Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion is among the strongest known genetic risk factors for neuropsychiatric disorders, including autism and schizophrenia. Brain imaging studies have reported disrupted large-scale functional connectivity in people with 22q11 deletion syndrome (22q11DS). However, the significance and biological determinants of these functional alterations remain unclear. Here, we use a cross-species design to investigate the developmental trajectory and neural underpinnings of brain dysconnectivity in 22q11DS. We find that LgDel mice, an established mouse model of 22q11DS, exhibit age-specific patterns of functional MRI (fMRI) dysconnectivity, with widespread fMRI hyper-connectivity in juvenile mice reverting to focal hippocampal hypoconnectivity over puberty. These fMRI connectivity alterations are mirrored by co-occurring developmental alterations in dendritic spine density, and are both transiently normalized by developmental GSK3ß inhibition, suggesting a synaptic origin for this phenomenon. Notably, analogous hyper- to hypoconnectivity reconfiguration occurs also in human 22q11DS, where it affects hippocampal and cortical regions spatially enriched for synaptic genes that interact with GSK3ß, and autism-relevant transcripts. Functional dysconnectivity in somatomotor components of this network is predictive of age-dependent social alterations in 22q11.2 deletion carriers. Taken together, these findings suggest that synaptic-related mechanisms underlie developmentally mediated functional dysconnectivity in 22q11DS.

Biomechanical and metabolic aspects of backward (and forward) running on uphill gradients: another clue towards an almost inelastic rebound.

PURPOSE: On level, the metabolic cost (C) of backward running is higher than forward running probably due to a lower elastic energy recoil. On positive gradient, the ability to store and release elastic energy is impaired in forward running. We studied running on level and on gradient to test the hypothesis that the higher metabolic cost and lower efficiency in backward than forward running was due to the impairment in the elastic energy utilisation. METHODS: Eight subjects ran forward and backward on a treadmill on level and on gradient (from 0 to + 25%, with 5% step). The mechanical work, computed from kinematic data, C and efficiency (the ratio between total mechanical work and C) were calculated in each condition. RESULTS: Backward running C was higher than forward running at each condition (on average + 35%) and increased linearly with gradient. Total mechanical work was higher in forward running only at the steepest gradients, thus efficiency was lower in backward running at each gradient. CONCLUSION: Efficiency decreased by increasing gradient in both running modalities highlighting the impairment in the elastic contribution on positive gradient. The lower efficiency values calculated in backward running in all conditions pointed out that backward running was performed with an almost inelastic rebound; thus, muscles performed most of the mechanical work with a high metabolic cost. These new backward running C data permit, by applying the recently introduced 'equivalent slope' concept for running acceleration, to obtain the predictive equation of metabolic power during level backward running acceleration.

La via laparoscópica para la restitución del tránsito intestinal luego de la operación de Hartmann: Consideraciones técnicas y resultados

Antecedentes: El abordaje laparoscopico en la restitución del tránsito luego de operación tipo Hartmann es una opción razonable, aunque con alto índice de conversión. Objetivo: Análisis de resultados en la restitución de Hartmann por laparoscopia y convencional. Diseño: Estudio retrospectivo comparativo. Población: Pacientes operados en un período (1991/2009) en forma sucesiva. Abordaje laparoscópico, 29; convencional, 30. Método: Evaluación del dolor, recuperación del tránsito intestinal, internación y recuperación laboral. La conversión fue analizada en relación a la curva de aprendizaje, antecedente de peritonitis y tiempo transcurrido desde la primer intervención. Resultados: Causas principales de la primera cirugía: Enfermedad diverticular, 27 y cáncer, 15. Hubo 6 accidentes intraoperatorios, laparoscópico, 2; convencional, 4 (Lesión del delgado) (p=0,42%). Las complicaciones fueron 3, y 5 respectivamente. (p= 0,67). La mortalidad fue de 2 para el grupo laparoscópico. (p=0,49). Hubo 5 conversiones (17,2 %). Sin diferencias entre tiempo transcurrido de la primer cirugía (p = 0,32); curva de aprendizaje (p = 0,16) y antecedente de peritonitis (0,65), tiempo de internación (p=0,80), recuperación laboral (p=0,87), curva de aprendizaje (p=0,16), tiempo transcurrido de la primer cirugía (p=0,32) y presencia de peritonitis (p=0,65). El dolor y la recuperación del tránsito fueron menores en el grupo laparoscópico (p=0.0001). Conclusión: La restitución del tránsito luego de operación de Hartmann mediante laparoscopia es posible; aunque con un alto índice de conversión en relación al resto de la cirugía colorrectal, con una morbimortalidad aceptable, menor dolor y recuperación del tránsito intestinal; con respecto a la técnica abierta.(AU)

Background: The laparoscopic approach in the restitution of the intestinal transit after operation type Hartmann is a reasonable option, though with high index of conversion. Objetive: Analysis of results in Hartmanns restitution by laparoscopic and conventional approach. Design: Retrospective, comparative study. Population: Patients produced in a period (1991/2009) in successive form. Laparoscopic approach 29; conventional, 30. Method: Evaluation of the pain, recovery of the intestinal movement, surgery and labor recovery. The conversion went in relation to the curve of learning, precedent of peritonitis and time passed from the first intervention. Results: Mainsprings of first surgery: Disease diverticular, 27 and cancer, 15. There were 6 intraoperative accidents, laparoscópic, 2; conventional, 4 ( Intestinal Injury) (p=0,42 %). The complications were 3, and 5 respectively. (P = 0,67) The mortality was of 2 patients for the laparoscopic group. (P=0,49) There were 5 conversions (17.2 %). Without differences between time passed of the first surgery (p = 0,32); curve of learning (p = 0,16) and precedent of peritonitis (0,65), time of recovery (p=0,80), labor recovery (p=0,87), curved of learning (p=0,16), time passed of the first surgery (p=0,32) and presence of peritonitis (p=0,65). The pain and the recovery of the intestinal movements were minor in the laparoscopic group (p=0.0001) Conclusions: The restitution of the intestinal transit after Hartmanns operation by laparoscopic approach is possible; though with a high index of conversion in relation to the rest of the colorectal surgery, with an acceptable complication and mortality rate, minor pain and recovery of the intestinal transit; that the open approach.(AU)

La vía laparoscópica para la restitución del tránsito intestinal luego de la operación de Hartmann: consideraciones técnicas y resultados / Laparoscopy for the return of intestinal transit after Hartmann operation: technical considerations and results

Antecedentes: El abordaje laparoscopico en la restitución del tránsito luego de operación tipo Hartmann es una opción razonable, aunque con alto índice de conversión. Objetivo: Análisis de resultados en la restitución de Hartmann por laparoscopia y convencional. Diseño: Estudio retrospectivo comparativo. Población: Pacientes operados en un período (1991/2009) en forma sucesiva. Abordaje laparoscópico, 29; convencional, 30. Método: Evaluación del dolor, recuperación del tránsito intestinal, internación y recuperación laboral. La conversión fue analizada en relación a la curva de aprendizaje, antecedente de peritonitis y tiempo transcurrido desde la primer intervención. Resultados: Causas principales de la primera cirugía: Enfermedad diverticular, 27 y cáncer, 15. Hubo 6 accidentes intraoperatorios, laparoscópico, 2; convencional, 4 (Lesión del delgado) (p=0,42%). Las complicaciones fueron 3, y 5 respectivamente. (p= 0,67).La mortalidad fue de 2 para el grupo laparoscópico. (p=0,49).Hubo 5 conversiones (17,2 %). Sin diferencias entre tiempo transcurrido de la primer cirugía (p = 0,32); curva de aprendizaje (p = 0,16) y antecedente de peritonitis (0,65), tiempo de internación (p=0,80), recuperación laboral (p=0,87), curva de aprendizaje (p=0,16), tiempo transcurrido de la primer cirugía (p=0,32) y presencia de peritonitis (p=0,65). El dolor y la recuperación del tránsito fueron menores en el grupo laparoscópico (p=0.0001). Conclusión: La restitución del tránsito luego de operación de Hartmann mediante laparoscopia es posible; aunque con un alto índice de conversión en relación al resto de la cirugía colorrectal, con una morbimortalidad aceptable, menor dolor y recuperación del tránsito intestinal; con respecto a la técnica abierta.

The velo-uvulo-pharyngeal lift or "roman blinds" technique for treatment of snoring: a preliminary report.

Snoring is caused by vibrating anatomical structures in the upper aerodigestive tract. It can be treated surgically and non-surgically, although resective procedures are associated with high postoperative morbidity and failure rate. We describe a new non-resective surgical procedure called the velo-uvulo-pharyngeal lift in which the soft palate is lifted, shortened, advanced and stiffened by means of permanent threads anchored to fibro-osseous attachments at the level of the posterior nasal spine and both pterygoid hamuli. Four adult patients (median age 44.5 years; range 42-65) affected by snoring and mild obstructive sleep apnoea-hypopnoea syndrome (apneoa-hypopnoea index, AHI < 20) requiring septal surgery under general anesthesia also underwent velo-uvulo-pharyngeal lift. There were no significant intra- or post-operative complications, and all of the patients reported immediate snoring relief. The main complaints were slight pain and a sensation of local fullness, both of which spontaneously disappeared within two days. The subjective clinical improvement in snoring was confirmed during post-operative follow-up (median 15.5 months; range 6-25), as was the stable reshaping of the soft velo-uvulo-pharyngeal tissues and enlargement of the mesopharyngeal space. There was also a decrease in daytime sleepiness. Our preliminary results suggest that velo-uvulo-pharyngeal lift is a simple, cost-effective and minimally invasive means of widening the mesopharyngeal space in snoring patients with or without mild sleep apnoea-hypopnoea syndrome. The widening of the mesopharyngeal space prevents contact-induced wall vibrations and its inspiratory obstruction causing hypopnoea and apnoea. It can also be combined with other procedures if indicated.

Validation of a subject specific 3-actuator torque-driven model in human vertical jumping.

In this study, a forward dynamic subject specific 3-actuator torque-driven model of the human musculoskeletal system was created based on measurements of individual characteristics of a subject. Simulation results were compared with experimental vertical squat jumping with and without adding weights. By analyzing kinematic and kinetic experimental data at the instant of the toe-off for the same initial conditions, it was shown that a simple computer simulation using a suitable cost function could reproduce the real task performed by humans. This investigation is the first step in a wider project that will incorporate elastic components, and that will evaluate the advantages of the individual subject approach in modeling.

Efficacy of complex herbal compound of Echinacea angustifolia (Imoviral® Junior) in recurrent upper respiratory tract infections during pediatric age: preliminary results.

AIM: Among pediatric population the recurrent upper respiratory tract infections are very common. Several phytotherapies are been proposed as support therapies and, in particular, the efficacy of Echinacea angustifolia is controversial. This paper presents an evaluation of a new herbal compound in the treatment of recurrent upper respiratory tract infections in a pediatric cohort. METHODS: An immunostimulant herbal compound of Echinacea angustifolia, Arabinogalactan, Acerola (Vitamin C), Beta- Glucan e Zinc (Imoviral® Junior) was given to 37 children affected by recurrent pharyngotonsillitis or otitis media. RESULTS: The mean number of inflammatory episodes (i.e. tonsillitis or otitis media) during 6 months before treatment was 3±2.19, during the 6 months following treatment initiation it was 1±0.93 (P=0.04). After the complete treatment, 77% of children reported an improvement of chronic inflammatory in frequency of acute episodes. The total score of a questionnaire about life quality is improved (P=0.04). Finally, none collateral effects was occurred. CONCLUSION: The herbal compound of echinacea, beta-glucan, vitamin c, arabinoglactan and zinc (Imoviral® Junior) can improve the quality of life in pediatric patients affected by recurrent pharyngotonsillitis and otitis media without contralateral effects.

Skyscraper running: physiological and biomechanical profile of a novel sport activity.

Skyscraper running is here analyzed in terms of mechanical and metabolic requirements, both at the general and at the individual level. Skyscraper runners' metabolic profile has been inferred from the total mechanical power estimated in 36 world records (48-421 m tall buildings), ranked by gender and age range. Individual athlete's performance (n=13) has been experimentally investigated during the Pirelli Vertical Sprint, with data loggers for altitude and heart rate (HR). At a general level, a non-linear regression of Wilkie's model relating maximal mechanical power to event duration revealed the gender and age differences in terms of maximum aerobic power and anaerobic energy resources particularly needed at the beginning of the race. The total mechanical power was found to be partitioned among: the fraction devolved to raise the body center of mass , the need to accelerate the limbs with respect to the body , and running in turns between flights of stairs . At the individual level, experiments revealed that these athletes show a metabolic profile similar to middle-distance runners. Furthermore, best skyscraper runners maintain a constant vertical speed and HR throughout the race, while others suddenly decelerate, negatively affecting the race performance.

Tuberculosis treatment in a refugee and migrant population: 20 years of experience on the Thai-Burmese border.

SETTING: Although tuberculosis (TB) is a curable disease, it remains a major global health problem and an important cause of morbidity and mortality among vulnerable populations, including refugees and migrants. OBJECTIVE: To describe results and experiences over 20 years at a TB programme in refugee camps on the Thai-Burmese border in Tak Province, Thailand, and to identify risk factors associated with adverse outcomes (e.g., default, failure, death). DESIGN: Retrospective review of routine records of 2425 patients admitted for TB treatment in the Mae La TB programme between May 1987 and December 2005. RESULTS: TB cases notified among refugees decreased over 20 years. Among patients treated with a first-, second- or third-line regimen, 77.5% had a successful outcome, 13.5% defaulted, 7.6% died and 1.3% failed treatment. Multivariate analysis for new cases showed higher likelihood of adverse outcomes for patients who were Burmese migrants or Thai villagers, male, aged >15 years or with smear-negative pulmonary TB. CONCLUSION: These findings suggest that treatment outcomes depend on the programme's capacity to respond to specific patients' constraints. High-risk groups, such as migrant populations, need a patient-centred approach, and specific, innovative strategies have to be developed based on the needs of the most vulnerable and marginalised populations.

Impact of the shift from NCHS growth reference to WHO(2006) growth standards in a therapeutic feeding programme in Niger.

OBJECTIVES: To describe the implementation of the WHO(2006) growth standards in a therapeutic feeding programme. METHODS: Using programme monitoring data from 21,769 children 6-59 months admitted to the Médecins Sans Frontières therapeutic feeding programme during 2007, we compared characteristics at admission, type of care and outcomes for children admitted before and after the shift to the WHO(2006) standards. Admission criteria were bipedal oedema, MUAC <110 mm, or weight-for-height (WFH) of <-70% of the median (NCHS) before mid-May 2007, and WFH <-3 z score (WHO(2006)) after mid-May 2007. RESULTS: Children admitted with the WHO(2006) standards were more likely to be younger, with a higher proportion of males, and less malnourished (mean WFH -3.6 z score vs. mean WFH -4.6 z score). They were less likely to require hospitalization or intensive care (28.4%vs. 77%; 12.8%vs. 36.5%) and more likely to be treated exclusively on an outpatient basis (71.6%vs. 23%). Finally, they experienced better outcomes (cure rate: 89%vs. 71.7%, death rate: 2.7%vs. 6.4%, default rate: 6.7%vs. 12.3%). CONCLUSIONS: In this programme, the WHO(2006) standards identify a larger number of malnourished children at an earlier stage of disease facilitating their treatment success.

Gastrocnemius muscle-tendon behaviour during walking in young and older adults.

AIM: Age-related differences in muscle architectural and tendon mechanical properties have been observed in vivo under static conditions and during single joint contractions. The aim of this study was to determine if there are age-related differences in gastrocnemius fascicle-tendon interactions during a fundamental locomotor task - walking. METHODS: Eight young adults (YA; 27 +/- 4 years) and eight older adults (OA; 77 +/- 4 years) walked on a treadmill at 1.11 m s(-1) whilst length changes in the gastrocnemius lateralis muscle tendon complex (MTC), fascicles and tendinous tissue (TT) were determined from joint angles, ultrasonography and a geometric MTC model (combining MTC and fascicle measurements) respectively. RESULTS: There was no age-related difference in lengthening of the MTC during stance. However, the fascicle and TT contribution to MTC lengthening was altered; TT lengthening was larger in OA than in YA (P = 0.05) and fascicle lengthening was less in OA than YA (P < 0.05). There were no differences between groups in MTC, fascicle or TT shortening amplitude during push-off. CONCLUSION: The observations are consistent with previous reports of increased compliance of TT in older adults.

Adenocarcinoma del canal anal relacionado con fístula / Adenocarcinoma of the anal canal associated with a fistula

El cáncer del conducto anal es relativamente raro, constituye el 1 a 2 por ciento de los tumores gastrointestinales y el 3 a 4 por ciento de los colorrectoanales. El adenocarcinoma representa entre el 5 y 17 por ciento de los cánceres anales. El objetivo del trabajo es una presentación clínica de un paciente operado y la actualización bibliográfica en los aspectos anatomopatológicos de clasificación, origen, diagnóstico y tratamiento(AU)

Adenocarcinoma del canal anal relacionado con fístula / Adenocarcinoma of the anal canal associated with a fistula

El cáncer del conducto anal es relativamente raro, constituye el 1 a 2 por ciento de los tumores gastrointestinales y el 3 a 4 por ciento de los colorrectoanales. El adenocarcinoma representa entre el 5 y 17 por ciento de los cánceres anales. El objetivo del trabajo es una presentación clínica de un paciente operado y la actualización bibliográfica en los aspectos anatomopatológicos de clasificación, origen, diagnóstico y tratamiento

[Left colon necrosis after endoscopic para-aortic lymph node exploration in a cervical carcinoma stage IIB]. / Nécrose colique gauche après un curage lomboaortique coelioscopique pour cancer du col utérin de stade IIB.

Authors report a left colon ischemia six days after laparoscopic para-aortic lymphadenectomy in the staging of advanced cervical carcinoma. Before surgery, positron emission tomography scanning was performed: there were no para-aortic nodal metastasis. The histologic examination confirmed the radiological staging. Positron emission tomography scanning could avoid surgery in the case of patients with high risks morbidity factors.

Metabolic cost, mechanical work, and efficiency during walking in young and older men.

AIM: To investigate mechanical work, efficiency, and antagonist muscle co-activation with a view to better understand the cause of the elevated metabolic cost of walking (C(W)) in older adults. METHODS: Metabolic, mechanical and electromyographic measurements were made as healthy young (YOU; n = 12, age = 27 +/- 3 years) and older (OLD; n = 20, age = 74 +/- 3 years) men of equivalent body mass and leg length walked on a treadmill at four speeds (ranging from 0.83 to 1.67 m s(-1)). RESULTS: Net (above resting) C(W), determined by indirect calorimetry was 31% higher (average across speeds) in OLD (P < 0.05). The integrity of the passive pendulum like interchange of mechanical energies of the centre of mass (COM(B)), an energy-saving mechanism, was maintained in OLD. Furthermore, total mechanical work, determined from fluctuations in mechanical energy of COM(B) and of body segments relative to COM(B), was not significantly elevated in OLD. This resulted in a lower efficiency in OLD (-17%, P < 0.05). Co-activation, temporally quantified from electromyography recordings, was 31% higher in OLD for antagonist muscles of the thigh (P < 0.05). Thigh co-activation was moderately correlated with C(W) at three speeds (r = 0.38-0.52, P < 0.05). CONCLUSION: Healthy septuagenarians with no gait impairment have an elevated C(W) which is not explained by an elevation in whole body mechanical work. Increased antagonist muscle co-activation (possibly an adaptation to ensure adequate joint stability) may offer partial explanation of the elevated C(W).

[Immediate and long term complications of episiotomy]. / Complications immédiates et à long terme de l'épisiotomie.

OBJECTIVE: The objective of this review was to describe the complications of episiotomy. MATERIAL AND METHODS: A systematic review on Medline Database set was performed with the key words: episiotomy, dyspareunia, fecal incontinence, urinary incontinence, maternal morbidity, pelvic floor defects and sexual function. Four hundred seventy two articles were selected. RESULTS: When performed liberally, episiotomy appears to increase the risk of post partum bleeding. More restrictive use does not appear to increase the risk of serious perineal injury. In the event of instrumental extraction, use of episiotomy appears to be associated with more severe damage. Medial episiotomy does not appear to be associated with third or fourth degree tears. Following delivery, patients who had an episiotomy complain of perineal pain more than those with an intact perineum or first or second degree tears. Three months after delivery, there is no difference. While episiotomy appears to be a source of dyspareunia during the first weeks after delivery in comparison with spontaneous tears, this does not appear to be true later after delivery. CONCLUSION: Episiotomy appears to be the cause of more perineal pain and dyspareunia during the early post partum weeks.

Biomechanics and energetics of basketball wheelchairs evolution.

The aim of this study was to investigate metabolic demand and mechanical work of different basketball wheelchairs that represented significant stages of its evolution from 1960 to date. Four subjects pushed each model on a basketball court at different speeds (from 0.90 to 2.35 m.s(-1)). During the trials, oxygen consumption was measured. Also, the different forms of mechanical work involved in the exercise were investigated. The oxygen consumption decreased from the oldest model to the next ones, remaining then quite constant. This was also the same with breathing and pushing frequencies. Both the work against air drag and rolling resistance decreased, air drag always played a minor role due to the low speeds investigated. The total mechanical work was highest in the oldest wheelchair and lowest in the newest one. The efficiencies were found similar for all the chairs but the most recent one (less efficient). Already by the 1970's the wheelchair economy had reached an acceptable level, at least partially because of its improved ergonomics. Yet, when focusing on the efficiency, the surprisingly low value with the newest model suggests factors other than the economy (need of better balance, responsiveness, and ground grip) as determinants of the evolution of this device.

An energy balance of front crawl.

With the aim of computing a complete energy balance of front crawl, the energy cost per unit distance (C = Ev(-1), where E is the metabolic power and v is the speed) and the overall efficiency (eta(o) = W(tot)/C, where W(tot) is the mechanical work per unit distance) were calculated for subjects swimming with and without fins. In aquatic locomotion W(tot) is given by the sum of: (1) W(int), the internal work, which was calculated from video analysis, (2) W(d), the work to overcome hydrodynamic resistance, which was calculated from measures of active drag, and (3) W(k), calculated from measures of Froude efficiency (eta(F)). In turn, eta(F) = W(d)/(W(d) + W(k)) and was calculated by modelling the arm movement as that of a paddle wheel. When swimming at speeds from 1.0 to 1.4 m s(-1), eta(F) is about 0.5, power to overcome water resistance (active body drag x v) and power to give water kinetic energy increase from 50 to 100 W, and internal mechanical power from 10 to 30 W. In the same range of speeds E increases from 600 to 1,200 W and C from 600 to 800 J m(-1). The use of fins decreases total mechanical power and C by the same amount (10-15%) so that eta(o) (overall efficiency) is the same when swimming with or without fins [0.20 (0.03)]. The values of eta(o) are higher than previously reported for the front crawl, essentially because of the larger values of W(tot) calculated in this study. This is so because the contribution of W(int) to W(tot )was taken into account, and because eta(F) was computed by also taking into account the contribution of the legs to forward propulsion.

The optimal locomotion on gradients: walking, running or cycling?

On level ground, cycling is more economical than running, which in turn is more economical than walking in the high speed range. This paper investigates whether this ranking still holds when moving on a gradient, where the three modes are expected to be mainly facing the same burden, i.e. to counter gravity. By using data from the literature we have built a theoretical framework to predict the optimal mode as a function of the gradient. Cycling was found to be the mode of choice only below 10-15% gradient, while above it walking was the least expensive locomotion type. Seven amateur bikers were then asked to walk, run and ride on a treadmill at different gradients. The speed was set so as to maintain almost constant the metabolic demand across the different gradients. The results indicate that the "critical slope", i.e. the one above which walking is less expensive than cycling (and running), is about 13-15%. One subject was loaded during bipedal gaits with a bicycle-equivalent mass, to simulate to cross-country cycling situation. The critical slope was close to 20%, due to the higher metabolic cost of loaded walking and running. Part of the findings can be explained by the mechanically different paradigms of the three locomotion types.