Outcomes assessment for forensic neuropsychology: recommendations and considerations.
Neuropsychologists are frequently retained by attorneys or the courts to assist in the resolution of legal disputes. Yet, an outcomes assessment demonstrating the utility of neuropsychological evaluations in the forensic arena has not been implemented, nor has a method for conducting an outcomes assessment of forensic neuropsychology been delineated. This article offers recommendations and considerations for the formulation of outcomes assessments. These include defining an outcomes assessment, identifying the consumers of forensic neuropsychological assessments, and specifying potential moderator and dependent variables in the context of study designs that may be feasibly implemented. Moreover, the ethical implications of outcomes assessments are discussed.


Awake Prone Positioning in COVID-19 Hypoxemic Respiratory Failure: Exploratory Findings in a Single-center Retrospective Cohort Study.
Awake prone positioning has been widely used in patients with COVID-19 respiratory failure to avoid intubation despite limited evidence. Our objective was to evaluate if prone positioning is associated with a reduced intubation rate when compared to usual care. This was a retrospective cohort study in the emergency department of a large quaternary hospital in Sao Paulo. We retrieved data from all admitted patients in need of oxygen supplementation (>3 L/min) and tachypnea (>24 ipm) from March 1 to April 30, 2020, excluding those who had any contraindication to the prone position or who had an immediate need for intubation. The primary endpoint was endotracheal intubation up to 15 days. Secondary outcomes included a 6-point clinical outcome ordinal scale, mechanical ventilation-free days, admission to the intensive care unit, and need of hemodialysis and of vasoactive drugs, all assessed at or up to 15 days. We analyzed unadjusted and adjusted effect estimates with Cox proportional hazards models, logistic regression, quantile regression, and sensitivity analyses using propensity score models. Of 925 suspected COVID-19 patients admitted off mechanical ventilation, 166 patients fulfilled inclusion and exclusion criteria: 57 were exposed to prone positioning and 109 to usual care. In the intervention group, 33 (58%) were intubated versus 53 (49%) in the control group. We observed no difference in intubation rates in the univariate analysis (hazard ratio = 1.21, 95% confidence interval [CI] = 0.78 to 1.88, p = 0.39) nor in the adjusted analysis (hazard ratio = 0.90, 95% CI = 0.55 to 1.49, p = 0.69). Results were robust to the sensitivity analyses. Secondary outcomes did not differ between groups. Awake prone positioning was not associated with lower intubation rates. Caution is necessary before widespread adoption of this technique, pending results of clinical trials.


[The lived experiences of stroke caregivers three months after discharge of patients from rehabilitation hospitals].
Caregiving of stroke patients has a long trajectory and the experiences of caregi- vers may change over time. Few studies have described the experience of stroke caregi- vers three months after discharge of patients from rehabilitation hospitals. This study describes the experience of stroke caregivers three months after patients are discharged home from a rehabilitation hospital. phenomenological study Seven themes emerged from analysis: deeply-changed life; re-appreciation of the relationship with patient and family members; increased workload; difficulties in getting support from the national health-care system; lack of preparation for caregiving; difficulties in coordinating caregiving, family and personal life; relief after patient's recovery. A comprehensive understanding of stroke caregivers' experience during the three months after patient discharge can support the development of educational interventions aimed at improving the caregiver preparation for the care of patients.


Nonsurgical collection and nonsurgical transfer of preimplantation embryos in the domestic rabbit (Oryctolagus cuniculus) and domestic ferret (Mustela putorius furo).
The objective of this study was to develop nonsurgical methods of embryo collection and transfer in domestic rabbits (Oryctolagus cuniculus) and domestic ferrets (Mustela putorius furo) to serve as models for use in mammals in which surgical procedures are the usual means for applying embryo transfer technology. Specially designed transcervical catheters were used together with a fibre optic endoscope to visualize and then catheterize the rabbit and ferret cervices. Five consecutive transcervical uterine flushes in each of eight superovulated female rabbits 78-89 h after an ovulatory injection of LH resulted in the retrieval of 187 embryos, for an average of 23 embryos per rabbit. A total of 116 embryos were nonsurgically transferred to the uteri of ten recipients, and resulted in 23 young (20%). Eight rabbits (80%) produced young with an average litter size of 2.88 (range 1-7). Ten consecutive transcervical uterine flushes in each of 37 female ferrets 145-178 h after an ovulatory injection of hCG resulted in the retrieval of 324 embryos, an average of 8.76 embryos per ferret. A total of 251 embryos from 27 donors were nonsurgically transferred to the uteri of 31 recipients, and resulted in 65 young (26%). Twenty-eight of the recipients (90%) were initially pregnant, as indicated by postpartum necropsies, and twenty-two ferrets (71%) produced young. The average litter size was 2.95 (range 1-7). This is the first report of live births resulting from the nonsurgical collection of embryos from a donor followed by nonsurgical transfer of those same embryos to a synchronous recipient. The methods reported here can serve as models for use in other mammals in which direct visualization and manipulation of the cervix are not possible, and will be particularly useful in endangered species.


The oasis effect: response of birds to exurban development in a southwestern savanna.
Ranches are being converted to exurban housing developments in the southwestern United States, with potentially significant but little-studied impacts on biological diversity. We counted birds in grasslands and savannas in southeastern Arizona that were grazed by livestock, embedded in low-density exurban housing developments, or both, or neither. Species richness and bird abundance were higher in exurban neighborhoods than in undeveloped landscapes, independent of livestock grazing. The positive response to development was particularly evident among doves, quail, hummingbirds, aerial insectivores, and some but not all ground-foraging sparrows. Effects of livestock grazing were comparatively minor and mostly involved birds with requirements for tall ground cover or the lack of it. The average rank correlation between counts of individual species and housing density was positive across all transects. However, this relationship disappeared among the exurban transects alone, and bird species richness on the exurban transects was negatively correlated with the number of homes nearby. These results suggest that the positive influence of exurban development on avian abundance and variety was greatest at the lowest housing densities. We attribute the attraction of many birds to exurban development to an oasis effect, in which resources otherwise scarce in arid southwestern environments (shade, nectar, nest sites, and especially water) are relatively abundant around exurban home sites. This finding is consistent with the hypothesis that exurban home sites represented resource supply points inside birds' home ranges otherwise consisting mostly of natural vegetation.


Attacks on postmen in Northern Ireland. What features of the attacks are associated with prolonged absence from work?
The sickness absence records of 228 postmen who had been attacked on duty in Northern Ireland between 1985 and 1989 were examined. The pattern of absences due to psychological causes in the six months after the attack was recorded. The presence of relevant sickness absence and the amount was correlated to three specific features of the attacks, ie use of arms, use of violence and abduction. Armed attacks produced a significantly more frequent and larger amount of sickness absence. The proportion of victims taking any sickness absence after violent attacks was not significantly greater but those who did so were off work for much longer. Abduction of victims from the scene produced much more frequent absence from work but there was no significant difference in the duration of the absence. The 20 employees who were attacked for a second time during the study period showed a five-fold increase in the length of sickness absence taken.


Influence of Total Anthocyanins from Bitter Melon (Momordica charantia Linn.) as Antidiabetic and Radical Scavenging Agents.
The majority of the antioxidant and antidiabetic activities of fruits are anthocyanins; a group of polyphenolics that are responsible for the color of many fruits, vegetables and flowers. The harvesting time, storage conditions, maturity, extraction steps etc. are very important for the biological activities based on the alteration of chemical composition. The free radical scavenging and antidiabetic activities of total anthocyanins from bitter melon (Momordica charantia Linn) fruit (TAMC) were evaluated by considering four harvesting times. The free radical scavenging activities of the TAMC samples were assessed using DPPH(•), DMPD(•+) and ABTS(•+) assays against BHA, rutin and trolox standards. September as a harvesting period (TAMC-S) had effective DPPH(•) (SC50 2.55 ± 0.08 μg/mL), DMPD(•+) (SC50 2.68 ± 0.09 μg/mL) and ABTS(•+) (SC50 8.19 ± 0.09 μg/mL) scavenging activities compared with other samples and standards. In addition, August (TAMC-A) as a harvesting period showed very influential inhibitory activity against α-amylase (IC50 56.86 ± 1.12 μg/mL) and moderate inhibitory activity against α-glucosidase (IC50 88.19 ± 0.74 μg/mL). In comparison, pharmaceutical active ingredients such as acarbose exhibited anti-amylase and anti-glucosidase activities with IC50 values of 93.07 ± 1.49 μg/mL and 77.25 ± 1.20 μg/mL respectively. These results suggest that the correct selection of harvest period can significantly increase anthocyanin quantity because of the pharmaceutic properties of TAMC. Consequently, TAMC may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia that can be also used as food additives due to its antiradical activity.


Fall of Community-Acquired Pneumonia in Children following COVID-19 Non-Pharmaceutical Interventions: A Time Series Analysis.
Non-pharmaceutical interventions (NPIs) were implemented to reduce the spread of coronavirus disease 2019 (COVID-19). A first national lockdown was decided in France on the 17 March 2020. These measures had an impact on other viral and non-viral infectious diseases. We aimed to assess this impact on community-acquired pneumonia (CAP) in children. We performed a quasi-experimental interrupted time series analysis. We used data from a French prospective surveillance system of six pediatric emergency departments (PEDs). All visits from 1 January 2017 to 31 December 2020 were included. Pre-intervention period was before 17 March 2020 and post-intervention period was after 18 March 2020. We estimated the impact on the weekly number of visits for CAP and CAP admission using quasi-Poisson regression modeling. A total of 981,782 PEDs visits were analyzed; among them, 8318 visits were associated with CAP, and 1774 of these were followed by a hospital admission. A major decrease was observed for CAP visits (-79.7% 95% CI [-84.3; -73.8]; p < 0.0001), and CAP admission (-71.3% 95 CI [-78.8; -61.1]; p < 0.0001). We observed a dramatic decrease of CAP in children following NPIs implementation. Further studies are required to assess the long-term impact of these measures.


Low molecular weight heparin (Logiparin) as thromboprophylaxis in elective abdominal surgery. A dose finding study.
The efficacy and safety of a new not yet registered low molecular weight heparin (LMWH) (Logiparin) as thromboprophylactic agent was assessed in 51 patients undergoing major elective surgery. The patients were divided into three groups receiving either 2,500 anti-Xa international units (IU) (group 1), 50 IU per kg body weight (group 2) or 3,500 IU (group 3) subcutaneously once daily. All patients were screened with the 125I-fibrinogen uptake test, and whenever a FUT was abnormal or when clinical signs were present ascending phlebography was performed. Thrombosis occurred in 12.5% of the patients in group 1 and 0% of the patients in groups 2 and 3 (p greater than 0.05). In groups 1 and 2 only minor bleeding complications were recorded. In group 3 there was one haemorrhagic episode requiring interruption of the LMWH treatment. The optimal doses of this new LMWH seems to be in the range 2,500 IU-3,500 IU once daily. The final dose recommendation has to be established in large scale clinical trials.


Fear conditioning following unilateral temporal lobectomy: dissociation of conditioned startle potentiation and autonomic learning.
The present study investigated fear-potentiated startle and autonomic learning in brain-lesioned patients in a classical fear-conditioning paradigm. Startle blink and skin conductance responses of 30 patients who underwent unilateral temporal lobectomy because of drug-resistant epilepsy were compared with those of 32 healthy controls. As expected, temporal lobectomy patients showed a general impairment in fear conditioning relative to controls. This impairment did not differ with respect to the affected hemisphere. Moreover, while fear-conditioned startle potentiation in healthy controls was independent of contingency awareness, skin conductance discrimination was only observed for those participants who correctly recognized the stimulus contingencies. Patients who acquired a declarative memory of the contingencies also showed intact skin conductance discrimination but failed to exhibit fear-potentiated startle. The present findings support a two-levels-of-learning account of human fear conditioning and also demonstrate that the amygdala is crucially involved in fear learning.


Do-not-resuscitate orders in intensive care units. Current practices and recent changes.
To describe the characteristics of patients with do-not-resuscitate (DNR) orders and the frequency and timing of these orders in a representative sample of intensive care units (ICUs) and to compare practices from 1980 to 1990. Prospective inception cohort. A total of 42 ICUs in 40 US hospitals with 200 or more beds; 26 randomly selected hospitals and 14 large, tertiary care hospitals that volunteered to be studied. A consecutive sample of 17,440 ICU admissions from 1988 to 1990. Patient demographic characteristics, comorbid conditions, disease, and physiological abnormalities. Frequency and timing of DNR orders; ICU resource use before and after DNR orders; and patients' hospital and ICU discharge status. Physicians wrote DNR orders for 1577 ICU admissions (9%) (hospital range, 1.5% to 22%). Patients with ICU DNR orders were older, more functionally impaired, had more comorbid illness, a higher severity of illness, and required the use of more ICU resources compared with patients without DNR orders. Compared with data from a similar survey from 1979 to 1982, ICU DNR orders were more frequent in 1988 to 1990 (9% vs 5.4%; P < .001) and preceded 60% of all in-unit deaths compared with only 39% in 1979 to 1982 (P < .001). Do-not-resuscitate orders were written sooner (for 3.6% vs 2.0% of patients on day 1 in the ICU) and patients with DNR orders remained in the ICU longer in 1988 to 1990 (2.8 vs 1.4 days) than in 1979 to 1982, and had lower ICU and hospital mortality rates (64% vs 74%, P < .001; and 85% vs 94%, P < .001). Over the last decade physicians and patients' families set limits earlier and more frequently in cases likely to have poor outcomes. We attribute this change to a greater dialogue about setting limits to care and a greater knowledge of treatment outcomes among physicians and families. These changes in practice preceded implementation of the Patient Self-determination Act, designed to ensure patient autonomy for decisions about life-sustaining therapy.


Coverage and cost of a large oral cholera vaccination program in a high-risk cholera endemic urban population in Dhaka, Bangladesh.
A feasibility study of an oral cholera vaccine was carried out to test strategies to reach high-risk populations in urban Mirpur, Dhaka, Bangladesh. The study was cluster randomized, with three arms: vaccine, vaccine plus safe water and hand washing practice, and no intervention. High risk people of age one year and above (except pregnant woman) from the two intervention arms received two doses of the oral cholera vaccine, Shanchol™. Vaccination was conducted between 17th February and 16th April 2011, with a minimum interval of fourteen days between two doses. Interpersonal communication preceded vaccination to raise awareness amongst the target population. The number of vaccine doses used, the population vaccinated, left-out, drop out, vaccine wastage and resources required were documented. Fixed outreach site vaccination strategy was adopted as the mode of vaccine delivery. Additionally, mobile vaccination sites and mop-up activities were carried out to reach the target communities. Of the 172,754 target population, 141,839 (82%) and 123,666 (72%) received complete first and second doses of the vaccine, respectively. Dropout rate from the first to the second dose was 13%. Two complete doses were received by 123,661 participants. Vaccine coverage in children was 81%. Coverage was significantly higher in females than in males (77% vs. 66%, P<0.001). Vaccine wastage for delivering the complete doses was 1.2%. The government provided cold-chain related support at no cost to the project. Costs for two doses of vaccine per-person were US$3.93, of which US$1.63 was spent on delivery. Cost for delivering a single dose was US$0.76. We observed no serious adverse events. Mass vaccination with oral cholera vaccine is feasible for reaching high risk endemic population through the existing national immunization delivery system employed by the government.


Breast Cancer Presenting As Onconeural Antibody Negative Opsoclonus-Myoclonus Syndrome.
Breast cancer can rarely present with or be preceded by paraneoplastic syndromes such as opsoclonus-myoclonus syndrome (OMS). OMS is a rare neurological syndrome that commonly presents with symptoms of rapid, chaotic eye movements (opsoclonus), jerking involuntary muscle movements (myoclonus) and is frequently associated with ataxia. We describe a case of a woman in her early 50s who presented to the emergency room (ER) with vertigo, jerking movements, loss of fine motor skills and gait abnormalities. She was initially thought to have likely vestibular neuritis and was treated symptomatically and discharged home. However, the symptoms persisted and she presented once again to the ER, at which time she also incidentally discovered a lump in her breast. This led to her being investigated more extensively leading to a diagnosis of underlying primary breast cancer. Based on her neurological clinical findings, she was diagnosed with onconeural antibody negative OMS. Treatment of her underlying malignancy led to a significant improvement in her symptoms. Paraneoplastic neurological syndromes (PNSs) are an important differential diagnosis to consider in patients presenting with persistent, treatment-resistant and non-specific neurological symptoms. Any suspicion of the same should prompt a search for an underlying malignancy that could greatly influence patient outcomes.


Activation of group II metabotropic glutamate receptors underlies microglial reactivity and neurotoxicity following stimulation with chromogranin A, a peptide up-regulated in Alzheimer's disease.
Regulation of microglial reactivity and neurotoxicity is critical for neuroprotection in neurodegenerative diseases. Here we report that microglia possess functional group II metabotropic glutamate receptors, expressing mRNA and receptor protein for mGlu2 and mGlu3, negatively coupled to adenylate cyclase. Two different agonists of these receptors were able to induce a neurotoxic microglial phenotype which was attenuated by a specific antagonist. Chromogranin A, a secretory peptide expressed in amyloid plaques in Alzheimer's disease, activates microglia to a reactive neurotoxic phenotype. Chromogranin A-induced microglial activation and subsequent neurotoxicity may also involve an underlying stimulation of group II metabotropic glutamate receptors since their inhibition reduced chromogranin A-induced microglial reactivity and neurotoxicity. These results show that selective inhibition of microglial group II metabotropic glutamate receptors has a positive impact on neuronal survival, and may prove a therapeutic target in Alzheimer's disease.


Diagnostic accuracy of Xpert MTB/RIF ultra for detection of Mycobacterium tuberculosis in children: a prospective cohort study.
The Xpert MTB/RIF Ultra is a recent advancement in molecular diagnostics of tuberculosis (TB) with higher sensitivity compared to its predecessor, the Xpert MTB/RIF assay. Prospective studies evaluating the performance of Xpert MTB/RIF Ultra in children with suspected TB are lacking. In this study, we evaluated the Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis in samples from 156 children, of which one was excluded from the analysis. Of the remaining 155 samples, 6·5% (10/155), 21·3% (33/155), 20% (31/155) and 21·9% (34/155) were positive by smear examination, MGIT culture, Xpert MTB/RIF and Xpert MTB/RIF Ultra, respectively. The Xpert MTB/RIF and Xpert MTB/RIF Ultra had a similar overall sensitivity of 81·8% (95% CI: 64·5-93) and 84·8% (95% CI: 68·1-94·9), respectively. In suspected pediatric TB patients, the Xpert MTB/RIF Ultra had higher sensitivity compared to the Xpert MTB/RIF (72·7 vs 63·6). The AUC (area under the curve) of 0·905 for the Xpert MTB/RIF and 0·893 for the Xpert MTB/RIF Ultra indicate similar and good overall performance. Both Xpert assays were found to be equally efficient, however Xpert MTB/RIF Ultra showed better detection rate in suspected TB cases.


[p-ANCA and ASCA antibodies in the differential diagnosis between ulcerative rectocolitis and Crohn's disease].
Anti-Saccaromyces cerevisiae antibodies (ASCA) seem to be associated with Crohn's disease (CD), while anti-neutrophil cytoplasm antibodies (p-ANCA) seem to be a recognised marker for ulcerative colitis (UC). Of our study was to determine whether the presence of ASCA and p-ANCA antibodies could differentiate CD from UC and IBD from aspecific chronic colitis (ACC). Serum samples were obtained from 23 patients with CD and 32 with UC, and from 13 patients with aspecific chronic colitis. Diagnosis was established on clinical findings, endoscopy and histology. Determination of ASCA and p-ANCA antibodies was performed using indirect immunofluorescence technique and ELISA, respectively. 20% CD patients against 50% UC patients expressed p-ANCA (p < 0.05). Vice versa 61% CD patients against 16% UC patients expressed ASCA (p < 0.05). The combination of positive ASCA and negative p-ANCA determined a sensibility, specificity and positive predictive value of 45%, 91% and 75% respectively, for diagnosis of CD. The combination of positive p-ANCA and negative ASCA determined a sensibility, specificity and positive predictive value of 44%, 95% and 94% respectively, for diagnosis of UC. Our results indicate that ASCA are principally expressed in patients with CD, by contrast p-ANCA seem to be strongly associated with UC. The combination of these two tests can be useful in evaluating patients with indeterminate colitis, distinguishing UC from CD.


The effects of tackle height on inertial loading of the head and neck in Rugby Union: A multibody model analysis.
There is evidence of chronic injury to the head-and-neck region of Rugby Union players. The aim of this study was to use multibody simulations to examine the effects of tackle height on both Tackler and Ball Carrier head kinematics and neck dynamics. Quantitative Exploratory Study Methods and procedures: 45 front-on shoulder tackles with no direct contact to the head/neck were simulated with the MADYMO pedestrian model and used to assess differences between upper body tackles and lower body tackles. The average resultant head linear and angular accelerations as well as neck forces and moments were assessed. Much higher Ball Carrier head kinematic values and neck loading were predicted for upper body tackles compared to lower body tackles, and principal findings were unaffected by a sensitivity analysis. Tackler results were less straightforward and trends were influenced by the sensitivity analysis for muscle activation. Although further model validation is required, the results of this study indicate the need for further research on tackle heights and inertial head-and-neck loading in the tackle phase of play in Rugby Union.


Is human classification by experienced untrained observers a gold standard in fixation detection?
Manual classification is still a common method to evaluate event detection algorithms. The procedure is often as follows: Two or three human coders and the algorithm classify a significant quantity of data. In the gold standard approach, deviations from the human classifications are considered to be due to mistakes of the algorithm. However, little is known about human classification in eye tracking. To what extent do the classifications from a larger group of human coders agree? Twelve experienced but untrained human coders classified fixations in 6 min of adult and infant eye-tracking data. When using the sample-based Cohen's kappa, the classifications of the humans agreed near perfectly. However, we found substantial differences between the classifications when we examined fixation duration and number of fixations. We hypothesized that the human coders applied different (implicit) thresholds and selection rules. Indeed, when spatially close fixations were merged, most of the classification differences disappeared. On the basis of the nature of these intercoder differences, we concluded that fixation classification by experienced untrained human coders is not a gold standard. To bridge the gap between agreement measures (e.g., Cohen's kappa) and eye movement parameters (fixation duration, number of fixations), we suggest the use of the event-based F1 score and two new measures: the relative timing offset (RTO) and the relative timing deviation (RTD).


T-regulatory cells in primary immune deficiencies.
To summarize studies on the development and function of T-regulatory (TR) cells in primary immune deficiencies (PIDs). PIDs are associated with high rates of autoimmunity. TR cells, which are critical to the control of autoimmunity, appear involved in the pathogenesis of PID-related autoimmunity. A number of PIDs, including Omenn's syndrome and Wiskott-Aldrich syndrome, have been associated with impaired production and/or function of thymus-derived (natural) TR cells. Recently defined primary immunodeficiencies, including Stim1 deficiency, IL-10 receptor deficiency, and xIAP deficiency, have been associated with defects in TR cells. De-novo generated TR cells from peripheral CD4 conventional T cells is impaired in the hyper IgE syndrome. Gene defects underlying PIDs may also compromise the TR cell, leading to breakdown of peripheral tolerance.


Highly sensitive determination of C-reactive protein on the Innotrac Aio! immunoanalyzer.
C-reactive protein (CRP) is a widely recognized indicator of inflammation. Prospective studies have shown that CRP can be used to predict the risk of future cardiovascular events in apparently healthy subjects. Clinical and laboratory studies have also shown that inflammation has an important role in the inititation, progression and destabilization of atheromas, which makes high-sensitivity CRP determinations valuable in cardiovascular risk assessment. Innotrac Aio! is a fully automated random-access immunoanalyzer using a unique all-in-one (Aio!) dry reagent concept and time-resolved fluorometric detection. In this study, the analytic performance of the Innotrac Aio! ultrasensitive CRP assay (usCRP) was evaluated. The analytical detection limit was 0.003 mg/L, the limit of quantification was <or= 0.03 mg/L and the carry-over result was within acceptable limits. Within-assay CVs obtained in lithium-heparin plasma at five concentrations ranged within 3.2 and 24.9%. Inter-assay precision using lithium-heparin plasma pools and commercial controls was 6.2-8.6% at concentrations of 0.17-33.3 mg/L. The inter-assay precision at a concentration of 0.04 mg/L using the serum pool was 67%. Regression analysis between Aio! usCRP and Cobas Integra CRP latex (Roche Diagnostics) using lithium-heparin plasma samples yielded the following results: correlation coefficient 0.983, slope 1.17 (< 50 mg/L) and correlation coefficient 0.974, slope 1.137 (< 10 mg/L). The correlation coefficient between Integra and Aio! usCRP assays using serum samples was 0.979 and the slope 1.106. Regresssion analysis between Aio! usCRP and Hitachi CRP (Latex) HS using serum samples revealed the following results: correlation coefficient 0.942, slope 0.879 (< 20 mg/L) and correlation coefficient 0.973, slope 0.983 (< 10 mg/L). EDTA whole blood samples correlated well with the corresponding plasma samples. Innotrac Aio! usCRP assay was found to be linear in the CRP concentration range of 0.09-62 mg/L. In the first quartile (0-25th percentile), 2nd quartile (25th-50th percentile), 3rd quartile (50th-75th percentile) and 4th quartile (75th-100th percentile), the mean CRP values were 0.16 mg/L, 0.52 mg/L, 1.24 mg/L and 4.39 mg/L, respectively.


Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia.
Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Schizophrenia has a range of cognitive deficits that may evolve from decreased BDNF, and this study examines this association of BDNF with cognitive deficits in schizophrenia. We recruited 251 chronic schizophrenic patients and 206 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF in both groups. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale. BDNF levels were significantly lower in patients than controls (p < 0.001). Cognitive scores on the RBANS and nearly all of its five subscales (all p < 0.001) except for the visuospatial/constructional index (p > 0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, BDNF was positively associated with immediate memory in schizophrenia. Our findings suggest that BDNF may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment, especially immediate memory.


Identification of a major cluster of Klebsiella pneumoniae isolates from patients with liver abscess in Taiwan.
Klebsiella pneumoniae has emerged as the leading liver abscess pathogen in Taiwan, with the percentage rising from 30% in the 1980s to over 80% in the 1990s. Most of the patients with K. pneumoniae liver abscess are diabetic and without biliary tract disease. Some patients develop serious extrahepatic complications such as endophthalmitis, meningitis, lung abscess, and necrotizing fasciitis. Pulsed-field gel electrophoresis (PFGE) was used for cluster analysis of 96 isolates from patients with liver abscess and 60 isolates from patients with other diseases. A total of 136 PFGE types were identified. Among the 96 liver abscess-associated isolates, 60 (62.5%) were classified in major cluster A. Cluster A included 41 PFGE types (types 1 to 41) which had a genetic similarity of at least 72.4% +/- 9.4%. The PFGE patterns of cluster A strains are so similar that they could have originated from the same ancestor. This study demonstrates that cluster A plays an important role in the high incidence of K. pneumoniae liver abscess in Taiwan.


Trastuzumab aggravates radiation induced cardiotoxicity in mice.
Some breast cancer patients with overexpression of human epidermal growth factor receptor 2 need both chest radiotherapy and targeted therapy with trastuzumab (TRZ). The cardiotoxicity associated with combined treatment potentially restricts the clinical benefits of antitumor therapy. There is no consensus on whether and how chest radiotherapy can be given in concurrent with TRZ at present, considering the cardiotoxicity. This study intends to establish an in vitro and in vivo heart injury model by irradiation and TRZ, analyze whether there is a synergistic effect in heart, and to explore the molecular changes. First, an in vitro irradiation model of H9C2 cardiomyocytes was established. The effects of TRZ and radiation on cardiomyocyte injury were observed by cell flow cytometry, CCK-8 test, Western blot, γ-H2AX fluorescence focus formation and cell Reactive Oxygen Species (ROS) content test. Second, the mouse heart injury model was set up by X-ray cardiac irradiation combined with TRZ. Six months later, the cardiac function was analyzed by small animal ultrasound and 18FDG-micro PET/CT. The morphological changes of heart tissue were assessed by histological section. We found that concurrent TRZ aggravates the injury effect of irradiation on cardiomyocytes in vitro. The influence of TRZ might be consequence of inhibiting Akt phosphorylation, promoting the excessive accumulation of ROS in cells and promoting intracellular DNA damage. In animal experiments, the dysfunction of diastolic and myocardial ischemia of mouse heart was observed by echocardiography and 18FDG-micro PET/CT, respectively; myocardial fibrosis and cardiomyocyte apoptosis were also observed. Therefore, our in vitro and in vivo experiments have revealed that TRZ combined irradiation caused more cardiotoxicity than irradiation or TRZ alone. These results suggested that the concurrent management of TRZ and radiotherapy should be carefully made in clinical practice, and more attention is needed on cardiac safety.


Chronic kidney disease in children: the National Paediatric Hospital experience in Hanoi, Vietnam.
The goal of this descriptive study was to evaluate the aetiology and the socioeconomic status in hospitalized children in Hanoi and propose solutions to improve prevention and basic health care of patients with chronic kidney disease in Hanoi City. The records of all 152 hospitalized children with chronic kidney disease in the National Paediatric Hospital in Hanoi from January 2001 to December 2005 were analyzed. The incidence of paediatric chronic kidney disease native to Hanoi City was estimated to be 5.1/million-child population (pmcp). Median age was 11.29 years; 60.5% were boys and 39.5% were girls; 65% of patients were in end-stage renal disease. Causes of chronic kidney disease included glomerulonephritis (66.4%) and congenital/hereditary anomalies (13%). In 19.8% of children, the aetiology was unavailable. During hospitalization, five patients died and 76 patients (50%) refused the treatment although beneficiaries of health insurance. Thirty patients (19.74%) received peritoneal dialysis and haemodialysis, and seven patients received renal transplantation with a familial living donor. Late referral, and limited facilities for renal replacement therapy explain the poor outcome in this study. We need a program to delineate the burden of chronic kidney disease and improve primary health care for health promotion and prevention of paediatric chronic kidney disease.


Sustainability of outdoor school ground smoking bans at secondary schools: a mixed-method study.
Although increasing numbers of countries are implementing outdoor school ground smoking bans at secondary schools, less attention is paid to the post-implementation period even though sustainability of a policy is essential for long-term effectiveness. Therefore, this study assesses the level of sustainability and examines perceived barriers/facilitators related to the sustainability of an outdoor school ground smoking ban at secondary schools. A mixed-method design was used with a sequential explanatory approach. In phase I, 438 online surveys were conducted and in phase II, 15 semi-structured interviews were obtained from directors of relevant schools. ANOVA (phase I) and a thematic approach (phase II) were used to analyze data. Level of sustainability of an outdoor school ground smoking ban was high at the 48% Dutch schools with an outdoor smoking ban. Furthermore, school size was significantly associated with sustainability. The perceived barriers/facilitators fell into three categories: (i) smoking ban implementation factors (side-effects, enforcement, communication, guidelines and collaboration), (ii) school factors (physical environment, school culture, education type and school policy) and (iii) community environment factors (legislation and social environment). Internationally, the spread of outdoor school ground smoking bans could be further promoted. Once implemented, the ban has become 'normal' practice and investments tend to endure. Moreover, involvement of all staff is important for sustainability as they function as role models, have an interrelationship with students, and share responsibility for enforcement. These findings are promising for the sustainability of future tobacco control initiatives to further protect against the morbidity/mortality associated with smoking.


Mutual understanding in multi-disciplinary primary health care teams.
Empirical research on multi-disciplinary health care teams has yet to explore the development of mutual understanding between team members in the course of their collective clinical decision-making. This paper addresses this gap in the literature directly by examining changes in mutual understanding and the extent to which its facilitation is shared by individual members of multi-disciplinary health care teams. A Habermasian theoretical framework is used to operationalize mutual understanding. Social network analysis is used to analyze survey data on team-based clinical decision-making collected from multi-disciplinary health care teams in a Canadian province. The results of the study indicate that mutual understanding between team members ebbs and flows over the course of their collective clinical decisions. Further, as the extent of mutual understanding within the team increases, its facilitation becomes more equally shared among team members. The paper closes by specifying a practical outcome of the future work: a typology of clinical decisions that health care teams are able to use as an evaluation tool to assess how effectively they are making collective clinical decisions. As an evaluation tool, the typology would foster open and deliberative discussion, enable critical self-reflection, and thereby further enhancing mutual understanding within the teams.


Determination of interferon-gamma in Chinese hamster ovary cell culture supernatant by coupled-column liquid chromatography.
A robust tandem HPLC method coupling size-exclusion (Shodex Asahipak GS-320HQ) and reversed phase (Vydac 218TP54) columns with ultraviolet detection was developed for quantitative determination of interferon-gamma (IFN-gamma) in Chinese hamster ovary cell culture supernatant. The 2D-HPLC system was linked up by a 6-port 2-position low hold-up volume switch valve. Compared to a commercial ELISA kit for IFN-gamma, the coupled column LC approach was able to detect and quantify soluble IFN-gamma, regardless of the glycoprotein's molecular/conformational variability and sample background. Each LC-LC analysis took 90 minutes inclusive of column regeneration. The relative standard deviation of measurements (n = 5) was less than 3%. The limit of detection (LOD) was determined to be 0.35 microg IFN-gamma.


Continuous positive airway pressure ameliorates sleep-induced subclinical left ventricular systolic dysfunction: demonstration by two-dimensional speckle-tracking echocardiography.
We hypothesized that continuous positive airway pressure (CPAP) therapy could improve sleep-induced left ventricular (LV) dysfunction in patients with obstructive sleep apnoea syndrome (OSA). The aim of this study was to investigate the effects of CPAP therapy on LV systolic dysfunction during overnight sleep in patients with OSA using two-dimensional speckle-tracking echocardiography (2DSTE). 2D LV short-axis and apical views were acquired before and immediately after overnight sleeping in 32 patients with OSA and normal LV ejection fraction. Using 2D strain software, three-principal strains were measured. In a subset of 14 OSA patients who received chronic CPAP therapy, identical measurements were repeated 3 months after the therapy. Although no significant changes in global radial and circumferential strain were noted, global longitudinal strain was significantly reduced after overnight sleeping (-19.1 +/- 2.0) compared with before sleep (-20.7 +/- 1.8, P < 0.001). After CPAP therapy, improvements in apnoea-hypopnoea index and minimal oxygen saturation were accompanied by the disappearance of longitudinal strain reduction during overnight sleep. Repetitive obstructive apnoea produces acute impairment of LV longitudinal function, suggesting the development of subendocardial ischaemia. CPAP therapy not only decreases the severity of OSA, but also ameliorates sleep-induced longitudinal LV dysfunction, which can be assessed by 2DSTE.


A longitudinal evaluation of bronchial responsiveness to methacholine in children: role of baseline lung function, gender, and change in atopic status.
A longitudinal study was done to evaluate the determinants of bronchial responsiveness (BR) to methacholine in children and adolescents. A cohort of 892 7- to 11-yr-old schoolchildren was restudied after a 3.5-yr interval. The same protocol for methacholine challenge (up to 64.0 mg/ml) and skin prick testing was employed at both the baseline survey and follow-up. An overall decline in the level of BR was observed, the geometric mean slope (percent decline in FEV1 per mg/ml of methacholine) decreasing from 0.68 (95% CI=0.61 to 0.75) to 0.51 (95% CI=0.46 to 0.57) (p<0.001). At both surveys, the strongest determinants of slope were baseline pulmonary function level (FEF25-75) and degree of atopic status. After adjusting for log FEF25-75, no gender difference was found in the first survey, whereas girls had greater BR than boys at follow-up. Longitudinal changes in skin prick test reactivity were associated with the BR level. Subjects in whom an initially positive skin prick test became negative (5.3%) had an increased slope at baseline but a follow-up slope similar to that of never skin-reactors. Conversely, those whose skin prick test converted from negative to positive (13.0%) had a slope similar to that of never-reactors at baseline but became stronger responders to methacholine than never-reactors at follow-up. Finally, responsiveness was highest in the presence of persistently positive skin prick testing (13.5%). In conclusion, BR declines from childhood to adolescence, paralleling the increase in lung function during this period; the decline is less pronounced in females. Changes in atopic status are associated with modifications in the BR level.


[Creative mathematics with clopidogrel; exaggeration of the preventive effect by manufacturer].
A number of Dutch medical journals recently carried an advertisement stating that clopidogrel treatment reduced the number of ischaemic complications with 26%, compared with aspirin treatment. This is a miscalculation: the actual reduction is 0.51% in absolute rates, and 8.7% in relative terms. The error by Sanofi-Synthelabo arose by comparison of the event rates for clopidogrel (5.32%) as well as for aspirin (5.83%) with that in an imaginary placebo group (7.77%), yielding a reduction of ischaemic complications of 2.45% and 1.94% respectively; erroneous comparison of these two numbers leads to a difference of 26%.


Chronic hepatitis B in hepatocarcinogenesis.
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and has a wide geographical variation. Eighty per cent of HCC is attributed to hepatitis B virus (HBV). The predominant carcinogenic mechanism of HBV associated HCC is through the process of liver cirrhosis, but direct oncogenic effects of HBV may also contribute. Prevention of HBV infections as well as effective treatment of chronic hepatitis B is still needed for the global control of HBV associated HCC. Continued investigation of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformation in the liver.


Plasma levels of orally and subcutaneously administered pentoxifylline in rabbits.
In addition to its ability to improve microcirculation, pentoxifylline also has anti-tumor necrosis factor-alpha (TNF) actions which have prompted investigations into its potential efficacy in disease states involving elevated TNF levels. One such disease entity is AIDS where aberrant TNF seems to mediate axonal degeneration within thecentral nervous system. To this end, we have previously established a rabbit model of TNF-mediated axonal degeneration, and demonstrated that pentoxifylline attenuates this effect. Unfortunately, there has been to date only one limited report on the pharmacokinetics of pentoxifylline in rabbits. Therefore, the present report evaluates plasma levels of pentoxifylline and two of its primary metabolites through high-performance liquid chromatography after both the oral and subcutaneous administration of pentoxifylline. Our results indicate that in rabbits there is a very rapid absorption and metabolism of pentoxifylline after either oral or subcutaneous administration. In comparison with the mouse, the rabbit seems to absorb and metabolize pentoxifylline slower. In contrast to man, the rabbit had lower metabolite plasma levels than the parent drug itself.


Puberty onset curve in CD (Sprague Dawley) and Long Evans outbred male rats.
The exact timing of puberty is fundamental in preclinical studies. In male rats, the age at sexual maturity varies considerably between 40 and 60 days of age. Here, we summarize pubertal onset evaluation of two outbred rat strains (Crl:CD(SD) and Crl:LE), relying on the balano-preputial separation test. Evaluation was carried out on animals under standard barrier conditions, from four to nine weeks of age. In the Crl:CD(SD) population, 90% of males gained puberty at week 6, and 100% in the following weeks, whereas 75% of Crl:LE reached puberty at week 6, 90% at week 7 and 100% from week 8. Remarkably, in both strains, puberty onset was gained at the average weight of 200 g, suggesting that weight range, not only age range, can be considered a biomarker of puberty onset in these two strains. On the contrary, descended testes cannot be considered an additional factor to identify full puberty onset either in Crl:CD(SD) or Crl:LE rats.


Anabolic androgenic steroids in police cases in Sweden 1999-2009.
Anabolic Androgenic Steroids (AAS) are considered drugs of abuse and are controlled substances in Sweden since 1999. Traditionally AAS have been used by elite athletes to enhance performance, but in recent years it has become an increasing problem outside elite sport among athletes, bodybuilders and criminals. Use of AAS is associated with psychiatric side effects such as aggression, depression and violent behavior. Supraphysiological doses and long term use can cause serious physical harm such as cardiovascular toxicity and even premature death. We investigated and evaluated the drug analytical findings in forensic cases from suspected perpetrators in cases from the police where a screening for AAS was requested to get information about the prevalence of AAS use and the occurrence of poly-drug abuse. The study was based on samples submitted from the police authorities to the Department of Forensic Toxicology in Sweden during the period 1999-2009. Urines were analyzed by methods based on GC-MS and LC-MS-MS. We also analyzed the prevalence of AAS use at the prison and probation services. A total number of 12,141 urine samples (6362 police cases and 5779 inmates) were analyzed and 33.5% of the cases from the police and 11.5% of the inmates were tested positive for AAS. The users of AAS were mainly in 99.2% men with a mean age of 26.2±6.2 years whereas the women were 29.5±6.5 years old. The most frequently used AAS was nandrolone followed by testosterone and methandienone. Other illicit and licit drugs were detected in 60% of the cases from the police, strongly indicating a frequent poly-drug abuse among users of AAS.


The mixture of Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge. extract produces analgesic and anti-inflammatory effects in a collagen-induced arthritis mouse model.
Pain and inflammation typically manifest in patients with arthritis. It is now widely known that Agrimonia pilosa Ledeb (AP) and Salvia miltiorrhiza Bunge (SM) exert anti-inflammatory and antinociceptive effects. We have previously reported that the mixture extract (ME) from AP and SM produces antinociceptive and anti-inflammatory effects in gout arthritis and monoiodoacetate (MIA)-induced arthritis models. In the present study, we assessed the antinociceptive and anti-inflammatory effects on the collagen-induced arthritis (CIA) model. The antinociceptive effects in mice were measured using the von Frey test. ME administered once or for one week (once per day) once, and one-week reduced the pain in a dose-dependent manner (from 50 to 100 mg/kg) in the CIA-induced osteoarthritis (OA) model. ME treatment also reduced tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels in plasma and ankle tissues. Furthermore, COX-1, COX-2, NF-κB, TNF-α, and IL-6 expressions were attenuated after ME treatment. In most experiments, the antinociceptive and anti-inflammatory effects induced by ME treatment were almost equal to or slightly better than those induced by Perna canaliculus (PC) treatment, which was used as a positive control. Our results suggest that ME possesses antinociceptive and anti-inflammatory effects, indicating its potential as a therapeutic agent for arthritis treatment.


Polarization conserving light bending prisms and optimized fresnel rhombs.
The design of prisms utilizing total internal reflection to achieve particular phase retardation is considered. Two prisms are discussed that bend light by 90 degrees without changing its polarization. Optimum design for Fresnel rhombs is considered, and designs for quarter-wave and half-wave are presented. The effect of light beam divergence and prism dispersion is treated.


Targeting JAK3 in kidney transplantation: current status and future options.
This review will discuss the mechanism of action and important clinical trial data in renal transplantation for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib. JAKs are cytoplasmic tyrosine kinases that participate in the signaling of a broad range of cell surface receptors, particularly members of the cytokine receptor common gamma (cγ) chain family. JAK3 inhibition has immunosuppressive effects and treatment with tofacitinib in clinical trials has demonstrated efficacy in autoimmune disorders such as psoriasis and rheumatoid arthritis. Nonhuman primate models of renal transplantation demonstrated prolonged graft survival with tofacitinib compared with vehicle control. Renal transplant clinical trials in humans have demonstrated tofacitinib to be noninferior to cyclosporine in terms of rejection rates and graft survival. There was also a lower rate of new-onset diabetes after transplant. However, there was a trend toward more infections, including cytomegalovirus and BK virus nephritis. Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined.


Somite development without influence of the surface ectoderm in the chick embryo: the compartments of a somite responsible for distal rib development.
In the development of the somite, signals from neighboring tissues have been suggested to play critical roles. We have found that when interaction between the ectoderm and the somite is blocked by inserting a piece of polyethylene terephatalate film between them in 2-day-chicken embryo, one of the derivatives of somite, the distal rib, did not form. We examined somite development after the operation, to know the correlation between somite development and distal rib formation. In the operated embryo, the dermomyotome was medio-laterally shorter than in the normal embryo, and Pax3 and Sim1 expressions that are seen in the lateral part of normal dermomyotomes were not found, suggesting that the lateral part of the dermomyotome was missing. Although the sclerotome appeared to be normal in its histology and Pax1 expression pattern in the operated embryo, we could not detect the expression of either Scleraxis nor gamma-FBP that are expressed in the cells around the boundaries between the adjacent dermomyotomes in normal embryos. Thus, under the influence of surface ectoderm, the lateral part of dermomyotome and/or the mesenchyme around rostral and caudal edges of dermomyotomes are suggested to play an important role in the distal rib development.


Staff-perceived barriers to nutrition intervention in substance use disorder treatment.
While organisational change in substance use disorder (SUD) treatment has been extensively studied, there is no research describing facility-wide changes related to nutrition interventions. This study evaluates staff-perceived barriers to change before and after a wellness initiative. A pre-intervention questionnaire was administered to participating staff prior to facility-wide changes (n 40). The questions were designed to assess barriers across five domains: (1) provision of nutrition-related treatment; (2) implementation of nutrition education; (3) screening, detecting and monitoring (nutrition behaviours); (4) facility-wide collaboration and (5) menu changes and client satisfaction. A five-point Likert scale was used to indicate the extent to which staff anticipate difficulty or ease in implementing facility-wide nutrition changes, perceived as organisational barriers. Follow-up questionnaires were identical to the pre-test except that it examined barriers experienced, rather than anticipated (n 50). A multisite SUD treatment centre in Northern California which began implementing nutrition programming changes in order to improve care. Staff members who consented to participate. From pre to post, we observed significant decreases in perceived barriers related to the provision of nutrition-related treatment (P = 0·019), facility-wide collaboration (P = 0·036), menu changes and client satisfaction (P = 0·024). Implementation of nutrition education and the domain of screening, detecting and monitoring did not reach statistical significance. Our results show that staff training, food service changes, the use of targeted curriculum for nutrition groups and the encouragement of discussing self-care in individual counselling sessions can lead to positive shifts about nutrition-related organisational change among staff.


Measles, immunisation and disease: situation analysis in a resettlement area of northern India.
India has a goal of covering all infants with measles immunization between 9-12 months. The present study was conducted in a resettlement area of east Delhi, with a population of nearly one lac, to assess the extent of measles immunization and infection among children aged under three years. All the 21 blocks of the area were covered and 10% households were selected by systematic random sampling from each of the blocks to provide 944 households and 517 under-3 children, who were individually examined by a doctor. Two hundred and eighty one children aged 12 months or above were immunized at or after 9 months giving a coverage of 74.14%. Among the immunized children 7.78% and 8.36% were vaccinated before and after the recommended age-range (9-12 months) respectively. One fifth of the children aged 12 months or above were not immunized against measles at all. Among the surviving under-3 children, no child suffered measles before 6 months but 11.86% of the children had measles between 6-8 months. Six children were vaccinated even after measles episode and seven children had measles even after immunization. Systematic community contact and special attention to resistant and hostile parents is important in order to accomplish 100% coverage. In view of the sizeable proportion of measles infection among the age group of 6-8 months, there is a case for bringing forward the recommended age for measles immunization, if we are to eradicate the disease.


Concurrent Validity of PROMIS With DASH and DVPRS in Transhumeral Amputees.
We sought to assess whether select domains of the Patient-Reported Outcomes Measurement Information System (PROMIS) significantly correlate with the Disabilities of the Arm, Shoulder, and Hand (DASH) score and the Defense and Veterans Pain Rating Scale (DVPRS) among transhumeral amputees. We prospectively administered DASH, DVPRS, and PROMIS (including Upper Extremity, Pain Interference, and Pain Behavior domains) testing to patients presenting for consideration of osseointegration after transhumeral amputation. Concurrent validity was assessed via Pearson correlation testing. The mean DASH score of the cohort was 32.8. The mean DVPRS score was 1.8. The mean PROMIS scores were 33.8, 50.5, and 50.6 for Upper Extremity, Pain Interference, and Pain Behavior domains, respectively. Pearson testing demonstrated a significant, inverse correlation between DASH and PROMIS Upper Extremity scores (r = -0.85, P = .002). There was also significant correlation between DVPRS and PROMIS Pain Interference scores (r = 0.69, P = .03). The PROMIS Pain Behavior domain did not significantly correlate with either DASH or DVPRS. Patient-Reported Outcomes Measurement Information System Upper Extremity and Pain Interference scores demonstrated significant concurrent validity with traditional measures (DASH and DVPRS) of patient-reported outcome in our population of transhumeral amputees.


A quantitative approach for analysing bone modelling patterns from craniofacial surfaces in hominins.
Bone size and shape arise throughout ontogeny as a result of the coordinated activity of osteoblasts and osteoclasts, responsible for bone deposition and resorption, and growth displacements. The modelling processes leave specific microstructural features on the bone surface, which can be used to infer the mechanisms shaping craniofacial traits in extinct and extant species. However, the analysis of bone surfaces from fossils and archaeological samples faces some difficulties related to the bone loss caused by taphonomic factors, and the lack of formal methods for estimating missing information and comparing the patterns of bone modelling among several specimens and samples. The present study provides a new approach for the quantitative analysis of bone formation and resorption patterns obtained from craniofacial surfaces. First, interpolation techniques were used to estimate missing data on high-resolution replicas of the left maxilla in a sample of sub-adult and adult modern humans and sub-adult fossil hominins. The performance of this approach was assessed by simulating variable amounts of missing data. Then, we applied measures of dispersion and central tendency to represent the variation and average pattern of bone modelling within samples. The spatial interpolation resulted in reliable estimations of the type of cell activity (deposition or resorption) in the missing areas, even when large extensions of the bone surface were lost. The quantification of the histological data allowed us to integrate the information of different specimens and depict the areas with higher and lower variation in the bone modelling pattern of the maxilla among specimens. Overall, the main advantages of the quantitative approach used here for generating bone modelling patterns are the high replicability and the possibility of incorporating variation among specimens into the comparisons among samples.


Arabidopsis auxin response factor6 and 8 regulate jasmonic acid biosynthesis and floral organ development via repression of class 1 KNOX genes.
Two mutations in Arabidopsis thaliana, auxin response factor6 (arf6) and arf8, concomitantly delayed the elongation of floral organs and subsequently delayed the opening of flower buds. This phenotype is shared with the jasmonic acid (JA)-deficient mutant dad1, and, indeed, the JA level of arf6 arf8 flower buds was decreased. Among JA biosynthetic genes, the expression level of DAD1 (DEFECTIVE IN ANTHER DEHISCENCE1) was markedly decreased in the double mutant, suggesting that ARF6 and ARF8 are required for activation of DAD1 expression. The double mutant arf6 arf8 also showed other developmental defects in flowers, such as aberrant vascular patterning and lack of epidermal cell differentiation in petals. We found that class 1 KNOX genes were expressed ectopically in the developing floral organs of arf6 arf8, and mutations in any of the class 1 KNOX genes (knat2, knat6, bp and hemizygous stm) partially suppressed the defects in the double mutant. Furthermore, ectopic expression of the STM gene caused a phenotype similar to that of arf6 arf8, including the down-regulation of DAD1 expression. These results suggested that most defects in arf6 arf8 are attributable to abnormal expression of class 1 KNOX genes. The expression of AS1 and AS2 was not affected in arf6 arf8 flowers, and as1 and arf6 arf8 additively increased the expression of class 1 KNOX genes. We concluded that ARF6 and ARF8, in parallel with AS1 and AS2, repress the class 1 KNOX genes in developing floral organs to allow progression of the development of these organs.


Missing the mark with Latina women with type 2 diabetes: implications for educators.
The purpose of this qualitative study was to explore nutritional behaviors and attitudes among Latino women with type 2 diabetes. Women over 18 years old and previously diagnosed with type 2 diabetes were recruited to participate in semi-structured qualitative interviews in their homes in Los Angeles, California, and Las Vegas, Nevada. Recruitment was conducted through flyers posted in local businesses. Interviews were conducted in Spanish or English. Data were transcribed and analyzed using an iterative process that involves reading interview transcripts and designating themes that arise from the data. Acquisition of nutritional knowledge and behavioral capability were positively associated with observational learning, formal nutritional education, and culturally competent meal planners. The use of traditional remedies and the consultation of naturistas reveal a tendency toward medical pluralism. In the home environment, husbands had the greatest influence on Latina women's attitudes and perceived choices. The social environment, including support and reinforcement, is critical for Latinas' nutritional success. Observational learning is critical for Latinas' behavioral capability.


The use of biomarkers in the patient with heart failure.
Heart failure is a major burden to the health care system in terms of not only cost, but also morbidity and mortality. Appropriate use of biomarkers is critically important to allow rapid identification and optimal risk stratification and management of patients with both acute and chronic heart failure. This review will discuss the biomarkers that have the most diagnostic, prognostic, and therapeutic value in patients with heart failure. We will discuss established biomarkers such as natriuretic peptides as well as emerging biomarkers reflective of myocyte stress, myocyte injury, extracellular matrix injury, and both neurohormonal and cardio-renal physiology.


Ethanol production from glycerol using immobilized Pachysolen tannophilus during microaerated repeated-batch fermentor culture.
Herein, we established a repeated-batch process for ethanol production from glycerol by immobilized Pachysolen tannophilus. The aim of this study was to develop a more practical and applicable ethanol production process for biofuel. In particular, using industrial-grade medium ingredients, the microaeration rate was optimized for maximization of the ethanol production, and the relevant metabolic parameters were then analyzed. The microaeration rate of 0.11 vvm, which is far lower than those occurring in a shaking flask culture, was found to be the optimal value for ethanol production from glycerol. In addition, it was found that, among those tested, Celite was a more appropriate carrier for the immobilization of P. tannophilus to induce production of ethanol from glycerol. Finally, through a repeated-batch culture, the ethanol yield (Ye/g) of 0.126 ± 0.017 g-ethanol/g-glycerol (n = 4) was obtained, and this value was remarkably comparable with a previous report. In the future, it is expected that the results of this study will be applied for the development of a more practical and profitable long-term ethanol production process, thanks to the industrial-grade medium preparation, simple immobilization method, and easy repeated-batch operation.


Diagnosis of cardiovascular disease in patients with chronic kidney disease.
The major forms of cardiovascular disease including coronary atherosclerosis, valvular disease, myocardial dysfunction, and arrhythmias are observed either alone or in combination in a large fraction of patients with chronic kidney disease (CKD). As CKD progresses, these cardiovascular conditions become more prevalent and severe. The clinical implications of combined heart and kidney disease include challenges in diagnosis and management. In addition, the terminal events in CKD commonly involve one of these four domains of cardiovascular disease. This paper will explore the issue of early diagnosis of heart disease in patients with CKD with the major goal being early intervention to lessen the impact of this comorbidity.


Low frequency of autoantibodies against Ki-67 antigen in Japanese patients with systemic autoimmune diseases.
The Ki-67 antigen, which is recognized by the monoclonal antibody Ki-67, is a marker of cell proliferation. During cDNA cloning using sera from a patient with systemic lupus erythematosus, we obtained a positive clone encoding part of Ki-67. We determined the frequency of autoantibodies against Ki-67 in patients with systemic autoimmune diseases. Serum samples from 252 patients with rheumatic diseases were examined by immunoblotting with HeLa nuclear extract and the recombinant N-terminus of the Ki-67 antigen. Autoantibodies against Ki-67 antigen were detected in two out of 76 patients with systemic lupus erythematosus and one out of 90 patients with scleroderma. While, in a previous report, anti-Ki-67 antibodies were frequently targeted by a certain strain of autoimmune mice, our results indicated that Ki-67 was a minor target of autoantibodies among Japanese patients with systemic autoimmune diseases.


Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion.
In chronic infection, T cells become hyporesponsive to antigenic stimulation to prevent immunopathology. Here, we show that TMEM16F is required to curb excessive T cell responses in chronic infection with virus. TMEM16F-deficient T cells are hyperactivated during the early phase of infection, exhibiting increased proliferation and cytokine production. Interestingly, this overactivation ultimately leads to severe T cell exhaustion and the inability of the host to control viral burden. Mechanistically, we identify TMEM16F as the dominant lipid scramblase in T lymphocytes that transports phospholipids across membranes. TMEM16F is located in late endosomes, where it facilitates the generation of multivesicular bodies for TCR degradation and signal termination. Consequently, TMEM16F deficiency results in sustained signaling and augmented T cell activation. Our results demonstrate that scramblase restricts TCR responses to avoid overactivation, ensuring a well-balanced immune response in chronic infectious disease.


A chemistry/physics pathway with nanofibrous scaffolds for gene delivery.
This perspective is to introduce a new pathway for non-viral gene delivery by taking advantage of nanofibrous scaffolds as gene storage devices, gene carriers and homing devices. During gene delivery to the target, the DNA has to be protected in order to pass through a set of barriers before reaching the nucleus. The DNA can form a complex with polycations, and numerous publications exist on how to stabilize the DNA fragments by natural and synthetic materials. Electrospun nanofibrous scaffolds can be used to store the DNA, especially in the form of a more stabilized polyplex, and then to deliver the DNA (polyplex) to cells that are attached to the scaffold. While each essential step has been tested experimentally, the overall yet untested process, especially for in vivo experiments, may lead to a promising specific approach for gene/drug storage and delivery. The pathway described herein is based mainly on our understanding of the physics and chemistry of gene storage and delivery processes, in contrast to using pure biological concepts. Novel biodegradable, biocompatible nanofibrous materials with imbedded DNA (e.g., in the polyplex form) can then be designed to fabricate an intelligent scaffold for gene delivery. To achieve the above goal, the first step is to stabilize the DNA so that it can be incorporated into nanofibrous scaffolds. In this respect, we shall discuss the different methods of DNA/gene condensation and complex formation, and then explain the strategy used to incorporate DNA into electrospun nanofibers. Solvent-induced DNA condensation and then encapsulation were achieved. However, the released naked DNA was not sufficiently protected for gene transfection in cells. The objective of the current perspective is to suggest that, instead of the solvent-induced DNA condensation, one can combine the recently developed polyplex formation by using branched polyethyleneimine (bPEI). More importantly, free bPEI can be incorporated into the nanofibers separately so that during the gene delivery step, the presence of a predesigned amount of free bPEI can greatly increase the gene transfection efficiency, as has been reported recently by Chi Wu and his coworkers. Thus, a physics/chemistry-based pathway that utilizes nanofibrous scaffolds for gene delivery is within reach.


Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder.
Glial cells are more numerous than neurons in the cortex and are crucial to neuronal function. There is evidence for reduced neuronal size in schizophrenia, with suggestive evidence for reduced glial cell density in mood disorders. In this investigation, we have simultaneously assessed glial cell density and neuronal density and size in the anterior cingulate cortex in schizophrenia, major depressive disorder, and bipolar disorder. We examined tissue from area 24b of the supracallosal anterior cingulate cortex in 60 postmortem brain specimens from 4 groups of 15 subjects, as follows: major depressive disorder, schizophrenia, bipolar disorder, and normal controls. Glial cell density and neuronal size and density were examined in all subjects using the nucleator and the optical disector. Glial cell density (22%) (P =.004) and neuronal size (23%) (P =.01) were reduced in layer 6 in major depressive disorder compared with controls. There was some evidence for reduced glial density in layer 6 (20%) (P =.02) in schizophrenia compared with controls, before adjusting for multiple layerwise comparisons, but there were no significant changes in neuronal size. There was no evidence for differences in glial density or neuronal size in bipolar disorder compared with controls. Neuronal density was similar in all groups to that found in controls. These findings suggest that there is reduced frontal cortical glial cell density and neuronal size in major depressive disorder.


Two new polymorphisms in the arylsulfatase A gene and their haplotype associations with normal, metachromatic leukodystrophy and pseudodeficiency alleles.
Linkage disequilibrium exists between metachromatic leukodystrophy (MLD) and pseudodeficiency mutations and selected polymorphisms within the arylsulfatase A gene. We have identified 2 new polymorphic NlaIII sites, NlaIII1 and NlaIII2, in the gene that, when used in combination with the known BsrI and BamHI polymorphisms, extends the haplotype associations of the pseudodeficiency and the most common infantile onset MLD alleles. Fixed haplotypes have also been established for 3 other recurring MLD mutations, ala212val, pro426leu, and thr274met. The NlaIII2 site is relatively rare and was found only in association with the pseudodeficiency variant carrying the glycosylation site mutation alone.


Effect of dilazep on myocardial contractility following acute ischemia and reperfusion in isolated blood-perfused canine left ventricular muscle.
Myocardial protection by dilazep HCl, an antianginal drug and a potent calcium antagonist, against myocardial damage following acute ischemia and reperfusion was studied with respect to myocardial contractility in isolated blood-perfused canine left ventricular muscle. Myocardial function was expressed by percent recovery rate of maximal net developed tension. 1) The coronary infusion of dilazep revealed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. 2) The intravenous administration of dilazep to the support dog and Young's infusion also showed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. Dilazep showed no persistent depression of myocardial contractility due to its calcium antagonistic effect during reperfusion. 3) The combination of intravenous administration of dilazep to the support dog, Young's infusion, and hypothermia showed significant myocardial protection during prolonged ischemia and reperfusion even in hypertrophied ventricle. These results demonstrate that dilazep provides effective myocardial protection during ischemic arrest and reperfusion by preventing abnormal calcium accumulation in myocardial cells during reperfusion. No persistent depression of myocardial contractility during reperfusion may support dilazep's clinical application as a myocardial protective agent in open-heart surgery.


Evaluation of capacity-building strategies for mental health system strengthening in low- and middle-income countries for service users and caregivers, policymakers and planners, and researchers.
Strengthening of mental health systems in low- and middle-income countries (LMICs) requires the involvement of appropriately skilled and committed individuals from a range of stakeholder groups. Currently, few evidence-based capacity-building activities and materials are available to enable and sustain comprehensive improvements. Within the Emerald project, the goal of this study was to evaluate capacity-building activities for three target groups: (a) service users with mental health conditions and their caregivers; (b) policymakers and planners; and (c) mental health researchers. We developed and tailored three short courses (between 1 and 5 days long). We then implemented and evaluated these short courses on 24 different occasions. We assessed satisfaction among 527 course participants as well as pre-post changes in knowledge in six LMICs (Ethiopia, India, Nepal, Nigeria, South Africa, Uganda). Changes in research capacity of partner Emerald institutions was also assessed through monitoring of academic outputs of participating researchers and students and via anonymous surveys. Short courses were associated with high levels of satisfaction and led to improvements in knowledge across target groups. In relation to institutional capacity building, all partner institutions reported improvements in research capacity for most aspects of mental health system strengthening and global mental health, and many of these positive changes were attributed to the Emerald programme. In terms of outputs, eight PhD students submitted a total of 10 papers relating to their PhD work (range 0-4) and were involved in 14 grant applications, of which 43% (n = 6) were successful. The Emerald project has shown that building capacity of key stakeholders in mental health system strengthening is possible. However, the starting point and appropriate strategies for this may vary across different countries, depending on the local context, needs and resources. S.E.L. received consulting fees from Lundbeck.


The highs and lows of learning to be a children's nurse.
This study investigates student nurses' perceptions of the process of undergoing a programme of education leading to registration as a children's nurse. Three groups of students (n = 14, 12 and eight) were invited to participate in a focus group using the nominal group technique to address the following questions: What has helped you in the process of becoming a children's nurse? What has hindered you in the process of becoming a children's nurse? The factors which helped students most in their quest to become children's nurses included: the delivery of specialist lectures from child branch nurse lecturers, having good clinical placements with mentors who want to support students, and having the support of friends and family. An important factor was the desire to become a good children's nurse and wanting to work with children. Factors which hindered students included: having unsupportive mentors who misjudge student abilities, lack of academic resources including library reading materials, too many students in each clinical area and.


The Strong Black Woman versus Mental Health Utilization: A Qualitative Study.
Recent investigations have elucidated the influence of the strong Black woman (SBW) ideal on the mental health and treatment-seeking behaviors of Black women in the United States. However, factors related to how the SBW ideal affects Black women's positive and negative attitudes toward seeking professional psychological help have yet to be identified. The current study fills this void in the literature through a qualitative examination of how the SBW ideal affects Black women's mental health utilization. Analyses were based on 62 participants, including college students and community members, ranging in age from 18 to 72 years. The present study advances the idea that endorsement of the SBW ideal affects Black women's mental utilization. These results offer evidence and clarification of the impact of the SBW ideal on Black women's mental health and identity-specific points of intervention for mental health practitioners conducting therapeutic work with Black women. Authors provide practice recommendations for practitioners and suggestions for future research.


Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy.
Intervertebral disc degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to loss of disc integrity. Degeneration of the disc can be a normal process of ageing, but can also be precipitated by other factors. Literature has made substantial progress in understanding the biological basis of intervertebral disc, which is reviewed here. Current medical and surgical management strategies have shortcomings that do not lend promise to be effective solutions in the coming years. With advances in understanding the cell biology and characteristics of the intervertebral disc at the molecular and cellular level that have been made, alternative strategies for addressing disc pathology can be discovered. A brief overview of the anatomic, cellular, and molecular structure of the intervertebral disc is provided as well as cellular and molecular pathophysiology surrounding intervertebral disc degeneration. Potential therapeutic strategies involving stem cell, protein, and genetic therapy for intervertebral disc degeneration are further discussed.


Hypothalamic GLP-1: the control of BAT thermogenesis and browning of white fat.
Brown adipose tissue (BAT) is a specialized organ responsible for thermogenesis, a process required for maintaining body temperature. Since the discovery that BAT and brite/beige cells are functional in adult humans, many studies have been focusing on the physiology and functionality of this organ. The brain is controlling the maintenance of body temperature through a complex neuronal network. One of the candidates to modulate thermogenesis at central level is glucagon-like peptide-1 (GLP-1), with GLP-1 receptors widely expressed throughout the brain. Our group has recently reported that stimulation of brain GLP-1 receptors in the ventromedial nucleus of the hypothalamus is essential for the activation not only of BAT thermogenesis, but also browning of white fat. Notably, both actions are mediated by specific inhibition of the energy sensor AMP-activated protein kinase (AMPK). In this commentary, we summarize the latest results on this topic, as well as the potential clinical relevance of the brain GLP-1 system to treat obesity.


Prognostic value of neglected biomarker in sepsis patients with the old and new criteria: predictive role of lactate dehydrogenase.
This study examined the pH, lactate dehydrogenase (LDH), and heart rate values on the first day of hospitalization in patients with a prediagnosis of sepsis and biomarkers that may predict mortality. Patients hospitalized in an emergency intensive care unit with a diagnosis of systemic inflammatory response syndrome were classified as having sepsis (n = 28), septic shock (n = 8), or severe sepsis (n = 8) according to International Sepsis Guidelines (old criteria). Forty-four patients were classified as having sepsis (n = 4), septic shock (n = 30), or infection (n = 10) according to The Third International Consensus Definitions for Sepsis and Septic Shock (new criteria). The effects of these patients' laboratory values on survival between groups were compared. Significant values were evaluated by χ2 automatic interaction detection analysis. When the patients were categorized according to the new classification criteria, there was an increase in the number of septic shock patients and a decrease in the number of sepsis patients. In addition, 10 patients were removed from the sepsis category. There was a significant difference between ex and discharged patients in terms of heart rate, pH, sodium bicarbonate, lactate, and LDH (P= .007, P= .002, P= .034, P= .009, and P= .002, respectively). Based on a χ2 automatic interaction detection analysis of the significant values, pH, LDH, and heart rate were prominent predictors of prognosis. Systemic pH, LDH, and heart rate values may be used to determine the best time to discharge patients from intensive care to other, more affordable hospital units.


Association Between Socioeconomic Disadvantage and Decline in Function, Cognition, and Mental Health After Critical Illness Among Older Adults : A Cohort Study.
Older adults admitted to an intensive care unit (ICU) are at risk for developing impairments in function, cognition, and mental health. It is not known whether socioeconomically disadvantaged older persons are at greater risk for these impairments than their less vulnerable counterparts. To evaluate the association between socioeconomic disadvantage and decline in function, cognition, and mental health among older survivors of an ICU hospitalization. Retrospective analysis of a longitudinal cohort study. Community-dwelling older adults in the National Health and Aging Trends Study (NHATS). Participants with ICU hospitalizations between 2011 and 2017. Socioeconomic disadvantage was assessed as dual-eligible Medicare-Medicaid status. The outcome of function was defined as the count of disabilities in 7 activities of daily living and mobility tasks, the cognitive outcome as the transition from no or possible to probable dementia, and the mental health outcome as the Patient Health Questionnaire-4 score in the NHATS interview after ICU hospitalization. The analytic sample included 641 ICU hospitalizations for function, 458 for cognition, and 519 for mental health. After accounting for sociodemographic and clinical characteristics, dual eligibility was associated with a 28% increase in disability after ICU hospitalization (incidence rate ratio, 1.28; 95% CI, 1.00 to 1.64); and nearly 10-fold greater odds of transitioning to probable dementia (odds ratio, 9.79; 95% CI, 3.46 to 27.65). Dual eligibility was not associated with symptoms of depression and anxiety after ICU hospitalization (incidence rate ratio, 1.33; 95% CI, 0.99 to 1.79). Administrative data, variability in timing of baseline and outcome assessments, proxy selection. Dual-eligible older persons are at greater risk for decline in function and cognition after an ICU hospitalization than their more advantaged counterparts. This finding highlights the need to prioritize low-income seniors in rehabilitation and recovery efforts after critical illness and warrants investigation into factors leading to this disparity. National Institute on Aging.


LXA4 actions direct fibroblast function and wound closure.
Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A4 (LXA4), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA4 on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA4 receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a "scratch" assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA4 receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA4 slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA4 tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA4 in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function.


Reproducibility of the anti-Factor Xa and anti-Factor IIa assays applied to enoxaparin solution.
Enoxaparin is a widely used subcutaneously administered antithrombotic agent comprising a complex mixture of glycosaminoglycan chains. Owing to this complexity, its antithrombotic potency cannot be defined by physicochemical methods and is therefore evaluated using an enzymatic assay of anti-Xa and anti-IIa activity. Maintaining consistent anti-Xa activity in the final medicinal product allows physicians to ensure administration of the appropriate dosage to their patients. Bioassays are usually complex and display poorer reproducibility than physicochemical tests such as HPLC assays. Here, we describe the implementation of a common robotic platform and standard release potency testing procedures for enoxaparin sodium injection (Lovenox, Sanofi, Paris, France) products at seven quality control sites within Sanofi. Qualification and analytical procedures, as well as data handling, were optimized and harmonized to improve assay reproducibility. An inter-laboratory study was performed in routine-release conditions. The coefficients of variation for repeatability and reproducibility in assessments of anti-Xa activity were 1.0% and 1.2%, respectively. The tolerance interval in reproducibility precision conditions, expressed as percentage potency, was 96.8-103.2% of the drug product target of 10,000 IU/ml, comparing favorably with the United States of America Pharmacopeia specification (90-110%). The maximum difference between assays in two different laboratories is expected to be 4.1%. The reproducibility characteristics of anti-IIa activity assessments were found to be similar. These results demonstrate the effectiveness of the standardization process established and allow for further improvements to quality control in Lovenox manufacture. This process guarantees closeness between actual and target potencies, as exemplified by the results of release assays obtained during a three-year period.


Shifting Developmental Trajectories During Critical Periods of Brain Formation.
Critical periods of brain development are epochs of heightened plasticity driven by environmental influence necessary for normal brain function. Recent studies are beginning to shed light on the possibility that timely interventions during critical periods hold potential to reorient abnormal developmental trajectories in animal models of neurological and neuropsychiatric disorders. In this review, we re-examine the criteria defining critical periods, highlighting the recently discovered mechanisms of developmental plasticity in health and disease. In addition, we touch upon technological improvements for modeling critical periods in human-derived neural networks in vitro. These scientific advances associated with the use of developmental manipulations in the immature brain of animal models are the basic preclinical systems that will allow the future translatability of timely interventions into clinical applications for neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD) and schizophrenia.


Tangled in the web: countertransference in the therapy of factitious disorders.
Patients who simulate or actually self-induce illnesses to assume the "sick role" present a number of imposing psychotherapeutic challenges. The purpose of this article is to discuss the countertransferential reactions that are mobilized in therapy with these patients. Literature searches of the MEDLINE and HEALTH databases were performed using the term "factitious disorder." The resulting citations were examined for descriptions of the potential and actual countertransference responses in therapy with such patients. The few citations with relevant material were supplemented with other clinical literature on countertransference as well as observations from cases in which the authors have served as therapists or consultants. Once the medical dissimulation has been exposed, the most conspicuous difficulty is in persuading the patient to agree to therapy. When therapy does take place, both the patient's overt behaviors, such as actual bodily damage, and his or her underlying emotional issues can mobilize particularly intense reactions in the therapist. Recognition and management of the countertransference reactions likely to emerge in therapy with factitious disorder patients are particularly important if the therapy is to be maximally effective.


Development and validation of a high performance liquid chromatographic method for the separation of exo and endo isomers of granatamine (9-methyl-9-azabicyclo[3.3.1]nonan-3-amine); a key intermediate of granisetron.
A simple and accurate high-performance liquid chromatographic method was developed for the determination of exo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine in endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine, commercially known as grantamine and used as a key intermediate in the preparation of granisetron bulk drug. Chromatographic separation of the exo and endo isomers of 9-methyl-9-azabicyclo[3.3.1]nonan-3-amine was achieved on an Inertsil C8 column using a mobile phase containing 0.3% trifluoroacetic acid. The resolution between the two isomers was found to be more than 4. The limit of detection (LOD) and limit of quantification (LOQ) of exo isomer were 0.8 and 2.5 microg x mL(-1) respectively, for a 10 microL injection volume. The percentage recovery of exo-isomer ranged from 99 to 102% w/w in the endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine sample. The test solution and mobile phase were observed to be stable up to 48 h after preparation. The validated method yielded good results for precision, linearity, accuracy, robustness and ruggedness. The proposed method was found to be suitable and accurate for the quantitative determination of exo-isomer in bulk samples of endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine.


Tailoring counseling on physical activity and inactivity for African-American women.
Physician counseling is one potential avenue to decrease levels of inactivity among African-American (AA) women and, possibly, to decrease the prevalence of adverse health outcomes, which can be reduced through regular participation in physical activity. Physical inactivity has been associated with increased morbidity and mortality, as well as risk for various health outcomes, including cardiovascular disease, stroke, diabetes, and some forms of cancer. The problem of inactivity applies to all US adults, but national data consistently show that levels are highest among AA women. The first section of this brief review provides background information related to the prevalence of physical activity, current physical activity recommendations for various outcomes, and the healthcare provider's role in increasing physical activity. The second section suggests practical approaches for physicians who wish to counsel AA women about increasing physical activity. Many of the approaches are also applicable to AA men and to the general population.


The assembly and organisation of photosynthetic membranes in Rhodobacter sphaeroides.
Recent AFM data demonstrate that mature photosynthetic membranes of R. sphaeroides are composed of rows of dimeric RC-LH1-PufX complexes with some LH2 complexes 'sandwiched' between these rows of core complexes, and others in discrete LH2-only domains which might form the light-responsive complement of the LH2 antenna. The present work applies membrane fractionation, radiolabelling and LDS-PAGE techniques to investigate the response of R. sphaeroides to lowered light intensity. The kinetics underlying this adaptation to low light conditions were revealed by radiolabelling with the bacteriochlorophyll (bchl) biosynthetic precursor, delta-aminolevulinate, which allowed us to measure only the bchls synthesised after the light intensity shift. We show that (1) the increase in LH2 antenna size is mainly restricted to the mature ICM membrane fraction, and the antenna composition of the precursor upper pigmented band (UPB) membrane remains constant, (2) the precursor UPB membrane is enriched in bchl synthase, the terminal enzyme of the bchl biosynthetic pathway, and (3) the LH2 and the complexes of intermediate migration in LDS-PAGE exhibit completely different labelling kinetics. Thus, new photosynthetic complexes, mainly LH2, are synthesised and assembled at the membrane initiation UPB sites, where the LH2 rings pack between the rows of dimeric cores fostering new LH2-LH1 interactions. Mature membranes also assemble new LH2 rings, but in this case the 'sandwich' regions between the rows of core dimers are already fully occupied and the bulk antenna pool is the favoured location for these new LH2 complexes.


Intraphagocytic penetration of antibiotics.
The penetration of several antibiotics into human polymorphonuclear leucocytes was measured with a bioassay. The aminoglycosides (gentamicin, netilmicin), oxacillin and LY146032, a new lipopeptidic antibiotic, had a penetration which was generally less than 60%, whereas new fluoro-quinolones (enoxacin, ciprofloxacin, CI934, Ro236240) and rifamycins (rifampicin, LM427) were concentrated 2.4 to 14.2-fold. The concentration of vancomycin and teicoplanin associated with the neutrophils appeared to be saturable over the range of extracellular concentrations tested (5-20 mg/l). Coumermycin, an inhibitor of DNA-gyrase, was highly concentrated (11.3 to 16.6-fold) within the neutrophils. The penetration of clindamycin and erythromycin was low (0.60- to 1.48-fold).


Carbon "onions" as point electron sources.
The novel type of an electron field emitter is demonstrated by welding a single carbon "onion" onto the end of a tungsten tip inside a high-resolution transmission electron microscope. Such merged structure is found to markedly reduce the onset voltage peculiar to a standard tungsten field emitter due to the small size of the onion and its highly curved surface. Similar to short carbon nanotubes, individual C-onion emitters can sustain large emission currents, more than 100 muA, and exhibit good long-term emission stability. Moreover the insertion of a high electrical resistance in series can suppress the current fluctuation to only 1.9%. All these properties make these newly created field emitters promising candidates for the advanced point electron sources.