Autism in a child with congenital cytomegalovirus infection.
A case is reported of early infantile autism associated with a congenital cytomegalovirus infection. The diagnosis of autism is based on the child's failure to develop good interpersonal relationships, poor eye contact, delayed and deviant use of language, and her rote and nonthematic use of objects and playthings. Resistance to change and self-stimulatory behavior were also present. Onset was before 2 years of age. Congenital cytomegalovirus infection was suggested by the presence of an antibody response to the virus, culture of the virus from the urine, sensorineural hearing loss, and inflammatory damage to the retina of the eye. Although over time improvement was noted, at last examination at the age of 5 years her behavior is still markedly deviant. This and other reported cases suggest that congenital viral infection may be an important cause of infantile autism. It is hypothesized that an ability of the agent to establish chronic infection may predispose to behavioral aberration.


[The correction of dysbiotic disorders of the vaginal microflora by using a preparation made from highly adhesive lactobacteria].
The effectiveness of a new bacterial preparation obtained from highly adhesive lactobacteria and intended for the correction of dysbiotic disturbances of vaginal microflora was studied in the treatment of 60 pregnant women with dysbacteriosis of the maternal passages. 30 pregnant women were simultaneously treated by the vaginal application of Lactobacterin. The study showed that the use of the preparation of highly adhesive lactobacteria caused the pronounced and stable correction of the microflora of the maternal passages. This correction was manifested by the domination of lactic acid bacterial flora and a decrease in the number of opportunistic microorganisms.


No evidence of the effect of cognitive load on self-paced cycling performance.
To test the hypothesis that cognitive load (low vs. high load) during a 20 min self-paced cycling exercise affects physical performance. A pre-registered (https://osf.io/qept5/), randomized, within-subject design experiment. 28 trained and experienced male cyclists completed a 20 min self-paced cycling time-trial exercise in two separate sessions, corresponding to two working memory load conditions: 1-back or 2-back. We measured power output, heart rate, RPE and mental fatigue. Bayes analyses revealed extreme evidence for the 2-back task being more demanding than the 1-back task, both in terms of accuracy (BF10 = 4490) and reaction time (BF = 1316). The data only showed anecdotal evidence for the alternative hypothesis for the power output (BF10 = 1.52), moderate evidence for the null hypothesis for the heart rate (BF10 = 0.172), anecdotal evidence for RPE (BF10 = 0.72) and anecdotal evidence for mental fatigue (BF10 = 0.588). Our data seem to challenge the idea that self-paced exercise is regulated by top-down processing, given that we did not show clear evidence of exercise impairment (at the physical, physiological and subjective levels) in the high cognitive load condition task with respect to the low working memory load condition. The involvement of top-down processing in self-pacing the physical effort, however, cannot be totally discarded. Factors like the duration of the physical and cognitive tasks, the potential influence of dual-tasking, and the participants' level of expertise, should be taken into account in future attempts to investigate the role of top-down processing in self-paced exercise.


Influence of short-interval intracortical inhibition on short-interval intracortical facilitation in human primary motor cortex.
Using the paired-pulse paradigm, transcranial magnetic stimulation (TMS) has revealed much about the human primary motor cortex (M1). A preceding subthreshold conditioning stimulus (CS) inhibits the excitability of the motor cortex, which is named short-interval intracortical inhibition (SICI). In contrast, facilitation is observed when the first pulse (S1) is followed by a second one at threshold (S2), named short-interval intracortical facilitation (SICF). SICI and SICF have been considered to be mediated by different neural circuits within M1, but more recent studies reported relations between them. In this study, we performed triple-pulse stimulation consisting of CS-S1-S2 to further explore putative interactions between these two effects. Three intensities of CS (80-120% of active motor threshold: AMT) and two intensities of S2 (120 and 140% AMT) were combined. The SICF in the paired-pulse paradigm exhibited clear facilitatory peaks at ISIs of 1.5 and 3 ms. The second peak at 3 ms was significantly suppressed by triple-pulse stimulation using 120% AMT CS, although the first peak was almost unaffected. Our present results obtained using triple-pulse stimulation suggest that each peak of SICF is differently modulated by different intensities of CS. The suppression of the second peak might be ascribed to the findings in the paired-pulse paradigm that CS mediates SICI by inhibiting later I waves such as I3 waves and that the second peak of SICF is most probably related to I3 waves. We propose that CS might inhibit the second peak of SICF at the interneurons responsible for I3 waves.


Ketogenesis from butyrate and acetate by the caecum and the colon of rabbits.
1. When studied in vitro, tissue from the caecum and the proximal colon of rabbits converted butyrate into ketone bodies. The conversion was similar to that observed with liver slices. The ketogenic activity was associated with the mucosa rather than the muscle of the gut wall and, in the colon, diminished as the distance from the caecal-colonic junction increased. 2. Tissue from the wall of the ileum, caecum, proximal colon and distal colon was also shown to metabolize [1-(14)C]butyrate to carbon dioxide. 3. Enzyme assays showed that in both liver tissue and caecal mucosa the activity of hydroxymethylglutaryl-CoA synthase was more than ten times that of acetoacetyl-CoA deacylase. Labelling experiments in vitro gave confirmation of the hydroxymethylglutaryl-CoA pathway. 4. The significance of the conversion of butyrate into ketone bodies is discussed.


Some factors that may alter consumption of animal products. A review.
Trends in consumption of animal products are discussed, including reasons for changes. Although consumption of some products has increased--notably that of broilers and beef--for other products, it has declined, i.e., total dairy products and eggs. Evidence shows that consumers desire a lower fat content in both meat and dairy products, although, in the case of meat, minimal levels are necessary for palatability. Overall, it is suggested that consumers are concerned with nutritional quality and are influenced by health-related concerns. The use of vegetable proteins as extenders and substitutes for animal proteins is reviewed, with the conclusion that they will continue to influence consumption of animal products.


Antagonism of PACAP or microglia function worsens the cardiovascular consequences of kainic-acid-induced seizures in rats.
Seizures are accompanied by cardiovascular changes that are a major cause of sudden unexpected death in epilepsy (SUDEP). Seizures activate inflammatory responses in the cardiovascular nuclei of the medulla oblongata and increase neuronal excitability. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with autocrine and paracrine neuroprotective properties. Microglia are key players in inflammatory responses in the CNS. We sought to determine whether PACAP and microglia mitigate the adverse effects of seizure on cardiovascular function in a rat model of temporal lobe epilepsy. Kainic acid (KA)-induced seizures increased splanchnic sympathetic nerve activity by 97%, accompanied by increase in heart rate (HR) but not blood pressure (BP). Intrathecal infusion of the PACAP antagonist PACAP(6-38) or the microglia antagonists minocycline and doxycycline augmented sympathetic responses to KA-induced seizures. PACAP(6-38) caused a 161% increase, whereas minocycline and doxycycline caused a 225% and 215% increase, respectively. In intrathecal PACAP-antagonist-treated rats, both BP and HR increased, whereas after treatment with microglial antagonists, only BP was significantly increased compared with control. Our findings support the idea that PACAP and its action on microglia at the level of the spinal cord elicit cardioprotective effects during seizure. However, intrathecal PACAP did not show additive effects, suggesting that the agonist effect was at maximum. The protective effect of microglia may occur by adoption of an M2 phenotype and expression of factors such as TGF-β and IL-10 that promote neuronal quiescence. In summary, therapeutic interventions targeting PACAP and microglia could be a promising strategy for preventing SUDEP.


Dehydroascorbate reductase affects leaf growth, development, and function.
Ascorbic acid (Asc) is a major antioxidant in plants that detoxifies reactive oxygen species (ROS) and maintains photosynthetic function. Expression of dehydroascorbate reductase (DHAR), responsible for regenerating Asc from an oxidized state, regulates the cellular Asc redox state, which in turn affects cell responsiveness and tolerance to environmental ROS. Because of its role in Asc recycling, we examined whether DHAR is important for plant growth. Suppression of DHAR expression resulted in a preferential loss of chlorophyll a, a lower steady state of Rubisco as measured by the amount of the large subunit of Rubisco (RbcL), and a lower rate of CO(2) assimilation. As a consequence, a slower rate of leaf expansion and reduced foliar dry weight were observed. In addition, an accelerated rate of loss of chlorophyll, RbcL, light-harvesting complex II, and photosynthetic functioning was observed in mature leaves, resulting in premature leaf aging. Reduced growth rate as measured by plant height and leaf number was consistent with the DHAR-mediated reduction of photosynthetic function. Increasing DHAR expression maintained higher levels of chlorophyll, RbcL, light-harvesting complex II, and photosynthetic functioning, resulting in delayed leaf aging. The effect of DHAR expression on leaf aging inversely correlated with the level of lipid peroxidation, indicating that DHAR functions to protect against ROS-mediated damage. These observations support the conclusion that through its Asc recycling function, DHAR affects the level of foliar ROS and photosynthetic activity during leaf development and as a consequence, influences the rate of plant growth and leaf aging.


Supraependymal cells of hypothalamic third ventricle: identification as resident phagocytes of the brain.
Cells lying on the ventricular surface of the hypothalamic ependyma of the tegu lizard exhibit the pseudopodial and flaplike processes characteristic of macrophages found elsewhere. Since they ingest latex beads, they may be considered a resident phagocytic system of the brain. The importance of ependyma and ventricular phagocytes as a first line of defense against viral invasion of the brain, as well as their role in the pathogenesis of certain virus-related diseases, is suggested by a number of experimental and clinical observations.


Experimental infection of subperiodic Brugia malayi in laboratory rats with emphasis on evaluation by four techniques.
Infective larvae of subperiodic B. malayi from South Kalimantan (Borneo), Indonesia collected from laboratory-raised Ae. togoi mosquitoes after feeding on infected mongolian gerbils (Meriones unguiculatus) were inoculated subcutaneously into the groin areas of 15 SD and 36 LE rats. Blood was examined weekly by membrane filtration and thick smears starting 10 weeks post-infection. Microfilariae were found in 3 SD and 4 LE rats, the mf infection rate of 20% and 11% respectively. The prepatent period was significantly shorter in the SD rats (99-112 days) than those in the LE rats (110-153 days). The patent period was longer in the LE rats (208-703 days) than in the SD rats (236-543 days), and the mf density was similar (17.5 mf/20 c.mm blood against 16 mf/20 c.mm blood). At necropsy, 6 (3 female and 3 male) adult worms were recovered from 3 of 6 SD rats and 12 (9 female and 3 male) adult worms from 4 of 20 LE rats; all worms were found in the testes. The results of xenodiagnostic, histochemical staining and measuring spicules and protuberances, demonstrated clearly the difference between both species of Brugia. All dissected Ar. subalbatus mosquitoes exposed to B. pahangi became infected (100%), but none of those to subperiodic B. malayi were infected (0%). The mf of both species of Brugia in thick films stained with naphthol-AS-TR-phosphate showed that the excretory and anal pores of subperiodic B. malayi mf exhibited acid phosphatase activity and only a little activity was seen in other parts; while B. pahangi mf showed heavy diffuse acid phosphatase activity along the entire length of the body.(ABSTRACT TRUNCATED AT 250 WORDS)


The mechanism of tubocurarine action on mechanoreceptor channels in the protozoan Stentor coeruleus.
(+)-Tubocurarine (TC) decreases the probability that the protozoan, Stentor coeruleus Ehrenberg, will contract in response to mechanical stimulation, because it selectively depresses mechanoreceptor currents. Resting membrane properties and action potentials are not significantly altered by the drug. Stentor incubated in media containing radioactively labelled TC (TC*) retain TC* after extensive washing despite a rather high apparent KD (19.7 mumol l-1). The incubation curve for TC* binding exhibits an initial exponential rise followed by a linear increase. Wash-out of bound TC* and elimination of the exponential component of the incubation curve is observed if the TC* incubation is followed by a 5-s exposure to 8% urea; therefore, the exponential component represents a reversible binding process. TC* binding in the exponential component is highly correlated (r less than -0.96) with the depression in receptor current and response probability when incubation time, drug concentration and drug (gallamine, TC, decamethonium and succinylcholine) are varied. These correlations suggest that the exponential binding is to functional mechanoreceptors. Mechanoreceptor currents are decreased by hyperpolarization and increased by depolarization, indicating that the mechanoreceptor channel is voltage-dependent. At hyperpolarized potentials the channels are in a form (the U form) which cannot be opened by mechanical stimulation; at depolarized potentials they are in a form (the R form) which can be opened. TC appears to bind to the U form with higher affinity than to the R form, since depolarization reduces the amount of bound TC* and relieves the depression of mechanoreceptor current produced by TC.


Combiner and HyperCombiner networks: Rules to combine multimodality MR images for prostate cancer localisation.
One of the distinct characteristics of radiologists reading multiparametric prostate MR scans, using reporting systems like PI-RADS v2.1, is to score individual types of MR modalities, including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced, and then combine these image-modality-specific scores using standardised decision rules to predict the likelihood of clinically significant cancer. This work aims to demonstrate that it is feasible for low-dimensional parametric models to model such decision rules in the proposed Combiner networks, without compromising the accuracy of predicting radiologic labels. First, we demonstrate that either a linear mixture model or a nonlinear stacking model is sufficient to model PI-RADS decision rules for localising prostate cancer. Second, parameters of these combining models are proposed as hyperparameters, weighing independent representations of individual image modalities in the Combiner network training, as opposed to end-to-end modality ensemble. A HyperCombiner network is developed to train a single image segmentation network that can be conditioned on these hyperparameters during inference for much-improved efficiency. Experimental results based on 751 cases from 651 patients compare the proposed rule-modelling approaches with other commonly-adopted end-to-end networks, in this downstream application of automating radiologist labelling on multiparametric MR. By acquiring and interpreting the modality combining rules, specifically the linear-weights or odds ratios associated with individual image modalities, three clinical applications are quantitatively presented and contextualised in the prostate cancer segmentation application, including modality availability assessment, importance quantification and rule discovery.


Vestibular Function in Adults With Epilepsy of Unknown Etiology.
This study aimed to evaluate vestibular function in adults with chronic epilepsy of unknown etiology in the inter-ictal period. Epilepsy is a chronic medical disorder. Life-long therapy may be required in one-third of patients. Epilepsy is associated with comorbid somatic conditions which impairs patients' quality of life. This cross-sectional study included 28 with generalized tonic clonic (GTC) convulsions and 14 and 3 with temporal (TLE) and frontal lobe (FLE) epilepsies with secondary generalization (all were on regular carbamazepine therapy) and 40 healthy control subjects. The patients' mean age was 34.97 ± 7.35 years and the duration of illness was 18.75 ± 7.99 years. All underwent videonystagmography (VNG). Compared with controls, patients had frequent vestibular symptoms including dizziness (62.22%) (p = 0.0001) and sense of imbalance (44.44%) (p = 0.0001). Eleven patients (24.44%) had central vestibular dysfunction (p = 0.0001); 9 (20%) had mixed vestibular dysfunction and one (2.22%) had peripheral vestibular dysfunction (p = 0.0001). Abnormalities were observed in saccadic (44.4%) and pursuit (42.2%) eye movements, optokinetic nystagmus (42.2%) and positioning/positional (11.11%) and caloric (13.33%) testing. TLE and FLE were associated with more VNG abnormalities than GTC. No significant differences were observed in the demographic and clinical characteristics between patients with and without VNG abnormalities. Vestibular manifestations are frequent in patients with epilepsy. This may be a result of the permanent damaging effect of chronic epilepsy on the vestibular cortical areas and/or a toxic effect from prolonged carbamazepine therapy on the peripheral and central vestibular systems.


Strategies for the structural analysis of multi-protein complexes: lessons from the 3D-Repertoire project.
Structural studies of multi-protein complexes, whether by X-ray diffraction, scattering, NMR spectroscopy or electron microscopy, require stringent quality control of the component samples. The inability to produce 'keystone' subunits in a soluble and correctly folded form is a serious impediment to the reconstitution of the complexes. Co-expression of the components offers a valuable alternative to the expression of single proteins as a route to obtain sufficient amounts of the sample of interest. Even in cases where milligram-scale quantities of purified complex of interest become available, there is still no guarantee that good quality crystals can be obtained. At this step, protein engineering of one or more components of the complex is frequently required to improve solubility, yield or the ability to crystallize the sample. Subsequent characterization of these constructs may be performed by solution techniques such as Small Angle X-ray Scattering and Nuclear Magnetic Resonance to identify 'well behaved' complexes. Herein, we recount our experiences gained at protein production and complex assembly during the European 3D Repertoire project (3DR). The goal of this consortium was to obtain structural information on multi-protein complexes from yeast by combining crystallography, electron microscopy, NMR and in silico modeling methods. We present here representative set case studies of complexes that were produced and analyzed within the 3DR project. Our experience provides useful insight into strategies that are more generally applicable for structural analysis of protein complexes.


Synthesis of deoxyribomononucleotides in Mollicutes: dependence on deoxyribose-1-phosphate and PPi.
Cell extracts of Acholeplasma laidlawii B-PG9, Acholeplasma morum S2, Mycoplasma capricolum 14, and Mycoplasma gallisepticum S6 were examined for 37 cytoplasmic enzyme activities involved in the salvage and biosynthesis of purines. All of these organisms had adenine phosphoribosyltransferase activity (EC 18.104.22.168) and hypoxanthine phosphoribosyltransferase activity (EC 184.108.40.206). All of these organisms had purine-nucleoside phosphorylase activity (EC 22.214.171.124) in the synthetic direction using ribose-1-phosphate (R-1-P) or deoxyribose-1-phosphate (dR-1-P); this activity generated ribonucleosides or deoxyribonucleosides, respectively. The pyrimidine nucleobase uracil could also be ribosylated by using either R-1-P or dR-1-P as a donor. The synthesis of deoxyribonucleosides from nucleobases and dR-1-P has been reported from only one other procaryote, Escherichia coli (L. A. Mason and J. O. Lampen, J. Biol. Chem. 193:539-547, 1951). The reverse of this phosphorylase reaction is more widely known, and we found such activity in all mollicutes studied. Some Acholeplasma species but not the Mycoplasma species can phosphorylate deoxyribonucleosides to deoxyribomononucleotides by a PPi-dependent deoxyribonucleoside kinase activity, which was first reported in this group for the ribose analogs (V. V. Tryon and J. D. Pollack, Int. J. Syst. Bacteriol. 35:497-501, 1985). This is the first report of PPi-dependent purine deoxyribonucleoside kinase activity. An ATP-dependent purine deoxyribonucleoside kinase activity is known only in salmon milt extracts (H. L. A. Tarr, Can. J. Biochem. 42:1535-1545, 1964). Deoxyribomononucleotidase activity was also found in cytoplasmic extracts of these mollicutes. This is the first report of deoxyribomononucleotidase activity.


Three dimensional optical coherence tomography imaging: advantages and advances.
Three dimensional (3D) ophthalmic imaging using optical coherence tomography (OCT) has revolutionized assessment of the eye, the retina in particular. Recent technological improvements have made the acquisition of 3D-OCT datasets feasible. However, while volumetric data can improve disease diagnosis and follow-up, novel image analysis techniques are now necessary in order to process the dense 3D-OCT dataset. Fundamental software improvements include methods for correcting subject eye motion, segmenting structures or volumes of interest, extracting relevant data post hoc and signal averaging to improve delineation of retinal layers. In addition, innovative methods for image display, such as C-mode sectioning, provide a unique viewing perspective and may improve interpretation of OCT images of pathologic structures. While all of these methods are being developed, most remain in an immature state. This review describes the current status of 3D-OCT scanning and interpretation, and discusses the need for standardization of clinical protocols as well as the potential benefits of 3D-OCT scanning that could come when software methods for fully exploiting these rich datasets are available clinically. The implications of new image analysis approaches include improved reproducibility of measurements garnered from 3D-OCT, which may then help improve disease discrimination and progression detection. In addition, 3D-OCT offers the potential for preoperative surgical planning and intraoperative surgical guidance.


Midwifery students training in oral care of pregnant patients: an interventional study.
Midwives may play an important role in oral health promotion of pregnant women, whom they are in close contact with. Our aim was to evaluate an educational intervention on the oral health attitude and practices among the junior midwifery students of Tehran University of Medical Sciences in 2010. The junior midwifery students were divided into intervention (n=29) and control (n=33) groups. The intervention group was first educated about general oral health, oral hygiene practices during pregnancy, and tooth brushing and flossing on models. Subsequently, the students performed role playing to ensure they understood the aforementioned lessons correctly. Before and three months after the training course the students filled out a validated self-administered questionnaire and a simplified plaque index was recorded. Statistical analysis was done by Mann-Whitney test and linear regression models. Before the intervention, the mean scores of attitude in general oral health for the intervention and control groups were 5.8 and 5.4, respectively, which improved to 8.9 and 5.4 after the intervention (P<0.001). The mean score of oral health attitude in pregnancy was 20.4 in the intervention group and increased to 30.9 (P<0.001). The intervention group demonstrated much better oral health practices in pregnancy and lower plaque index score after the intervention. The promising finding about attitude and practice improvement in midwifery students after participating in a short course on oral health promotion in pregnancy shows the necessity to enrich their training program by including this subject.


Laser-Fabricated Fluorescent, Ligand-Free Silicon Nanoparticles: Scale-up, Biosafety, and 3D Live Imaging of Zebrafish under Development.
This work rationalizes the scalable synthesis of ultrasmall, ligand-free silicon nanomaterials via liquid-phase pulsed laser ablation process using picosecond pulses at ultraviolet wavelengths. Results showed that the irradiation time drives hydrodynamic NP size. Isolated, monodisperse Si-NPs are obtained at high yield (72%) using post-treatment process. The obtained Si-NPs have an average size of ∼10 nm (not aggregated) and display photoemission in the green spectral range. We directly characterized the ligand-free Si-NPs in a vertebrate animal (zebrafish) and assessed their toxicity during the development. In vivo assay revealed that Si-NPs are found inside in all the early life stages of embryos and larvae growth, showing that the biosafety of Si-NPs and malformation types are independent of the Si-NP dose. Si-NPs were directly imaged inside developing embryos by spinning disk-imaging technique with optical sectioning capability. We showed that Si-NPs can passively enter inside embryos by the pore canals of chorion, can diffuse in the circulatory system, i.e., blood vessel, and accumulate inside larvae midgut and yolk sac, and in the eye lens, indicating the crossing of the blood barrier.


The effect of demineralized bone matrix on the healing of intramembranous bone grafts in rabbit skull defects.
A clinical dilemma exists regarding the type of bone that should be used to replace diseased or traumatized osseous tissue. Oral, plastic, and orthopedic surgeons normally implant viable mineralized endochondral (EC) autografts or demineralized EC allografts. A few clinicians have recognized the disadvantages of using EC bone in craniofacial surgery and advocated the replacement of intramembranous (IM) bone with healthy IM bone. However, controversy and uncertainty surround our understanding of these matrices to induce bone formation. Recent studies have advocated the use of other materials with osteoinductive properties, such as demineralized bone matrix (DBM). The proposed delivery system used in this study included IM bone grafts, DBM, and fixation of the IM bone graft. The purpose of this work was to gain further insights into the mechanism of healing of IM bone, in both the presence and the absence of DBM, and to compare the healing of IM bone grafts with that of DBM alone. Critical-sized (10 x 5 mm), full-thickness bony defects in rabbit parietal bone, devoid of periosteum, were filled with IM bone graft (mandible) alone, demineralized cortical bone matrix (DBM) alone, or combined DBM-IM bone graft, or were left unfilled. Histologic changes were examined 14 days later. The IM bone graft healed through IM ossification with no intermediate cartilage stage. DBM and composite DBM-IM healed through an EC ossification with an intermediate cartilage stage. It is hypothesized that the role of the IM graft is to induce neovascularization into the defect site, and that the undifferentiated mesenchymal cells in the perivascular region of the new blood vessels are induced by the bone morphogenetic protein(s) in the DBM into bone-forming cells.


Expanded AIDS case definition increases Pennsylvania's reported AIDS cases.
At the beginning of 1993, the Centers for Disease Control and Prevention adopted an expanded case definition of AIDS and a revision of the classification system for HIV infection for persons ages 13 years or older. This article explains the changes and their effects, defines the new system categories, and offers resources for physicians treating HIV-infected patients.


Interaction between RAX and PKR modulates the effect of ethanol on protein synthesis and survival of neurons.
Ethanol exposure inhibits protein synthesis and causes cell death in the developing central nervous system. The double-stranded RNA (dsRNA)-activated protein kinase (PKR), a serine/threonine protein kinase, plays an important role in translational regulation and cell survival. PKR has been well known for its anti-viral response. Upon activation by viral infection or dsRNA, PKR phosphorylates its substrate, the alpha-subunit of eukaryotic translation initiation factor-2 (eIF2alpha) leading to inhibition of translation initiation. It has recently been shown that, in the absence of a virus or dsRNA, PKR can be activated by direct interactions with its protein activators, PACT, or its mouse homologue, RAX. We have demonstrated that exposure to ethanol increased the phosphorylation of PKR and eIF2alpha in the developing cerebellum. The effect of ethanol on PKR/eIF2alpha phosphorylation positively correlated to the expression of PACT/RAX in cultured neuronal cells. Using PKR inhibitors and PKR null mouse fibroblasts, we verified that ethanol-induced eIF2alpha phosphorylation was mediated by PKR. Overexpression of a wild-type RAX dramatically enhanced sensitivity to ethanol-induced PKR/eIF2alpha phosphorylation, as well as translational inhibition and cell death. In contrast, overexpression of a mutant (S18A) RAX inhibited ethanol-mediated PKR/eIF2alpha activation. Ethanol promoted PKR and RAX association in cells expressing wild-type RAX but not in cells expressing S18A RAX. S18A RAX functioned as a dominant negative protein and blocked ethanol-induced inhibition of protein synthesis and cell death. Our results suggest that the interactions between PKR and PACT/RAX modulate the effect of ethanol on protein synthesis and cell survival in the central nervous system.


Protective effect of gossypitrin on carbon tetrachloride-induced in vivo hepatotoxicity.
Carbon tetrachloride (CCl4) is a known environmental biohazard, which induces lipid peroxidation (LPO) and oxidative damage in rat liver. In this study, the hepatoprotective effect of Gossypitrin, a flavonoid extracted from Hibiscus elatus S.W, was investigated against the CCl4-induced in vivo hepatotoxicity. The levels of malondialdehyde (MDA) were assayed as an index of LPO and the levels of catalase (CAT) activity as a biomarker of oxidative damage. Leakage of aspartate aminotransferase (ALT) and lactate dehydrogenase (LDH), liver weight/body weight ratio as well as morphological parameters were used as signs of hepatotoxicity. CCl4 (1 ml/kg), intraperitoneally injected into rats, caused increased MDA production and CAT activity, and also a significant ALT and LDH leakage as compared to levels of these constituents in the control group. Changes in morphology, including steatosis, cells forming balloon cells and necrosis were evaluated in the hepatotoxin-induced damage. Treatment of rats with Gossypitrin (3.98, 5.97 and 8.95 mg/kg) 2 h before and 2 h after CCl4 injection, protected hepatocytes against cell injury induced by CCl4 and its efficacy as an antioxidant was similar to vitamin E (used as a reference antioxidant). These results are consistent with the conclusion that the toxicity of CCl4 is due to LPO and the generation of reactive oxygen species (ROS), and that Gossypitrin's protective effects relate to its direct radical scavenging ability and other antioxidative processes induced by its structure.


Rifampicin induces MDR1 expression in Candida albicans.
Overexpression of efflux pumps such as MDR1 has been identified as an important mechanism contributing to fluconazole resistance in Candida albicans. This phenomenon is frequently observed in fluconazole-resistant strains isolated from AIDS patients treated with various pharmaceuticals. Therefore, we hypothesized that some of these compounds might influence the expression of genes responsible for fluconazole resistance. We examined a variety of clinically relevant compounds for their in vitro effects on MDR1 expression with a C. albicans reporter strain containing a transcriptional fusion of the MDR1 promoter (MDR1P) with the gfp gene. Activation of the MDR1 promoter and subsequent green fluorescent protein production was determined by fluorescence microscopy and flow cytometry. Additionally, MDR1 transcription was confirmed and quantified by RT-PCR analysis, followed by Mdr1p detection by western blot. Finally, the effect of a selected agent on resistance to fluconazole was tested by chequerboard titration of both substances. Of 15 compounds tested, only rifampicin induced a rapid and dose-dependent increase in MDR1 expression (up to 122-fold induction), whereas structurally related molecules such as rifabutin and rifamycin were not active. Induction of MDR1 expression upon rifampicin exposure was also observed in 10 blood culture isolates. In contrast, rifampicin exposure did not markedly affect the expression of the transporters CDR1 and CDR2. Increased MDR1 expression was accompanied by elevated MICs for fluconazole after exposure of C. albicans to rifampicin, whereas Mdr1p expression was only moderately induced. Out of the compounds examined, only rifampicin specifically induced MDR1 expression in all C. albicans strains tested. Rifampicin may play a general role in signal transduction or another means of modulation of gene expression in C. albicans.


Cumulative exposure to childhood adversity, and treated attention deficit/hyperactivity disorder: a cohort study of 543 650 adolescents and young adults in Sweden.
Though childhood adversity (CA) has been associated with the risk of attention deficit/hyperactivity disorder (ADHD), little is known about the effect of cumulative CAs and whether there are clusters of CAs that are more closely related with ADHD. We used a Swedish cohort of 543 650 individuals born 1987-1991. Register-based CAs included familial death, substantial parental substance abuse and psychiatric disorder, substantial parental criminality, parental separation, household public assistance recipiency, and residential instability. Individuals were followed from year 2006 when they were 15-19 years of age, for treated ADHD, defined as a registered ICD diagnosis and/or prescription of medications to treat ADHD. Logistic regression analysis was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Latent Class Analyses (LCA) were used to identify clusters based on the different CAs. All CAs increased the odds of ADHD in late adolescence and early adulthood; ORs ranged from 1.6 (95% CI 1.5-1.8) for familial death to 2.7 (95% CI 2.6-2.9) for household public assistance. We found a dose-response relationship between cumulative CA and ADHD; individuals with 4+ CAs had a markedly increased risk for ADHD (OR 5.5, 95% CI 5.0-6.0). LCA analyses revealed six distinct classes of CA associated with ADHD, of which 'exposure to most adversities' entailed highest risk. CA is a strong risk factor for ADHD, particularly when accumulated. Early and efficient detection of CA is of importance for interventions targeted to improve long-term mental health outcomes among disadvantaged children.


THE NEWER ANTIBIOTICS IN DERMATOLOGY.
From the experimental and clinical observations published to date it appears that three new antibiotics, polymyxin, chloramphenicol and aureomycin, will prove to be highly efficacious against many of the infectious dermatoses and venereal diseases.


DNA polymerase delta Exo domain stabilizes mononucleotide microsatellites in human cells.
In prokaryotes and yeasts, DNA polymerase proofreading (PPR) and DNA mismatch repair (MMR) cooperatively counteracts replication errors leading to repeat sequence destabilization (i.e. insertions/deletions of repeat units). However, PPR has not thus far been regarded as a mechanism stabilizing repeat sequences in higher eukaryotic cells. In a human cancer cell line, DLD-1, which carries mutations in both MSH6 and the Exo domain of POLD1, we previously observed that mononucleotide microsatellites were markedly destabilized whereas being stable in the simple MMR-defective backgrounds. In this study, we introduced the Exo domain mutation found in DLD-1 cells into MSH2-null HeLa cell clones, using CRISPR/Cas9 system. In the established Exo-/MMR-mutated HeLa clones, mononucleotide repeat sequences were remarkably destabilized as in DLD-1 cells. In contrast, dinucleotide microsatellites were readily destabilized in the parental MMR-deficient backgrounds, and the instability was not notably increased in the genome-edited HeLa clones. Here, we show an involvement of the Exo domain functions of DNA polymerase delta in mononucleotide repeat stabilization in human cells, which also suggests a possible role division between DNA polymerase and MMR in repeat maintenance in the human genome.


Psychotropic drugs: implications for dental practice.
Appropriate preoperative assessment of dental patients should always include analysis of their medications. Psychiatric illnesses including panic/anxiety disorder, depression, psychoses, and manic disorders are prevalent within our society. An impressive number of drug formulations are prescribed for these disorders, and they introduce concern regarding side effects and possible drug interactions with medications the dentist may deem necessary for dental care. This article will address essential pharmacology of these psychotropic medications.


Quantifying the nonclassicality of operations.
Deep insight can be gained into the nature of nonclassical correlations by studying the quantum operations that create them. Motivated by this we propose a measure of nonclassicality of a quantum operation utilizing the relative entropy to quantify its commutativity with the completely dephasing operation. We show that our measure of nonclassicality is a sum of two independent contributions, the generating power--its ability to produce nonclassical states out of classical ones, and the distinguishing power--its usefulness to a classical observer for distinguishing between classical and nonclassical states. Each of these effects can be exploited individually in quantum protocols. We further show that our measure leads to an interpretation of quantum discord as the difference in superdense coding capacities between a quantum state and the best classical state when both are produced at a source that makes a classical error during transmission.


Electrophosphorescent heterobimetallic oligometallaynes and their applications in solution-processed organic light-emitting devices.
By combining the iridium(III) ppy-type complex (Hppy=2-phenylpyridine) with a square-planar platinum(II) unit, some novel phosphorescent oligometallaynes bearing dual metal centers (viz. Ir(III) and Pt(II)) were developed by combining trans-[Pt(PBu(3))(2)Cl(2)] with metalloligands of iridium possessing bifunctional pendant acetylene groups. Photophysical and computational studies indicated that the phosphorescent excited states arising from these oligometallaynes can be ascribed to the triplet emissive Ir(III) ppy-type chromophore, owing to the obvious trait (such as the longer phosphorescent lifetime at 77 K) also conferred by the Pt(II) center. So, the two different metal centers show a synergistic effect in governing the photophysical behavior of these heterometallic oligometallaynes. The inherent nature of these amorphous materials renders the fabrication of simple solution-processed doped phosphorescent organic light-emitting diodes (PHOLEDs) feasible by effectively blocking the close-packing of the host molecules. Saliently, such a synergistic effect is also important in affording decent device performance for the solution-processed PHOLEDs. A maximum brightness of 3,356 cd m(-2) (or 2,708 cd m(-2)), external quantum efficiency of 0.50% (or 0.67%), luminance efficiency of 1.59 cd A(-1) (or 1.55 cd A(-1)), and power efficiency of 0.60 Lm W(-1) (or 0.55 Lm W(-1)) for the yellow (or orange) phosphorescent PHOLEDs can be obtained. These results show the great potential of these bimetallic emitters for organic light-emitting diodes.


Utilization of hyperbaric oxygen therapy and induced hypothermia after hydrogen sulfide exposure.
Hydrogen sulfide is a toxic gas produced as a by-product of organic waste and many industrial processes. Hydrogen sulfide exposure symptoms may vary from mild (dizziness, headaches, nausea) to severe lactic acidosis via its inhibition of oxidative phosphorylation, leading to cardiac arrhythmias and death. Treatment is generally supportive. We report the case of a patient presenting with cardiac arrest secondary to hydrogen sulfide exposure treated with both hyperbaric oxygen therapy and therapeutic hypothermia to achieve full neurologic recovery.


Antigenic relationships between type a influenza viruses of human, porcine, equine, and avian origin.
This paper summarizes the available information on the relationship of two envelope antigens (haemagglutinin and neuraminidase) of influenzaviruses isolated from different hosts. The relationship of the haemagglutinin antigens was based on the results of haemagglutination inhibition tests with postinfection sera and that of the neuraminidase antigens on the results of neuraminidase inhibition and gel precipitation tests with hyperimmune and monospecific sera. On the basis of the antigenic specificity of the haemagglutinin, the influenzaviruses of human origin are divided into several subtypes (H0, H1, H2); viruses of equine origin could be divided into two subtypes (Heq1, Heq2). Porcine influenza strains are regarded as belonging to a single subtype, all of them being related to the prototype swine influenzavirus A (swine/Iowa/15/30). Within the avian influenzaviruses, 6 antigenic subtypes were described in earlier studies. Antigenic relationships between the haemagglutinin of strains from different hosts were infrequent but were demonstrated and confirmed between human A/Hong Kong/68 and equine viruses and between A/Hong Kong/68 and swine/Taiwan/69. The swine/Taiwan/69 virus also shared the related neuraminidase with A/Hong Kong/68 virus, and represents the only isolation from nonhuman sources of an influenzavirus identical with a human pandemic strain. The studies on the antigenic specificity of the neuraminidases demonstrated 8 antigenic varieties of neuraminidase among avian influenzaviruses and also that the neuraminidase grouping did not correspond with the antigenic grouping with regard to haemagglutinin. The relationships between human and nonhuman influenzaviruses are emphasized because of their significance to studies on the origin of influenza pandemics in man.


Diabetes mortality in Panama and related biological and socioeconomic risk factors.
To estimate mortality from diabetes mellitus (DM) for the period 2001-2011 in the Republic of Panama, by province/indigenous territory, and determine its relationship with biological and socioeconomic risk factors. Cases for the years 2001-2011 with DM listed as the principal cause of death were selected from Panama's National Mortality Registry. Crude and adjusted mortality rates were generated by sex, age, and geographic area. Linear regression analyses were performed to determine the relationship between DM mortality and biological and socioeconomic risk factors. A composite health index (CHI) calculated from biological and socioeconomic risk factors was estimated for each province/indigenous territory in Panama. DM mortality rates did not increase for men or women during 2001-2011. Of the biological risk factors, being overweight had the strongest association with DM mortality. Of the socioeconomic risk factors, earning less than US$ 100 per month had the strongest association with DM mortality. The highest socioeconomic CHI scores were found in a province that is predominantly rural and in areas with indigenous populations. The highest biological CHI scores were found in urban-rural provinces and those with the highest percentage of elderly people. Regional disparities in the association between DM mortality and DM risk factors reaffirm the heterogeneous composition of the Panamanian population and the uneven distribution of biological and social determinant risk factors in the country and point to the need to vary management strategies by geographic area for this important cause of disability and death in Panama.


Prenatal BRCA1 epimutations contribute significantly to triple-negative breast cancer development.
Normal cell BRCA1 epimutations have been associated with increased risk of triple-negative breast cancer (TNBC). However, the fraction of TNBCs that may have BRCA1 epimutations as their underlying cause is unknown. Neither are the time of occurrence and the potential inheritance patterns of BRCA1 epimutations established. To address these questions, we analyzed BRCA1 methylation status in breast cancer tissue and matched white blood cells (WBC) from 408 patients with 411 primary breast cancers, including 66 TNBCs, applying a highly sensitive sequencing assay, allowing allele-resolved methylation assessment. Furthermore, to assess the time of origin and the characteristics of normal cell BRCA1 methylation, we analyzed umbilical cord blood of 1260 newborn girls and 200 newborn boys. Finally, we assessed BRCA1 methylation status among 575 mothers and 531 fathers of girls with (n = 102) and without (n = 473) BRCA1 methylation. We found concordant tumor and mosaic WBC BRCA1 epimutations in 10 out of 66 patients with TNBC and in four out of six patients with estrogen receptor (ER)-low expression (< 10%) tumors (combined: 14 out of 72; 19.4%; 95% CI 11.1-30.5). In contrast, we found concordant WBC and tumor methylation in only three out of 220 patients with 221 ER ≥ 10% tumors and zero out of 114 patients with 116 HER2-positive tumors. Intraindividually, BRCA1 epimutations affected the same allele in normal and tumor cells. Assessing BRCA1 methylation in umbilical WBCs from girls, we found mosaic, predominantly monoallelic BRCA1 epimutations, with qualitative features similar to those in adults, in 113/1260 (9.0%) of individuals, but no correlation to BRCA1 methylation status either in mothers or fathers. A significantly lower fraction of newborn boys carried BRCA1 methylation (9/200; 4.5%) as compared to girls (p = 0.038). Similarly, WBC BRCA1 methylation was found less common among fathers (16/531; 3.0%), as compared to mothers (46/575; 8.0%; p = 0.0003). Our findings suggest prenatal BRCA1 epimutations might be the underlying cause of around 20% of TNBC and low-ER expression breast cancers. Such constitutional mosaic BRCA1 methylation likely arise through gender-related mechanisms in utero, independent of Mendelian inheritance.


Convalescence care for seniors of lower Manhattan: an interdisciplinary outreach, rehabilitation, and education model.
The purpose of this study was to test the efficacy of an interdisciplinary geriatric outreach, rehabilitation, and education program for seniors. Community-dwelling Chinese seniors in lower Manhattan were recruited through outreach activities (17 educational workshops, three community health fairs, media interviews) and community physician referrals to offer rehabilitation services. The instrument administered at entry and exit included questions about pain intensity, quality of life, activities of daily living (ADLs), and an assessment of a variety of intrinsic and extrinsic barriers to life participation. The sample included 70 seniors (53 women) with a mean age of 70.5 +/- 7.48 years (range 60-93 years old) of whom 86% were Cantonese-speaking Chinese. The barriers-to-life participation assessment revealed cultural, communication, transportation, and physical environmental barriers as well as insufficient financial resources. Thirty-four patients who completed the program showed a significant improvement in quality of life. Patients' reports reflected a high degree of satisfaction with the program. Interdisciplinary team-oriented patient care, including a physiatrist, social worker, and rehabilitation staff, may result in good outcomes and high patient satisfaction in ambulatory community seniors.


No Difference Between Low- and Regular-dose Aspirin for Venous Thromboembolism Prophylaxis After THA.
Aspirin is established as an effective prophylaxis for venous thromboembolism (VTE) after THA; however, there is no consensus as to whether low- or regular-dose aspirin is more effective at preventing VTE. (1) Is there a difference in the incidence of symptomatic VTE within 90 days of elective THA using low-dose aspirin compared with regular-dose aspirin? (2) Is there a difference in the risk of significant bleeding (gastrointestinal and wound bleeding) and mortality between low- and standard-dose aspirin within 90 days after surgery? We retrospectively evaluated 7488 patients in our database who underwent THA between September 2012 and December 2016. A total of 3936 (53%) patients received aspirin alone for VTE prophylaxis after THA. During the study period, aspirin was prescribed as a monotherapy for VTE prophylaxis after surgery in low-risk patients (no history of VTE, recent orthopaedic surgery, hypercoagulable state, history of cardiac arrhythmia requiring anticoagulation, or receiving anticoagulation for any other medical conditions before surgery). Patients were excluded if aspirin use was contraindicated because of peptic ulcer disease, intolerance, or other reasons. Patients received aspirin twice daily (BID) for 4 to 6 weeks after surgery and were grouped into two cohorts: a low-dose (81 mg BID) aspirin group (n = 1033) and a standard-dose (325 mg BID) aspirin group (n = 2903). The primary endpoint was symptomatic VTE (deep vein thrombosis [DVT] and pulmonary embolism [PE]). Secondary endpoints included significant bleeding (gastrointestinal [GI] and wound) and mortality. Exploratory univariate analyses were used to compare confounders between the study groups. Multivariate regression was used to control for confounding variables (including age, sex, body mass index, comorbidities, and surgeon) as we compared the study groups with respect to the proportion of patients who developed symptomatic VTE, bleeding (GI or wound), and mortality within 90 days of surgery. The 90-day incidence of symptomatic VTE was 1.0% in the 325-mg group and 0.6% in the 81-mg group (p = 0.35). Symptomatic DVT incidence was 0.8% in the 325-mg group and 0.5% in the 81-mg group (p = 0.49), and the incidence of symptomatic PE was 0.3% in the 325-mg group and 0.2% in the 81-mg group (p = 0.45). Furthermore, bleeding was observed in 0.8% of the 325-mg group and 0.5% of the 81-mg group (p = 0.75), and 90-day mortality was not different (0.1%) between the groups (p = 0.75). After accounting for confounders, regression analyses showed no difference between aspirin doses and the 90-day incidence of symptomatic VTE (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.29-2.85; p = 0.85) or symptomatic DVT (OR, 0.96; 95% CI, 0.26-3.59; p = 0.95). We found no difference in the incidence of symptomatic VTE after THA with low-dose compared with standard-dose aspirin. In the absence of compelling evidence to the contrary, low-dose aspirin appears to be a reasonable option for VTE prophylaxis in otherwise healthy patients undergoing elective THA. Level III, therapeutic study.


Coagulation disorders and blood product use in patients undergoing thoracoabdominal aortic aneurysm repair.
Repair of thoracoabdominal aortic aneurysms (TAAA) is associated with major blood loss, often exceeding the patient's intravascular volume, and complex intraoperative and postoperative coagulopathies necessitating large-volume transfusion of blood products. Abnormalities sufficient to cause thrombocytopenia or clinically important prolongation of clotting parameters are rarely present before surgery in elective aneurysms but are more common with ruptured aneurysms. The finding of intraoperative and postoperative deficiencies of clotting factors, along with thrombin generation and activation of the thrombolytic system, is reflective of massive blood losses, visceral ischemia, and massive transfusions. An aggressive strategy of transfusion of blood products is critical to the prevention of clinically significant coagulopathy during surgery. Adjuncts to reduce blood losses and blood product use include low-dose aprotinin or epsilon -aminocaproic acid, intraoperative blood salvaging, and acute normovolemic hemodilution. In TAAA repair, an average blood loss of 5000 to 6000 mL and average transfusion of allogeneic blood products of 50 to 60 U are to be anticipated.


Cryptococcal pyelonephritis and disseminated cryptococcosis in a renal transplant recipient.
Symptomatic cryptococcal pyelonephritis, meningitis, and disseminated cryptococcosis are described in a renal cadaver transplant recipient who subsequently died of Klebsiella pneumoniae sepsis. The presence of cryptococcuria and a subsequent positive CSF India ink stain led to the initial diagnosis of disseminated cryptococcosis. Therapy with 0.511 g of amphotericin B and 112.5 g of flucytosine for four weeks did not eradicate Cryptococcus from the kidney and was associated with hepatotoxicity. The importance of urinary examination and culture for C neoformans is emphasized. Cryptococcal pyelonephritis should be considered in the differential diagnosis of allograft rejection in the renal transplant patient.


Geometry-based demosaicking.
Demosaicking is a particular case of interpolation problems where, from a scalar image in which each pixel has either the red, the green or the blue component, we want to interpolate the full-color image. State-of-the-art demosaicking algorithms perform interpolation along edges, but these edges are estimated locally. We propose a level-set-based geometric method to estimate image edges, inspired by the image inpainting literature. This method has a time complexity of O(S) , where S is the number of pixels in the image, and compares favorably with the state-of-the-art algorithms both visually and in most relevant image quality measures.


Direct observations of conformational distributions of intrinsically disordered p53 peptides using UV Raman and explicit solvent simulations.
We report the first experimental measurements of Ramachandran Ψ-angle distributions for intrinsically disordered peptides: the N-terminal peptide fragment of tumor suppressor p53 and its P27S mutant form. To provide atomically detailed views of the conformational distributions, we performed classical, explicit-solvent molecular dynamics simulations on the microsecond time scale. Upon binding its partner protein, MDM2, wild-type p53 peptide adopts an α-helical conformation. Mutation of Pro27 to serine results in the highest affinity yet observed for MDM2-binding of the p53 peptide. Both UV resonance Raman spectroscopy (UVRR) and simulations reveal that the P27S mutation decreases the extent of PPII helical content and increases the probability for conformations that are similar to the α-helical MDM2-bound conformation. In addition, UVRR measurements were performed on peptides that were isotopically labeled at the Leu26 residue preceding the Pro27 in order to determine the conformational distributions of Leu26 in the wild-type and mutant peptides. The UVRR and simulation results are in quantitative agreement in terms of the change in the population of non-PPII conformations involving Leu26 upon mutation of Pro27 to serine. Finally, our simulations reveal that the MDM2-bound conformation of the peptide is significantly populated in both the wild-type and mutant isolated peptide ensembles in their unbound states, suggesting that MDM2 binding of the p53 peptides may involve conformational selection.


Antiaphrodisiacs in pierid butterflies: a theme with variation!
Male Pieris napi butterflies previously have been shown to synthesize and transfer an antiaphrodisiac, methyl salicylate (MeS), to females at mating. This substance curtails courtship and decreases the likelihood of female remating. Here, we show that similar systems occur in Pieris rapae and Pieris brassicae. In P. rapae, 13C-labeling studies showed that males utilize the amino acids phenylalanine and tryptophan as precursors to MeS and indole, respectively. These volatiles are transferred to females at mating and function as antiaphrodisiacs, as demonstrated by field tests entailing painting MeS, indole, or a mixture on the abdomens of virgin females and assessing their attractiveness to wild males. With P. brassicae, 13C-labeling studies showed that males use phenylalanine as a precursor to synthesize benzyl cyanide, which was demonstrated to function as an antiaphrodisiac by field tests similar to those for P. rapae. This communication system exhibits both similarities and differences among the three species; in P. napi and P. rapae, males are fragrant but transfer a volatile antiaphrodisiac to females that is completely different from the male odor, whereas in P. brassicae the antiaphrodisiac transferred by male to female is identical with male odor.


Cooperative Clustering Digitizes Biochemical Signaling and Enhances its Fidelity.
Many membrane-bound molecules in cells form small clusters. It has been hypothesized that these clusters convert an analog extracellular signal into a digital intracellular signal and that this conversion increases signaling fidelity. However, the mechanism by which clusters digitize a signal and the subsequent effects on fidelity remain poorly understood. Here we demonstrate using a stochastic model of cooperative cluster formation that sufficient cooperation leads to digital signaling. We show that despite reducing the number of output states, which decreases fidelity, digitization also reduces noise in the system, which increases fidelity. The tradeoff between these effects leads to an optimal cluster size that agrees with experimental measurements.


Return to Work and Sport Following High Tibial Osteotomy: A Systematic Review.
The purpose of this study was to examine (1) timelines for return to sport and work following high tibial osteotomy (HTO), and (2) whether patients return to sport and work at levels similar to preoperative levels. A systematic search was conducted across 3 databases (MEDLINE, Embase, and PubMed). Two reviewers independently screened the results for relevant articles. Data regarding patient demographics, indications, surgical technique, return to work and sport, and complication and failure rates were abstracted from eligible studies. Nineteen studies were included, involving 1,189 patients (64% male, 21% female, 15% unspecified) and 1,224 knees. Mean age was 46.2 years (range, 16 to 80 years). Opening-wedge HTO was most commonly used, followed by closing-wedge HTO and hemicallotasis. Mean follow-up was 65.4 months (range, 8 to 253 months). Overall, 87.2% of patients returned to sport postoperatively, and 78.6% returned at an equal or greater level. Among competitive athletes, 54% returned to competition. Overall, 84.5% of patients returned to work postoperatively, and 65.5% returned at an equal or greater level. Approximately 90% of patients who returned to work or sport did so within 1 year. The complication rate was 5.8%, with infection being the most common complication; 7.0% of patients progressed to a total knee arthroplasty at a mean of 6.7 years (range, 0.8 to 15 years) following HTO. The majority of patients undergoing HTO return to sport and work, and most return within 1 year of the operation. Most patients return to sport at a level equal to or greater than the preoperative level. Approximately two-thirds of patients return to an equal or greater level of physical work. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Experimental Validation of Dynamic Response of Small-Scale Metaconcrete Beams at Resonance Vibration.
Structures and their components experience substantially large vibration amplitudes at resonance, which can cause their failure. The scope of this study is the utilization of silicone-coated steel balls in concrete as damping aggregates to suppress the resonance vibration. The heavy steel cores oscillate with a frequency close to the resonance frequency of the structure. Due to the phase difference between the vibrations of the cores and the structure, the cores counteract the vibration of the structure. The core-coating inclusions are randomly distributed in concrete similar to standard aggregates. This mixture is referred to as metaconcrete. The main goal of this work is to validate the ability of the inclusions to suppress mechanical vibration through laboratory experiments. For this purpose, two small-scale metaconcrete beams were cast and tested. In a free vibration test, the metaconcrete beams exhibited a larger damping ratio compared to a similar beam cast from conventional concrete. The vibration amplitudes of the metaconcrete beams at resonance were measured with a frequency sweep test. In comparison with the conventional concrete beam, both metaconcrete beams demonstrated smaller vibration amplitudes. Both experiments verified an improvement in the dynamic response of the metaconcrete beams at resonance vibration.


[The assessment of functional capacity in workers with the thoracic outlet syndrome. A pilot study].
Occupational specialists are well aware of the lack of objective measurements for the diagnosis and the functional evaluation of workers affected by thoracic outlet syndrome (TOS). Subjects affected by TOS refer pain, sensation of fatigue in the arm frequently aggravated by overhead work. A "stick-up" position tends to close the costoclavicular space and tense the neck and shoulder muscles to bring into play the abnormal compression mechanism that may affect the brachial plexus nerves and the subclavian vessels. In a previous study, we demonstrated the reliability of an isokinetic hand grip endurance test. In this pilot study we asked 7 industrial workers affected by TOS to perform a 30-second isokinetic endurance test for hand gripping with a Lido WorkSET dynamometer. Tests were performed in two positions (resting and "stick-up" position) before and after a 3-week intensive rehabilitation program. In addition, the subjects performed daily aerobic exercise with an arm crank ergometer. Objective indexes of posttreatment improvement were found. Subjects were able to generate higher grip forces during the isokinetic hand grip endurance test and to sustain higher mechanical workload with the arm ergometer at the same intensity level for longer duration after completion of the rehabilitation program.


Serum Galectin-3 and Subsequent Risk of Coronary Heart Disease in Subjects With Childhood-Onset Type 1 Diabetes: A Cohort Study.
To study whether serum galectin-3 and other biomarkers of inflammation predict coronary heart disease (CHD) in subjects with long-standing childhood-onset type 1 diabetes. A population-based nationwide cohort of 299 subjects with type 1 diabetes diagnosed in Norway at <15 years of age during 1973-1982 was examined in 2002-2003 at a mean age of 33 years (range 21-44), with mean diabetes duration of 24 years (range 19-30). Subjects were followed through 31 December 2017 for their first CHD event registered by a hospitalization or cause of death using nationwide registries. Stored serum samples were available for 296 subjects and analyzed for interleukin-6 (IL-6), IL-6 receptor, IL-18, hs-CRP, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), galectin-3, and high-sensitivity troponin T. Adjusted hazard ratios (aHRs) for CHD per SD increase in biomarker were estimated using Cox regression. Of 295 subjects, 40 (13.6%) had a documented CHD event during a mean follow-up of 14.4 years (range 0.5-16). IL-6 (aHR 1.32 [95% CI 1.07-1.63]), galectin-3 (aHR 1.44 [95% CI 1.09-1.80]), and TIMP-1 (aHR 1.37 [95% CI 1.04-1.81]) were significant predictors of CHD after adjustment for conventional risk factors. Galectin-3 was significantly associated with future CHD in subjects with type 1 diabetes, and if the results are replicated in larger studies, it may aid in prediction together with conventional risk factors for CHD.


Potential for bleeding with the new beta-lactam antibiotics.
Several new beta-lactam antibiotics impair normal hemostasis. Hypoprothrombinemia has occurred frequently with cephalosporins that possess a methylthiotetrazole substitution (cefamandole, moxalactam, and cefoperazone). The incidence ranges from 4% to 68%, and the risk is greatest in debilitated patients with cancer, intra-abdominal infection, or renal failure. Impaired platelet function caused by perturbation of agonist receptors on the platelet surface has occurred primarily with beta-lactam antibiotics having an alpha-carboxyl substitution (moxalactam, carbenicillin, and ticarcillin). These antibiotics often cause the template bleeding time to be markedly prolonged (greater than 20 minutes). Acylureidopenicillins, which lack the alpha-carboxyl marker, impair platelet function less frequently and only modestly prolong the bleeding time. If serious hemorrhage occurs, hypoprothrombinemia associated with methylthiotetrazole-substituted cephalosporins should be treated with fresh frozen plasma. Likewise, dangerous bleeding due to impaired platelet aggregation requires treatment with platelet concentrates.


[Ebstein's disease associated with Fallot's tetralogy. Apropos of a familial case, review of the literature, embryologic and genetic implications].
Ebstein anomaly is a rare congenital cardiac malformation, representing 0.3 p. 100 of all congenital heart disease. The authors report a case of a child with Ebstein anomaly associated with tetralogy of Fallot, whose father had an apparently simple Ebstein anomaly. The association of Ebstein-Fallot is extremely rare with only 5 previously reported cases in the literature. The association Ebstein-VSD-pulmonary stenosis is more frequent (13 cases), whilst the association Ebstein-isolated VSD (33 cases) and Ebstein-pulmonary stenosis/atresia (38 cases) are relatively common. Other very varied associations have also been described. Atrial septal defect is practically an integral part of Ebstein anomaly with an ostium secundum or patent foramen ovale in 51 to 80 p. 100 of cases. The possibility of 2 subjects in the same family with Ebstein anomaly is far from negligible. A review of the literature revealed 7 other reported "pairs". A certain number of other cases also demonstrate the association of Ebstein anomaly with another congenital cardiac malformation in the same family, usually a VSD or tetralogy of Fallot. Our familial case raises the question of a possible embryological link between Ebstein anomaly and tetralogy of Fallot. Our experimental embryological studies also suggest the presence of a common denominator between these two conditions.


Structure and organization of the living mitotic spindle of Haemanthus endosperm.
New details of mitotic spindle structures in the endosperm of Haemanthus katherinae (Bak) have been demonstrated by differential interference microscopy. Spindle fibers are clearly seen in the living spindle extending from the kinetochores to the polar region. Individual spindle fibers consist of a bundle of smaller filaments which diverge slightly from the kinetochore and intermingle with filaments from other spindle fibers as they approach the polar region. The degree of intermingling increases during metaphase and anaphase. The chromosomes stop moving when the spindle fibers are still 5 to 10microns long; then the fibers disappear. These observations explain some aspects of spindle movements which were difficult to reconcile with earlier concepts of spindle organization.


Robust statistical label fusion through COnsensus Level, Labeler Accuracy, and Truth Estimation (COLLATE).
Segmentation and delineation of structures of interest in medical images is paramount to quantifying and characterizing structural, morphological, and functional correlations with clinically relevant conditions. The established gold standard for performing segmentation has been manual voxel-by-voxel labeling by a neuroanatomist expert. This process can be extremely time consuming, resource intensive and fraught with high inter-observer variability. Hence, studies involving characterizations of novel structures or appearances have been limited in scope (numbers of subjects), scale (extent of regions assessed), and statistical power. Statistical methods to fuse data sets from several different sources (e.g., multiple human observers) have been proposed to simultaneously estimate both rater performance and the ground truth labels. However, with empirical datasets, statistical fusion has been observed to result in visually inconsistent findings. So, despite the ease and elegance of a statistical approach, single observers and/or direct voting are often used in practice. Hence, rater performance is not systematically quantified and exploited during label estimation. To date, statistical fusion methods have relied on characterizations of rater performance that do not intrinsically include spatially varying models of rater performance. Herein, we present a novel, robust statistical label fusion algorithm to estimate and account for spatially varying performance. This algorithm, COnsensus Level, Labeler Accuracy and Truth Estimation (COLLATE), is based on the simple idea that some regions of an image are difficult to label (e.g., confusion regions: boundaries or low contrast areas) while other regions are intrinsically obvious (e.g., consensus regions: centers of large regions or high contrast edges). Unlike its predecessors, COLLATE estimates the consensus level of each voxel and estimates differing models of observer behavior in each region. We show that COLLATE provides significant improvement in label accuracy and rater assessment over previous fusion methods in both simulated and empirical datasets.


Primary tuberculosis of the glans penis in male kidney transplant recipients: a report on two cases.
An extremely rare form of genitourinary tract tuberculosis (TB) is TB of the glans penis. Here, we report on two men with TB of the glans, both occurring secondary to their wives having genital TB. To the best of our knowledge, this is the first report of this nature from Iran. One case is a 48 year-old blind male with an asymptomatic papulo-pustular eruption over the glans and, the other is a 51 year-old male who had kidney transplantation in March 2004, and was referred to our transplantation clinic nine months later with papulonecrotic ulcer on the glans which did not respond to antibiotic therapy. Both patients responded well to anti-TB treatment. Our cases suggest that every papulonecrotic lesion on the glans must raise the suspicion of TB, and an underlying active or healed focus of TB should be thoroughly searched. Also, it is very important, particularly in endemic areas, that prior to transplanting a male patient, his female partner must be examined for TB of the genitalia.


Further contributions to the understanding of nitrogen removal in waste stabilization ponds.
A set of experiments were conducted in Brazil in a pilot-scale waste stabilization pond (WSP) system (a four-maturation-pond series) treating an upflow anaerobic sludge blanket (UASB) reactor effluent. Over a year and a half the pond series was monitored under two flow rate conditions, hence also different hydraulic retention times and surface loading rates. On-site and laboratory trials were carried out to assess: (i) ammonia losses by volatilization using acrylic capture chambers placed at the surface of the ponds; (ii) organic nitrogen sedimentation rates using metal buckets placed at the bottom of the ponds for collecting settled particulate matter; (iii) nitrogen removal by algal uptake based on the nitrogen content of the suspended particulate matter in samples from the ponds' water column. In addition, nitrification and denitrification rates were measured in laboratory-based experiments using pond water and sediment samples. The pond system achieved high nitrogen removal (69% total nitrogen and 92% ammonia removal). The average total nitrogen removal rates varied from 10,098 to 3,849 g N/ha·d in the first and the last ponds, respectively, with the following fractions associated with the various removal pathways: (i) 23.5-45.6% sedimentation of organic nitrogen; (ii) 13.1-27.8% algal uptake; (iii) 1.2-3.1% ammonia volatilization; and (iv) 0.15-0.34% nitrification-denitrification.


Patient-Reported Outcome Measures: How to Maximize Their Utility and Mitigate Health Care Disparities.
Patient-reported outcome measures (PROMs) provide a standardized assessment from the patient about their own health status. Although originally developed as research tools, PROMs can be used in clinical orthopaedic care to complement objective functional measures (eg, range of motion). When PROMs are used during clinical care, they can improve patient outcomes, engagement, well-being, and patient-physician communication. Therefore, PROMs are increasingly integrated into shared decision-making approaches to guide treatment decisions, enhance treatment plans, and predict outcomes. They are also being used in quality measurement and value-based health care arrangements. However, methods to communicate PROMs with patients have not been fully developed, and there continue to be barriers to implementing their collection and communication at scale. In addition, measuring care quality and communicating PROMs with patients may have unintended consequences, such as when used in measurement without accounting for confounding factors (eg, psychological and social health), or in perpetuating health care disparities when used imprecisely (eg, lack of linguistic or cultural validation). It is important to describe the current state of PROM use in orthopaedic surgery, highlight opportunities and challenges of PROM use in clinical care, and provide a roadmap for how to incorporate PROMs to equitably improve patient health and build orthopaedic surgery practices.


Towards delimitation of the Echinococcus multilocularis parasite's southernmost range in France.
Alveolar echinococcosis is a severe, potentially fatal, parasitic disease caused by ingestion of microscopic eggs of Echinococcus multilocularis. The lifecycle of the parasite is essentially sylvatic, and based on a prey-predator relationship between red foxes and small rodents. A westward expansion from the eastern historical focus has been reported in France, though the parasite has also been detected in the southern Alps. While the focus in the Auvergne region (central France) was described in the 1980s, the southern delimitation of the actual endemic area, especially in the south, was unknown in the absence of dedicated surveys. Red fox samples were collected from 2013 to 2020 in the framework of other transversal epidemiological studies in five sampling areas from southwestern and southeastern France. One hundred and seven intestines were analysed by SSCT, and 221 faecal samples from intestines were analysed by copro-qPCR. None of the 328 foxes exhibited E. multilocularis worms or DNA. Although the presence of E. multilocularis cannot be totally excluded in the departments from the study areas, the sample size tested argues for an absence of the parasite in these studied areas, which is in accordance with the currently known endemic situation in France. These new data are helpful in determining the southernmost limit of E. multilocularis distribution in France. The warm, dry Mediterranean climate in the southeastern areas is less favourable to the transmission of E. multilocularis and especially to the survival of eggs in the environment than the climate in the French Alps or Liguria (Italy) climate where the parasite is present. The intermediate area between the southwestern study areas and the historical focus of Auvergne, which is separated by around 150 km, will be investigated in the coming years. Moreover, an ongoing national surveillance programme on E. multilocularis in foxes is targeting French departements along the edge of the known endemic area both in the southeast and southwest. The data produced will supplement the results of this study, thus greatly helping to define the current distribution of E. multilocularis in France and to target prevention measures to reduce human exposure.


Task Partitioning in Insect Societies. I. Effect of Colony Size on Queueing Delay and Colony Ergonomic Efficiency.
The collection and handling of colony resources such as food, water, and nest construction material is often divided into subtasks in which the material is passed from one worker to another. This is known as task partitioning. When material is transferred directly from one individual to another, queueing delays frequently occur because individuals must sometimes wait for a transfer partner. A stochastic simulation model was written to study the effect of colony size on these delays. Queueing delay decreases roughly exponentially with colony size because stochastic fluctuations in the arrival of individuals are lower in larger colonies. These results support empirical studies of Polybia occidentalis and other theoretical studies of honeybees. The effect of the relative number of individuals in the two subtask groups was also studied. There is a unique optimal ratio of the number of workers associated with each of the subtasks that simultaneously minimizes mean queueing delay and maximizes colony nectar-processing rate. Deviations from this optimal ratio, for example, as a result of forager mortality or changes in nectar productivity that affect foraging trip duration, increase mean queueing delays greatly, especially in smaller colonies.


Technologies for whole-cell modeling: Genome-wide reconstruction of a cell in silico.
With advances in high-throughput, large-scale in vivo measurement and genome modification techniques at the single-nucleotide level, there is an increasing demand for the development of new technologies for the flexible design and control of cellular systems. Computer-aided design is a powerful tool to design new cells. Whole-cell modeling aims to integrate various cellular subsystems, determine their interactions and cooperative mechanisms, and predict comprehensive cellular behaviors by computational simulations on a genome-wide scale. It has been applied to prokaryotes, yeasts, and higher eukaryotic cells, and utilized in a wide range of applications, including production of valuable substances, drug discovery, and controlled differentiation. Whole-cell modeling, consisting of several thousand elements with diverse scales and properties, requires innovative model construction, simulation, and analysis techniques. Furthermore, whole-cell modeling has been extended to multiple scales, including high-resolution modeling at the single-nucleotide and single-amino acid levels and multicellular modeling of tissues and organs. This review presents an overview of the current state of whole-cell modeling, discusses the novel computational and experimental technologies driving it, and introduces further developments toward multihierarchical modeling on a whole-genome scale.


Myopathy associated BAG3 mutations lead to protein aggregation by stalling Hsp70 networks.
BAG3 is a multi-domain hub that connects two classes of chaperones, small heat shock proteins (sHSPs) via two isoleucine-proline-valine (IPV) motifs and Hsp70 via a BAG domain. Mutations in either the IPV or BAG domain of BAG3 cause a dominant form of myopathy, characterized by protein aggregation in both skeletal and cardiac muscle tissues. Surprisingly, for both disease mutants, impaired chaperone binding is not sufficient to explain disease phenotypes. Recombinant mutants are correctly folded, show unaffected Hsp70 binding but are impaired in stimulating Hsp70-dependent client processing. As a consequence, the mutant BAG3 proteins become the node for a dominant gain of function causing aggregation of itself, Hsp70, Hsp70 clients and tiered interactors within the BAG3 interactome. Importantly, genetic and pharmaceutical interference with Hsp70 binding completely reverses stress-induced protein aggregation for both BAG3 mutations. Thus, the gain of function effects of BAG3 mutants act as Achilles heel of the HSP70 machinery.


Particle Coupling Mechanism inspired Adsorption Optimization in Autonomous in Vivo Computing.
While some commercial transceivers are available for capsule millirobots, no one has yet tackled the challenge of wireless communication between nanorobots inside the human body, which could be crucial for the control, and coordination of nanorobots. The Multi-agent system relies on information exchange by physical interactions or chemical secretions to perform complex tasks. Our previous work proposed a swarm coordination mechanism for tumor-target in an autonomous manner. To perform deterministic tasks, the method does not require prior knowledge of tumor location but the nanoparticles (NPs) swarm that follows simple migration principles. The biological gradient field (BGF) generated by tumors allows nanoswarms (NS) to cooperate and passively migrate to potential tumor sites. An autonomous computation strategy in vivo (ACS) is proposed based on particle coupling and adsorption optimization to improve NS aggregation and overall targeting efficiency in vivo. In addition, an evaluation system is established to evaluate the aggregation degree of NS and the drug leakage caused by the dissipation of NPs in complex vascular networks. By increasing the aggregation degree NS and reducing the effect of drug leakage, We are able to achieve an increase in global targeting efficiency to about 95%, which can be helpful in early-tumor detection, which can be helpful in early-tumor detection.Clinical relevance-Our investigation into autonomous swarm coordination and targeting of nanorobots in vivo represents a novel approach for early tumor detection, potentially achieving targeting efficiency of approximately 95% in complex vascular networks.


TP53 mutations in human meningiomas.
Overexpression of p53 has been reported to play a role in the development of neoplasms of the central nervous system. Meningiomas are generally benign intracranial tumors originating from the meninges. Overexpression of the p53 protein in meningiomas and an association with histological type and recurrence has been reported. Mutation of the TP53 gene leads to a more stable p53 protein in quantities high enough for detection by immunohistochemistry. In the search for these mutations the core domain of the TP53 gene of meningiomas has been analyzed. Only a very low incidence of mutations was reported. The apparent discordance between overexpression of p53 protein and TP53 gene mutations may be explained by mutations located outside the core domain. This issue was addressed in the present study. All 11 exons of 17 meningiomas were analyzed for DNA alterations by PCR single-strand conformation polymorphism (PCR-SSCP) analysis with subsequent sequencing. PCR-SSCP analysis showed a various number of band shifts and nucleotide alterations, caused either by alterations in the flanking introns or common polymorphisms (codon 36 and 72). The allele frequencies of the polymorphisms found in this small population of tumors resemble the frequencies reported in the literature. In addition, three nucleotide changes located in introns 2, 3 and 7 were found in 11, 3 and 4, respectively, of 17 specimens. Based on this study and on reports by others we conclude that it is not very likely that TP53 mutations are involved in the etiology of meningiomas.


[Viral vaccines produced by gene technology and synthesis].
The gradual evolution of vaccine development from Jenner's smallpox vaccine to recombinant genetechnology has provided the basis for prophylactic control of a lot of important infectious diseases of humans and animals. Modern biotechnology has accomplished antigen identification and isolation of antigen determinants as well as the preparation of proteins and synthetic peptides. The application of such techniques has failed, however, to develop a better vaccine in case of FMD-Virus. Present efforts are directed on the improvement of antigen presentation and immunogenicity of such protein- and peptide vaccines.


Persistent kidney dysfunction in swine renal artery stenosis correlates with outer cortical microvascular remodeling.
Percutaneous transluminal renal stenting (PTRS) does not consistently improve renal function in patients with atherosclerotic renovascular disease, but the mechanisms underlying irreversible kidney injury have not been fully elucidated. We hypothesized that renal dysfunction after PTRS is linked to ongoing renal microvascular (MV) remodeling. Pigs were studied after 10 wk of atherosclerosis and renal artery stenosis (ARAS), ARAS treated with PTRS 4 wk earlier, and normal controls (n = 10 each). Renal blood flow (RBF) and glomerular filtration rate (GFR) were studied using multidetector computer tomography. Renal microvascular architecture (micro-CT), angiogenic activity, oxidative stress, and fibrosis were evaluated ex vivo. Four weeks after PTRS, blood pressure was normalized. However, GFR and RBF remained similarly decreased in untreated ARAS and ARAS+PTRS (P < 0.05 vs. normal). MV rarefaction was unaltered after revascularization, and the spatial density of outer cortical microvessels correlated with residual GFR. Interstitial fibrosis and altered expression of proangiogenic and profibrotic factors persisted after PTRS. Tubulointerstitial injury in ARAS persisted 4 wk after mechanically successful PTRS, and vessel loss correlated with residual renal dysfunction. MV loss and fibrosis in swine ARAS might account for persistent renal dysfunction after PTRS and underscore the need to assess renal parenchymal disease before revascularization.


CUPID COVID-19: emergency department attendance by paediatric patients during COVID-19 - project protocol.
Background: Measures introduced to delay the spread of COVID-19 may result in avoidance of emergency departments (EDs) for non-COVID related illness. Clinicians and medical representative bodies such as the Irish Association for Emergency Medicine (IAEM) have expressed concern that some patients may not seek timely urgent medical intervention. Evidence from previous epidemics found that hospital avoidance during outbreaks of MERS and SARS was common. While ED attendance returned to normal following SARS and MERS, both outbreaks lasted 2-3 months. As the COVID-19 pandemic is forecast to extend into 2021, little is known about the impact COVID-19 will have on paediatric attendance at EDs as the pandemic evolves. Aims: This project aims to assess the impact of COVID-19 on paediatric emergency healthcare utilisation, to understand how the health seeking behaviour of parents may have altered due to the pandemic, and to identify how any barriers to accessing care can be removed. Methods: Administrative data records from five EDs across Ireland and one Urgent Care Centre will be analysed to identify temporal trends in attendances for emergency care. Qualitative inquiry will be utilised to capture the experience of staff providing emergency healthcare to paediatric patients during COVID-19, and their feedback on identified trends will inform the interpretation of findings. A cross-sectional survey of parents will capture experiences, concerns and decision-making on accessing healthcare for their children during the pandemic. Results and Conclusion: This information will help decision makers respond rapidly to meet the clinical needs of paediatric patients as the circumstances of the pandemic unfold and reduce the disruption to normal paediatric ED services during the onset of COVID-19. As the health of a child can deteriorate more rapidly than that of an adult, any delay in seeking care for an acutely ill child may have serious consequences.


Polaris, a protein involved in left-right axis patterning, localizes to basal bodies and cilia.
Mutations in Tg737 cause a wide spectrum of phenotypes, including random left-right axis specification, polycystic kidney disease, liver and pancreatic defects, hydrocephalus, and skeletal patterning abnormalities. To further assess the biological function of Tg737 and its role in the mutant pathology, we identified the cell population expressing Tg737 and determined the subcellular localization of its protein product called Polaris. Tg737 expression is associated with cells possessing either motile or immotile cilia and sperm. Similarly, Polaris concentrated just below the apical membrane in the region of the basal bodies and within the cilia or flagellar axoneme. The data suggest that Polaris functions in a ciliogenic pathway or in cilia maintenance, a role supported by the loss of cilia on the ependymal cell layer in ventricles of Tg737(orpk) brains and by the lack of node cilia in Tg737(Delta2-3betaGal) mutants.


Aggregation of colon cancer in family data.
Although only a small proportion of common cancers show familial aggregation, studying such families can elucidate the roles of shared environment and genes in the development of neoplasia. We report an analysis of nine colon cancer pedigrees using new nonparametric objective methods to measure familial aggregation as a means of determining the existence of heterogeneity in the data. Each family was selected through a proband with nonpolyposis colon cancer who had a first-degree relative with documented colon cancer. To assess the aggregation of different cancers in these families we employ a method which evaluates both excess number of cases as well as distribution by risk in family members. We find that eight of the nine families exhibit significant aggregation of colon cancer: endometrial cancer aggregates in three families, breast in none, kidney in one, and all sites in eight. In this way, we show that two families fit the criteria for Cancer Family Syndrome, and that one is not a high-risk cancer family.


Urban-Rural Dimension of Falls and Associated Risk Factors among Community-Dwelling Older Adults in West Java, Indonesia.
Falls are one of the common problems among older adults; it is estimated that 684,000 fatal cases of falls occur every year. Furthermore, falls constitute one of the leading causes of mortality due to accidental injury. This study aims to identify the risk factors for falls in the older adults who live in the community, according to the dimensions of the living area: in urban and rural. The proportional sampling method was used to identify the rural and urban areas in West Java Prefecture; meanwhile, the incidence of fall in the last 12 months was selected as the outcome variable. Furthermore, sociodemographic background, chronic medical condition, fear of falling, visual and hearing impairments, Activity of Daily Living (ADL), Barthel index, physical performance (Short Performance Physical Battery (SPPB)), and living environment were analyzed to identify the risk factors that contribute to the incidence of falls. A total of 611 older adults participated in this study: 62% of them are living in rural area and 38% of them are living urban areas. More than 70% of study participants were aged 60-69 years, while 73% were females. There is no significant difference in fall prevalence in rural (16.5%) and urban (10.7%) areas (p value = 0.228). Furthermore, the multiple logistic regression analysis showed that the male gender (OR = 0.29, 95%CI [0.09-0.88]), chronic illness (OR = 3.25, 95%CI [1.24-8.53]), and visual impairment (OR = 3.6, 95%CI [1.52-8.54]) were associated with fall among older adults in urban areas. Meanwhile, visual impairment (OR = 1.81, 95%CI [1.03-3.18]) and living environment (OR = 3.36, 95% CI [1.14-9.93]) were significantly associated with falls in rural areas. Based on the associated risk factors identified in this study, a different approach is needed to reduce the falling risk among older adults in urban and rural areas in Indonesia.


[Psychological aspects of radiotherapy of children and adolescents (author's transl)].
The increasing importance of radiotherapy in tumor of childhood demands the investigation and consideration of the psychological aspects of this afflicting therapy. In this paper the results obtained by questioning and observing 28 children of different ages, their parents, attendants and employees of several radiological departments are discussed. As the children's fantasies and the resulting anxieties and reactions are depending on the respective intellectual and emotional developmental stage detailed proposals concerning the preparation and performance of radiation in toddlers, school children and adolescents are presented.


[Binding by glutamate dehydrogenase of 14C from bicarbonate buffer].
Different levels of carbon dioxide (10,20, 40, 80, mM) at pH 6.7, 7.3, 7.6 and 8.5 of incubation media were studied for their effect on the intensity of binding of 14C from bicarbonate buffer by crystalline NAD(P)+-dependent glutamate dehydrogenase from the bovine liver. The effect of a variety of substrates and effectors on this process is investigated. The intensity of the radioactive label binding is shown to increase with pH of the incubation medium and carbon dioxide concentration in it. When acidifying the medium (up to pH 6.5) the enzyme under study does not bind 14C. The preincubation of the enzyme with pyridoxal-5-phosphate decreases considerably the intensity of the label binding with the protein. On the basis of these data a conclusion is drawn about the interaction of CO2 with free amino groups of the enzyme molecule by the type of the carbamate formation. GTP and NADH inhibit this process as well.


Measurement of iron stores in cirrhosis using diethylenetriamine penta-acetic acid.
The chelating agent diethylenetriamine penta-acetic acid was used to measure iron stores in 83 patients with chronic liver disease. Iron chelation was normal in patients with chronic cholestasis. Chelation was increased above the control range in 14 out of 26 patients with alcoholic cirrhosis, in nine out of 28 patients with non-alcoholic cirrhosis, and in 11 out of 15 cirrhotics with a portacaval anastomosis. Iron stores in excess of 1.5 g were predicted from the results in 24 subjects; however, in only three were the values in the range found in propositi with untreated idiopathic haemochromatosis. Increased chelation did not correlate with hepatocellular impairment per se but was associated in 18 cases with surgical or large spontaneous portal systemic shunts. Exogenous factors for excess iron were present in three cases with alcoholic cirrhosis and portal systemic collaterals in one, but no special factor apart from alcoholism was apparent in the remainder. The correlation between chelatable iron and stainable liver iron content was not close and was better in haemochromatosis than in other forms of cirrhosis; in some cases considerable siderosis was present with normal or only slightly increased chelation values.


Maternal Sweeteners Intake Modulates Gut Microbiota and Exacerbates Learning and Memory Processes in Adult Male Offspring.
Background: There is increasing evidence that gut microbiota in offspring is derived in part from maternal environment such as diet. Thus, sweeteners intake including caloric or non-caloric during perinatal period can induce gut dysbiosis and program the offspring to develop cognitive problems later in life. Objective: To determine the effect of maternal high-sweeteners intake during gestation and lactation on gut microbiota shifts in adult male offspring rats and the impact on cognitive dysfunction. Methods: Thirty-four male pups from dams fed standard diet (Control-C, n = 10), high-sucrose diet (HS-C, n = 11), high-honey diet (Ho-C, n = 8), and high-stevia diet (HSt-C, n = 5) were fed standard diet after weaning, and body weight and food intake were recorded once a week for 26 weeks. Learning and memory tests were performed at week 23 of life using the Barnes maze. Fecal samples from the breastfeeding and adulthood periods were collected and analyzed by sequencing the 16S rRNA V3-V4 region of gut microbiota. Results: Maternal high-sucrose and stevia diets programmed the male offspring, and changes in microbial diversity by Shannon index were observed after weaning (p < 0.01). Furthermore, maternal high-stevia diet programming lasted into adulthood. The increase of Firmicutes abundance and the decrease in phylum Bacteroidetes were significant in HS-C and HSt-C groups. This led to an increase in the Firmicutes/Bacteroidetes index, although only in HS-C group was statistically significant (p < 0.05). Of note, the downstream gram-negative Bacteroidales and the upregulation of the gram-positive Clostridiales abundance contribute to cognitive dysfunction. Conclusion: These results suggest that dams fed a high-sucrose and stevia diets during gestation and lactation favor a deficient memory performance in adult male offspring rats through shifts gut microbiota diversity and relative abundance at several taxa.


Scintigraphic imaging of infections with 99m-Tc-labelled glutathione liposomes.
In this study, liposomes containing glutathione were evaluated to detect infection in mice. Glutathione liposomes were labelled by using 99mTc-labelled-HMPAO (hexamethyl propylamine oxime). Mice were infected in the thigh by intramuscular injection with turbentine. Labelled liposomes were applied to the tail vein of the mice intravenously. At fixed time intervals they were sacrificed. The animals were imaged under a gamma camera. Then, tissue samples were excised and radioactivity of all organs was counted. Abscess-to-muscle, abscess-to-liver, and abscess-to-spleen ratios were calculated. The ratios of abscess-to-muscle were found to be 1.6 and 11.6 at 1 h and 24 h, respectively. According to these data, the abscess can be defined at 1 h and it became more clear with time.