[Influence of food quality and quantity on children's teeth].
Sugar and tooth decays are bound closely. The mechanisms of destruction of the tooth from the glycolyse are known. The role played by the food in the development of the caries is unique. Foods sweetened of all ways, rich in sucrose are responsible of the intervening of the carious lesions. The transformation of the fermentable sugars in lactic with the absence of hygiene and the action conjugated of the bacteria leads to tooth decays in temporary and permanent denture that evolve very quickly in the absence of treatment. Reasons for which the authors put in evidence in this survey, the influence of the food sweetened on the teeth at the children while showing the cases of caries and its complications due to the excessive consumption of fermentable hydrates of carbon.


Lack of in vitro-in vivo correlation of a novel investigational anticancer agent, SH 30.
In solid tumors, the reasons for the lack of in vitro and in vivo correlation of drug activities are multifold and includes permeability to the tumor cells, interstitial hypertension and metabolic degradation. So, it is important to study the permeability and metabolic disposition of new compounds early in discovery and development of anticancer drugs. An experimental anti-cancer drug, SH 30 demonstrated highly selective and potent cytotoxic activity against a number of multi-drug resistant tumor cell lines in vitro. However, it was inactive in a murine tumor model. This study was conducted to identify the barriers that result in lack of correlation between in vitro and in vivo cytotoxic activity of novel anticancer agents. Two important barriers: physical (permeability) and metabolic (enzymatic inactivation) to poor delivery of SH 30 to solid tumors were investigated in this study. Tumors were sliced to separate the vascular and avascular sections. The concentrations of the drug at various regions of the tumor after single and multiple doses were investigated to determine the permeability barrier. The permeability barrier was also probed using two in vitro model systems, namely, matrigel films representing extracellular matrix and caco-2 multilayer cell cultures that simulate solid tumors. The drug and its metabolite concentrations were determined in the plasma and tumors to determine the metabolic barrier to the drug cytotoxic action. The metabolic barrier was further probed using in vitro mouse hepatocytes and liver microsome preparations. Our examination revealed the metabolic barrier to be the major contributor to the ineffectiveness of SH 30 in vivo. Examination of concentration of the drug across various regions of the tumor corroborated by data from in vitro permeation studies suggested that, for SH 30, permeability barrier did not exist. After single injection, the concentrations of SH 30 and its metabolites in plasma and tumor were comparable to another investigational drug with similar features (XK 469). Contrary to day 1, after 8 consecutive days of administration, SH 30 concentrations were significantly lower, while the metabolites concentrations were higher, suggesting extensive metabolism due to induction of enzyme(s). The in vitro hepatocytes and liver microsome results also showed SH 30 biotransformation to the same metabolites. Neither drug penetration, nor drug distribution into regions of the tumors distal to vasculature were impeded. The inactivity of SH 30 in vivo is primarily due to induction of extensive metabolism to inactive metabolites. This metabolism prevents adequate drug levels being achieved in the tumor.


Exclusion of orphan drugs for certain covered entities under 340B Program. Final rule.
HHS is issuing this final rule to clarify how section 340B(e) of the Public Health Service Act (PHSA) will be implemented. The final rule applies section 340B(e) of the PHSA only to drugs transferred, prescribed, sold, or otherwise used for the rare condition or disease for which the orphan drug was designated under section 526 of the Federal Food, Drug, and Cosmetic Act (FFDCA). The final rule also sets forth that it is the responsibility of the 340B covered entity to maintain auditable records that demonstrate compliance with the terms of the orphan drug exclusion requirements. This rule will provide clarity in the marketplace, maintain the 340B savings for newly-eligible covered entities, and protect the financial incentives for manufacturing orphan drugs designated for a rare disease or condition as indicated in the Affordable Care Act and intended by Congress.


Neural population encoding and decoding of sound source location across sound level in the rabbit inferior colliculus.
At lower levels of sensory processing, the representation of a stimulus feature in the response of a neural population can vary in complex ways across different stimulus intensities, potentially changing the amount of feature-relevant information in the response. How higher-level neural circuits could implement feature decoding computations that compensate for these intensity-dependent variations remains unclear. Here we focused on neurons in the inferior colliculus (IC) of unanesthetized rabbits, whose firing rates are sensitive to both the azimuthal position of a sound source and its sound level. We found that the azimuth tuning curves of an IC neuron at different sound levels tend to be linear transformations of each other. These transformations could either increase or decrease the mutual information between source azimuth and spike count with increasing level for individual neurons, yet population azimuthal information remained constant across the absolute sound levels tested (35, 50, and 65 dB SPL), as inferred from the performance of a maximum-likelihood neural population decoder. We harnessed evidence of level-dependent linear transformations to reduce the number of free parameters in the creation of an accurate cross-level population decoder of azimuth. Interestingly, this decoder predicts monotonic azimuth tuning curves, broadly sensitive to contralateral azimuths, in neurons at higher levels in the auditory pathway.


Understanding satisfaction and dissatisfaction of patients with telemedicine during the COVID-19 pandemic: An exploratory qualitative study in primary care.
Due to the COVID-19 pandemic, healthcare organizations had to face challenging circumstances and modify the usual modality of service provision, introducing telehealth services in their routine patient care to lessen the risk of direct human-to-human exposure. Patients expressed concerns about personal visits to healthcare units and the possibility of accessing telemedicine turned out to be an effective tool for the continuity of care. Due to the limited experience with telemedicine before the COVID-19 pandemic in Poland, we sought to fill this gap by studying the experiences of Polish patients. Our study aimed to understand how patients define satisfaction and dissatisfaction with telemedicine during the COVID-19 pandemic in primary care. Twenty semi-structured interviews with primary care patients in the Podlaskie Voivodeship, Poland were conducted to understand satisfaction with telemedicine. Interview transcripts were analyzed using qualitative content analysis. The qualitative content analysis process involved familiarizing ourselves with the data, extracting text regarding satisfaction and dissatisfaction with the teleconsultation, condensing it into meaningful units assigning codes to them, and organizing codes into subcategories and categories. The entire analysis process was done through reflection and discussion until a consensus was reached between the researchers. From the participants' perspective, satisfaction with telemedicine was associated with receiving enough space to express their concerns. It was reported that they trusted their primary care physicians and felt comfortable during telemedicine consultations. Participants noted that connecting with a known, trusted doctor was more important than having a face-to-face visit with an unfamiliar physician. In our study, the participants equated satisfaction with treatment effectiveness. It was emphasized that in the event of unknown or unstable conditions, patients would prefer to be seen in person and receive a physical examination. In our research telemedicine met with a positive reception and was recognized by the majority of patients who made use of it as a valuable channel of contact with a primary care physician. In order to increase the level of patient satisfaction, the focus should be on improving aspects such as physician engagement and showing empathy during telemedicine, as well as providing complete, exhaustive information on the treatment process. Respecting patient needs and preferences during performing telemedicine visits is the goal of patient-centered care.


Study of serum level of kisspeptin and interferon-beta in genital wart patients.
Researchers are interested in genital wart (GW) studies due to their increased incidence. In a single experimental research, virally infected mouse models showed elevated kisspeptin levels and low interferon levels. The objective of the study was to evaluate the serum levels of kisspeptin and interferon (INF)-beta in GW patients. Forty patients with GWs and forty healthy participants of comparable age and sex as a control group were included in this case-control study. Serum levels of kisspeptin and IFN-beta were measured using ELISA during the period from December 2021 to April 2022. Kisspeptin was significantly higher among cases than controls, whereas IFN-beta level was lower among cases than controls (P < 0.001). There were no significant relations between kisspeptin and IFN-beta levels and the clinical data for the studied participants, and there was no significant correlation between both (P > 0.05). The reported increased kisspeptin level which was associated with decreased interferon-beta level in patients with GWs might indicate a new insight into viral infection pathogenesis. Further research including all steps in kisspeptin/G protein-coupled receptor 54 pathway is required. Targeted therapy for this pathway may be of value for those patients.


The AtNFS2 gene from Arabidopsis thaliana encodes a NifS-like plastidial cysteine desulphurase.
NifS-like proteins are cysteine desulphurases required for the mobilization of sulphur from cysteine. They are present in all organisms, where they are involved in iron-sulphur (Fe-S) cluster biosynthesis. In eukaryotes, these enzymes are present in mitochondria, which are the major site for Fe-S cluster assembly. The genome of the model plant Arabidopsis thaliana contains two putative NifS-like proteins. A cDNA corresponding to one of them was cloned by reverse-transcription PCR, and named AtNFS2. The corresponding transcript is expressed in many plant tissues. It encodes a protein highly related (75% similarity) to the slr0077-gene product from Synechocystis PCC 6803, and is predicted to be targeted to plastids. Indeed, a chimaeric AtNFS2-GFP fusion protein, containing one-third of AtNFS2 from its N-terminal end, was addressed to chloroplasts. Overproduction in Escherichia coli and purification of recombinant AtNFS2 protein enabled one to demonstrate that it bears a pyridoxal 5'-phosphate-dependent cysteine desulphurase activity in vitro, thus being the first NifS homologue characterized to date in plants. The putative physiological functions of this gene are discussed, including the attractive hypothesis of a possible role in Fe-S cluster assembly in plastids.


Anti-inflammatory, cyclooxygenase (COX)-2, COX-1 inhibitory, and free radical scavenging effects of Rumex nepalensis.
Evaluation of the topical anti-inflammatory activity of chloroform and ethyl acetate extracts of RUMEX NEPALENSIS roots in a TPA-induced acute inflammation mouse model demonstrated a significant reduction in ear edema. The extracts were further tested on purified enzymes for COX-1 and COX-2 inhibition to elucidate their mechanism of action, and a strong inhibition was observed. Six anthraquinones and two naphthalene derivatives were isolated from the ethyl acetate extract. Among the isolated compounds, emodin was found to be a potent inhibitor with slight selectivity towards COX-2, and nepodin exhibited selectivity towards COX-1. Emodin, endocrocin, and nepodin also exhibited significant topical anti-inflammatory activity in mice. Interestingly, nepodin showed better radical scavenging activity than trolox and ascorbic acid against DPPH and ABTS radicals. The strong radical scavenging activity of chloroform and ethyl acetate extracts could be explained by the presence of nepodin as well as by the high phenolic content of the ethyl acetate extract. Thus, the anti-inflammatory effect of R. NEPALENSIS roots was assumed to be mediated through COX inhibition by anthraquinones and naphthalene derivatives and through the radical scavenging activities of naphthalene derivatives.


Amniotic membrane with living related corneal limbal/conjunctival allograft for ocular surface reconstruction in Stevens-Johnson syndrome.
To report the use of preserved amniotic membrane and living related corneal limbal/conjunctival transplantation in total limbal stem cell and conjunctival deficiency secondary to severe Stevens-Johnson syndrome. Prospective, noncomparative, interventional case series. Ten eyes of 10 patients with total limbal stem cell and conjunctival deficiency secondary to Stevens-Johnson syndrome underwent excision of cicatricial tissue followed by amniotic membrane and living related corneal limbal/conjunctival transplantation. Reconstruction of corneal epithelium (clear appearance without epithelial defect, normal fluorescein permeability, and the absence of conjunctiva-derived goblet cells on impression cytologic testing), decrease in corneal vascularization, and improvement in visual acuity. During a mean follow-up of 16.7 months, satisfactory ocular surface reconstruction was obtained in 2 eyes (20%), with reduced inflammation and vascularization and a mean epithelialization time of 3 weeks. Surgical failure was observed in 4 cases (40%) and complications (infection) in 4 cases (40%). Visual acuity improved in 4 eyes (40%), remained stable in 5 eyes (50%), and decreased in 1 eye (10%). Amniotic membrane and living related corneal limbal/conjunctival transplantation were successful in 20% of severe cases of total limbal stem cell and conjunctival deficiency secondary to Stevens-Johnson syndrome. A high proportion of postoperative complications, in particular, infection, seemed to jeopardize a favorable outcome.


Different negative priming impairments in schizophrenia and subgroups of obsessive-compulsive disorder.
Inhibitory functioning is assumed to be deficient in some psychiatric disorders, most notably in patients with schizophrenia and obsessive-compulsive disorder (OCD). In order to investigate inhibitory functioning, priming tasks are commonly used. The present paradigm offers the opportunity to isolate specific distractor features (identity, location) for independent examination. Negative priming (NP) for stimulus identity and location was examined in patients with schizophrenia (N = 16), patients with OCD (N = 15) and matched controls (N = 16). All groups performed a referent size-selection task in which they were instructed successively to select the larger one of two cardinal numbers. The deeper processing of both stimuli was expected to yield large NP effects that allow the detection of subtle group differences. Large NP effects were found for stimulus identity in all three groups. Schizophrenic patients differed from normal controls with respect to the amount of incidental location priming. Subgroup analyses of OCD patients showed NP impairments for checkers when the response-stimulus interval (RSI) was short, but large identity NP when the RSI was long. OCD non-checkers showed normal NP patterns with short RSI, but reduced identity NP with longer RSI. Schizophrenic patients do not show the ability to use spatial selective attention in order to guide their actions as shown by normal controls. Information processing was differentially impaired in OCD subgroups (checkers and non-checkers) dependent on RSI variation. This result supports those studies that found reduced NP in OCD patients and points to the necessity of differential subgroup studies.


New method for assessing changes in growth and sexual dimorphism in paleoepidemiology.
This paper has three goals. First, traditional methods used for analyzing growth disruption (GD) and sexual dimorphism (SD) in prehistoric skeletal populations are critiqued. Second, a new method, using adult vertebrae, is presented which helps overcome these limitations. Third, this new method is then tested in the Dickson Mounds skeletal population. Between A.D. 950 and 1300 this population underwent a transition from hunting and gathering (PreMississippian: PreMiss.) to maize horticulture (Mississippian: Miss.). Previous research has found a decrease in long bone length in Miss. children, but no difference in adults, or a change in SD. Could this be due to catch-up growth? In the adult skeleton vertebral neural canals (VNCs) size and vertebral body heights (VBHs) can easily be measured. VNCs generally cease growth by early childhood, whereas VBHs grow through young adulthood. This new method offers inference into prehistoric GD and SD previously thought impossible. For example, if VNCs are reduced, but not VBHs, it implies early GD with subsequent catch-up growth. If both VNCs and VBHs are reduced, GD was presumably chronic. Moreover, within this framework, preadult SD can be examined. Results from Dickson show that early GD was followed by catch-up growth. There was a significant change in SD, with females becoming smaller. They had chronic GD. Miss. males had early GD, followed by catch-up growth. Indeed, Miss. males, compared to PreMiss. males, had significantly larger VBHs. Together, these results suggest females lost, but males gained, social status. Thus, vertebral morphometrics may be an invaluable new tool for paleoepidemiologists.


Tropism of CPMV to Professional Antigen Presenting Cells Enables a Platform to Eliminate Chronic Infections.
Chronic viral infections (e.g., HIV, HBV, HCV) represent a significant source of morbidity and mortality with over 500 million people infected worldwide. Dendritic cells (DCs) and macrophages are key cell types for productive viral replication and persistent systemic infection. We demonstrate that the plant virus cowpea mosaic virus (CPMV) displays tropism for such antigen presenting cells in both mice and humans, thus making it an ideal candidate for targeted drug delivery toward viral infections. Furthermore, we show inhibition of a key host protein for viral infection, site-1 protease (S1P), using the small molecule PF-429242 in the model pathogen arenavirus lymphocytic choriomeningitis virus (LCMV) limits viral growth. By packaging PF-429242 in CPMV, we are able to control drug release and efficiently deliver the drug. This sets the groundwork for utilizing the natural tropism of CPMV for a therapeutic approach that specifically targets cell types most commonly subverted by chronic viruses.


Hsa-miR-27b is up-regulated in cytomegalovirus-infected human glioma cells, targets engrailed-2 and inhibits its expression.
Human cytomegalovirus (HCMV) dormant infection can alter the expression of the hosts' microRNAs (miRNAs) and impact on the regulation of target genes. To investigate the differentially expressed miRNAs induced by HCMV in human glioma U251 cells, a comprehensive miRNA screen was performed. As a result, 19 up-regulated and 14 down-regulated miRNAs were determined. Of these, hsa-miR-27b (miR-27b) attracted our attention. MiR-27b levels in U251 cells increased 7.70-fold, 8.64-fold, and 4.78-fold, respectively, post 24 h, 48 h, and 72 h HCMV infection, compared to those in the mimic-infected cells, and this up-regulation was further confirmed by quantitative RT-PCR. The bioinformatic analyses show that miR-27b targets engrailed-2 (EN2) gene; however, the effect of miR-27b on EN2 is rarely encountered. In this study, we initially conducted dual luciferase assay to validate the target function of miR-27b on EN2. The results manifested that EN2 is a novel target of miR-27b, which could directly target the 3' untranslated region (3'-UTR) of the gene. We further found that the miR-27b transfected glioma U251 cells exhibited longer cell bodies with more synapses and multiple-angle shapes; moreover, Western blot detection revealed that the EN2 protein levels in these cells were significantly low. In conclusion, our study originally reports the up-regulation of miR-27b in HCMV-infected glioma cells. Our study also provides the first experimental evidence that miR-27b could affect glioma cells' growth, target EN2 and inhibit its expression in glioma cells. Our data indicate that miR-27b may be related to the development of neurological disorders with HCMV infection. The newly identified miR-27b/EN2 signal pathway may provide new insights into the glioma pathogenesis and a novel target for glioma therapy. Impact statement Our study is the first to demonstrate that the HCMV infection could alter the expression of cellular microRNAs of the host glioma cells, which may develop an understanding of the pathogenesis of the HCMV infection in the microRNA level. Recently, HCMV infection and engrailed-2 have been reported to be related to the autism spectrum disorder (ASD). In this study, we confirmed that engrailed-2 is the target of hsa-miR-27b. As far as we know, our findings of the hsa-miR-27b up-regulation in the HCMV-infected glioma cells, targeting engrailed-2 and inhibiting its expression have never been reported or documented. Our data indicate that miR-27b may be related to the development of neurological disorders with the HCMV infection. The newly identified miR-27b/EN2 signal pathway may provide new insights into the glioma pathogenesis and a novel target for glioma therapy.


Gossypium herbaceam extracts inhibited NF-kappaB activation to attenuate spatial memory impairment and hippocampal neurodegeneration induced by amyloid-beta in rats.
Amyloid-beta (Abeta) is considered to be responsible for the pathogenesis of Alzheimer's disease. In the present study, the protective effect of Gossypium herbaceam extracts (GHE) on learning and memory impairment induced by Abeta were examined in vivo using Morris water maze and step through task. Furthermore, the antioxidant activity and neuroprotective effect of GHE was investigated with methods of histochemistry and biochemistry. These data showed that oral administration with GHE at the doses of 35, 70 and 140 mg/kg exerted an improved effect on the learning and memory impairment in rats induced by intracerebroventricular (i.c.v.) injection of 10 microg of Abeta(25-35). Subsequently, the GHE afforded a beneficial action on promotion on the activity of glutathione peroxidase and catalase, as well as inhibition on the NF-kappaB activation in the hippocampus followed by the presence of Abeta(25-35). Meanwhile, the number of degenerating neurons with an apoptotic feature was dramatically decreased in hippocampus after treatment with GHE, implicating that its antioxidant stress and inhibition of NF-kappaB activation could be involved in the mechanism underlying neuroprotection of GHE against Abeta-induced cell death. These findings suggested that GHE might be a potential agent for treatment of Alzheimer's disease.


Physical fitness training: outcomes for adult oncology patients.
Physical activity and exercise participation are important considerations in the study and management of acute and long-term care for cancer patients. Although excessive rest and lack of physical activity are related to diminished physical fitness, reduced functional status, impaired cognition, and diminished quality of life, exercise prescription is not a standard treatment support for patients or survivors of cancer. In this retrospective study, it was hypothesized that routine participation in exercise could improve physical fitness for adults recently completing months of cancer treatment. Forty-five cancer patients were able to make considerable fitness gains over an 8-week period. A fitness program coordinated by an exercise physiologist, certified trainers, and an advanced practice cancer nurse was an effective method of organizing referral, monitoring individual patient concerns, and avoiding unnecessary risks.


Selective inhibition of liver cancer growth realized by the intrinsic toxicity of a quantum dot-lipid complex.
Using the intrinsic toxicity of nanomaterials for anticancer therapy is an emerging concept. In this work, we discovered that CdTe/CdS quantum dots, when coated with lipids (QD-LC) instead of popular liposomes, polymers, or dendrimers, demonstrated extraordinarily high specificity for cancer cells, which was due to the difference in the macropinocytosis uptake pathways of QD-LC between the cancer cells and the normal cells. QD-LC-induced HepG2 cell apoptosis was concomitant with the activation of the JNK/caspase-3 signaling pathway. Moreover, QD-LC treatment resulted in a delay in the latent period for microtumor formation of mouse hepatocarcinoma H22 cells and inhibited tumor growth, with a reduction of 53.2% in tumor volume without toxicity in major organs after intratumoral administrations to tumor-bearing mice. Our results demonstrate that QD-LC could be a very promising theranostic agent against liver cancer.


[Hand involvement in Thevenard's disease: a new "phlegmonous" form. An exceptional case report].
Thévenard's disease is a rare familial ulcero-mutilating acropathology involving the peripheral nervous system. It typically begins on the feet and only rarely spreads to the hands late in the course of the disease. It first causes cutaneous ulcerations and then secondary osseous deformations and osteoarticular destruction, due to a distal loss of temperature sensation. We report the case of an 87 year old patient who suffered from a particular clinical form, undescribed as yet in the literature and characterized by local and general superinfections predominately on the hands. We term this the "cellulitic" presentation or form of Thévenard's disease.


Counterion density profile around charged cylinders: the strong-coupling needle limit.
Charged rod-like polymers are not able to bind all their neutralizing counterions: a fraction of them evaporates, while the others are said to be condensed. We study here counterion condensation and its ramifications, both numerically by means of Monte Carlo simulations employing a previously introduced powerful logarithmic sampling of radial coordinates and analytically, with special emphasis on the strong-coupling regime. We focus on the thin rod or needle limit that is naturally reached under strong Coulombic couplings, where the typical intercounterion spacing a' along the rod is much larger than its radius R. This regime is complementary and opposite to the simpler thick rod case where a' ≪ R. We show that due account of counterion evaporation, a universal phenomenon in the sense that it occurs in the same clothing for both weakly and strongly coupled systems, allows one to obtain excellent agreement between the numerical simulations and the strong-coupling calculations.


A high-flux upgrade for the BRISP spectrometer at ILL.
To date, the BRISP spectrometer represents the state-of-the-art for every instrument aiming to perform Brillouin neutron scattering. Exploiting accurate ray-tracing McStas simulations, we investigate an improved configuration of the BRISP primary spectrometer to provide a higher flux at the sample position, while preserving all the present capabilities of the instrument. This configuration is based on a neutron guide system and is designed to fit the instrument platform with no modifications of the secondary spectrometer. These evaluations show that this setup can achieve a flux gain factor ranging from 3 to 6, depending on the wavelength. This can expand the experimental possibilities of BRISP towards smaller samples, possibly using also complex sample environments.


Efficacy of continuous positive airway pressure for treatment of hypernasality.
To determine whether speech hypernasality in subjects born with cleft palate can be reduced by graded velopharyngeal resistance training against continuous positive airway pressure (CPAP). Pretreatment versus immediate posttreatment comparison study. Eight university and hospital speech clinics. Forty-three subjects born with cleft palate, aged 3 years 10 months to 23 years 8 months, diagnosed with speech hypernasality. Eight weeks of 6 days per week in-home speech exercise sessions, increasing from 10 to 24 minutes, speaking against transnasal CPAP increasing from 4 to 8.5 cm H(2)0. MAIN OUTCOME MEASURES Pretreatment to immediate posttherapy change in perceptual nasality score based on blinded comparisons of subjects' speech samples to standard reference samples by six expert clinician-investigators. Participating clinical centers treated from two to nine eligible subjects, and results differed significantly across centers (interaction p =.004). Overall, there was statistically significant reduction in mean nasality score after 8 weeks of CPAP therapy, whether weighted equally across patients (mean reduction = 0.20 units on a scale of 1.0 to 7.0, p =.016) or across clinical centers (mean = 0.19, p =.046). This change was about one-sixth the maximum possible reduction from pretreatment. Nine patients showed reductions of at least half the maximum possible, but hypernasality of eight patients increased at least 30% above pretreatment level. Most improvement was seen during the second month when therapy was more intense (p =.045 for nonlinearity). No interactions with age or sex were detected. Patients receiving 8 weeks of velopharyngeal CPAP resistance training showed a net overall reduction in speech hypernasality, although response was quite variable across patients and clinical centers. The net reduction in hypernasality is not readily explainable by random variability, subject maturation, placebo effect, or regression to the mean. CPAP appears capable of substantially reducing speech hypernasality for some subjects with cleft palate.


Journey from food toxins to food safety: Transition over a century in service of nation.
Since the first report of lathyrism in 1926, the ICMR-National Institute of Nutrition (NIN) at Hyderabad, India, has made tremendous contributions in the field of food toxins/food safety for the benefit of the people. The present article highlights the Institute's work on various food toxins/foodborne diseases since its inception and discusses the important contributions made in the context of public health protection that formed the basis for several national policies on their prevention and control. The investigations on food toxins, in the initial decades, were limited to the description of lathyrism and its endemicity. Subsequently, the horizon was broadened to include the problem of mycotoxins and mycotoxicosis, which had received global attention and variety of other disease outbreaks investigations leading to total food safety transition in the forthcoming decades. Important contributions in epidemiological investigations, reproduction of the disease in experimental animals, surveillance and monitoring studies, development of methods for detection of food toxins and contaminants, evolving strategies for prevention and control and developing the concept of risk assessment and risk management for addressing food safety issues in the country are discussed.


Theoretical studies of conjugation effects on excited state intramolecular hydrogen-atom transfer reactions in model systems.
Intramolecular hydrogen-atom transfer dependence on electronic conjugation of curcumin and related molecular models in the ground state and 1pipi* excited state are computationally studied at the first-principles electronic structure level. The larger, more conjugated, systems exhibit a lower reaction barrier in the ground state but a higher barrier in the excited state. This is associated with a smaller increase in the conjugation upon excitation in the larger systems. Our studies provide a detailed description and analysis of these energy trends as well as an insight into the physical nature of the intramolecular hydrogen-atom transfer reactions.


Low-noise low-jitter 32-pixels CMOS single-photon avalanche diodes array for single-photon counting from 300 nm to 900 nm.
We developed a single-photon counting multichannel detection system, based on a monolithic linear array of 32 CMOS SPADs (Complementary Metal-Oxide-Semiconductor Single-Photon Avalanche Diodes). All channels achieve a timing resolution of 100 ps (full-width at half maximum) and a photon detection efficiency of 50% at 400 nm. Dark count rate is very low even at room temperature, being about 125 counts/s for 50 μm active area diameter SPADs. Detection performance and microelectronic compactness of this CMOS SPAD array make it the best candidate for ultra-compact time-resolved spectrometers with single-photon sensitivity from 300 nm to 900 nm.


A series of papers for those yearning to propel telehealth to new heights.
If you are taking the time to read this essay, you are most likely interested in telemedicine and its future in some capacity. This introductory essay and accompanying series of white papers have a relatively simple goal, namely, to highlight a broad array of issues that must be addressed in order to propel telemedicine to its next stage in evolutionary development.


MRI of the cat brain in the study of vascular permeability after intraarterial carotid injection of triolein.
Triolein emulsion embolization into the carotid artery depicts reversible increased vascular permeability that can promote the effect of chemotherapy or can reduce the amount of chemotherapeutic drugs for equivalent effectiveness. To establish the minimum dosage of 0.5% triolein for studying vascular permeability changes in a triolein emulsion model. Sixty-six cats were divided into six groups based on the amount of emulsified triolein (0.5%) infused into the carotid artery: group 1 (n=12, 6 ml/kg), group 2 (n=12, 4.5 ml/kg), group 3 (n=12, 3 ml/kg), group 4 (n=10, 1.5 ml/kg), group 5 (n=10, 1 ml/kg), and group 6 (n=10, 3 ml/kg of saline (control group)). T1-weighted, T2-weighted, and post-contrast T1-weighted MRI was performed 2 h after the infusion of the triolein emulsion. Contrast enhancement ratios (CERs) were obtained with pre- and post-contrast T1-weighted images in the ipsilateral and contralateral hemispheres. Signal intensity ratios (SIRs) of the ipsilateral and contralateral hemispheres were evaluated on T2-weighted images. After removal of the brain tissues, edema ratios in the ipsilateral and contralateral hemispheres were obtained from wet versus dry brain weights. Data were statistically evaluated by analysis of variance, followed by the Tukey honestly significant difference test to compare the difference in the mean CER of the ipsilateral and contralateral hemispheres, mean SIR on T2-weighted image, and mean edema ratio between each group when overall significance was attained. In the ipsilateral hemispheres, the difference in the CER between the control group and groups 1 (P=0.004), 2 (P=0.043), and 3 (P=0.008) were statistically significant. The difference in the CERs between the triolein emulsion groups was not statistically significant (P>0.05). The T2-weighted SIRs were significantly different between the control group and groups 1 (P=0.027) and 2 (P=0.004). However, the edema ratios of all doses in the triolein emulsion groups showed no significant differences compared with the control group. The minimum dosage of 0.5% triolein emulsion to achieve increased vascular permeability in the hemisphere in cat brains appears to be 3 ml/kg. This minimum dosage of triolein emulsion can be useful for acquiring basic data in further studies of vascular permeability changes in a triolein emulsion model.


Desire or Disease? Framing Obesity to Influence Attributions of Responsibility and Policy Support.
The way we describe health threats affects perceptions of severity and preferred solutions to reduce risk. Most people agree obesity is a problem, but differ in how they attribute responsibility for development and decline of the disease. We explored effects of message framing on attributions of responsibility and support for public obesity policies using a 3 × 2 factorial design. Participants read one of six versions of a health message describing the negative effects of obesity. Message frames influenced respondent attributions and their support for policies to reduce obesity. Those who read a message that assigned agency to the disease (e.g., Obesity causes health problems) endorsed genetics as the cause to a greater degree than those who read a semantically equivalent message that instead assigned agency to people (e.g., Obese people develop health problems). In contrast, assigning agency to people rather than to the disease prompted higher attributions of individual responsibility and support for public policies. Explicit message frames that directly connected responsibility for obesity to either individual or societal factors had no effect on respondent perceptions. Findings suggest explicit arguments may be less effective in shifting perceptions of health threats than arguments embedded in agentic message frames. The results demonstrate specific message features that influence how people attribute responsibility for the onset and solution of obesity.


Food allergy phenotypes: The key to personalized therapy.
Food allergies (FAs) are of increasing public health concern and are characterized by a large spectrum of diseases. Their diversity is well known for immunologic pathways (IgE, non-IgE-mediated FAs) and natural history. Many other factors and patient characteristics are involved including type of food, exposure route, allergic comorbidities, gender, racial and ethnic backgrounds, cofactors and health conditions. Food allergen components and sensitization profiles are also involved in FA phenotypes. A new approach to chronic disorders based on the identification of phenotypes through extensive knowledge of all the complex components is also applicable to FAs and could lead towards integrative care management. Diagnostic biomarkers for FAs are emerging which also contribute to better care modalities. The aim of this article was to highlight current knowledge regarding the phenotypic diversity of FA. This review will focus on IgE-mediated FAs and how identifying phenotypes may help to better understand the pathophysiological complexity, improve diagnosis and lead to personalized treatment strategies.


Resting energy expenditure and food-induced thermogenesis in diabetic children receiving continuous subcutaneous insulin infusion.
The effect of short-term (8-10 days) optimal glycaemic control achieved by continuous subcutaneous insulin infusion on resting energy expenditure and food-induced thermogenesis was studied. Oxygen consumption and carbon dioxide production were measured by indirect calorimetry in six newly-diagnosed and six chronically-treated diabetic children before and following the consumption of a standardized test meal. The metabolic and hormonal responses to the test meal and nutrient utilization were also assessed and compared with those measured in nine non-diabetic children. The restoration of normoglycaemia was accompanied by hypoglucagonaemia, hypoketonaemia, increased insulin:glucagon ratio and abnormal postmeal fall in free fatty acid levels in spite of normal fasting and post-prandial plasma free insulin levels. These changes suggesting increased insulin action were most pronounced in newly-diagnosed diabetic children. Possibly as a result of increased insulin action high carbohydrate, low fat utilization and increased food-induced thermogenesis were observed in the newly-diagnosed diabetic children. In the chronically-treated group these parameters were approaching the normal. Resting energy expenditure was normal in both groups of diabetics. These findings suggest that precise glycaemic control can be achieved only at the expense of some degree of peripheral hyperinsulinisation which leads to altered nutrient utilization and food-induced thermogenesis in the newly-diagnosed diabetic children.


Prevalence of EBV, HPV and MMTV in Pakistani breast cancer patients: A possible etiological role of viruses in breast cancer.
Breast cancer being a multifactorial disease, the role of infectious agent in development of disease is of great interest. The high incidence of breast cancer around the world has woken the interest in a viral etiology of breast cancer. Despite decades of research, no etiologic factor(s) for human breast cancer has been known and the quest for a contributing cause has all but been abandoned during the past years. Recent investigations have linked breast cancer to viral infections, such as Epstein-Barr virus (EBV), Human papillomavirus (HPV) and mouse mammary tumor virus. To investigate the possible association of EBV, HPV and MMTV infection with breast cancer development and progression. Screening of isolated genomic DNA from FFPE breast cancer tissue biopsies (n=250) using standard polymerase chain reaction and correlation of virus prevalence with BC disease outcomes using statistical analysis software (SPSS 16.0). Our findings suggest the prevalence of EBV (24.4%), HPV (18.1%) and MMTV (29.3%), while coinfection of HPV and EBV was detected in 9.2% (23/250), co infection of HPV and MMTV in 3.2% (8/250) and coinfection of EBV and MMTV in 6% (15/250) of breast cancer samples. No virus was detected in 59.5% of the breast cancer samples. Mono infection of EBV and HPV do not statistically co-relate with the clinico-pathological outcomes of breast cancer disease, though MMTV infection does co-relate with age and grade of breast cancer disease. In our study, the prevalence of coinfection of HPV, EBV and MMTV in Pakistani breast cancer patients is rare, still there is a possibility of synergistic carcinogenic effect of different viruses in the development of breast cancer disease. The significant percentage of virus prevalence shows potential role in breast cancer development. However, this study provides substantial but not conclusive evidence for the involvement of viruses in BC disease development and progressiveness.


Lower Rate of CTNNB1 Mutations and Higher Rate of APC Mutations in Desmoid Fibromatosis of the Breast: A Series of 134 Tumors.
Desmoid fibromatosis (DF) is a rare, locally aggressive, nonmetastasizing fibroblastic/myofibroblastic tumor with a tendency to recur and an unpredictable clinical course. A "wait-and-see" policy is the new standard of care. DF are characterized by activating alterations of the wnt/β-catenin pathway: CTNNB1 or adenomatous polyposis coli gene (APC) mutations (these mutations being mutually exclusive). Desmoid-type fibromatosis of the breast (DFB) is rare with an incidence of 0.2% of breast tumors. The diagnosis of DFB is difficult, as it must be distinguished from metaplastic carcinoma and other spindle cell lesions. Sequencing of 128 DFB identified a lower rate of CTNNB1 mutations using Sanger (65.6%) or Sanger+next-generation sequencing (77.7%) and a higher rate of APC mutations (11.8%) than in all-site DF. By excluding patients with familial adenomatous polyposis (n=2), the rate of APC mutations in DFB was high (10.7%). The distribution of CTNNB1 mutations in DFB was different from all-site DF, with a higher rate of T41A (68.9%), a lower rate of S45F (5.7%), and a similar rate of S45T (12.6%). By combining the 2 molecular techniques in a 2-step manner (Sanger, then next-generation sequencing), we increased the detection rate of CTNNB1 mutations and lowered the rate of wild-type tumors from 34.4% to 9.8%, therefore improving the diagnosis of DFB. The identification of the exon 3 CTNNB1 mutation in breast spindle cell lesions is a highly specific tool for the diagnosis of DFB, in addition to extensive immunohistochemical analysis. Our study also underlines the importance of APC in DFB tumorigenesis. These findings have significant implications for patient care and management.


Prognostic Factors in Epithelioid Hemangioendothelioma: Analysis of a Nationwide Molecularly/Immunohistochemically Confirmed Cohort of 57 Cases.
Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study, we aimed to investigate prognostic factors based on clinicopathologic findings in a molecularly/immunohistochemically confirmed nationwide multicenter cohort of 57 EHE cases. Patients had unifocal disease (n = 29), multifocal disease (n = 5), lymph node metastasis (n = 8) and/or distant metastasis (n = 15) at the time of diagnosis. The overall survival rate was 71.4% at 1 year and 50.7% at 5 years. Survival did not correlate with sex, age or histopathological parameters. No survival differences were observed between multifocal and metastatic disease, suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al., dividing the cases into low- (n = 4), intermediate- (n = 15) and high- (n = 3) risk groups. No clinical or histopathological parameters were associated with progressive unifocal disease course. Lymph node metastases at the time of diagnosis occurred in 14.0% of the cases and were mainly associated with tumor localization in the head and neck area, proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previously described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis.


Statistics and public health at CDC.
Since CDC's inception, an important function of the agency has been the compilation, analysis, and interpretation of statistical information to guide actions and policies to improve health. Sources of data include vital statistics records, medical records, personal interviews, telephone and mail surveys, physical examinations, and laboratory testing. Public health surveillance data have been used to characterize the magnitude and distribution of illness and injury; to track health trends; and to develop standard curves, such as growth charts. Beyond the development of appropriate program study designs and analytic methodologies, statisticians have played roles in the development of public health data-collection systems and software to analyze collected data. CDC/ATSDR employs approximately 330 mathematical and health statisticians. They work in each of the four coordinating centers, two coordinating offices, and the National Institute for Occupational Safety and Health.


Alcohol misuse as a response to perceived powerlessness in the organization.
The relationship between the perceived characteristics of a job and employee alcoholism was examined. Research has determined that it is a perceived lack of power that better distinguishes an alcoholic from a nonalcoholic, and that such a perceived lack of power causes an alcoholic to suffer frustration because of the inability to feel competent and self-determining. The job has been shown to influence psychological functioning in all aspects of an individual's life, and specific job characteristics which contribute to feelings of competence and self-determination were studied. These included (1) personal power in the organizational hierarchy, (2) participation in decision making, (3) job autonomy and (4) job responsibility. Regression analysis of data from questionnaires administered to 293 full-time employees demonstrated significant F ratios for perceived job responsibility and perceived lack of personal power in the organization when regressed against the CAGE questionnaire, which identified covert alcoholics. These data support the notion that aspects of the job are associated with and may help to induce alcoholism among employees.


High-performance liquid chromatographic determination of multi-mycotoxin in cereals and bean foodstuffs using interference-removal solid-phase extraction combined with optimized dispersive liquid-liquid microextraction.
A novel pre-treatment was proposed for the simultaneous determination of aflatoxins, ochratoxin A and zearalenone in foodstuffs using high-performance liquid chromatography with fluorescence detection. The analytical procedure was based on a first step using a quick, easy, cheap, effective, rugged, and safe based extraction procedure, followed by salting out and purification with a C18 solid-phase extraction column as interference removal clean-up. Subsequently, collected supernatant was subjected to dispersive liquid-liquid microextraction. Response surface methodology based on central composite design was employed to optimize conditions in the microextraction procedure. Under the optimum conditions, satisfactory analytical performance with recoveries ranging from 63.22 to 107.6% were achieved in different types of cereals and beans, as well as desirable precisions (0.81-8.13%). Limits of detections and quantifications for these six mycotoxins ranging from 0.03 to 13 μg/kg and 0.22 to 44 μg/kg, respectively, were obtained. Finally, the established method was successfully validated by four certified reference materials (P = 0.897 > 0.05) and applied to 79 samples from local markets.


Genetic gain in dairy cattle populations is increased using sexed semen in commercial herds.
Using stochastic simulation, the effect of using sexed semen to cow dams (CD) in a dairy cattle breeding scheme, with or without use of multiple ovulation and embryo transfer (MOET) to bull dams (BD), on annual genetic gain at the population level was examined. Three levels of sexed semen were combined with three levels of MOET: no sexed semen, sexed semen to the best CD and sexed semen to all heifers, combined with no MOET, MOET on all BD and MOET randomly on 20% of the BD. In total, nine scenarios were compared. The simulated population was monitored for 30 years and included 450 herds with 100 cows each. Each year 50 young bulls (YB), 10 active sires and 215 BD were selected on best linear unbiased prediction estimated breeding values by truncation selection across the simulated population, and the YB were tested within the population. Use of sexed semen alone gave a positive increase in the annual genetic gain of 2.1% when used on the best CD and 2.7% when used on all heifers, but only the latter was statistically significant. The increased annual genetic gain was caused by a larger contribution from the CD to the BD. Use of sexed semen together with MOET on BD increased the annual genetic gain by 1.8-2.5% compared with schemes without sexed semen and MOET on all BD. Performing MOET on all BD enables selection of offspring with high Mendelian deviations, which increase the annual genetic gain. Use of sexed semen decreased the genetic lag between the sires and the CD by 12-14% when used on the best CD and by 6% when used to all heifers. The decrease in the genetic lag is caused by the increased selection intensity of the cow dams.


Multifaceted role of glycosylation in transfusion medicine, platelets, and red blood cells.
Glycosylation is highly prevalent, and also one of the most complex and varied posttranslational modifications. This large glycan diversity results in a wide range of biological functions. Functional diversity includes protein degradation, protein clearance, cell trafficking, cell signaling, host-pathogen interactions, and immune defense, including both innate and acquired immunity. Glycan-based ABO(H) antigens are critical in providing compatible products in the setting of transfusion and organ transplantation. However, evidence also suggests that ABO expression may influence cardiovascular disease, thrombosis, and hemostasis disorders, including alterations in platelet function and von Willebrand factor blood levels. Glycans also regulate immune and hemostasis function beyond ABO(H) antigens. Mutations in glycogenes (PIGA, COSMC) lead to serious blood disorders, including Tn syndrome associated with hyperagglutination, hemolysis, and thrombocytopenia. Alterations in genes responsible for sialic acids (Sia) synthesis (GNE) and UDP-galactose (GALE) and lactosamine (LacNAc) (B4GALT1) profoundly affect circulating platelet counts. Desialylation (removal of Sia) is affected by human and pathogenic neuraminidases. This review addresses the role of glycans in transfusion medicine, hemostasis and thrombosis, and red blood cell and platelet survival.


Spatiotemporal modulation of abscisic acid and gibberellin metabolism and signalling mediates the effects of suboptimal and supraoptimal temperatures on seed germination in wheat (Triticum aestivum L.).
Seed germination is a complex process regulated by intrinsic hormonal cues such as abscisic acid (ABA) and gibberellin (GA), and environmental signals including temperature. Using pharmacological, molecular and metabolomics approaches, we show that supraoptimal temperature delays wheat seed germination through maintaining elevated embryonic ABA level via increased expression of ABA biosynthetic genes (TaNCED1 and TaNCED2), increasing embryo ABA sensitivity through upregulation of genes regulating ABA signalling positively (TaPYL5, TaSnRK2, ABI3 and ABI5) and decreasing embryo GA sensitivity via induction of TaRHT1 that regulates GA signalling negatively. Endospermic ABA and GA appeared to have minimal roles in regulating germination at supraoptimal temperature. Germination inhibition by suboptimal temperature is associated with elevated ABA level in the embryo and endosperm tissues, mediated by induction of TaNCEDs and decreased expression of endospermic ABA catabolic genes (TaCYP707As), and increased ABA sensitivity in both tissues via upregulation of TaPYL5, TaSnRK2, ABI3 and ABI5 in the embryo and TaSnRK2 and ABI5 in the endosperm. Furthermore, suboptimal temperature suppresses GA synthesis in both tissues and GA sensitivity in the embryo via repressing GA biosynthetic genes (TaGA20ox and TaGA3ox2) and inducing TaRHT1, respectively. These results highlight that spatiotemporal modulation of ABA and GA metabolism and signalling in wheat seeds underlies germination response to temperature.


Angling-induced injuries have a negative impact on suction feeding performance and hydrodynamics in marine shiner perch, Cymatogaster aggregata.
Fishing is a popular and lucrative sport around the world and, in some cases, may contribute to declining fish stocks. To mediate this problem and maintain fish biomass in aquatic ecosystems, catch-and-release fishing, whereby a fish is caught and immediately released, has been implemented in many countries. It is unclear whether the injuries to the mouth that are caused by the hook have an impact on feeding performance of fishes. Using high-speed video and computational fluid dynamics (CFD), we asked whether injuries around the mouth caused by fishing hooks have a negative impact on suction feeding performance (measured as maximum prey velocity) of the commonly angled marine shiner perch (Cymatogaster aggregata). We hypothesized that fish with mouth injuries would exhibit decreased feeding performance compared with controls. Ten shiner perch were caught using scientific angling and 10 were caught using a seine net. Feeding events were then recorded at 500 frames per second using a high-speed camera. Compared with the control group, maximum prey velocity was significantly lower in the injured group (P<0.01). Maximum gape, time to peak gape, maximum jaw protrusion and predator-prey distance were comparable between the control and injured groups, leading us to conclude that the injury-induced hole in the buccal cavity wall reduced the pressure gradient during mouth expansion, thereby reducing the velocity of water entering the fish's mouth. This was confirmed with our CFD modelling. Fishing injuries in nature are likely to depress feeding performance of fish after they have been released, although it is currently unclear whether this has a significant impact on survival.


Prevalence of sleep disturbances in Chinese university students: a comprehensive meta-analysis.
This is a meta-analysis of the pooled prevalence of sleep disturbances and its associated factors in Chinese university students. English (PubMed, PsycINFO, Embase) and Chinese (SinoMed, Wan Fang Database and Chinese National Knowledge Infrastructure) databases were systematically and independently searched from inception until 16 August 2016. The prevalence of sleep disturbances was pooled using random-effects model. Altogether 76 studies involving 112 939 university students were included. The overall pooled prevalence of sleep disturbances was 25.7% (95% CI: 22.5-28.9%). When using the screening scales Pittsburgh Sleep Quality Index, Athens Insomnia Scale and Self-Rating Sleeping State Scale, and the diagnostic criteria of the Chinese Classification of Mental Disorders (Second Edition), the pooled prevalence of sleep disturbances was 24.1% (95% CI: 21.0-27.5%) and 18.1% (95% CI: 16.4-20.0%), respectively. The percentages of students dissatisfied with sleep quality and those suffering from insomnia symptoms were 20.3% (95% CI: 13.0-30.3%) and 23.6% (95% CI: 18.9-29.0%), respectively. Subgroup analyses revealed that medical students were more vulnerable to sleep disturbances than other student groups. There was no significant difference between males and females, and across geographic locations. Sleep disturbances are common in Chinese university students. Appropriate strategies for prevention and treatment of sleep disturbances in this population need greater attention.


Robotics, motor learning, and neurologic recovery.
Robotic devices are helping shed light on human motor control in health and injury. By using robots to apply novel force fields to the arm, investigators are gaining insight into how the nervous system models its external dynamic environment. The nervous system builds internal models gradually by experience and uses them in combination with impedance and feedback control strategies. Internal models are robust to environmental and neural noise, generalized across space, implemented in multiple brain regions, and developed in childhood. Robots are also being used to assist in repetitive movement practice following neurologic injury, providing insight into movement recovery. Robots can haptically assess sensorimotor performance, administer training, quantify amount of training, and improve motor recovery. In addition to providing insight into motor control, robotic paradigms may eventually enhance motor learning and rehabilitation beyond the levels possible with conventional training techniques.


Upper extremity disorders in performing artists.
Studies in the past decade have shown that a significant proportion of instrumentalists report musculoskeletal problems severely affecting their musical performance. Musicians endure daily intensive use of their upper extremities, frequently placing them in bizarre positions. Their training schedules are rigorous and long term Predisposing factors to, and treatment for, overuse syndromes, tendinitis, and tendon trauma commonly encountered by musical performers are discussed at length. Nerve entrapment has also surfaced as a major problem in musicians, and the means of evaluation and treatment and the role of surgery are put forth. Techniques for studying and analyzing the difficulties faced by instrumentalists are summarized.


Surgical pathology of the infected gut.
In the normal digestive tract, interaction of the mucosa with a large and varied microbial flora is inevitable. In fact, the "normal" state of the digestive tract reflects the impact of the resident flora to a significant degree. The pathogenesis of various infectious conditions encountered by the surgical pathologist in the gut is understood more readily when the gastrointestinal tract is viewed as a complex ecosystem. Significant disease may result from perturbation of the normal flora, as well as from exogenous infection, and susceptibility of the host may vary with disturbances of the digestive ecosystem. An ecologic perspective is essential in the consideration not only of the "infected" gut, but of conditions as diverse as ischemia or even carcinogenesis in the gastrointestinal mucosa.


U.S. Immigration Policy Regimes and Physical Disability Trajectories Among Mexico-U.S. Immigrants.
Although immigration policies have shifted dramatically over the course of U.S. history, few have examined their role as a source of health heterogeneity among immigrants. We address this gap by evaluating whether exposure to U.S. Immigration Policy Regimes (IPRs) corresponds with later-life disability disparities among Mexico-U.S. migrant women and men, and assess the degree to which observed differences may also be associated with immigration policies and occupational composition. We analyze 8 waves of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly (3,044 individuals and 14,474 observations from 1993/1994-2013). Using hierarchical linear models, we estimate trajectories of physical disability associated with gender, occupation, and IPR. We find differences in disability trajectories by IPR. Associations are not different between men and women, and are not mediated by occupational composition. We also observe an additive effect for certain occupations among women, but not among men. Findings demonstrate that exposure to different IPRs is associated with disparate disability trajectories among Mexico-U.S. migrants. Future research is needed to contextualize the role of IPRs amid other mechanisms of gendered racialization that powerfully contribute to cumulative health differences across the life course.


Macrophage production of fibronectin, a chemoattractant for fibroblasts.
Activation of macrophages results in the production of numerous enzymes and effector molecules. One of these monokines released by macrophages can cause directed migration of connective tissue fibroblasts in vitro. Production of this macrophage-derived chemotactic factor for fibroblasts requires activation of the macrophages either in vivo or in vitro and de novo protein synthesis. The chemotactic activity in the macrophage supernatants could be removed by a fibronectin-specific affinity column and was inhibited in the presence of antibodies to fibronectin. Furthermore, chemotactic activity in the depleted macrophage supernatants could be restored by the addition of exogenous fibronectin. Fibronectin was identified in activated macrophage supernatants by an enzyme-linked immunoassay for fibronectin. From these findings it was concluded that activated macrophages release a chemoattractant for fibroblasts and that the primary chemoattractant molecule is fibronectin. The production of fibronectin by activated macrophages may thus serve as an inflammatory mediator that in addition to its other functions can recruit fibroblasts to an area of damaged tissue, where they can proliferate and form the scar tissue necessary for tissue repair. Furthermore, in chronic inflammation, the prolonged activation of macrophages may be related to the extensive fibroblast infiltration and fibrosis that can accompany these lesions.


[Surgical management in complex trauma of the lower limb with soft tissue defects].
This work is studying the treatment for the complex trauma of the lower limb, followed by soft tissue defects, with bones exposure, that necessitate immediate coverage with adequate tissues. The reconstructive method should be chosen according to the location and soft tissue requirement of the defect (local/regional flap, or free tissue transfer). Aggressive management of acute trauma of the lower limb provides good results. First condition for the intervention success is working together: plastic surgeon, orthopaedic surgeon, neurosurgeon, physiotherapist.


Modelling mechanical and chemical treatment of biofilms with two phenotypic resistance mechanisms.
Bacterial biofilms are notoriously difficult to eradicate owing to a number of tolerance mechanisms including physiological, physical, genotypic and phenotypic variations. Recent focus has shifted to phenotypic tolerance which is apparently the main defence mechanism that protects biofilms against long-term disinfection. Previous mathematical models have addressed phenotypic dynamics by considering adaptive response and persister formation separately. The aim of this manuscript is to consider a combined model to understand the interplay between these two defence mechanisms. We find that each mechanism protects the biofilm differently and hence responds differently to antibiotic challenge. We focus on on-off dosing that has been shown to eradicate each subpopulation alone. Our results indicate that the combined resistance exhibits qualitatively similar behavior to persister formation for short dosing times, and similar behavior to adaptive resistance for long dosing times. To further contrast the behavior of the model under different parameter regimes, we explore two classes of combination treatment that include mechanical and chemical treatments. The examples focus on different applications - pipe clearance and dental carrie prevention - and demonstrate the underlying conclusion that adaptive and persister mechanism provide protection for different challenges and are thus not redundant systems and each may require specific treatment plans.


Rapid type-specific diagnosis of adenovirus type 4 infection using a hexon-based quantitative fluorogenic PCR.
A hexon-based fluorogenic polymerase chain reaction (PCR) assay utilizing the 5'-nuclease activity of DNA Taqpolymerase was developed as a rapid and type-specific diagnostic system for adenovirus type 4 (Ad4) detection and quantification. The assay consists of a pair of flanking primers and an internal fluorescence labeled probe that allows real time amplification to quantify the Ad4 virus. One out of 12 flanking primer pairs evaluated (combinations of three forward primers and four reverse primers) was found to be optimal for Ad4 virus detection that yielded background-free operation, i.e., no fluorescent signal generated by non-template controls. The assay was employed to detect Ad4 reference virus strain RI-67, Wyeth Ad4 vaccine strain and 71 different clinical Ad4 isolates from US military recruits used in this study with consistent sensitivity (lower detection limit) of 2-4 pfu per PCR reaction. The assay showed linear Ad4 detection with a dynamic range of greater than five logs (from 2-4 pfu/assay to greater than 10(5) pfu/assay). This Ad4-specific assay did not crossreact with representative members of Ad subgroups A, B, C, D and F at viral concentrations greater than 10(8) pfu/ml. It was also demonstrated that Ad4 viruses could be efficiently detected from throat swabs (71/72 specimens or 98.6% detection sensitivity) of infected patients by the Ad4-specific PCR. In general, there was a good correlation between PCR determined viral titers in throat swabs and time required to detect viral cytopathic effects (CPE) in cell culture. Evaluation of the simple Ad4 specific assay developed in this study could be used to provide a rapid clinically relevant diagnosis of Ad4 infections in patients with acute respiratory disease (ARD).


Low skeletal muscle mass and liver fibrosis in children with cerebral palsy.
The purpose of the study was to conduct a nutritional and metabolic assessment of children with cerebral palsy, including an investigation of liver status, body composition, and bone mineral density. In this cross-sectional study we included 22 children with cerebral palsy. By using ultrasound, transient elastography, dual x-ray absorptiometry (DXA) scan, blood samples, anthropometric measurements, and a three-day diet registration, the nutritional and metabolic status was evaluated. Liver fibrosis and steatosis were found in four patients (18.2%), all with severe motor impairments, low skeletal muscle mass, and epilepsy. All patients with liver involvement had normal liver-related blood samples. Decreased bone mineral density was found in 26.3%, and 91.0% had low skeletal muscle mass. Fat mass and muscle mass were significantly lower in the patients with severe motor impairments compared to the patients with less severe motor impairments. Within the children classified as 'underweight' or 'normal' according to body mass index, body fat determined by DXA scan was normal or high in 50% of these patients. This study is the first to report liver fibrosis and steatosis in children with cerebral palsy. Possible causes of liver fibrosis and/or steatosis are altered body composition with low skeletal muscle mass, decreased mobility and medical drug intake. Further investigations of liver involvement and risk factors are needed. • Children and adolescents with cerebral palsy are at risk of malnutrition and altered body composition, both of which can lead to fatty liver disease. • It is unknown whether children with cerebral palsy are at increased risk of metabolic disturbances such as fatty liver disease. • Altered body composition and low skeletal muscle mass, regardless of ambulation is present in 91% of the children with cerebral palsy. • Liver fibrosis and/or steatosis were found in 18.2% of the patients. Possible causes are altered body composition, decreased mobility and medical drug intake.


Retraction.
Foster WM, Adler KB, Crews AL, Potts EN, Fischer BM, Voynow JA. MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac. Am J Physiol Lung Cell Mol Physiol 299: L345–L352; doi: 10.1152/ajplung.00067.2010. The authors have discovered that Figs. 1, 2, and 6 are not reliable. We offer our sincere apologies for the errors and for any inconvenience associated with the publication of the article. The paper is therefore being retracted by the American Physiological Society at the request of Dr. Voynow, and with the approval of the coauthors.


Effect of oral iron chelation therapy with deferiprone (L1) on the psychosocial status of thalassaemia patients.
Beta-thalassemia requires life-long treatment, including regular blood transfusion and daily iron chelation by desferrioxamine, which places considerable burden on the social and psychological life of patients. It is expected that oral chelation therapy, which is easier to administer, would improve their psychosocial status. In this sutdy, interviews were conducted with a series of 44 patients recently placed on oral chelation therapy to evaluate their reactions to the new treatment. Eighty-six per cent of patients complied better with the oral chelation therapy. Fifty per cent of patients mentioned that relief from the desferrioxamine pump was the major improvement, while 47% felt psychologically better. Fifty per cent of patients noted improvements in their relationships, while 63% noted increased social activities. Evaluation of a larger sample of patients over a longer period of time is needed in order to confirm the favourable results obtained in this study.


Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction.
Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991-1993) were also examined. The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case-control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.


Obesity, arterial function and arterial structure - a systematic review and meta-analysis.
Obesity is an established risk factor for cardiovascular disease. The mechanisms by which obesity affects cardiovascular risk have not been fully elucidated. This paper reports a comprehensive systematic review and meta-analysis on obesity and two key aspects of vascular health using gold-standard non-invasive measures - arterial endothelial function (brachial flow-mediated dilatation) and subclinical atherosclerosis (carotid intima-media thickness). Electronic searches for 'Obesity and flow-mediated dilatation' and 'Obesity and intima-media thickness' were performed using Ovid Medline and Embase databases. A meta-analysis was undertaken for brachial flow-mediated dilatation and carotid intima-media thickness to obtain pooled estimates for adults with obesity and those with healthy weight. Of the 5,810 articles retrieved, 19 studies on flow-mediated dilatation and 19 studies on intima-media thickness were included. Meta-analysis demonstrated that obesity was associated with lower flow-mediated dilatation (-1.92 % [95% CI -2.92, -0.92], P = 0.0002) and greater carotid intima-media thickness (0.07 mm [95% CI 0.05, 0.08], P < 0.0001). Obesity is associated with poorer arterial endothelial function and increased subclinical atherosclerosis, consistent with these aspects of vascular health at least partially contributing to the increased risk of cardiovascular events in adults with obesity. These estimated effect sizes will enable vascular health benefits in response to weight loss treatment to be put in greater perspective, both in the research setting and potentially also clinical practice.


Multiple inflammatory prognostic factors in acute coronary syndromes: a prospective inception cohort study.
Inflammatory basis in pathopoiesis of coronary artery disease (CAD) have been demonstrated in recent decades. Elevated C-Reactive Protein (CRP) and leukocytosis were associated with an elevated risk for acute coronary syndrome (ACS). To evaluate the relationship between quantitative CRP and cardiac troponin I in conjunction with white blood cell (WBC) count and 30 days outcomes and treatment planning in patients with ACS. A concurrent inception cohort study was designed involving 200 patients as exposed and 200 patients as non exposed groups. We evaluated the relationship between baseline CRP and WBC count and cardiac troponin I , other risk factors and biomarkers, angiographic and other para-clinical tests and clinical outcomes with ACS. Higher CRP and WBC count were associated with additional coronary care unite (CCU) admission days (P = 0.002), hospitalization days (P = 0.007), arrhythmia type (P = 0.007), receiving streptokinase (P = 0.001), angiographic findings (P = 0.003), final myocardial infarction versus unstable angina (P = 0.001), date of complication (P = 0.001) and the date of cardiopulmonary resuscitation (if incident) (P = 0.015). In a multivariate Cox proportional hazard model high CRP and WBC count remained strong predictor of mortality (P = 0.028), angiography findings (three Vessel disease (3VD) and left main (LM) disease) (P = 0.001), and readmission in CCU (P = 0.002). A cardiac troponin I above 0.1 microg/lit was considered elevated. Elevated troponin level, demonstrated a significant relationship with MI incidence between two groups (P = 0.001) (89% in troponin positive group versus 11% in troponin less than 0.1 microg/lit). Inflammatory markers including, CRP and WBC count can be used to predict mortality, readmission, 3VD and LM disease in patients with ACS. In a Cox Proportional Hazard Model cardiac troponin above 0.1 microg/lit was significant predictors of MI (P = 0.003) and CPR (P = 0.044) at 30 days follow up period.


A review on the phytochemical and pharmacological properties of Hyptis suaveolens (L.) Poit.
Plants are the repository of variable number of valuable secondary metabolites that bears pharmacognostic and pharmacological implications having potentiality to emerge as super drugs in future. In-vivo production of these metabolites is influenced by the biotic and abiotic stresses resulting in continuous accumulation of diverse phytochemicals and their derivatives that can be useful in designing and developing potential drugs for future. The aim of the present study is to review the existence of medicinally important secondary metabolites and possible pharmacological and pharmacognostic importance of under-explored weed plant species Hyptis suaveolens (L.) Poit., to explore the potentiality of the plant for developing and designing the drugs for future. Hyptis suaveolens belonging to family Lamiaceae is the rich source of medicinally important phytochemicals like essential oils, tannins, saponins, phenols, flavonoids, terpenoids, alkaloids, and sterols. One or many of these compounds have antioxidative, anti-inflammatory, antispasmodic, anti-septic, anti-cancer, anti-ulcer, antimicrobial, antibacterial, antiviral, antifungal, anti-diabetic, anti-fertility, diaphoretics, anticutaneous, anticatarrhal, antirheumatic, anti-ulcer, gastroprotective, immunomodulatory, analgesic, and antiviral activity. Hyptis suaveolens contains unique terpenoid metabolites like suaveolic acid, suaveolol, methyl suaveolate, beta-sitosterol, ursolic acid, and phenolic compound like rosamarinic acid, methyl rosamarinate that have potentiality to substitute the traditional drugs as therapeutic agent against the resistant and newly emerged bacterial and viral pathogens. Pentacyclic triterpenoid, ursolic acid have been reported to have effective antiviral response against the SARS-CoV2 responsible for the present COVID-19 pandemic and HIV virus for which no effective vaccines are available till date. Ursolic acid has the ability to modulate the activity of main protease (Mpro) that is essential for processing of SARS-CoV2 replicase-transcriptase machinery needed for viral replication and particle assembly.


Theoretical design of a new family of two-dimensional topological insulators.
A new family of two-dimensional topological insulator, hydrogenated monolayer Pb2XY (X = Ga/In, Y = Sb/Bi), has been predicted using first-principles density functional theory. The electronic bulk band gap of the proposed systems can be induced in the presence of a spin-orbit coupling effect and its highest value (0.25 eV) was observed in the hydrogenated monolayer Pb2GaBi, which is suitable for practical application. Our simulation study points out that the nanoribbons derived from this new family harbor gapless edge channels. The non-trivial topological nature was further confirmed by calculating the Z2 topological invariant. These novel systems provide a new platform for topological phenomena observation and spintronic applications.


Small intestinal glucose transport. Proximal-distal kinetic gradients.
Proximal and distal small intestinal segments of the rat were perfused in situ at two different rates with isotonic solutions containing glucose in concentrations ranging from 25 to 600 mg/100 ml. Absorption was measured as glucose disappearance rate from the lumen. Glucose absorption had not previously been studied at intraluminal concentrations above and below blood glucose. Absorption was more rapid from the proximal segment. In both segments absorption was independent of perfusion rate and of whether glucose was analyzed by counting (14)C or by the Somogyi method. The latter finding suggests that of the unidirectional fluxes, flux out of the bowel is much greater than flux into the bowel. In contrast to the findings in previous studies neither segment showed rate-limiting kinetics, and the Michaelis-Menten analysis was not applicable. The form of the curve depicting absorption rate in relation to concentration differed between the two segments. At the higher concentrations absorption rate continued to increase much more rapidly in the proximal than in the distal segment. The observations could not be explained by known mechanisms of glucose transport and illustrate the difficulties of achieving biochemically and physiologically meaningful in vivo studies of intestinal absorption.


The sarcoplasmic-endoplasmic reticulum Ca2+ ATPase 2b regulates the Ca2+ transients elicited by P2Y2 activation in PC Cl3 thyroid cells.
In PC Cl3 cells, a continuous, fully differentiated rat thyroid cell line, P2Y(2) purinoceptor activation provoked a transient increase of [Ca(2+)](i), followed by a decreasing sustained phase. The alpha and beta1 protein kinase C (PKC) inhibitor Gö6976 decreased the rate of decrement to the basal [Ca(2+)](i) level and increased the peak of Ca(2+) entry of the P2Y(2)-provoked Ca(2+)transients. These effects of Gö 6976 were not caused by an increased permeability of the plasma membrane, since the Mn(2+) and Ba(2+) uptake were not changed by Gö 6976. Similarly, the Na(+)/Ca(2+) exchanger was not implicated, since the rate of decrement to the basal [Ca(2+)](i) level was equally decreased in physiological and Na(+)-free buffers, in the presence of Gö 6976. On the contrary, the activity of the sarcoplasmic-endoplasmic reticulum Ca(2+)ATPase (SERCA) 2b was profoundly affected by Gö 6976 since the drug was able to completely inhibit the stimulation of the SERCA 2b activity elicited by P2-purinergic agonists. Finally, the PKC activator phorbol myristate acetate had effects opposite to Gö 6976, in that it markedly increased the rate of decrement to the basal [Ca(2+)](i) level after P2Y(2) stimulation and also increased the activity of SERCA 2b. These results suggest that SERCA 2b plays a role in regulating the sustained phase of Ca(2+) transients caused by P2Y(2) stimulation.


Ultrasonographic evaluation of entheses in patients with spondyloarthritis: a systematic literature review.
Enthesitis represents a characteristic features of spondyloarthritis (SpA) and, in the context of the early management of the disease, its reliable assessment has emerged as a central issue. Musculoskeletal ultrasonography (US) has proven to be of value in the assessment of peripheral entheses. Our aim was to systematically review the literature from 2010 to 2013 in order to summarise the evidence on the evaluation of entheses by US in patients with diagnosed or suspected SpA. PubMed and Embase were searched developing a search strategy based on terms related to SpA and US. The target population were patients with SpA or suspected SpA, the intervention was entheseal US, the outcomes were the prevalence of US abnormalities, the reliability, the diagnostic accuracy, the sensitivity to change. The possible comparators were clinical evaluation and other imaging techniques. Cohort studies (cross-sectional or longitudinal), case-control studies, diagnostic accuracy studies, systematic literature reviews and meta-analyses were eligible for inclusion. Out of 3368 retrieved references, 34 papers were finally included. 22 of which reported information on the prevalence of US findings, yielding highly variable results. US was sufficiently reliable, as reported in 6 papers. A minority of studies reported data on sensitivity to change, which was good, and on the application of US for differential diagnosis and diagnosis of SpA, thus demonstrating the value of US also in this context. US confirms its validity and reliability in the assessment of entheseal involvement in patients with SpA. Further application in the help of diagnosis will be provided by future research.


Molecular-cytogenetic analysis of Aegilops triuncialis and identification of its chromosomes in the background of wheat.
Species belonging to the genus Aegilops L. are an important source of genetic material for expanding genetic variability of wheat. Ae. triuncialis is an allotetraploid in this genus which was originated from hybridization of Ae. umbellulata and Ae. markgrafii (Greuter) Hammer. Although the Ae. triuncialis karyotype was thoroughly examined by conventional chromosome staining and Giemsa C-banding, it is still poorly characterized using FISH markers. The objective of this study was to test the fluorescence in situ hybridization (FISH) patterns of Ae. triuncialis (2n = 4x = 28, C(t)C(t)U(t)U(t)) chromosomes using different repetitive sequences and to compare the produced patterns to the chromosomes of its diploid ancestors, with the aim of establishing a generalized Ae. triuncialis idiogram and detection of Aegilops chromosomes in the background of wheat. The probes pSc119.2-1, pTa535-1, pAs1-1, (CTT)10 and the 45S rDNA clone from wheat (pTa71) were hybridized to chromosomes of Ae. triuncialis and compared with its diploid progenitors (Ae. umbellulata Zhuk., 2n = 2x = 14, UU and Ae. markgrafii (Greuter) Hammer, 2n = 2x = 14, CC) and Ae. cylindrica Host. (2n = 4x = 28, D(c)D(c)C(c)C(c)), another tetraploid species containing the C-genome. Ae. cylindrica was further analyzed by genomic in situ hybridization (GISH) using C genome probe in order to identify any possible translocation. In general, FISH patterns of the U(t)- and C(t)-genome chromosomes of Ae. triuncialis were similar to those of U- and C-genome chromosomes of the diploid progenitor species Ae. umbellulata and Ae. markgrafii respectively, although some differences were observed. Two major 45S rDNA loci were revealed in the short arm of chromosomes A and C, of the C(t) genome which correspond to homoeologous groups 1 and 5 respectively. Minor 45S rDNA loci were mapped on the short arm of chromosomes 1U(t) and 5U(t). GISH analysis revealed three different non-reciprocal homologous or heterologous translocations between C(c) and D(c) chromosomes in all studied accessions of Ae. cylindrica.


Does GDNF exert its neuroprotective effects on photoreceptors in the rd1 retina through the glial glutamate transporter GLAST?
We previously demonstrated that exogenous glial cell line-derived neurotrophic factor (GDNF) induces histological and functional protection of photoreceptors in the retinal degeneration (rd1) mouse model. The mechanisms underlying such neuroprotection remain elusive. In parallel to this work, we provided evidence for the occurrence of glutamate-mediated excitotoxic phenomena contributing to rod photoreceptor death in the rd1 retina in the companion paper. In the present study, we investigated whether, as demonstrated in other models, GDNF could exert its neuroprotective effect on photoreceptors through Müller glial cells (MGC) by promoting the expression of the glial L-glutamate/L-aspartate transporter (GLAST), an endogenous neuroprotective mechanism against glutamate-mediated excitotoxicity. Reverse transcription-polymerase chain reaction (RT-PCR) was used to compare the mRNA expression levels of GDNF receptors between rd1 and wild-type mouse retinas as well as between MGC and mixed retinal cell cultures. Recombinant GDNF was applied to pure MGC cultures, to rd1 retinal organ cultures and injected subretinally into rd1 mouse eyes. GLAST expression following GDNF treatment was measured by RT-PCR, immunoblotting and immunohistochemistry. Free glutamate and glutamine levels were quantified in rd1 retinas after GDNF or control treatment using an amino acid analyzer. mRNA expression studies of GDNF receptors, GFRalpha-1 and Ret, demonstrated that GDNF receptors were not exclusively expressed by the degenerating photoreceptor cells but mainly by MGC. Exogenous GDNF application to MGC cultures, rd1 mouse retinal explants and in vivo rd1 mouse retinas increased the expression of GLAST by 48% in retinal explants (p<0.005) and by 25% in vivo (p<0.0005). GLAST protein expression in MGC was particularly increased around degenerative photoreceptors. Free glutamate and glutamine levels in the rd1 retina were not significantly modified by exogenous GDNF. Our data suggest that, in the rd1 mouse retina, GDNF neuroprotective effect on photoreceptors can be mediated indirectly through the activation of MGC. We demonstrate that injection of recombinant GDNF enhances the expression of GLAST and more particularly around the degenerating photoreceptors. Since we failed to demonstrate that GDNF decreases free glutamate levels, we could not ascertain whether GDNF promoted photoreceptor-survival via an increase of glutamate uptake and, therefore, a change in glutamate distribution.


Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.
Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.


Ligand crowding at a nascent signal sequence.
We have systematically analyzed the molecular environment of the signal sequence of a growing secretory protein from Escherichia coli using a stage- and site-specific cross-linking approach. Immediately after emerging from the ribosome, the signal sequence of pOmpA is accessible to Ffh, the protein component of the bacterial signal recognition particle, and to SecA, but it remains attached to the surface of the ribosome via protein L23. These contacts are lost upon further growth of the nascent chain, which brings the signal sequence into sole proximity to the chaperone Trigger factor (TF). In its absence, nascent pOmpA shows extended contacts with L23, and even long chains interact in these conditions proficiently with Ffh. Our results suggest that upon emergence from the ribosome, the signal sequence of an E. coli secretory protein gradually becomes sequestered by TF. Although TF thereby might control the accessibility of pOmpA's signal sequence to Ffh and SecA, it does not influence interaction of pOmpA with SecB.


Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans.
Aged individuals have increased morbidity and mortality following influenza and other viral infections, despite previous exposure or vaccination. Mouse and human studies suggest increased senescence and/or exhaustion of influenza virus-specific CD8 T cells with advanced age. However, neither the relationship between senescence and exhaustion nor the underlying transcriptional pathways leading to decreased function of influenza virus-specific cellular immunity in elderly humans are well-defined. Here, we demonstrate that increased percentages of CD8 T cells from aged individuals express CD57 and KLRG1, along with PD-1 and other inhibitory receptors, markers of senescence, or exhaustion, respectively. Expression of T-box transcription factors, T-bet and Eomes, were also increased in CD8 T cells from aged subjects and correlated closely with expression of CD57 and KLRG1. Influenza virus-specific CD8 T cells from aged individuals exhibited decreased functionality with corresponding increases in CD57, KLRG1, and T-bet, a molecular regulator of terminal differentiation. However, in contrast to total CD8 T cells, influenza virus-specific CD8 T cells had altered expression of inhibitory receptors, including lower PD-1, in aged compared with young subjects. Thus, our data suggest a prominent role for senescence and/or terminal differentiation for influenza virus-specific CD8 T cells in elderly subjects.


Application of Spontaneous Photon Emission in the Growth Ages and Varieties Screening of Fresh Chinese Herbal Medicines.
Ultraweak photon emission emitted by all living organisms has been confirmed to be a noninvasive indicator for their physiological and pathological characteristics. In this study, we investigated the characteristics of spontaneous photon emission (SPE) and the contents of specific active compounds of roots and flowers buds of several fresh Chinese herbal medicines (natural medicines) with different growth ages and varieties. The results revealed that the contents of specific active compounds from same species herbs with different growth ages and varieties were significantly different, and this difference could be reflected by their SPE. Because the contents of specific bioactive constituents in Chinese herbs are closely related to their quality and curative effect, the SPE measurement technique may contribute to the quality control of Chinese herbal medicine in the future.


Biopsy findings in acute pulmonary histoplasmosis: unusual histologic features in 4 cases mimicking lymphomatoid granulomatosis.
Most examples of pulmonary histoplasmosis, including histoplasmoma and chronic histoplasmosis, are characterized by typical necrotizing granulomatous inflammation. Only disseminated histoplasmosis is recognized as causing a different reaction which consists of ingestion of organisms by macrophages without granuloma formation. The histologic features of acute pulmonary histoplasmosis are not well described as this form of the disease is rarely biopsied. We report the biopsy findings in 4 cases of acute pulmonary histoplasmosis, which seem to be unique to this form of Histoplasma infection. There were 3 men and 1 woman who ranged in age from 40 to 68 years. All presented acutely with fever and other flu-like symptoms. Radiographically, a solitary nodular infiltrate was present in 3 and bilateral reticulonodular infiltrates in one. Histologically, all 4 biopsies showed a nodular parenchymal inflammatory infiltrate composed of lymphocytes and histiocytes filling alveolar spaces and expanding the adjacent interstitium. Areas of parenchymal necrosis were additionally present in 3 cases. Vasculitis composed of lymphocytes and histiocytes was present in all, and was striking in 3, resulting in a resemblance to grade 1 lymphomatoid granulomatosis (LYG). Tip-offs to the correct diagnosis were small necrotizing granulomas scattered within the lymphohistiocytic infiltrate (3 cases), scattered histiocyte aggregates, and a few multinucleated giant cells. The diagnosis was confirmed in all by the presence of Histoplasma yeasts in Grocott methenamine silver-stained slides. Acute pulmonary histoplasmosis may cause a lymphohistiocytic infiltrate with necrosis and vasculitis that is suggestive of LYG. This observation emphasizes the importance of examining special stains for organisms before diagnosing grade 1 LYG.


Effects of transcutaneous electric acupoint stimulation on drug use and responses to cue-induced craving: a pilot study.
Transcutaneous electric acupoint stimulation (TEAS) avoids the use of needles, and instead delivers a mild electric current at traditional acupoints. This technique has been used for treating heroin addiction, but has not been systematically tested for other drugs of abuse. This study aims to investigate the effects of TEAS on drug addiction. Volunteers who were either cocaine-dependent (n = 9) or cannabis-dependent (n = 11) but were not seeking treatment for their dependence participated in a within-subject, single-blind study. Treatment consisted of twice daily 30-minute sessions of TEAS or sham stimulation for 3.5 days. The active TEAS levels were individually adjusted to produce a distinct twitching response in the fingers, while the sham stimulation involved 2 minutes of stimulation at threshold levels followed by 28 minutes of stimulation below the detection levels. The participants recorded their drug use and drug cravings daily. At 1 hour after the last morning session of TEAS or sham stimulation, a cue-induced craving EEG evaluation was conducted. Event-related P300 potentials (ERPs) were recorded, sorted, and analyzed for specific image types (neutral objects, non-drug-related arousing images, or drug-related images). TEAS treatment did not significantly reduce the drug use or drug cravings, or significantly alter the ERP peak voltage or latency to peak response. However, the TEAS treatment did significantly modulate several self-reported measures of mood and anxiety. The results of this pilot study with a limited sample size suggest that the acupoint stimulation techniques and protocol used in this trial alone do not significantly reduce cravings for or use of cocaine or cannabis. The findings that TEAS modulates mood and anxiety suggest that TEAS could be used as an adjunct in a multimodal therapy program to treat cocaine and cannabis dependence if confirmed in a full randomized controlled clinical trial.