Biological motion during inflammation in humans.
Biological motion is a powerful perceptual cue that can reveal important information about the inner state of an individual. Activation of inflammatory processes likely leads to changes in gait, posture, and mobility patterns, but the specific characteristics of inflammation-related biological motion have not been characterized. The aim of this study was to determine the effect of inflammation on gait and motion in humans. Systemic inflammation was induced in 19 healthy volunteers with an intravenous injection of lipopolysaccharide (2 ng/kg body weight). Biological motion parameters (walking speed, stride length and time, arm, leg, head, and shoulder angles) were assessed during a walking paradigm and the timed-up-and-go test. Cytokine concentrations, body temperature, and sickness symptoms were measured. During inflammation, compared to placebo, participants exhibited shorter, slower, and wider strides, less arm extension, less knee flexion, and a more downward-tilting head while walking. They were also slower and took a shorter first step in the timed-up-and-go test. Higher interleukin-6 concentrations, stronger sickness symptoms, and lower body temperature predicted the inflammation-related alterations in biological motion. These findings show that biological motion contains clear information about the inflammatory status of an individual, and may be used by peers or artificial intelligence to recognize that someone is sick or contagious.


N-butyldeoxynojirimycin-mediated inhibition of human immunodeficiency virus entry correlates with changes in antibody recognition of the V1/V2 region of gp120.
The alpha-glucosidase inhibitor N-butyldeoxynojirimycin (NB-DNJ) is an inhibitor of human immunodeficiency virus (HIV) replication and HIV-induced syncytium formation in vitro. Although NB-DNJ appears to inhibit HIV entry at the level of post-CD4 binding (P.B. Fischer, M. Collin, G.B. Karlsson, W. James, T.D. Butters, S.J. Davis, S. Gordon, R.A. Dwek, and F.M. Platt, J. Virol. 69:5791-5797, 1995), the exact mechanism of action remains to be established. In this study we have examined the effect of NB-DNJ on the structure of recombinant gp120 (rgpl20), expressed in CHO cells, by using a panel of 40 monoclonal antibodies. The levels of binding of antibodies to rgp120 produced in the presence [rgpl20(+)] and absence [rgpl20(-)] of NB-DNJ were compared by enzyme-linked immunosorbent assay and surface plasmon resonance (BIAcore; Pharmacia). The results showed an increase in the binding to rgp120(+) of antibodies directed against the C1 and C2 regions and a decrease in the binding of antibodies directed against the V1/V2 loops compared with antibody binding to rgpl20(-). A decrease in the binding to rgpl20(+) of antibodies directed against discontinuous epitopes was also observed. No differences were seen in the binding of antibodies directed against the crown of the V3 loop and the C4 region of gp120. Treatment of rgpl20 with alpha-glucosidases I and II had no effect on the differential binding observed, whereas treatment with sialidase abolished the differences seen in the binding of antibodies directed against the C1 and C2 regions of gp120. In addition to these findings, rgpl20(+) showed increased sensitivity to proteases released by CHO cells during expression, as well as to exogenous thrombin. Taken together, the data presented in this paper suggest that production of gp120 in the presence of NB-DNJ affects the conformation of the Vl/V2 loops of gpl20, as well as the overall charge of the C1 and C2 regions. These effects may play a role in the previously described NB-DNJ-mediated inhibition of HIV entry at the level of post-CD4 binding.


The effects of low temperatures on intracellular transport of newly synthesized albumin and haptoglobin in rat hepatocytes.
Isolated rat hepatocytes were pulse-labelled with [35S]methionine at 37 degrees C and subsequently incubated (chased) for different periods of time at different temperatures (37-16 degrees C). The time courses for the secretion of [35S]methionine-labelled albumin and haptoglobin were determined by quantitative immunoprecipitation of the detergent-solubilized cells and of the chase media. Both proteins appeared in the chase medium only after a lag period, the length of which increased markedly with decreasing chase temperature: from about 10 and 20 min at 37 degrees C to about 60 and 120 min at 20 degrees C for albumin and haptoglobin respectively. The rates at which the proteins were externalized after the lag period were also strongly affected by temperature, the half-time for secretion being 20 min at 37 degrees C and 200 min at 20 degrees C for albumin; at 16 degrees C no secretion could be detected after incubation for 270 min. Analysis by subcellular fractionation showed that part of the lag occurred in the endoplasmic reticulum and that the rate of transfer to the Golgi complex was very temperature-dependent. The maximum amount of the two pulse-labelled proteins in Golgi fractions prepared from cells after different times of chase decreased with decreasing incubation temperatures, indicating that the transport from the Golgi complex to the cell surface was less affected by low temperatures than was the transport from the endoplasmic reticulum to the Golgi complex.


Half versus full vacuum suction drainage after modified radical mastectomy for breast cancer- a prospective randomized clinical trial[ISRCTN24484328].
Suction drains are routinely used after modified radical mastectomy and are an important factor contributing to increased hospital stay as the patients are often discharged only after their removal. Amongst various factors that influence the amount of postoperative drainage, the negative suction pressure applied to the drain has been reported to be of great significance. While a high negative suction pressure is expected to drain the collection and reduce the dead space promptly, it may also prevent the leaking lymphatics from closing and lead to increased drainage from the wound. Against this background a prospective randomized clinical study was conducted to compare the amount and duration of drainage between a half negative suction and full vacuum suction drainage in patients following modified radical mastectomy. The associated postoperative morbidity was also compared between the two groups. 85 FNAC (fine needle aspiration cytology) proven cases of locally advanced breast cancer were randomized. (Using randomly ordered sealed envelops, which were opened immediately before the closure of the wound) in to 50 patients with full vacuum suction (pressure = 700 g/m2) and 35 cases in to half vacuum suction drainage (pressure = 350 g/m2) groups. The two groups were comparable in respect of age, weight, and technique of operation and extent of axillary dissection. Surgery was performed by the same surgical team comprising of five surgeons (two senior and three resident surgeons) using a standardized technique with electrocautery. External compression dressing was provided over the axilla for first 48 hrs and following that patients were encouraged to do active and passive shoulder exercises. The outcomes measured were postoperative morbidity and the length of hospital stay. Statistical methods used: Descriptive studies were performed with SPSS version 10 and group characteristics were compared using student t-test. Half vacuum suction drains were removed earlier than the full suction vacuum suction drains. There was no significant difference in the incidence of seroma formation in the two groups and there was a significant reduction in the total hospital stay in patients with half vacuum suction drainage systems as compared to the full suction drainage group (p < 0.001) without any added morbidity. Half negative suction drains provide an effective compromise between no suction and full or high suction drainage after modified radical mastectomy by reducing the hospital stay and the post operative morbidity including post operative seromas.


Immunoassay detection of drugs in racing horses. IX. Detection of detomidine in equine blood and urine by radioimmunoassay.
Detomidine is a potent non-narcotic sedative agent which is currently in the process of being approved for veterinary clinical use in the United States. Since no effective screening method in horses is available for detomidine, we have developed an 125I radioimmunoassay for detomidine in equine blood and urine as part of a panel of tests for illegal drugs in performance horses. Our 125I radioimmunoassay has an I-50 for detomidine of approximately 2 ng/ml. Our assay shows limited cross-reactivity with the pharmacodynamically similar xylazine, but does not cross-react with acepromazine, epinephrine, haloperidol or promazine. The plasma kinetic data from clinical (greater than or equal to 5 mg/horse) as well as sub-clinical doses indicate first-order elimination in a dose-dependent manner. Within the first 30 minutes after intravenous (IV) administration of 30 mg/horse, plasma levels peak at approximately 20 ng/ml and then decline with an apparent plasma half-life of 25 minutes. Diuresis can occur with administration of clinical doses of detomidine and this effect was accounted for in the analysis of urine samples. Using this method, administration of 30 mg/horse can be readily detected in equine urine for up to 8 hours after IV injection. Additionally, doses as low as 0.5 mg/horse can be detected for short periods of time in blood and urine with use of this assay. Utilization of this assay by research scientists and forensic analysts will allow for the establishment of proper guidelines and controls regarding detomidine administration to performance horses and assurance of compliance with these guidelines.


Directional Limits on Persistent Gravitational Waves from Advanced LIGO's First Observing Run.
We employ gravitational-wave radiometry to map the stochastic gravitational wave background expected from a variety of contributing mechanisms and test the assumption of isotropy using data from the Advanced Laser Interferometer Gravitational Wave Observatory's (aLIGO) first observing run. We also search for persistent gravitational waves from point sources with only minimal assumptions over the 20-1726 Hz frequency band. Finding no evidence of gravitational waves from either point sources or a stochastic background, we set limits at 90% confidence. For broadband point sources, we report upper limits on the gravitational wave energy flux per unit frequency in the range F_{α,Θ}(f)<(0.1-56)×10^{-8} erg cm^{-2} s^{-1} Hz^{-1}(f/25 Hz)^{α-1} depending on the sky location Θ and the spectral power index α. For extended sources, we report upper limits on the fractional gravitational wave energy density required to close the Universe of Ω(f,Θ)<(0.39-7.6)×10^{-8} sr^{-1}(f/25 Hz)^{α} depending on Θ and α. Directed searches for narrowband gravitational waves from astrophysically interesting objects (Scorpius X-1, Supernova 1987 A, and the Galactic Center) yield median frequency-dependent limits on strain amplitude of h_{0}<(6.7,5.5, and 7.0)×10^{-25}, respectively, at the most sensitive detector frequencies between 130-175 Hz. This represents a mean improvement of a factor of 2 across the band compared to previous searches of this kind for these sky locations, considering the different quantities of strain constrained in each case.


25th ANNIVERSARY OF CLONING BY SOMATIC-CELL NUCLEAR TRANSFER Twenty-five years after Dolly: how far have we come?
For more than a century, the scientific consensus stated that a nucleus from a terminally differentiated cell would not be able to control the development of offspring. This theory was refuted by the birth of Dolly, the first animal generated by nuclear transfer using an adult somatic cell as a nuclear donor. Following this paradigm shift, a wide variety of animals has been cloned using somatic cell nuclear transfer. Coupled with modern genome engineering technology, somatic cell nuclear transfer has become the method of choice for the generation of genetically modified farm animals. This has opened new opportunities to study the function of genes and has led to the establishment of animal models for a variety of human conditions and diseases or to improve the health of livestock animals.


An extended case study on the phenomenology of sequence-space synesthesia.
Investigation of synesthesia phenomenology in adults is needed to constrain accounts of developmental trajectories of this trait. We report an extended phenomenological investigation of sequence-space synesthesia in a single case (AB). We used the Elicitation Interview (EI) method to facilitate repeated exploration of AB's synesthetic experience. During an EI the subject's attention is selectively guided by the interviewer in order to reveal precise details about the experience. Detailed analysis of the resulting 9 h of interview transcripts provided a comprehensive description of AB's synesthetic experience, including several novel observations. For example, we describe a specific spatial reference frame (a "mental room") in which AB's concurrents occur, and which overlays his perception of the real world (the "physical room"). AB is able to switch his attention voluntarily between this mental room and the physical room. Exemplifying the EI method, some of our observations were previously unknown even to AB. For example, AB initially reported to experience concurrents following visual presentation, yet we determined that in the majority of cases the concurrent followed an internal verbalization of the inducer, indicating an auditory component to sequence-space synesthesia. This finding is congruent with typical rehearsal of inducer sequences during development, implicating cross-modal interactions between auditory and visual systems in the genesis of this synesthetic form. To our knowledge, this paper describes the first application of an EI to synesthesia, and the first systematic longitudinal investigation of the first-person experience of synesthesia since the re-emergence of interest in this topic in the 1980's. These descriptions move beyond rudimentary graphical or spatial representations of the synesthetic spatial form, thereby providing new targets for neurobehavioral analysis.


The Munich Wrist Questionnaire (MWQ) - development and validation of a new patient-reported outcome measurement tool for wrist disorders.
Although self-assessment questionnaires for the wrist joint are numerous, most validation studies focus on a specific pathology and patient collectives. In addition the available questionnaires focus on subjective parameters such as pain, usual and specific activities but the range of motion (ROM) as an essential objective parameter in wrist disorders is rarely considered. Therefore the purpose of the presented study was to develop and validate a new universally applicable self-assessment score, the Munich Wrist Questionnaire (MWQ), which allows for the assessment of subjective as well as objective parameters of the wrist joint. The MWQ consists of 16 items addressing three domains: pain, work and activities of daily living and wrist function including range of motion and grip strength. In a prospective clinical study validity, reliability and responsiveness of the MWQ of physical active patients were evaluated. Validation study included 100 patients (mean age 41 years, SD 16.3 years; range, 18-77 years). Test-retest reliability was substantial, with intraclass correlation coefficients ranging from 0.75 to 0.83 for the three domains. Construct validity and responsiveness were confirmed by correlation coefficients of at least 0.86 for construct validity and for responsiveness ranging from 0.61 to 0.65. The MWQ presents a valid and reliable instrument for a qualitative self-assessment of subjective and objective parameters (e.g. range of motion) of the wrist joint. Quantitative measurement of wrist function may not longer be limited to specific wrist disorders or patient groups. The MWQ seems to allow for a broad application in clinical research and may facilitate the comparison of treatment results in wrist disorders.


Disease awareness advertising - women's intentions following exposure.
In Australia, where direct to consumer advertising of prescription medicines is prohibited, pharmaceutical companies can sponsor disease awareness advertising targeting consumers. This study examined the impact of disease awareness advertising exposure on older women's reported behavioural intentions. Women were approached in a shopping centre and randomly assigned mock advertisements for two health conditions. Disease information and sponsors were manipulated. Two hundred and forty-one women responded to 466 advertisements. Almost half reported an intention to ask their doctor for a prescription or referral as a result of seeing the advertisement, but more reported they would talk to their doctor and ask about treatments and tests. Participants were more likely to report an intention to ask for prescriptions if they perceived the health condition to be severe and themselves susceptible or if they had viewed advertisements containing limited information on the disease. Disease awareness advertising may stimulate demand for prescription medicine products. This has serious implications for general practitioners and regulators.


Does Walkability Contribute to Geographic Variation in Psychosocial Distress? A Spatial Analysis of 91,142 Members of the 45 and Up Study in Sydney, Australia.
Walkability describes the capacity of the built environment to promote walking, and has been proposed as a potential focus for community-level mental health planning. We evaluated this possibility by examining the contribution of area-level walkability to variation in psychosocial distress in a population cohort at spatial scales comparable to those used for regional planning in Sydney, Australia. Data on psychosocial distress were analysed for 91,142 respondents to the 45 and Up Study baseline survey between January 2006 and April 2009. We fit conditional auto regression models at the postal area level to obtain smoothed "disease maps" for psychosocial distress, and assess its association with area-level walkability after adjusting for individual- and area-level factors. Prevalence of psychosocial distress was 7.8%; similar for low (7.9%), low-medium (7.9%), medium-high (8.0%), and high (7.4%) walkability areas; and decreased with reducing postal area socioeconomic disadvantage: 12.2% (most), 9.3%, 7.5%, 5.9%, and 4.7% (least). Unadjusted disease maps indicated strong geographic clustering of psychosocial distress with 99.0% of excess prevalence due to unobserved and spatially structured factors, which was reduced to 55.3% in fully adjusted maps. Spatial and unstructured variance decreased by 97.3% and 39.8% after adjusting for individual-level factors, and another 2.3% and 4.2% with the inclusions of area-level factors. Excess prevalence of psychosocial distress in postal areas was attenuated in adjusted models but remained spatially structured. Postal area prevalence of high psychosocial distress is geographically clustered in Sydney, but is unrelated to postal area walkability. Area-level socioeconomic disadvantage makes a small contribution to this spatial structure; however, community-level mental health planning will likely deliver greatest benefits by focusing on individual-level contributors to disease burden and inequality associated with psychosocial distress.


What a difference a methyl group makes - probing choline-urea molecular interactions through urea structure modification.
There is a lack of fundamental knowledge on deep eutectic solvents, even for the most extensively studied mixtures, such as the mixture of cholinium chloride and urea, which prevents a judicious choice of components to prepare new solvents. The objective of this work is to study and understand the fundamental interactions between cholinium chloride and urea that lead to the experimentally observed melting temperature depression. To do so, the structure of urea was strategically and progressively modified, in order to block certain interaction centres, and the solid-liquid equilibrium data of each new binary system was experimentally measured. Using this approach, it was concluded that the most important interaction between cholinium chloride and urea occurs through hydrogen bonding between the chloride anion and the amine groups. Any blockage of these groups severely hampers the melting point depression effect. Raman spectroscopy and DFT calculations were utilized to study in more detail this hydrogen bonding and its nuances.


Immediate and Short-term Effects of Thoracic Spine Manipulation in Patients With Cervical Radiculopathy: A Randomized Controlled Trial.
Thoracic spine thrust manipulation has been shown to improve patient-rated outcomes for individuals with neck pain. However, there is limited evidence of its effectiveness in patients with cervical radiculopathy. To compare the immediate and short-term effects of thoracic manipulation to those of a sham thoracic manipulation in patients with cervical radiculopathy. In this multicenter randomized controlled trial, participants with cervical radiculopathy were randomized to receive either manipulation (n = 22) or sham manipulation (n = 21) of the thoracic spine. Outcomes were measured at baseline, immediately after treatment, and at a follow-up 48 to 72 hours after manipulation. A repeated-measures analysis of variance was used to analyze neck and upper extremity pain (numeric pain-rating scale), disability (Neck Disability Index), cervical range of motion (ROM), and endurance (deep neck flexor endurance test). The chi-square test was used to analyze changes in neck and upper extremity pain, centralization of symptoms, and beliefs about receiving the active manipulation treatment using a global rating of change scale. Neck and upper extremity pain, cervical ROM, disability, and deep neck flexor endurance all showed significant interactions between group and time (P<.01). Immediately after treatment and at the 48-to-72-hour follow-up, the manipulation group had lower neck pain (P<.01), better cervical ROM (P<.01), lower disability (P<.01), and better deep neck flexor endurance (P = .02) compared to the sham manipulation group. The manipulation group had moderate to large effect-size changes over time. No between-group differences for upper extremity pain were found immediately following the intervention (P = .34) and at 48 to 72 hours after the intervention (P = .18). At 48 to 72 hours after treatment, a greater proportion of participants in the manipulation group reported improvement (global rating of change scale score of 4 or greater) in neck and upper extremity symptoms (P<.01), centralization of symptoms (P<.01), and beliefs about receiving an active manipulation (P = .01) compared to the sham manipulation group. One session of thoracic manipulation resulted in improvements in pain, disability, cervical ROM, and deep neck flexor endurance in patients with cervical radiculopathy. Patients treated with manipulation were more likely to report at least moderate change in their neck and upper extremity symptoms up to 48 to 72 hours following treatment. Therapy, level 2. J Orthop Sports Phys Ther 2019;49(5):299-309. doi:10.2519/jospt.2019.8150.


Anti-angiogenic effect of high doses of ascorbic acid.
Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA.


Childbearing, breastfeeding, other reproductive factors and the subsequent risk of hospitalization for gallbladder disease.
While parous women are known to be at an increased risk of gallbladder disease, little is known about the effects of other reproductive factors such as breastfeeding, age at menarche and age at menopause. The Million Women Study is a prospective cohort study of 1.3 million middle-aged women in England and Scotland recruited from 1996 to 2001. Participants were followed-up by record-linkage for a mean of 6.1 years for admissions to hospital. The adjusted relative risk of hospital admission for cholelithiasis, cholecystitis or cholecystectomy according to parity, breastfeeding, age at menarche and age at menopause was examined. During follow-up of 1 289 029 eligible women, 25 111 were admitted to hospital for gallbladder disease, of whom 21 735 (87%) had a cholecystectomy. The hospital admission rate over 5 years for gallbladder disease was 1.6/100 women and for cholecystectomy was 1.4/100 women. The adjusted relative risk of gallbladder disease increased with increasing parity by 8% (95% CI 7-9%, P < 0.0001) for each birth. Among women of a given parity, breastfeeding reduced the risk of gallbladder disease, the relative risk decreasing by 7% (95% CI 5-10%, P < 0.0001) per year of breastfeeding. Women's age of menarche and age at menopause did not alter the risk of gallbladder disease (P = 0.4 and P = 0.3, respectively for linear trend). Hospitalization for gallbladder disease is common in middle-aged women. The risk increases the more children a woman has had, but decreases the longer she breastfeeds. The increased risk of gallbladder disease associated with having children can be offset by breastfeeding.


Paradoxical use of frontalis muscle and the possible role of botulinum a toxin in permanent motor relearning.
To report 7 patients with paradoxical use of the frontalis muscle despite postsurgical correction of ptosis with good postoperative eyelid position. Successful treatment with botulinum A toxin facilitated motor relearning and cessation of muscle contraction. Interventional case series. Seven patients, in 2 eye-plastic clinics, who underwent successful surgical correction of upper eyelid ptosis. Review of clinical history, clinical photographs, treatment, and follow-up. Frontalis muscle contraction and upper eyelid position. Patients underwent successful surgical correction of ptosis but continued using the frontalis muscle despite good eyelid position postoperatively. Frontalis contraction ceased spontaneously in 2 patients, but required botulinum A toxin injection in 5. The effects of a single treatment of botulinum A toxin lasted from 3 months to 2 years, longer than the expected effect of the toxin. Patients with long-standing eyelid ptosis may paradoxically continue utilizing the frontalis after successful surgical correction and despite good postoperative eyelid position. Cessation of frontalis contraction can be achieved with a single injection of botulinum A toxin. We hypothesize that chemodenervation, achieved with the toxin, may influence the central nervous system to relearn the set point for muscle contraction and may be associated with permanent motor relearning. Spontaneous resolution of muscle contraction can occur in the first months after surgery.


Overview of indications for nipple sparing mastectomy.
The introduction of more targeted systemic therapies, better screening modalities with earlier diagnosis and dramatically improved reconstructive techniques has allowed more minimally invasive approaches to breast surgery. The recent introduction of nipple sparing mastectomy (NSM) has dramatically improved the cosmetic outcomes and quality of life (QoL) for patients undergoing mastectomy. This technique involves preservation of both the skin envelope including the nipple areolar complex commonly through a barely visible inframammary skin incision followed by immediate breast reconstruction. An ideal candidate includes women with small breasts, absence of ptosis, low BMI and not actively smoking. High risk patients include those with radiation treatment, active smokers, macromastia, high BMI >30 kg/m2, grade 2 or 3 ptosis and active smokers. There are several new techniques to approach complex high risk patients which have expanded the candidates for NSM.


Application of a depositional facies model to an acid mine drainage site.
Lower Red Eyes is an acid mine drainage site in Pennsylvania where low-pH Fe(II) oxidation has created a large, terraced iron mound downstream of an anoxic, acidic, metal-rich spring. Aqueous chemistry, mineral precipitates, microbial communities, and laboratory-based Fe(II) oxidation rates for this site were analyzed in the context of a depositional facies model. Depositional facies were defined as pools, terraces, or microterracettes based on cm-scale sediment morphology, irrespective of the distance downstream from the spring. The sediments were composed entirely of Fe precipitates and cemented organic matter. The Fe precipitates were identified as schwertmannite at all locations, regardless of facies. Microbial composition was studied with fluorescence in situ hybridization (FISH) and transitioned from a microaerophilic, Euglena-dominated community at the spring, to a Betaproteobacteria (primarily Ferrovum spp.)-dominated community at the upstream end of the iron mound, to a Gammaproteobacteria (primarily Acidithiobacillus)-dominated community at the downstream end of the iron mound. Microbial community structure was more strongly correlated with pH and geochemical conditions than depositional facies. Intact pieces of terrace and pool sediments from upstream and downstream locations were used in flowthrough laboratory reactors to measure the rate and extent of low-pH Fe(II) oxidation. No change in Fe(II) concentration was observed with (60)Co-irradiated sediments or with no-sediment controls, indicating that abiotic Fe(II) oxidation was negligible. Upstream sediments attained lower effluent Fe(II) concentrations compared to downstream sediments, regardless of depositional facies.


A prospective population-based cohort study of lactation and cardiovascular disease mortality: the HUNT study.
Recent studies suggest that lactation has long-term effects on risk for cardiovascular disease in women, but the effects on cardiovascular mortality are less well known. In a Norwegian population-based prospective cohort study, we studied the association of lifetime duration of lactation with cardiovascular mortality in 21,889 women aged 30 to 85 years who attended the second Nord-Trøndelag Health Survey (HUNT2) in 1995-1997. The cohort was followed for mortality through 2010 by a linkage with the Cause of Death Registry. Adjusted hazard ratios (HR) for death from all causes and cardiovascular disease were calculated using Cox regression. During follow-up, 1,246 women died from cardiovascular disease. Parous women younger than 65 years who had never lactated had a higher cardiovascular mortality than the reference group of women who had lactated 24 months or more (HR 2.77, 95% confidence interval [CI]: 1.28, 5.99). There was some evidence of a U-shaped association, where women who reported lactating 7-12 months had a HR of 0.55 (95% CI: 0.27, 1.09). No clear associations were observed among women 65 years or older. Excess cardiovascular mortality rates were observed among parous women younger than 65 years who had never lactated. These findings support the hypothesis that lactation may have long-term influences on maternal cardiovascular health.


Review Article: blood-brain barrier in falciparum malaria.
Plasmodium falciparum malaria is the most important parasitic disease infecting the central nervous system of humans worldwide. The pathogenesis of the neurological complications of falciparum malaria remains unclear. In particular, how do asexual parasites confined to the vascular space of the brain cause neuronal impairment? The evidence for a breakdown in the blood-brain barrier (BBB) is conflicting. In some animal models of malaria, there is evidence of breakdown of the BBB, but the data from humans suggests the BBB is mildly impaired only, with few morphological changes. Whether these changes in the BBB are sufficient to account for the neurological complications remains to be determined.


Do women with ovaries of polycystic morphology without any other features of PCOS benefit from short-term metformin co-treatment during IVF? A double-blind, placebo-controlled, randomized trial.
Women with ovaries of polycystic morphology (PCO), without any other features of polycystic ovary syndrome (PCOS), respond similarly to women with PCOS when stimulated with exogenous gonadotrophins, and both groups share various endocrinological disturbances underlying their pathology. In women with PCOS, metformin co-treatment during IVF has been shown to increase pregnancy rates and reduce the risk of ovarian hyperstimulation syndrome (OHSS). The aim of this study was to investigate whether metformin co-treatment before and during IVF can also increase the live birth rate (LBR) and lower severe OHSS rates for women with PCO, but no other manifestations of PCOS. This study was a double-blind, multi-centre, randomized, placebo-controlled trial. The study population included 134 women with ovulatory PCO (and no evidence of clinical or biochemical hyperandrogenism) undergoing IVF treatment at three tertiary referral IVF units. The primary outcome was LBR. In total, 134 women were randomized, 69 to metformin and 65 to placebo. There were no statistically significant differences between the two groups in baseline characteristics. With regard to IVF outcome, no significant improvements were found in the metformin group when compared with the placebo group. In particular, there was no difference between the groups in rates of live birth [metformin n = 27 (39.1%), placebo n = 30 (46.2), (95% confidence interval 0.38, 1.49, odds ratio = 0.75)], clinical pregnancy [metformin n = 29 (42.0%), placebo n = 33 (50.8%)] or severe OHSS [metformin n = 6 (8.7%), placebo n = 5 (7.7%)]. There appears to be no benefit in metformin co-treatment before and during IVF in women with PCO without any other features of PCOS. Clinical Trials.gov: NCT01046032.


Classifying RNA-binding proteins based on electrostatic properties.
Protein structure can provide new insight into the biological function of a protein and can enable the design of better experiments to learn its biological roles. Moreover, deciphering the interactions of a protein with other molecules can contribute to the understanding of the protein's function within cellular processes. In this study, we apply a machine learning approach for classifying RNA-binding proteins based on their three-dimensional structures. The method is based on characterizing unique properties of electrostatic patches on the protein surface. Using an ensemble of general protein features and specific properties extracted from the electrostatic patches, we have trained a support vector machine (SVM) to distinguish RNA-binding proteins from other positively charged proteins that do not bind nucleic acids. Specifically, the method was applied on proteins possessing the RNA recognition motif (RRM) and successfully classified RNA-binding proteins from RRM domains involved in protein-protein interactions. Overall the method achieves 88% accuracy in classifying RNA-binding proteins, yet it cannot distinguish RNA from DNA binding proteins. Nevertheless, by applying a multiclass SVM approach we were able to classify the RNA-binding proteins based on their RNA targets, specifically, whether they bind a ribosomal RNA (rRNA), a transfer RNA (tRNA), or messenger RNA (mRNA). Finally, we present here an innovative approach that does not rely on sequence or structural homology and could be applied to identify novel RNA-binding proteins with unique folds and/or binding motifs.


Walk to me when I smile, step back when I'm angry: emotional faces modulate whole-body approach-avoidance behaviors.
Facial expressions are potent social cues that can induce behavioral dispositions, such as approach-avoidance tendencies. We studied these tendencies by asking participants to make whole-body forward (approach) or backward (avoidance) steps on a force plate in response to the valence of social cues (happy or angry faces) under affect-congruent and incongruent mappings. Posturographic parameters of the steps related to automatic stimulus evaluation, step initiation (reaction time), and step execution were determined and analyzed as a function of stimulus valence and stimulus-response mapping. The main result was that participants needed more time to initiate a forward step towards an angry face than towards a smiling face (which is evidence of a congruency effect), but with backward steps, this difference failed to reach significance. We also found a reduction in spontaneous body sway prior to the step with the incongruent mapping. The results provide a crucial empirical link between theories of socially induced action tendencies and theories of postural control and suggest a motoric basis for socially guided motivated behavior.


Health condition of Afghan refugees residing in Iran in comparison to Germany: a systematic review of empirical studies.
The re-emerging dominance of the Taliban in Afghanistan in 2021 caused a new wave of Afghan refugees heading Iran and neighboring countries. Iran in the Middle East and Germany in Europe are two major host countries to the largest populations of Afghan refugees. In both countries, several studies have been done to assess the health condition of refugees. To systematically review the existing literature to identify similarities and differences of health conditions of Afghan refugees living in the two countries, and to synthesize evidence on the health status and health care access of these populations. Related electronic databases and grey literature of Iran and Germany on the health of Afghan refugees were scanned and searched up for the period 2000-2020. Key terms were formed by combining "Afghan refugees or immigrants or populations or asylum seekers", "Physical or mental health", "Healthcare service or access or use", "Iran or Germany". Empirical studies were considered if they contained samples of Afghan refugees with particular outcomes for Afghans. Results were categorized for both countries in the three main areas of physical health, mental health, and access/use of healthcare services. Nine hundred twenty-two documents were extracted, of which 75 full-texts were finally reviewed. 60 documents belonged to the health condition of Afghan refugees residing in Iran including 43 in physical health, 6 in mental health, 8 in healthcare access and use, and 3 in multiple aspects of health, and 15 belonged to Germany including 7 in physical health, 4 in mental health, 2 in healthcare access and use, and 2 in multiple aspects of health. A less explicit evaluation of the overall health condition of Afghan refugees was observable, particularly for Germany. While matches on the study subject exist for both countries, in comparison to Germany, we extracted more quantitative and qualitative health studies on Afghan refugees of the mentioned areas from Iran. German health studies were rare, less qualitative, and more on the health condition of diverse refugee groups in general. Wide gaps and unanswered questions related to mental health and overall health status of the Afghan refugee population are observable, especially in Germany. Our systematic review identified the gap in evidence, which we would recommend to bridge using a wider lens to comprehensively assess the overall condition of refugees considering associations between health and socio-economic and cultural determinants instead of a one-dimensional approach. Further, within health studies on refugee populations, we recommend stratification of results by the country of origin to capture the within-group diversity among refugees with different countries of origin.


Local Intra-wound Administration of Powdered Antibiotics in Orthopaedic Surgery.
Surgical site infection (SSI) is one of the most common complications after orthopaedic surgery, leading to significant morbidity and its associated costs. Surgical guidelines strongly recommend the use of systemic antibiotic prophylaxis to reduce the risk for developing SSI. Locally administered powdered antibiotics have the potential to provide remarkably high intra-wound concentrations without risk for systemic toxicity. However, a paucity of high quality evidence in the orthopaedic literature has prevented widespread adoption of this technique. The majority of clinical studies on local intra-wound antibiotics have evaluated the use of topical powdered vancomycin in spinal surgery, though only a single prospective study currently exists. This review will discuss all the available evidence describing the effectiveness, pharmacokinetics, and potential adverse effects with the use of topical powdered antibiotics in orthopedic surgery.


Detecting intratumoral heterogeneity in routine breast-HER2 testing: low yield of testing multiple blocks.
Intratumoral heterogeneity can lead to uncertainty in breast carcinoma HER2 testing, both with respect to pathology reporting and clinical significance. The standard practice is to perform breast biomarker testing on a single representative section of tumor; however, concern over heterogeneity often leads to testing on additional tissue blocks. Our objective was to assess the diagnostic yield of testing multiple blocks of a single invasive breast carcinoma. We performed a retrospective review of 139 consecutive cases (between 2006 and 2012) in which clinical HER2 testing was performed in multiple blocks. Tumor characteristics and HER2 studies (both immunohistochemistry and data from in situ hybridization) were reviewed. Regional differences in morphology and HER2 immunoreactivity were recorded. In situ hybridization was performed in 25 of 139 of the cases; patterns of genetic heterogeneity were reviewed. We audited discordances in HER2 result between blocks. Testing of multiple blocks yielded no additional HER2 information in 134 (96.4%) of 139 cases. Morphologic differences or heterogeneity in HER2 expression was observed in 22 (15.8%) of 139 of cases. Only 5 of these showed differences in HER2 between blocks, of which 4 were associated with equivocal HER2 immunohistochemistry, and 4 were high-grade. In the vast majority of cases, even those with heterogeneity, testing of a single block is sufficient for an accurate HER2 determination. High-grade tumors with equivocal HER2 status and observable heterogeneity are more likely to yield a different result on testing of additional blocks.


Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective.
The vulnerability to suicidal behavior has been modeled in deficits in both valuation and cognitive control processes, mediated by ventral and dorsal prefrontal cortices. To uncover potential markers of suicidality based on this model, we measured several brain morphometric parameters using 1.5T magnetic resonance imaging in a large sample and in a specifically designed study. We then tested their classificatory properties. Three groups were compared: euthymic suicide attempters with a past history of mood disorders and suicidal behavior (N=67); patient controls with a past history of mood disorders but not suicidal behavior (N=82); healthy controls without any history of mental disorder (N=82). A hypothesis-driven region-of-interest approach was applied targeting the orbitofrontal cortex (OFC), ventrolateral (VLPFC), dorsal (DPFC) and medial (including anterior cingulate cortex; MPFC) prefrontal cortices. Both voxel-based (SPM8) and surface-based morphometry (Freesurfer) analyses were used to comprehensively evaluate cortical gray matter measure, volume, surface area and thickness. Reduced left VLPFC volume in attempters vs both patient groups was found (P=0.001, surviving multiple comparison correction, Cohen's d=0.65 95% (0.33-0.99) between attempters and healthy controls). In addition, reduced measures in OFC and DPFC, but not MPFC, were found with moderate effect sizes in suicide attempters vs healthy controls (Cohen's d between 0.34 and 0.52). Several of these measures were correlated with suicidal variables. When added to mood disorder history, left VLPFC volume increased within-sample specificity in identifying attempters in a significant but limited way. Our study, therefore, confirms structural prefrontal alterations in individuals with histories of suicide attempts. A future clinical application of these markers will, however, necessitate further research.


Is normal body mass index a good indicator of metabolic health in Azar cohort population?
Introduction: Metabolic syndrome (Mets) has become most important public health problem in the world. We examined the association between Mets and different cardiometabolic phenotype in Azar cohort population. Methods: In the present study, the data of 13099 subjects who participated in Azar cohort study were cross-sectionally analyzed. Mets was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII) criteria. Participants were categorized into four cardiometabolic phenotypes including metabolically healthy Lean (MHL), metabolically unhealthy lean (MUHL), metabolically healthy Obese (MHO), metabolically unhealthy obese (MUHO) according to BMI cut-off point (25 kg/m2 ), and the presence of Mets. Results: Totally, the prevalence of Mets was 33.20% with the higher prevalence in women (40.1%). About 46.7% of participants were MHO and 1.6% of them were MHL. In both genders, MUHL had the highest prevalence of hyperglycemia, hypertrigliceridemia, hypo-HDL-cholestrolemia and Frahmingham 10-year CVD risk. In both MUHL and MUHO phenotypes, hypertriglyceridemia (OR: 31.97 [95% CI: 22.31, 45.81] and OR: 20.28 [95% CI: 17.32, 23.75]) and hypo-HDL cholestrolemia (OR:27.97 [95% CI: 17.35, 45.09] and OR:11.0 [95% CI: 9.62, 12.58]) are the strongest predictor of incidence of Mets. Also, the results of multinominal regression analyses indicated that in all cardiometabolic phenotypes, Framingham 10- year CVD risks had the lowest power for predicting of Mets incidence. Conclusion: Based on the results, in addition to obese individuals, multiple metabolic abnormalities were seen in normal weight individuals and these subjects are even at higher risk of developing Mets compared with metabolically obese individuals. So, it seems that decision on initiation of lifestyle interventions should not be only based on the BMI; rather metabolic status seems to be even more important.


When bacteria target the nucleus: the emerging family of nucleomodulins.
The nucleus, at the heart of the eukaryotic cell, hosts and protects the genetic material, governs gene expression and regulates the whole cell physiology, including cell division. A growing number of studies indicate that various animal and plant pathogenic bacteria can deliver factors to this central organelle to subvert host defences by directly interfering with transcription, chromatin-remodelling, RNA splicing or DNA replication and repair. Such bacterial molecules entering the nucleus, which we propose to term 'nucleomodulins', use diverse strategies to hijack nuclear processes by targeting host DNA or an array of nuclear proteins. In some cases, bacteria can even enter the nucleus. These bacterial 'nuclear attacks' might have permanent genetic or long-term epigenetic effects on the host. Studying nucleomodulins and endonuclear bacteria can thus generate new insights into long-term impacts of infectious diseases and create novel tools for biotechnological applications and for deciphering the regulation of nuclear dynamics.


Reasons for participating and genetic information needs among racially and ethnically diverse biobank participants: a focus group study.
In order for DNA biobanks to be a valuable reservoir of genetic information, large numbers of participants from all racial and ethnic backgrounds need to be recruited. This study explored reasons for participating in a new biobank among primarily Hispanic and African American individuals, as well as their general attitudes towards genetic research, and their views on obtaining genetic tests. Focus groups were conducted with Mount Sinai Biobank participants recruited from predominantly lower income, minority communities. The topic guide included questions on The Mount Sinai Biobank, genetic research, and genetic testing. All focus groups were audio recorded, transcribed, and analyzed using thematic analysis. The six focus groups comprised 43 participants: 39 females and four males, aged 27-76 years, with a median household income category of $20,000-$39,999. Twenty-one participants were Hispanic, 20 African American, one Asian, and one White. Participants' reasons for participating in the biobank included altruism, personal and family benefit, and general curiosity. Although there was evidence of conflation between genetic research and genetic testing, most participants held positive views of genetic research and expressed interest in receiving personal genetic test results. Participants wanted to learn more about genetic research and suggested various venues such as health fairs for disseminating information. Participation in biobanks by racial and ethnic minorities is apparently driven by altruism, and desire for personal or collective health benefits. Participants had generally positive attitudes, limited understanding of genetics and genetic research, and made useful suggestions regarding information dissemination mechanisms.


Screening experiments and the use of fractional factorial designs in behavioral intervention research.
Health behavior intervention studies have focused primarily on comparing new programs and existing programs via randomized controlled trials. However, numbers of possible components (factors) are increasing dramatically as a result of developments in science and technology (e.g., Web-based surveys). These changes dictate the need for alternative methods that can screen and quickly identify a large set of potentially important treatment components. We have developed and implemented a multiphase experimentation strategy for accomplishing this goal. We describe the screening phase of this strategy and the use of fractional factorial designs (FFDs) in studying several components economically. We then use 2 ongoing behavioral intervention projects to illustrate the usefulness of FFDs. FFDs should be supplemented with follow-up experiments in the refining phase so any critical assumptions about interactions can be verified.


Mechanisms of dorsal-ventral patterning in noggin-induced neural tissue.
We have investigated mechanisms of dorsal-ventral patterning of neural tissue, using Xenopus ectoderm neuralized by noggin protein. This tissue appears to be patterned dorsoventrally; cp1-1, a gene expressed in the dorsal brain, and etr-1, a gene largely excluded from the dorsal brain, are expressed in separate territories in noggin-treated explants (Knecht, A. K., Good, P. J., Dawid, I. B. and Harland, R. M. (1995) Development 121, 1927-1936). Here we show further evidence that this pattern represents a partial dorsal-ventral organization. Additionally, we test two mechanisms that could account for this pattern: a dose-dependent response to a gradient of noggin protein within the explant, and regulative cell-cell interactions. We show that noggin exhibits concentration-dependent effects, inducing cp1-1 at low doses but repressing it at high doses. Since noggin acts by antagonizing Bone Morphogenetic Protein (BMP) signaling, this result suggests that BMPs also may act in a dose-dependent manner in vivo. However, in the absence of a noggin gradient, regulative cell-cell interactions can also pattern the tissue. Such regulation is facilitated by increased motility of noggin-treated cells. Finally, the response of cells to both of these patterning mechanisms is ultimately controlled by a third process, the changing competence of the responding tissue.


Acrosin activity is a good predictor of boar sperm freezability.
The main aim of this study was to determine whether acrosin activity could predict boar sperm freezability. For this purpose, we characterized the changes in sperm quality and acrosin activity throughout the cryopreservation procedure of sperm samples from 30 Pietrain boars by analyzing four critical steps: step 1 (extended sperm at 15 °C), step 2 (cooled sperm at 5 °C), step 3 (30 minutes postthaw), and step 4 (240 minutes postthaw). Freezability ejaculate groups were set on the basis of sperm motility and membrane integrity after freeze-thawing. Results obtained highlighted the low predictive value in terms of freezability of sperm motility and kinematics and sperm membrane integrity, as no differences between good and poor freezability ejaculates were seen before cryopreservation. Significant differences (P < 0.05) between ejaculate groups were observed in the cooling step at 5 °C for sperm kinetic parameters, and after thawing for sperm motility and membrane integrity. In contrast, acrosin activity appeared as an indicator of boar sperm freezability because the differences (P < 0.05) between good and poor freezability ejaculates manifested yet in extended samples at 15 °C. On the other hand, we also found that variations in sperm kinematics, membrane lipid disorder, intracellular calcium content, acrosome integrity, and acrosin activity throughout the cryopreservation procedure were indicative of a significant damage in spermatozoa during the cooling step in both ejaculate groups. In conclusion, the main finding of our study is that acrosin activity can be used as a reliable predictor of boar sperm freezability because it differs significantly between good and poor freezability ejaculates yet before freeze-thawing procedures took place, i.e., in the refrigeration step at 15 °C.


Comparing 'doctor' and 'patient' beliefs about the role of illicit drug use in gay men's depression.
High rates of both illicit drug use and depression are consistently reported among gay men. However, little is known about how beliefs about drug use shape clinical encounters between gay men and health professionals, and that in turn affect clinical communication and care, particularly in relation to depression. We compared 'doctor' and 'patient' beliefs about the role of illicit drug use in gay men's depression. Semi-structured interviews were conducted during August-December 2006 with 16 general medical practitioners working in seven 'gay-friendly' practices in Sydney, Adelaide and a rural-coastal city in New South Wales, and during February-May 2008 with 40 gay men with depression recruited through four Sydney and Adelaide practices. A thematic analysis of these two sets of interviews found that doctors expressed the beliefs that: illicit drug use is related to depression in gay men; illicit drug use impedes effective diagnosis and treatment of depression in gay men; and illicit drug use increases the level of complexity involved in caring for gay men with depression. Gay men expressed the beliefs that: illicit drug use is closely related to depression; illicit drug use can be helpful in dealing with difficult experiences; and illicit drug use is just what you do as a gay man living in a big city. Both groups believed drug use and depression were related, but doctors emphasised the negative outcomes of drug use and interpreted these in relation to health. Gay men believed that drugs could have both negative and positive uses and differentiated between health and social outcomes. While the doctors articulated a pragmatic position on drug use, which is consistent with harm reduction principles, communication with gay male patients could be enhanced if both groups acknowledged their divergent views of illicit drugs and their potential role in mental health.


Identification of a rare blood group, "Bombay (Oh) phenotype," in Bhuyan tribe of Northwestern Orissa, India.
Blood group serology plays a vital role in transfusion medicine. The Bombay (Oh) phenotype is characterized by the absence of A, B, and H antigens on red cells and occurs rarely, especially in tribal populations of India. This is a field-based random population study in the Bhuyan tribal community. The study reports three cases of the rare Bombay (Oh) phenotype for the first time in the Bhuyan tribe of Sundargarh district in North-Western Orissa. Taking informed consent, red blood cells of 836 Bhuyan subjects were tested with three antisera, i.e., anti-A, anti-B, and anti-H (lectin) for forward reaction. Agglutinations of plasma with A, B, and O (H) red cells (reverse reaction) were also tested for the presence or absence of antibodies in the serum. Specialized tests like absorption-elution, titration of naturally occurring antibodies at different temperatures, inhibition of anti-H by O saliva secretor, and determination of secretor status were performed. Three cases of a rare blood group, Bombay (Oh) phenotype, (2 out of 244 Khandayat Bhuyan and 1 out of 379 Paudi Bhuyan from Hemgiri and Lahunipara blocks, respectively) in the Bhuyan tribe of Sundargarh district in North-Western Orissa were detected, giving an incidence of 1 in 122 in Khandayat Bhuyan and 1 in 379 in Paudi Bhuyan, with an average of 1 in 278 among the Bhuyan tribal population. This incidence is high in comparison to earlier studies reported from India. The practice of tribal and territorial endogamy in a smaller effective populations (for example, there are only 3,521 individuals in Paudi Bhuyan) results in smaller marital distance and inbreeding, leading to increased homozygous expression of rare recessive genetic characters like the Bombay (Oh) phenotype. This study further testifies that the incidence is higher in those states of India where the consanguinity is a common practice.


A field study of virus removal in septic tank drainfields.
Two field studies were conducted at a research station in Tampa, Florida to assess the removal of bacteriophage PRD1 from wastewater in septic tank drainfields. Infiltration cells were seeded with PRD1 and bromide and the effects of effluent hydraulic loading rate and rainfall on virus removal were monitored. Septic tank effluent samples were collected after passage through 0.6 m of unsaturated fine sand and PRD1 was detected over an average of 67 d. Bacteriophage PRD1 breakthrough was detected at approximately the same time as bromide in all three cells except for the low-load cell (Study 1), where bromide was never detected. Log10 removals of PRD1 were 1.43 and 1.91 for the high-load cells (hydraulic loading rate = 0.063 m/d) and 2.21 for the low-load cell (hydraulic loading rate = 0.032 m/d). Virus attenuation is attributed to dispersion, dilution, and inactivation. Significant increases in PRD1 elution with rainfall were observed in the first 10 d of the study. Approximately 125 mm of rainfall caused a 1.2 log10 increase of PRD1 detected at the 0.6-m depth. Current Florida onsite wastewater disposal standards, which specify a 0.6-m distance from the drainfield to the water table, may not provide sufficient removal of viruses, particularly during the wet season.


The association between neurocognitive functioning and smoking in adolescence: the TRAILS study.
This study examines the association between neurocognitive functioning and tobacco smoking in adolescence. Data from three measurements of the longitudinal Tracking Adolescents' Individual Lives Survey (TRAILS), a large regional population-based cohort study of Dutch adolescents, were used. The first measurement took place in 2001-2002 (T1) when participants were age 11, with two follow-up measurements (2003-2004 and 2005-2007; T2 and T3, respectively). A total of 1,797 adolescents participated in all three waves. At T1, they performed a selection of tasks from the Amsterdam Neuropsychological Tasks program (De Sonneville, 1999), which enabled the assessment of the main aspects of neurocognitive functioning. Smoking was assessed with a self-report questionnaire at T1, T2, and T3. In the multivariate analyses we controlled for gender, age, socioeconomic status (SES) and baseline speed. Multivariate logistic regression analyses showed that poor sustained attention increased the likelihood that the adolescent would initiate smoking between T1 and T2. Low inhibition of prepotent responses increased the likelihood of smoking initiation between T1 and T3. An increased ability to inhibit biased response tendencies reduced the likelihood of being a daily smoker at T2. Poor sustained attention increased the likelihood of being a daily smoker at T3. Poor sustained attention and low inhibition predicted adolescent smoking. However, the proportion of the variance in smoking risk accounted for by these neurocognitive predictors proved to be small. Thus, although neurocognitive functioning is related to adolescent smoking, it seems to explain only a small part of why adolescents initiate and continue smoking.


Methodological modifications for accurate and efficient determination of contaminant biodegradation in unsaturated calcareous soils.
Many techniques for quantifying microbial biodegradation of C-labeled compounds use soil-water slurries and trap mineralization-derived CO(2) in solution wells suspended within the incubation flasks. These methods are not satisfactory for studies of arid-region soils that are highly calcareous and unsaturated because (i) slurries do not simulate unsaturated conditions and (ii) the amount of CO(2) released from calcareous soils exceeds the capacity of the suspended well. This report describes simple, inexpensive methodological modifications for quantifying microbial degradation of [C]benzene and 1,2-dichloro[U-C]ethane in calcareous soils under unsaturated conditions. Soils at 50% water holding capacity were incubated with labeled contaminants for periods up to 10 weeks, followed by acidification of the soil and trapping of the evolved CO(2) in a separate container of 2 N NaOH. The CO(2) was transferred from the incubation flask to the trap solution by a gas transfer shunt containing activated charcoal to remove any volatilized labeled organics. The amount of CO(2) in the trap solution was measured by scintillation counting (disintegrations per minute). The method was tested by using two regional unamended surface soils, a sandy aridisol and a clay-rich riparian soil. The results demonstrated that both [C]benzene and 1,2-dichloro[U-C]ethane were mineralized to release substantial amounts of CO(2) within 10 weeks. Levels of mineralization varied with contaminant type, soil type, and aeration status (anaerobic vs. aerobic); no significant degradation was observed in abiotic control samples. Methodological refinements of this technique resulted in total CO(2) recovery efficiency of approximately 90%.


Estrogen attenuates neuronal excitability in the insular cortex following middle cerebral artery occlusion.
The current investigation examined the role of estrogen in the insular cortex (IC) under both normal and ischemic conditions. Experiments were done in anaesthetized male Sprague-Dawley rats. The effect of systemic 17beta-estradiol (estrogen) administration on levels of amino acids and of endogenous estrogen obtained by microdialysis and its effect on neuronal activity of cells located in the insular cortex were measured in the absence of, and following permanent occlusion of, the right middle cerebral artery (MCA). In normal rats, intravenous (i.v.) injection of estrogen resulted in a significant increase (greater than 25 spikes/bin) in the spontaneous activity of neurons located within the insular cortex, while there was a significant decrease in gamma-aminobutyric acid (GABA) levels measured in IC dialysate. Middle cerebral artery occlusion (MCAO) resulted in a biphasic response consisting of a transient increase in the extracellular concentration of glutamate, aspartate, and GABA, followed by sustained elevations in glutamate and aspartate, but reduced GABA levels 4 h post-MCAO. MCAO also resulted in a significant increase in neuronal activity in the IC (from 28 +/- 9 to 120 +/- 88 spikes/bin). This MCAO-induced excitation was completely blocked following the prior intravenous administration of estrogen. Systemic estrogen administration also resulted in a delay in the progression and decrease in the final infarct volume by approximately 56%. Taken together, these results suggest that under normal conditions, estrogen excites neurons in the insular cortex by decreasing GABA release (disinhibition) and it plays a role in attenuating the MCAO-induced excitability and death of these neurons.


Chemoprevention of lung cancer by non-steroidal anti-inflammatory drugs among cigarette smokers.
We conducted an epidemiologic case control study of NSAIDs among 489 lung cancer patients and 978 control subjects. The case patients were diagnosed and treated during 1996-1999 at the James Cancer Hospital and Research Institute, Columbus, OH. Each lung cancer diagnosis was verified by examination of the pathology report. Population controls free of disease were obtained from health screening clinics and frequency-matched to the cases at a 2:1 rate. Matching characteristics included age, gender, and pack-years of cigarette smoking. In order to assess the effects of NSAIDs on tobacco carcinogenesis, only heavy smokers were included in the control group. Information on the use of aspirin, ibuprofen, and prescription NSAIDs was obtained by personal interviews. Effects of NSAIDs on lung cancer risk were assessed by estimating odds ratios (relative risks) with 95% confidence intervals and performing trend tests. Daily intake of NSAIDs for at least 2 years prior to interview was associated with a 68% reduction in the relative risk of lung cancer (RR, 0.32; 95% CI, 0.23-0.44; p<0.01). The inverse trend of lung cancer risk with increasing NSAID use was highly significant (p<0.01). Results were similar for men (RR, 0.41) and women (RR, 0.22), and for the individual compounds, aspirin (RR, 0.25) and ibuprofen (RR, 0.39). These results combined with the current molecular evidence suggest that regular NSAID intake may prevent tobacco carcinogenesis through COX-2 blockade.


Isolation and sequencing of cDNA clones coding for juvenile hormone esterase from Heliothis virescens. Evidence for a catalytic mechanism for the serine carboxylesterases different from that of the serine proteases.
Three cDNA clones containing the entire coding sequence for JH esterase from the noctuid moth Heliothis virescens have been isolated from an expression library using specific antibodies and oligonucleotide probes. The complete sequence of one of the clones shows a 2989-base pair insert that is approximately the length of the single 3.0-kilobase pair mRNA transcript detected by Northern blotting. The clone has an open reading frame of 1714 base pairs that predicts a mature protein (minus signal peptide 19 residues long) of 61,012 Da. The 3'-nontranslated region has three signals for polyadenylation although only one apparently is used. Edman degradation of purified juvenile hormone lesterase indicates two slightly different proteins (one being 75% of the total) while the three cDNA clones differ at three bases in their 5' region causing their predicted sequence to differ at one or two residues of the 35 amino acids sequenced from the major form. Comparison of the predicted protein sequence to other carboxylesterase sequences indicates extensive similarity in the NH2-terminal half of the protein and the active site serine to be at position 201. The lack of conserved histidine and aspartate residues and the presence of conserved arginine and glutamate residues in appropriate positions in the NH2-terminal half of the homologous serine carboxylesterases suggests a catalytic mechanism for the serine carboxylesterases that is different from that of the serine proteases.


In vivo effects of a synthetic 2-kilodalton macrophage-activating lipopeptide of Mycoplasma fermentans after pulmonary application.
Mycoplasmas can cause interstitial pneumonias inducing critical illness in humans and animals. Mycoplasma infections are characterized by an influx of neutrophils, followed by an accumulation of macrophages and lymphocytes. The present study deals with the question of which mycoplasmal components cause this host reaction. The mycoplasma-derived, macrophage-activating lipopeptide 2S-MALP-2 was used to mimic the sequelae of a mycoplasma infection. To this end, 2S-MALP-2 was intratracheally instilled into the lungs of Lewis rats, and the bronchoalveolar lavage cells were examined at different times after different doses of 2S-MALP-2. Application of 2.5 microg induced a pronounced leukocyte accumulation in the bronchoalveolar space. At 24 h after 2S-MALP-2 administration, the majority of leukocytes consisted of neutrophils, followed by macrophages, peaking on days 2 and 3. Lymphocyte numbers, although amounting to only a few percent of the total bronchoalveolar lavage cells, also increased significantly, with maximal lymphocyte accumulation occurring by 72 h after instillation. The leukocyte count of the lung interstitium was increased on day 3 after treatment. After 10 days all investigated cell populations returned to control levels. Transient chemotactic activity for neutrophils was detected in the bronchoalveolar lavage fluid early after 2S-MALP-2 application, followed by monocyte chemoattractant protein-1 activity (MCP-1) in lung homogenates. MCP-1 was produced by bronchoalveolar lavage cells upon stimulation with 2S-MALP-2. Our data indicate that mycoplasmal lipoproteins and lipopeptides are probably the most relevant mycoplasmal components for the early host reaction. The primary target cells are likely to be the alveolar macrophages liberating chemokines, which attract further leukocytes.


A 10-year review of frontal sinus fractures: clinical outcomes of conservative management of posterior table fractures.
Frontal sinus cranialization is commonly indicated for posterior table fractures with significant comminution, displacement, or cerebrospinal fluid leaks. This study assessed the clinical outcomes of conservative management. A 10-year retrospective review of all frontal sinus fractures treated at a level 1 trauma center was performed using medical records and radiographic images. A total of 875 patients with frontal sinus fractures were identified, and 68 had posterior table involvement. Nine died within the first 48 hours from other injuries. The remaining 59 patients constituted the study population. Average follow-up approached 1 year (342 days). The more common mechanisms of injury were blunt interpersonal violence (29 percent) and motor vehicle accidents (27 percent). Concurrent central nervous system injury was common (73 percent), and the average Glasgow Coma Scale score was 12.7. Posterior wall fracture pattern was nondisplaced and noncomminuted in 33 patients (54 percent) and comminuted and/or displaced in 27 (46 percent). Cerebrospinal fluid leak was recorded in 11 patients (19 percent). Conservative management was the more common strategy (78 percent), followed by open reduction and internal fixation with sinus preservation (12 percent), obliteration (8 percent), and cranialization (2 percent). Of the 27 patients with comminuted and/or displaced fractures, 16 (59 percent) underwent conservative management, and 11 (41 percent) underwent surgical management, but only one patient (2 percent) underwent cranialization. There was no incidence of intracranial infection, except for one patient who died from encephalitis secondary to a gunshot wound to the head. The vast majority of frontal sinus fractures involving the posterior table, including those with comminution, displacement, or cerebrospinal fluid leaks, can be safely managed without cranialization. Therapeutic, IV.


NICE guidance: a comparative study of the introduction of the single technology appraisal process and comparison with guidance from Scottish Medicines Consortium.
Objectives To compare the timelines and recommendations of the Scottish Medicines Consortium (SMC) and National Institute of Health and Clinical Excellence (NICE), in particular since the single technology assessment (STA) process was introduced in 2005. Design Comparative study of drug appraisals published by NICE and SMC. Setting NICE and SMC. Participants All drugs appraised by SMC and NICE, from establishment of each organisation until August 2010, were included. Data were gathered from published reports on the NICE website, SMC annual reports and European Medicines Agency website. Primary and secondary outcome measures Primary outcome was time from marketing authorisation until publication of first guidance. The final outcome for each drug was documented. Drug appraisals by NICE (before and after the introduction of the STA process) and SMC were compared. Results NICE and SMC appraised 140 drugs, 415 were appraised by SMC alone and 102 by NICE alone. NICE recommended, with or without restriction, 90% of drugs and SMC 80%. SMC published guidance more quickly than NICE (median 7.4 compared with 21.4 months). Overall, the STA process reduced the average time to publication compared with multiple technology assessments (median 16.1 compared with 22.8 months). However, for cancer medications, the STA process took longer than multiple technology assessment (25.2 compared with 20.0 months). Conclusions Proportions of drugs recommended for NHS use by SMC and NICE are similar. SMC publishes guidance more quickly than NICE. The STA process has improved the time to publication but not for cancer drugs. The lengthier time for NICE guidance is partly due to measures to provide transparency and the widespread consultation during the NICE process.


Psychosocial impact of living-related kidney transplantation on donors and partners.
Living-related kidney transplantation (LRKT) is an option for children with end-stage renal failure. In addition to medical concerns, there is uncertainty about the psychological impact of living-related donation on parent donors and families. A survey was conducted on the decision making process and medical and psychosocial consequences of LRKT. Between 1992 and 1999, 20 parents donated a kidney for their child. A questionnaire including 24 items was sent to parent donors and their partners. Nineteen parents and partners responded; the median time after LRKT was 3 years. Donors and partners reported an independent decision making process with no significant influence of partners, relatives, or hospital staff. Partners were more concerned about medical problems than donors themselves (P <0.02). Donors and partners cited no medical problems except sustained pain. Both reported an improved personal relationship towards the transplanted child. Donors and partners also cited an improved personal relationship. The vast majority (18/19) of couples still supported the decision for organ donation. In conclusion, there was a high degree of satisfaction with the decision making process in LRKT. The great majority of donors and partners did not report negative medical or psychological consequences. The relationship between donor, partner, and recipient child improved after LRKT.


Acoustic interaction of humpback whales and whale-watching boats.
The underwater acoustic noise of five representative whale-watching boats used in the waters of west Maui was measured in order to study the effects of boat noise on humpback whales. The first set of measurements were performed on 9 and 10 March, close to the peak of the whale season. The ambient noise was relatively high with the major contribution from many chorusing humpback whales. Measurements of boat sounds were contaminated by this high ambient background noise. A second set of measurements was performed on 28 and 29 April, towards the end of the humpback whale season. In both sets of measurements, two of the boats were inflatables with outboard engines, two were larger coastal boats with twin inboard diesel engines and the fifth was a small water plane area twin hull (SWATH) ship with inter-island cruise capabilities. The inflatable boats with outboard engines produced very complex sounds with many bands of tonal-like components. The boats with inboard engines produced less intense sounds with fewer tonal bands. One-third octave band measurements of ambient noise measured on 9 March indicated a maximum sound pressure level of about 123 dB re 1 microPa at 315 Hz. The maximum sound pressure level of 127 dB at 315 Hz was measured for the SWATH ship. One of the boats with outboard engines produced sounds between 2 and 4 kHz that were about 8-10 dB greater than the level of background humpback whale sounds at the peak of the whale season. We concluded that it is unlikely that the levels of sounds produced by the boats in our study would have any grave effects on the auditory system of humpback whales.


Mental Health Community and Health System Issues in COVID-19: Lessons from Academic, Community, Provider and Policy Stakeholders.
The coronavirus pandemic of 2019 (COVID-19) has created unprecedented changes to everyday life for millions of Americans due to job loss, school closures, stay-at-home orders and health and mortality consequences. In turn, physicians, academics, and policymakers have turned their attention to the public mental health toll of COVID-19. This commentary reporting from the field integrates perceptions of academic, community, health system, and policy leaders from state, county, and local levels in commenting on community mental health needs in the COVID-19 pandemic. Stakeholders noted the broad public health scope of mental health challenges while expressing concern about exacerbation of existing disparities in access and adverse social determinants, including for communities with high COVID-19 infection rates, such as African Americans and Latinos. They noted rapid changes toward telehealth and remote care, and the importance of understanding impacts of changes, including who may benefit or have limited access, with implications for future services delivery. Needs for expanded workforce and training in mental health were noted, as well as potential public health value of expanding digital resources tailored to local populations for enhancing resilience to stressors. The COVID-19 pandemic has led to changes in delivery of health care services across populations and systems. Concerns over the mental health impact of COVID-19 has enhanced interest in remote mental care delivery and preventive services, while being mindful of potential for enhanced disparities and needs to address social determinants of health. Ongoing quality improvement across systems can integrate lessons learned to enhance a public mental well-being.


Shiftwork, functional bowel symptoms, and the microbiome.
There are about 15 million Americans working full-time on evening, night, or rotating shifts. Between 48% and 81.9% of those working rotating or night shifts report abdominal pain, constipation, diarrhea and other symptoms of functional bowel disorders. The basis for this high prevalence of functional bowel disorders, including irritable bowel syndrome (IBS), among shift workers is unknown. Animal studies, however, suggest that circadian disruption, similar to that in shift workers, may contribute to the development of GI complaints among shift workers by altering the composition and normal diurnal rhythmicity of the resident intestinal microbes. Therefore, the present study was designed to determine if there were differences in (1) composition and diversity of the microbiome of night shift workers compared to day shift workers; and (2) the composition and diversity of the microbiome among shift workers experiencing functional bowel symptoms compared to shift workers who did not experience functional bowel symptoms. Fifty-one full time staff nurses who worked either 12-hour day or night shifts completed demographic information, and the Rome III IBS module. They also collected two samples of gut microbiota before the beginning and at the end of their last work shift on day 14, using validated field-tested methods consistent with the Human Microbiome Project. After DNA extraction, 16S rRNA sequencing and assignment to the genus level was completed, samples were then compared to determine if there were (1) differences in the diversity and profile of the microbiome by shift type; (2) if there were differences in the microbiome by time of day for collection; and (3) whether there were differences in the diversity and profile of the microbiome of nurses with IBS and those without IBS. There were no differences in alpha or beta diversity of gut microbiota when specimens from day and night shift nurses were compared. There were however marginal differences in beta diversity when specimens collected at the beginning and end of the shifts were compared, with seven OTUs being differentially abundant when collected from day shift workers in the evening. There were also three OTUs to be differentially abundant in participants reporting IBS symptoms.


Long-term outcomes after in-hospital CPR in older adults with chronic illness.
Outcomes after in-hospital CPR in older adults with chronic illness are unclear. We examined inpatient Medicare data from 1994 through 2005 to identify CPR recipients. We grouped beneficiaries aged ≥ 67 years by severity of six chronic diseases-COPD, congestive heart failure (CHF), chronic kidney disease (CKD), malignancy, diabetes, and cirrhosis-and investigated survival to discharge, discharge destination, rehospitalizations, and long-term survival. We identified 358,682 CPR recipients. Most patients with chronic disease were less likely to survive to discharge (eg, 14.8% in the advanced COPD group [P < .001] and 11.3% in the advanced malignancy group [P < .001]) than patients without chronic illness (17.3%). Among discharge survivors, the median long-term survival was shorter in patients with chronic illness (eg, 5.0, 3.5, and 2.8 months in the advanced COPD, malignancy, and cirrhosis groups, respectively; P < .001 for all) than without (26.7 months). Although 7.2% of CPR recipients without chronic disease were discharged home and survived at least 6 months without readmission, ≤ 2.0% of recipients with advanced COPD, CHF, malignancy, and cirrhosis (P < .001 for all) met these criteria. Adjusted analyses confirmed that most subgroups with chronic illness had lower hospital discharge survival, and among discharge survivors, most were discharged home less often, experienced more hospital readmissions, and had worse long-term survival. Older CPR recipients with any of the six underlying chronic diseases investigated generally have much worse outcomes than CPR recipients without chronic disease. These findings may substantially affect decisions about CPR in patients with chronic illness.


Fructose-1,6-diphosphate attenuates acute lung injury induced by ischemia-reperfusion in rats.
To determine whether fructose-1,6-diphosphate (FDP) pretreatment can attenuate acute lung injury induced by ischemia-reperfusion in our isolated lung model in rats. Randomized, controlled study. Animal care facility procedure room. Twenty-four adult male Sprague-Dawley rats each weighing 250-350 g. Typical acute lung injury in rats was induced successfully by 10 mins of hypoxia followed by 75 mins of ischemia and 50 mins of reperfusion. Ischemia-reperfusion significantly increased microvascular permeability as measured by the capillary filtration coefficient, lung weight gain, lung weight to body weight ratio, pulmonary arterial pressure, and protein concentration of bronchoalveolar lav-age fluid. Pretreatment with FDP significantly attenuated the acute lung injury induced by ischemia-reperfusion as shown by a significant decrease in all of the assessed variables (p <.05 p <.001). The protective effect of FDP was nearly undetectable when promazine (an ecto-adenosine 5-triphosphatase inhibitor) was added before FDP pretreatment. Pretreatment with FDP significantly ameliorates acute lung injury induced by ischemia-reperfusion in rats.


Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX.
Fifteen per cent of cancers maintain telomere length independently of telomerase by the homologous recombination (HR)-associated alternative lengthening of telomeres (ALT) pathway. A unifying feature of these tumours are mutations in ATRX. Here we show that expression of ectopic ATRX triggers a suppression of the pathway and telomere shortening. Importantly ATRX-mediated ALT suppression is dependent on the histone chaperone DAXX. Re-expression of ATRX is associated with a reduction in replication fork stalling, a known trigger for HR and loss of MRN from telomeres. A G-quadruplex stabilizer partially reverses the effect of ATRX, inferring ATRX may normally facilitate replication through these sequences that, if they persist, promote ALT. We propose that defective telomere chromatinization through loss of ATRX promotes the persistence of aberrant DNA secondary structures, which in turn present a barrier to DNA replication, leading to replication fork stalling, collapse, HR and subsequent recombination-mediated telomere synthesis in ALT cancers.


PDK-1/FoxO1 pathway in POMC neurons regulates Pomc expression and food intake.
Both insulin and leptin signaling converge on phosphatidylinositol 3-OH kinase [PI(3)K]/3-phosphoinositide-dependent protein kinase-1 (PDK-1)/protein kinase B (PKB, also known as Akt) in proopiomelanocortin (POMC) neurons. Forkhead box-containing protein-O1 (FoxO1) is inactivated in a PI(3)K-dependent manner. However, the interrelationship between PI(3)K/PDK-1/Akt and FoxO1, and the chronic effects of the overexpression of FoxO1 in POMC neurons on energy homeostasis has not been elucidated. To determine the extent to which PDK-1 and FoxO1 signaling in POMC neurons was responsible for energy homeostasis, we generated POMC neuron-specific Pdk1 knockout mice (POMCPdk1(-/-)) and mice selectively expressing a constitutively nuclear (CN)FoxO1 or transactivation-defective (Delta256)FoxO1 in POMC neurons (CNFoxO1(POMC) or Delta256FoxO1(POMC)). POMCPdk1(-/-) mice showed increased food intake and body weight accompanied by decreased expression of Pomc gene. The CNFoxO1(POMC) mice exhibited mild obesity and hyperphagia compared with POMCPdk1(-/-) mice. Although expression of the CNFoxO1 made POMCPdk1(-/-) mice more obese due to excessive suppression of Pomc gene, overexpression of Delta256FoxO1 in POMC neurons had no effects on metabolic phenotypes and Pomc expression levels of POMCPdk1(-/-) mice. These data suggest a requirement for PDK-1 and FoxO1 in transcriptional regulation of Pomc and food intake.


Medical student socio-demographic characteristics and attitudes toward patient centered care: do race, socioeconomic status and gender matter? A report from the Medical Student CHANGES study.
To determine whether attitudes toward patient-centered care differed by socio-demographic characteristics (race, gender, socioeconomic status) among a cohort of 3191 first year Black and White medical students attending a stratified random sample of US medical schools. This study used baseline data from Medical Student CHANGES, a large national longitudinal cohort study of medical students. Multiple logistic regression was used to assess the association of race, gender and SES with attitudes toward patient-centered care. Female gender and low SES were significant predictors of positive attitudes toward patient-centered care. Age was also a significant predictor of positive attitudes toward patient-centered care such that students older than the average age of US medical students had more positive attitudes. Black versus white race was not associated with attitudes toward patient-centered care. New medical students' attitudes toward patient-centered care may shape their response to curricula and the quality and style of care that they provide as physicians. Some students may be predisposed to attitudes that lead to both greater receptivity to curricula and the provision of higher-quality, more patient-centered care. Medical school curricula with targeted messages about the benefits and value of patient-centered care, framed in ways that are consistent with the beliefs and world-view of medical students and the recruitment of a socioeconomically diverse sample of students into medical schools are vital for improved care.


The nasotemporal division of retinal ganglion cells with crossed and uncrossed projections in the fetal rhesus monkey.
The development of the partial decussation pattern in the primate retina was studied in fetal rhesus monkeys of known gestational ages. Retinal ganglion cells with either crossed or uncrossed projections were identified by labeling with HRP following unilateral injections of this tracer into the optic tract. At all fetal ages, very few cells (less than 0.5% of the total ganglion cell population) were found to project to the inappropriate hemisphere. The nasotemporal overlap zone, defined as the retinal region along the vertical meridian containing cells with either crossed or uncrossed projections, also appeared equivalent to that described for the adult animal. A temporal offset in the decussation pattern of large ganglion cells, similar to that of the mature retina, could be recognized as early as 50 d before birth. These results indicate that an adultlike retinal decussation pattern is evident in the fetal primate at a stage when projections from the 2 eyes are completely intermingled within retinorecipient nuclei, and prior to the onset of retinal ganglion cell loss. Moreover, the primate visual system exhibits a degree of precision in the specification of the nasotemporal division unrivaled among the mammalian species studied to date. The developmental specificity evident in the decussation pattern of the fetal rhesus monkey appears to reflect the specialized organization of this primate's retina for binocular focal vision.


Synergistic interaction of sprouting and intussusceptive angiogenesis during zebrafish caudal vein plexus development.
Intussusceptive angiogenesis (IA) is a complementary method to sprouting angiogenesis (SA). The hallmark of IA is formation of trans-capillary tissue pillars, their fusion and remodeling of the vascular plexus. In this study, we investigate the formation of the zebrafish caudal vein plexus (CVP) in Tg(fli1a:eGFP) y7 and the synergistic interaction of IA and SA in crafting the archetypical angio-architecture of the CVP. Dynamic in vivo observations and quantitative analyses revealed that the primitive CVP during development was initiated through SA. Further vascular growth and remodeling occurred by IA. Intussusception contributed to the expansion of the CVP by formation of new pillars. Those pillars arose in front of the already existing ones; and in a subsequent step the serried pillars elongated and fused together. This resulted in segregation of larger vascular segments and remodelling of the disorganized vascular meshwork into hierarchical tree-like arrangement. Blood flow was the main driving force for IA, particularly shear stress geometry at the site of pillar formation and fusion. Computational simulations based on hemodynamics showed drop in shear stress levels at locations of new pillar formation, pillar elongation and fusion. Correlative 3D serial block face scanning electron microscopy confirmed the morphological substrate of the phenomena of the pillar formation observed in vivo. The data obtained demonstrates that after the sprouting phase and formation of the primitive capillary meshwork, the hemodynamic conditions enhance intussusceptive segregation of hierarchical vascular tree i.e. intussusceptive arborization resulting in complex vascular structures with specific angio-architecture.


Comparative ultrastructure of Langerhans-like cells in spleens of ray-finned fishes (Actinopterygii).
We studied the morphology and occurrence of splenic Langerhans-like (LL) cells in species representing 11 orders of ray-finned fishes, Actinopterygii. LL cells were frequent in spleen tissue of species among Cypriniformes, Esociformes, Salmoniformes, and Pleuronectiformes. These cells contained granules which resembled Birbeck granules known to occur in mammalian Langerhans cells. The ultrastructure of LL cells in Northern pike, Esox lucius, and in Atlantic halibut, Hippoglossus hippoglossus were similar to those reported in salmonids. LL cells found in cyprinids shared some characteristics with the LL cells in other Actinopterygii species, although unique structures distinguished them from the latter. They contained dense bodies within the Birbeck-like (BL) granules, a characteristic that was never observed in species outside the Cypriniformes. Two types of BL granules were characterized in cyprinid LL cells. The ultrastructure of BL granules across the species is discussed. LL cells in all Actinopterygii species demonstrated close contacts with nearby cells, characterized by adherens-like junctions. Additionally, multivesicular bodies were present within the cytoplasm and large aggregates of exosomes were observed closely associated with the plasma membrane suggesting their release from the cells. These structures are discussed in relation to mammalian dendritic cells. Macrophages found in European perch, Perca fluviatilis, blue gourami, Trichogaster trichopterus, and Atlantic halibut, Hippoglossus hippoglossus contained lysosomes and residual bodies with structures resembling Birbeck granules. These granules and cells were clearly distinct from LL cells.


[Study on acupuncture treatment of diabetic neurogenic bladder].
To probe into a better therapy for diabetic neurogenic bladder. The patients were randomly divided into a treatment group and a control group, 35 cases in each group. The control group were treated with intramuscular injection of Methycobal 250 microg, once every other day; the treatment group were treated with intramuscular injection of Methycobal 250 microg, once every other day, and acupuncture at Guanyuan (CV 4), Shenshu (BL 23), Ciliao (BL 32), Huiyang (BL 35), once every day. The residual urine were compared before and after treatment in the two groups; the effective rate for improvement of symptoms were compared between the two groups. The mental and healthy nursing were conducted for the patients. After treatment, the improving rate for the urgency of urination, frequency of micturition, dribbling urination, urinary incontinence and dysuria in the treatment group was significantly better than that in the control group, but with no significant difference between the two groups in prolongation of urination time. After treatment, the residual urine in the bladder significantly improved in the two groups with more significantly improved in the treatment group than in the control group. Methycobal plus acupuncture has a better result than the simple Methyeobal for treatment of diabetic neurogenic bladder, and strengthening nursing care in the treatment can significantly enhance life quality of the patient.


Morbidity and mortality characteristics of infants hospitalized in the Pediatrics Department of the largest Turkish military hospital in 2001.
A descriptive study was conducted in the pediatric inpatient unit of Gulhane Military Medical Academy, to investigate the morbidity and mortality characteristics of 532 infants hospitalized between January 1 and December 31, 2001, for treatment purposes. Of the study participants, 55.8% were boys and 44.2% were girls. The most common cause of hospitalization was neonatal hyperbilirubinemia (19.7%). The most common admission month was January (12.4%). Of 532 infants, 510 (95.9%) were discharged, whereas 22 patients died in the hospital. Twenty-one patients died in the neonatal period, and respiratory distress syndrome and neonatal sepsis were identified as the most common causes of death. Our finding of associations between male gender and low birth weight and hospital death is consistent with previous knowledge. Despite the high frequencies of pneumonia and gastroenteritis as admission diagnoses, the finding of only one pneumonia-related death and no gastroenteritis-related deaths in the study population is pleasing.