged >65yr. There has been no prospectively designed study assessing treatment efficacy with the β3-adrenoreceptor agonist, mirabegron, specifically in this age group. A phase IV study comparing flexibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence. Community-dwelling patients aged ≥65yr with OAB for ≥3mo. Following a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/24h were randomised 1:1 to double-blind 25mg/d mirabegron or matched placebo, for 12wk. After week 4 or 8, the dose could be increased to 50mg/d mirabegron/matched placebo based on patient and investigator discretion. Coprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24h and incontinence episodes/24h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24h, and mean number of urgency incontinence episodes/24h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24h, mean volume voided/micturition, and mean number of urgency episodes/24h. Stratified rank ANCOVA was used for the mean numbers of incontinence episodes/24h and urgency incontinence episodes/24h. Statistically significant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24h, mean number of incontinence episodes/24h, mean volume voided/micturition, mean number of urgency episodes/24h, and mean number of urgency incontinence episodes/24h. Safety and tolerability were consistent with the known mirabegron safety profile. Mirabegron efficacy, safety, and tolerability over 12 wk were confirmed in patients aged ≥65yr with OAB and incontinence. We examined the effect of mirabegron compared with placebo in people aged 65yr or older with overactive bladder and incontinence. Mirabegron improved the symptoms of overactive bladder compared with placebo. Side effects were similar to those already known for mirabegron.


Bis[1,2-bis-(4-chloro-phen-yl)-ethyl-ene-1,2-dithiol-ato(1-)]nickel(II).
The title compound, [Ni(S2C2(C6H4-p-Cl)2)2] or [Ni(C14H8Cl2S2)2], crystallizes in the triclinic space group P as pairs of mol-ecules disposed about an inversion center at the bc face of the cell. Close inter-molecular C-H⋯S (2.884 Å) and C-H⋯Ni (3.032 Å) contacts that are less than the sum of the van der Waals radii appear to induce slight bowing of the mol-ecular planes toward one another. The angles at which the four p-ClC6H4- rings join the NiS2C2 chelate rings [39.37 (9)- 53.41 (6)°] are similarly influenced by these inter-molecular contacts. In the larger packing arrangement, sheets of mol-ecules extend in the direction of the ac face diagonal.


Valsalva retinopathy associated with intranasal cocaine abuse: A case report.
The purpose of this report is to describe a case of Valsalva retinopathy in an intranasal cocaine user. A 49-year-old male presented with a history of sudden loss of vision and inferior visual field defect in his left eye. Clinical evaluation of the affected eye showed best corrected visual acuity of 20/25 and fundus examination revealed a preretinal hemorrhage superior to the disk with multiple intraretinal hemorrhages in and around the posterior pole. On further questioning, the patient revealed intranasal cocaine use the day before the onset of his visual symptoms. Blood tests were requested to exclude blood dyscrasias or predisposition to vascular occlusive disorders and no further treatment measures were taken. The patient was reviewed a month later when his hemorrhages had completely resolved and his visual acuity had improved to 20/20. His blood results were within normal limits. Although never been reported before, Valsalva retinopathy can be associated with intranasal cocaine abuse and should be considered in the differential diagnosis of visual reduction in such population.


Growth charts in Cockayne syndrome type 1 and type 2.
Cockayne syndrome (CS) is a multisystem degenerative disorder divided in 3 overlapping subtypes, with a continuous phenotypic spectrum: CS2 being the most severe form, CS1 the classical form and CS3 the late-onset form. Failure to thrive and growth difficulties are among the most consistent features of CS, leaving affected individuals vulnerable to numerous medical complications, including adverse effects of undernutrition, abrupt overhydration and overfeeding. There is thus a significant need for specific growth charts. We retrospectively collected growth parameters from genetically-confirmed CS1 and CS2 patients, used the GAMLSS package to construct specific CS growth charts compared to healthy children from WHO and CDC databases. Growth data were obtained from 88 CS patients with a total of 1626 individual growth data points. 49 patients were classified as CS1 and 39 as CS2 with confirmed mutations in CSB/ERCC6, CSA/ERCC8 or ERCC1 genes. Individuals with CS1 initially have normal growth parameters; microcephaly occurs from 2 months whereas onset of weight and height restrictions appear later, between 5 and 22 months. In CS2, growth parameters are already below standard references at birth or drop below the 5th percentile before 3 months. Microcephaly is the first parameter to show a delay, appearing around 2 months in CS1 and at birth in CS2. Height and head circumference are more severely affected in CS2 compared to CS1 whereas weight curves are similar in CS1 and CS2 patients. These new growth charts will serve as a practical tool to improve the nutritional management of children with CS.


Characteristics of immigrant Latino men who utilize formal healthcare services: baseline findings from the HoMBReS study.
Despite the burgeoning immigrant Hispanic/Latino community in the southeastern United States, little is known about the utilization of healthcare services by this population. We sought to identify demographic, behavioral and psychosocial characteristics of immigrant Hispanic/Latino men who report utilizing formal healthcare services. Using an interviewer-administered assessment, data were collected from a random sample of members of a multicounty adult Latino men's soccer league in North Carolina. Of the 222 participants, the mean (+/-SD) age was 29.8 +/-8.3, with a range of 18-71 years. More than half of the sample reported Mexico as their country of origin and grade < or =8 as their highest level of education. The mean length of time living in the United States was 8.8 (+/- 7.6) years. An increased likelihood of reporting having ever utilized formal healthcare services associated with decreased perceived barriers to utilization, increased acculturation, increased adherence to traditional notions of masculinity and increased coping. Effective strategies to increase the utilization of formal healthcare services among Hispanic/Latino men may include diffusing information about the availability of services and how to access services and linking healthcare utilization with positive aspects of what it means to be a man.


Does the Na channel conduct ions through a water-filled pore or a condensed-state pathway?
Many investigators assert that the ion-conducting pathway of the Na channel is a water-filled pore. This assertion must be reevaluated to clear the way for more productive approaches to channel gating. The hypothesis of an aqueous pore leaves the questions of voltage-dependent gating and ion selectivity unexplained because a column of water can neither serve as a switch nor provide the necessary selectivity. The price of believing in an aqueous pore therefore is a futile search for separate ad hoc mechanisms for gating and selectivity. The fallacy is to assume that only water is available to carry ions rapidly, ignoring the role of the glycoprotein, which can form an elastomeric phase with water. The elastomer is a state of matter, neither liquid nor solid, in which the molecules of a liquid are threaded together with cross-linked polymer chains; it supports fast ion motion (Owen, 1989). An alternative hypothesis for channel gating, based on condensed-state materials science, already exists (Leuchtag, 1988, 1991a). The ferroelectric-superionic transition hypothesis (FESITH) postulates that the Na channel exists in a metastable ordered (closed) state at resting potential and, on threshold depolarization, undergoes a reversible order-disorder phase transition to a less-ordered, ion-conducting (open) state. The ordered state is ferroelectric; the disordered state is a fast ion conductor selective for Li+ and Na+. The basis of the voltage dependence is elevation of transition temperature with electric field, well established in ferroelectrics. FESITH is consistent with single-channel transitions, gating currents, heat and cold block, and other phenomena observed at channel or membrane level. An implication of FESITH, the Curie-Weiss law, has been shown to explain existing data on membrane capacitance versus temperature in squid axon (Leuchtag, 1991c). Only on the basis of a clear understanding of function can we expect new structural data on the Na-channel glycoprotein to generate realistic structure-function models at the molecular level.


The dark side of fear expression: Infant crying as a trigger for maladaptive parental responses.
While infant fearfulness, and its expression via crying, may have been adaptive in our evolutionary history, for modern parents, crying can be challenging to respond to. We discuss how and why prolonged crying can raise the risk for difficulties with adult care. Given that crying is the most-reported trigger for shaking, its potential to elicit maladaptive responses should not be overlooked.


Leukotrienes and inflammation.
The leukotrienes are synthesized from essential fatty acids via a 5-lipoxygenase enzyme. Most is known about the four-series leukotrienes derived from arachidonic acid. Leukotriene B4 is a potent chemotactic agent for leukocytes and it induces neutrophil-dependent increased microvascular permeability. Leukotrienes C4, D4 and E4 are bronchoconstrictors; and potent mediators of microvascular tone and permeability. The leukotrienes have been suggested to have a role in many inflammatory conditions in man in the skin (e.g. psoriasis), the lung (e.g. allergic asthma), joints (e.g. rheumatoid arthritis) and in the heart (e.g. myocardial infarction). Drugs which inhibit the generation and the actions of leukotrienes are under development and are being tested clinically as potential anti-inflammatory agents.


Unravelling the regulation pathway of photosynthetic AB-GAPDH.
Oxygenic phototrophs perform carbon fixation through the Calvin-Benson cycle. Different mechanisms adjust the cycle and the light-harvesting reactions to rapid environmental changes. Photosynthetic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key enzyme in the cycle. In land plants, different photosynthetic GAPDHs exist: the most abundant isoform is formed by A2B2 heterotetramers and the least abundant by A4 homotetramers. Regardless of the subunit composition, GAPDH is the major consumer of photosynthetic NADPH and its activity is strictly regulated. While A4-GAPDH is regulated by CP12, AB-GAPDH is autonomously regulated through the C-terminal extension (CTE) of its B subunits. Reversible inhibition of AB-GAPDH occurs via the oxidation of a cysteine pair located in the CTE and the substitution of NADP(H) with NAD(H) in the cofactor-binding site. These combined conditions lead to a change in the oligomerization state and enzyme inhibition. SEC-SAXS and single-particle cryo-EM analysis were applied to reveal the structural basis of this regulatory mechanism. Both approaches revealed that spinach (A2B2)n-GAPDH oligomers with n = 1, 2, 4 and 5 co-exist in a dynamic system. B subunits mediate the contacts between adjacent tetramers in A4B4 and A8B8 oligomers. The CTE of each B subunit penetrates into the active site of a B subunit of the adjacent tetramer, which in turn moves its CTE in the opposite direction, effectively preventing the binding of the substrate 1,3-bisphosphoglycerate in the B subunits. The whole mechanism is made possible, and eventually controlled, by pyridine nucleotides. In fact, NAD(H), by removing NADP(H) from A subunits, allows the entrance of the CTE into the active site of the B subunit, hence stabilizing inhibited oligomers.


LapSim virtual reality laparoscopic simulator reflects clinical experience in German surgeons.
The aim of this study was to analyze the ability of a training module on a virtual laparoscopic simulator to assess surgical experience in laparoscopy. One hundred and fifteen participants at the 120th annual convent of the German surgical society took part in this study. All participants were stratified into two groups, one with laparoscopic experience of less than 50 operations (group 1, n=61) and one with laparoscopic experience of more than 50 laparoscopic operations (group 2, n=54). All subjects completed a laparoscopic training module consisting of five different exercises for navigation, coordination, grasping, cutting and clipping. The time to perform each task was measured, as were the path lengths of the instruments and their respective angles representing the economy of the movements. Results between groups were compared using chi(2) or Mann-Whitney U-test. Group 1 needed more time for completion of the exercises (median 424 s, range 99-1,376 s) than group 2 (median 315 s, range 168-625 s) (P<0.01). Instrument movements were less economic in group 1 with larger angular pathways, e.g. in the cutting exercise (median 352 degrees , range 104-1,628 degrees vs median 204 degrees , range 107-444 degrees , P<0.01), and longer path lengths (each instrument P<0.05). As time for completion of exercises, instrument path lengths and angular paths are indicators of clinical experience, it can be concluded that laparoscopic skills acquired in the operating room transfer into virtual reality. A laparoscopic simulator can serve as an instrument for the assessment of experience in laparoscopic surgery.


Experience with a transfusion recipient education program about hepatitis C.
Shortly after test kits for antibodies to the hepatitis C virus (HCV) were licensed in May of 1990, our medical community undertook a public education program encouraging previous transfusion recipients to see their physicians about the wisdom of being tested for anti-HCV. In response, 1034 samples were received for testing. All samples repeatably reactive (RR) with anti-HCV enzyme-linked immunoassay (EIA) were tested further with a research recombinant immunoblot assay (RIBA). Overall, 76 of the 1034 (7.4%) recipient samples were RR and 64 of these (84.2%) were reactive with RIBA. Recipients transfused prior to surrogate testing (alanine aminotransferase [ALT] and anti-hepatitis B core [anti-HBc]) in 1986 showed a 8.6 percent reactivity with RIBA and those transfused after surrogate testing showed a 4.8 percent reactivity, a 44 percent reduction. Of the 57 recipient samples reactive with RIBA and suitable for assay, 11 (19.3%) had an elevated ALT. Among 76 randomly selected blood donors with RR EIAs studied for comparison with recipients, 20 (26.3%) were reactive with RIBA, 9 of which had an abnormal surrogate test that would have disqualified them. ALT concentrations were abnormal in 6 (30%) of the donors who were reactive on RIBA. We conclude that an education program that encourages previous transfusion recipients to seek medical advice about anti-HCV testing is practical from the standpoint of the blood center. We believe more widespread implementation of similar programs should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)


Unmyelinated sensory neurons use Neuregulin signals to promote myelination of interneurons in the CNS.
The signaling mechanisms neurons use to modulate myelination of circuits in the central nervous system (CNS) are only partly understood. Through analysis of isoform-specific neuregulin1 (nrg1) mutants in zebrafish, we demonstrate that nrg1 type II is an important regulator of myelination of two classes of spinal cord interneurons. Surprisingly, nrg1 type II expression is prominent in unmyelinated Rohon-Beard sensory neurons, whereas myelination of neighboring interneurons is reduced in nrg1 type II mutants. Cell-type-specific loss-of-function studies indicate that nrg1 type II is required in Rohon-Beard neurons to signal to other neurons, not oligodendrocytes, to modulate spinal cord myelination. Together, our data support a model in which unmyelinated neurons express Nrg1 type II proteins to regulate myelination of neighboring neurons, a mode of action that may coordinate the functions of unmyelinated and myelinated neurons in the CNS.


Nicotinic acetylcholine receptors: a comparison of the nAChRs of Caenorhabditis elegans and parasitic nematodes.
Nicotinic acetylcholine receptors (nAChRs) play a key role in the normal physiology of nematodes and provide an established target site for anthelmintics. The free-living nematode, Caenorhabditis elegans, has a large number of nAChR subunit genes in its genome and so provides an experimental model for testing novel anthelmintics which act at these sites. However, many parasitic nematodes lack specific genes present in C. elegans, and so care is required in extrapolating from studies using C. elegans to the situation in other nematodes. In this review the properties of C. elegans nAChRs are reviewed and compared to those of parasitic nematodes. This forms the basis for a discussion of the possible subunit composition of nAChRs from different species of parasitic nematodes. Currently our knowledge on this is largely based on studies using heterologous expression and pharmacological analysis of receptor subunits in Xenopus laevis oocytes. It is concluded that more information is required regarding the subunit composition and pharmacology of endogenous nAChRs in parasitic nematodes.


Urticarial vasculitis associated with a monoclonal IgM gammopathy: Schnitzler's syndrome.
We describe two cases of Schnitzler's syndrome presenting with urticarial vasculitis, in which there was a monoclonal IgM of kappa light-chain isotype. Skin histology showed a perivascular leucocytic infiltrate and leucocytoclasis. One patient had an abnormal complement profile and positive rheumatoid factor while the other had antibodies to unidentified soluble nuclear antigens, anti-cytoplasmic antibodies and circulating immune complexes. In addition, in the first case deposits of IgM, C3 and, to a lesser degree, of IgG were observed in the walls of small blood vessels.


Atypical prosodic realization by Mandarin-speaking autistic children: Evidence from tone sandhi and neutral tone.
Introduction Atypical prosodic features have been widely reported in autism spectrum disorder (ASD), primarily in non-tonal language speakers. Nevertheless, the prosodic realizations in autistic people who speak tonal languages were relatively understudied. This study aimed to investigate the acoustic and phonetic patterns at the word-level speech in Mandarin-speaking autistic and typically developing (TD) children at different age ranges. Methods Thirty Mandarin-speaking autistic children (15 three- to five-year-olds and 15 six- to eight-year-olds) were recruited into the ASD group. The TD group consisted of 30 age- and gender-matched children. We employed a picture-naming task to elicit the spontaneous speech production of Mandarin disyllabic words in which tone change processes occur, namely Tone 3 (T3) sandhi and neutral tone (T0). Results The phonetic analysis showed that the ASD group generally could produce typical-like T3 sandhi and T0 in terms of pitch height. However, relative to the TD group, they exhibited flatter pitch contours during T3 sandhi production. Moreover, the acoustic pitch mean of citation tones in the ASD group was also significantly higher, accompanied by more rigid pitch curves in contour tones. In addition, the atypical temporal realization in the ASD group was manifested by the longer duration of T0 and the earlier inflection position of T3. Conclusions Mandarin-speaking autistic children under eight had the phonological ability to produce context-dependent tones based on connected tonal information at the word level. Nevertheless, their phonetic prosodic realization of tone change processes was atypical. Our findings provide evidence of atypical prosody in autistic children who speak tone languages. Clinically, these findings may be attributable to underlying neural differences in autistic children.


Development of novel lipid-peptide hybrid compounds with antibacterial activity from natural cationic antibacterial peptides.
Seven depsipeptides were synthesized by appending seven amino acids (Lys, Leu, Val, Phe, Ser, Gln, and Pro) at the N-terminus of the active fragment [TE-(33-43)], respectively corresponding to the C-terminal beta sheet domain of tenecin 1, an antibacterial protein and their activities were measured against Staphylococcus aureus. Considering the relationship between the activity and the characteristic of amino acid at the N-terminal of the peptide, novel derivatives were designed and synthesized from TE-(33-43) by introduction of fatty acids at the N-terminal. In this process, we synthesized novel lipid-peptide hybrid compounds with a potent antibacterial activity and more improved bioavailabilities. We characterized the important structural parameters of the lipid-peptide hybrid compounds for the antibacterial activities.


Dietary Lecithin Supplementation Can Improve the Quality of the M. Longissimus thoracis.
Forty crossbred (Large White × Landrace × Duroc) female pigs (16.4 kg ± 0.94 kg) were used to investigate the effect of dietary lecithin supplementation on growth performance and pork quality. Pigs were randomly allocated to a commercial diet containing either 0, 3, 15 or 75 g lecithin/kg of feed during the grower and finisher growth phase. Pork from pigs consuming the diets containing 15 g and 75 g lecithin/kg had lower hardness ( P < 0.001) and chewiness ( P < 0.01) values compared to the controls. Dietary lecithin supplementation at 75 g/kg significantly increased ( P < 0.05) the linoleic acid and reduced ( P < 0.05) the myristic acid levels of pork compared to the control and the 3 g/kg and 15 g/kg lecithin supplemented treatments. Pigs fed the 75 g/kg lecithin supplemented diet had lower plasma cholesterol ( P < 0.05) at slaughter compared to pigs fed the control diet and the 3 g/kg and 15 g/kg lecithin supplemented treatments. These data indicate that dietary lecithin supplementation has the potential to improve the quality attributes of pork from female pigs.


[Bloodstream infections with Candida glabrata in a neonatal intensive care unit that uses prophylaxis with fluconazole].
Candida glabrata is an emerging pathogen with the ability to develop tolerance and resistance to azole antifungals, which creates uncertainty about the usefulness of antifungal prophylaxis in newborns. The aim of this study was to describe the factors associated with C. glabrata infection in a NICU that uses prophylaxis with fluconazole. A case-control study paired by gestational age was designed and conducted at the Civil Hospital of Guadalajara Dr. Juan I. Menchaca. Newborns with C. glabrata infection were studied and for each one a matched control was selected by gestational age. Odds ratios (OR) were estimated with 95% confidence intervals (95% CI) and McNemar test for contrast of hypothesis was applied. Twenty-one infected patients were identified, from whom 66.7% were male; the median gestational age was 31.5 weeks. Increased risk of infection with C. glabrata was observed when there was a prescription of more than one antimicrobial scheme (OR 21, 95% CI, 1.23 - 358.3; p=0.006) and also among patients with surgical comorbidities (OR 8, 95% CI 1.01 - 63.9; p=0.04). During the study period, exposure to fluconazole showed no difference in the risk of infection. Neonates with more than one antimicrobial regimen and those with surgical comorbidities had a higher risk of C. glabrata infection.


BRAF and NRAS mutated melanoma: Different Ca2+ responses, Na+/Ca2+ exchanger expression, and sensitivity to inhibitors.
Calcium is a ubiquitous intracellular second messenger, playing central roles in the regulation of several biological processes. Alterations in Ca2+ homeostasis and signaling are an important feature of tumor cells to acquire proliferative and survival advantages, which include structural and functional changes in storage capacity, channels, and pumps. Here, we investigated the differences in Ca2+ homeostasis in vemurafenib-responsive and non-responsive melanoma cells. Also, the expression of the Na+/Ca2+ exchanger (NCX) and the impact of its inhibition were studied. For this, it was used B-RAFV600E and NRASQ61R-mutated human melanoma cells. The intracellular Ca2+ chelator BAPTA-AM decreased the viability of SK-MEL-147 but not of SK-MEL-19 and EGTA sensitized NRASQ61R-mutated cells to vemurafenib. These cells also presented a smaller response to thapsargin and ionomycin regarding the cytosolic Ca2+ levels in relation to SK-MEL-19, which was associated to an increased expression of NCX1, NO basal levels, and sensitivity to NCX inhibitors. These data highlight the differences between B-RAFV600E and NRASQ61R-mutated melanoma cells in response to Ca2+ stimuli and point to the potential combination of clinically used chemotherapeutic drugs, including vemurafenib, with NCX inhibitors as a new therapeutic strategy to the treatment of melanoma.


Physical mapping of the wheat genes in low-recombination regions: radiation hybrid mapping of the C-locus.
This work reports the physical mapping of an important gene affecting spike compactness located in a low-recombination region of hexaploid wheat. This work paves the way for the eventual isolation and characterization of the factor involved but also opens up possibilities to use this approach to precisely map other wheat genes located on proximal parts of wheat chromosomes that show highly reduced recombination. Mapping wheat genes, in the centromeric and pericentromeric regions (~ 2/3rd of a given chromosome), poses a formidable challenge due to highly suppressed recombination. Using an example of compact spike locus (C-locus), this study provides an approach to precisely map wheat genes in the pericentromeric and centromeric regions that house ~ 30% of wheat genes. In club-wheat, spike compactness is controlled by the dominant C-locus, but previous efforts have failed to localize it, on a particular arm of chromosome 2D. We integrated radiation hybrid (RH) and high-resolution genetic mapping to locate C-locus on the short arm of chromosome 2D. Flanking markers of the C-locus span a physical distance of 11.0 Mb (231.0-242 Mb interval) and contain only 11 high-confidence annotated genes. This work demonstrates the value of this integrated strategy in mapping dominant genes in the low-recombination regions of the wheat genome. A comparison of the mapping resolutions of the RH and genetic maps using common anchored markers indicated that the RH map provides ~ 9 times better resolution that the genetic map even with much smaller population size. This study provides a broadly applicable approach to fine map wheat genes in regions of suppressed recombination.


Function Based Brain Modeling and Simulation of an Ischemic Region in Post-Stroke Patients using the Bidomain.
Several studies have shown that post-stroke patients develop divergent activity in the sensorimotor areas of the affected hemisphere of the brain compared to healthy people during motor tasks. Proper mathematical models will help us understand this activity and clarify the associated underlying mechanisms. New Method. This research describes an anatomically based brain computer model in post-stroke patients. We simulate an ischemic region for arm motion using the bidomain approach. Two scenarios are considered: a healthy subject and a post-stroke patient with motion impairment. Next, we limit the volume of propagation considering only the sensorimotor area of the brain. Comparison with existing methods. In comparison to existing methods, we combine the use of the bidomain for modeling the propagation of the electrical activity across the brain volume with functional information to limit the volume of propagation and the position of the expected stimuli, given a specific task. Whereas just using the bidomain without limiting the functional volume, propagates the electrical activity into non-expected areas. To validate the simulation, we compare the activity with patient measurements using functional near-infrared spectroscopy during arm motion (n=5) against controls (n=3). The results are consistent with empirical measurements and previous research and show that there is a disparity between position and number of spikes in post-stroke patients in contrast to healthy subjects. These results hold promise in improving the understanding of brain deterioration in stroke patients and the re-arrangement of brain networks. Furthermore, shows the use of functionality based brain modeling.


Cognitive control can modulate intersensory facilitation: speeding up visual antisaccades with an auditory distractor.
Although saccadic reaction times to a visual stimulus are facilitated if an auditory accompanying stimulus is presented at the same location, this intersensory facilitation effect (IFE) has not been explored for antisaccades (saccades directed opposite to a visual target). In this study participants were asked to make an antisaccade opposite to a point of light presented right or left of fixation while accompanied by an auditory stimulus either at the same or at the opposite location with different stimulus onset asynchronies. Antisaccade reaction times for unimodal auditory and bimodal stimuli were shorter than for unimodal visual stimulation, in line with prosaccade studies. The auditory accompanying stimulus afforded antisaccade reaction times approximately as fast as prosaccades in the direction of a visual target, especially when it was presented 40 ms before the spatially congruent visual target. Moreover, predictiveness of the target position facilitated performance only when the auditory stimulus was presented at the opposite location and 40 ms before the visual target (interstimulus contingency effect). We conclude that intersensory facilitation is a mandatory, bottom-up process, but in the particular case of a response conflict due to a visual target, IFE can be shown to be modulated by the predictability of the target location.


Retrospective analysis of early outcomes after a single-armed suture technique for microsurgical intussusception vasoepididymostomy.
Longitudinal intussusception microsurgical vasoepididymostomy (LIVE) increases the patency rate in men with epididymal obstructive azoospermia (EOA). Here, we retrospectively analyzed the early outcomes of our modified single-armed suture technique for LIVE in men with EOA. From February 2012 to November 2013, 51 men received the modified technique and 39 men provided at least one post-operative semen sample. The mean age was 31.4 years old for the men and 29.2 years old for their female partners. The mean duration of obstruction was 34.3 months. Patency was noted in 24 (61.5%) men and pregnancy was reported in 15 (38.5%) female partners. Motile spermatozoa in the epididymal fluid were observed intraoperatively in 14 (58.3%) patent men and 3 (20%) non-patent men, respectively (p < 0.05). In the patent cohort, the mean ages of the pregnant and non-pregnant female partners were 26.5 and 32.7 years old, respectively (p < 0.05). Our modified technique resulted in favorable patency and pregnancy rates in this study. Sperm motility in epididymal fluid and female partner age were important factors associated with the patency and pregnancy rates.


Notes on the routine intravenous use of isometamidium in the control of bovine trypanosomiasis on the Kenya coast.
Various chemotherapeutic regimes were used to control trypanosomiasis in 3,000 Boran cattle on an estate on the Kenya coast. Recently the therapeutic use of isometamidium by the intravenous route was adopted to treat individual trypanosome-infected cattle. This was in order to overcome tissue reactions encountered after intramuscular injection and also to control a "thin cow" syndrome attributed to chronic trypanosomiasis. Toxic side effects were eliminated by careful attention to the intravenous technique which was safely used in calves, pregnant cattle and bulls. Weekly blood sampling and treatments of infected individuals resulted in a reduction of cases from 2,187 to 208 out of 46,495 and 46,329 samples examined in 1985 and 1986 respectively. The standard of management was very high and although this routine successfully controlled bovine trypanosomiasis on this estate its application elsewhere is likely to be limited.


Analysis of the genes for transferrin, transferrin receptor as well as H and L subunits of ferritin in idiopathic hemochromatosis.
In the attempt to define the abnormalities responsible for the severe iron overload found in patients with idiopathic hemochromatosis (IH) we analyzed, in 8 patients with IH and in 7 normal subjects, by using specific cDNA probes, the genes coding for the main iron-related proteins, i.e., transferrin, transferrin receptor, as well as H and L subunits of ferritin. In all the patients tested all the probes failed to evidentiate rearranged bands with any of the restriction enzymes employed. These findings suggest the absence of gross structural alterations of the genes examined. The lack of polymorphic sites recognized by the restriction enzymes employed in this study within or around the genes examined does not allow to associate a specific gene with the disease.


A modeling framework to evaluate blending of seawater and treated wastewater streams for synergistic desalination and potable reuse.
A modeling framework was developed to evaluate synergistic blending of the waste streams from seawater reverse osmosis (RO) desalination and wastewater treatment facilities that are co-located or in close proximity. Four scenarios were considered, two of which involved blending treated wastewater with the brine resulting from the seawater RO desalination process, effectively diluting RO brine prior to discharge. One of these scenarios considers the capture of salinity-gradient energy. The other two scenarios involved blending treated wastewater with the intake seawater to dilute the influent to the RO process. One of these scenarios incorporates a low-energy osmotic dilution process to provide high-quality pre-treatment for the wastewater. The model framework evaluates required seawater and treated wastewater flowrates, discharge flowrates and components, boron removal, and system energy requirements. Using data from an existing desalination facility in close proximity to a wastewater treatment facility, results showed that the influent blending scenarios (Scenarios 3 and 4) had several advantages over the brine blending scenarios (Scenarios 1 and 2), including: (1) reduced seawater intake and brine discharge flowrates, (2) no need for second-pass RO for boron control, and (3) reduced energy consumption. It should be noted that the framework was developed for use with co-located seawater desalination and coastal wastewater reclamation facilities but could be extended for use with desalination and wastewater reclamation facilities in in-land locations where disposal of RO concentrate is a serious concern.


Hyoid expansion as a treatment for obstructive sleep apnea: a pilot study.
Hyoid expansion is a novel procedure that was developed to widen and stabilize the lateral walls of the hypopharynx in order to improve obstructive sleep apnea. This study was conducted to evaluate the safety, efficacy and feasibility of hyoid expansion. A prospective, non-randomized multicenter pilot study with a follow-up of 6 months was conducted. An implantable device (the Air-Frame system) was used to surgically expand the hyoid bone. Subjective and objective outcome measures were evaluated. The procedure was successfully performed in all patients without technical adverse events. There were three clinical adverse events, and tolerance was good. Although there was a significant improvement in snoring and excessive daytime sleepiness, there was no objective improvement of the apnea-hypopnea index as measured by polysomnography. Hyoid expansion did not provide objective improvement of obstructive outcome measures in patients with obstructive sleep apnea syndrome.


Neck lumps and head and neck tumours in children.
This article discusses the presentation, investigation and treatment of both benign and malignant lumps encountered in the head and neck region in children.


Polymorphisms in common antihypertensive targets: Pharmacogenomic implications for the treatment of cardiovascular disease.
The idea of personalized medicine came to fruition with sequencing the human genome; however, aside from a few cases, the genetic revolution has yet to materialize. Cardiovascular diseases are the leading cause of death globally, and hypertension is a common prelude to nearly all cardiovascular diseases. Thus, hypertension is an ideal candidate disease to apply tenants of personalized medicine to lessen cardiovascular disease. Herein is a survey that visually depicts the polymorphisms in the top eight antihypertensive targets. Although there are numerous genome-wide association studies regarding cardiovascular disease, few studies look at the effects of receptor polymorphisms on drug treatment. With 17,000+ polymorphisms in the combined target proteins examined, it is expected that some of the clinical variability in the treatment of hypertension is due to polymorphisms in the drug targets. Recent advances in techniques and technology, such as high throughput examination of single mutations, structure prediction, computational power for modeling, and CRISPR models of point mutations, allow for a relatively rapid and comprehensive examination of the effects of known and future polymorphisms on drug affinity and effects. As hypertension is easy to measure and has a plethora of clinically viable ligands, hypertension makes an excellent disease to study pharmacogenomics in the lab and the clinic. If the promises of personalized medicine are to materialize, a concerted effort to examine the effects polymorphisms have on drugs is required. A clinician with the knowledge of a patient's genotype can then prescribe drugs that are optimal for treating that specific patient.


Instructed polarisation of sister chromatids.
We discuss a mechanism leading to antipodal polarisation of sister chromatids. The information to migrate to opposite poles originates from the interaction between spindle microtubules and the kinetochores when two sister chromatids disentangle from each other at the centromeric braid.


Treatment of folliculitis with monochromatic excimer light (308 nm).
308-nm excimer light has been reported to be safe and effective in the treatment of chronic skin diseases. The aim of the study was to prove the efficacy of 308-nm monochromatic excimer light in the treatment of recalcitrant and antibiotic-resistant folliculitis. Eight patients affected with folliculitis were enrolled and treated twice weekly with the 308-nm excimer light. The follow-up was 12 weeks from the end of the treatment. A mean number of 13 sessions (range 10-20) was performed with increasing dosage according to the patient's photo-type and response. Remission, in terms of number and infiltration of papulopustular elements, was achieved in all patients after 4-16 therapeutic sessions. At the end of the follow-up period, recurrence of folliculitis was observed in 2 patients. These results suggest that the 308-nm excimer light is a valid therapeutic option for the treatment of resistant forms of folliculitis especially in difficult-to-treat areas.


Amplification of the COX/TXS/TP receptor pathway enhances uridine diphosphate-induced contraction by advanced glycation end products in rat carotid arteries.
Advanced glycation end products (AGEs) play a pivotal role in vascular functions under various pathophysiological conditions. Although uridine diphosphate (UDP) is an important extracellular nucleotide, the relationship between AGEs and UDP regarding their effect on vascular functions remains unclear. Therefore, we investigated the effects of AGE-bovine serum albumin (AGE-BSA) on UDP-mediated responses in rat thoracic aorta and carotid arteries. In rat thoracic aorta, UDP-induced relaxation was observed and this relaxation was similar between control (1.0 v/v% PBS) and AGE-BSA-treated (0.1 mg/mL for 60 min) groups. In contrast, contraction but not relaxation was obtained following UDP application to carotid arteries with and without endothelia; contraction was greater in the AGE-BSA-treated group than in the control group. The difference in UDP-induced contraction between the two groups was not abolished by the use of a nitric oxide synthase (NOS) inhibitor, whereas it was abolished by the use of cyclooxygenase (COX), thromboxane synthase (TXS), and thromboxane-prostanoid (TP) receptor antagonist. Further, the difference in UDP-induced contraction was not abolished by the use of a cPLA2 inhibitor, whereas it was abolished by the use of an iPLA2 inhibitor. UDP increased TXA2 release in both groups, and its level was similar in both groups. Moreover, the release of PGE2, PGF2α, and PGI2 was similar among the groups. Under NOS inhibition, TP receptor agonist-induced contraction increased in the AGE-BSA-treated group (vs. control group). In conclusion, the increase in UDP-induced carotid arterial contraction by AGE-BSA can be attributed to an increase in the COX/TXS/TP receptor pathway, particularly, TP receptor signaling.


Role of JNK and NF-κB in mediating the effect of combretastatin A-4 and brimamin on endothelial and carcinoma cells.
The 4,5-diarylimidazole brimamin is an analog of the natural vascular-disrupting agent combretastatin A-4 (CA-4) with improved water solubility, tolerance by animals and efficacy in multidrug-resistant tumors. Here, we aimed at identifying the major mechanisms underlying the in vitro and in vivo actions of brimamin on endothelial and carcinoma cells, including vascularization. The contribution of specific signaling kinases to the effects of brimamin on cytoskeleton organization and the viability and differentiation of endothelial cells was assessed by MTT and tube formation assays in the presence or absence of specific kinase inhibitors. Changes in DNA affinity and expression of NF-κB in endothelial and carcinoma-derived cells and their solid tumors (xenografts) treated with brimamin were ascertained by electrophoretic mobility shift assays and Western blotting. The anti-vascular effect of brimamin in solid tumors was verified by CD31 immunostaining. We found that brimamin can inhibit tubulin polymerization and cause a reorganization of F-actin in Ea.hy926 endothelial cells. Its inhibitory effect on tube formation was found to depend on functional Rho kinase and JNK. JNK inhibition was found to suppress the induction of endothelial cell apoptosis by brimamin. In CA-4-refractory human BxPC-3 pancreas carcinoma-derived and triple-negative MDA-MB-231 breast carcinoma-derived cells brimamin was found to inhibit growth and to induce apoptosis at low nanomolar concentrations by blocking NF-κB activation in a dose-dependent manner. Brimamin was also found to reduce the in vivo growth rate and vascularization of MDA-MB-231 xenografts in mice. Residual tumor cells of these treated xenografts showed a relatively low expression of the p65 subunit of NF-κB. Our data indicate that cellular JNK and Rho kinase activities are crucial for the cytotoxic and cytoskeleton reorganizing effects of brimamin on endothelial cells. In addition, we found that in resistant carcinoma cells and xenografts brimamin can induce down-regulation of anti-apoptotic NF-κB expression and signaling. Its chemical properties and efficacy against clinically relevant cancer entities make brimamin a promising candidate vascular-disrupting agent.


Analysis of the low part of stress-strain curves in rat skin. Influence of age and desmotropic drugs.
Stress-strain behaviour of skin strips in rats at different ages or after treatment with prednisolone or D-penicillamine has been analyzed. Special attention has been paid to the lower part of the stress-strain curves. A "hump" at an extension degree of 30% of original length was noted. When rats of different ages were compared this phenomenon was observed predominantly at an age of 2 months. Futhermore, this hump was remarkable in rats treated with prednisolone. When the stress-strain curves of rats at different ages or after treatment were averaged and normalized, the most pronounced deviations were found at an age of 2 months or after prednisolone treatment. The maximum of deviation from Hooke's law occurred at a relative extension degree of 70%. Thus, the maturation process and the influence of corticosteroid affected mostly the second part of the stress-strain curve. In order to evaluate further the stress-strain curves 3 consecutive tangents of the stress-strain curves indicating modules of elasticity were evaluated. The first and second modules of elasticity showed a minimum at an age of 2 months, whereas the ultimate elasticity modules increased with maturation up to a maximum at 12 months followed by a decrease similar to that observed in tensile strength at an age of 24 months.


Age and novelty: event-related potentials to visual stimuli within an auditory oddball--visual detection task.
Age-related change of event-related potentials to novel visual stimuli was investigated while participants attended to both auditory and visual stimulation. Meaningful but irrelevant pictures (novel stimuli) were presented to younger (mean=21.8, range=18-26 years) and older (mean=70.0, range=60-78) participants (10 in each group). The participants were performing an auditory oddball task and counting silently the changes of a visually presented letter. In the younger group novel stimuli elicited a posterior positivity in the 220-255 ms range. This component habituated to the repetition of the same picture. In the older group this component had longer latency, and did not habituate. A later positivity had shorter latency and larger amplitude in the younger group, but this positivity was preceded by a negative component (N2b) only in the elderly. Results show decreased sensitivity to the content of the visual stimuli in an earlier stage of novelty processing in the elderly, and the age-related slowing of both orientation-related and task-related processes.


A national burden of disease calculation: Dutch disability-adjusted life-years. Dutch Burden of Disease Group.
This study estimated the burden of disease due to 48 major causes in the Netherlands in 1994 in disability-adjusted life-years (DALYs), using national epidemiologic data and disability weights, and explored associated problems and uncertainties. We combined data from Dutch vital statistics, registrations, and surveys with Dutch disability weights to calculate disease-specific health loss in DALYs, which are the sum of years of life lost (YLLs) and years lived with disability (YLDs) weighted for severity. YLLs were primarily lost by cardiovascular diseases and cancers, while YLDs were mostly lost by mental disorders and a range of chronic somatic disorders (such as chronic nonspecific lung disease and diabetes). These 4 diagnostic groups caused approximately equal numbers of DALYs. Sensitivity analysis calls for improving the accuracy of the epidemiologic data in connection with disability weights, especially for mild and frequent diseases. The DALY approach appeared to be feasible at a national Western European level and produced interpretable results, comparable to results from the Global Burden of Disease Study for the Established Market Economies. Suggestions for improving the methodology and its applicability are presented.


A simple methods for labeling BSP with 131I.
BSP was labeled with 131I using the Greenwood and Hunter method, which was rapid and simple. The chromatoelectrophoresis of the labeled compound showed that the labeling efficiency was 100%. Scintigraphic studies gave good results in accordance with radioactive BSP distribution reported in the literature.


Studies on the modification of the cellular response to injury. III. Electron microscopic studies on the protective effect of acidosis on p-chloromercuribenzene sulfonic acid-(PCMBS) induced injury of Ehrlich ascites tumor cells.
Extracellular acidosis (pH 6.5) was found to significantly retard the response of Ehrlich ascites tumor cells (EATC) to direct plasma membrane injury with the non-penetrating organic mercurial compound, p-chloromercuribenzene sulfonic acid (PCMBS). Treatment of cells with 1 mM PCMBS resulted in loss of viability of all cells by 45 minutes at pH 7.4, and by 90 minutes at pH 6.5. Pregression of cellular changes through the various stages of cell injury at the ultrastructural level was correspondingly slower at pH 6.5. The results support the concept that stage 3 of cell injury, associated with condensed mitochondria, dilated ER and swollen cell sap is compatible with cell survival, while stage 5 with high amplitude swelling of mitochondria, fragmentation of membrane systems, and beginning of karyolysis is characteristic of irreversible injury. All cells entered stage 3 at 7.5 minutes at pH 7.4, while essentially all cells entered stage 5 by 45 minutes. At pH 6.5, stage 3 was maintained for 45 minutes and 100% of the cells entered stage 5 by 90 minutes. Although the mechanism of the protection against PCMBS-induced injury is not known, the present electron microscopical results are compatible with the hypothesis that the extracellular acidosis acts to partially stabilize plasma membrane, perhaps by interaction with sulfhydryl (SH) groups.


The design of a new insert for calibration of LDR and HDR 192Ir sources in a well-type ionization chamber.
Some well-type ionization chambers, present a very small sweet spot that are sufficient for small HDR sources. However, if a longer HDR source or LDR wires are calibrated, the positional uncertainty increases and an approximated correction factor must be applied, resulting in an increased uncertainty. One of the ways to avoid this problem would be to flatten the well chamber response by increasing its sweet spot region. This work uses the Monte Carlo code PENELOPE to simulate the response of a well-type chamber HDR-1000, with its original insert, by using an HDR 192Ir source and proposes a new insert design that increases its flatness region from 1.0 cm to approximately 4.0 cm (+/- 2.0 cm about the peak response).


Capsule endoscopy findings in patients with established and suspected small-bowel Crohn's disease: correlation with radiologic, endoscopic, and histologic findings.
Little is known about the accuracy of capsule endoscopy (CE) in evaluation of small-bowel Crohn's disease. Symptomatic eligible patients had ileocolonoscopy and biopsies from the terminal ileum, followed by small-bowel radiologic studies before CE. Endoscopic, radiologic, CE, and histologic findings were compared. Histology (terminal ileum biopsy specimens or a tissue sample after small-bowel resection) served as a criterion standard. Fifty-four patients were enrolled; 15 of the 54 patients were excluded from data analysis (critical small-bowel strictures, 14, identified on radiology; incomplete CE, 1). Data were analyzed for 39 patients. All patients had histologic evaluation of the small bowel. Final diagnosis of active small-intestine Crohn's disease was made in 29/39 patients (74.4%). When calculated, CE yielded a sensitivity and a specificity of 89.6% and 100.0%, respectively, and a positive predictive value and a negative predictive value of 100.0% and 76.9%, respectively, whereas small-bowel series were 27.6%/100.0% and 100.0%/32.3%. CE is more accurate in detecting small-bowel inflammatory changes suggestive of Crohn's disease than conventional studies. CE, combined with ileocolonoscopy, may be proposed as a first-line investigation of the small intestine in cases of uncomplicated known or suspected Crohn's disease.


Implications of epigallocatechin-3-gallate in cultured human Sertoli cells glycolytic and oxidative profile.
Sertoli cells are crucial for the success of spermatogenesis, which is the biological process that ensures male fertility. These cells present high metabolic rates, being often subjected to high oxidative stress levels that, if uncontrolled, may compromise male fertility. Since the most abundant tea catechin, epigallocatechin-3-gallate (EGCG), has demonstrated a potent preventive activity against oxidative stress, we have evaluated its effect at concentrations of 5 and 50μM, on the metabolism, mitochondrial functionality and oxidative profile of human Sertoli cells (hSCs). While, the highest concentration of EGCG (50μM) increased glucose and pyruvate consumption, it decreased the conversion of pyruvate to alanine to sustain a regular lactate production. However, despite maintaining Krebs cycle functionality, EGCG (50μM) decreased mitochondrial membrane potential of hSCs, which could compromise the normal rates of ATP production. Interestingly, oxidative damages to proteins and lipids decreased in this experimental group, which may be valuable for the nutritional support of spermatogenesis.


Detection of vulnerable atherosclerotic plaque and prediction of thrombosis events in a rabbit model using 18F-FDG -PET/CT.
Detection of vulnerable plaques could be clinically significant in the prevention of cardiovascular events. We aimed to compare Fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in vulnerable and stable plaques, and investigate the feasibility of predicting thrombosis events using Positron Emission Tomography/Computed Tomography (PET/CT) angiography. Atherosclerosis was induced in 23 male New Zealand white rabbits. The rabbits underwent pharmacological triggering to induce thrombosis. A pre-triggered PET/CTA scan and a post-triggered PET/CTA scan were respectively performed. (18)F-FDG uptake by the aorta was expressed as maximal standardized uptake value (SUVmax) and mean SUV (SUVmean). SUVs were measured on serial 7.5 mm arterial segments. Thrombosis was identified in 15 of 23 rabbits. The pre-triggered SUVmean and SUVmax were 0.768 ± 0.111 and 0.804 ± 0.120, respectively, in the arterial segments with stable plaque, and 1.097 ± 0.189 and 1.229 ± 0.290, respectively, in the arterial segments with vulnerable plaque (P<0.001, respectively). The post-triggered SUVmean and SUVmax were 0.849 ± 0.167 and 0.906 ± 0.191, respectively in the arterial segments without thrombosis, and 1.152 ± 0.258 and 1.294 ± 0.313, respectively in the arterial segments with thrombosis (P<0.001, respectively). The values of SUVmean in the pre-triggered arterial segments were used to plot a receiver operating characteristic curve (ROC) for predicting thrombosis events. Area under the curve (AUC) was 0.898. Maximal sensitivity and specificity (75.4% and 88.5%, respectively) were obtained when SUVmean was 0.882. Vulnerable and stable plaques can be distinguished by quantitative analysis of (18)F-FDG uptake in the arterial segments in this rabbit model. PET/CT may be used for predicting thrombosis events and risk-stratification in patients with atherosclerotic disease.


Excess dietary iron is the root cause for increase in childhood autism and allergies.
Autism is a profoundly and poorly understood developmental disorder that impairs a person's social and communication abilities. I propose a hypothesis that the excessive dietary iron consumed by today's infants is the root cause of increased cases of Autism, allergies and other childhood diseases. Iron is a powerful immune system modulator. Excess iron causes hyperactive immune system. This hyperactive immune system attacks undigested food peptides. The chemicals released during these intense allergic reactions can damage surrounding tissue. Neurodegeneration is caused by combination of, oxidative stress induced by free iron radicals and intense immune reactions. Iron chelators have shown beneficial results in Autism and allergies.


The integrated common-sense model of illness self-regulation: predicting healthy eating, exercise behaviors, and health among individuals at risk of metabolic syndrome.
Little is known about the potential mechanisms of healthy eating and exercise change, and design interventions which aim to promote healthy eating and exercise change among individuals at risk of metabolic syndrome. This study aimed to identify key determinants of healthy eating, exercise behaviors, and health among individuals at risk of metabolic syndrome using the integrated common-sense model of illness self-regulation. A cross-sectional study with a multi-wave data collection strategy. A total of 275 participants at risk of metabolic syndrome based on the clinical prediction model were included in the final analysis. Path analysis was employed to explore the pattern of relationships between key variables using AMOS. The mediation analysis suggested that personal and treatment control, and coherence can positively affect self-reported health via intentions and health behaviors (exercise and healthy eating). Additionally, relationships between self-efficacy (exercise and healthy eating) and health outcomes can be mediated by health behaviors, and both intentions and health behaviors. This current research used the integrated common-sense model of illness self-regulation to predict healthy eating, exercise behaviors, and self-reported health among individuals at risk of metabolic syndrome. The results suggested that self-efficacy, intention, consequences, personal control, treatment control, and coherence were the key determinants of behavior and health, which can help design interventions to encourage healthy eating and exercise changes among individuals with a high risk of MetS.


Abdominal binder use in people with spinal cord injuries: a systematic review and meta-analysis.
Systematic review and meta-analysis. To review the evidence for the use of an abdominal binder on breathing, speech and cardiovascular function in people who have suffered a spinal cord injury (SCI). Brisbane, Australia. A search of multiple databases (Medline, Cinahl, Cochrane, Embase, PEDro) was undertaken accompanied by the reference list evaluation of each relevant publication identified. Methodological quality of studies identified was assessed using the PEDro scale. The size of effect of an abdominal binder on outcomes was also calculated where sufficient data were reported. Further descriptive analysis was performed. Eleven studies met the review inclusion criteria and employed either crossover or within subject designs. Comparison of studies involving elastic and non-elastic binders was performed. A PEDro mean score of 4.3 out of 8 (range: 3-6) was found. Meta-analysis indicated that the use of abdominal binders improved vital capacity (VC) by (weighted mean difference (95% confidence interval (CI)) 0.32 (0.09, 0.55) litres, decreased functional residual capacity (FRC) by 0.41 (0.14, 0.67) litres, but did not significantly influence total lung capacity (TLC). This review found some evidence that the use of an abdominal binder improves VC, but decreases FRC when assuming the sitting or tilted position in people who have suffered SCI. Overall, the quality of the studies was poor. Available evidence is not yet sufficient to either support or discourage the use of an abdominal binder in this patient population. Further studies utilizing more methodologically rigorous designs are required.


Comparison of the surgical resection and infarct 5/6 nephrectomy rat models of chronic kidney disease.
The 5/6 nephrectomy rat remnant kidney model is commonly used to study chronic kidney disease (CKD). This model requires the removal of one whole kidney and two-thirds of the other kidney. The two most common ways of producing the remnant kidney are surgical resection of poles, known as the polectomy model, or ligation of superior and inferior segmental renal arteries, resulting in pole infarction. These models have much in common, but also major phenotypic differences, and thus respectively model unique aspects of human CKD. The purpose of this review is to summarize phenotypic similarities and differences between these two models and their relation to human CKD while emphasizing their vascular phenotype. In this article, we review studies that have evaluated arterial blood pressure, the renin-angiotensin-aldosterone-system, autoregulation, nitric oxide, single-nephron physiology, angiogenic and antiangiogenic factors, and capillary rarefaction in these two models. In terms of phenotypic similarities, both models spontaneously develop hallmarks of human CKD including uremia, fibrosis, capillary rarefaction, and progressive renal function decline. They both undergo whole organ hypertrophy, hyperfiltration of functional nephrons, reduced renal expression of vascular endothelial growth factor, increased renal expression of antiangiogenic thrombospondin-1, impaired renal autoregulation, and abnormal vascular nitric oxide physiology. In terms of key phenotypic differences, the infarction model develops rapid-onset, moderate to severe systemic hypertension and the polectomy model develops early normotension followed by mild to moderate hypertension. Rats subjected to the infarction model have a markedly more active renin-angiotensin-aldosterone system. Comparison of these two models facilitates understanding of how they can be used for studying CKD pathophysiology.


Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan.
The gene that codes for dopamine receptor D2 (DRD2 on chromosome 11q23) has long been a prime functional and positional candidate risk gene for schizophrenia. Collectively, prior case-control studies found a reliable effect of the Ser311Cys DRD2 polymorphism (rs1801028) on risk for schizophrenia, but few other polymorphisms in the gene had ever been evaluated and no adequately powered family-based association study has been performed to date. Our objective was to test 21 haplotype-tagging and all three known nonsynonymous single-nucleotide polymorphisms (SNPs) in DRD2 for association with schizophrenia in a family-based study of 2408 Han Chinese, including 1214 affected individuals from 616 families. We did not find a significant effect of rs1801028, but we did find significant evidence for association of schizophrenia with two multi-marker haplotypes spanning blocks of strong linkage disequilibrium (LD) and nine individual SNPs (Ps<0.05). Importantly, two SNPs (rs1079727 and rs2283265) and both multi-marker haplotypes spanning entire LD blocks (including one that contained rs1801028) remained significant after correcting for multiple testing. These results further add to the body of data implicating DRD2 as a schizophrenia risk gene; however, a causal variant(s) in DRD2 remains to be elucidated by further fine mapping of the gene, with particular attention given to the area surrounding the third through fifth exons.


Effect of caffeic acid on tert-butyl hydroperoxide-induced oxidative stress in U937.
Nonvitamin phenolic compounds are ubiquitous in food plants and therefore potentially present in human plasma in a diet-dependent concentration. The aim of this study was to evaluate the ability of caffeic acid, a phenolic acid with antioxidant activity, to affect cellular response in U937 human monocytic cells to t-butyl hydroperoxide-induced oxidative stress. In our experimental conditions caffeic acid was incorporated into cells without any cytotoxic effect. Caffeic acid-treated cells showed an increased resistance to oxidative challenge, as revealed by an higher percent of survival and the maintenance of an higher proliferative capacity in respect to control cells. This effect seems to be due to the ability of caffeic acid to reduce glutathione depletion and to inhibit lipid peroxidation during tBOOH treatment. It can be concluded that caffeic acid exerts an antioxidant action inside the cell, responsible for the observed modulation of the cellular response to oxidative challenge. Due to its presence in the diet, therefore, caffeic acid may play a role in the modulation of oxidative processes in vivo.


Assignment of the gene for enolase to mouse chromosome 4 using somatic cell hybrids.
Somatic cell hybrids between mouse peritoneal macrophages (MPM) and human fibrosarcoma cells (HT-1080) or Chinese hamster cells (A3) were analyzed by starch-gel electrophoresis for the expression of murine enolase. Data obtained indicate that the locus for enolase is on chromosome 4 in the mouse.


Enzyme linked immunosorbent assay for the measurement of nonenzymatically glucosylated proteins in serum and in tissues.
We have developed an enzyme linked immunosorbent assay (ELISA) for glucosylated proteins. The polyclonal antiserum was prepared against reduced glucosylated lipoproteins and was specific for the glucose-lysine bond. The antiserum recognized, in a dose-dependent manner, all reduced glucosylated proteins tested, including albumin, fibrinogen, low density lipoprotein, high density lipoprotein and hemoglobin, yet had no affinity for native proteins or to glucosylated but nonreduced proteins. The sensitivity of the assay was in the order of 1-5 pmol glucosylated lysine/ml and half maximal displacement occurred at 8-24 pmol glucosylated lysine/ml. The inter- and intraassay variables were 10.8% and 13.5%, respectively. Serum proteins from diabetic patients (n = 30) contained 84 +/- 6 picomoles of glucosylated lysine/mg protein, compared to 28 +/- 3 in controls (n = 20), and the concentration of glycosylated proteins correlated with fasting blood glucose (r = 0.56, p less than 0.02), but not with glucosylated hemoglobin levels (r = 0.29, p greater than 0.1). Proteins from diabetic glomeruli and aortae similarly contained more glucosylated lysine residues than controls.


Sperm aminopeptidase N identifies the potential for high-quality blastocysts and viable embryos in oocyte-donation cycles.
Is there a relationship between human sperm aminopeptidase N (APN) and embryo development in humans? Human sperm APN could possibly become a new molecular biomarker for identifying the potential for high-quality and usable embryos. The diagnosis of male fertility is one of the major concerns of reproductive medicine. Approximately 30-40% of men with otherwise normal fertility parameters are still unable to achieve pregnancy. The predictive clinical value of semen analysis to identify fertile or infertile males is limited; therefore, new diagnostic methodologies for sperm are urgently required. Sperm APN may be a relevant molecular marker due to its high concentration in sperm cells and its important roles in sperm physiology, such as its functions in motility, acrosome reaction and embryo development. This study included 81 couples who underwent oocyte-donation cycles at Clínica IVI Bilbao (Spain), yielding 611 embryos, between September 2014 and July 2015. This study was conducted in an assisted reproduction unit and an academic research laboratory. All the semen samples were examined and classified following World Health Organization guidelines. Spermatozoa were isolated from semen using the discontinuous colloidal silica gradient (45-90%) technique. Embryo quality and development were determined according to the Spanish Association of Reproduction Biology Studies (ASEBIR) criteria. Human sperm APN levels were analyzed by quantitative and semiquantitative flow cytometry. The most well-developed and usable blastocysts were associated with low sperm APN levels. Semen samples that had lower APN levels generated more expanded, hatched and usable blastocysts and fewer early, arrested and non-usable blastocysts. The cumulative probability of having well-developed blastocysts increased by 1.38-fold at Day 5 and 1.90-fold at Day 6 of embryo development, and the likelihood of having usable embryos increased by 1.48-fold, when semen samples with low APN levels were used during the ICSI technique. The data were obtained from a single fertility clinic. A multicentre study will be required to confirm the results. Human sperm APN has the potential to become a new molecular biomarker to help identify the potential for high-quality embryos and diagnose male infertility, especially when seminal parameters are close to the threshold values. It could be a crucial tool for couples for whom the number of usable blastocysts is critical for ART success. This study was supported by grants from the Basque Government (GIC15/165) and the University of the Basque Country (UPV/EHU) (EHUA14/17). The authors declare that they have no conflicts of interest. N/A.


A mechanism for cognitive dynamics: neuronal communication through neuronal coherence.
At any one moment, many neuronal groups in our brain are active. Microelectrode recordings have characterized the activation of single neurons and fMRI has unveiled brain-wide activation patterns. Now it is time to understand how the many active neuronal groups interact with each other and how their communication is flexibly modulated to bring about our cognitive dynamics. I hypothesize that neuronal communication is mechanistically subserved by neuronal coherence. Activated neuronal groups oscillate and thereby undergo rhythmic excitability fluctuations that produce temporal windows for communication. Only coherently oscillating neuronal groups can interact effectively, because their communication windows for input and for output are open at the same times. Thus, a flexible pattern of coherence defines a flexible communication structure, which subserves our cognitive flexibility.


Alkoxy-position effects on piezofluorochromism and aggregation-induced emission of 9,10-bis(alkoxystyryl)anthracenes.
Changing the linking positions of alkoxy chains can significantly alter the aggregation-induced emission and piezofluorochromic activities of 9,10-bis(alkoxystyryl)anthracenes.


Inhibitory effects of human and porcine alpha-amylase on CCK-8-stimulated lipase secretion of isolated rat pancreatic acini.
Previously we have demonstrated inhibitory effects of the plant lectin wheat germ agglutinin (WGA) on (125)I-CCK-8 binding to pancreatic AR42J cells as well as on CCK-8-stimulated Ca(2+) release and alpha-amylase secretion of rat pancreatic acini or acinar cells. Therefore, it is entirely conceivable that alpha-amylase having several lectin-like carbohydrate recognition domains can modulate the CCK-8 stimulated lipase secretion. Human alpha-amylase, purified from pancreatic juice by affinity chromatography to homogeneity, and commercial porcine pancreatic alpha-amylase inhibit CCK-8-stimulated lipase secretion of rat pancreatic acini in a concentration-dependent manner. Acarbose, a specific inhibitor of alpha-amylase, was without effect on CCK-8-induced cellular lipase secretion. The data presented here provide evidence for a regulatory function of alpha-amylase in CCK-8-stimulated pancreatic secretion.


Reviewing the Health Care Impacts of Attacks on Critical Infrastructure.
Health care provision depends on reliable critical infrastructure (CI) to power equipment and to provide water for medication and sanitation. Attacks on CI limiting such functions can have a profound and prolonged influence on delivery of care. A retrospective analysis of the Global Terrorism Database (GTD) was performed of all attacks occurring from 1970-2020. Data were filtered using the internal database search function for all events where the primary target was "Utilities," "Food or Water Supply," and "Telecommunications." For the purposes of this study, the subtype "Food Supply" was excluded. Events were collated based on year, country, region, and numbers killed and wounded. The GTD listed 7,813 attacks on CI, with 6,280 of those attacks targeting utilities, leading to 1,917 persons directly killed and 1,377 persons wounded. In total, there were 1,265 attacks targeting telecommunications causing 205 direct deaths and 510 wounded. Lastly, 268 attacks targeted the water supply with 318 directly killed and 261 wounded. Regionally, South America had the most attacks with 2,236, followed by Central America and the Caribbean with 1,390. Based on infrastructure type, the most attacks on utilities occurred in El Salvador (1,061), and the most attacks on telecommunications were in India (140). Peru (46) had the most attacks on its water supply. The regions with the highest number of total attacks targeting CI have historically been in South America, with more attacks against power and utilities than other infrastructure. Although the numbers of persons directly killed and wounded in these attacks were lower than with other target types, the true impacts on lack of health care delivery are not accounted for in these numbers. By understanding the pattern and scope of these attacks, Counter-Terrorism Medicine (CTM) initiatives can be created to target-harden health care-related infrastructure.


Acetaminophen induced hepatotoxicity: An overview of the promising protective effects of natural products and herbal formulations.
The liver plays an important role in regulating the metabolic processes and is the most frequently targeted organ by toxic chemicals. Acetaminophen (APAP) is a well-known anti-allergic, anti-pyretic, non-steroidal anti-inflammatory drug (NSAID), which upon overdose leads to hepatotoxicity, the major adverse event of this over-the-counter drug. APAP overdose induced acute liver injury is the second most common cause that often requires liver transplantation worldwide, for which N-acetyl cysteine is the only synthetic drug clinically approved as an antidote. So, it was felt that there is a need for the novel therapeutic approach for the treatment of liver diseases with less adverse effects. This review provides detailed analysis of the different plant extracts; phytochemicals and herbal formulations for the amelioration of APAP-induced liver injury. The data was collected using different online resources including PubMed, ScienceDirect, Google Scholar, Springer, and Web of Science using keywords given below. Over the past decades various reports have revealed that plant-based approaches may be a better treatment choice for the APAP-induced hepatotoxicity in pre-clinical experimental conditions. Moreover, herbal compounds provide several advantages over the synthetic drugs with fewer side effects, easy availability and less cost for the treatment of life-threatening diseases. The current review summarizes the hepatoprotective effects and therapeutic mechanisms of various plant extracts, active phytoconstituents and herbal formulations with potential application against APAP induced hepatotoxicity as the numbers of hepatoprotective natural products are more without clinical relativity. Further, pre-clinical pharmacological research will contribute to the designing of natural products as medicines with encouraging prospects for clinical application.


Transformation of attitude through brief psychoeducation program for the husbands of women with postpartum psychiatric disorders.
According to existing literature on Perinatal Psychiatric Services, husbands have not often been involved in the treatment of their spouses with Perinatal Psychiatric disorders, especially in India, despite the advantages as an adjunctive form of therapy. The current study aimed at evaluating the effectiveness of brief psychoeducation on the attitude of husbands of women with postpartum psychiatric disorder through a biopsychosocial based informative and supportive model of intervention. A 3 session based Brief Psychoeducation Program (BPP) was developed for the targeted population and its effectiveness was evaluated through quasi-experimental research design. Using Community Attitude towards Mentally Ill Scale (CAMI) assessment of the outcome variable was done at 3 levels i.e., Pre (baseline), Post (immediately after the intervention) and Follow-up post (1 month after the intervention). A total of 21 participants were recruited meeting the study criteria. Friedmans test and descriptive statistics were used to analyze the data. Results indicated the transformation in the attitude of the participants in all the 4 domains of the scale from pre-intervention to post-intervention phase. The study has a strong implication for mental health professionals in this area at both clinical (medical and psychiatry settings) and nonclinical settings.


Effect of an unstable shoe construction on lower extremity gait characteristics.
To compare kinematics, kinetics and muscle activity during standing and walking for healthy subjects using an unstable test shoe (Masai Barefoot Technology, MBT) and a stable control shoe. Eight subjects volunteered for this study. During quiet standing, center of pressure excursion and muscle activity were determined. During walking, lower extremity kinematics, kinetics, and muscle electromyographic (EMG) signals were determined. Data were collected for the two shoe conditions after a 2week accommodation period. Statistics included repeated measures ANOVAs (alpha = 0.05) and post hoc tests where appropriate. During quiet standing, the center of pressure excursion was significantly and substantially greater in the unstable compared to the control shoe. Electromyographic intensity increased in the unstable test shoe for all tested muscles, but only significantly for the tibialis anterior. During locomotion, kinematics were similar in the two shoe conditions except for the initial plantar-dorsiflexion, which showed a significant more dorsiflexed position during the first half of stance in the unstable test shoe compared to the stable control shoe. The angular impulses did not show any significant differences between the two shoe conditions for all three joints but some trends towards a reduction for the knee and hip joint. There were no significant differences in electromyographic activities between the control and the unstable shoe. However, several muscles showed some trends. The unstable shoe produced changes and trends in kinematic, kinetic and electromyographic characteristics that seemed to be advantageous for the locomotor system. Further studies should investigate muscle strength, dynamic stability, pain reduction for arthritic knees and injury prevention for high performance athletes when using the unstable shoes.


In ischemic stroke, thrombectomy alone was noninferior to thrombectomy plus alteplase for functional outcome at 90 days.
Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med. 2020;382:1981-93. 32374959.


Assessment of trace metal contamination in a historical freshwater canal (Buckingham Canal), Chennai, India.
The present study was done to assess the sources and the major processes controlling the trace metal distribution in sediments of Buckingham Canal. Based on the observed geochemical variations, the sediments are grouped as South Buckingham Canal and North Buckingham Canal sediments (SBC and NBC, respectively). SBC sediments show enrichment in Fe, Ti, Mn, Cr, V, Mo, and As concentrations, while NBC sediments show enrichment in Sn, Cu, Pb, Zn, Ni, and Hg. The calculated Chemical Index of Alteration and Chemical Index of Weathering values for all the sediments are relatively higher than the North American Shale Composite and Upper Continental Crust but similar to Post-Archaean Average Shale, and suggest a source area with moderate weathering. Overall, SBC sediments are highly enriched in Mo, Zn, Cu, and Hg (geoaccumulation index (I(geo)) class 4-6), whereas NBC sediments are enriched in Sn, Cu, Zn, and Hg (I(geo) class 4-6). Cu, Ni, and Cr show higher than Effects-Range Median values and hence the biological adverse effect of these metals is 20%; Zn, which accounts for 50%, in the NBC sediments, has a more biological adverse effect than other metals found in these sediments. The calculated I(geo), Enrichment Factor, and Contamination Factor values indicate that Mo, Hg, Sn, Cu, and Zn are highly enriched in the Buckingham Canal sediments, suggesting the rapid urban and industrial development of Chennai Metropolitan City have negatively influenced on the surrounding aquatic ecosystem.


The curfew bill as it relates to the juvenile and his family.
Curfew laws have been instituted in cities across the United States in an attempt to control the rise in juvenile crime. This article discusses the advantages and disadvantages of a curfew law for Baltimore City based on interviews with city officals and concludes that the law in its present form will not bring about any significant change in the rate of delinquency. Alternative are suggested that might better get to the source of the problem. These include more youth and family counseling services, rehabilitative facilities, work study programs and shelter areas.


MgO and ZnO nanoparticles anti-nociceptive effect modulated by glutamate level and NMDA receptor expression in the hippocampus of stressed and non-stressed rats.
The anti-nociceptive mechanisms of MgO and ZnO nanoparticles have not been thoroughly investigated; in this study, we evaluated the effects of anti-nociceptive dose of MgO and ZnO NPs on glutamate level and NMDA receptor subunits expression (NR1, NR2 and NR2B) in the rat whole hippocampus with and without acute restraint stress. Adult rats were divided into control, MgO and ZnO NPs 5 mg/kg, the stress of 90 min alone and with MgO or ZnO NPs 5 mg/kg groups. All components injected intraperitoneally and the nociceptive response was measured with hot plate apparatus 90 min after injections or stress induction. Magnesium, zinc, glutamate levels and NMDA receptor subunits expression were measured in the animal hippocampus. MgO NPs, ZnO NPs and acute stress induced anti-nociceptive effect. MgO NPs observably decreased glutamate and increased magnesium levels and NR2B subunit expression. ZnO NPs decreased glutamate level. Stress elevated endogenous magnesium and zinc levels and also the NR2B expression, but did not change glutamate level. MgO and ZnO NPs in the presence of stress increased the glutamate level and ZnO NPs increased the zinc and the NR2A expression. Stress decreased endogenous magnesium in the hippocampus. MgO and ZnO NPs could affect pain perception by changing glutamate level in the whole hippocampus tissue, while ion level changes followed by injection could probably affect the gene expression in the presence and the absence of stress. It seems that stress indirectly could adverse nanoparticles effects on glutamate level and increase zinc ion releasing from ZnO NPs by activating the gene expression without affecting pain perception.