Hand-Eye Coordination Predicts Joint Attention.
The present article shows that infant and dyad differences in hand-eye coordination predict dyad differences in joint attention (JA). In the study reported here, 51 toddlers ranging in age from 11 to 24 months and their parents wore head-mounted eye trackers as they played with objects together. We found that physically active toddlers aligned their looking behavior with their parent and achieved a substantial proportion of time spent jointly attending to the same object. However, JA did not arise through gaze following but rather through the coordination of gaze with manual actions on objects as both infants and parents attended to their partner's object manipulations. Moreover, dyad differences in JA were associated with dyad differences in hand following.


Very young patient with peculiar squamous cell carcinoma of the lung.
A 20-year-old man with squamous cell carcinoma of the lung is described. Histology of the open lung biopsy specimen revealed squamous cell carcinoma with definite keratinization. Interestingly, the tumor cells were characterized by partial expression of CD34 antigen and neuroendocrine differentiation. The diagnosis was delayed in this case because of his young age. This delayed diagnosis resulted in rapid progression and short survival time. In our review of 667 cases of lung cancers at Okayama University Hospital, only 3 (0.4%) of them were under 30 years of age and also showed advanced stage and very poor prognosis. It is important to take note of lung cancer as a differential diagnosis to detect early-stage lung cancer in young patients when they present with abnormal shadow on chest radiograph.


Reduction in the incidence of invasive pneumococcal disease after general vaccination with 7-valent pneumococcal conjugate vaccine in Germany.
General vaccination with the 7-valent pneumococcal conjugate vaccine was recommended in Germany in July 2006 for all children <2 years. The proportion of reported invasive pneumococcal disease (IPD) caused by vaccine serotypes before vaccine introduction was considerably lower than in the US. We report data from nationwide surveillance of IPD in children with two reporting sources, pediatric hospitals and microbiological laboratories in Germany. Incidence rates with regard to age groups and pneumococcal serotypes are based on capture recapture estimates combining the two reporting sources. Between July 1, 1997 and June 30, 2003, 2680 cases (an average 447 yearly cases) of IPD were observed in children <16 years in Germany compared to 223 cases between July 1, 2007 and June 30, 2008. A significant reduction in overall incidence (4/100,000-3.2/100,000) was attributed to significant reductions in children younger than 2 years (20.0/100,000-11.0/100,000). While the incidence of all serotypes included in the vaccine was reduced in the age group <2 years, the incidence of non-vaccine serotypes remained stable. These data show a first success of the pneumococcal vaccination program in Germany. Further changes in incidence and serotype distribution of IPD are subject to future surveillance.


Hydrogen peroxide acts as an EDHF in the piglet pial vasculature in response to bradykinin.
We investigated the mechanism of EDHF-mediated dilation to bradykinin (BK) in piglet pial arteries. Topically applied BK (3 micromol/l) induced vasodilation (62 +/- 12%) after the administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin, which was inhibited by endothelial impairment or by the BK(2) receptor antagonist HOE-140 (0.3 micromol/l). Western blotting showed the presence of BK(2) receptors in brain cortex and pial vascular tissue samples. The cytochrome P-450 antagonist miconazole (20 micromol/l) and the lipoxygenase inhibitors baicalein (10 micromol/l) and cinnamyl-3,4-dyhydroxy-alpha-cyanocinnamate (1 micromol/l) failed to reduce the BK-induced dilation. However, the H(2)O(2) scavenger catalase (400 U/ml) abolished the response (from 54 +/- 11 to 0 +/- 2 microm; P < 0.01). The ATP-dependent K(+) (K(ATP)) channel inhibitor glibenclamide (10 micromol/l) had a similar effect as well (from 54 +/- 11 to 16 +/- 5 microm; P < 0.05). Coapplication of the Ca(2+)-dependent K(+) channel inhibitors charybdotoxin (0.1 micromol/l) and apamin (0.5 micromol/l) failed to reduce the response. We conclude that H(2)O(2) mediates the non-nitric oxide-, non-prostanoid-dependent vasorelaxation to BK in the piglet pial vasculature. The response is mediated via BK(2) receptors and the opening of K(ATP) channels.


Outcomes of Intramedullary Nail Fixation for Metastatic Disease: Impending and Pathologic Fractures.
Intramedullary nail (IMN) fixation has become a treatment mean for impending and pathologic femur fractures. Currently there continues to be a lack of data examining functional outcomes, complications, and survivorship of patients treated with IMNs for metastatic disease of the femur. We retrospectively identified 183 IMNs placed for impending (n=145) or pathologic (n=38) metastatic fractures from 2010 to 2018. Functional outcomes and complications including blood transfusions, venous thromboembolisms (VTEs) and reoperations were studied. Patients with impending lesions were more likely to be ambulatory at final follow-up (pathologic: 82%, impending: 99%, p<0.0001) and reported greater musculoskeletal tumor society scores (p<0.0001). Likewise, pathologic fractures were associated with greater discharge to non-home locations (p<0.0001) and were more likely to require a postoperative transfusion (pathologic: 66%, impending: 22%, p=0.0001). However, there was no difference in the incidence of VTEs (p=1.00) or reoperations (p=0.69) between cohorts. Patients treated for impending fractures had improved overall survival at 1 year (54% vs. 26%, p<0.0001). IMN fixation was durable in impending and pathologic femoral fractures. Early identification of metastases remains critical as patients treated for impending lesions had greater functional outcomes, fewer complications and improved survivorship compared to patients treated for pathologic fractures.


Pattern formation on nonuniform surfaces by correlated random sequential absorptions.
The pattern formation on nonuniform surfaces by correlated-random sequential absorption (CRSA) process has been investigated by computer simulations. The nonuniform surfaces are represented by percolation clusters with probabilities p(s) and p(s) stands for the nonuniform degree of surfaces. The interactions between the particles and the defects in surfaces are involved by introducing a sticking coefficient s. When s-->0, the CRSA process is controlled by the absorption of surfaces and the correlation between particles. With the correlation increasing from a weak limit to a strong one, the cluster consisting of absorbed particles changes from the dispersed pattern of site percolation to correlated percolation, and then to Leath percolation clusters. When s-->1 and p(s)-->p(c), the CRSA process is dominated by the absorption of the defects, where p(c) is the threshold of percolations. The patterns appear randomly dispersed in spite of the correlation. With the decrease of s and increase of p(s), the interaction controlling the CRSA process changes from the absorption of defects to that of surface and the correlation between particles gradually. For the system s-->0, the transition correlation exponent alpha(c)=d(s), where d(s) is the fractal dimension of the percolation surfaces.


Detection of volcanic unrest onset in La Palma, Canary Islands, evolution and implications.
La Palma island is one of the highest potential risks in the volcanic archipelago of the Canaries and therefore it is important to carry out an in-depth study to define its state of unrest. This has been accomplished through the use of satellite radar observations and an original state-of-the-art interpretation technique. Here we show the detection of the onset of volcanic unrest on La Palma island, most likely decades before a potential eruption. We study its current evolution seeing the spatial and temporal changing nature of activity at this potentially dangerous volcano at unprecedented spatial resolutions and long time scales, providing insights into the dynamic nature of the associated volcanic hazard. The geodetic techniques employed here allow tracking of the fluid migration induced by magma injection at depth and identifying the existence of dislocation sources below Cumbre Vieja volcano which could be associated with a future flank failure. Therefore they should continue being monitored using these and other techniques. The results have implications for the monitoring of steep-sided volcanoes at oceanic islands.


Cascade-coupled racetrack resonators based on the Vernier effect in the mid-infrared.
In this paper we report the experimental demonstration of racetrack resonators in silicon-on-insulator technology platform operating in the mid-infrared wavelength range of 3.7-3.8 μm. Insertion loss lower than 1 dB and extinction ratio up to 30 dB were measured for single resonators. The experimental characterization of directional couplers and bending losses in silicon rib waveguides are also reported. Furthermore, we present the design and fabrication of cascade-coupled racetrack resonators based on the Vernier effect. Experimental spectra of Vernier architectures were demonstrated for the first time in the mid-infrared with insertion loss lower than 1 dB and maximum interstitial peak suppression of 10 dB.


Acanthosis nigricans with severe obesity, insulin resistance and hypothyroidism: improvement by diet control.
We report on a 27-year-old man with acanthosis nigricans (AN) associated with severe obesity, insulin resistance and hypothyroidism. A very low-calorie diet treatment decreased his weight and then ameliorated the insulin-resistant state. These effects were followed by remarkable improvement of the AN prior to the correction of the hypothyroidism. This confirms that AN may be mainly attributed to insulin resistance rather than hypothyroidism per se.


Ensifer meliloti is the preferred symbiont of Medicago arborea in eastern Morocco soils.
Polyphasic characterization of 61 bacteria isolated from root nodules of Medicago arborea (Medic tree) plants growing in 4 arid soils of the arid eastern area of Morocco was studied. All the isolates characterized were fast growers. The phenotypic, symbiotic, and cultural characteristics analyzed allowed the description of a broad physiological diversity among the isolates. The results obtained suggest that the phenotype of these rhizobia might have evolved to adapt to the local conditions. The genetic characterization consisted of an analysis of the rep-PCR (repetitive extragenic palindromic polymerase chain reaction) fingerprints and a PCR-based RFLP (restriction fragment length polymorphism) of the 16S rDNA patterns. The diversity of the isolates was investigated by rep-PCR, giving a similarity of 62%, delineated into 3 clusters, 4 groups, and 6 subclusters. This wide diversity was also observed by a phenotypic approach, where the carbohydrate assimilation test was the most discriminating. The results show a relationship between rep-PCR fingerprinting and sugar assimilation, which are complementary in diversity investigation. The nearly complete 16S rRNA gene sequence from representative strains of each soil showed they are closely related to members of the genus Ensifer of the family Rhizobiaceae within the Alphaproteobacteria and shows the highest similitude values (99.93%/100%) with Ensifer meliloti LMG 6133(T) (X67222). Sequencing of the symbiotic nodC gene from 7 representative strains revealed they had 94.89% identity with the nodC sequence of the type strain E. meliloti LMG 6133(T) (EF428922). Therefore, the 61 M. arborea isolates from the 4 different soils have the same phylogenetic affiliation, which proves the restricted host specificity among M. arborea species.


Tris{2-[(2,6-dimethyl-phen-yl)amino]-eth-yl}amine.
The title compound, C(30)H(42)N(4), is an aryl-ated tris-(amino-eth-yl)amine derivative which was obtained by reducing the corresponding tris-amide with AlH(3). The asymmetric unit consists of one third of a C(3v)-symmetric mol-ecule with the tertiary N atom lying on a crystallographic threefold axis.


Individualized Assessment of Exercise Capacity in Response to Acute and Long-Term Enzyme Replacement Therapy in Pediatric Pompe Disease.
Enzyme replacement therapy (ERT) with alglucosidase alfa improves the prospect of patients with infantile-onset Pompe disease (IOPD). However, a progressive decline has been reported. Objective quantification of the response to ERT when assessing newer strategies is warranted. This combined retrospective-prospective study assessed the acute and long-term effects of ERT on exercise in IOPD patients. Evaluation included cardiopulmonary exercise testing (CPET), 6-min walking test (6MWT), spirometry, motor function test (GMFM-88) and enzyme blood levels. Thirty-four CPETs (17 pre- and 17 two days-post ERT) over variable follow-up periods were performed in four patients. Two days following ERT, blood enzyme levels increased (median, 1.22 and 10.15 μmol/L/h (p = 0.003)). However, FEV1, FVC and GMFM-88, the median 6MWD and the peak VO2 were unchanged. Long-term evaluations showed stabilization in young patients but progressive deterioration in adolescents. Clinical deterioration was associated with more pronounced deterioration in peak VO2 followed in the decreasing order by 6MWD, FVC and GMFM-88. The peak VO2 and 6MWD might serve as more sensitive markers to assess clinical deterioration. More studies are needed to clarify the sensitivity of the peak VO2 and 6MWT for quantification of individualized response. This may be important when assessing newer strategies and formulations in IOPD.


Proton-induced transformation in gating and selectivity of the calcium channel in neurons.
Steady-state elevation of [H+]o inhibits both Ca2+ and Na+ currents in neurons. Step changes in [H+]o, however, induce a transient inward Na+ current (INa(H] in isolated neurons. In outside-out patches of dorsal root ganglion cells, INa(H) was fully activated within 2 ms at pH 6.7, and inactivated with a time constant of 300 ms. Deactivation t1/2 was 3 ms at pH 7.9. INa(H) was blocked by Ca2+ channel blockers. This observation, and the finding that the voltage-gated ICa disappeared rapidly during activation of INa(H) and reappeared with inactivation of INa(H), suggested that INa(H) occurs through a transformed Ca2+ channel. The proton-sensitive site was located at the external mouth of Ca2+ channel. The single channel conductance of INa(H) was 28 ps in symmetrical 120 mM NaCl solutions. Increase of [H+]o during the activation of ICa suppressed ICa within 2 ms. Our studies suggest that the Ca2+ channel exists in two conformational states; a voltage-gated Ca2+-transporting state, and a proton-gated Na+-transporting state. The dominance of the proton-gated state over the voltage-gated state suggests that proton modification of the Ca2+ channel may be extremely important in neurophysiological and neurosecretory function.


A cross-sectional evaluation of knowledge, attitudes, practices, and perceived challenges among Palestinian pharmacists regarding COVID-19.
This study aims to evaluate knowledge, attitudes, practices, and perceived challenges regarding coronavirus disease 2019 among pharmacists in Palestine. An online method was used to collect the data. Three hundred sixty-four pharmacists participated in the study from all areas in the Palestinian territories. The questionnaire consisted of three sections: sociodemographics; knowledge, attitudes, practices regarding coronavirus disease 2019; and barriers that prevent the implementation of infection control measures. The Statistical Package for the Social Sciences program Version 21 was used to analyze the data. Variables were expressed as frequencies, percentages, mean, and median. The chi-square test, Kruskal-Wallis test, Mann-Whitney U test, and Pearson's test were applied, along with logistic regression analysis. The median age of the participants was 29 years old, and most of them were female (70.9%). The analysis found that 76.4% of pharmacists had good knowledge regarding coronavirus disease 2019, and 52.7% had good practices. The median attitude score recorded by the participants was 32 points [Q1-Q3: 30-34] out of 35. Notably, the level of concern regarding coronavirus disease 2019 was significantly associated with all three tools of measurement; knowledge (p = 0.001), attitudes (p = 0.001), and practices (p = 0.001). It also appears that more years of experience had higher odds (3-5 years of experience: odds ratio, 2.560; 95% confidence interval, 1.413-4.639; p = 0.002, more than 5 years: odds ratio, 2.931; 95% confidence interval, 1.188-7.232; p = 0.020) of good practice. Although an acceptable level of knowledge was found, it might be considered inadequate. Moreover, there is a lack of appropriate adherence to safety measures from pharmacists. Therefore, we recommend the responsible authorities generate an organized training program to expand pharmacists' knowledge and experience regarding coronavirus disease 2019.


Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells.
Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells.


Analysis of the BadA stalk from Bartonella henselae reveals domain-specific and domain-overlapping functions in the host cell infection process.
Human pathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders. An important pathogenicity factor of B. henselae is the trimeric autotransporter adhesin Bartonella adhesin A (BadA) which is modularly constructed and consists of a head, a long and repetitive neck-stalk module with 22 repetitive neck/stalk repeats and a membrane anchor. The BadA head is crucial for bacterial adherence to host cells, binding to several extracellular matrix proteins and for the induction of vascular endothelial growth factor (VEGF) secretion. Here, we analysed the biological role of the BadA stalk in the infection process in greater detail. For this purpose, BadA head-bearing and headless deletion mutants with different lengths (containing one or four neck/stalk repeats in the neck-stalk module) were produced and functionally analysed for their ability to bind to fibronectin, collagen and endothelial cells and to induce VEGF secretion. Whereas a head-bearing short version (one neck/stalk element) of BadA lacks exclusively fibronectin binding, a substantially truncated headless BadA mutant was deficient for all of these biological functions. The expression of a longer headless BadA mutant (four neck/stalk repeats) restored fibronectin and collagen binding, adherence to host cells and the induction of VEGF secretion. Our data suggest that (i) the stalk of BadA is exclusively responsible for fibronectin binding and that (ii) both the head and stalk of BadA mediate adherence to collagen and host cells and the induction of VEGF secretion. This indicates overlapping functions of the BadA head and stalk.


Gastric perforation in an extremely low birth weight infant recovered with percutaneous peritoneal drainage.
Neonatal gastric perforation is an uncommon but life-threatening condition, which is mainly encountered in premature infants. Primary surgical repair is the principal mode of the treatment. Gastric perforation in neonates improving with percutaneous peritoneal drainage alone has not been described previously. Therefore, an extremely low birth weight infant is presented herein in order to emphasize that gastric perforation may improve with percutaneous peritoneal drainage alone. Isolated gastric perforations in newborn infants may be improved with percutaneous peritoneal drainage alone without need for primary surgical repair.


Clinical and epidemiological aspects of Crohn's disease in children and adolescents.
Between 1971 and 1980 34 children (18 boys and 16 girls) were diagnosed as having Crohn's disease in Orebro county, Sweden, corresponding to a yearly incidence of 6.1 and a prevalence of 41 per 100,000 children. Classical gastrointestinal symptoms were common, but initially only five patients presented with extraintestinal symptoms and had a normal ESR. Of the patients 13 have only been treated medically and 21 have been operated on. Nine of the children have had a quiescent course, whereas 13 had a recurrent and 11 a chronic course. Most of the children have a good quality of life, which we think is the result of a carefully individualized therapy. One child died.


Improved food intake and reduced nausea and vomiting in patients given a restricted diet while receiving cisplatin chemotherapy.
Administration of cisplatin alone or in combination with other cytotoxic agents commonly produces intractable nausea and vomiting, which is currently controlled through high-dose antiemetic drugs. However, patients often refuse continued therapy because of suboptimal control of nausea and vomiting and substantial decline in nutritional status. In this pilot study, 19 patients receiving cisplatin were evaluated for nausea and vomiting, amount of food intake, and subjective assessment of well-being. The study group received a colorless, odorless, predetermined meal three times daily; the meal included cottage cheese, apple sauce, vanilla ice cream, and other selected foods. Control-group patients selected their own meal. Study-group patients exhibited higher overall food intake, decreased nausea and vomiting, and a higher scored estimation of well-being. The findings of this preliminary study indicate that the study diet helps provide nutrition care to cancer patients receiving cisplatin chemotherapy and helps create an atmosphere where the patient believes he or she has some control in the treatment outcome.


Risk factors for drug use among adolescents: concurrent and longitudinal analyses.
We examined the concurrent and longitudinal associations between risk factors and substance use for a sample of high school students. Ten risk factors were defined that assessed numerous important personal and social areas of life. These factors were found to be associated with ever using, frequency of use, and heavy use of cigarettes, alcohol, cannabis, and hard drugs. Few effects were noted for nonprescription medication. No sex differences were evident for number of risk factors. Finally, the number of different risk factors was predictive of increases in use of all types of substances over a one-year period, after controlling for initial level of use.


One-pot anti-Markovnikov hydroamination of unactivated alkenes by hydrozirconation and amination.
A one-pot anti-Markovnikov hydroamination of alkenes is reported. The synthesis of primary and secondary amines from unactivated olefins was accomplished in the presence of a variety of functional groups. Hydrozirconation, followed by amination with nitrogen electrophiles, provides exclusive anti-Markovnikov selectivity. Most products are isolated in high yields without the use of column chromatography.


Still Lost in Transition? Perspectives of Ongoing Cancer Survivorship Care Needs from Comprehensive Cancer Control Programs, Survivors, and Health Care Providers.
Public health agencies have played a critical role in addressing the complex health and mental health needs of cancer survivors. We conducted a mixed-methods evaluation via a Web-based survey (n = 51) and focus groups (n = 11) with National Comprehensive Cancer Control Program (NCCCP) recipients and interviews (n = 9) with survivors, health care providers (HCPs), and patient navigators to explore these audiences' cancer survivorship information needs and strategies to improve resource dissemination. Participants revealed a need for tailored resources and support for survivors on healthy lifestyle, post-treatment survivorship concerns, psychosocial health, and navigating the health system. HCP needs included education on survivorship care plans and care coordination to facilitate the transition between oncology and primary care. HCPs were survivors' most trusted source for information; however, participants noted difficulties engaging HCPs in survivorship care. These findings can help public health practitioners focus their efforts to better meet the needs of cancer survivors and their HCPs.


The local treatment of burns with antibiotics.
After presenting an analysis of the principal antiseptics used for the local treatment of burns, highlighting their toxicity and the limitations of their antibacterial effectiveness, we describe the therapeutic protocol used in our burns centre (where antibacterial treatment consists exclusively of antibiotics for both local and systemic use). We review the data regarding actual and predicted mortality, and mortality due to septicaemia during the years 2000-2003.


Self-reported acne severity, treatment, and belief patterns across multiple racial and ethnic groups in adolescent students.
Acne vulgaris is a common condition among adolescents regardless of age, gender, and race. We compare the frequency, severity, help-seeking behavior, treatment, and beliefs about acne among students based on race, ethnicity, gender, and age. Anonymous surveys were administered to 1,214 students aged 10-19 years of varied gender, race, and ethnicity in public middle and high schools in New Jersey. Results showed the frequency and severity of acne were high (76% and 65%, respectively) and more prevalent in white compared to non-white respondents (RR = 1.13, 95% CI = 1.04-1.24 and RR = 1.22, 95% CI = 1.09-1.37, respectively), and also in older compared to younger ages (RR = 1.24, 95% CI = 1.17-1.32 and RR = 1.43, 95% CI = 1.32-1.55, respectively). The majority of respondents (83%) reported never having seen a physician for their acne; however, those reporting acne of some severity were more likely to have seen a physician compared with those who did not report acne (21% vs. 8%, p < 0.001). Blacks who reported mild or moderate severity of acne were more likely to have seen a health professional compared to white respondents with same the acne severity (RR = 3.63, 95% CI = 2.06-6.37 and RR = 3.06, 95% CI = 2.02-4.65, respectively). Conversely, Hispanic respondents with mild or moderate acne were less likely to have seen a health professional compared to whites with the same acne severity (RR = 0.56, 95% CI = 0.35-0.89 and RR = 0.47, 95% CI = 0.26-0.86, respectively). Beliefs about external factors affecting acne also varied by race and ethnicity. In conclusion, the severity, frequency, and beliefs about acne all play a role in help-seeking behaviors, which vary to a significant extent by race and ethnicity.


Diospyrin derivative, an anticancer quinonoid, regulates apoptosis at endoplasmic reticulum as well as mitochondria by modulating cytosolic calcium in human breast carcinoma cells.
Diospyrin diethylether (D7), a bisnaphthoquinonoid derivative, exhibited an oxidative stress-dependent apoptosis in several human cancer cells and tumor models. The present study was aimed at evaluation of the increase in cytosolic calcium [Ca(2+)](c) leading to the apoptotic cell death triggered by D7 in MCF7 human breast carcinoma cells. A phosphotidylcholine-specific phospholipase C (PC-PLC) inhibitor, viz. U73122, and an antioxidant, viz. N-acetylcysteine, could significantly prevent the D7-induced rise in [Ca(2+)](c) and PC-PLC activity. Using an endoplasmic reticulum (ER)-Ca(2+) mobilizer (thapsigargin) and an ER-IP3R antagonist (heparin), results revealed ER as a major source of [Ca(2+)](c) which led to the activation of calpain and caspase12, and cleavage of fodrin. These effects including apoptosis were significantly inhibited by the pretreatment of Bapta-AM (a cell permeable Ca(2+)-specific chelator), or calpeptin (a calpain inhibitor). Furthermore, D7-induced [Ca(2+)](c) was found to alter mitochondrial membrane potential and induce cytochrome c release, which was inhibited by either Bapta-AM or ruthenium red (an inhibitor of mitochondrial Ca(2+) uniporter). Thus, these results provided a deeper insight into the D7-induced redox signaling which eventually integrated the calcium-dependent calpain/caspase12 activation and mitochondrial alterations to accentuate the induction of apoptotic cell death.


Assessment of sympathovagal imbalance by spectral analysis of heart rate variability in prehypertensive and hypertensive patients in Indian population.
Though the incidence of hypertension has increased considerably in recent years, the pathophysiologic mechanism that causes progression from stage of prehypertension to hypertension has not been fully elucidated. Therefore, the present study was conducted to assess the sympathovagal imbalance in prehypertensives and hypertensives by spectral analysis of heart rate variability (HRV) to understand the nature of change in autonomic balance in this common dysfunction of mankind. Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), and spectral indices of HRV such as total power (TP), normalized low frequency power (LFnu), normalized high frequency power (HFnu), ratio of low frequency power to high frequency power (LF-HF ratio), mean heart rate (mean RR), square root of the mean squared differences of successive normal to normal intervals (RMSSD), the number of interval differences of successive NN intervals greater than 50 ms (NN50), and the proportion derived by dividing NN50 by the total number of NN intervals (pNN50) were assessed in three groups of subjects: normotensives (n = 32), prehypertensives (n = 28), and hypertensives (n = 31). Sympathovagal balance was analyzed and correlated with BMI, BHR, and BP in all the groups. It was observed that autonomic imbalance in prehypertensives was due to proportionate increased sympathetic activity and vagal inhibition, whereas in hypertensives, vagal withdrawal was more prominent than sympathetic overactivity. The LF-HF ratio, the sensitive indicator of sympathovagal balance, was significantly correlated with BMI, BHR, and BP. It was concluded that vagal inhibition plays an important role in the critical alteration of sympathovagal balance in the development of clinical hypertension in prehypertensive subjects.


Dopamine-D2S receptor inhibition of calcium influx, adenylyl cyclase, and mitogen-activated protein kinase in pituitary cells: distinct Galpha and Gbetagamma requirements.
The G protein specificity of multiple signaling pathways of the dopamine-D2S (short form) receptor was investigated in GH4ZR7 lactotroph cells. Activation of the dopamine-D2S receptor inhibited forskolin-induced cAMP production, reduced BayK8644- activated calcium influx, and blocked TRH-mediated p42/p44 MAPK phosphorylation. These actions were blocked by pretreatment with pertussis toxin (PTX), indicating mediation by G(i/o) proteins. D2S stimulation also decreased TRH-induced MAPK/ERK kinase phosphorylation. TRH induced c-Raf but not B-Raf activation, and the D2S receptor inhibited both TRH-induced c-Raf and basal B-Raf kinase activity. After PTX treatment, D2S receptor signaling was rescued in cells stably transfected with individual PTX-insensitive Galpha mutants. Inhibition of adenylyl cyclase was partly rescued by Galpha(i)2 or Galpha(i)3, but Galpha(o) alone completely reconstituted D2S-mediated inhibition of BayK8644-induced L-type calcium channel activation. Galpha(o) and Galpha(i)3 were the main components involved in D2S-mediated p42/44 MAPK inhibition. In cells transfected with the carboxyl-terminal domain of G protein receptor kinase to inhibit Gbetagamma signaling, only D2S-mediated inhibition of calcium influx was blocked, but not inhibition of adenylyl cyclase or MAPK. These results indicate that the dopamine-D2S receptor couples to distinct G(i/o) proteins, depending on the pathway addressed, and suggest a novel Galpha(i)3/Galpha(o)-dependent inhibition of MAPK mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase.


Joint ventures for mobile equipment reduce hospital costs.
Many hospitals cannot afford to purchase all of the high-technology equipment necessary to provide a full range of services. Healthcare organizations should consider entering a joint venture to gain access to mobile equipment. However, changes pending in Washington (see Up-data, p. 5) dictate caution for all healthcare joint ventures, particularly those involving physician investments.


[Pneumocardiodilatation in patients with esophageal achalasia].
Patients with esophageal achalasia, treated by pneumocardiodilatation with "Esophageal balloon dilatation" of the firm "Cook"--Denmark with a size of 22 mm in an inflamed state, were followed up for a period of 8 years. The result of the first course of pneumocardiodilatation treatment was unsatisfactory in 13.9% of the patients and they were recommended a surgical treatment. In the remaining patients the duration of the treatment effect lasted from 10 months up to 8 years. In 16.1% of the patients repeated redilatations were needed at intervals of 10 to 22 months. For this group of patients a decision should be made how to proceed further--with repeated pneumocardiodilatations or with surgical treatment.


Postmortem examination in cases of custodial death in India.
Death in custody causes one of the most embarrassing situation for the law enforcement agencies and medicolegal experts. The doctors has to follow the guidelines given by National Human Rights Commission while conducting postmortem examination in such cases and many a times doctors have been blamed for giving a biased opinion under influence to protect the interests of police and jail officials. This paper discusses postmortem examination in cases of custodial deaths and incidence of custodial death in India as well as other parts of the world. The cases of custodial deaths for which autopsy was conducted at AIIMS has also been discussed.


The Probiotics in Pediatric Asthma Management (PROPAM) Study in the Primary Care Setting: A Randomized, Controlled, Double-Blind Trial with Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706).
Type-2 inflammation commonly marks asthma in childhood. Also, gut and lung dysbiosis is detectable in patients with asthma. Strain-related probiotic supplementation may restore a physiological immune response, dampen airway inflammation, and repair dysbiosis. Therefore, the probiotics in pediatric asthma management (PROPAM) study is aimed at demonstrating that Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) mixture could reduce asthma exacerbations in children, followed in a primary care setting. The study was randomized, placebo-controlled, and double-blind. It involved 11 Italian primary care pediatricians. The probiotic mixture (containing Ligilactobacillus salivarius LS01 1 × 109 live cells and Bifidobacterium breve B632 1 × 109 live cells) or placebo was taken twice daily (1 sachet in the morning and 1 in the evening) for eight weeks and subsequently once daily for a further eight weeks. Outcomes included number, severity, and duration of asthma exacerbations, intensity of maintenance and as need treatments, and safety. The per-protocol population included 422 children (mean age seven years, 240 males and 182 females). The probiotic mixture significantly reduced the number of asthmatic exacerbations (OR = 3.17). In addition, the number of children with two exacerbations was less than a third in the active group (OR = 3.65). This PROPAM study demonstrated that probiotic strains Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) were safe and significantly reduced by more than a third the frequency of asthma exacerbations. At present, the first-line treatment of asthma is still drug-based, but specific strains of probiotics may be auxiliary remedies.


Mesenchymal stromal cell therapy alone does not lead to complete restoration of skin parameters in diabetic foot patients within a 3-year follow-up period.
Introduction: Mesenchymal stromal cells (MSCs) administration is an effective option for the treatment of diabetic foot ulcers (DFUs). However, to date, studies assessing long-term outcomes and evaluating skin parameters after cell-based therapy are lacking. We presented the clinical outcomes of 3 patients, treated for DFUs with the bone marrow MSCs 3 years earlier. Methods: Ultrasound examination was used to compare collagen density and epidermal thickness in areas of healed ulcers in comparison with non-affected skin used as a control. Ultrasound and dermatoscopy were used to exclude neoplasm formation, to assess scar contracture and wound recurrence. Results: In all patients, no ulcer recurrence was detected, which was lower than the expected 60% rate of re-ulceration in diabetic patients in a 3-year period (OD [odds ratio] = 0.095, P = 0.12). No neoplasm formation, no contracture of hypertrophic scar, and adjacent tissue were registered. Collagen ultrasound density was decreased by 57% (P = 0.053) and epidermal thickness was increased by 72% (P = 0.01) in the area of healed ulcers in all patients. Conclusion: MSCs therapy alone did not result in the complete restoration of the skin parameters within a 3-year period. MSCs may represent important adjuvant to the therapy, however, other novel approaches are required to achieve better results.


Feto-maternal microchimerism: Memories from pregnancy.
There is a bidirectional transplacental cell trafficking between mother and fetus during pregnancy in placental mammals. The presence and persistence of fetal cells in maternal tissues are known as fetal microchimerism (FMc). FMc has high multilineage potential with a great ability to differentiate and functionally integrate into maternal tissue. FMc has been found in various maternal tissues in animal models and humans. Its permanence in the maternal body up to decades after delivery suggests it might play an essential role in maternal pathophysiology. Studying the presence, localization, and characteristics of FMc in maternal tissues is key to understanding its impact on the woman's body. Here we comprehensively review the existence of FMc in different species and organs and tissues, aiming to better characterize their possible role in human health and disease. We also highlight several methodological considerations that would optimize the detection, quantification, and functional determination of FMc.


Association between IgM anti-herpes simplex virus and plasma amyloid-beta levels.
Herpes simplex virus (HSV) reactivation has been identified as a possible risk factor for Alzheimer's disease (AD) and plasma amyloid-beta (Aβ) levels might be considered as possible biomarkers of the risk of AD. The aim of our study was to investigate the association between anti-HSV antibodies and plasma Aβ levels. The study sample consisted of 1222 subjects (73.9 y in mean) from the Three-City cohort. IgM and IgG anti-HSV antibodies were quantified using an ELISA kit, and plasma levels of Aβ(1-40) and Aβ(1-42) were measured using an xMAP-based assay technology. Cross-sectional analyses of the associations between anti-HSV antibodies and plasma Aβ levels were performed by multi-linear regression. After adjustment for study center, age, sex, education, and apolipoprotein E-e4 polymorphism, plasma Aβ(1-42) and Aβ(1-40) levels were specifically inversely associated with anti-HSV IgM levels (β = -20.7, P=0.001 and β = -92.4, P=0.007, respectively). In a sub-sample with information on CLU- and CR1-linked SNPs genotyping (n=754), additional adjustment for CR1 or CLU markers did not modify these associations (adjustment for CR1 rs6656401, β = -25.6, P=0.002 for Aβ(1-42) and β = -132.7, P=0.002 for Aβ(1-40;) adjustment for CLU rs2279590, β = -25.6, P=0.002 for Aβ(1-42) and β = -134.8, P=0.002 for Aβ(1-40)). No association between the plasma Aβ(1-42)-to-Aβ(1-40) ratio and anti-HSV IgM or IgG were evidenced. High anti-HSV IgM levels, markers of HSV reactivation, are associated with lower plasma Aβ(1-40) and Aβ(1-42) levels, which suggest a possible involvement of the virus in the alterations of the APP processing and potentially in the pathogenesis of AD in human.


Merci Retriever in acute stroke treatment.
The Merci Retriever is a device used for mechanical clot extraction in cerebral arteries. It obtained US FDA clearance in August 2004 for recanalization of cerebral arteries in acute stroke. Previously, intravenous recombinant tissue plasminogen activator administered within 3 h from symptom onset was the only other FDA-approved treatment in acute stroke. Stroke from large brain artery occlusion, which has the highest morbidity and mortality rate, is inefficiently treated with intravenous recombinant tissue plasminogen activator and has a high likelihood of hemorrhagic complication. In the multicenter prospective Mechanical Embolus Removal in Cerebral Ischemia trial that led to FDA clearance, the Merci Retriever achieved 48% vessel recanalization when used within 8 h of stroke onset, and resulted in lower morbidity and mortality in revascularized patients. Clinical efficacy trials are needed to determine the place of this device in the treatment of stroke patients.


Atrial fibrillation is associated with decreased total cerebral blood flow and brain perfusion.
Atrial fibrillation (AF) has been associated with cognitive impairment. Additionally, brain volume may be reduced in individuals with AF. Potential causes may include cerebral micro-embolism or reduced stroke volume due to the beat-to-beat variation in AF. The aims of this study were to measure cerebral blood flow and estimate whole brain perfusion in elderly individuals with and without AF. Blood flow in the cervical arteries was measured with phase contrast MRI and brain perfusion estimated in a large cohort from the AGES-Reykjavik Study. Individuals were divided into three groups at the time of the MRI: persistent AF, paroxysmal AF, and no history of AF. Of 2291 participants (mean age 79.5 years), 117 had persistent AF and 78 had paroxysmal AF but were in sinus rhythm at the time of imaging AF. Those with persistent AF had lower cholesterol and used more anti-hypertensive medication and warfarin. The three groups were similar with regard to other cardiovascular risk factors. Those in the persistent AF group had significantly lower total cerebral blood flow on average, 472.1 mL/min, both when compared with the paroxysmal AF group, 512.3 mL/min (P < 0.05) and the no AF group, 541.0 mL/min (P < 0.001). Brain perfusion was lowest in the persistent AF group, 46.4 mL/100 g/min compared with the paroxysmal AF group, 50.9 mL/100 g/min in (P < 0.05) and those with no AF, 52.8 mL/100 g/min (P < 0.001). Persistent AF decreases blood flow to the brain as well as perfusion of brain tissue compared with sinus rhythm.


RhoH, a hematopoietic-specific Rho GTPase, regulates proliferation, survival, migration, and engraftment of hematopoietic progenitor cells.
Rho guanosine triphosphatases (GT-Pases) are recognized as critical mediators of signaling pathways regulating actin assembly, migration, proliferation, and survival in hematopoietic cells. Here, we have studied a recently identified hematopoietic-specific Rho GTPase, RhoH. Unlike most members of the Rho GTPase family, RhoH is GTPase deficient and does not cycle between GTP- and guanosine diphosphate (GDP)-bound forms, suggesting that regulation of RhoH expression may be critical in its activity. We found that RhoH is expressed in murine hematopoietic progenitor cells (HPCs) and fully differentiated myeloid and lymphoid lineages. In cytokine-stimulated HPCs, knockdown of RhoH expression via RNA interference stimulates proliferation, survival, and stromal cell-derived factor-1 alpha (SDF-1 alpha)-induced migration in vitro. Conversely, RhoH overexpression in these cells via retrovirus-mediated gene transfer is associated with impaired activation of Rac GTPases, reduced proliferation, increased apoptosis, and defective actin polymerization and chemotaxis. In vivo, HPCs with RhoH overexpression demonstrate defective hematopoietic reconstitution capability compared with control vector-transduced cells. Our results suggest that RhoH serves as a negative regulator of both growth and actin-based function of HPCs possibly via suppression of Rac-mediated signaling.


Induced orbital paramagnetism and paratropism in closed-shell molecules.
Three-dimensional models of the quantum-mechanical current density induced by a uniform magnetic field in the electron cloud have been obtained for closed-shell systems BeH(-), BH, and CH(+), characterized by induced orbital paramagnetism, and in planar unsaturated hydrocarbons C(4)H(4) and clamped C(8)H(8), exhibiting pi paramagnetism. It is shown that, even for these paramagnetic systems, the paramagnetic contributions to magnetic susceptibilities and nuclear magnetic shielding, customarily taken into account in perturbation theory approaches, can formally be eliminated via the procedure of continuous transformation of the origin of the current density-paramagnetic zero. The definition of magnetic response properties can therefore be recast as a sum of two formally "diamagnetic" terms for any molecule, including systems showing strong induced orbital paramagnetism. It is shown that the paramagnetism in the compounds studied arises from the nodal topology of the electronic wave function. In particular, paratropic vortices circulate about stagnation lines at the intersection of nodal surfaces of the highest-occupied zero-order molecular orbital and corresponding first-order orbital.


Physical activity and nutritional status of children of low socioeconomic status. Two interrelated problems: undernutrition and overweight.
The aim of this study was to analyse the level of habitual physical activity (HPA) and nutritional status of children attending selected public schools in Brazil. The sample comprised 1719 participants who ranged in age from 11 to 14 yrs with 861 females (F) aged 12.7+/-1.0 yr and 858 males (M) aged 12.7+/-1.0 yr. The short form of the International Physical Activity Questionnaire (IPAQ) was used to measure HPA. Nutritional status was assessed using the body mass index (BMI). Statistical analyses included ANOVA followed by the post-hoc Tukey-test (P<0.05) which showed a statistically significant difference between M and F in time spent in moderate intensity physical activity. F completed more moderate intensity physical activity than M whereas time in vigorous physical activities was higher in M than F. Analyses of BMI and IPAQ categorical score using Pearson product moment correlations with subsequent Fisher Z transformation showed values of Z = 0.49 for females and Z = 0.44 for males, indicating a low relationship between these variables. HPA levels showed 93.7% of the M and 91.1% of the F were at least minimally active. According to BMI values, 7.3% of the cohort was underweight; 83.0% normal weight; 8.3% overweight and 1.3% obese. These results demand attention, particularly for children at the lower end of nutritional status and HPA levels due to the potential negative impact on their growth and development. At the other end of the nutritional spectrum, one needs to be concerned regarding the levels of excess body weight, mainly considering the poor region in which the children live.


Generation of membrane-bound catechol-O-methyl transferase deficient mice with disctinct sex dependent behavioral phenotype.
Catechol-O-methyltransferase (COMT) has two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-MT), anchored to intracellular membranes. COMT is involved in the O-methylation of L-DOPA, dopamine and other catechols. The exact role of MB-COMT is still mostly unclear. We wanted to create a novel genetically modified mouse model that specifically lacks MB-COMT activity and to study their behavioral phenotype. MB-COMT knock-in mutant mice were generated by introducing two point mutations in exon 2 of the Comt gene (ATGCTG->GAGCTC disabling the function of the P2 promoter and allowing only the P1-regulated S-COMT transcription. The first mutation changes methionine to glutamic acid whereas the second one does not affect coding. The expression of the two COMT isoforms, total COMT activity in several areas of the brain and peripheral tissues and extracellular dopamine concentrations after L-DOPA (10 mg/kg) and carbidopa (30 mg/kg) subcutaneous administration were assessed. A battery of behavioral tests was performed to compare MB-COMT deficient mice and their wild type littermates of both sexes. MB-COMT deficient mice were seemingly normal, bred usually and had unaltered COMT activity in the brain and periphery despite a complete lack of the MB-COMT protein. MB-COMT deficient male mice showed higher extracellular dopamine levels than their wild-type littermates in the striatum, but not in the mPFC. In addition, the MB-COMT deficient male mice exhibited a distinct endophenotype characterized by schizophrenia-related behaviors like aggressive behavior and reduced prepulse inhibition. They also had prolonged immobility in the tail suspension test. Both sexes were sensitized to acute pain and had normal motor activity but disturbed short-term memory. Hence the behavioral phenotype was not limited to schizophrenia-related endophenotype and some behavioural findings were not sex-dependent. Our findings indicate that MB-COMT is critical for behavior, and its function in COMT-dependent brain areas cannot be entirely substituted by the remaining S-COMT.


Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults.
For prevention of obesity in Chinese population, it is necessary to define the optimal range of healthy weight and the appropriate cut-off points of BMI and waist circumference for Chinese adults. The Working Group on Obesity in China under the support of International Life Sciences Institute Focal point in China organized a meta-analysis on the relation between BMI, waist circumference and risk factors of related chronic diseases (e.g., high diabetes, diabetes mellitus, and lipoprotein disorders). 13 population studies in all met the criteria for enrollment, with data of 239,972 adults (20-70 year) surveyed in the 1990s. Data on waist circumference was available for 111,411 persons and data on serum lipids and glucose were available for more than 80,000. The study populations located in 21 provinces, municipalities and autonomous regions in mainland China as well as in Taiwan. Each enrolled study provided data according to a common protocol and uniform format. The Center for data management in Department of Epidemiology, Fu Wai Hospital was responsible for statistical analysis. The prevalence of hypertension, diabetes, dyslipidemia and clustering of risk factors all increased with increasing levels of BMI or waist circumference. BMI at 24 with best sensitivity and specificity for identification of the risk factors, was recommended as the cut-off point for overweight, BMI at 28 which may identify the risk factors with specificity around 90% was recommended as the cut-off point for obesity. Waist circumference beyond 85 cm for men and beyond 80 cm for women were recommended as the cut-off points for central obesity. Analysis of population attributable risk percent illustrated that reducing BMI to normal range (< 24) could prevent 45%-50% clustering of risk factors. Treatment of obese persons (BMI > or = 28) with drugs could prevent 15%-17% clustering of risk factors. The waist circumference controlled under 85 cm for men and under 80 cm for women, could prevent 47%-58% clustering of risk factors. According to these, a classification of overweight and obesity for Chinese adults is recommended.


Paternal vs maternal kangaroo care for procedural pain in preterm neonates: a randomized crossover trial.
To test paternal vs maternal kangaroo care (KC) to reduce pain from heel lance. Randomized crossover design. Three university-affiliated level III neonatal intensive care units. Sixty-two preterm neonates at 28 to 36 weeks' gestational age who were expected to stay in the neonatal intensive care unit for at least 2 blood sampling procedures, without major congenital anomalies, grade III or IV intraventricular hemorrhage, or periventricular leukomalacia; without surgical interventions; not receiving parenteral analgesics or sedatives within 72 hours; and with parental consent. During 2 separate medically ordered heel lance procedures at least 24 hours apart, infants were held in KC for 30 minutes before and during the procedure with the mother or with the father, and with the other parent in the subsequent session. Which parent came first was randomized. The Premature Infant Pain Profile and time for heart rate to return to baseline were the primary outcomes. At 30 and 60 seconds after the heel lance, infants in maternal KC displayed significantly lower scores on the Premature Infant Pain Profile than when in paternal KC (30 seconds mean difference, 1.435 [95% confidence interval, 0.232-2.632]); 60 seconds mean difference, 1.548 [95% confidence interval, 0.069-3.027]). At 90 and 120 seconds, there were no differences. The difference in time to return to KC heart rate before the heel lance was significant, with the time in maternal KC being 204 seconds and in paternal KC, 246 seconds (mean difference, 42 seconds [95% confidence interval, 5.16-81.06 seconds]). Mothers were marginally more effective than fathers in decreasing pain response. Future research should address feasibility issues and nonparent providers of KC during painful procedures. clinicaltrials.gov Identifier: ISRCTN51481987.


[Cloning and characterization of a novel carbonyl reductase for asymmetric reduction of bulky diaryl ketones].
Asymmetric reduction of bulky diaryl ketones is still one of the challenging tasks in biocatalysis. By genomic data mining, a putative carbonyl reductase gene pascr was found in Pichia pastoris GS115. pascr was cloned and over-expressed in Escherichia coli Rosseta2 (DE3). The recombinant enzyme was purified to homogeneity by Ni-NTA column and its catalytic properties were studied. PasCR strictly used NADPH as cofactor, gel filtration and SDS-PAGE analysis suggested that the native form of PasCR was a dimmer. PasCR exhibited the highest activity at 35 degrees C in phosphate buffer at pH 6.5. The enzyme catalyzed the reduction of some bulky diaryl ketones, such as 4-methylbenzophenone, 2-methylbenzophenone and 4-chlorobenzophenone, especially for 4-methylbenzophenone, the product S--alcohol was obtained with 85% ee.


Transient electrophoresis of spherical particles at low potential and arbitrary double-layer thickness.
A theoretical study is presented for the dynamic electrophoretic response of a charged spherical particle in an unbounded electrolyte solution to a step change in the applied electric field. The electric double layer surrounding the particle may have an arbitrary thickness relative to the particle radius. The transient Stokes equations modified with the electrostatic effect which govern the fluid velocity field are linearized by assuming that the system is only slightly distorted from equilibrium. Semianalytical results for the transient electrophoretic mobility of the particle are obtained as a function of relevant parameters by using the Debye-Huckel approximation. The results demonstrate that the electrophoretic mobility of a particle with a constant relative mass density at a specified dimensionless time normalized by its steady-state quantity decreases monotonically with a decrease in the parameter kappaa, where kappa(-1) is the Debye screening length and a is the particle radius. For a given value of kappaa, a heavier particle lags behind a lighter one in the development of the electrophoretic mobility. In the limits of kappaa --> infinity and kappaa = 0, our results reduce to the corresponding analytical solutions available in the literature. The electrophoretic acceleration of the particle is a monotonic decreasing function of the time for any fixed value of kappaa. In practical applications, the effect of the relaxation time for the transient electrophoresis is negligible, regardless of the value of kappaa or the relative mass density of the particle.


Psychological impact of isotretinoin treatment in patients with moderate and severe acne.
Acne patients are subject to different degree of psychosocial distress. The emotional impact of acne vulgaris due to disfigurement caused by the disease is undisputed. Most common reactions to the acne are depression and anxiety. The use of isotretinoin, one of the most effective options in acne treatment, increases depression symptoms. The aim of this study was to investigate the psychological status of the patients with moderate to severe acne and to compare patients treated with isotretinoin with patients treated with vitamin C. A total of 85 patients suffering from acne vulgaris were included in the study. The results of this study do not find a significant correlation between the use of isotretinoin and the psychological effects of the drug.


[The determination of the glycogen phosphorylase activity in blood serum].
A method for measuring blood serum glycogen phosphorylase (GP) activity is described, informative at early stages of myocardial infarction. The method is sensitive and available for clinical biochemistry laboratories. It consists in preliminary purification of GP from serum proteins and metabolites by affinity chromatography in micro-columns and subsequent measurement of the activity in the eluate. The procedure involves selective GP sorption on starch, washing, and subsequent desorption with glycogen solution. GP activity is measured by the kinetic spectrophotometric technique, based on enzymic measurement of glucose-1-phosphate, the product of glycogen consumption reaction, at a wavelength of 340 nm. Conditions of serum GP chromatographic purification are modified in the suggested procedure, this improving the sensitivity of the enzyme measurement. Blood serum GP activities were measured in patients with various cardiac diseases--myocardial infarction (15 cases), angina of rest and effort (53), essential hypertension (30). Different methods of GP activity measurements are considered. Recommendations on the use of the described method, a sensitive test for the diagnosis of myocardial infarction, are given.


Purification and characterization of methylmalonyl-CoA mutase from a methanol-utilizing bacterium, Methylobacterium extorquens NR-1.
High activity (about 50 mU x mg protein(-1)) of methylmalonyl-CoA mutase (82-95% apo-enzyme) was constantly found during the cell growth of a methanol-utilizing bacterium, Methylobacterium extorquens NR-1. The apo-enzyme was purified to homogeneity and characterized. The purified enzyme was colorless. An apparent Mr of M. extorquens NR-1 enzyme was calculated to be 150,000 +/- 5,000 by Superdex 200 HR gel filtration. SDS-polyacrylamide gel electrophoresis of the purified enzyme gave two protein bands with an apparent Mr of 85.000 +/- 2,000 and 70,000 +/- 2,000, indicating that the M. extorquens NR-1 enzyme is composed of two nonidentical subunits. NH2-terminal amino acid sequences of the small and large subunits of M. extorquens NR-1 enzyme showed no significant homology to those of the enzyme from other species. Some enzymological properties of the M. extorquens NR-1 enzyme were studied.


p53 and the CNS: tumors and developmental abnormalities.
This article reviews the recent molecular and clinical studies that characterize the role of p53 in pathologies of the central nervous system, p53 has many important biological functions, notably, maintenance of DNA stability and regulation of apoptosis. These features are essential to avoid cellular transformation and ensure normal brain development. Lack of p53 function in the brain results in tumor formation in the astrocytic and lymphoid lineages and in severe neurodevelopmental diseases, such as exencephaly.


Effects of oestrogen on hypothalamic beta-endorphin in ovariectomized and old rats.
Immunocytochemical beta-endorphin (beta-EP) staining and ultrastructural observations in the hypothalamus were compared in normal mature female rats, ovariectomized rats, and aged female rats. The effects of oestradiol benzoate (EB) on the hypothalamus were studied. The female Wistar rats were divided into seven groups, as follows: 40-day-old rats (Mature), 54-day-old rats ovariectomized at 40 days (Ovx), rats ovariectomized at 40 days and injected with 0.1 mg EB daily for 7 days (Ovx + e) rats ovariectomized and injected with one dose of 1 mg EB (Ovx + E), 500-day-old (Old), old rats injected with 0.1 mg EB daily for 7 days (Old + e), and old rats injected with 1 mg EB (Old + E). In the Ovx and Old groups, beta-EP-positive cells in the arcuate nucleus were rarely seen, as compared with the Mature group. The staining of beta-EP-positive cells in Ovx + e was slightly recovered and that in Ovx + E was almost completely recovered. However, no recovery of beta-EP-positive cells was seen in the Old + e or Old + E groups. The number of nerve fibers in the median eminence were reduced in both the Ovx and Old groups, as compared with the Mature group. There was no relationship between changes in these numbers and oestrogen replacement in the Old group, but in the Ovx group oestrogen replacement brought about recovery of these numbers. The number of glial cells increased after oestrogen replacement in both the Ovx and Old groups. The frequency of giant mitochondria in the neurons in the arcuate nucleus decreased after oestrogen replacement in the Old group.


Clinicopathological significance of fascin-1 expression in patients with non-small cell lung cancer.
Fascin-1 promotes the formation of filopodia, lamellipodia, and microspikes of cell membrane after its cross-linking with F-actin, thereby enhancing the cell movement and metastasis and invasion of tumor cells. This study explored the fascin-1 protein's expression in non-small cell lung cancer (NSCLC) tissues and its relationship with clinical pathology and prognostic indicators. Immunohistochemical analysis was used to determine the expression of fascin-1 in NSCLC tissues. We used quantitative real-time polymerase chain reaction and western blot analysis to further verify the results. The fascin-1 expression and statistical method for clinical pathological parameters are examined by χ (2). Kaplan-Meier method is used for survival analysis. Cox's Proportional Hazard Model was used to conduct a combined-effect analysis for each covariate. In 73 of the 128 cases, NSCLC cancer tissues (57.0%) were found with high expression of fascin-1, which was significantly higher than the adjacent tissues (35/128, 27.3%). The results suggested that the high expression of fascin-1 was significantly correlated with lymph node metastasis (P=0.022) and TNM stage (P=0.042). The high fascin-1 expression patients survived shorter than those NSCLC patients with low fascin-1 expression (P<0.05). Univariate analysis revealed that lymph node metastasis, TNM stage, and fascin-1 expression status were correlated with the overall survival. Similarly, lymph node metastasis, TNM stage, and fascin-1 expression status were significantly associated with the overall survival in multivariate analyses by using the Cox regression model. The fascin-1 protein may be a useful prognostic indicator and hopeful new target for NSCLC patients.


The Edinburgh Postnatal Depression Scale: validation for an Australian sample.
One hundred and three post-partum women completed the Edinburgh Postnatal Depression Scale (EPDS) and were interviewed using the Diagnostic Interview Schedule. A cut-off score of 12.5 on the Edinburgh Postnatal Depression Scale identified all nine women who reached criteria for major depression. At this threshold the sensitivity (the percentage of true "cases" identified) of the EPDS was 100%, its specificity (the percentage of true "non-cases" identified as such) 95.7% and its positive predictive value (the percentage of all those tested as positive who were correctly identified as such) 69.2%. Although this study supported the validity of the EPDS, a replication of this study on a larger sample is suggested.


Determination of 226Ra in biological samples by adsorption on specific adsorbers.
The determination of 226Ra in biological samples, such as milk and grass, was studied. 226Ra analysis of cow's milk was studied starting from de-fatted milk. The proteins were eliminated by coagulation of the colloidal phase with trichloroacetic acid. Phosphorus was then removed by precipitating it as molybdophosphate and finally adsorption was carried out by using two different adsorbers in order to concentrate and purify radium. Lead rhodizonate (LEHRO) adsorbed on charcoal and partially reduced tin dioxide (PRTD) were utilised. A method for the determination of 226Ra in grass ashes was also investigated. The main interference, due to magnesium, hinders the use of LERHO, so the proposed procedure is based on adsorption of radium on PRTD at pH 9.5. The magnesium concentration was depleted by precipitating barium (carrier) and radium with calcium carbonate at pH 8 before the adsorption step. The high phosphorus concentration in grass also interferes in the determination of 226Ra; phosphorus was eliminated as above via molybdophosphate precipitation. The radium was carried by barium and spiked with 133Ba. The yield of the chemical procedure was evaluated on the basis of 133Ba activity. Radium samples were alpha-counted and the activity was evaluated with a suitable calibration curve. Both exchangers in the milk analysis and PRTD in grass analysis were shown to be helpful in order to set up an easily performed procedure, which allows many samples to be processed simultaneously. All the methods adopted were shown to be very sensitive. Under the experimental conditions used, with 1 L of milk or 5 g of grass ashes, the limit was about 3 mBq 226Ra L-1 milk and < 1 mBq 226Ra g-1 grass ashes.


Gastrointestinal illness associated with a long-haul flight.
An in-flight incident of vomiting in the cabin and toilet on a trans-Pacific aircraft flight resulted in an outbreak of gastrointestinal (GI) illness among passengers, some of whom subsequently joined a 14-day cruise in New Zealand and Australia. A retrospective cohort analysis of illness occurring in aircraft passengers was undertaken using routine GI illness surveillance data collected by medical staff on a cruise vessel. This was supplemented with data collected from some other passengers and crew on the aircraft. Information was gathered on 224 of the 413 (54.2%) people on the flight (222 passengers and 2 crew members). GI illness within 60 h of arrival in Auckland was reported by 41 of the 122 (33.6%, Fisher's 95% confidence interval 25.3-42.7) passengers seated in the two zones adjacent to the vomiting incident. The pattern of illness suggests a viral infection and highlights the potential of aerosol transmission as well as surface contamination in a closed environment. The spread of infection may have been enhanced by cross-contamination in the toilet cubicle. The significance of the vomiting event was not recognized by the aircraft cabin crew and no pre-arrival information about on-board illness was given to airport health authorities. Isolation of vomiting passengers, where possible, and promotion of appropriate hand hygiene on aircraft has the potential to reduce the spread of infection in passengers on long-haul flights.


A Multiple Indicators Multiple Causes (MIMIC) model of Behavioural and Psychological Symptoms in Dementia (BPSD).
Although there is evidence for distinct behavioural sub-phenotypes in Alzheimer's disease (AD), their inter-relationships and the effect of clinical variables on their expression have been little investigated. We have analysed a sample of 1850 probable AD patients from the UK and Greece with 10 item Neuropsychiatric Inventory (NPI) data. We applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of MMSE, disease duration, gender, age and age of onset on the structure of a four-factor model consisting of "psychosis", "moods", "agitation" and "behavioural dyscontrol". Specific clinical variables predicted the expression of individual factors. When the inter-relationship of factors is modelled, some previously significant associations are lost. For example, lower MMSE scores predict psychosis, agitation and behavioural dyscontrol factors, but psychosis and mood predict the agitation factor. Taking these associations into account MMSE scores did not predict agitation. The complexity of the inter-relations between symptoms, factors and clinical variables is efficiently captured by this MIMIC model.


Water-Tolerant Trifloaluminate Ionic Liquids: New and Unique Lewis Acidic Catalysts for the Synthesis of Chromane.
The first example of triflometallate ionic liquids, named in analogy to chlorometallate ionic liquids, is reported. Trifloaluminate ionic liquids, synthesized from 1-alkyl-3-methylimidazolium triflates and aluminum triflate, were characterized by multinuclear NMR spectroscopy and FT-IR spectroscopy, revealing the existence of oligonuclear, multiply-charged trifloaluminate anions, with multiple bridging triflate modes. Acceptor numbers were determined to quantify their Lewis acidity, rendering trifloaluminate ionic liquids as medium-strength Lewis acids (AN = ca. 65). Used as acidic catalysts in the cycloaddition of 2,4-dimethylphenol and isoprene (molar ratio 2:1) to prepare chromane, trifloaluminate systems outperformed literature systems, showing high activity (conversions 94-99%, selectivities 80-89%) and at low loadings (0.2 mol%) at 35°C. Using these new systems as supported ionic liquid phase (SILP) on multi-walled carbon nanotubes (ionic liquid loading 16 wt%) delivered a recyclable catalytic system, with activity enhanced with respect to the homogenous regime.


Graphene hybrids: synthesis strategies and applications in sensors and sensitized solar cells.
Graphene exhibits unique 2-D structural, chemical, and electronic properties that lead to its many potential applications. In order to expand the scope of its usage, graphene hybrids which combine the synergetic properties of graphene along with metals/metal oxides and other nanostructured materials have been synthesized and are a widely emerging field of research. This review presents an overview of the recent progress made in the field of graphene hybrid architectures with a focus on the synthesis of graphene-carbon nanotube (G-CNT), graphene-semiconductor nanomaterial (G-SNM), and graphene-metal nanomaterial (G-MNM) hybrids. It attempts to identify the bottlenecks involved and outlines future directions for development and comprehensively summarizes their applications in the field of sensing and sensitized solar cells.


Profiling condition-specific, genome-wide regulation of mRNA stability in yeast.
The steady-state abundance of an mRNA is determined by the balance between transcription and decay. Although regulation of transcription has been well studied both experimentally and computationally, regulation of transcript stability has received little attention. We developed an algorithm, MatrixREDUCE, that discovers the position-specific affinity matrices for unknown RNA-binding factors and infers their condition-specific activities, using only genomic sequence data and steady-state mRNA expression data as input. We identified and computationally characterized the binding sites for six mRNA stability regulators in Saccharomyces cerevisiae, which include two members of the Pumilio-homology domain (Puf) family of RNA-binding proteins, Puf3p and Puf4p. We provide computational and experimental evidence that regulation of mRNA stability by these factors is modulated in response to a variety of environmental stimuli.


A case-control study of lung cancer and environmental tobacco smoke among nonsmoking women living in Shanghai, China.
The incidence of lung cancer in women living in China is among the highest in the world but it does not appear that tobacco smoking is a major risk factor for lung cancer. As tobacco smoking is highly prevalent in Chinese men, exposure to environmental tobacco smoke (ETS) may play an important role in the development of lung cancer in Chinese women who never smoked. We conducted the present investigation because previous studies did not account for dietary habits or indoor air pollution from Chinese-style cooking and they did not assess the effect of occupational exposure to ETS. A population-based, case-control study was conducted to evaluate the relationship between lung cancer and exposure to ETS among nonsmoking women living in Shanghai, China. Five-hundred and four women diagnosed with incident, primary lung cancer between February 1992 and January 1994 were identified through the population-based Shanghai Cancer Registry. A control group of 601 nonsmoking women was selected randomly from the Shanghai Residential Registry, and was approximately frequency-matched to the age distribution of the lung cancer cases. Information on lifetime domestic and occupational exposure to ETS was obtained through face-to-face interviews. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression. The OR for ever exposed to ETS from spouses was 1.1 (95% CI: 0.8-1.5), and the OR for ever exposed to ETS at work was 1.7 (95% CI: 1.3-2.3). Furthermore, the OR increased with increasing number of hours of daily exposure to ETS in the workplace and with increasing number of smoking co-workers. No associations were found for exposure to ETS during childhood. The main findings of the present study are that long-term occupational exposure to ETS, both alone or in combination with exposures at home, conferred an increased risk of lung cancer among women who never smoked. The inconsistency of the results regarding exposure to ETS at home and at work may have been due to lower exposures at home.


Near-Infrared Triggered Self-Accelerating Nanozyme Camouflaged with a Cancer Cell Membrane for Precise Targeted Imaging and Enhanced Cancer Immunotherapy.
Although cancer immunotherapy has made encouraging progress, clinical therapeutic efficiency is often modest due to inadequate immunogenicity and immune resistance. Developing promising nanoagents for simultaneously activating tumor-specific immunity and suppressing immune resistance to achieve efficient immunotherapy is still challenging. Herein, we developed a biomimetic nanozyme consisting of a gold nanorod@mesoporous ceria core-shell scaffold with gold nanoparticle deposition and cancer cell membrane camouflage. The nanozyme exhibited near-infrared (NIR)-enhanced GOx-mimicking activity at high temperatures and performed well under hypoxic environments due to an increased in situ oxygen supply. In cancer cells, the nanozyme induced and amplified hyperthermia by triggering self-accelerating cascade reactions to deplete glucose and inhibiting the expression of heat shock protein under NIR irradiation, which can cause mitochondrial dysfunction and redox balance disruption to activate pyroptosis and elicit a robust immune response. Additionally, the immune checkpoint blockade caused by encapsulated JQ1-mediated PD-L1 downregulation synergistically contributed to excellent immune therapeutic effects. Besides, we demonstrated that cancer cell membrane coating endows the nanozyme targeting ability to tumor. The proposed nanozyme will broaden the application of GOx and have the potential as the nanoplatform for imaging-guided and O2-consuming combined treatments.


Quality of Life for Diverse Older Adults in Assisted Living: The Centrality of Control.
This pilot project asked: How do ethnically diverse older adult residents of assisted living (AL) facilities in British Columbia (BC) experience quality of life? And, what role, if any, do organizational and physical environmental features play in influencing how quality of life is experienced? The study was conducted at three AL sites in BC: two ethnoculturally targeted and one nontargeted. Environmental audits at each site captured descriptive data on policies, fees, rules, staffing, meals, and activities, and the built environment of the AL building and neighborhood. Using a framework that understands the quality of life of older adults to be contingent on their capability to pursue 5 conceptual attributes-attachment, role, enjoyment, security, and control-we conducted 3 focus groups with residents (1 per site) and 6 interviews with staff (2 per site). Attributes were linked to the environmental features captured in the audits. All dimensions of the environment, especially organizational, influence tenants' capability to attain the attributes of quality of life, most importantly control. Although many tenants accept the trade-off between increased safety and diminished control that accompanies a move into AL, more could be done to minimize that loss. Social workers can advocate for the necessary multi-sectoral changes.


[Memory and executive functions in multiple sclerosis: preliminary findings with a cognitive battery].
Twenty one MS patients suffering from a relapsing-remitting (four patients), a secondary progressive (12 patients) or a primary progressive form of the disease (five patients) were assessed using a cognitive battery specifically devoted to executive and memory processes. Results showed that, patients without significant depressive state evaluated by the MADR scale, exhibited significant impairments in executive processes, working, episodic and procedural memories whereas short term memory, language and global intellectual efficiency were normal. The preliminary data suggest an impairment of encoding, a process previously underestimated in this disease. In addition, the battery was easily administered to the patients and relevant for the cognitive assessment of MS.


Barriers to Clozapine Use for Competency Restoration and the Value of Further Study.
Hospital-based restoration of adjudicative competence can be challenging, especially for patients who have treatment-resistant psychosis. Clozapine, which has helped many such individuals in the community, has not been well-studied in individuals who are incapable of proceeding with trial. In their small study, Ghossoub and colleagues have brought attention to the potential for this protocol and advocate for further study. This commentary examines potential barriers to conducting larger studies, including Institutional Review Board requirements for research with individuals who are under court supervision. Also, factors that can result in patients relapsing and being readmitted to the hospital for competency restoration due to poor treatment adherence are described. This adverse outcome burdens the judicial and health care systems and prolongs the time between the patient's arrest and trial. Clozapine may be a promising treatment for competency restoration as long as we are cognizant of barriers to further study and treatment adherence.


Human morality and temperament.
This chapter has tried to make two points. First, the concept of morality refers to a developmental cascade of phenomena whose essential features are (a) inhibition of punished acts; (b) a representation of prohibited actions; (c) the emotions of uncertainty, empathy, shame, and guilt; (d) the semantic concepts of good and bad; (e) accepting the moral obligations of social categories; and (f) the concepts of fairness and the ideal. The inhibition of prohibited actions and the cognitive representation of prohibited behaviors, as well as the affect states that follow violations, appear by the end of the second year of life. The concepts of good and bad appear early in the third year, the experience of guilt and awareness of social categories by 4-6 years, and the notions of fairness, the ideal, and relational social categories during the school years. Second, some of the variation in the intensity and frequency of the moral emotions is attributable to the child's temperament. Eleven-year-old children who had been high-reactive infants and admitted to feelings of guilt when they violated a family standard were cortically and autonomically more aroused than the low reactives who reported equally frequent experiences of guilt. Further, high reactives who were perceived by their mothers as highly sensitive to punishment were biologically more aroused than high reactives perceived as less sensitive. Both universal developmental phenomena tied to brain maturation and temperamental variation associated with neurochemistry contribute to the complex phenomena that constitute the moral domain. The role of affect in promoting the adherence to standards remains controversial. Kant believed that people acted morally because acceptance of the categorical imperative required proper behavior-reason was the guardian of social harmony. Peirce and Dewey, by contrast, argued that anticipation of the emotions of anxiety, shame, and guilt motivated loyalty to the community's ethical standards. The fact that adults pay to watch a film that they know will generate a deep feeling of sadness--an emotion most do not seek or welcome in their daily lives--and will remark that they enjoyed the movie warrants an explanation. One possibility is that the experienced emotion affirms their moral values. The Australian film The Rabbit Proof Fence describes three aboriginal sisters who have been taken from their mother to a camp a thousand miles away to be socialized in Australian values. The three girls run away, and most of the film illustrates the hardships that they endure and their close escapes from the authorities who are pursuing them as they walk the thousand miles to reach their home. The audience's empathic sadness for the children affirms their moral belief that children should love their parents and miss their home. I suspect that those in the audience who felt the most intense sadness would praise the film with greater enthusiasm than those who had muted feelings. Because sadness is an emotion that few enjoy or try to attain, there must be another reason for deciding that the film was gratifying. The affirmation of one's moral beliefs could be that source of gratification. The tension between the importance of a rational and the importance of an affective basis for morality is seen in modern industrialized societies where the balance between the feeling of virtue that follows enhancing another and the pleasure that follows the enhancing of self has shifted toward favoring the latter state. Increasing numbers of Americans do not regard their gender, ethnicity, vocation, place of residence, or friendships or the religion of their parents as distinctive sources of virtue. As a result, they are freed from the moral obligations that were attached to these categories in the past and rely primarily on the anticipation of sensory delight and self-enhancement as guides for action and sources of reassurance that they are managing their lives correctly. Although it is likely that future scientists will synthesize a drug that blocks feelings of guilt without affecting the knowledge that an act is wrong, it is less certain that broad use of this drug would eliminate loyalty to the mutual obligations that make a society habitable. Nonetheless, a posture of vigilance is appropriate, for humans, unlike gorillas, can hold representations of envy, hostility, and anger, even toward those whom they have never met, for a very long time. Therefore, empathy and the anticipation of guilt or shame may restrain rudeness, dishonesty, and aggression when reason fails.


Modulation and the linewidth enhancement factor of a diode-pumped Nd:YVO4 laser.
A technique based on an FM/AM method is proposed for measuring the linewidth enhancement factor a of a diode-pumped Nd:YVO4 laser. A standard rate equation model is complemented with temperature effects to explain the observed behavior under pump modulation. The result alpha = 0.25 +/- 0.13 agrees with values deduced from recent optical injection experiments.


Evaluation of useful neutron flux for accelerator boron neutron capture therapy using the 7Li(p,n) reaction.
Accelerator neutron sources for epithermal neutron capture therapy utilising the 7Li(p,n) nuclear reaction are proposed to operate in the range of 1.88 to 2.5 MeV proton energy. Operation with proton energies closer to the reaction threshold decreases neutron yield but allows for smaller reflector and moderator, with less reduction of the epithermal flux, whereas high energies allow thicker targets to be used. The neutron yields for thick lithium targets are estimated in the energy range of 1.881 MeV to 2.5 MeV and useful neutron flux determined. The optimal range of proton energy is found to be 1.89-1.95 MeV, and this is recommended for more detailed studies of neutron transport properties for accelerator BNCT.


Cutaneous infection caused by a novel Francisella sp.
A 69-year-old patient presented with a tender, thickly crusted skin lesion of 1 week's duration. A bacterial culture swab taken from the underlying granular tissue yielded a pure isolate of a Gram-negative coccobacillus, presumptively identified as a novel Francisella species via 16S rRNA and multilocus gene sequence analysis.


Pleomorphic xanthoastrocytoma as a component of a temporal lobe cystic ganglioglioma: a case report.
We report a case of pleomorphic xanthoastrocytoma (PXA) as a component of a ganglioglioma in a 13-year-old Japanese boy. Magnetic resonance imaging showed a large cystic lesion with an enhanced mural nodule of the left temporal lobe. Microscopic examination of the tumor showed that it was composed of two distinct neoplastic components: dysplastic ganglion cells and a PXA. There were gradual transitions between the two neoplastic components, and the PXA constituted the gliomatous component of the ganglioglioma. The PXA component showed spindle-shaped and pleomorphic large cells with lipidized cytoplasm. The tumor cells were surrounded by numerous reticulin fibers. Immunohistochemically, the ganglion cells were negative for glial fibrillary acidic protein (GFAP), but showed positive staining for a 70-kDa neurofilament protein, synaptophysin, and NeuN. In contrast, PXA cells were positive for GFAP but negative for neuronal markers. Our case is therefore histologically classified as ganglioglioma with PXA as the glial component. These results suggested that PXA and ganglioglioma share a common origin and that the combination of PXA-ganglioglioma would be positioned along the spectrum between PXA and ganglioglioma. Alternatively, these results may support the hypothesis that PXA originates from glioneuronal progenitor cells capable of generating astrocytic and neuronal cell types.


Quest for Tangible Biomarkers for Triple-Negative Breast Cancer.
Identification of key molecular networks involved in triple-negative breast cancer (TNBC) growth and metastasis will increase our mechanistic understanding of this disease and pave the way for the development of novel therapeutic interventions. The study by Khawaled and colleagues points to a direct antimetastatic function of WW domain-containing oxidoreductase (WWOX) in TNBC and identifies the Myc/miR-146a/fibronectin axis as a molecular mediator of the tumor-suppressive function of WWOX. This information can potentially be used to identify actionable nodes for targeting TNBC, a breast cancer subtype otherwise characterized by the absence of markers.See related article by Khawaled et al., p. 1784.


Simultaneous primary and contralateral revision total knee arthroplasty.
Seven patients underwent primary and contralateral revision total knee arthroplasty (TKA) under one anesthetic in a sequential fashion. The average patient age was 67.6+/-6.9 years. Average blood loss was 764+/-568 cc, average operative time was 269+/-107 minutes, and average length of hospital stay was 9.6+/-3.4 days. One patient with a history of hypertension, diabetes, and coronary heart disease died from pulmonary embolism 7 days after surgery. Deep infection with enterococcus developed in the revised knee of another patient 3 months after surgery. For the six surviving patients, knee pain and function were improved by surgery. However, in this small series of patients, two major complications occurred. These results indicate that if this procedure is considered at all, it should be reserved for only healthy patients with relatively uncomplicated knee reconstructions.


Disorders of the inner-ear balance organs and their pathways.
Disorders of the inner-ear balance organs can be grouped by their manner of presentation into acute, episodic, or chronic vestibular syndromes. A sudden unilateral vestibular injury produces severe vertigo, nausea, and imbalance lasting days, known as the acute vestibular syndrome (AVS). A bedside head impulse and oculomotor examination helps separate vestibular neuritis, the more common and innocuous cause of AVS, from stroke. Benign positional vertigo, a common cause of episodic positional vertigo, occurs when otoconia overlying the otolith membrane falls into the semicircular canals, producing brief spells of spinning vertigo triggered by head movement. Benign positional vertigo is diagnosed by a positional test, which triggers paroxysmal positional nystagmus in the plane of the affected semicircular canal. Episodic spontaneous vertigo caused by vestibular migraine and Ménière's disease can sometimes prove hard to separate. Typically, Ménière's disease is associated with spinning vertigo lasting hours, aural fullness, tinnitus, and fluctuating hearing loss while VM can produce spinning, rocking, or tilting sensations and light-headedness lasting minutes to days, sometimes but not always associated with migraine headaches or photophobia. Injury to both vestibular end-organs results in ataxia and oscillopsia rather than vertigo. Head impulse testing, dynamic visual acuity, and matted Romberg tests are abnormal while conventional neurologic assessments are normal. A defect in the bony roof overlying the superior semicircular canal produces vertigo and oscillopsia provoked by loud sound and pressure (when coughing or sneezing). Three-dimensional temporal bone computed tomography scan and vestibular evoked myogenic potential testing help confirm the diagnosis of superior canal dehiscence. Collectively, these clinical syndromes account for a large proportion of dizzy and unbalanced patients.


Oligomers of cyclopentadithiophene-vinylene in aromatic and quinoidal versions and redox species with intermediate forms.
A new series of π-conjugated oligomers based on the 4,4 dihexyl-4H-cyclopenta[2,1-b:3,4-b']dithiophene vinylene repeating unit has been prepared and characterized by X-ray, electrochemical, spectroscopic (UV-Vis absorption, emission and Raman) and density functional theory methods. The oligomers in their neutral, oxidized and reduced forms have been investigated. The neutral compounds show a longer mean conjugation length than oligothiophenes and oligothiophene-vinylenes and display very rich redox chemistry with the stabilization of polycationic states of which the radical cations and dications are strong NIR absorbers, the latter displaying singlet diradicaloid character. An interesting complementarity between the sequence of aromatic-quinoidal structural segments in the radical cations and dications has been described and interpreted. Two derivatives with the 4,4 dihexyl-4H-cyclopenta[2,1-b:3,4-b']dithiophene vinylene unit, disubstituted either with electron donor, bis(triaryl amino) groups, or acceptors bis(dicyano-methylene) caps enforcing a quinoidal structure in the dithiophene-vinylene bridge, have been also synthesized and characterized. The radical cation of the triarylamine compound and the radical anion of the tetracyano compound similarly display hole and electron charge localization, or confinement, in the nitrogen and dicyano surrounding parts, or class II mixed valence systems, while their dication and dianion species, conversely, are open-shell diradical (i.e., polaron pair) and closed-shell (i.e., bipolaron), respectively. The preparation of these new π-conjugated oligomers gives way to the realization of compounds with new electronic properties and unique structures potentially exploitable in organic electronics.


Enhanced skin carcinogenesis in cyclin D1-conditional transgenic mice: cyclin D1 alters keratinocyte response to calcium-induced terminal differentiation.
Cyclin D1 is a critical gene involved in the regulation of progression through the G(1) phase of the cell cycle, thereby contributing to cell proliferation. Gene amplification and abnormal expression of Cyclin D1 have been described in several human cancers. To understand their biological significance in skin carcinogenesis, we established Cyclin D1-conditional transgenic mice with C57BL/6J background, in which skin-specific overexpression of Cyclin D1 transgene was observed. The mice were subjected to dimethylbenz[a]anthracene complete skin carcinogenesis studies. After 40 weeks of repeated administration of dimethylbenz[a]anthracene on the skin (once a week), all of the mice with high Cyclin D1 expression had papillomas, whereas only 9.5% of the control mice without the transgene developed papillomas. Primary cultured keratinocytes with induced Cyclin D1 transgene expression showed resistance to calcium-induced terminal differentiation and continued to replicate in vitro. These results clearly provide us with direct experimental evidence that overexpression of CyclinD1 induces excessive dermal cell proliferation via the altered differentiation state of keratinocytes. The conditional transgenic mice described here provide excellent in vivo and in vitro model systems to understand the role of cyclin D1 and deregulation of the cell cycle in carcinogenesis.


Downregulation of miR-219 enhances brain-derived neurotrophic factor production in mouse dorsal root ganglia to mediate morphine analgesic tolerance by upregulating CaMKIIγ.
Increasing evidence suggests that microRNAs are functionally involved in the initiation and maintenance of pain hypersensitivity, including chronic morphine analgesic tolerance, through the posttranscriptional regulation of pain-related genes. We have previously demonstrated that miR-219 regulates inflammatory pain in the spinal cord by targeting calcium/calmodulin-dependent protein kinase II gamma (CaMKIIγ). However, whether miR-219 regulates CaMKIIγ expression in the dorsal root ganglia to mediate morphine tolerance remains unclear. MiR-219 expression was downregulated and CaMKIIγ expression was upregulated in mouse dorsal root ganglia following chronic morphine treatment. The changes in miR-219 and CaMKIIγ expression closely correlated with the development of morphine tolerance, which was measured using the reduction of percentage of maximum potential efficiency to thermal stimuli. Morphine tolerance was markedly delayed by upregulating miR-219 expression using miR-219 mimics or downregulating CaMKIIγ expression using CaMKIIγ small interfering RNA. The protein and mRNA expression of brain-derived neurotrophic factor were also induced in dorsal root ganglia by prolonged morphine exposure in a time-dependent manner, which were transcriptionally regulated by miR-219 and CaMKIIγ. Scavenging brain-derived neurotrophic factor via tyrosine receptor kinase B-Fc partially attenuated morphine tolerance. Moreover, functional inhibition of miR-219 via miR-219-sponge in naive mice elicited thermal hyperalgesia and spinal neuronal sensitization, which were both suppressed by CaMKIIγ small interfering RNA or tyrosine receptor kinase B-Fc. These results demonstrate that miR-219 contributes to the development of chronic tolerance to morphine analgesia in mouse dorsal root ganglia by targeting CaMKIIγ and enhancing CaMKIIγ-dependent brain-derived neurotrophic factor expression.