Introduction and Aims. Congenital absence of the vas deferens is an uncommon anomaly and this clinical condition is responsible for up to 1-2% of male infertility. It can be either unilateral or bilateral and the associated anomalies include cryptorchidism, seminal vesicles and ejaculatory ducts anomalies, and renal anomalies such as renal agenesis. We hereby present a case of congenital unilateral absence of vas deferens, which was found incidentally during an evaluation of undescended testis in a patient with ipsilateral renal agenesis. Case Presentation. A 10-month-old boy was referred to the urology clinic with an undescended right testis. Preoperative abdominal ultrasonography showed agenesis of the right kidney and the absence of right vas deferens and epididymis was confirmed during laparoscopic orchiectomy performed due to short right spermatic cord. There were no other concomitant anomalies of the genitourinary system observed in evaluation. Conclusion. Congenital unilateral absence of the vas deferens with cryptorchidism and renal agenesis is a rare diagnostic entity. Cryptorchidism or absent vas deferens found incidentally should lead the physician to evaluate the status of the contralateral vas deferens and conduct a renal tract ultrasound study. Congenital unilateral absence of the vas deferens (CUAVD) is an uncommon anomaly, which may contribute to male infertility and it has been associated with renal agenesis and a variety of other anomalies that was first described in 1870 by Reverdin , 3. TherA 10-month-old boy was referred to the urology clinic with an undescended right testis. A presurgical history of the patient revealed that the patient had agenesis of the right kidney and no other concomitant anomalies of the genitourinary system had been evaluated before surgery. The clinical examination presented orthotopically positioned left testis but right testis was palpable neither in the inguinal region nor in scrotum. Left hemiscrotum showed no redness or swelling and left epididymis was also verified by palpation. The inguinal area had no palpable mass referring to inguinal hernia. However, an absence of the vas deferens on the right hemiscrotum was found. Then a scrotal ultrasonography was undertaken and it confirmed cryptorchidism of right testis located at the level of right internal inguinal ring and the suspected diagnosis of agenesis of the right epididymis. Left epididymis and testis had no pathological signs seen . MoreoveDevelopment of renal system is closely integrated with the development of genital system. The ureteric bud develops from the mesonephric duct during the 5th week of gestation and the elongated stalk of the ureteric bud that is called the metanephric duct later forms the ureter. Moreover, the ingrowth of the branching ureteric buds into the metanephric blastema results in the characteristic lobulated appearance of the definitive kidney. The mesonephric duct differentiates into the bladder trigone, the seminal vesicle, the ductus deferens, and the distal two-thirds of the epididymis. An essential requirement for renal genesis after induction and differentiation of the intermediate mesoderm is the development of the ureteric bud at the caudal area of the mesonephric duct. The possible reasons for renal agenesis include the lack of induction of the metanephric blastema by the ureteral bud, primary absence of the caudal nephrogenic core, ureteral bud malformation, and dysplasia of mesonephric duct –6. CongeCUAVD with cryptorchidism and renal agenesis is a rare diagnostic entity. The exact pathophysiology of CUAVD still remains poorly understood. The absent vas deferens found in scrotal or laparoscopic abdominal surgery should lead the surgeon to explore the status of the contralateral vas deferens and conduct a renal tract ultrasound study. Genetic study for the evaluation of CFTR gene might be also helpful to evaluate the presence of latent cystic fibrosis. Moreover, scrotal palpation to confirm the presence of vas deferens should be recommended as a part of the routine physical exam in males.


The epidemiological transition has provided the theoretical background for the expectation of convergence in mortality patterns. We formally test and reject the convergence hypothesis for a sample of industrialized countries in the period from 1960 to 2008. After a period of convergence in the decade of 1960 there followed a sustained process of divergence with a pronounced increase at the end of the 1980's, explained by trends within former Socialist countries (Eastern countries). While Eastern countries experienced abrupt divergence after the dissolution of the Soviet Union, differences within Western countries remained broadly constant for the whole period. Western countries transitioned from a strong correlation between life expectancy and variance in 1960 to no association between both moments in 2008 while Eastern countries experienced the opposite evolution. Taken together, our results suggest that convergence can be better understood when accounting for shared structural similarities amongst groups of countries rather than through global convergence. Whether there is global convergence in well-being across countries remains in the realm of scientific debate. The hypothesis of convergence has been studied for a variety of dimensions of well-being, with mixed results. While economic convergence is not a general reality Our research advances the current understanding of mortality convergence by, first, formally testing the implications of the theory on the epidemiological transition, then second, uncovering trends in mortality patterns beyond the evolution of the mean, i.e. life expectancy, and variance of the considered distribution. Our chosen indicator of divergence, the Kullback-Leibler divergence (KLD), provides a comprehensive measure of the overall differences between distributions.Studies of convergence classify differences between countries using two broad categories: first there is consideration for the unequal positions of countries in the stages of their development; second are structural differences, dissimilarities that persist even should countries become equally developed In this work, we test and reject the convergence hypothesis for industrialized countries in the period 1960–2008. However, we acknowledge that the lack of convergence for our whole sample does not necessarily imply that there are not subgroups of countries converging. In fact, the concept of convergence among subgroups or clubs of countries has already received some attention in the mortality convergence literature Our findings on the lack of convergence are coherent with recent findings that highlight the relatively high variability of mortality at young adult ages across countries and its contribution to international differences in mortality patterns Our object of study, mortality patterns, is extracted from the period life-tables available in the Human Mortality Database The divergence of the age-at-death distribution for country Instead of focusing on the particular value of the KLD, in our exercise we set 1960 as the base year.Motivated by concerns of structural similarities and dissimilarities, we turn to the well-known literature on the effect of political and economic transitions of former Soviet countries, a process which has exerted a major influence in the form of a mortality shock for said countries Our first set of results, before we turn to the KLD trends, are based on the traditional mean and variance study of the mortality distribution. We provide a graphical analysis of the mean and variance of the ages-at-death distributions over time that also uncovers some interesting features of the epidemological transition. A remarkable feature of the data is the organization of Western countries in 1960 is mostly along a line that orders countries in the space of high life expectancy — low inequality and low life expectancy — high inequality. This correlation reflects the reality of countries in different stages of their epidemiological transitions. After 50 years, the picture that emerges is drastically different. Although there have been common trends among the majority of countries, i.e. the generalized reduction of variance and the increase in life expectancy, the resulting distribution of countries encompasses a heterogenous landscape. The previous correlation is less apparent, with countries with new profiles emerging from the distribution. For instance, we observe countries with similar variances  but with large differences in life expectancy. Performing a similar exercise for Eastern countries yields an interesting contrast. In the latter case, the historical evolution is reversed, with countries evolving from many different profiles to the single dimension ordering as seen amongst Western countries in the 1960's. The mean-variance profiles we report are coherent with previous work In the next section we provide an evaluation of convergence based on the KLD. The main strength of the KLD is that it encompasses the whole differences in distributions, providing a clearer picture than analysis based on only a collection of moments. This is particularly relevant for the analysis of the mortality distributions as infant mortality breaks the normality of the ages-at-death distribution. The ages-at-death distributions of the earlier periods contained a considerably larger number of infant deaths than the contemporary distributions, making mean-variance comparisons a less accurate evaluation.Our results indicate a clear pattern of divergence in our sample of industrialized countries . The KLDThe relevance of taking into account the existence of clubs of countries becomes apparent when observing the differences in the trends between the two groups of countries. In the sample of Western countries we find a relatively flat profile of convergence for mortality patterns ; that isOur main finding suggests that, while the reduction in differences due to the catching up process of countries at earlier stages of development is an important catalyst towards convergence While our results uncover group specific trends, our classification of countries does not identify convergence clubs. There exists a period of convergence for Eastern countries prior to the 1990s but the recent history of development shows that Eastern countries are no longer approaching a common distribution. Given the robustness of the lack of overall convergence and the crucial role that group-specific dynamics play, further research is needed to uncover the determinants of club membership and pertinence.The discussion on the determinants of club membership can be divided into two areas of study depending on whether the focus is on the differences between developed and developing countries or the differences amongst industrialized countries. When focusing on the former, the literature has highlighted the existence of mortality traps


As maternal deaths become rarer, monitoring near-miss or severe maternal morbidity becomes important as a tool to measure changes in care quality. Many calls have been made to use routinely available hospital administration data to monitor the quality of maternity care. We investigated 1) the feasibility of developing an English Maternal Morbidity Outcome Indicator (EMMOI) by reproducing an Australian indicator using routinely available hospital data, 2) the impact of modifications to the indicator to address potential data quality issues, 3) the reliability of the indicator.We used data from 6,389,066 women giving birth in England from April 2003 to March 2013 available in the Hospital Episode Statistics (HES) database of the Health and Social care Information centre (HSCIC). A composite indicator, EMMOI, was generated from the diagnoses and procedure codes. Rates of individual morbid events included in the EMMOI were compared with the rates in the UK reported by population-based studies.EMMOI included 26 morbid events (17 diagnosis and 9 procedures). Selection of the individual morbid events was guided by the Australian indicator and published literature for conditions associated with maternal morbidity and mortality in the UK, but was mainly driven by the quality of the routine hospital data. Comparing the rates of individual morbid events of the indicator with figures from population-based studies showed that the possibility of false positive and false negative cases cannot be ruled out.While routine English hospital data can be used to generate a composite indicator to monitor trends in maternal morbidity during childbirth, the quality and reliability of this monitoring indicator depends on the quality of the hospital data, which is currently inadequate. Most women in high resource settings give birth in hospitals or birth centres . In bothOutcome measures such as maternal and perinatal mortality are frequently monitored at both health centre and population levels. However as, in particular, maternal death becomes rarer, this becomes less meaningful as it is not very responsive to changes in care quality. The WHO introduced a complex maternal near miss/ morbidity indicator, which requires collection of detailed data including laboratory based parameters indicating organ system dysfunction . HoweverIn the UK the Royal College of Obstetrics and Gynaecology have developed a series of “maternity indicators” which include elements such as caesarean section rate . HoweverHowever, it is not clear whether data quality is sufficiently high in England to adopt the Australian approach. The aim of this study was to investigate the feasibility of reproducing the Australian Maternal Morbidity Outcome Indicator using routinely available English hospital maternity data; the impact of modifications to the Indicator to address potential data quality issues as well as known maternal health concerns in the UK; and the reliability of the indicator.We used routine hospital data from the Hospital Episode Statistics (HES) database of the Health and Social care Information Centre (HSCIC)  to develth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and procedures are coded using the OPCS Classification of Interventions and Procedures used by the NHS hospitals in the UK [We generated a list of diagnoses and procedures to be included in the composite indicator for England (EMMOI) by reviewing both the initial and final lists of the components of the Australian Maternal Morbidity Outcome Indicator developed by Roberts et al  as well n the UK .We calculated the frequency and rate of the individual morbid events (diagnoses and procedures) in the study population and their annual rates over the period of 10 years in order to examine potential variation in coding practice or data quality. We calculated the incidence rate and 95% confidence intervals (CI) of maternal morbidity outcomes per 1000 women giving birth in England using the EMMOI for each year from April 2003 to March 2013 and conducted tests for linearity to examine their trend over time. We also calculated the percentage change in incidence of maternal morbidity during childbirth in England in 2012–13 compared to 2003–04 and 95% CI.2 test for trend. This was followed by univariable and multivariable logistic regression analyses to examine whether the change in the odds of maternal morbidity outcomes over the period of 10 years were attributable to the changes in maternal and pregnancy characteristics in England. A core logistic regression model was built including the nine maternal and pregnancy characteristics shown in We examined changes in the maternal sociodemographic and pregnancy characteristics by conducting χ2 tests for differences in proportions and χThe composite indicator, EMMOI, included all 14 diagnoses and nine out of 10 procedures from the final list of components of the Australian indicator as well as sepsis, eclampsia and cerebral venous thrombosis, which are important causes of maternal morbidity and mortality in the UK –23. DiagOf the 6,389,066 women giving birth in England from 2003 to 2013, the EMMOI classified 24,427 women as having experienced one or more maternal morbidity during childbirth. There was an increase in the annual rate of maternal morbidity outcomes from 2003 to 2013  with a lThe overall frequency and rate of the individual component diagnoses and procedures  included in the EMMOI are shown in Using routine hospital data on episodes of childbirth in England from April 2003 to March 2013 we were able to generate a composite indicator, EMMOI, to measure maternal morbidity outcomes during childbirth in England which included 26 morbid events (17 diagnoses and 9 procedures). Selection of individual morbid events was driven by the quality of the routine hospital data, which was variable and thus necessitated a number of adaptations. The composite indicator showed an increase in maternal morbidity outcomes during childbirth in England across the 10 years examined, with a 29% overall absolute increase in incidence. However, questions on reliability of the indicator remain due to mismatches between the rates of individual morbid events and the incidence of these conditions in the UK reported by population-based studies.Comparing the overall rate of the individual component diagnoses and procedures included in the EMMOI with incidence of these morbid events in the UK reported by population-based studies and with the rates of the individual components of the Australian indicator estimated in the Australian population health datasets , showed Irrespective of the variations in definitions and indicators used to measure maternal morbidity, several studies from across the world show an increase in the incidence of maternal morbidity outcomes –43. The The incidence of sepsis in the UK between 1 June 2011 and 31 May 2012 was estimated as 4.7 per 10,000 maternities  and confThe HES data includes diagnosis of acute psychosis among women during the childbirth episode , which would be expected to be lower than the overall incidence of acute psychosis in the UK   as this Incidence rates of 10 out of 26 morbid events constituting the EMMOI were in agreement with the rates of the individual morbid events included in the Australian indicator estimated in the Australian population health datasets . IncidenThis study was an attempt to create a composite indicator to measure maternal morbidity outcomes during childbirth using routine hospital data from 6,389,066 women giving birth in England from 2003 to 2013. Although we were able to demonstrate that a composite indicator to measure maternal morbidity outcomes during childbirth can be constructed using routine hospital data, we were not able to validate the accuracy of the composite indicator in classifying women as having suffered a morbidity event, since data protection and privacy laws allowed only for access to anonymised data. The use of a composite measure helps to avoid or reduce concerns about false negatives, but we cannot exclude the possibility of false positives.It is important to acknowledge the limitation of not being able to use the data on blood transfusion, PPH and ‘repair of ruptured or inverted uterus’ which we did not find to be reliable. While the information collated from the NHS hospitals goes through a process of cleaning and quality checks, the quality of routine data collected by the HSCIC including HES has been questioned by a number of audits –47. It hBeyond the coding limitations we describe, it is difficult to determine the reasons for the observed differences in codes and procedures relating to uterine rupture and postpartum haemorrhage. We could speculate that procedures, particularly where these require an operation under anaesthesia, such as repair of ruptured uterus, are more reliably coded than diseases/disorders when codes could be included in error simply from a list of differential diagnoses. Similarly, since blood transfusion is a more clearly defined procedure, requiring detailed checking, it may be more accurately recorded than postpartum haemorrhage; estimation of blood loss post-delivery is known to be inaccurate . ConversA single measure of maternal morbidity could be a reliable indicator of quality of pregnancy care in some settings, and an indicator which uses routine data could be a cost-effective tool to monitor the quality of pregnancy care in England. However, while our study showed that routine English hospital data can be used to generate a composite indicator to monitor trends in maternal morbidity outcomes during childbirth, the quality and reliability of this monitoring indicator is dependent on the quality of the hospital data. Using the available data, we found that some codes were unusable due to major concerns about their validity. We could not confirm the reliability of the indicator due to mismatches between the rates of the individual components of the EMMOI calculated using the HES data and the rates reported by population-based epidemiological studies in the UK. The ongoing efforts to improve the reporting and quality of NHS hospital data , could m


Researchers and patients agree that rare diseases require new and better therapies. Trials in rare diseases have many challenges, relating to the scarcity of patients and experts, with the inevitable conclusion that large scale studies will require recruitment of patients from multiple centres in different countries. We describe the challenges of setting up an international  trial of three steroid regimes in the management of children with Duchenne muscular dystrophy, funded by the US-based NIH(NINDS).Contract negotiations proved difficult. Differences in the definition of sponsorship between the US and the UK required a major discussion before resolution could be achieved. Risk aversion on behalf of all parties caused major delays. Concerns about exchange rate fluctuations meant that individual researchers were asked to bear the risk of an adverse shift in the exchange. Most of the 40 participating sites requested individual amendments to the model contract, in part because of a lack of compatibility with standard contracts commonly used in the different participating countries; recurrent issues included the currency to be used for payments and who bore responsibility for indemnification.The discrepancies in the interpretation of the EU Clinical Trials Directive across European countries and the differences between the regulatory and ethical approval processes in Europe, US and Canada meant that we had five separate and distinct timelines and frameworks to deal with in terms of getting regulatory, ethical and local approvals.A concerted approach is needed to resolve the specific challenges of setting up multicentre studies in rare diseases


The force, mechanical work and power produced by muscle fibers are profoundly affected by the length changes they undergo during a contraction. These length changes are in turn affected by the spatial orientation of muscle fibers within a muscle (fiber architecture). Therefore any heterogeneity in fiber architecture within a single muscle has the potential to cause spatial variation in fiber strain. Here we examine how the architectural variation within a pennate muscle and within a fusiform muscle can result in regional fiber strain heterogeneity. We combine simple geometric models with empirical measures of fiber strain to better understand the effect of architecture on fiber strain heterogeneity. We show that variation in pennation angle throughout a muscle can result in differences in fiber strain with higher strains being observed at lower angles of pennation. We also show that in fusiform muscles, the outer/superficial fibers of the muscle experience lower strains than central fibers. These results show that regional variation in mechanical output of muscle fibers can arise solely from architectural features of the muscle without the presence of any spatial variation in motor recruitment. The mechanical output of a muscle is strongly affected by the length changes and shortening velocity of muscle fibers. The well-described force-length and force-velocity properties of muscles have long been considered important constraints on muscle performance Hill, . These fUnderstanding the relationship between the mechanical output of a muscle and the length trajectories of the muscle fibers has been complicated by the presence of spatial heterogeneity within muscles. The strain experienced along a muscle fascicle has been shown to vary along its length , the pennation angle of the fibers (α) and the length change of the muscle  in two regions of the muscle using the following equation . In this muscle, the proximal fibers have the largest pennation angles in the muscle and pennation angle decreases distally , the maximum radius (midbelly) prior to contraction (R2), the initial lengths of the muscle (M), the initial lengths of inner (Li1) and outer (Lo1) fibers, and the muscle strain (εm). We first use these inputs to solve for the maximum radius (midbelly) at the end of the contraction (R3) using the following equation:We used a simple geometric model to map fiber strains in various regions of a fusiform muscle. We model the muscle as an isovolumetric barrel Otten, . As the o2) using the following equations:We then solve the geometry of the muscle at the end of the contraction and solve for the final length of the fiber . This muscle has a fusiform shape and lacks any internal tendinous inscriptions. The shape of the muscle is ideal given some of the geometric assumptions made in the model.The dimensions inputted to the model were based on the palmaris longus muscle of leopard frogs  and that regional differences in fiber strain followed the predicted trend but were not statistically significant (p = 0.071).Our simple pennate muscle model predicts that the fibers with a lower pennation angle will undergo larger strains for a given amount of muscle shortening. Since the model is based on the architectural properties of the lateral gastrocnemius of wild turkeys, this suggests fibers from the distal part of the muscle will see greater strains Figure . This reIn many cases, the simple geometric model predicted larger strains than those actually observed. The most likely cause of this discrepancy is the explicit assumption in the model that the thickness of the muscle remains constant during the contraction. It has been previously shown that the thickness of a pennate muscle does increase during a contraction  and that regional differences in fiber strain followed the predicted trend but were not statistically significant (p = 0.089).Our empirical measures of fiber strain in a fusiform muscle generally support the predictions of the simple model Figure . We consAn implicit assumption made in both our model and our empirical measurements is that the strain measured along fiber is representative of the strain at the level of sarcomeres. Here we are assuming that on average sarcomere lengths are homogeneous throughout the muscle. However, it is possible that alterations in the number of sarcomeres in series in fibers from different regions can function to counteract the effects of muscle architecture. For example, if the inner region of fusiform muscle has more sarcomeres in series the larger fiber strain observed would be distributed over more sarcomeres thereby reducing any effects on force production. We believe that the model and empirical data presented here can serve to inform hypothesis about regional variation in sarcomere length and number.The empirical data presented in this study were all performed at loads corresponding to 50% of maximum isometric force. The use of isotonic contractions allowed us to make measurements of fiber length without dynamic changes in length of series elastic elements. However, previous studies have shown that the relationship between fiber strain and muscle strain can vary as a function of force  where all the motor units of the muscle are recruited. Any regional variation in fiber strain can be reasonably attributed to regional variation in architecture. In studies where isolated muscle experiments are not possible or practical, investigators can track regional fiber strain while passively actuating the joint or joints of interest. Again, any regional variation in fiber strain can be reasonably attributed to regional variation in architecture since the muscle is not active. Unraveling the relative contributions of structural and neural drivers of regional heterogeneity within a muscle will be an important future step in understanding muscle function during movement.The goal of this paper has been to highlight the potential for regional variation in strain and work within a muscle. Such variation may arise from purely architectural variation or could arise from regionally specific motor control strategies and well-defined neuromuscular compartmentalization (Higham and Biewener, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background and Objectives : It has been suggested previously that increased width of midfacial structure is associated with the development of palatal clefting. One of the most important heritable characteristics predisposing towards the development of orofacial clefting in an embryo is craniofacial morphology. The aim of the study was to compare nasomaxillary width of parents of children with unilateral complete cleft lip alveolus and palate with parents of noncleft children.Methods : 25 biologic parent sets of children with unilateral complete cleft lip alveolus and palate and 25 biologic parents of noncleft children were included in this study for PA cephalometric analysis.Results : There was no statistically significant difference between study and control groups. An association was found between the side of the cleft in the affected children and the parents in the same side with narrower nasomaxillary width.Interpretation and conclusion : The result of this study was in contrast with other previous studies. We observed a narrower nasomaxillary width, which suggested that this feature may be of morphogenetic importance in the etiopathogenesis of orofacial clefting in this geographic and ethnic group. Perhaps one of the most important heritable characteristics predisposing towards the development of OFC in an embryo is the craniofacial morphology Fully defining the parental craniofacial morphology in OFC will aid both the identification of the OFC morphogenes and the detection and counseling of parents determined to be at risk of having more children with OFC.Moreover, the identification of microform features in the relatives of the subjects with OFC, including cranio-facial form, lip pits and nasal deformities will also assert in the elucidation of gene-gene and gene environment interactions.Transverse asymmetry of the facial and nasomaxillary skeleton is commonly present in individuals with unilateral complete cleft lip alveolus and palate (UCLP) with the nasomaxillary complex being more asymmetric in affected individuals than noncleft controls.Interestingly, nasomaxillary asymmetry is also present in the general population as previously demonstrated by various investigators employing frontal (posteroanterior) cephalometric radiographs. Furthermore, the parents of children with cleft lip and palate also display asymmetric craniofacial features when compared with parents of noncleft children. Children born with clefts of the lip and palate have disruption of the hard tissues of the nasomaxillary skeleton.Asymmetries in the nasomaxillary complex are very common in patient with unilateral complete cleft lip alveolus and palate and have been previously studied by means of posteroanterior radiographs.Although a number of cephalometric studies have identified morphological differences between the parents of children with OFC and comparison groups, no study has investigated craniofacial asymmetry perse as a heritable predisposing factor towards the development of OFC in their offsprings. Specifically, the localization and quantification of craniofacial asymmetry could prove to be a crucial significant research for the morphogenes involved in OFC.Some clefts are caused by single mutant genes, some are due to chromosomal aberrations, and some are caused by specific environmental agents. The great majority are caused by the interaction of genetic and environmental factors each with relatively small effect.Many investigators inferred that if facial shape is genetically determined and also related to predisposing the cleft anomaly, the parents of children with cleft lip/palate should have facial dimensions different from those of general population.The identification of the parental craniofacial form in the etiopathogenesis of OFC may be important for several reasons:1. The parental craniofacial form (the phenotype) represents the hereditary influences on the craniofacial form of their offspring (the genotype). The craniofacial form in orofacial cleft is considered to be a predisposing factor in the development of OFC. For example, increased head and facial widths would logically mitigate against the palatal shelves for making contact  The identification of microform features in the relatives of subjects with OFC  will assert in the elucidation of the interaction of genes, both with other genes and their products, and with environmental factors. The identification of craniofacial features that are similar in several biological relationships  may assert in the identification of genes involved in the etiopathogenesis of OFC.Hence, the current study was designed to evaluate the parental nasomaxillary asymmetry as a risk factor for development of palatal clefts in their offsprings.The subjects for the study were 25 sets of parents (25 biologic mothers and 25 biologic fathers) of children with unilateral complete cleft lip alveolus and palate. The study group consisted of parents of siblings reporting with unilateral complete cleft lip alveolus and palate deformities to the Dept. of Maxillofacial Surgery and Research Center, SDM College of Dental Sciences and Hospital, Dharwad with an average age of 27 for males and 24 for females.The affected children included 12 males and 13 females suffering from nonsyndromic unilateral complete cleft lip alveolus and palate. 68% (n = 17) of affected children had left side cleft and 32% (n = 8) had right side cleft.There were no subjects with syndromic cleft based on family and patient history as well as clinical examination.17 patients had unilateral complete cleft lip alveolus and palate on the left side of which 9 were males and 8 were females.8 patients had unilateral complete cleft lip alveolus and palate on the left side of which 3 were males and 5 were females.The 25 sets of parents constituting the study group had no evidence of any type of cleft while their progenies exhibited unilateral complete cleft lip alveolus and palate. 9 parents sets in the study group had a history of consanguinity.The control group subjects for comparison with study group were 25 sets of parents (25 biologic mothers and 25 biologic fathers) of noncleft children. The control group consisted of parents of noncleft children visiting for routine dental treatment to the Dept. of Pedodontics, SDM College of Dental Sciences and Hospital, Dharwad with an average age of 28 for males and 25 for females. Subjects for both the groups were Indian nationals.The criteria of selection for the control group were: Parents whose children had no orofacial clefts, no anomaly of skeletal, genetic, endocrinal or any other nature. Subjects with no gross skeletal defects. Although malocclusion was accepted. A full compliment of teeth from second molar to second molar in both jaws. Individuals who had no diseases of skeletal genetic or endocrine nature.A total of 100 posteroanterior  cephalometric radiographs were obtained using a standard technique on a Planemecca PM 2002 CC Proline Panoramic X-ray unit within a period of 6 months  and 2. EFollowing the standard technique, the head was stabilized in the cephalostat with the help of ear rods . The posEach radiograph  was trac5 and Laspos et al (1997)9:For analysis of these frontal (PA) cephalometric radiographs, five bilateral landmarks were identified and traced on each radiograph and each measurement was assessed , as demoEuryon (REU and LEU), the most lateral point at the parietal surface.Medioorbitale (RMO andLMO), the most medial point on the medial orbital margin.Nasal point (RNA andLNA), the most lateral point in the nasal cavity.The maxillary notch (RMX andLMX), the most medial point on the maxilloalveolar surface.Zygoma (RZA and LZA), the most lateral point on the zygomatic arch.The line connecting latero-orbitale (RLO and LLO) ROL, the intersection between the lateral margin of the orbit and linea innominata, was used as the reference line for vertical measurements.A line drawn perpendicular to ROL at the midpoint of RLO-LLO was used as the reference line, LOM, for horizontal measurements.Following measurements of horizontal asymmetry were assessed on the basis of these landmarks : Head asymmetry, the difference of the perpendicular distance of REU and LEU from LOM. Orbital asymmetry, the difference of perpendicular distance of RMO and LMO from LOM. Nasal asymmetry, the difference of perpendicular difference of the perpendicular distance of RNA and LNA from LOM. Maxillary asymmetry, the difference of perpendicular distance of RMX and LMX from LOM. Zygomatic asymmetry, the difference of perpendicular distance of RZA and LZA from LOM.One examiner traced and measured all the 100 PA cephalogram.The readings of the 25 study parent sets (25 biologic mother and 25 biologic father) and 25 control parent set (25 biologic mother and 25 biologic father) were subjected to the following statistical tests Mean, Standard Deviation, Student’s unpaired ‘t’ test.The ratio of children with left sides unilateral complete cleft lip alveolus and palate versus right side unilateral cleft lip alveolus and palate (UCLAP) was 2:1 in this study.The side of increased parental nasal and maxillary asymmetry was significantly associated  with the opposite side of cleft in their children . In the Similarly, in the majority of parents with children suffering from the right sided cleft, nasal and maxillary width was larger on left compared with the right side.The association of the linear cephalometric variables of parents of nonsyndromic unilateral complete cleft lip alveolus and palate children (study group) and parents of healthy noncleft children (control group) is presented in The comparison of left and right side of affected children with their parents is summarized in The aim of the study was to evaluate the parental nasomaxillary asymmetry as a risk factor for development of palatal clefts in their offspring by comparing the nasomaxillary width obtained from PA cephalograms of parents of children with nonsyndromic unilateral complete cleft lip alveolus and palate with parents of noncleft children. The genetic contribution of characteristic craniofacial structure (nasomaxillary asymmetry) in parents of children with nonsyndromic unilateral complete cleft lip alveolus and palate has related to predisposition of non-syndromic unilateral complete cleft lip alveolus and palate in offspring was hypothesized. The focus of this study was to determine differences in craniofacial morphology on PA cephalogram among parents of nonsyndromic unilateral complete cleft lip alveolus and palate children and control group.The results from our study showed that the parental craniofacial morphology in nonsyndromic unilateral complete cleft lip alveolus and palate statistically does not differ from that of control group and association of side of parental asymmetry with the side of cleft in their children showed that majority of parents with children suffering from cleft in the left side, the nasal and maxillary width was larger on the right side compared to the left side, i.e. children with cleft in left side had small nasal and maxillary width in ipsilateral side of their parents.4, Suzuki A et al (1991)6, Raghavan R et al (1994)7, Mossey PA et al (1997)9, Laspos CP et al (1997)9, Mossey PA (1999)10, AL Emran SE et al (1999)11, Yoon YJ et al (2003)13], they found significant association between study and control groups of parental asymmetry and suggested a possible role of craniofacial form in orofacial clefting.Because there is no association between the control and study group, it does not exclude that the importance of craniofacial form has a genetic etiologic factor in the genesis of clefting. Various other studies is in contrast with our study .Some studies did not compare the study group with control group but found ipsilateral increase in the nasomaxillary width in the parents as one of the possible causes for development of unilateral complete cleft lip alveolus and palate [Yoon YJ et al (2003)Our study compared only parents of complete cleft lip alveolus and palate with control group. There were no quantitative difference of craniofacial structure identified in parents of nonsyndromic unilateral complete cleft lip alveolus and palate (study group) in this investigation as compared to the parents of noncleft children (control group). This study was unable to associate craniofacial form of parents with unilateral complete cleft lip alveolus and palate children. This does not indicate that such predisposing facial structures are unlikely to be only the determinant of cleft susceptibility. Further studies are required in this field, which might include large appropriate sample size.9 parent sets in study group gave the history of consanguinity. This adds to the etiologic heterogenicity of orofacial clefting in our study group. This consanguinity between the parents could be stronger feature compared to the craniofacial form for the development of orofacial clefting in their offsprings.This investigation suggested that unilaterally decreased nasomaxillary width in parents may play as a risk factor for development of palatal cleft in the offspring in our study group. This study suggested that a systematic approach in selection of subjects in both study and control group can help better understanding of genetic factors of craniofacial form associated with development of unilateral complete cleft lip alveolus and palate. This may ultimately contribute in the assessment of risk for palatal clefting in their offsprings. The features of this study was in contrast with many other previous studies suggesting that this feature may be of morphogenetic importance in the etiopathogenesis of OFC in this geographical and ethnic group.


The paper deals with a formation of artificial rock (clinker). Temperature plays the capital role in the manufacturing process. So, it is useful to analyze a poor clinker to identify the different phases and defects associated with their crystallization. X-ray fluorescence spectroscopy was used to determine the clinker's chemical composition. The amounts of the mineralogical phases are measured by quantitative XRD analysis (Rietveld). Scanning electron microscopy (SEM) was used to characterize the main phases of white Portland cement clinker and the defects associated with the formation of clinker mineral elements. The results of a study which focused on the identification of white clinker minerals and defects detected in these noncomplying clinkers such as fluctuation of the amount of the main phases  and belite (C2S)), excess of the free lime, occurrence of C3S polymorphs, and occurrence of moderately-crystallized structures are presented in this paper. Clinker is a multiphase mixture and, so far, more than 30 constituent phases have been identified . Th. Th15]. Poor crystallization is reflected by the presence of incomplete crystalline phases SO6 01,  and gelsLeafy and lamellar structures were observed SO4 11,  and accuIt is possible to distinguish different morphologies  and sizes of alite within the same sample. This indicates that baking is inhomogeneous in the oven and that the temperature fluctuates at least at the chamber level relative to the formation of alite. It is known from the literature that, at room temperature, only the monoclinic phase exists.The presence of free lime, the vitreous phase, and lamellar structures proves the instability of the oven temperature during baking or cooling.Excess lime and silica gels also seem to be related to the formulation and even the homogenization of the raw material. In fact, the kaolin is exceptionally rich in silica which results in baking being affected by the uncombined silica gel.SEM observation provides information on the degrees of cooking of clinker.The SEM observations of the poor quality clinker samples (noncompliant with the regulations in force) identified the following points:


Lactobacillus reuteri which is used in women in the last pregnancy trimester, prevalence of atopic dermatitis in children of the first 6 months of life. One group of women took Lactobacillus reuteri as chewing tablets of probiotic Lactobacillus reuteri, with dairy-limited diet excluding walnuts prior delivery. The second group of pregnant women took only proposed diet. Cumulative prevalence of atopic dermatitis was lower in group of children which mothers took Lactobacillus reuteri (6.7%) during pregnancy than in group of children of mothers from control group (24.2%). Analysis of the clinical features of disease showed that in children of the main group was observed mild atopic dermatitis . In children of the control group was middle and severe of atopic dermatitis .To establish effect of probiotic Lactobacillus reuteri by women in the last pregnancy trimester was positive for general condition and status of gastrointestinal tract. Pregnant women which took Lactobacillus reuteri had increased metabolic activity of lactic flora and recovered balance between aerobic/anaerobic microorganisms. Disorders of intestinal microbial balance in pregnant women in control group were not recovered to the end of pregnancy.The use of


Until recently, parasitic infections have been primarily studied as interactions between the parasite and the host, leaving out crucial players: microbes. The recent realization that microbes play key roles in the biology of all living organisms is not only challenging our understanding of host-parasite evolution, but it also provides new clues to develop new therapies and remediation strategies. In this paper we provide a review of promising and advanced experimental organismal systems to examine the dynamic of host-parasite-microbe interactions. We address the benefits of developing new experimental models appropriate to this new research area and identify systems that offer the best promises considering the nature of the interactions among hosts, parasites, and microbes. Based on these systems, we identify key criteria for selecting experimental models to elucidate the fundamental principles of these complex webs of interactions. It appears that no model is ideal and that complementary studies should be performed on different systems in order to understand the driving roles of microbes in host and parasite evolution. Figure 1). Alteration of any partner may cause a chain of responses in those remaining and change the outcome of infection.The term ‘symbiosis’ (from Greek “living together”) was first coined by Albert Bernhardt Frank in 1877, when he described the relationship between fungi and algae in lichens, and was then used to define “the living together of unlike organisms” by Drosophila melanogaster resistance to Drosophila C virus when associated with the defensive symbiont Wolbachia  as early as 1969 and facilitation in 1971 , 1977. Wolbachia . The intolbachia  or “microlbachia .Acyrthosiphon pisum, the facultative symbionts Hamiltonella and Serratia provide defense against the parasitic wasp Aphidius ervi  and Lota lota (burbot), respectively,  and increased production of reactive oxygen species to modify the gut microbial community and insure its own development  The host and parasite could be bred and maintained in the laboratory. It is a necessary step to perform controlled experimental infections and understand the transmission mechanisms of symbionts of interest. It is also crucial for testing the environmental and host genetic factors that regulate the abundance, diversity and stability of the microbiome.(2) A core microbiome would have been identified in the host suggesting that it selects for specific microbes. This in itself suggests that the host should be considered as a holobiont.(3) The parasite shares the same environment as microbes in the host body, which would suggest potential direct parasite-host-associated microbe interaction that remain to be tested.(4) The parasite would be associated with microbes for which the role in virulence will be assessed. The presence of a core microbiome in parasites and the role of parasite-associated microbes in driving the evolution of host defenses remain to be demonstrated.(5) Techniques have been developed to manipulate the composition of the microbiome of the host and/or parasite. The role of microbes in the result of infection can only be tested through manipulation of the microbiome and injection of isolated microbes. It is necessary to characterize the role of microbes individually and as a community in susceptibility, resistance, and infectivity.(6) The host and the parasite would have a wide geographical species range and ecological diversity, which would allow comprehensive fields studies to understand how environmental factors influence host-parasite-microbe interaction. It would allow to examine the role of microbes in local adaptation of parasites through cross-infection experiments.(7) The host and/or parasite would have short generation time, which would facilitate the use experimental evolution to test the role of microbes in host or parasite adaptation. For instance, the hologenome theory would predict that associated microbes participate in the arms race through shorter generation time and higher mutation rate but this hypothesis remains to be tested.(8) Closely related species of hosts could be parasitized with closely related species of parasites, thus allowing comparative studies of the role of microbes in the interaction and testing their role during parasite evolution, host switch, and host or parasite speciation.(9) The parasite would have various effects on the phenotype of its host, so that the role of microbes in any aspect of the ’normal’ behavior or appearance of infected organism may be more readily detected and more reliably assessed for fitness consequences.(10) The genome of the host and parasite would have been sequenced, facilitating the use of high throughput comparative genomics approaches to characterize the genes involved inAll authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The purpose of the study was to compare the knowledge scores of medical students in Problem-based Learning and traditional curriculum on public health topics.We planned a cross-sectional study including the fifth and sixth year medical students of Dokuz Eylul University in Turkey. The fifth year students  were the pioneers educated with PBL curriculum since the 1997–1998 academic year. The sixth year students  were the last students educated with traditional education methods. We prepared 25 multiple-choice questions in order to assess knowledge scores of students on selected subjects of Public Health. Our data were collected in year 2002.Mean test scores achieved in PBL and traditional groups were 65.0 and 60.5 respectively. PBL students were significantly more successful in the knowledge test (p = 0.01). The knowledge scores of two topics were statistically higher among PBL students. These topics were health management and chronic diseases.We found that mean total evaluation score in the PBL group was 4.5 points higher than in the traditional group in our study. Focusing only on the knowledge scores of students is the main limitation of our study. Upon the graduation of the first PBL students in the 2002–2003 academic year, we are planning additional studies regarding the other functions of a physician such as skill, behaviour and attitude. During the last 25 years, ideas concerning the aim, structure and system of medical education have been discussed. Debates generally have arisen from the perception that medical education couldn't serve the purpose of improving health standards of the communities ."Health for All" was adopted in 1977 and launched at the Alma Ata Conference in 1978 to underline the fact that large numbers of people and even whole countries were not enjoying an acceptable standard of health . In ordeIn the Edinburgh Declaration of the World Medical Association in 1988, similar problems were mentioned and the purpose of the medical education was declared as training physicians capable of improving communities' health standards. This declaration suggested that medical education should be focused on common health problems of the large communities, and the medical school curriculum should be restructured according to the health requirements of the community. According to the declaration, medical students must gain professional skills and social values in addition to theoretical knowledge and the principle of lifelong medical education should be adopted .The ideas and suggestions mentioned above have aroused strong winds of change in the medical education arena. Mc Donald et al. from Mc Master University determined an approach based on the community's main health problems and stressed the importance of focusing on these problems while designing their medical school's curriculum .Since then, this approach has been adopted by many medical schools all over the world. The schools which designed their curriculum according to the priority health problems of the community, managed to raise the physicians' awareness of their community and the preventive measures and solutions of their main health problems.In Turkey, problems of medical education have been discussed since early 1970s. Several studies showed that the goals of medical education did not overlap with the health requirements of the Turkish community. The education of health professionals was abstracted from the realities of the country. In 1990s Turkish Parliament and Turkish Medical Association determined and reported the difficulties of medical education. In a 1991 report of the Turkish Parliament, the facts that the number of qualified physicians who were trained according to the health needs of the country was limited and that this number was not sufficient to improve its health standards were underlined. Several deans from different medical schools of the country contributed to Turkish Parliament's study and reported that a greater importance should be given to the health problems of the population while planning the educational programs and the medical education should not be restricted to the university hospitals .In The Turkish Medical Association's report the fact that medical education was not relevant to health needs of the country was emphasized. New medical graduates were not fully aware of common national health problems. The recommendations of the Turkish Medical Association to improve the health standards of the Turkish population were; training the general practitioners capable of working effectively in the primary health care and restructuring the medical education on a community basis and implementing Problem-based Learning methods .International developments and the reports of Turkish Parliament and Turkish Medical Association led the faculty of Dokuz Eylül University School of Medicine (DEUSM) to seek solutions to the problems mentioned in the reports. As a result, Problem-based Learning (PBL) a more active and student-centred learning- was adopted and launched in the 1997–98 academic year. One of the main features of the education program was its relevancy to the philosophy of community-based medical education .The curriculum of DEUSM was structured considering social, biological, behavioural and ethics objectives of medical education. The curriculum was structured in a modular system and adopted to a spiral configuration providing horizontal and vertical integration. During the first three years of undergraduate education, PBL sessions are the main focus of a modular structure. The weekly schedule of a module allowed for all the educational activities such as PBL sessions, lectures, field studies, communication skills and clinical skills courses lectures existing one hour a day in the weekly program support the PBL sessions and independent learning .PBL sessions were based on written problems, which are likely to happen in real life. Special emphasis was also given to the integration of knowledge, acquisition of professional and moral values and to the development of communication skills.Medical knowledge and practical skills that a physician is supposed to have were on the basis of the advice of Turkish Medical Association and the faculty departments. The Department of Public Health also contributed to the education program by setting social standards and determining the most important health problems of the community.PBL Curriculum of DEUSM aimed to teach the students the main health problems of the community, their prevention and ways of treatment.Public Health topics of Dokuz Eylül University School of Medicine consists of;• Holistic approach in health,• Basic principles of Public Health,• Personal and social points of view on health events,• Bio-psychosocial (holistic) approach to any individual,• Principles of preventive medicine,• Structure and mechanisms of national health organization,• Demographic structure and trends, factors affecting them,• Basic principles of planning and conducting a scientific research on health,• Sound knowledge on leading health problems of the country, personal and social approaches for their solutions,• Environmental and occupational factors threatening community health and their prevention.Cases in the scenarios of the PBL modules were selected among common and important health problems, for which early diagnosis or prevention is possible. Lectures and small group studies with students were also organized to contribute to the educational effectiveness of the modules. Public Health topics of the medical education may be achieved more easily when theoretical knowledge and practical skills are complemented by field studies . It is rPrior to the implementation of PBL curriculum in the 1997–1998 academic year, lectures on Public Health were presented to the first, the third and the last year students by the faculty members of the Department of Public Health. Lectures on bio-statistics and research methods were given weekly throughout the first year. The other topics of Public Health were held in 72-hour Public Health Courses at the end of the third year . In the Comparison of old and new curriculum using some measurement tools is mandatory to observe the effects of innovations. In the literature, the determination of students' performances in scientific or licensing examinations was used to compare the efficiency of traditional education and PBL. Nandi P. et al. reviewed the studies and meta-analyses comparing PBL and traditional lecture-based education methods. In meta-analysis of the data published between 1980–1999, they concluded that PBL helped students show slightly but not significantly better performance than the others on clinical examinations . SimilarBlake et al. compared formerly lecture-based educated and recently Problem-based educated graduates of Missouri-Columbia School of Medicine concerning their performances on medical licensing examinations. They reported that mean scores achieved on these examinations were better among graduates of PBL, but the difference between old and new graduates' scores was not statistically significant .Some other studies have attempted to compare students' performances on special areas of medicine instead of general evaluation. Antepohl and Herzig conducted a randomized controlled study among the students who enrolled for the course of basic pharmacology at the University of Cologne. They randomly divided the students into two groups of PBL and traditional lecture based learning in order to compare their final examination scores. They could not find any significant difference between the two groups. However, in short essay questions there was a tendency towards higher scores among the students in the PBL group. The authors also found that the PBL students reached almost identical scores in their multiple choice questions and their short essay questions whereas the students who had been in the lecture based group scored significantly lower scores in their short essays than in their multiple choice questions .In a multi-centric study conducted by Schmidt et al., comparison of PBL and lecture based learning students showed that PBL students had higher knowledge scores on the areas of primary care services, psychological health, collaboration of different sectors on health and occupational ethics .The purpose of our study was to compare the knowledge scores of medical students in PBL and traditional curriculum on public health topics.We planned a cross-sectional study including the fifth and sixth year medical students of DEUSM. The fifth year students (PBL students) were the pioneers educated with PBL curriculum since the 1997–1998 academic year. The sixth year students  were the last students educated with traditional education methods. The knowledge scores of students on Public Health topics were evaluated. In both of the PBL and Traditional curriculum, all the knowledge acquired in the first five years of the school was reviewed during the two-month Public Health internship period in the sixth year. Since this period may remind the students of some issues which may have been previously forgotten, we decided to exclude the sixth year students who have completed their internship period. 56 fifth year students and 78 sixth year students who have not so far completed their internship period in the Department of Public Health were included in our study. Participation rates were 96.4% (54 out of 56 students) in the fifth year and 100%  in the sixth.Before the application of the inquiry form, the purpose of the study was explained to the students and their oral consents were obtained.We analyzed the knowledge scores of the two groups of students' on Public Health issues. PBL and traditional programs were the independent variables. Descriptive variables were age and gender.By reviewing a five yearlong section of educational programs, we determined that nine Public Health main topics were common to both PBL and traditional programs. The main topics were communicable diseases, epidemiology, mother and child health, health management, chronic diseases, occupational health, nutritional principles in community, demography and environmental health.We prepared 25 multiple-choice questions in order to assess knowledge scores of students on selected subjects. The number of questions related to each topic was proportional to the time allocated for each of the topic in the curriculum. The content validity of the questions was tested by consulting experts in relevant fields. All the data were collected between February and March 2002. Scoring procedure was implemented over "100 points" where each correct answer was scored "four points" and each wrong answer was scored "zero point".Data were subjected to statistical analysis by the chi-square test and the t-test in SPSS 10.0.Overall mean age was 23.6 ± 2.1 (21–45) years. The rates of male and female students were 55.4 % and 44.6 % respectively. There were no statistically significant differences between the two groups regarding mean ages, gender distribution or other personal variables.Mean scores achieved at the 25 question-test were 65.0 in PBL group and 60.5 in the traditional group. Students in the PBL group were significantly more successful in the knowledge test Table-.The knowledge scores of seven topics were higher among students in PBL curriculum. These topics were communicable diseases, epidemiology, health management, chronic diseases, occupational health, demography and environmental health. Traditional curriculum students were found to be more knowledgeable on two topics; mother and child health and nutritional principles in the community. However, the differences between PBL and traditional students' knowledge scores in only two topics, chronic diseases and health management, were statistically significant Table-.In our study, we found a statistically significant difference between knowledge scores of PBL and Traditional education groups in favour of the PBL group Table .The students of the PBL group had higher knowledge scores on 7 of the 9 identified topics. But the difference between mean scores of the groups was statistically significant in only two topics, "health management" and "chronic diseases". The reason of significantly higher knowledge scores among the students in PBL group may be that these students have more opportunities such as observations during field studies, work-shops or presentations to study on these two topics than those in the other group. They experienced a two week training period in a "community health center" at the end of the first year and observed the health center services and prepared a structured form concerning the procedures of health centers. They also studied in "community health centers" as small groups including two students in each fortnightly during their third year in the school and completed comprehensive forms about the topics on which they studied. The reason of better knowledge scores of PBL group on "chronic diseases" may result from the special educational efforts improving the effects of relevant modules on this topic. Actually special learning opportunities were provided for all topics and we were expecting to find a difference on remaining 7 topics too. On the other hand, the students in the traditional education group had slightly higher mean scores about the topics of "mother and child health" and "nutritional principles in community" although the differences between the groups' mean scores were not statistically significant. These knowledge deficiencies among PBL students were already revealed and an additional module was implemented in the curriculum to compensate them. Curriculum of DEUSM is being looked over by curriculum committee continuously and the departments try to make interventions for problematic parts.We found that the mean total evaluation score in the PBL group was 4.5 points higher than in the traditional group in our study. Actually, we expected a much larger difference between the two groups in favour of PBL students for their education was supported by lectures, small group studies and field studies in addition to the PBL sessions. They also had the advantage of studying on Public Health issues in each year of the school by means of homogenous allocation of the modules and blocks in the first five years instead of accumulation in a short period of time as it was in the traditional curriculum. Therefore, the difference between the evaluation scores of the groups did not meet our expectations although it was statistically significant. The reason for this underachievement of Public Health objectives among our PBL students may be related to both students and PBL tutors. The common perception among the students that they have enough knowledge to say something about social and behavioural aspects of PBL modules lead them to focus on biological objectives more and they do not need to study on social issues in depth. Furthermore, a common misunderstanding among faculty members that achieving the Public Health objectives in PBL is just the responsibility of the Department of Public Health may have led the PBL tutors to withdraw from the responsibility of focusing on these subjects sufficiently. Additionally, when they are less informed or less equipped with supporting material about Public Health objectives, they may not have felt very competent while facilitating their groups by asking appropriate questions.One assumption of curricular comparison studies, included this one, is that students will do better either in one or the other type of curriculum. However, each curriculum demands different skills and deployment of learning strategies from the students. This is important because, it is well known in the educational literature that not all students do well in one particular learning program and that they do better when the program adapts to their preferred way of learning. The studies of learning styles may shed light in why the differences between performance scores are always so close when medical curricula are compared.As we mentioned before, in DEUSM, the written problem used in PBL sessions are oriented to biological as well as social and behavioural objectives. In order to achieve all these three objectives the tutors must attach the same importance to each subject and ensure that their groups give enough time and effort for each objective. But when the tutors get inadequate information and support from the experts of the related subjects, they generally focus only on biological objectives and their groups can't manage to integrate all objectives. If the tutors are less sensitive to objectives other than biological ones, then their students will be less motivated to learn and, like their educators, will be equally insensitive to Public Health topics. In order to prevent this, faculty members of the department of Public Health who take place in the scenario committees review the PBL problems regarding Public Health objectives. They make every effort to insure that the Public Health objectives are included while writing the problems and that the tutors are sufficiently informed on these objectives before their sessions. Field Work Committee has been trying to increase students' motivation and raise their awareness on Public Health issues to increase the effectiveness of field studies.Focusing only on the knowledge scores of students is the main limitation of our study. Upon the graduation of the first PBL students in the 2002–2003 academic year, we are planning additional studies regarding the other functions of a physician such as skill, behavior and attitude.The authors declare that they have no competing interests.EG conceived of the study, participated in the design of the study and drafted the manuscript, BM conceived of the study, participated in the design of the study and coordination, performed the statistical analysis, GA participated in the design of the study and performed the statistical analysis, RU conceived of the study, participated in the design of the study. All authors read and approved the final manuscript.primary prevention method?While working in a health center as a general practitioner, you have noticed that hypertension prevalence is high among the people living in the region under your responsibility. Which of the following would be your choice as a) I would educate the hypertensive patients on their disease.b) I would treat the hypertensive patients with antihypertensive drugs.c) I would send the hypertensive patients to a secondary care hospital for further investigation and treatment.d) I would educate healthy individuals on risk factors associated with hypertension and prevention methods.most common childhood nutritional disorder in Turkey?Which of the followings is the a) Protein calorie deficiencyb) Marasmusc) Iron deficiency anaemiad) Ricketswrong?Which of the following is a) Demography is a science that analyse the body, structure and differentiations of human populations.b) The goal of family planning is to decrease current number of population.c) Dependent population ratio is found by dividing the total number of population younger than fifteen years and older than 65 years of age by the total number of population between 15–65 years of age.d) Principal of pronatalist population policy is to increase the total number of population.is not one of the basic records kept in a health center?Which of the followings a) Household determination card.b) Follow-up card for the females between 15–49 years old.c) Follow-up card for aged individuals.d) Antenatal and postnatal follow up card.e) Infant and child follow-up card.Which of the followings is not among the responsibilities of an occupational health unit?a) Health prevention services in work settingsb) Work safety preventionsc) Following up the health and safety conditions in work settingsd) Preventing any interruption in productione) Giving outpatient clinic services in work setting.not required as an immediate intervention?An 11 year old girl was bitten by a neighbour-dog while she was playing in her house-garden. Which of the followings is a) To investigate if the dog is vaccinated.b) To vaccinate the girl for rabies prevention.c) To clean the wound by soap and water.d) To apply one dose of tetanus vaccine.e) To try to understand how the dog bit the girl.most common used effective family planning (contraception) methods?Which of the followings is the a) Intrauterine deviceb) Withdrawal (coitus interruptus)c) Combined oral contraceptivesd) Condome) Subcutaneous implantsbest represents the environmental health related responsibilities of a general practitioner who works in a health centre?Which of the followings a) Waste control and giving education to correct misapplicationsb) Analyzing and chlorinating drinking water, control of potable waterc) Controlling and improving the condition of toilets,d) Coordination of conduction of above mentioned services by auxiliary personnel of health centre, although these services are among the tasks of municipality.e) All of the statements above are true.After looking over one-year medical records of an internal medicine outpatient clinic, it was found that 25 % of the diagnoses were Diabetes mellitus. Regarding this result a screening procedure was conducted in the field and Diabetes mellitus prevalance was found 5 %.can not be the conclusion of above mentioned situation?Which of the followings I) Outpatient clinic may admit people coming from other regions.II) Outpatient clinic records represent the health status of the community.III) One-fourth of the patients have Diabetes mellitus diagnosis.IV) Field studies are needed to determine the real prevalance of a disease.a) I, IIb) I, IIIc) II, IIId) I, II, IVe) II, III, IVThe pre-publication history for this paper can be accessed here:


The development of miniature sensors that can be unobtrusively attached to the body or can be part of clothing items, such as sensing elements embedded in the fabric of garments, have opened countless possibilities of monitoring patients in the field over extended periods of time. This is of particular relevance to the practice of physical medicine and rehabilitation. Wearable technology addresses a major question in the management of patients undergoing rehabilitation, i.e. have clinical interventions a significant impact on the real life of patients? Wearable technology allows clinicians to gather data where it matters the most to answer this question, i.e. the home and community settings. Direct observations concerning the impact of clinical interventions on mobility, level of independence, and quality of life can be performed by means of wearable systems. Researchers have focused on three main areas of work to develop tools of clinical interest: 1)the design and implementation of sensors that are minimally obtrusive and reliably record movement or physiological signals, 2)the development of systems that unobtrusively gather data from multiple wearable sensors and deliver this information to clinicians in the way that is most appropriate for each application, and 3)the design and implementation of algorithms to extract clinically relevant information from data recorded using wearable technology. Journal of NeuroEngineering and Rehabilitation has devoted a series of articles to this topic with the objective of offering a description of the state of the art in this research field and pointing to emerging applications that are relevant to the clinical practice in physical medicine and rehabilitation. Understanding the impact of clinical interventions on the real life of individuals is an essential component of physical medicine and rehabilitation. While assessments performed in the clinical setting have value, it is difficult to perform thorough, costly evaluations of impairment and functional limitation within the time constraints and limited resources available in outpatient units of rehabilitation hospitals. Furthermore, it is often questioned whether assessments performed in the clinical setting are truly representative of how a given clinical intervention affects the real life of patients. While this observation has fostered a great deal of interest for the development and validation of outcome measures that largely rely on the use of questionnaires , researcA number of clinical applications of wearable systems in physical medicine and rehabilitation emerged in the past few years. They range from simple monitoring of daily activities, for the purpose of assessing mobility and level of independence in individuals, to integrating miniature sensors to enhance the function of devices utilized by patients to perform motor tasks that they would be otherwise unable to accomplish.Monitoring functional motor activities was one of the first goals of research teams interested in clinical applications of wearable technology. The focus was initially on using accelerometers -8 or a cA level of complexity was added when researchers started investigating motor disorders and the possibility of utilizing wearable technology to assess the effect of clinical interventions on the quality of movement observed while patients performed functional tasks. Two applications worth mentioning are the one to assess symptoms and motor complications in patients with Parkinson's disease -14 and tFinally, recent studies have been focused on integrating wearable, miniature sensor technology with orthoses, prostheses, and mobility assistive devices. Sensor technology is particularly appealing in these applications because it allows implementing closed-loop strategies that take advantage of the increased complexity and flexibility that robotics is contributing to the design of orthoses, prostheses, and mobility assistive devices. Namely, the characteristics of such devices can be constantly modified as a function of the task individuals are engaged into and environmental disturbances ,24.In all the emerging applications summarized above, either continuous recording of sensor data or at least monitoring over extended periods of time are necessary to design and implement an effective clinical intervention. Unobtrusive, wearable systems providing ease of data gathering and some processing capabilities are essential to achieve the objective of making the leap between the preliminary results obtained as part of the research carried on so far and the daily clinical practice of physical medicine and rehabilitation. Three areas of work are essential to achieve this objective: 1)the development of wearable sensors that unobtrusively and reliably record movement and other physiological data relevant to rehabilitation; 2)the design and implementation of systems that integrate multiple sensors, record data simultaneously from wearable sensors of different types, and relay sensor data to a remote location at the time and in the way that is most appropriate for the clinical application of interest; and 3)the development of methodologies to manipulate wearable sensor data to extract information in a clinically relevant manner to perform clinical assessments or control devices aimed at enhancing mobility in individuals with conditions that limit their level of independence. A series of papers have been assembled to provide the readership of Journal of NeuroEngineering and Rehabilitation with a description of the state of the art of the application of wearable technology in physical medicine and rehabilitation.A first set of the papers that have been assembled for publication on Journal of NeuroEngineering and Rehabilitation on the topic of wearable technology in physical medicine and rehabilitation has the objective of describing recent advances in wearable sensor technology. Two manuscripts describe attempts by different groups of measuring angular displacements for upper and lower extremity joints by embedding conductive fibers into the fabric of undergarments. The paper by Gibbs and Asada, entitled "Wearable conductive fiber sensors for multi-axis human joint angle measurements", reports encouraging preliminary results concerning monitoring lower limb joint displacements during ambulation by utilizing such technology. The manuscript by Tognetti et al, entitled "Wearable kinesthetic system for capturing and classifying upper limb gesture in post-stroke rehabilitation", describes the design and implementation of a system similar to the one proposed by Gibbs and Asada but geared toward monitoring movements of the upper extremities. The authors also explore the application of these wearable sensors to monitoring motor recovery in post-stroke individuals. Simone and Kamper focus their contribution on unobtrusively measuring finger movements in patients undergoing rehabilitation. Their manuscript "Design considerations for a wearable monitor to measure finger posture" summarizes the authors' recent work toward developing ways to record fine motor control tasks involving manipulation of objects requiring fine motor control of the hand and fingers. This technology has immediate application in patients such as post-stroke individuals undergoing rehabilitation that targets fine motor control skills. While initial research in the area of wearable technology was aimed at combining existing, miniature sensors with special fabrics or wireless technology, recent advances in this field have been focused on the development of sensing elements that can be even more easily embedded in clothing items. An example of such effort is reported in the paper by Dunne et al entitled "Initial development and testing of a novel foam-based pressure sensor for wearable sensing". This paper summarizes positive preliminary results by the research team aimed at measuring shoulder movements, neck movements, and scapular pressure. The sensing elements can also be used to monitor respiratory rate. Devoted to monitoring systemic responses is the last of the papers focused on wearable sensors. In this manuscript, Yan et al describe a new method to reliably measure heart rate and oxygen saturation. The paper is entitled "Reduction of motion artifacts in pulse oximetry by smoothed pseudo Wigner-Ville distribution" and demonstrates how advanced processing techniques may be necessary to derive reliable data when recordings are performed in the field.A second area of research relevant to the application of wearable technology in physical medicine and rehabilitation concerns the integration of wearable sensors into systems. Following the seminal work by Park and Jayaraman , severalA final set of papers is focused on applications that are relevant to physical medicine and rehabilitation. Sherrill et al describe in their paper entitled "A clustering technique to assess feasibility of motor activity identification in COPD patients via analysis of wearable-sensor data" a method to design classifiers of motor activities such as walking and stair climbing. The proposed technique relies on the examination of small datasets via clustering methods. Measures are derived from clusters associated with different motor activities to evaluate whether the set of wearable sensors and features derived from the recorded data are suitable to reliably identify the motor tasks of interest. Wang and Winters put the information gathered via wearable systems into a clinical context via processing that relies on neuro-fuzzy models. Their paper entitled "A dynamic neuro-fuzzy model providing bio-state estimation and prognosis prediction for wearable intelligent assistants" presents encouraging results indicating that the proposed method can put in the correct context dynamic changes observed in post-stroke individuals undergoing rehabilitation. Wang and Kiryu in their manuscript entitled "Personal customizing exercise with a wearable measurement and control unit" summarize their results on customizing machine-based exercise routines on the basis of physiological data that are continuously gathered from individuals performing such routines. Their results demonstrate the feasibility of a closed-loop system that optimally adapts workload. Dozza et al describe a wearable system designed to reduce body sway in individuals with severe vestibular problems. Their manuscript entitled "Influence of a portable audio-feedback device on structural properties of postural sway" summarizes positive results obtained with a prototype wearable system that utilizes audio-feedback to improve balance. Finally, Mavroidis et al describe how miniature sensor technology can be used to design a new generation of smart rehabilitation devices. Three devices are described in their paper entitled "Smart portable rehabilitation devices": a passive motion elbow device, a knee brace that provides variable resistance by controlling damping via the use of an electro-rheological fluid, and a portable knee device that combines electrical stimulation and biofeedback. These devices combine sensing technology and control strategies to enhance rehabilitation.This collection of papers provides an up-to-date description of the state of the art in the field of wearable technology applied to physical medicine and rehabilitation. The field is rapidly advancing and numerous research groups have already demonstrated applications of great clinical relevance. The potential impact of this technology on the clinical practice of physical medicine and rehabilitation is remarkable. A significant shift in focus is possible thanks to wearable technology. While the main focus of clinical assessment techniques is currently on methods that are implemented in the clinical setting, wearable technology has the potential to redirect such focus on field recordings. This is expected to allow clinicians to eventually benefit from both data gathered in the home and the community settings during the performance of activities of daily living and data recorded in the clinical setting under controlled conditions. Complementarities are expected between field and clinical evaluations. Future research will surely address optimal ways to combine these two types of assessment to optimize the design of rehabilitation interventions.


We have hypothesized that these PGE2 dependent effects on firing rate are due to changes in the inherent electrical properties of VMPO neurons, which are regulated by the activity of specific ionic currents.Physiological and morphological evidence suggests that activation of the ventromedial preoptic area of the hypothalamus (VMPO) is an essential component of an intravenous LPS-dependent fever. In response to the endogenous pyrogen prostaglandin E2 dependent firing rate responses were not the result of changes in resting membrane potential, action potential amplitude and duration, or local synaptic input. However, PGE2 reduced the input resistance of all VMPO neurons, while increasing the excitability of temperature insensitive neurons and decreasing the excitability of warm sensitive neurons. In addition, the majority of temperature insensitive neurons responded to PGE2 with an increase in the rate of rise of the depolarizing prepotential that precedes each action potential. This response to PGE2 was reversed for warm sensitive neurons, in which the prepotential rate of rise decreased.To characterize the electrical properties of VMPO neurons, whole-cell recordings were made in tissue slices from male Sprague-Dawley rats. Our results indicate that PGE2 is having an effect on the ionic currents that regulate firing rate by controlling how fast membrane potential rises to threshold during the prepotential phase of the action potential.We would therefore suggest that PGE This criterion is based on previous studies that indicate a functional difference for neurons which show this degree of inherent thermosensitivity .HJR, carried out the majority of cellular recordings and data analysis. JDG conceived of the study and participated in its design, coordination and completion. Both authors contributed equally to the drafting of this manuscript.