Effect of dynamic three-dimensional culture on osteogenic potential of human periodontal ligament-derived mesenchymal stem cells entrapped in alginate microbeads.

BACKGROUND AND OBJECTIVE: Bioreactors are devices that efficiently create an environment that enables cell cultures to grow in a three-dimensional (3D) context mimicking in vivo conditions. In this study, we investigate the effect of dynamic fluid flow on the osteogenic potential of human mesenchymal stem cells obtained from periodontal ligament and entrapped in alginate microbeads. MATERIAL AND METHODS: After proper immunophenotyping, cells were encapsulated in barium alginate, cultured in 3D static or 3D dynamic conditions represented by a bioreactor system. Calcein-AM/propidium iodide staining was used to assess cellular viability. Quantitative real-time polymerase chain reaction was used to analyze the expression of osteogenic markers (Runx2 and COL1). Alizarin Red S staining and the Fourier transform infrared spectroscopy were used to assess mineral matrix deposition. RESULTS: Optimal encapsulation procedure, in terms of polymer pumping rate, distance from droplet generator to the gelling bath and atomizing airflow was assessed. Cell viability was not affected by encapsulation in alginate microbeads. Bioreactor cell exposure was effective in anticipating osteogenic differentiation and improving mineral matrix deposition. CONCLUSION: For the first time human mesenchymal stem cells obtained from periodontal ligaments encapsulated in alginate microbeads were cultured in a bioreactor system. This combination could represent a promising strategy to create a cell-based smart system with enhanced osteogenic potential useful for many different dental applications.

Aripiprazole for schizophrenia. Systematic review.

BACKGROUND: Aripiprazole is an atypical antipsychotic that is reported to be effective in the treatment of schizophrenia. AIMS: To investigate the effects of aripiprazole on patients with schizophrenia and schizophrenia-like psychoses by conducting a systematic review of randomised controlled trials (RCTs). METHOD: Database and manual searches and direct contact were used to identify relevant RCTs. RESULTS: We included 10 randomised controlled studies (involving a total of 4125 patients), but study attrition was large and the standard of data reporting was poor. Compared with placebo, aripiprazole treatment was associated with a significant decrease in relapse rates, increased compliance with the study protocol, and a decrease in prolactin levels below the expected values. Compared with risperidone, aripiprazole caused less elevation of prolactin levels and less prolongation of the average QTc interval. CONCLUSIONS: Aripiprazole has been licensed despite the fact that few reliable data on this drug are publicly available. It may be effective for treatment of schizophrenia, but in terms of tolerability and global outcomes it shows little difference from existing antipsychotics.

Aripiprazole for schizophrenia.

BACKGROUND: Treatment of people with schizophrenia using older typical antipsychotic drugs such as haloperidol can be problematic. Many fail to respond to these older antipsychotics and more people experience disabling adverse effects. Aripiprazole is said to be one of a new generation of atypical antipsychotics with good antipsychotic properties and minimal adverse effects. OBJECTIVES: To evaluate the effects of aripiprazole for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (September 2005) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant pharmaceutical companies, the FDA and authors of trials for additional information. SELECTION CRITERIA: All clinical randomised trials comparing aripiprazole with placebo, typical or atypical antipsychotic drugs for schizophrenia and schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: Despite the fact that 7110 people participated in fifteen randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. Study attrition was very large and data reporting poor. Compared with placebo, aripiprazole significantly decreased relapse in both the short and medium term (n=300, 1 RCT, RR 0.66 CI 0.5 to 0.8, NNT 5 CI 4 to 8). It also produced better compliance with study protocol (n=2271, 8 RCTs, RR 0.72 CI 0.5 to 0.97, NNT 26 CI 16 to 239). Aripiprazole may decrease prolactin levels below that expected from placebo (n=305, 1 RCT, RR 0.32 CI 0.1 to 0.8, NNT 14 CI 11 to 50). Compared with typical antipsychotics there were no significant benefits for aripiprazole with regards to global state, mental state, quality of life or leaving the study early. Both groups reported similar rates of adverse effects, with the exception of akathisia (n= 955 RR 0.31 CI 0.2 to 0.6, NNT 20 CI 17 to 32) and the need for antiparkinson medication (n=1854, 4 RCTs, RR 0.45 CI 0.3 to 0.6, NNT 4 CI 3 to 5) which were lower in those receiving aripiprazole. When compared with olanzapine and risperidone, aripiprazole was no better or worse on outcomes of global state and leaving the study early. The rates of adverse effects were also similar, with the exception of less elevation of prolactin (n=301, 1 RCT, RR 0.04 CI 0.02 to 0.1, NNT 2 CI 1 to 2.5) and less prolongation of the average QTc (30 mg/day) (n=200, 1 RCT, WMD -10.0, CI -16.99 to -3.0) compared with risperidone. When compared with standard care (mixed group receiving typical and atypical antipsychotics) one aripiprazole study did have significantly less people not responding to treatment (n=1599, RR 0.70 CI 0.7 to 0.8, NNT 5 CI 4 to 6 ), not satisfied with care (n=1599, RR 0.62 CI 0.6 to 0.7, NNT 4 CI 4 to 5) and less people leaving the study early (n=1599, 1 RCT, RR 0.81 CI 0.7 to 0.9, NNT 13 CI 8 to 39). Results from the five new papers identified from the updated review search, did not significantly alter the main results or conclusions of the original review. AUTHORS' CONCLUSIONS: Aripiprazole may be effective for the treatment of schizophrenia, but it does not differ greatly from typical and atypical antipsychotics with respect to treatment response, efficacy or tolerability. In comparison with typical antipsychotics, aripiprazole may have a lower risk of akathisia, and in comparison to atypical antipsychotics, less risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short, medium and long term randomised controlled trials should be undertaken to determine its position in everyday clinical practice.

Aripiprazole for schizophrenia.

BACKGROUND: Treatment of people with schizophrenia using older typical antipsychotic drugs such as haloperidol can be problematic. Many fail to respond and more experience disabling adverse effects. Aripiprazole is said to be one of a new generation of atypical antipsychotics with good antipsychotic properties and minimal adverse effects. OBJECTIVES: To evaluate the effects of aripiprazole for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's Register (May 2003) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. The authors contacted relevant pharmaceutical companies, the FDA and authors of trials for additional information. SELECTION CRITERIA: All clinical randomised trials comparing aripiprazole with placebo, typical or atypical antipsychotic drugs for schizophrenia and schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: Despite the fact that 4125 people participated in ten randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. Study attrition was very large and data reporting poor. Compared with placebo, aripiprazole significantly decreased relapse in both the short and medium term (n=300, 1 RCT, RR 0.66 CI 0.53 to 0.81, NNT 5 CI 4 to 8). It also produced better compliance with study protocol (n=1348, 5 RCTs, RR 0.66 CI 0.49 to 0.88, NNT 15 CI 10 to 41). Aripiprazole may decrease prolactin levels below that expected from placebo (n=305, 1 RCT, RR 0.32 CI 0.13 to 0.81, NNT 14 CI 11 to 50). Compared with typical antipsychotics there were no significant benefits for aripiprazole with regards to global state, mental state, quality of life or leaving the study early. Both groups reported similar rates of adverse effects, including akathisia (RR 0.44 CI 0.17 to 1.12) and general extrapyramidal effects (RR 0.53 CI 0.18 to 1.53). Aripiprazole did however cause more insomnia than perphenazine (n=300, 1 RCT, RR 2.23 CI 1.57 to 3.18, NNH 4 CI 3 to 9) and less need for antiparkinson drugs than 10-20mg/day haloperidol (n=1854, 4 RCTs, RR 0.45 CI 0.33 to 0.60, NNT 4 CI 3 to 5). When compared with olanzapine and risperidone, aripiprazole was no better or worse on outcomes of global state and leaving the study early. The rates of adverse effects were also similar, with the exception of less elevation of prolactin (n=301, 1 RCT, RR 0.04 CI 0.02 to 0.08, NNT 2) and less prolongation of the average QTc (30mg/day) (n=200, 1 RCT, WMD -10.0, CI -16.99 to -3.01) compared with risperidone. REVIEWERS' CONCLUSIONS: Aripiprazole may be effective for the treatment of schizophrenia, but it is not much different from typical antipsychotics and atypical antipsychotics with respect to treatment response, efficacy or tolerability. In comparison with typical antipsychotics, aripiprazole may have a higher risk of insomnia, but in comparison to atypical antipsychotics, less risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short, medium and long term randomised controlled trials should be carried out to determine its position in everyday clinical practice.

Dose related association of impact activity and bone mineral density in pre-pubertal girls.

Impact activity is an important contributor to bone accrual. Children engaging in such activity have been shown to have greater bone mineral density (BMD) than their peers. This cross-sectional study was designed to quantify the association between BMD and impact activity in pre-pubescent girls, specifically examining for a dose-dependent relationship. Fifty 7-11-year-old Caucasian female gymnasts were grouped by hours of gymnastics participation during a 6-month period: LOW, 1-8 hours/week (hrs/wk); HIGH, >8 hrs/wk. They were compared with 20 controls, with height, weight, age, and Tanner stage averages matched to the gymnasts. Total body, forearm, hip, lumbar spine BMD, and body composition were measured by dual energy X-ray absorptiometry (DXA). Strength was measured by one repetition maximum testing, calcium intake was quantified by questionnaire, and physical activity was measured by questionnaire and activity monitors. Total and regional BMD were greater in the HIGH group than the controls (P<0.05). Furthermore, both total and forearm BMD were greater in the HIGH group than in the LOW group, and greater in the LOW group than in the controls (P<0.05). Simple regression analysis between hrs/wk of gymnastics activity versus total and regional BMD (using maturation-adjusted Z scores) yielded a positive slope for each site. R2 was greatest for hip BMD (R2 = 0.25), and least for lumbar spine (R2 = 0.10) (P<0.0001). In conclusion, in this group of pre-pubescent girls, we observed a dose-dependent relationship between BMD and hrs/wk of impact activity; even moderate doses of impact activity were associated with increased BMD.

Return to play after cervical spine injury.

STUDY DESIGN: A questionnaire survey was mailed to members of the Cervical Spine Research Society, the Herodiuus Sports Medicine Society, and to members of the authors' Department of Orthopaedics. OBJECTIVES: The purpose of our study was to evaluate what influence, if any, factors such as published guidelines, type of sport of the patient, number of years in practice, subspecialty interest, and sports participation of the respondent held in the "return to play" decision-making process after a cervical spine injury. SUMMARY OF BACKGROUND DATA: The consequences of cervical spine injury are potentially catastrophic, and return to play decisions in athletes with a history of neck injury can be agonizing. Although recent publications have addressed some of the concerns regarding cervical spine injuries in the athletic population, many questions remain unanswered. Factors such as published guidelines, type of sport of the patient, number of years in practice, subspecialty interest, and sports participation of the respondent have all been suggested as having a possible role in return to play decisions. METHODS: Representative radiographs and case histories of 10 athletes who had sustained neck injury were mailed to 346 physicians. For each case physicians selected every type of play (of six categories) that they felt comfortable recommending. Type of play was divided into six categories: Type 1, collision sports; Type 2, contact sports; Type 3, noncontact, high velocity sports; Type 4, noncontact, repetitive load sports (e.g., running); Type 5, noncontact, low impact sports; Type 6, no sports. In addition, demographic data regarding board certification, subspecialty interest, number of years in practice, use of guidelines in return to play decisions, and personal participation in sports were queried from all respondents. Statistical analysis was completed with Statview (Berkeley, CA). Basic descriptive statistics, chi2, and ANOVA were used where appropriate. RESULTS: Three hundred forty-six questionnaires were mailed and 113 were returned (response rate 32.7%). One hundred ten (97%) of the respondents who completed the questionnaire were board certified. Seventy-five were subspecialists in spine, 22 were subspecialists in sportsmedicine, and 13 reported interests in both sports medicine and spine. Use of Published Guidelines. Although 49% of respondents reported using guidelines in decision-making, the use of guidelines was statistically significant in only one case (P = 0.04). Hierarchy of Risk. In general, those physicians who participated in the study followed the hierarchy of risk that we established in this study (Type 1 [collision sports; highest level of risk] through Type 6 [no sports; lowest level of risk]). Twelve (10.6%) respondents, however, deviated from it in one or more cases. Years in Practice. In three cases there was a statistically significant association between the number of years a physician was in practice and the type of play selected (P < 0.05). In each case a lower level of play tended to be recommended by more senior physicians. Subspecialty Interest. In three cases those respondents with a spine subspecialty interest recommended returned to a higher level of play (P < 0.05). CONCLUSIONS: There is no consensus on the postinjury management of many cervical spine-injured patients. Further research, education, and discussion on this topic are needed.

The effect of gender and body composition method on the apparent decline in lean mass-adjusted resting metabolic rate with age.

BACKGROUND: Declining resting energy expenditure (REE) is a hallmark of normal aging, but the cause of this decline remains controversial. Some, but not all, studies have shown that the decline in REE with age is eliminated after adjustment for fat-free mass (FFM). METHODS: We examined the effect of four body composition methods used to assess FFM (underwater weighing [UWW], bioimpedance analysis [BIA], tritium dilution, and total body potassium [TBK]) on the relationship between REE and age in 30 healthy men and 101 healthy women aged 18 to 87 years. RESULTS: The decline in REE with age was significant in women (-80.3 kJ/d/y, p < .004) but not in men (-46.9 kJ/d/y, p = .328). After adjustment for FFM, the decline in REE with age persisted when FFM was measured by BIA, UWW, or tritium dilution, but no decline was seen when TBK was used to adjust for FFM. In both women and men, fat mass was significantly associated with REE after adjusting for age and FFM. CONCLUSION: It is the decline in cell mass with age, detectable by TBK but not by other methods, rather than any metabolic alteration, that explains the decline in FFM-adjusted REE with age.

Failure to find a chromosome 18 pericentric linkage in families with schizophrenia.

A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small.

Strength improvements with 1 yr of progressive resistance training in older women.

Thirty-nine healthy women (59.5 +/- 0.9 yr) were randomized to either a control group (CON) or a progressive resistance training group (PRT) that trained twice weekly for 12 months. PRT trained at 80% or more (average of 84%) of their most recent one repetition maximum (1RM) on the lateral pull-down (LPD), knee extensor (KE), and double leg press (DLP) apparatus. One RM was measured for each exercise once monthly in PRT and at baseline, midstudy, and end of study in CON. One RM significantly increased in PRT for all muscle groups trained compared to CON (P < 0.0001). Increases of 73.7 +/- 12%, 35.1 +/- 3%, and 77.0 +/- 5%, respectively, for KE, DLP, and LPD in PRT and 12.7% +/- 8%, 3.7% +/- 3%, and 18.4% +/- 4%, respectively, in CON were observed. Approximately 50% of the gains in KE and LPD and 40% in the DLP were seen in the first 3 months of the study. In all three exercises, strength gains in PRT continued over the entire 12-month period. These data indicate that high-intensity strength training results in substantial, continual increases in strength in postmenopausal women for at least 12 months, with the greatest gains seen in the first 3 months of training.

Language and thought disorder in schizophrenia: brain morphological correlates.

In this magnetic resonance imaging study, the authors analyzed the relationships between frontal and temporal lobe volumes, volumes of ventricular system subdivisions and clinical and neuropsychological aspects of language and thought disorder in a group of 19 young schizophrenic patients. Schizophrenics showed enlargement of lateral ventricles, especially of the central and occipital segments compared with 15 age and sex matched healthy controls but no differences were present in prefrontal, temporal lobe and superior temporal gyrus volumes. Prefrontal volume was inversely correlated with Thought, Language and Communication (TLC) scale total scores; left superior temporal gyral (STG) volume was positively correlated with verbal fluency test performance; higher total ventricular volume was significantly correlated with poor performance to a sentence generation test; STG laterality index was correlated with global TLC scores, the more severe the thought and language disorders, the relatively smaller the left and larger the right STG. These results suggest a complex neuroanatomical substrate for thought and language disorders in schizophrenia.

Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures. A randomized controlled trial.

OBJECTIVE: To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women. DESIGN: Randomized controlled trial of 1-year duration. SETTING: Exercise laboratory at Tufts University, Boston, Mass. POPULATION: Forty postmenopausal white women, 50 to 70 years of age, participated in the study; 39 women completed the study. The subjects were sedentary and estrogen-deplete. INTERVENTIONS: High-intensity strength training exercises 2 days per week using five different exercises (n = 20) vs untreated controls (n = 19). MAIN OUTCOME MEASURES: Dual energy x-ray absorptiometry for bone status, one repetition maximum for muscle strength, 24-hour urinary creatinine for muscle mass, and backward tandem walk for dynamic balance. RESULTS: Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 +/- 0.039 g/cm2 (0.9% +/- 4.5%) (mean +/- SD) and 0.009 +/- 0.033 g/cm2 (1.0% +/- 3.6%), respectively, in the strength-trained women and decreased by -0.022 +/- 0.035 g/cm2 (-2.5% +/- 3.8%) and -0.019 +/- 0.035 g/cm2 (-1.8% +/- 3.5%), respectively, in the controls (P = .02 and .04). Total body bone mineral content was preserved in the strength-trained women (+2.0 +/- 68 g; 0.0% +/- 3.0%) and tended to decrease in the controls (-33+77 g; -1.2% +/- 3.4%, P = .12). Muscle mass, muscle strength, and dynamic balance increased in the strength-trained women and decreased in the controls (P = .03 to < .001). CONCLUSIONS: High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass, strength, and balance in postmenopausal women.

A reconsideration of the relationship between cerebral structural abnormalities and family history of schizophrenia.

In a study of 229 schizophrenic patients for whom reliable family history information was available, ventricular size and incidence of ventricular enlargement were found to be greater in male cases without a family history of schizophrenia. A significant sex by family history interaction on cerebral ventricular dimension was detected. The age-corrected morbid risk for schizophrenia was lower among first degree relatives of male probands with ventricular enlargement vs. those with normal ventricles, but similar in relatives of females with and without ventricular enlargement. On the other hand, no association was found between family history and degree of cortical atrophy. A meta-analysis of published studies on the issue revealed 20% larger ventricles in patients without any known genetic predisposition for schizophrenia.

Search for linkage to schizophrenia on the X and Y chromosomes.

Markers for X chromosome loci were used in linkage studies of a large group of small families (n = 126) with at least two schizophrenic members in one sibship. Based on the hypothesis that a gene for schizophrenia could be X-Y linked, with homologous loci on both X and Y, our analyses included all families regardless of the pattern of familial inheritance. Lod scores were computed with both standard X-linked and a novel X-Y model, and sib-pair analyses were performed for all markers examining the sharing of maternal alleles. Small positive lod scores were obtained for loci pericentromeric, from Xp11.4 to Xq12. Lod scores were also computed separately in families selected for evidence of maternal inheritance and absence of male to male transmission of psychosis. The lod score for linkage to the locus DXS7 reached a maximum of 1.83 at 0.08% recombination, assuming dominant inheritance on the X chromosome in these families (n = 34). Further investigation of the X-Y homologous gene hypothesis focussing on this region is warranted.

Male siblings with schizophrenia share alleles at the androgen receptor above chance expectation.

In families that included two or more siblings with schizophrenia or schizo-affective disorder male-male pairs were found to share alleles at the androgen receptor (AR) gene (in Xq11.2-q12) above chance expectation (p < 0.003); female-female and mixed sex pairs showed no such tendency. The findings are compatible with X-Y linkage or with an X-linked contribution to liability in males.

Substantivity of sunscreens: an appraisal of some quaternary ammonium sunscreens.

Synopsis Two series of quaternary ammonium UV-B sunscreens, derived from salicylic acid (S) and from p-methoxycinnamic acid (C), and containing N-alkyl chains of different length (C(2) to C(16)) were prepared and submitted to substantivity tests on animal (wool) keratin, and to microbiological tests. A direct correlation between substantivity and antimicrobial/antifungal activity was observed in all cases, the compounds bearing C(12) alkyl chains displaying peak values. The C-derivatives, when compared with the S-derivatives, showed relatively higher substantivity and sunscreen index (SI) values, coupled with lower antibacterial activity. The substantivity-microbiological activity correlations and the particular behaviour of the C(12) derivatives are briefly discussed in the light of the existing literature data. On the basis of the experimental results, possible guidelines for the development of substantive and non-antibacterial (and possibly, non-irritant) quaternary ammonium sunscreens are indicated.