Research Status of the Safety and Efficacy of Mesenchymal Stem Cells in the Treatment of COVID-19-Related Pneumonia: A Systematic Review and Meta-Analysis.
Mesenchymal stem cell (MSC) therapy is considered one of the most promising treatments in the context of the coronavirus disease 2019 (COVID-19) pandemic. However, the safety and effectiveness of MSCs in the treatment of COVID-19-associated pneumonia patients need to be systematically reviewed and analyzed. Two independent researchers searched for relevant studies published between October 2019 and April 2021 in the PubMed, Embase, Cochrane Library, WAN FANG, and CNKI databases. All relevant randomized controlled trials, clinically controlled studies, retrospective studies, case reports, letters (with valid data), and case series were included in this meta-analysis. A fixed-effects model and 95% confidence interval (CI) were used to analyze the results. A total of 22 studies involving 371 patients were included in the present study. Allogeneic MSCs from umbilical cord, adipose tissue, menstrual blood, placental tissue, Wharton's jelly, or unreported sources were administered in 247 participants. Combined results revealed that MSC therapy significantly reduced the incidence of adverse events [AEs; odds ratio (OR) = 0.43, 95% CI = 0.22-0.84, P = 0.01] and mortality (OR = 0.17, 95% CI = 0.06-0.49, P < 0.01), and the difference compared with control group was statistically significant. No serious MSC treatment-related AEs were reported. Lung function, radiographic outcomes, and inflammation- and immunity-related biomarker levels all showed improving trends. Therefore, MSC therapy is an effective and safe method for the treatment of COVID-19-associated pneumonia and shows advantages in reducing AEs and mortality. However, a standard and effective MSC treatment program must be developed.


Medications for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline.
Medications are the most frequently prescribed therapy for low back pain. A challenge in choosing pharmacologic therapy is that each class of medication is associated with a unique balance of risks and benefits. To assess benefits and harms of acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, benzodiazepines, antiepileptic drugs, skeletal muscle relaxants, opioid analgesics, tramadol, and systemic corticosteroids for acute or chronic low back pain (with or without leg pain). English-language studies were identified through searches of MEDLINE (through November 2006) and the Cochrane Database of Systematic Reviews (2006, Issue 4). These electronic searches were supplemented by hand searching reference lists and additional citations suggested by experts. Systematic reviews and randomized trials of dual therapy or monotherapy with 1 or more of the preceding medications for acute or chronic low back pain that reported pain outcomes, back-specific function, general health status, work disability, or patient satisfaction. We abstracted information about study design, population characteristics, interventions, outcomes, and adverse events. To grade methodological quality, we used the Oxman criteria for systematic reviews and the Cochrane Back Review Group criteria for individual trials. We found good evidence that NSAIDs, acetaminophen, skeletal muscle relaxants (for acute low back pain), and tricyclic antidepressants (for chronic low back pain) are effective for pain relief. The magnitude of benefit was moderate (effect size of 0.5 to 0.8, improvement of 10 to 20 points on a 100-point visual analogue pain scale, or relative risk of 1.25 to 2.00 for the proportion of patients experiencing clinically significant pain relief), except in the case of tricyclic antidepressants (for which the benefit was small to moderate). We also found fair evidence that opioids, tramadol, benzodiazepines, and gabapentin (for radiculopathy) are effective for pain relief. We found good evidence that systemic corticosteroids are ineffective. Adverse events, such as sedation, varied by medication, although reliable data on serious and long-term harms are sparse. Most trials were short term (< or =4 weeks). Few data address efficacy of dual-medication therapy compared with monotherapy, or beneficial effects on functional outcomes. Our primary source of data was systematic reviews. We included non-English-language trials only if they were included in English-language systematic reviews. Medications with good evidence of short-term effectiveness for low back pain are NSAIDs, acetaminophen, skeletal muscle relaxants (for acute low back pain), and tricyclic antidepressants (for chronic low back pain). Evidence is insufficient to identify one medication as offering a clear overall net advantage because of complex tradeoffs between benefits and harms. Individual patients are likely to differ in how they weigh potential benefits, harms, and costs of various medications.


Exploring the Health Effectiveness of a Physical Activity Program Co-Constructed with Students after the COVID-19 Pandemic.
University students have low levels of physical activity and high levels of sedentary behaviors that were exacerbated by the COVID-19 pandemic. Even before the pandemic, there was poor uptake of university sports activities. Therefore, it is essential to develop and test innovative programs to increase students' motivation to engage in physical activity in order to prevent any future deterioration in their general health. This exploratory study was conducted to test the effectiveness of a physical activity program that was co-constructed with students. First, a workshop drawing on social design methodologies and the fundamentals of physical activity programs was conducted to assess students' needs and desires in terms of physical activity. Second, the effectiveness of a program co-constructed with students on the basis of this workshop was assessed on physical and mental health parameters. The results showed that the workshop outcomes allowed the physical activity program to be tailored to meet students' expectations (e.g., session duration and type of activities). This innovative physical activity program was found to improve body image, autonomous motivation, and certain physical parameters. At the end of the 8-week program, the adherence rate was 89%, and 83% of the final respondents expressed a wish to re-enroll for the following semester. Involving students and considering their wishes, needs, and objectives could facilitate the development of attractive and innovative programs.


Post-traumatic stress disorder due to childbirth: the aftermath.
Childbirth qualifies as an extreme traumatic stressor that can result in post-traumatic stress disorder. The reported prevalence of post-traumatic stress disorder after childbirth ranges from 1.5% to 6%. The aim of this phenomenologic study was to describe the essence of mothers' experiences of post-traumatic stress disorder after childbirth. The qualitative research design used for this study was descriptive phenomenology. The main recruitment approach was via the Internet through the help of Trauma and Birth Stress, a charitable trust in New Zealand. Purposive sampling was used and resulted in 38 mothers participating from the countries of New Zealand, the United States, Australia, and the United Kingdom. The participants were asked to describe their experiences with post-traumatic stress disorder after childbirth. Their stories were analyzed using Colaizzi's method of data analysis. Mothers with post-traumatic stress disorder attributable to childbirth struggle to survive each day while battling terrifying nightmares and flashbacks of the birth, anger, anxiety, depression, and painful isolation from the world of motherhood. This glimpse into the lives of mothers with post-traumatic stress disorder attributable to childbirth provides an impetus to increase research efforts in this neglected area.


Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex.
Investigations of pain using functional imaging techniques have revealed an extensive central network associated with nociception. This network includes the thalamus, insula, prefrontal cortex and anterior cingulate cortex (ACC) as well as the somatosensory cortices. Positron emission tomography (PET) of regional cerebral blood flow (rCBF) has demonstrated activation of the ACC during cognitively challenging tasks such as the Stroop interference task and divided attention. One interpretation of this research is that ACC is involved in the general features of attention and that it does not play a specific role in pain processing per se. Three-dimensional PET imaging provides a method for assessments of rCBF in a single individual during multiple tasks. In addition, coregistration of PET and magnetic resonance (MR) images allows for better localisation of the PET signals so that differences in cortical activation sites can be more accurately determined. This approach was used to assess rCBF during the experience of pain by subtracting images collected during heat from those during noxious heat stimulation. Two regions of the ACC had elevated rCBF, one in the perigenual region and one in the mid-rostrocaudal region (i.e. midcingulate cortex). During the execution of the Stroop task, the group result showed the midcingulate region overlapping with the site seen during the experience of pain. This group result, however, was not confirmed in the individual subject analysis, which revealed widespread and independent areas of ACC response to pain and Stroop. It is concluded that the ACC contributes to multiple cognitive procedures. It is inadequate to describe the primary contribution of ACC to pain processing as "attention" because it is unlikely that the multiple small and independent activation sites produced by pain and Stroop subserve attentive processing throughout the brain.


Molecular insight into the formation of adsorption clusters based on the zeta isotherm.
This work presents a series of molecular dynamics simulations of argon adsorption on a silicon substrate with different lattice orientations. From the simulation results, the density profiles are discussed and the amount of adsorbed particles is obtained at different pressures. It is found that the solid surface orientation has a great influence on the density distributions and atomic arrangements near the surface. With the collected data, the thermal constants derived from the expression of zeta adsorption isotherms are determined. The calculated isotherms agree well with the simulation results. Also, from a microscopic point of view, the molecular insights show that the structures of the adsorbates are present as clusters with different numbers of particles. The size of the clusters changes with pressure. At a relatively small pressure ratio, most of the clusters consist of a single molecule. As the pressure ratio increases, larger sized clusters appear, forming various cluster-types. The molecular cluster distributions are closely consistent with the basic approximation of the zeta adsorption isotherm. Furthermore, the surface adsorption sites determined from molecular dynamics simulation show good agreement with that predicted by the zeta isotherm model, which reaffirms the effectiveness of the theoretical model. When the isotherm is extended to a pressure ratio greater than unity, a finite amount of adsorption is predicted and the wetting conditions are obtained. Affected by the solid surface orientations, the pressure ratio at wetting for the silicon substrate with the (111) surface plane is larger than those of the (100) and (110) surfaces, indicating that a higher subcooling is required for the wetting transition.


Probable statin-induced testicular pain.
To describe a case of a patient experiencing testicular pain on 3 occasions after taking 3 different statins. A 54-year-old man with hyperlipidemia was started on lovastatin therapy. His other medications included aspirin, levothyroxine, buspirone, and atenolol. Seven months after starting lovastatin, the patient experienced testicular discomfort that resolved upon discontinuation of the drug. Afterward, he started simvastatin and again experienced testicular discomfort. The simvastatin was changed to atorvastatin, and the pain resolved. However, 3 months after starting atorvastatin, the patient developed testicular pain, which resolved after the drug was stopped. During each of the episodes, the patient's pain increased when he was sitting, driving, or wearing tight clothing. The Naranjo probability scale indicates that statins probably caused the patient's pain. Testicular pain is rarely caused by medications. Product labeling for statins does not list urinary adverse events as common. However, labeling for atorvastatin and pravastatin lists rare urologic adverse effects. A literature search did not reveal any previously reported cases of testicular adverse effects from statins. However, statins have been shown to inhibit cholesterol synthesis in the testis. Some data indicate that statins reduce serum testosterone concentrations, but other data indicate that statins have no effect on sex hormones or spermatogenesis. Data are also available indicating that aspirin might affect testosterone concentrations and testicular function. It is difficult to know whether either of the above hormonal mechanisms was associated with our patient's testicular discomfort, but the time course and challenge/rechallenge aspects of the case suggest that the statins were the cause. Urologic adverse effects of statins rarely occur but should not be overlooked by medical providers.


Primary pelvic hydatid cyst in a postmenopausal female: a surgical challenge.
Primary pelvic hydatid cysts are a rare entity and are often overlooked as a differential diagnosis of a pelvic-space-occupying lesion particularly in non-endemic regions. Unpreparedness and a hasty decision on the surgical approach may end in life-threatening complications and systemic dissemination of the disease. We report the case of a 55-year-old postmenopausal woman with a history of two previous unsuccessful surgeries to remove pelvic cystic lesions due to dense adhesions between the surrounding gut wall, bladder, and the cyst wall. Clinical and imaging findings failed to diagnose the nature of the cysts, and a laparotomy was contemplated. On the third surgical attempt, the clinical suspicion was considered and by meticulous dissection the cysts were removed thoroughly without undue complications. In the postoperative follow-up period there was no sign of disease recurrence or dissemination.


Sleep: a marker of physical and mental health in the elderly.
The objective of this study was to determine the occurrence and recognition of common sleep-related problems and their relationship to health-related quality-of-life measures in the elderly. A total of 1,503 participants with a mean age of 75.5 (+/- 6.8, range: 62-100) years from 11 primary care sites serving primarily elderly patients were interviewed. Subjects completed a five-item sleep questionnaire and the SF-12. A Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) score was calculated. A systematic medical chart review was conducted to determine whether sleep problems were identified by the healthcare providers. A total of 68.9% of patients reported at least one sleep complaint and 40% had two or more. Participants most commonly endorsed (45%) that they had "difficulty falling asleep, staying asleep, or being able to sleep." The number and type of sleep problems endorsed was associated with both physical and mental health quality-of-life status. Excessive daytime sleepiness was the best predictor of poor mental and physical health-related quality of life. Even when all five sleep questions were endorsed, a sleep complaint was only reported in the chart 19.2% of the time. When elicited, sleep complaints predicted the general physical and mental health-related quality-of-life status in elderly populations with comorbid medical and mental illnesses. Yet, questions regarding sleep are not an integral component of most clinical evaluations. Given the growing evidence of a relationship between sleep and health, identification of sleep disorders could lead to improved management of common age-related chronic illnesses and quality of life of elderly patients.


Inhibitory effect of enalapril on neurally mediated syncope in elderly patients.
A dramatic increase in catecholamine (CA) concentration is believed to be a primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The hypercontractile state of the heart might be alleviated by angiotensin-converting enzyme (ACE) inhibitor through depression of CA release from the sympathetic nerve ending. Thus ACE inhibitor might have positive effect on the prevention of NMS. In this study, 24 elderly subjects who had reproducible NMS induced with head-up tilt test (HUT) were randomized and double-blind divided into placebo and ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS were observed in the two groups. Before administration of enalapril, plasma CA concentrations were significantly increased during HUT compared with those in the supine position; In contrast, administration of the enalapril (10 mg/day) for >1 year inhibited the concentration of plasma CA increase and prevented syncope in all 12 patients (p < 0.05); however, placebo had no effect on plasma CA concentrations and syncope disappeared in only two of 12 patients after administration of placebo. From this study, we conclude that enalapril can prevent NMS in patients, presumably because of its part in the inhibition of CA release from sympathetic nerve endings.


[The law of medical responsibility. New stakes].
The law of March 4, 2002, concerning the rights of patients and the quality of cares, establishes an extra jurisdictional way to solve conflicts of medical responsibility. After reminding the rules of common law which apply to this type of litigation, the text explains the outline of law goals, means used and established procedures. A medico-juridical critical study highlights confusions, imperfections and unvoiced comments of the text. Corrections might be necessary. The gravity of the stakes for medicine is underlined.


Pathological modes of human relating and therapeutic mutuality: A dialogue between Buber's existential relational theory and object-relations theory.
There is, in my opinion, a rapprochement between the theories of psychoanalysis and existential-phenomenology. It is my major theoretical interest to articulate the points at which true dialogue between these different perspectives is possible. Such an effort is not an attempt to merge the two theories or subordinate one to the other; rather, I hope that the theoretical positions of both will be clarified and that the therapeutic dialogue of practitioners who represent both perspectives will be benefited.


Combined gene therapy of endostatin and interleukin 12 with polyvinylpyrrolidone induces a potent antitumor effect on hepatoma.
To study the antitumor effect of combined gene therapy of endostatin and interleukin 12 (IL-12) with polyvinylpyrrolidone (PVP) on mouse transplanted hepatoma. Mouse endostatin eukaryotic plasmid (pSecES) with a mouse Igkappa signal sequence inside and mouse IL-12 eukaryotic plasmid (pmIL-12) were transfected into BHK-21 cells respectively. Endostatin and IL-12 were assayed by ELISA from the supernant and used to culture endothelial cells and spleen lymphocytes individually. Proliferation of the latter was evaluated by MTT. H22 cells were inoculated into the leg muscle of mouse, which was injected intratumorally with pSecES/PVP, pmIL-12/PVP or pSecES+pmIL-12/PVP repeatedly. Tumor weight, serum endostatin and serum IL-12 were assayed. Tumor infiltrating lymphocytes, tumor microvessel density and apoptosis of tumor cells were also displayed by HE staining, CD31 staining and TUNEL. Endostatin and IL-12 were secreted after transfection, which could inhibit the proliferation of endothelial cells or promote the proliferation of spleen lymphocytes. Tumor growth was highly inhibited by 91.8% after injection of pSecES+pmIL-12/PVP accompanied by higher serum endostatin and IL-12, more infiltrating lymphocytes, fewer tumor vessels and more apoptosis cells compared with injection of pSecES/PVP, pmIL-12/PVP or vector/PVP. Mouse endostatin gene and IL-12 gene can be expressed after intratumoral injection with PVP. Angiogenesis of hepatoma can be inhibited synergisticly, lymphocytes can be activated to infiltrate, and tumor cells are induced to apoptosis. Hepatoma can be highly inhibited or eradiated.


[Traumatic asphyxia with permanent visual loss. Case report].
Traumatic asphyxia is a rare condition that occurs after compressive thoracoabdominal trauma, which is characterized by subconjunctival hemorrhage, cervicofacial cyanosis, edema and petechiae. Serious life-threatening thoracic and abdominal injuries may coexist. After conservatory treatment in most cases complete recovery is achieved, but in isolated cases permanent neurological lesions may occur. We present the case of the 39-year-old male patient who suffered a compressive thoracoabdominal trauma. The physical examination showed the characteristic "ecchymotic mask". After surgical treatment of the abdominal injuries and intensive therapy the patient was discharged with permanent vision loss. The high retrograde venous pressure in the head and neck may be associated with neuronal ischemia, which can lead to irreversible optic nerve atrophy. It is therefore important to carry out an early, routine and complete ophtalmologic examination, especially in the intubated and poorly cooperative patients. Orv Hetil. 2017; 158(22): 864-868.


Presence of alpha 2-macroglobulin in normal but not in malignant human syncytiotrophoblasts.
alpha 2-Macroglobulin (alpha 2M) was demonstrated in normal syncytiotrophoblasts of both early and full-term human placentas using immunocytological staining. alpha 2M was also detected in hydatidiform moles, the benign tumors of proliferating syncytiotrophoblasts. In contrast, no alpha 2M was detected in invasive moles or choriocarcinomas. In culture conditions, both normal syncytiotrophoblasts and choriocarcinoma cells, identified by production of human chorionic gonadotropin, were negative when stained for alpha 2M or when studied using metabolic labeling and immunoprecipitation or radioimmunoassay. However, alpha 2M was taken up from added human serum by the cultured syncytiotrophoblasts, whereas choriocarcinoma cells remained negative also under these conditions. The possible role of alpha 2M in the regulation of proteolysis in cell invasion is considered.


Phenotypic expression of the targeted null-mutation in the dopamine transporter gene varies as a function of the genetic background.
The dopamine transporter (DAT) plays a critical role in calibrating the duration and intensity of dopamine (DA) neurotransmission. Mice in which the DAT gene has been genetically deleted exhibit constitutively high levels of extrasynaptic DA and spontaneous hyperactivity. Numerous studies have characterized the adaptive molecular, physiological, and behavioural consequences of abnormal DA neurotransmission in these mice. In order to determine the genetic background contribution to these phenotypes, the DAT mutation was transferred on C57BL/6JOrl (B6) or DBA/2JOrl (D2) inbred backgrounds for more than ten generations of back-crossing to derive three B6-, D2-, and B6xD2(F(1))-DAT strains. We observed that the genetic background dramatically affects phenotypes previously reported on DAT knockout (KO) mice. Depending on the genetic background, it was possible to restore survival, growth rate and ability to lactate. Interactions with the genetic background were found to modulate both quantitative and qualitative patterns of novelty-driven spontaneous hyperactivity. The paradoxical calming effect of cocaine was observed for all DAT-KO mice. However, the genetic background influenced individual threshold responses to both locomotor and rewarding effects of cocaine. These findings reveal the extent of phenotypic variation associated with the DAT mutation. They also provide concrete arguments against the assumption that the normal function of a gene can be inferred directly from its mutant phenotype.


Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation.
Dynamic measurements of regional changes in cerebral blood volume (CBV) were performed in rat models of hypercarbia and focal neuronal activation using T2-weighted imaging after injection of an intravascular contrast agent with a very long blood half-life. Calculated percent CBV change during hypercarbia was consistent with literature results from other non-invasive modalities. Equivalent percent CBV increases were found using spin- and gradient-echo images, suggesting proportional changes in blood volume for capillaries and small veins. During electrical stimulation of rat forepaw, focal CBV response to stimulation (24+/-4%) was significantly delayed relative to blood oxygen level dependent (BOLD) signal after both onset and cessation of stimulation. Poststimulus CBV decay was temporally consistent with the BOLD poststimulus undershoot. The use of exogenous agent increased the functional contrast-to-noise ratio relative to BOLD imaging by 5.7+/-1.3 at a magnetic field strength of 2 Tesla and 1.5+/-0.2 at 4.7 Tesla.


Post-conditioning by a short administration of desflurane reduced renal reperfusion injury after differing of ischaemia times in rats.
'Anaesthetic post-conditioning', that is administration of anaesthetics during early reperfusion, is known to have positive effects on several organs. For the kidney, however, the effects of post-conditioning by volatile anaesthetics are not well researched. We examined renal function and morphology after post-conditioning by desflurane. Anaesthetized rats were subjected to 30 or 45 min of renal ischaemia 14 days after contralateral nephrectomy. Post-conditioning was achieved by administration of 1 MAC desflurane (6.7 vol%) for 15 min during early reperfusion (all groups n=8). Cystatin C (CyC), creatinine clearance (Cl(Cr)) and fractional sodium excretion (FE(Na)) were measured in the awake rats over 3 days. Cell damage was graded from 1 to 4 in histological sections. Functional variables [mean (SD)] were compared statistically by a one-way anova followed by Bonferroni's multiple comparison test and histological scores (median and range) by Kruskal-Wallis test followed by Dunn's multiple comparison test. Pre-ischaemia function did not differ between the groups, but was markedly reduced after ischaemia. After 30 min ischaemia, the area under the curve (AUC) for Cl(Cr) was smaller in the desflurane than in the control group [21.5 (5.0) vs 31.6 (5.1) ml min(-1) h, P<0.05]. After 45 min desflurane reduced the AUC compared with the control group for both CyC [15 (4) vs 21 (3) mg litre(-1) h] and FE(Na) [1054 (221) vs 1570 (572)% h, both P<0.05). Morphological differences were greater between the 30 min groups [control: 2.75 (2.0-3.5) vs desflurane: 1.5 (1.0-2.5); P<0.05] than between the 45 min groups [control: 3.5 (3.0-4.0) vs desflurane: 3.0 (1.5-4.0)]. Desflurane post-conditioning protects renal function and tissue. This protection was greater after the short episode than after the long episode of ischaemia.


High speed nonlinear interferometric vibrational analysis of lipids by spectral decomposition.
Unlike other CARS-based (coherent anti-Stokes Raman scattering) spectroscopy techniques, nonlinear interferometric vibrational spectroscopy (NIVS) is linear in analyte concentration and has a Raman line shape free of nonresonant background distortions. We use spontaneous Raman scattering as a high accuracy benchmark for NIVS. As a challenging comparison, we examine spectra in the CH stretching region of six lipid samples. Singular value decomposition and reference to an independent chemical assay are used to directly compare NIVS and spontaneous Raman scattering. We demonstrate that NIVS can determine the relative degree of unsaturation in six different lipid samples as accurately as spontaneous Raman spectroscopy, but 200 times faster. A skin tissue sample is mapped out to demonstrate quantitative lipid-protein differentiation with spatial resolution.


Ocular indigo dye injury.
To describe the clinical course, management, and final outcome in a case of ocular injury caused by accidental fall of indigo dye in both eyes. Review of patient's record and relevant literature. A 32-year-old man sustained ocular injury caused by inadvertent indigo dye in both eyes. He presented with bluish staining of the entire ocular surface, subtotal corneal epithelial breakdown in both eyes, and entry of dye into the anterior chamber in the left eye. This was treated as acute alkali burns with lubricants and steroids. Over a period of 3 to 4 months, the ocular surface staining resolved completely, and visual acuity improved remarkably. Although the clinical presentation was initially a cause for concern, the condition resolved completely with the same conservative management as applicable for other chemical injuries.


Time of day determines Arabidopsis transcriptome and growth dynamics under mild drought.
Drought stress is a major problem for agriculture worldwide, causing significant yield losses. Plants have developed highly flexible mechanisms to deal with drought, including organ- and developmental stage-specific responses. In young leaves, growth is repressed as an active mechanism to save water and energy, increasing the chances of survival but decreasing yield. Despite its importance, the molecular basis for this growth inhibition is largely unknown. Here, we present a novel approach to explore early molecular mechanisms controlling Arabidopsis leaf growth inhibition following mild drought. We found that growth and transcriptome responses to drought are highly dynamic. Growth was only repressed by drought during the day, and our evidence suggests that this may be due to gating by the circadian clock. Similarly, time of day strongly affected the extent, specificity, and in certain cases even direction of drought-induced changes in gene expression. These findings underscore the importance of taking into account diurnal patterns to understand stress responses, as only a small core of drought-responsive genes are affected by drought at all times of the day. Finally, we leveraged our high-resolution data to demonstrate that phenotypic and transcriptome responses can be matched to identify putative novel regulators of growth under mild drought.


Listeria monocytogenes infection in pregnant macaques alters the maternal gut microbiome†.
The bacterium Listeria monocytogenes (Lm) is associated with adverse pregnancy outcomes. Infection occurs through consumption of contaminated food that is disseminated to the maternal-fetal interface. The influence on the gastrointestinal microbiome during Lm infection remains unexplored in pregnancy. The objective of this study was to determine the impact of listeriosis on the gut microbiota of pregnant macaques. A non-human primate model of listeriosis in pregnancy has been previously described. Both pregnant and non-pregnant cynomolgus macaques were inoculated with Lm and bacteremia and fecal shedding were monitored for 14 days. Non-pregnant animal tissues were collected at necropsy to determine bacterial burden, and fecal samples from both pregnant and non-pregnant animals were evaluated by 16S rRNA next-generation sequencing. Unlike pregnant macaques, non-pregnant macaques did not exhibit bacteremia, fecal shedding, or tissue colonization by Lm. Dispersion of Lm during pregnancy was associated with a significant decrease in alpha diversity of the host gut microbiome, compared to non-pregnant counterparts. The combined effects of pregnancy and listeriosis were associated with a significant loss in microbial richness, although there were increases in some genera and decreases in others. Although pregnancy alone is not associated with gut microbiome disruption, we observed dysbiosis with listeriosis during pregnancy. The macaque model may provide an understanding of the roles that pregnancy and the gut microbiota play in the ability of Lm to establish intestinal infection and disseminate throughout the host, thereby contributing to adverse pregnancy outcomes and risk to the developing fetus.


Correlation of nuclear factor-κB, regulatory T cell and transforming growth factor β with rheumatoid arthritis.
Objective: Investigated the correlation of nuclear factor-κB, regulatory cells and transforming growth factor-β with rheumatoid arthritis. Methods: Included 65 cases of RA patients admitted in our hospital from June 2015 to December 2016 into case group, and included 50 healthy people into control group during the same period. Collected the peripheral detection of nuclear factor-κB, regulatory cells and transforming growth factor beta levels, and compared them between two groups. Results: The percentage of CD4+, CD25+ T cells in the case group was significantly lower than that in the control group (P < .05); There was no significant difference in the percentage of CD4+, CD25+ CD127low/-, T cells between groups (P > .05); The levels of TGF - beta and NF - kappa B in the case group were higher than those in the control group, and the difference between the two groups was statistically significant (P < .05); The levels of ESR, CRP and RF in the case group were higher than those in the control group (P < .05). There was a negative correlation between the expression of nuclear factor-κB, transforming growth factor-β and RF level in RA patients by pearson correlation analysis, r = -0.652, P < .05. Conclusion: The expression levels of CD4+, CD25+ T cells in patients with RA are significantly decrease, which has a negative correlation with RA activity index RF, and showed that the pathogenesis of RA is related to the regulation of immune system.


Flexner 2.0-Longitudinal Study of Student Participation in a Campus-Wide General Pathology Course for Graduate Students at The University of Arizona.
Faculty members from the Department of Pathology at The University of Arizona College of Medicine-Tucson have offered a 4-credit course on enhanced general pathology for graduate students since 1996. The course is titled, "Mechanisms of Human Disease." Between 1997 and 2016, 270 graduate students completed Mechanisms of Human Disease. The students came from 21 programs of study. Analysis of Variance, using course grade as the dependent and degree, program, gender, and year (1997-2016) as independent variables, indicated that there was no significant difference in final grade (F = 0.112; P = .8856) as a function of degree (doctorate: mean = 89.60, standard deviation = 5.75; master's: mean = 89.34, standard deviation = 6.00; certificate program: mean = 88.64, standard deviation = 8.25), specific type of degree program (F = 2.066, P = .1316; life sciences: mean = 89.95, standard deviation = 6.40; pharmaceutical sciences: mean = 90.71, standard deviation = 4.57; physical sciences: mean = 87.79, standard deviation = 5.17), or as a function of gender (F = 2.96, P = .0865; males: mean = 88.09, standard deviation = 8.36; females: mean = 89.58, standard deviation = 5.82). Students in the physical and life sciences performed equally well. Mechanisms of Human Disease is a popular course that provides students enrolled in a variety of graduate programs with a medical school-based course on mechanisms of diseases. The addition of 2 new medically oriented Master of Science degree programs has nearly tripled enrollment. This graduate level course also potentially expands the interdisciplinary diversity of participants in our interprofessional education and collaborative practice exercises.


Synthesis of the Natural Product Marthiapeptide A.
The first total synthesis of marthiapeptide A is reported. Two synthetic procedures are described: the first, which was unsuccessful, attempts to close the ring at position I, and the second, which was successful, closes the ring at position II. It appears that the first route was unsuccessful because it required cyclization next to the rigid thiazole moiety, whereas the second route closed next to the more flexible thiazoline ring.


Kimmerle's anomaly as a possible causative factor of chronic tension-type headaches and neurosensory hearing loss: case report and literature review.
Kimmerle's anomaly also known as ponticulus posticus is a common anatomical variation of the atlas, the first cervical vertebra. It is the product of the complete or incomplete ossification of the posterior atlanto-occipital membrane over the vertebral artery groove resulting in the formation of a foramen (arcuate foramen) containing the vertebral artery and the posterior branch of the C-1 spinal nerve. This variation has been associated with vertebro-basilar insufficiency symptoms, various types of headaches, and acute hearing loss. The aim of the present study is to substantiate whether Kimmerle's anomaly is the possible cause of chronic tension-type headaches and neurosensory-type hearing loss in a patient with a known history of headaches and accompanied unilateral hearing loss. The headaches demonstrated the characteristics of the chronic tension-type; the audiometric investigation concluded the hearing loss to be of the neurosensory type; whereas, the imaging examinations revealed the existence of a partial osseous bridge, that is an incomplete arcuate foramen (ponticulus posticus or Kimmerle's anomaly) on the upper surface of atlas. Both the clinical and the radiological findings of this case are indicative of a possible connection between Kimmerle's anomaly and the manifestation of chronic tension-type headaches and neurosensory-type hearing loss.


Biofeedback-based cognitive-behavioral treatment compared with occlusal splint for temporomandibular disorder: a randomized controlled trial.
Cognitive-behavioral treatment has proven efficacy for chronic temporomandibular disorder (TMD). However, most patients receive dental treatment that may not address psychological comorbidities often present in TMD. The aim of the present study was to evaluate the efficacy of biofeedback-based cognitive-behavioral treatment (BFB-CBT) versus dental treatment with occlusal splint (OS). Moreover, changes in nocturnal masseter muscle activity (NMMA) were investigated. Fifty-eight patients with chronic TMD were randomly assigned to receive either 8 weekly sessions of BFB-CBT or 8 weeks of OS treatment. Diagnoses were established using Research Diagnostic Criteria for TMD. Pain intensity and disability were defined as primary outcomes. Secondary outcomes included emotional functioning, pain coping, somatoform symptoms, treatment satisfaction, and adverse events. NMMA was assessed during 3 nights pretreatment and posttreatment with portable devices. Follow-up assessment took place 6 months after the treatment. Both treatments resulted in significant reductions in pain intensity and disability, with similar amounts of clinically meaningful improvement (45% for BFB-CBT and 48% for OS). Patients receiving BFB-CBT showed significantly larger improvements in pain coping skills. Satisfaction with treatment and ratings of improvement were higher for BFB-CBT. Effects were stable over 6 months, and tended to be larger in the BFB-CBT group for all outcomes. No significant changes were observed in NMMA. The fact that BFB-CBT resulted in larger improvements in pain coping skills, and was well accepted by the patients, underlines the importance and feasibility of psychological treatments in the clinical management of TMD.


Association of Upper Eyelid Ptosis Repair and Blepharoplasty With Headache-Related Quality of Life.
Headache can be a functional indication for ptosis repair and blepharoplasty. To evaluate the changes in headache-related quality of life in patients who underwent upper eyelid ptosis repair or blepharoplasty. A prospective cohort study was conducted among 108 patients who underwent standard upper eyelid blepharoplasty and 44 patients who underwent ptosis repair (levator resection, Müller muscle resection, or frontalis suspension) for obscuration of the superior visual field at an ophthalmology clinic's oculoplastic department from September 1, 2014, to September 1, 2015. A validated headache-related quality-of-life survey, the Headache Impact Test-6 (HIT), was administered preoperatively and postoperatively to patients who had tension-type headache. The minimum time interval after the operation was 3 months (mean, 13.5 weeks; range, 12-17 weeks). Postoperative HIT scores, decline in HIT scores, and marginal reflex distance test 1 scores. Of the 108 patients (66 women and 42 men; mean [SD] age, 49.8 [10.7] years) who underwent blepharoplasty and the 44 patients (26 women and 18 men; mean [SD] age, 45.6 [17.8] years) who underwent ptosis repair, 38 (35.2%) and 28 (63.6%), respectively, had symptoms of tension-type headaches. In both groups, the mean (SD) postoperative HIT scores were statistically significantly better than the preoperative HIT scores (blepharoplasty group: preoperative score, 55.9 [6.6] vs postoperative score, 46.4 [9.0]; ptosis repair group: preoperative score, 60.0 [7.2] vs postoperative score, 42.3 [9.3]; P = .001). In the patients who underwent ptosis repair, the mean (SD) preoperative HIT score was significantly higher than in those who underwent blepharoplasty (60.0 [7.2] vs 55.9 [6.6]; P = .007) and the postoperative HIT score was significantly lower than those who underwent blepharoplasty (42.3 [9.3] vs 46.4 [9.0]; P = .03). The mean (SD) decline in the HIT score was significantly higher in patients who underwent ptosis repair than in those who underwent blepharoplasty (17.8 [9.9] vs 9.5 [8.6]; P = .002). For patients who underwent ptosis repair, there was a statistically significant negative correlation between the results on the marginal reflex distance test 1 (median, 1.82; minimum, 1.0; maximum, 3.5) and change in the HIT score (median, 18; minimum, 0; maximum, 30) (P = .005; r = -0.645). In patients who underwent ptosis repair, the mean (SD) difference between the preoperative and postoperative HIT scores was significantly higher for the patients who underwent levator resection (3.1 [0.3]) than for those who underwent Müller muscle resection (1.5 [0.7]) and frontalis suspension procedures (1.9 [0.7]) (P = .001). The operations for ptosis and blepharoptosis provide significant relief for tension-type headache and result in improved headache-related quality of life. As a result, tension-type headache can be a functional indication for upper eyelid blepharoplasty and ptosis repair, especially for patients with lower results on the marginal reflex distance test 1. 3.


Dose emission characteristics of placebo PulmoSphere® particles are unaffected by a subject's inhalation maneuver.
Good compliance to the prescribed dosing regimen and inhaler instructions for use are critical for asthma/chronic obstructive pulmonary disease (COPD) patients to achieve good control of their disease. We investigated the extent to which a system comprising porous particles delivered with a passive dry powder inhaler could be designed to achieve significant reductions in dose inhalation errors. Porous placebo particles were prepared by an emulsion-based spray-drying method (PulmoSphere® technology). The formulations were administered as dry powders with a portable, blister-based dry powder inhaler (Simoon Inhaler). The inhalation profiles of 69 asthma/COPD subjects were determined with an inhaler simulator with resistance comparable to that of the Simoon Inhaler. Powder emptying from the device was assessed by laser photometry. Aerosol performance was assessed on a Next Generation Impactor, and with the idealized Alberta mouth-throat model using both square-wave and subject-inhalation profiles generated in the breathing study. Virtually all subjects could achieve a pressure drop of at least 1 kPa and an inhaled volume of at least 500 mL with the Simoon Inhaler. In vitro measures of particle deposition were found to be largely independent of the inhalation maneuver (flow rate, inhaled volume, ramp time) across the broad range of inhalation profiles observed in the breathing study. The rapid emptying of powder from the Simoon Inhaler minimizes the impact of dose-related errors, such as failure to exhale before inhalation and failure to breath-hold post inhalation. Inertial impaction that is largely independent of a subject's inhalation maneuver can be achieved with a drug/device combination product comprising a porous particle formulation and blister-based inhaler.


Methods of measuring splenic blood flow and platelet transit time with In-111-labeled platelets.
Following bolus intravenous injection of In-111-labeled autologous platelets in humans, splenic blood flow (SBF) was measured by compartmental analysis of the equilibration of platelets between blood and the intrasplenic platelet pool. The result correlated closely (r = 0.94, p less than 0.001) with SBF measured from analysis of the first-pass time-activity curve recorded over the spleen by external detection. The intrasplenic platelet transit time (tp), measured concurrently with SBF from compartmental analysis, correlated closely (r = 0.78, p less than 0.001) with tp measured from deconvolution analysis. These correlations appear to support the use of compartmental analysis of the equilibration of radiolabeled platelets between blood and the intrasplenic platelet pool as a valid technique for the simultaneous measurement of SBF and tp. Both of these parameters have potential clinical usefulness for the understanding of intrasplenic platelet kinetics in a variety of disorders.


Basal ultrasensitive LH assay: a useful tool in the early diagnosis of male pubertal delay?
The aim of this study was to evaluate the usefulness of basal measurements of gonadotropins in distinguishing between constitutionally delayed puberty (DP) and hypogonadotropic hypogonadism (HH), comparing its diagnostic efficiency with that of the dynamic GnRH infusion test (0.83 microg/min during 120 min). We studied 20 males, chronological age (CA) 14-18 years, with a final diagnosis of DP (n = 8), partial HH (n = 5) and complete HH (n = 7), confirmed by follow-up. We also evaluated basal samples of ultrasensitive LH and FSH in 117 healthy control males (CA 2-19 yr), classified according to Tanner stage. In the control group, ROC plot analysis showed a cutoff to differentiate prepuberty from puberty of 0.65 IU/l for LH (sensitivity: 91%, specificity: 98%). Differences were found (p < 0.05) in basal LH and in maximal responses to GnRH in complete HH in relation to DP and partial HH. The diagnostic efficiency of the GnRH infusion test was 85%. For basal LH, a cut-off limit of 0.65 IU/l showed a diagnostic efficiency of 85% for complete HH and 100% for partial HH and DP. We conclude that, in our experience, basal LH levels above 0.65 IU/l measured by ultrasensitive assay would rule out a complete deficiency. It was not possible to differentiate DP from partial HH, either in basal samples or with the infusion test.


[Stromal tumors of the small intestine. Retrospective analysis of 9 cases surgically treated].
The authors report on their experience with 9 patients with small bowel stromal tumours who underwent surgical treatment over the period 1974-2001. Seven were males and 2 females, with an average age of 63.1 years (range: 49-72 years). Histologically, 4 tumours showed evidence of differentiation towards smooth muscle elements (1 benign and 3 malignant), 4 towards neural elements (all malignant) and 1 lacked differentiation towards either cell type. Five tumours were located in the ileum, 3 in the jejunum and 1 in the duodenum. The main symptoms were abdominal pain and an abdominal mass, and the most sensitive diagnostic technique was abdominal CT scan. In the 8 jejunal or ileal stromal tumours we performed a typical intestinal resection, while undifferentiated duodenal stromal tumours were managed by pancreaticoduodenectomy. The diagnosis was only histological. There was no operative mortality, while 2 postoperative complications (1 pancreatic fistula and 1 myocardial infarction) occurred. The patient with jejunal benign muscular stromal tumour is still alive and in good health 73 months after the operation. Of the 3 patients with malignant muscular ileal stroma tumours, 1 is alive and free from disease 63 months after the operation, while the other 2 died of metastatic disease 39 and 29 months after surgery. Of the 4 patients with malignant neural stromal tumours (2 jejunal and 2 ileal) 1 with jejunal and 1 with ileal tumour were lost to follow-up, while 1 is still alive and in good health 101 months postoperatively; the 4th patient, with jejunal disease, developed liver metastasis 14 months after small bowel resection and died 12 months later. The patient with undifferentiated duodenal stromal tumour died of liver metastases 38 months after pancreaticoduodenectomy. Small bowel stromal tumours are more often than not malignant. The most frequent symptoms are abdominal pain and a palpable mass, but no specific signs have been detected. Abdominal CT scan is the most sensitive diagnostic technique in the evaluation of the location, size, invasion of adjacent organs and metastases. The treatment must be intestinal resection, and prognostic prediction on the basis of histological findings is difficult.


Intraspinal meningioma with malignant transformation and distant metastasis.
Meningioma is typically considered to be a benign tumor. Malignant transformation and metastasis of meningiomas are rare. Moreover, most meningiomas are intracranial, and there are few reports on intraspinal meningiomas. This report aimed to describe the clinical features and pathological findings of a case of malignant transformation and distant metastasis of intraspinal meningioma, with a review of the literature. A 44-year-old man with a bilateral lower limb paresis was diagnosed with an intradural extramedullary tumor of the thoracic spine. Primary tumor resection was performed, and the histological findings revealed atypical meningioma. The meningioma recurred 2 years after the primary surgery, and a second resection was performed, but only partial resection was possible because of decreased motor evoked potential. At age 48, the patient's lower limb weakness returned, and a third resection was performed, and the histological finding remained atypical meningioma. At age 54, the tumor increased and stereotactic irradiation was performed. At age 60, the patient was diagnosed with metastatic tumors of the rib, lumbar vertebra, cervical spine, and sacrum. Biopsy of the rib metastatic tumor was performed, and the histological findings revealed anaplastic meningioma. This case is the first report of an intraspinal meningioma that transformed from atypical to anaplastic meningioma with distant hematogenous metastasis.


Understanding the role of pore size homogeneity in the water transport through graphene layers.
Graphene is a versatile 2D material and attracts an increasing amount of attention from a broad scientific community, including novel nanofluidic devices. In this work, we use molecular dynamics simulations to study the pressure driven water transport through graphene layers, focusing on the pore size homogeneity, realized by the arrangement of two pore sizes. For a given layer number, we find that water flux exhibits an excellent linear behavior with pressure, in agreement with the prediction of the Hagen-Poiseuille equation. Interestingly, the flux for concentrated pore size distribution is around two times larger than that of a uniform distribution. More surprisingly, under a given pressure, the water flux changes in an opposite way for these two distributions, where the flux ratio almost increases linearly with the layer number. For the largest layer number, more distributions suggest the same conclusion that higher water flux can be attained for more concentrated pore size distributions. Similar differences for the water translocation time and occupancy are also identified. The major reason for these results should clearly be due to the hydrogen bond and density profile distributions. Our results are helpful to delineate the exquisite role of pore size homogeneity, and should have great implications for the design of high flux nanofluidic devices and inversely the detection of pore structures.


[Analysis on the atypical clinical accidents of acupuncture based on the individual factors in patients].
The hidden risk of acupuncture has become the factor of the high incidence of adverse reaction of acupuncture in clinical practice. The retrospective analysis and the typical cases analysis are especially important for the prevention from the hidden risk of acupuncture. In the paper, the relevant literatures were reviewed, the basic diseases were listed such as diabetes, hypertension and digestive gastric ulcer that were neglected by the physicians, and the adverse reactions induced by the therapeutic history and the body constitutions were analyzed. It was stated in the paper that because of the individual factors of patient, the risks of the atypical clinical accidents of acupuncture were extremely serious and easily neglected by the clinical acupuncture physicians. It is very necessary to remind the clinical acupuncture physicians to understand the basic diseases, basic treatment as well as the peculiarity of body constitution of the patients besides their chief complaints. Moreover, acupuncture should be applied very carefully after identifying the pulse condition and the contraindication so as to ensure the patient's safety and obtain the optimal efficacy.


A conserved retromer-independent function for RAB-6.2 in C. elegans epidermis integrity.
Rab proteins are conserved small GTPases that coordinate intracellular trafficking essential to cellular function and homeostasis. RAB-6.2 is a highly conserved C. elegans ortholog of human RAB6 proteins. RAB-6.2 is expressed in most tissues in C. elegans and is known to function in neurons and in the intestine to mediate retrograde trafficking. Here, we show that RAB-6.2 is necessary for cuticle integrity and impermeability in C. elegans RAB-6.2 functions in the epidermis to instruct skin integrity. Significantly, we show that expression of a mouse RAB6A cDNA can rescue defects in C. elegans epidermis caused by lack of RAB-6.2, suggesting functional conservation across phyla. We also show that the novel function of RAB-6.2 in C. elegans cuticle development is distinct from its previously described function in neurons. Exocyst mutants partially phenocopy rab-6.2-null animals, and rab-6.2-null animals phenocopy mutants that have defective surface glycosylation. These results suggest that RAB-6.2 may mediate the trafficking of one or many secreted glycosylated cuticle proteins directly, or might act indirectly by trafficking glycosylation enzymes to their correct intracellular localization.


The Orphan Nuclear Receptor Liver Homolog Receptor-1 (Nr5a2) Regulates Ovarian Granulosa Cell Proliferation.
In mouse ovaries, liver receptor homolog-1 [nuclear receptor subfamily 5, group A, member 2 (Nr5a2)] expression is restricted to granulosa cells. Mice with Nr5a2 depletion in this cell population fail to ovulate. To determine whether Nr5a2 is essential for granulosa cell proliferation during follicular maturation, we generated granulosa-specific conditional knockout mice (genotype Nr5a2 floxed Cre-recombinase driven by the anti-Müllerian type II receptor, hereafter cKO) with Nr5a2 depletion from primary follicles forward. Proliferation in cKO granulosa cells was substantially reduced relative to control (CON) counterparts, as assessed by bromodeoxyuridine incorporation, proliferative cell nuclear antigen expression, and fluorescent-activated cell sorting. Microarray analysis revealed >2000 differentially regulated transcripts between cKO and CON granulosa cells. Major gene ontology pathways disrupted were proliferation, steroid biosynthesis, female gamete formation, and ovulatory cycle. Transcripts for key cell-cycle genes, including Ccnd1, Ccnd2, Ccne1, Ccne2, E2f1, and E2f2, were in reduced abundance. Transcripts from other cell-cycle-related factors, including Cdh2, Plagl1, Cdkn1a, Prkar2b, Gstm1, Cdk7, and Pts, were overexpressed. Although the follicle-stimulating hormone and estrogen receptors were overexpressed in the cKO animals, in vivo treatment with estradiol-17β failed to rescue decreased proliferation. In vitro inactivation of Nr5a2 using the ML180 reverse agonist similarly decreased cell-cycle-related gene transcripts and downstream targets, as in cKO mice. Pharmacological inhibition of β-catenin, an Nr5a2 cofactor, decreased cyclin gene transcripts and downstream targets. Terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling immunofluorescence and quantitative polymerase chain reaction of pro/antiapoptotic and autophagic markers showed no differences between cKO and CON granulosa cells. Thus, Nr5a2 is essential for granulosa cell proliferation, but its depletion does not alter the frequency of apoptosis nor autophagy.


Probing ultrafast changes of spin and charge density profiles with resonant XUV magnetic reflectivity at the free-electron laser FERMI.
We report the results of resonant magnetic XUV reflectivity experiments performed at the XUV free-electron laser FERMI. Circularly polarized XUV light with the photon energy tuned to the Fe M2,3 edge is used to measure resonant magnetic reflectivities and the corresponding Q-resolved asymmetry of a Permalloy/Ta/Permalloy trilayer film. The asymmetry exhibits ultrafast changes on 240 fs time scales upon pumping with ultrashort IR laser pulses. Depending on the value of the wavevector transfer Qz , we observe both decreasing and increasing values of the asymmetry parameter, which is attributed to ultrafast changes in the vertical spin and charge density profiles of the trilayer film.


Effect of codeine on CYP450 isoform activity of rats.
Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported. In order to investigate the effects of codeine on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2 and CYP2C11. Sprague-Dawley rats were randomly divided into codeine group (low, medium, high) and control group. The codeine group rats were given 4, 8, 16 mg/kg (low, medium, high) codeine by continuous intragastric administration for 14 days. Five probe drugs bupropion, metroprolol, phenacetin, midazolam and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. The pharmacokinetic parameters of bupropion and metroprolol experienced obvious change with AUC(0-t), Cmax increased and CL decreased for bupropion in medium dosage group and midazolam low dosage group. This result indicates that the 14 day-intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rat. Additional, there are no statistical differences for albumin (ALB), alkaline phosphatase (ALP), creatinine (Cr) after 14 intragastric administration of codeine, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) increased compared to control group. The biomedical test results show continuous 14 day-intragastric administration of codeine would cause liver damage.


[Standardization of nailfold capillary microscopy in routine diagnosis].
Nailfold capillary microscopy is scientifically established and recognized as a diagnostic tool in clinical routine. It is, however, practiced in only a few centres. But since a more widespread use of the method is to be expected for the near future, a consensus-meeting was held, where all German-speaking clinicians and scientists, involved in capillary microscopy, were invited. Here, the technical procedure and the most important morphological parameters were evaluated and defined according to practical clinical aspects. The main task of the consensus-meeting was to develop a standard evaluation sheet, accompanied by an explanation sheet. This standard evaluation sheet focuses on semiquantitative registration of morphological parameters like density, dilation, avascular fields, perivascular edema, microbleeding, torsion, atypical capillaries and giant capillaries. This standard evaluation sheet is to be validated by determining the inter-observer-variance. Later-on an illustrated practical guideline will be published.


Dengue virus-elicited tryptase induces endothelial permeability and shock.
Dengue virus (DENV) infection causes a characteristic pathology in humans involving dysregulation of the vascular system. In some patients with dengue hemorrhagic fever (DHF), vascular pathology can become severe, resulting in extensive microvascular permeability and plasma leakage into tissues and organs. Mast cells (MCs), which line blood vessels and regulate vascular function, are able to detect DENV in vivo and promote vascular leakage. Here, we identified that a MC-derived protease, tryptase, is consequential for promoting vascular permeability during DENV infection, through inducing breakdown of endothelial cell tight junctions. Injected tryptase alone was sufficient to induce plasma loss from the circulation and hypovolemic shock in animals. A potent tryptase inhibitor, nafamostat mesylate, blocked DENV-induced vascular leakage in vivo. Importantly, in two independent human dengue cohorts, tryptase levels correlated with the grade of DHF severity. This study defines an immune mechanism by which DENV can induce vascular pathology and shock.


From HIS to IAIMS: expanding the scope of information processing applications in a German university hospital.
Since the mid eighties the department of medical informatics at the University Hospital of Giessen (Germany) has been engaged in the development of a comprehensive hospital information system. The installation of a campus wide network has set the basis to provide not only clinical patient-oriented information, but also general information resources for research, medical education and administrative purposes, thus creating an environment which in the U.S. became known as an integrated academic information management system (IAIMS). The underlying concept of the whole approach is to provide one-stop information shopping capabilities at the clinicians and administrators desktop in order to meet the increasing information needs of health professionals with the emerging reality of the potential benefits of computer and communication technologies. This paper describes the various steps performed to realize this concept at Giessen University Hospital and the evaluation results derived from analysis of the acceptance of these new technologies among our hospital staff.


Reduced Computed Tomography for Appendicitis in Children after Implementation of Next-day Surgery Clinic Follow-up.
The use of computed tomography (CT) in the emergency department (ED) evaluation of pediatric patients for suspected appendicitis can be safely reduced. However, published examples of reduced CT use also report increased MRI utilization, ED length of stay, hospitalization rates, and in-ED surgical consultation. In addition, previous studies recommended follow-up for undifferentiated abdominal pain, yet none with pediatric surgeons. Therefore, we implemented a diagnostic algorithm that includes an option for next-day surgery clinic follow-up in cases where uncertainty remains after appendix ultrasound (US) to reduce CT utilization without increasing hospital-based resources. We implemented a diagnostic algorithm in January 2014. We retrospectively identified 4,577 patients who underwent an evaluation for suspected appendicitis from January 2012 to September 2015. CT utilization was compared before and after implementation using Statistical Process Control. In addition, we evaluated secondary outcomes, including US utilization, hospital admission, surgery clinic follow-up, ED surgery consultation, ED return visits within 7 days, and ED length of stay. Following the implementation of the algorithm, CT utilization decreased significantly from 13.8% to 6%. Forty-eight patients were evaluated the next day in the optional pediatric surgery clinic for 21 months after implementation. There was no significant change in US utilization, hospital admission, ED surgery consultation, ED return visits within 7 days, or ED length of stay. We achieved decreased CT utilization without an increase in the utilization of other hospital-based resources after implementing a pediatric appendicitis evaluation algorithm that includes the option for next-day pediatric surgery clinic follow-up.


Gradient characterization using a Fourier-transform technique.
This paper describes a technique for characterizing the gradient subsystem of a magnetic resonance (MR) system. The technique uses a Fourier-transform analysis to directly measure the k-space trajectory produced by an arbitrary gradient waveform. In addition, the method can be easily extended to multiple dimensions and can be adapted to measuring residual gradient effects such as eddy currents. Several examples of gradient waveform and eddy-current measurements are presented. Also, it is demonstrated how the eddy-current measurements can be parameterized with an impulse-response formalism for later use in system tuning. When compared to a peak-fitting analysis, this technique provides a more direct extraction of the k-space measurements, which reduces the possibility of analysis error. This approach also has several advantages as compared to the conventional eddy-current measurement technique, including the ability to measure very short time constant effects.


Is Perceived Athlete Leadership Quality Related to Inside Sacrifice and Perceived Performance in Team Sports? The Mediating Role of Team Identification.
The study aimed to analyze the relationship between athletes' perceptions of athlete leadership quality, team identification, inside sacrifice, and performance. A total of 299 players of collective sports (soccer, beach soccer, basketball, volleyball; M age 19.05, SD = 5.10) participated through a cross-sectional design survey. Data were analyzed using structural equation modeling. Results highlight the positive relationships between perceived quality of athlete leaders, inside sacrifice, and perceived performance, and between inside sacrifice and perceived performance. Furthermore, inside sacrifice perceived by the athletes was a positive mediator between perceived athlete leadership quality and perceived performance. Also, team identification was a positive mediator in the association between inside sacrifice and perceived performance. These findings extend knowledge about the athlete leadership quality context. These results can also be useful for further research and implications in team sports' performance, as coaches and sports psychologists would have more information about their teams' perceptions of leadership quality to achieve positive outcomes in players' inside sacrifice and performance. The findings also highlight the importance of developing team identification to improve the relationships between perceived athlete leadership quality, inside sacrifice, and perceived performance.


Social-ecological assessment of Lake Manyara basin, Tanzania: A mixed method approach.
The social-ecological system of the Lake Manyara basin (Northern Tanzania), a UNESCO Biosphere reserve (BR) suffers from social-economic and environmental problems due to decreasing water levels, erosion and land and water use conflicts. We propose an integrated assessment of the social-ecological interactions of the area to support future sustainable management. Within the Drivers-Pressures-State-Impact-Response (DPSIR) framework an integrated literature review and several methods of knowledge collection were combined to identify future management priorities and challenges. During focus groups with farmers and pastoralists, stakeholders confirmed the role played by land use changes as driver and pressure in the landscape, e.g. through increased erosion rates and siltation of the lake. Moreover, economic and social issues were identified as prominent factors being influenced by, or influencing these processes. These statements match the scientific literature. During participatory mapping exercises different spatial and resource allocation perceptions appeared amongst pastoralists and farmers. The multidisciplinary approach proved to be useful to acquire an integrated and comprehensive understanding of the state, challenges and opportunities of Lake Manyara BR, to feed into a decision support system in service of an integrated management plan. Our assessment suggests that improved water governance in a multi-actor approach (with a focus on distribution of benefits, rights, and a specific role of the water authorities) should be a priority for future integrated management strategies. Also, awareness raising amongst decision makers, scientists and local communities is needed to demonstrate the advantages of an integrated approach. And finally, visible and fair mechanisms to share conservation revenues should be designed in a way that local benefits can be obtained together with incentive mechanisms for co-management and conservation.


Droplet-based lipid bilayer system integrated with microfluidic channels for solution exchange.
This paper proposes a solution exchange of a droplet-based lipid bilayer system, in which the inner solution of a droplet is replaced for the purpose of efficient ion channel analyses. In our previous report, we successfully recorded the channel conductance of alpha-hemolysin in a bilayer lipid membrane using a droplet contact method that can create a spontaneous lipid bilayer at the interface of contacting droplets; this method is widely used as highly efficient method for preparing planar lipid membranes. When only pipetting droplets of the solution, this method is highly efficient for preparing lipid membranes. However, the drawback of droplet-based systems is their inability to exchange the solution within the droplets. To study the effect of inhibitors and promoters of ion channels in drug discovery, it would be beneficial to conduct a solution exchange of droplets to introduce membrane proteins and to apply or wash-out the chemicals. In this study, we propose a droplet contact method that allows for the solution exchange of droplets via microfluidic channels. We experimentally and numerically investigated the bilayer stability with respect to exchanging flow rates, and then demonstrated a binding assay of an alpha-hemolysin using one of its blockers. The solution exchange in this system was conducted in less than 20 s without rupturing the membrane. We believe that the proposed system will enhance the efficiency of ion channel analyses.


[Idiopathic Inflammatory Myopathies].
Myositis is a rare and an extremely heterogeneous autoimmune disease, that causes muscle weakness. Currently, "idiopathic inflammatory myopathies (IIM)" is the preferred umbrella-term used to describe the disease complexity within individuals. IIM include dermatomyositis, polymyositis, inclusion body myositis, autoimmune necrotizing myopathy, overlap myositis and antisynthetase syndrome. Research activity concerning myositis was very intense over the past ten years and led to new diagnostic approach as well as to novel therapeutic strategies. Correct classification is the key for successful management. One single treatment regime for every possible organ involvement in all different forms of IIM is still not existing.


Pervasiveness of Staphylococcus carnosus over Staphylococcus xylosus is affected by the level of acidification within a conventional meat starter culture set-up.
Staphylococcus carnosus and Staphylococcus xylosus are commonly used, individually or in combination, within conventional starter cultures for the purposes of colour and flavour development during meat fermentation. Yet, little is known about the relative importance of both species under different processing conditions. The present study aimed at investigating the competitiveness of S. carnosus within a meat starter culture under different acidification profiles. The experimental set-up involved a gradient of decreasing experimental control but increasing realism, ranging from liquid meat fermentation models in a meat simulation medium, over solid mince-based meat fermentation models, to fermented sausage production on pilot-scale level. In general, S. carnosus gained a fitness advantage over S. xylosus in the most acidified variants of each set-up. In contrast, increasing persistence of S. xylosus was seen at the mildest acidification profiles, especially when approximating actual meat fermentation practices. Under such conditions, S. carnosus was reduced to co-prevalence in the mince-based meat fermentation models and was fully outcompeted on pilot-scale level. The latter was even the case when no S. xylosus starter culture was added, whereby S. carnosus was overpowered by staphylococci that originated from the meat background (mostly S. xylosus strains). The results of the present study suggested that conventional starter cultures behave differently when applied in different technological set-ups or using different recipes, with possible repercussions on fermented meat product quality.


Volatility of unevenly sampled fractional Brownian motion: an application to ice core records.
The analysis of many natural time series and especially those related to ice core records often suffers from uneven sampling intervals. For fractional Brownian motion, we show that standard estimates of the volatility can be strongly biased due to uneven sampling. Taking these limitations into account, we study high-resolution records of temperature proxies obtained from Antarctic ice cores. We find that the volatility properties reveal a strong nonlinear component in the temperature time series for time scales of 5-200 kyr extending earlier results. These findings suggest in particular that temperature increments over these time scales appear in clusters of big and small increments-a big (positive or negative) change is most likely followed by a big (positive or negative) change and a small change is most likely followed by a small change.


Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial.
To investigate the effect of melatonin treatment on health status and sleep in children with idiopathic sleep-onset insomnia. A randomized, double-blind, placebo-controlled trial was conducted in a Dutch sleep center, involving 62 children, 6 to 12 years of age, who suffered more than 1 year from idiopathic chronic sleep-onset insomnia. Patients received either 5 mg melatonin or placebo at 7 pm. The study consisted of a 1-week baseline period, followed by a 4-week treatment. Health status was measured with the RAND General Health Rating Index (RAND-GHRI) and Functional Status II (FS-II) questionnaires. Lights-off time, sleep onset, and wake-up time were recorded in a diary, and endogenous dim light melatonin onset was measured in saliva. The total scores of the RAND-GHRI and FS-II improved significantly more during melatonin treatment compared to placebo. The magnitude of change was much higher in the melatonin group than in the placebo group, with standardized response means for the RAND-GHRI of 0.69 versus 0.07 and for the FS-II of 1.61 versus 0.64. Melatonin treatment also significantly advanced sleep onset by 57 minutes, sleep offset by 9 minutes, and melatonin onset by 82 minutes, and decreased sleep latency by 17 minutes. Lights-off time and total sleep time did not change. Melatonin improves health status and advances the sleep-wake rhythm in children with idiopathic chronic sleep-onset insomnia.


Thermal stability of human albumin measured by differential scanning calorimetry. I. Effects of caprylate and N-acetyltryptophanate.
The thermal stability of 5% previously unheated, undefatted human albumin monomer in 145 mM Na+, pH 7.0 was investigated by differential scanning calorimetry (DSC) as a function of added caprylate and/or N-acetyl-DL-tryptophanate. Caprylate was substantially more effective than N-acetyl-DL-tryptophanate in protecting the protein against thermal denaturation at a given level or at a saturating level of stabilizer. The tracing of the differential heat capacity versus temperature (thermogram) for this undefatted monomer that contained 1.5 mol endogenous, long-chain fatty acid (LCFA)/mol monomer exhibits two denaturation peaks (endotherms) in the absence of stabilizer. The endotherm with the lower denaturation temperature (Td) comprises 70% of the total heat of denaturation and also corresponds to irreversible denaturation and precipitation of 70% of the albumin. This endotherm is associated with more thermally labile protein species containing low levels of LCFA. The endotherm with the higher Td is associated with more stable protein species containing high levels of LCFA. Thus, the two endotherms are not related to the proposed domain structure of the protein but result from an uneven LCFA distribution that is due to preexisting heterogeneity in the albumin and/or heterogeneity that arises during the DSC experiment. Binding data do not support a preexisting uneven distribution of sufficient magnitude to explain the experimental results. A complementary explanation is that an uneven fatty acid distribution arises during the DSC experiment by migration of LCFA from the more labile species to the more stable as the former unfold; such migration would cause further stabilization of the latter.


The role and strategy of IMRT in radiotherapy of pelvic tumors: Dose escalation and critical organ sparing in prostate cancer.
To investigate the intensity-modulated radiotherapy (IMRT) strategy in dose escalation of prostate and pelvic lymph nodes. Plan dosimetric data of 10 prostate cancer patients were compared with two-dimensional (2D) or IMRT techniques for pelvis (two-dimensional whole pelvic radiation therapy [2D-WPRT] or IM-WPRT) to receive 50 Gy or 54 Gy and additional prostate boost by three-dimensional conformal radiation therapy or IMRT (3D-PBRT or IM-PBRT) techniques up to 72 Gy or 78 Gy. Dose-volume histograms (DVHs), normal tissue complication probabilities (NTCP) of critical organ, and conformity of target volume in various combinations were calculated. In DVH analysis, the plans with IM-WPRT (54 Gy) and additional boost up to 78 Gy had lower rectal and bladder volume percentage at 50 Gy and 60 Gy, compared with those with 2D-WPRT (50 Gy) and additional boost up to 72 Gy or 78 Gy. Those with IM-WPRT (54 Gy) also had better small bowel sparing at 30 Gy and 50 Gy, compared with those with 2D-WPRT (50 Gy). In NTCP, those with IM-WPRT and total dose of 78 Gy achieved lower complication rates in rectum and small bowel, compared with those of 2D-WPRT with total dose of 72 Gy. In conformity, those with IM-WPRT had better conformity compared with those with 2D-WPRT with significance (p < 0.005). No significant difference in DVHs, NTCP, or conformity was found between IM-PBRT and 3D-PBRT after IM-WPRT. Initial pelvic IMRT is the most important strategy in dose escalation and critical organ sparing. IM-WPRT is recommended for patients requiring WPRT. There is not much benefit for critical organ sparing by IMRT after 2D-WPRT.


Level of stress and common coping strategies among physician assistant students.
This study assessed levels of stress and coping strategies in physician assistant (PA) students. The study used a descriptive, cross-sectional design. Data were collected through an electronic survey that was sent to all current student members of the Texas Academy of Physician Assistants (N = 560). The Perceived Stress Scale was used to measure level of stress, and the Brief COPE Inventory was used to measure coping strategies. A total of 146 (26.3%) students participated in the study. Most respondents were female, young, single, and Caucasian/non-Hispanic. The mean stress score was 33.3, higher than that reported in the overall general US population. Areas of most concern included feeling nervous and stressed, feeling upset about unexpected happenings, and an inability to control life's irritations and manage personal problems. Self-distraction, venting, and self-blame were the most frequently used unhealthy coping strategies. Acceptance, active coping, and emotional support were the most frequently used positive coping strategies. The results of this study indicated that students in PA training experience higher levels of stress than the general population in the United States, making healthy coping strategies among PA students particularly important. The results of this study can inform future research, curriculum design, teaching methods, and educational intervention in PA training programs.


Increased incidence trend of low-grade and high-grade neuroendocrine neoplasms.
The incidence of neuroendocrine neoplasms is increasing. This work aimed at: (i) establishing worldwide incidence trend of low-grade neuroendocrine neoplasms; (ii) defining the incidence and temporal trend of high-grade neuroendocrine neoplasms in USA utilizing the Surveillance Epidemiology and End Results database; (iii) comparing trends for low-grade vs. high-grade neuroendocrine neoplasms. We conducted a literature search on MEDLINE and Scopus databases and incidence trends were plotted for 1973-2012. The Surveillance Epidemiology and End Results database was used to identify incidence rates in USA for 1973-2012. Incidence rates were stratified according to histological grade, gender and ethnicity. Trends were summarized as annual percent change and corresponding 95% confidence interval. 11 studies were identified involving 72,048 cases; neuroendocrine neoplasm incidence rates increased over time in all countries for all sites, except for appendix. In Surveillance Epidemiology and End Results low-grade neuroendocrine neoplasm incidence rate increased from 1.09 in 1973 to 3.51 per 100,000 in 2012. During this interval, high-grade neuroendocrine neoplasm incidence rate increased from 2.54 to 10.52 per 100,000. African Americans had the highest rates of digestive neuroendocrine neoplasms with male prevalence in high-grade. Our data indicate an increase in the incidence of neuroendocrine neoplasms as a worldwide phenomenon, affecting most anatomical sites and involving both low-grade and high-grade neoplasms.


Hypoxia/reoxygenation induction of monocyte chemoattractant protein-1 in melanoma cells: involvement of nuclear factor-kappaB, stimulatory protein-1 transcription factors and mitogen-activated protein kinase pathways.
Monocyte chemoattractant protein-1 (MCP-1) expression is found in malignant melanoma and melanoma metastases. Since areas of hypoxia/reoxygenation (H/R) are a common feature of malignant tumours and metastases, we addressed the question whether melanoma cells produce MCP-1 upon exposure to H/R. In the present study, we show that melanoma cells up-regulate MCP-1 mRNA and protein under H/R. By means of reporter gene analysis, we further demonstrate that H/R induces transcriptional activation of the MCP-1 promoter carrying a stimulatory protein-1 (SP1) and two nuclear factor-kappaB (NF-kappaB) binding motifs. Accordingly, H/R-stimulated melanoma cells showed enhanced binding activity of both transcription factors NF-kappaB and SP1 in electrophoretic mobility-shift assay. A common upstream activator of NF-kappaB, inhibitory kappaBalpha kinase, was not significantly activated under H/R conditions. Further analysis of upstream signalling events revealed that members of the mitogen-activated protein kinases family, namely extracellular signal-regulated protein kinase, c-Jun N-terminal kinase/ stress-activated protein kinase and p38 stress kinase, may be involved in MCP-1 transcriptional regulation under H/R. In summary, we conclude that H/R induces MCP-1 production in melanoma cells via the co-operative action of both transcription factors NF-kappaB and SP1, and involves mitogen-activated protein kinase signalling pathways. Functionally, H/R-induced MCP-1 production may contribute to tumour progression by committing selective pressure on tumour cells via chemoattraction and activation of tumour-infiltrating monocytes/macrophages.


The prevalence of vitamin A deficiency in 1994 on an atoll of the Marshall Islands and its relationship to locally grown food.
In an area of the world not previously studied for the presence of nutritional deficiencies, this study conducted in 1994, examined the prevalence of Vitamin A deficiency on a representative atoll of the Marshall Islands. All children ages three through ten living on Mili atoll were surveyed. The study was conducted house-to-house with all 38 subjects on the atoll voluntarily enrolling in the study. Vitamin A status was assessed by conjunctival impression cytology with transfer ([CT), clinical ophthalmic signs, and nutritional survey in all children ages three through ten living on Mili atoll, Republic of the Marshall Islands. Forty-seven percent had xerophthannia (5% with XN, 39% with XN + XIA, and 3% with XN + XIB). More than three-quarters (78%) were ICT abnormal, indicating 31% of the population had mild sub-clinical vitamin A deficiency. Eighty-six percent of the children had not received the U.S. recommended daily allowance of vitamin A in the previous week. Oiven the World Health Organization's published guidelines that anything greater than a 1% prevalence, Vitamin A deficiency on Mili atoll may be classified as a significant public health problem.


[Anthelmintic control of multiresistant nematodes in the gastrointestinal tract of imported goats].
Multiple resistant strains of Ostertagia and Trichostrongylus were detected in a flock of cashmere and angora goats imported from New Zealand. The ED50 values detected by in vitro EHA test were from 0.27 to 0.36 micrograms/ml (while the reference value of sensitivity is 0.10 microgram/ml TBZ). Multiple resistance to all the types of currently used anthelmintics was confirmed by in vivo FECRT, when the efficacy of recommended doses was lower than 90% (albendazole 74%, levamisole 86%, ivermectin 83%). Two control schemes were investigated. In the simultaneous application of anthelmintics in the double or triple of recommended doses (0.4 mg/kg ivermectin s.c., 30 mg/kg levamisole and 20 mg/kg albendazole p.o.) was effective. Examination of goats 7 and 8 months after treatment revealed the repeated presence of multiple resistant gastrointestinal nematodes. It is the first published case of intercontinental transfer of resistant strains of nematodes when importing small ruminants.


A conventional new procedure for N-acylation of unprotected amino acids.
The preparation of amide derivatives (4) by N-acylation of unprotected alpha-amino acids is easily achieved via readily available benzotriazolyl carboxylates (2a-d) or succinimidyl carboxylates (2e-f). These intermediates (2) are prepared from reaction of carboxylic acids (1) with 1-hydroxybenzotriazole (HO-Bt) or N-hydroxysuccinimide (HO-Su) in the presence of equimolar amounts of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide hydrochloride (WSCI). The overall yields of the target compounds (4) were excellent, and this two-stage procedure could be applicable as an alternative procedure for one-pot reaction.


Discovery of Potent, Selective, and Orally Bioavailable Estrogen-Related Receptor-γ Inverse Agonists To Restore the Sodium Iodide Symporter Function in Anaplastic Thyroid Cancer.
An inverse agonist of estrogen-related receptor-γ (ERRγ), an orphan nuclear receptor encoded by E srrg, enhances sodium iodide symporter-mediated radioiodine uptake in anaplastic thyroid cancer (ATC) cells, thereby facilitating responsiveness to radioiodine therapy in vitro. We synthesized potent, selective, and orally bioavailable ERRγ-inverse agonists and evaluated their activity by analyzing in vitro pharmacology and absorption, distribution, metabolism, excretion, and toxicity profiles. X-ray crystallographic analysis of the ligand and ERRγ complex showed that 35 completely binds to the target protein (PDB 6A6K ). Our results showed improved radioiodine avidity in ATC cells through compound 35-mediated upregulation of iodide-handling genes, leading to enhanced responsiveness to radioiodine therapy in vitro. Importantly, in vivo 124I-positron emission tomography/computed tomography imaging revealed that 35 increases radioiodine avidity in CAL62 tumors. Collectively, these results demonstrated that 35 can be developed as a promising treatment for ERRγ-related cancer in the future.


Growth rates of children of subsaharan African ancestry born to immigrant parents and of French children in Paris.
This comparative survey is based on two populations of children born and raised in Paris or the Paris area: 320 French children and 129 children whose parents are both of African ancestry from the Subsaharan area. They are part of a first generation born outside of their respective countries. A longitudinal study of growth from birth to four years of age shows population differences. The length and weight at birth of full-term African babies are significantly less than of French newborns. But, African infants catch-up quickly and reach the same length as French infants during the first month of life; their weight is already significantly greater than that of French infants from 1 to 6 months. The body mass index (BMI, W/H2 ) during the breast-feeding period indicates that the infants are of well nourished status. After the first year of life, the means for the BMI of the children born to Subsaharan immigrant parents are lower than means for French children. This suggests poorer nutritional status, which may be associated with the marginal socioeconomic status of African families living in the Paris area. Am. J. Hum. Biol. 10:757-763, 1998. © 1998 Wiley-Liss, Inc.


Evaluation of clinical outcomes and bone loss around titanium implants with oxidized surface: six-year follow-up results from a prospective case series study.
The aim of this prospective study was to assess long-term clinical outcomes and peri-implant bone level changes around oxidized implants supporting partial fixed rehabilitations. Twenty-two partially edentulous patients were included in the study. A total of 33 fixed rehabilitations were placed, supported by 54 titanium implants with oxidized microtextured surface. Prostheses were delivered after 3 and 6 months of implant placement in the mandible and maxilla, respectively. Patients were scheduled for follow-up at 6 and 12 months and then yearly. At each follow-up, plaque level and bleeding scores were assessed and periapical radiographs were taken. The main outcomes were prosthesis success, implant survival, implant success, and marginal bone level change. Three patients were excluded from the study because they did not attend the 1-year follow-up. Nineteen patients, accounting for 49 implants, were followed for at least 6 years after prosthesis delivery. The mean follow-up duration was 81.8 months (range 75-96 months). One mandibular single-tooth implant failed after 1 year in a smoker woman. Cumulative implant survival and success at 6 years were 98.0% and 95.9%, respectively. Prosthesis success was 96.7%. The mean peri-implant bone loss at 6 years was 0.76 ± 0.47 mm. Not significantly (p = .75) greater bone loss was found in the maxilla (0.78 ± 0.14 mm, n = 19) as compared with the mandible (0.74 ± 0.59 mm, n = 30). In the maxilla, bone loss was significantly greater around implants supporting partial prostheses as compared with single-tooth implants (p = .03). Full patient satisfaction was reported. Implants with oxidized microtextured surface may achieve excellent long-term clinical outcomes in the rehabilitation of partial edentulism.


What is regressive autism and why does it occur? Is it the consequence of multi-systemic dysfunction affecting the elimination of heavy metals and the ability to regulate neural temperature?
There is a compelling argument that the occurrence of regressive autism is attributable to genetic and chromosomal abnormalities, arising from the overuse of vaccines, which subsequently affects the stability and function of the autonomic nervous system and physiological systems. That sense perception is linked to the autonomic nervous system and the function of the physiological systems enables us to examine the significance of autistic symptoms from a systemic perspective. Failure of the excretory system influences elimination of heavy metals and facilitates their accumulation and subsequent manifestation as neurotoxins: the long-term consequences of which would lead to neurodegeneration, cognitive and developmental problems. It may also influence regulation of neural hyperthermia. This article explores the issues and concludes that sensory dysfunction and systemic failure, manifested as autism, is the inevitable consequence arising from subtle DNA alteration and consequently from the overuse of vaccines.


Polygenic risk for depression and anterior and posterior hippocampal volume in children and adolescents.
Depression has frequently been associated with smaller hippocampal volume. The hippocampus varies in function along its anterior-posterior axis, with the anterior hippocampus more strongly associated with stress and emotion processing. The goals of this study were to examine the associations among parental history of anxiety/depression, polygenic risk scores for depression (PGS-DEP), and anterior and posterior hippocampal volumes in children and adolescents. To examine specificity to PGS-DEP, we examined associations of educational attainment polygenic scores (PGS-EA) with anterior and posterior hippocampal volume. Participants were 350 3- to 21-year-olds (46 % female). PGS-DEP and PGS-EA were computed based on recent, large-scale genome-wide association studies. High-resolution, T1-weighted magnetic resonance imaging (MRI) data were acquired, and a semi-automated approach was used to segment the hippocampus into anterior and posterior subregions. Children and adolescents with higher polygenic risk for depression were more likely to have a parent with a history of anxiety/depression. Higher polygenic risk for depression was significantly associated with smaller anterior but not posterior hippocampal volume. PGS-EA was not associated with anterior or posterior hippocampal volumes. Participants in these analyses were all of European ancestry. Polygenic risk for depression may lead to smaller anterior but not posterior hippocampal volume in children and adolescents, and there may be specificity of these effects to PGS-DEP rather than PGS-EA. These findings may inform the earlier identification of those in need of support and the design of more effective, personalized treatment strategies. none. None.


Neuropsychological outcome after percutaneous coronary intervention or coronary artery bypass grafting: results from the Stent or Surgery (SoS) Trial.
Coronary artery bypass surgery (CABG) has been associated with a range of neurological and neuropsychological complications from stroke to cognitive problems such as memory and problem solving disturbance. However, little is known about the impact of percutaneous coronary intervention (PCI) on neuropsychological outcome. In the Stent or Surgery Trial (SoS), 988 patients were randomized in equal proportions between PCI supported by stent implantation and CABG. As a substudy of this trial, we undertook an evaluation of neurological and neuropsychological outcomes after intervention. A clinical examination and neuropsychological assessment consisting of 5 tests (Digit Span Forwards and Backwards, Visual Reproduction, Bourdon, and Block Design) were performed at baseline and 6 and 12 months after the procedure. A total of 145 patients were included in the substudy analysis: 77 in the PCI group and 68 in the CABG group. One patient in the PCI arm had a stroke. There was no significant difference between treatment groups at 6 and 12 months for any of the 5 tests. The mean change from baseline was also similar in both groups. We were not able to demonstrate an important and significant difference in neuropsychological outcome in patients treated with different revascularization strategies. This important finding needs to be examined in further research.


RNA-Sequencing Analyses Demonstrate the Involvement of Canonical Transient Receptor Potential Channels in Rat Tooth Germ Development.
Tooth development depends on multiple molecular interactions between the dental epithelium and mesenchyme, which are derived from ectodermal and ectomesenchymal cells, respectively. We report on a systematic RNA sequencing analysis of transcriptional expression levels from the bud to hard tissue formation stages of rat tooth germ development. We found that GNAO1, ENO1, EFNB1, CALM1, SIAH2, ATP6V0A1, KDELR2, GTPBP1, POLR2C, SORT1, and members of the canonical transient receptor potential (TRPC) channel family are involved in tooth germ development. Furthermore, Cell Counting Kit 8 (CCK8) and Transwell migration assays were performed to explore the effects of these differentially expressed genes (DEGs) on the proliferation and migration of dental pulp stem cells. Immunostaining revealed that TRPC channels are expressed at varying levels during odontogenesis. The identified genes represent novel candidates that are likely to be vital for rat tooth germ development. Together, the results provide a valuable resource to elucidate the gene regulatory mechanisms underlying mammalian tooth germ development.