Recently, the recycling of waste glass has become a worldwide issue in the reduction of waste and energy consumption. Waste glass can be utilized in construction materials, and understanding its effects on material properties is crucial in developing advanced materials. In this study, recycled crushed and expanded glasses are used as lightweight aggregates for concrete, and their relation to the material characteristics and properties is investigated using several approaches. Lightweight concrete specimens containing only crushed and expanded waste glass as fine aggregates are produced, and their pore and structural characteristics are examined using image-based methods, such as scanning electron microscopy (SEM), X-ray computed tomography (CT), and automated image analysis (RapidAir). The thermal properties of the materials are measured using both Hot Disk and ISOMET devices to enhance measurement accuracy. Mechanical properties are also evaluated, and the correlation between material characteristics and properties is evaluated. As a control group, a concrete specimen with natural fine sand is prepared, and its characteristics are compared with those of the specimens containing crushed and expanded waste glass aggregates. The obtained results support the usability of crushed and expanded waste glass aggregates as alternative lightweight aggregates. These days, there are many concerns related to industrial by-products because of their harmful effects on the environment and energy consumption. Many efforts have been undertaken to find a way to reduce these negative effects and to enhance sustainability in technical and economic terms . The recSolid waste materials can be utilized as both powdered material and as aggregates for concrete. The use of waste materials from construction and demolition as aggregates is considered to be a promising approach due to a shortage in natural aggregates (which constitute 60–80 % concrete by volume) and the resultant reduction in the relatively large energy consumption associated with the processing of raw constituents . For insAt the same time, the use of WG has some disadvantages because of its broken, mixed colored, and diverse origin of waste glass which cause impractical and highly expensive in the recycling process ,10,11. AWG aggregates have been used to enhance the specific material property of concrete materials. For instance, Yu et al.  have useModern building materials should meet minimum mechanical property and durability requirements so as to be successfully used in construction fields. Furthermore, it has been suggested that energy savings can be made through the proper insulation of a structure; therefore, thermal conductivity is becoming an important factor in determining the properties of modern building materials . This stOrdinary Portland cement CEM I 42.5 N according to DIN EN 197-1 provided by HeidelbergCement  and condensed silica fume according to DIN EN 13263-1 provided by Sika Deutschland  were used to prepare the concrete specimens. Crushed glass aggregates were prepared from brown soda-lime waste glass obtained from a local recycling company; this glass is generally used for the production of beverage glass containers. Waste glass was washed with water (to remove organic contaminants), dried, and crushed in a planetary ball mill in order to obtain the desired particle size. The particle size distributions of the three aggregates used in the study were identical and are presented in he shell . ExpandeScanning electron microscope (SEM) micrographs of the tested aggregates are presented in The surface of crushed glass in In this study, three different mixes were designed and prepared. The concrete specimens with crushed waste glass, expanded waste glass, and natural sand are denoted as CG, EG, and NS, respectively. The aggregate grading of all the mixes were fixed in order to clarify the effects of aggregate type on the properties of concrete. Each aggregate was sieved separately, and the required amount of each fraction was taken to fit the grading curve of the mixture as shown in In this study, image based techniques, such as X-ray computed tomography (CT) and automated image analysis systems based on a linear traverse method, were incorporated to investigate microstructural characteristics, such as pore and solid structures. The results were supported with Tescan Vega 3 scanning electron microscope (SEM) microstructure analysis. A characterization of the air-void structure of hardened concrete, using a linear traverse method (EN 480-11) was performed automatically with a RapidAir 457 Automated-Air-Void-Analyzer , as reported in To investigate the pore structures of the specimens in 3D, X-ray micro-CT  and ISOMET . These tools are a transient plate source method (Hot Disk) and a direct hand-held measuring instrument (ISOMET), which meet ISO (22007-2:2015) and European (EN 12571) standards, respectively. For the accuracy of the measurements, three specimens of each case were repeatedly tested with the mean value being presented.The mechanical properties of the specimens were measured using sensitive experimental tools. Here, 28 days compressive and flexural strengths were evaluated to compare the mechanical performance of the lightweight concrete with different aggregates. To determine the strengths of the specimens, compression and flexural testing machines  were used according to EN 12390-3 and EN 12390-5, respectively. In addition, the dry densities of the specimens were measured at the age of 28 days. Three samples of each case were oven dried at 105 The material properties and characteristics of concrete specimens with three different aggregates were evaluated. For these purpose, the thermal  and mechanical  of the specimens were measured. In particular, the pore characteristics of the specimens were investigated using different image-based approaches, such as SEM, The fresh properties of lightweight concrete are important in regulating material performance . The congregates .However, in spite of the spherical shape and the very smooth surface of expanded glass , 634.4 (EG), and 2076.2 (NS) kg/mThe thermal conductivity of the specimens was measured using both the Hot Disk and ISOMET for more accuracy, and the results are presented in In sults in ,42.To investigate the mechanical performance of the specimens, both their flexural and compressive strengths after 28 days of curing are presented in As with flexural strength, the specimen with crushed glass aggregates exhibited about 19% higher compressive strength than the specimen with natural sand aggregate. There are several studies which have reported deterioration with the use of waste glass for concrete ,45,46, wd shapes h; in ourd shapes d,g. FiguFor more detailed investigation of the pore structures of the specimens, In addition, the pore distribution of the binder of EG is more dispersed than that of the NS and EG specimens. From the figure, the effect of the aggregates on the material characteristics can be predicted; the aggregate type affects both the porosity and the pore distribution of concrete materials.The detailed porosity of the specimens was calculated using the images in The pore size distributions of each specimen were also investigated using the From the results of the material properties and the pore characteristics, it is concluded that the use of crushed waste glass aggregates can reduce concrete density and thermal conductivity significantly with the beneficial effect of enhancing compressive and flexural strengths. The results indicate that aggregate characteristics, such as shape, pore size, porosity, and material properties, strongly affect concrete materials, and materials with advanced mechanical properties as well as insulation can be achieved by using crushed waste glass as a lightweight aggregate.Lightweight concrete specimens with different sources of aggregate were produced and investigated in this study. In particular, the effect of recycled crushed waste glass on concrete was examined according to several investigative approaches. To produce lightweight concrete specimens, crushed waste glass, natural sand, and expanded glass were adopted. Aggregate grading was also considered in maximizing the aggregate content. Pore and solid characteristics of specimens were evaluated using SEM, Lightweight concrete of density less than 2000 kg/mThe image-based methods adopted here, such as SEM and The shape of crushed glass aggregates affects the fresh properties of the material. The angularity of the aggregates influences workability due to mechanical interlocking of the glass particles resulting in a need for more superplasticizer and stabilizer to achieve appropriate concrete consistency.The specimen with crushed waste glass had about 20 % more compressive strength than the specimen with natural sand, with the thermal conductivity being less than one-third of normal concrete. Therefore, the use of crushed glass can enhance material properties significantly.When a material contains dense aggregates, such as crushed glass and natural sand, the porosity of the specimen is mainly determined by the binder phase. However, for a material with porous aggregates, e.g., expanded glass, the porosity of the aggregates is the dominant factor regulating material properties.The concluding remarks of this paper can be summarized as follows:In addition to the work reported in this paper, more parametric studies with different mix proportions using crushed waste glass are required to clarify the effects of recycled material on concrete properties.


Spermatocytogenesis starts from lumens of seminiferous cords and after migration to the basal membrane ends to the lumens again. We attempt to review the protective effects of melatonin and ghrelin on Spermatocytogenesis and in particular on spermatogonial stem cells, as two rather newly-discovered hormones. Testicular freezing prior to chemotherapy and radiotherapy is one of the ways of preserving fertility in children with cancer. The freezing has two methods of slow-freezing (cryopreservation) and rapid-freezing (vitrification). Administration of melatonin can maintain the quality of the germ cells underwent such processes, as well as ghrelin, can protect germ cells from the toxicities secondary to ischemic injuries, and pathologic apoptosis. This review indicates that in vitro or in vivo administration of melatonin or ghrelin, could be effective to preserve fertilization and also they can be used in assisted reproductive technologies to improve the quality of sperms. Future original studies should be propelled toward human studies, of course with observing the ethics.  Primordial germ cells (PGCs) are known as the origin of germ cells in both genders . HoweverThe gonocytes keep on proliferation till arresting phase after the embryonic day 14.5 (in mice) . After bs) which also is called as spermatogonial stem cell (SSC); and the next levels are respectively A paired spermatogonium (Ap) and A aligned spermatogonium   is the involving gene in the mentioned balance. Reduction in expression of this gene is along with the reduction of SSC proliferation and infertility. The protein NANOS2 existing in As and Ap, is also involved that its elimination or over-expression cause elimination or aggregation of SSCs  . Spermatum  , 13. Theem cells , 15. The of SSCs . The inducing agent of SSC proliferation is glial cell line-derived neurotrophic factor (GDNF) and its signaling pathway released from Sertoli cells. Over-expression of this cascade results in aggregation of undifferentiated spermatogonia. Gradual elimination of SSCs could be secondary to either elimination of the GDNF or its receptors . FormatiSpermatogenesis injuries could be due to the toxicity of chemotherapeutic drugs such as busulfan and cispelatin or toxicity of antibiotics like gentamicin, infectious agents like parasites, the oxidative stress modeled by ischemia-reperfusion in studies or exposing in electromagnetic fields -30. PrevTesticular freezing prior to chemotherapy  and radiotherapy is of the ways of preserving fertility in children with cancer , 33, 34.Melatonin has been found and proven in microorganisms such as primitive bacteria and green algae as a serve antioxidant.In addition, melatonin is also found in pluricellular organisms such as fungi, plants, insects, nematodes, and vertebrates like mammals . This hoAfter the narrative introduction presented above, we attempt to review the protective effects of melatonin and ghrelin on male reproduction system and in particular on SSCs, as two rather newly-discovered hormones.For the present narrative review, we used the scientific databases and meta-search engines including Google Scholar, PubMed, Scopus and Science Direct, and Web of Science core collection. Since the related articles were rare, the time period was not important to us. As key words and contents of search, at first we searched for all the articles of the first and corresponding authors related to male's reproduction as the self-referring which is necessary for review articles; second, searched for "melatonin AND spermatogonia" and "ghrelin AND sperm"; and finally searched for general information about spermatogenesis process in order to write the introduction. There were some duplications between the first and the second levels. Our literature review method was summery-comparison matrix, a method helping researchers to extract relevant information from the literature, categorize and visualize them . The founded literatures are summarized in Role of melatonin2SeO3, quersetine or other flavonoid compounds, magnesium sulfate or antioxidants in medical plants like ginger and onion, carrot seed extract  type 1a was observed in both Leydig and Sertoli cells . In 2009Cisplatin is an anti-cancer medicine which induces apoptosis both in cancerous and normal cells , 21. TheIn addition to cisplatin-induced damage, the studies done by Taati and the coworkers during recent years, show the protective effects of ghrelin from ischemia-reperfusion damage. They found that malondialdehyde values were significantly lowered in the treated group, and ghrelin significantly enhanced sperm movement, motility, and concentration. This protective effect is due to anti-apoptotic and anti-inflammatory effects of ghrelin -27. It sInfertility is a problem for a lot of couples. The male-based ones, either in real clinics or in research modeling, could be due to chemotherapy, radiotherapy, electromagnetic fields, ischemia-reperfusion and high oxidative stress, microbial and parasitic agents, or toxicity of antibiotics. This review indicates that in vitro or in vivo administration of melatonin and ghrelin as two newly discovered hormones, could be effective to preserve fertilization in such cases, and also they can be used in assisted reproductive technologies to improve the quality of the sperms. Future original studies should be propelled toward human studies of course with observing the ethics. Hereby we declare that there is no conflict of interest.


AhR-related gene may exert pathological influences on sexual differentiation of the brain, causing autistic traits. To ascertain the relationship between AhR-related gene polymorphisms and autism susceptibility, we identified genotypes of them in patients and controls and determined whether there are different gene and genotype distributions between both groups. In addition, to clarify the relationships between the polymorphisms and the severity of autism, we compared the two genotypes of AhR-related genes  with the severity of autistic symptoms. Although no statistically significant difference was found between autism spectrum disorder (ASD) patients and control individuals for the genotypic distribution of any of the polymorphisms studied herein, a significant difference in the total score of severity was observed in rs2228099 polymorphism, suggesting that the polymorphism modifies the severity of ASD symptoms but not ASD susceptibility. Moreover, we found that a significant difference in the social communication score of severity was observed. These results suggest that the rs2228099 polymorphism is possibly associated with the severity of social communication impairment among the diverse ASD symptoms.Exposure to environmental chemicals, such as dioxin, is known to have adverse effects on the homeostasis of gonadal steroids, thereby potentially altering the sexual differentiation of the brain to express autistic traits. Dioxin-like chemicals act on the aryl hydrocarbon receptor (AhR), polymorphisms, and mutations of  Reports of the incidence of autism spectrum disorder (ASD) – characterized by two core symptoms: communication and social deficits and fixed or repetitive behavior  – have bp-dioxin (TCDD), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and some polychlorinated biphenyls (PCBs), act on the aryl hydrocarbon receptor (AhR)  theory is one of the leading hypotheses for explaining the mechanism of ASD , 11. Theor (AhR) , 15. Recor (AhR) , 17. Theor (AhR) .AhR)-related gene polymorphisms.Epidemiological studies have shown that PCB exposure at low levels can exert adverse clinical and subclinical effects on sociocognitive functions –23. DepeAhR-related gene polymorphisms and reproductive system diseases, such as endometriosis or infertility  Val189Val as potential candidates  contribute to ASD susceptibility and/or severity.Numerous studies have investigated the association between ertility –27, becaertility . Variousndidates –27. Althorphisms . TherefoAhR-related gene polymorphisms and ASD susceptibility, we identified these genotypes in patients and controls and determined whether there are different gene and genotype distributions between the two groups. Second, to clarify the relationships between the polymorphisms and the severity of ASD, we compared the genotypes of AhR-related genes with the severity of ASD symptoms using the Childhood Autism Rating Scale (CARS)  . Finallye (CARS) . We alsoal cases , 33.Ninety-five children and adults with ASD participated in the present study. Participants with ASD were recruited in two different geographical regions, Tokyo and Nagasaki, in Japan. The participants in Tokyo consisted of 68 ASD patients  and were recruited from the outpatient clinics of the Department of Psychiatry in the University of Tokyo Hospital. The participants in Nagasaki consisted of 27 ASD patients , and they were recruited from two day-care facilities in Nagasaki prefecture for patients with developmental disorders. In both areas, the diagnoses were made by two or more senior pediatric-psychiatric clinicians through structured interviews and reviews of clinical records according to the DSM-IV criteria . Among tAdditionally, 527 adults  were recruited as control participants from the nearby community around the University of Tokyo Hospital, without any psychiatric disorder disturbing their work function. The Mini-International Neuropsychiatric Interview (MINI)  and otheThe race/ethnicity of all participants was Japanese. Potential participants were also excluded if they had any history of substance abuse, recent substance use, head trauma with loss of consciousness, significant fetal exposure to alcohol or drugs, perinatal or neonatal complications, and neurological disorders or medical conditions.The present study was approved by the Ethical Committees of the University of Tokyo Graduate School of Medicine and the Nagasaki University Graduate School of Biomedical Sciences. All participants or parents of the affected individuals provided written informed consent prior to their participation in this study. The experimental protocol was conducted in accordance with the Declaration of Helsinki.The severity of ASD was assessed on the basis of the Japanese version of the CARS . The assAhR codon 554 in exon 10  and ARNT codon 189 in exon 7   in set B. All participants were genotyped by real-time polymerase chain reaction (PCR) analysis using Roche LightCycler 480 II  for the following two single nucleotide polymorphisms (SNPs): 2066853) –28. ReacAhR-related gene polymorphism and susceptibility to ASD. Next, analysis of variance (ANOVA) was used to compare the severity of ASD among AhR-related gene polymorphisms. Third, to assess the severity corresponding to several core behavioral symptoms of ASD, factor analysis with Varimax rotation for CARS was performed, and the factor score was calculated by regression method for each subject. Finally, ANOVA was also used to assess the effects of AhR-related gene polymorphisms for each severity of discriminative behavioral symptoms of ASD identified by the prior factor analysis. The chi-squared test, factor analysis, and multinomial logistic regression analysis were performed using IBM SPSS 20.0 for Windows . The ANOVA was performed using Anovakun software . Comparisons between genotype groups did not demonstrate statistically significant differences with regard to children’s age, sex, or IQ level. To investigate the relationship between each AhR-related gene polymorphism and susceptibility to ASD, the chi-squared test was used to evaluate the genotype distribution according to developmental status. No statistically significant association was observed between any of the polymorphisms and susceptibility to ASD.The genotype and allele frequencies of AhR-related gene polymorphism and the severity of ASD, one-way ANOVA was used for the total CARS score of ASD patients as the dependent variable and the genotype of each AhR-related gene polymorphism as the independent variable. There was a statistically significant difference between genotype groups for ARNT polymorphism (rs2228099), as determined by ANOVA . Holm’s sequentially rejective Bonferroni post hoc test revealed that the total CARS score of the GG genotype was statistically significantly higher than those of the GC genotypes , whereas there were no statistically significant differences in score between the CC genotype and both genotype groups . Additionally, there were no statistically significant differences between genotype groups for AhR polymorphism (rs2066853) [F = 0.26]. Taken together, these results suggest that ARNT polymorphism modified the severity of ASD among the AhR-related genes examined in the current study.Next, to investigate the relationship between each AhR-related genes and the severity of each of the three behavioral symptoms of ASD.To assess the severity according to several core behavioral symptoms of ASD, factor analysis with Varimax rotation was performed for the CARS data. The analysis produced three factors with eigenvalues greater than one. These factors accounted for 55.1% of the common variance. Table AhR-related gene polymorphism and the severity of several of the core symptoms of ASD, one-way ANOVA was performed for the factor score of CARS of ASD patients as the dependent variable, with the genotype of each AhR-related gene polymorphism as the independent variable. Similar to the result for the total score, there were no statistically significant associations between factor scores and genotype groups for AhR polymorphism (rs2066853) (Table ARNT polymorphism (rs2228099), a significant difference was observed for the factor score of the “social communication” factor, but not for the “sensory and emotional response” factor or “stereotypies” factor. Holm’s sequentially rejective Bonferroni post hoc test revealed that the factor score of the GG genotype was statistically significantly higher than that of the GC genotypes , whereas there were no statistically significant differences in score between CC genotype and both genotype groups  . Although the exact molecular and physiological mechanisms underlying this effect remain unknown, a recent study suggested that silent mutations may contribute to mental disorders  may have provided a better index (ARNT gene polymorphism to aspects of social communication.Several limitations of the present study should be noted and taken into consideration in future studies. First, the main limitation is the relatively small patient group. We did not observe a significant association between genetic SNPs and susceptibility to ASD in this study, and one possible explanation is the small sample number, as a large number of subjects are needed for case–control studies based on the frequency distribution. Therefore, studies involving a larger number of subjects are essential to generalize our results. Second, the number and age of subjects between the cases and control groups were not well matched. It is possible that the risk modulation by er index . This heer index . TherefoARNT GG genotype had more severely impaired social communication than those with GC genotype in ASD, indicating that the differences in social functioning in ASD patients may be modulated by ARNT variants. Considering that ARNT is a component of AhR cascades, vulnerability to environment chemicals, especially dioxin-like chemicals may affect the severity of impaired social communication, although the functional analysis of ARNT gene polymorphism remains to be performed. To identify the neuronal mechanism underlying this effect, combining the present experimental paradigm with neurophysiological indicators of brain activities is warranted in future studies.In conclusion, the current results showed that individuals with the TF and SN were involved in conducting the experiment, analyzing and interpreting data, and drafting the article. RI, JM, and CK were involved in recruiting the participants and diagnosing the participants with ASD. MT, TS, and NK were involved in conducting the experiment, analyzing and interpreting data, and revising the article. KS conceived of the study, participated in its design and coordination, and drafted the manuscript. All the authors have read and approved the final manuscript.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 use of robots in surgery has been increasingly common today, allowing the emergence of numerous bioethical issues in this area.  To present review of the ethical aspects of robot use in surgery.  Search in Pubmed, SciELO and Lilacs crossing the headings "bioethics", "surgery", "ethics", "laparoscopy" and "robotic".  Of the citations obtained, were selected 17 articles, which were used for the preparation of the article. It contains brief presentation on robotics, its inclusion in health and bioethical aspects, and the use of robots in surgery.  Robotic surgery is a reality today in many hospitals, which makes essential bioethical reflection on the relationship between health professionals, automata and patients.  Eu, robôIn health, the development of robots was to assist some tasks considered basic. The hospital support robotic system Helpmate Pyxis Corp., San Diego, California, USA, for example, moves transporting drugs, food, utensils and other equipment. It can be effective for all hospital areas, and allows professionals to perform other functions that have irreplaceable role. Already robots RX and AHC, both of McKesson company of San Francisco, California, USA, are designed to prepare drugs for enteral and parenteral application,,,At present, some models are important and can become essential in the coming medical practice, such as the AESOP Robotic Surgical System , built by the company Computer Motion Inc., of Santa Barbara, California, USA,Exceeding these technological boundaries has allowed significant innovation in surgical activity, generating the need for new ways of evaluating its implementation, especially in the technical, legal and bioethic fields33,34 - which is concerned primarily with human behavior in interactions with robots and other machines that hold artificial intelligence,Another interesting composition involving robotics and ethics is the roboethics - a term coined by Gianmarco Veruggio,The interrelations between bioethics and robotics make up a very new field of study in the scientific literature; there are few publications directed to the topic that must be more explored and discussedThus, based on these preliminary considerations, this article presents a brief presentation on robotics - emphasizing their inclusion in health - as an initial step to address the ethical issues surrounding the use of robots in surgery.Through DeCS site (www.decs.bvs.br), the descriptors "ethics", "bioethics", "robotics", "surgery" and "laparoscopy" were selected and combined to determine search strategies of articles published in journals . The folOf total obtained citations, 17 articles were selected - using as criteria the existence in the text of ethical considerations directed to the use of robots in surgical procedures - which were used for the preparation of this text.,,,The term robotics derives from "robota" Czech word meaning "servant" or "worker"From fiction to real life, the application of robots started in the industry when General Motors introduced the Unimate,Not restricted to industry, from the 60s, robotics was present in different scenarios, from employment to explore the ocean depths to the use of rescue missionsRobots are already used in health care in surgical procedures for years. One of the first devices used in surgery was the forerunner of Neuromate - approved in 1999 by the Food and Drug Administration (FDA) - created to perform stereotactic brain biopsy accurately at 0.05 mmEvolving a little more in the field of surgery, was the telerobotics insertion by developing the da Vinci Surgical System - in which the surgeon performing the procedure through a console (or two consoles when performed by two surgeons), which controls three or four mechanical arms remotely  - and the surgical system Zeus - which made possible the realization of laparoscopic cholecystectomy in a patient who was in Strasbourg, France, by surgeon located in new York, USA. By allowing conducting operations without the physical presence of the surgeon's hand to the patient, the Advanced Research Projects Agency of the Pentagon's Defense envisions using this technology in battle fields,With robotics progress in health, and observing the current literature, we note that the implementation of robots has been beneficial in surgical operations of the head and neck, gastrointestinal, gynecological, cardiac and urologic proceduresIncreasing the degree of complexity of operations and the consequent difficulty of training some techniques by learners - particularly the ethical and legal issues involved - contributed to the invention of simulators that generate, with the aid of computer and robotic techniques, virtual reality environments,,,,,,,Regarding non-surgical treatments, note the use of robotic devices primarily in physical medicine and reabilitationThe progress of robotics, along with the favorable results obtained with the use of robots in operations, has raised ethical discussions on the possible limits on the use of automata in operative environmentThe question of responsibility - the indication and execution of surgery - does not differ in substance from medical situations in which there is no involvement of robots. In fact, the professional is responsible for robotics participation in surgical procedures, which can be defended using disparate contemporary bioethical currentsThe physician is prohibited:Art. 3. Failing to take responsibility for medical procedure indicated or attended, even when several doctors have assisted the patient.[...]Art. 6. Assign their failures to third parties and the occasional circumstances, except in cases where it can be duly substantiated. 10.The situation becomes more complex when is added to bioethics interface/robotics issues on the telemedicineThe Federal Medical Council regulates the provision of services through telemedicine since 2002, in Resolution No. 16439, which provides for the goals of this healthcare modality, appropriate methodologies, health research and appropriate technological infrastructure, including ethical aspects, with emphasis on confidentiality, professional secrecy and privacy, among othersArt. 2 - The services provided by the Telemedicine should have the appropriate technological infrastructure, relevant and comply with the technical standards of CFM relevant custody, handling, data transmission, confidentiality, privacy, and assurance of professional secrecy.The resolution brings manifestation in order to comment on the responsibility in Medical Code of EthicsArt. 4 - The professional responsibility of care is up to the doctor of the patient. The other involved jointly liable to the extent that contribute to any damage to him.Such resolutions must be considered in the case of operations using robots, especially when the use of artifacts is held at a distance, in which case the procedure becomes part precisely the scope of telemedicine.19,27 - with the advancement of techniques and artificial intelligence, especially towards strong AI19,27 - which would raise the question of what level of ethical consideration these thinking beings deserve; and 2) the use of robots in reprehensible acts - the legal and ethical point of view - for example, the action in order to take human lives and not human  ,,,,,Other bioethical issues - but that would flee the scope of this article - could be briefly mentioned: 1) emergency of machines with possibilities genuinely intelligentFrom these questions, it is necessary the effort to unite the two cultures - bioethics and robotics - so problems could be understood in their entirety and complexityRobots - coming art/fiction - have become increasingly present in contemporary reality. In fact, you can see them working in places where humans cannot go - because of its biological limitations - and helping women and men in different fields of knowledge, as the area of health.In this regard, there is emphasis on the advances in the use of these devices in surgical procedures, with good results in different types of interventions. In this scenario, the bioethical debate on robotic surgery - still incipient in educational environments and health research - becomes very salutary, to provide support to decision-making in situations where the robots are partakers of care actions to humans.


Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor) or NT-3 (neurotrophin-3) protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT (choline acetyltransferase). In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review, we summarize these evidences and discuss them in the context of other motor systems. During the last decades of the XXth century, increasing evidence pointed out the crucial role of neurotrophic factors, and in particular, neurotrophins, in the precise development of the nervous system. Target-derived neurotrophins regulate the extension of neuronal populations , and areSeveral studies carried out in our group have demonstrated the relevance of neurotrophins and other trophic factors on the developing and adult oculomotor system. In the present review, we summarize these results and place them in the context of recent neurotrophin research.The oculomotor system (and more precisely the abducens nucleus) has long been used as a model to study plasticity in the adult nervous system ,25,26,27Second, electrophysiological abducens neuron identification can be easily performed by antidromic activation from either the VIth nerve or the medial longitudinal fascicle for motor and internuclear neurons, respectively, and by their particular activity pattern in relation to eye movements. In fact, firing rate is closely related to eye position and velocity: both motoneurons and internuclear neurons exhibit a tonic firing rate that increases with more abducting ipsilateral eye fixations, and a phasic component of the firing rate that controls eye velocity ,37. MorpThird, both populations of neurons can be easily disconnected from their target, and in the case of motoneurons, it is also easy to provide them with exogenous neurotrophins from the periphery, without disturbing the integrity of the central nervous system.Many experiments have revealed the strong dependence of abducens neurons on target-derived factors to survive during development, as well as to maintain the normal adult phenotype. For instance, in the neonatal period, the removal of extraocular muscles induces the death of their afferent motoneurons. Even more, medial rectus motoneuron retrograde death has a secondary effect on abducens internuclear neurons, which remain disconnected from their natural target , and suffer the same process of cell death as a consequence of target loss . As statTarget dependence in the oculomotor system is not restricted to development. Instead, it is also crucial for the stability of mature neuron features. Experiments of toxin injection in the medial rectus muscle of adult animals, which led to motoneuron toxicity and death, were performed to produce the depletion of abducens internuclear neuron target cells. Target-deprived internuclear neurons suffered a process of soma shrinkage, dendritic retraction, and the loss of afferent contacts that, finally, produced changes in their normal firing pattern related to eye velocity and position ,21.Axotomy implies not only target disconnection, but also a direct damage to neuron integrity. However, the axotomy of both abducens populations produce similar results to those obtained after target depletion: loss of afferences and a reduction in the neuronal signals that codify eye position and velocity. In particular, firing modulation during eye fixations, spontaneous eye movements and the vestibulo-ocular reflex are clearly reduced ,23,24. ATo fully demonstrate that the alterations that follow abducens internuclear neuron axotomy were due to target disconnection and the absence of target-derived signals, axotomized abducens internuclear neurons were provided with a different source of trophic factors, i.e., an implant of embryonic cerebellar primordia at the lesion site . AbducenSumming up, these results indicate that all these alterations are induced by the lack of retrograde trophic support, rather than by axon damage. Thus, the new exogenous target would provide neurons with trophic molecules, restoring the retrograde flux of information, and therefore allowing the maintenance of afferent inputs and the electrophysiological properties. Our group has dedicated several years to understand which are the molecules implicated and how they control abducens neuron properties. The following sections explain these results in detail.Neurotrophins exert their function by binding to their high affinity receptors, the Trk subfamily of tyrosine protein kinases, which include the products of the trkA, trkB and trkC proto-oncogenes . The relThe alterations described in abducens neuron properties when deprived of retrograde trophic support could well be mediated by a deficit in neurotrophins. For this reason, as a first step in elucidating the role of neurotrophins in the plasticity of the oculomotor system, we characterized the distribution of Trk receptors in identified populations  of the extraocular motor nuclei of adult cats . These eThe presence of TrkB had been demonstrated previously in the cat abducens nucleus  and chicOur results showed that almost all motoneurons were positive for the three receptors, indicating that most cells must co-express two or more neurotrophin receptors. In addition, other neurons present in the oculomotor nucleus were immunopositive against Trk antibodies. The same results were obtained for trochlear and abducens motoneurons and internuclear neurons. Co-expression of more than one Trk receptor is not exclusive of extraocular motoneurons. Thus, the giant cells of the pontine reticular formation in the adult cat , embryonThe finding that extraocular motoneurons of the abducens nucleus contain two or three Trk receptors indicated that these cells might be responsive to more than one neurotrophin. The actions of these growth factors during adulthood are different from those described during development, as mature neurons do not depend on neurotrophins for survival ,21,48,61Although all receptors were present in the different extraocular motoneuron populations, TrkB expression was prevalent. This receptor is also predominant in other motor systems such as spinal motoneurons ,59. The Moreover, neurotrophins that bind to motoneuron Trk receptors might also arise from their afferent inputs ,67,68,69On the other hand, the presence of TrkA receptor in extraocular motoneurons was particularly surprising. Other motoneuronal types express both TrkB and TrkC in the adult ,58,76,77The expression of Trk receptors  in extraocular motoneurons indicates that their associated neurotrophins  intervene on the normal function of the oculomotor circuitry . As statExtraocular motoneurons can be disconnected from their target by enucleation, a procedure that involves both the injury to the extraocular motor nerves and the removal of target tissues within the eye orbit. In order to investigate the dependence of extraocular motoneurons on neurotrophins we analyzed changes in Trk receptor mRNA levels after enucleation by in situ hybridization . MotoneuIn contrast, the expression of TrkB mRNA after axotomy was significantly increased in extraocular motoneurons A. The inThe upregulation of calcitonin gene-related peptide (CGRP), a protein involved in the formation and maintenance of neuromuscular junctions and axonal regeneration, seems to be a common response of cranial motoneurons after axotomy . ExtraocAxotomized extraocular motoneurons also showed a marked decrease in their cholinergic phenotype 15 days after lesion, which was completely restored at longer post-lesion times A. The doTo summarize, expression of TrkB mRNA resulted significantly increased in rat extraocular motoneurons after enucleation whereas expression of TrkA and TrkC mRNAs were decreased. This indicates that, among neurotrophins, BDNF might have a main role in the restoration of the cholinergic phenotype as well as in the survival and regeneration of the axotomized motoneurons. We can conclude that extraocular motoneurons differentially modify their requirement of neurotrophins as a consequence of their target removal.Dependence on neurotrophic supply for motoneuronal survival varies throughout maturation. During development, motoneurons are strongly dependent on neurotrophic support arriving from the target muscle for survival, and any interruption of this retrograde flow leads to a massive loss of motoneurons. As motoneurons mature, they lose their dependence on neurotrophic factors for survival, but when they are disconnected from their target, they experiment several alterations in electrophysiological properties and protein expression that can be recovered if they are provided with a new target ,103,104,In the same way, extraocular motoneurons depend on their target muscles for survival during postnatal development, but this dependence is lost with maturation . PreviouNeonatal enucleation in P0 resulted in a massive death of approximately 65% of extraocular motoneurons by 10 days after lesion . The exoThe large percentage of survival obtained after the administration of NGF was surprising, as this result contrasts with previous findings showing that NGF is unable to rescue immature spinal or facial motoneurons in either lesioned neonatal rats or cultures ,112,115.We also found that the administration of BDNF to axotomized neonatal extraocular motoneurons was very effective in rescuing these cells from cell death. The effect of BDNF on survival of lesioned motoneurons has been studied in other neonatal models, resulting in the prevention of the axotomy-induced cell death of facial and spinal motoneurons ,111,113.In agreement with our data in extraocular motoneurons , NT-3 apAs mentioned previously, axotomy produces a transient but reversible loss of the cholinergic phenotype in extraocular motoneurons of the neonatal and adult rat . We founThe downregulation in ChAT is a common phenomenon described not only in the oculomotor system, but also in hypoglossal, facial and spinal motoneurons ,125,126.In neonatal rats, the effect of the administration of neurotrophins on extraocular motoneuron survival at a longer post-lesion time revealed that the prevention of motoneuronal death observed 10 days after axotomy was also present by 30 days post-lesion . These rOur results have shown that motoneuronal death in neonatal animals after axotomy occurred mainly in the first 10 days after lesion, consistent with observations made by other authors . In addiIn conclusion, our results showed that the administration of the neurotrophins NGF, BDNF or NT-3 were able to rescue extraocular motoneurons from axotomy-induced cell death after enucleation performed in newborn rats, showing long-lasting neuroprotective actions. NGF was the most effective neurotrophin in preventing death of axotomized extraocular motoneurons, followed by BDNF, while NT-3 showed the least effect as a neuroprotective factor. In addition, NGF and BDNF prevented the downregulation in ChAT expression induced by axotomy, though NT-3 failed to maintain the cholinergic phenotype of these motoneurons. It is remarkable the high efficacy of NGF as a neuroprotective factor for injured extraocular motoneurons in contrast with the results obtained in other motoneuronal types.As stated above, axotomy induces a plethora of changes in the damaged motoneurons, including modifications at both the structural and functional level ,130, whiIn the case of the oculomotor system, the fact that, first, extraocular motoneurons express the three Trk receptors, and second, their expression is modulated in response to target depletion, let us argue for a principal role of neurotrophins in the maintenance of oculomotor circuitry and the establishment of the adequate firing signals that govern all types of eye movements. If this hypothesis is correct, then not only neurotrophin removal by target depletion would diminish those eye-related firing signals, but also the exogenous administration of neurotrophins would be enough to restore normal firing after the interruption of the normal muscle-motoneuron retrograde trophic signaling.To test this prediction, different neurotrophins were administered to axotomized abducens motoneurons. In a first set of experiments, we injected either BDNF, or NT-3, or a combination of both neurotrophins, to the distal stumps of sectioned axons, following two different experimental paradigms: in the first one, we administered the neurotrophin immediately following axotomy, to test the maintenance of motoneuron properties; in the second one, we first axotomized motoneurons and then checked whether neurotrophins could revert the effects of the lesion. To prevent lesioned motoneurons to establish contacts with new targets, we developed an administration device for chronic neurotrophin delivery, which allowed controlling the extracellular environment that bathes the axonal stumps . In a seWe found that BDNF and NT-3 could not only prevent, but also revert, the effects of axotomy, although only partially. Thus, none of them, when administered alone, was able to maintain or restore completely motoneuron synaptic inputs, and thus, firing pattern. Instead, the administration of either BDNF or NT-3 produced complementary effects on the maintenance/recovery of motoneuron discharge activity, and, indeed, the combined administration of both neurotrophins led to a complete functional and morphological restoration of normal motoneuron characteristics  see Fig. NeurotrControl abducens motoneurons exhibit a typical tonic-phasic firing pattern, as recorded in vivo under alert conditions A. AxotomNeurotrophin expression is strongly affected by modification in synaptic activity, and vice versa, changes in neurotrophin availability can modify synaptic transmission ,140. In In abducens motoneurons, NT-3 produced specifically the recovery of the phasic pattern of firing. Phasic firing is coded through the combined action of pontine excitatory and inhibitory reticular neurons ,32,146, On the other hand, BDNF mediates tonic firing of abducens motoneurons as well as the maintenance of related synaptic inputs. The tonic component is codified by a velocity-to-position integrator  located Besides reticular and prepositus afferences, abducens motoneurons are also innervated by the medial vestibular nucleus, which provides reciprocal, excitatory-contralateral/inhibitory-ipsilateral input to the abducens motoneurons see . Thus, vAltogether, it can be concluded that BDNF and NT-3 exert their influence on different synaptic inputs to abducens motoneurons and therefore, the administration of only one of these molecules re-establishes partially the discharge activity of axotomized motoneurons. Complementary and additive effects of BDNF and NT-3 are revealed when both factors are administered simultaneously, leading to the complete recovery of axotomized motoneuronal firing.NTR), we combined the neurotrophin with two different drugs: K252a, a selective inhibitor in vivo and in vitro of Trk action [NTR [Skeletal muscle expresses NGF exclusively during development . In the k action ,137,138,ion [NTR .NTR, can produce cell death and massive pruning in developing retinal cells and other neurons lacking TrkA [NTR is not always detrimental for neurons. This receptor plays an important role increasing TrkA efficiency to enhance cell survival during development and in the adult [Although it has been previously described that NGF, acting through its low affinity receptor, p75ing TrkA ,164, thehe adult ,166. In he adult ,168,169.he adult .NTR [NTR dependent, as it is the NGF dependent glutamate release from cerebellar neurons [NTR alone was sufficient to restore the firing sensitivity of the motoneuron, but when acted together with the TrkA receptor, the effects were additive, resulting in sensitivities that rose above control.Administration of NGF to the nerve stump of abducens motoneurons immediately after the lesion, not only prevented the decay in eye position and velocity sensitivities caused by axotomy C,D that NTR . In agreNTR  showed t neurons  or dopam neurons . In our  neurons . In thisNTR. Furthermore, when both types of NGF receptors were blocked, the recruitment threshold returned to axotomized values. Since this variable is related to the signals that the cells receive, NGF-related high recruitment threshold registered on axotomized abducens motoneurons might be due to changes in the balance between inhibitory vs. excitatory afferences. In fact, these cells showed ample inhibition, as demonstrated by longer firing pauses during spontaneous eye movements  channel, and thus is involved in the maintenance of the firing regularity of these cells in the adult cerebellum [NTR [Finally, treatment with this neurotrophin produced changes in the variability of the firing discharge of abducens motoneurons. To study these changes we analyzed and compared the coefficient of variation  in the frequency range where this variable was relatively stable, that is, between 30 and 80 sp/s G. While rebellum . Moreoverebellum ,192. Onerebellum . In primlum [NTR ,194 or Tlum [NTR ,196,197 lum [NTR ). Since lum [NTR ,201,202 lum [NTR ,204, furNTR. Thus, while TrkA signaling supports synaptic afferences and regulates the eye-related burst and tonic signals of abducens motoneurons, p75NTR activation affects the recruitment threshold and the firing regularity of these motoneurons.In summary, extraocular motoneurons are peculiar in the sense that they respond to NGF, which is not the case for other motoneuronal types. The administration of NGF to axotomized abducens motoneurons not only recovers the tonic and the phasic components of the discharge, but even increases both components above control values. Using selective blockers, we have demonstrated different actions mediated by NGF depending on the receptor activated, i.e., TrkA or p75We have shown that target-derived dependencies extend from the mere survival during development and early postnatal life to the regulation of phenotypical properties in the adult state. Neurotrophins seem to play an essential role during both phases in the life of a motoneuron. In this section we might like to speculate that access to different sources and combinations of trophic factors could lead to variations in the expression of physiological  properties of motoneurons.Although the division of labor into different classes of motoneuron and muscle fiber is well established from the early work in spinal cord ,206, theOur past work summarized in We have shown that BDNF induces tonic firing in motoneurons via TrkB receptors, whereas NT-3 induces phasic firing through TrkC receptors . We postNTR receptors, whose expression is modulated in response to injury. In this review, we have focused on the oculomotor system, in which neurotrophins act as key regulators of cell survival and neuron function and structure, but we also have extended and discussed our results to those found in other systems.We have shown that target cells are powerful regulators of the phenotypical properties of innervating cells not only through early stages of development but also later throughout life in the adult state. Target disconnection by axotomy leads to a myriad of alterations that may range from cell death to physiological, metabolic and structural perturbations. The administration of neurotrophins to axotomized neurons can restore, at least in part, some of the axotomy-induced alterations, although each neurotrophin recovers different aspects of cell physiology. Moreover, neurotrophins show complementary and additive effects and may mediate different actions through Trk and p75


Osgood-schlatter disease, non-articular osteochondrosis, is characterized by pain of anterior tibial tuberosity (TTA), which mainly affects the growing adolescent sportsman. It corresponds to “chronic lesions, due to microtrauma of repeated tractions on the area of insertion of the patellar tendon at the level of the anterior tibial tuberosity”. This condition remains benign if the young patient rests well, the only treatment proven effective to avoid complications such as the removal of the anterior tibial tuberosity. The case reported in this article illustrates this complication. He is a 15-year-old boy, followed for Osgood-Schlatter disease, who did not respect the advice given by his attending physician; and who was the victim of an accident during a soccer match: brutal contraction of the quadriceps during an upset extension of the left knee, causing pain and total functional impotence. The examination showed a large oedematous knee with pain on palpation of TTA, with a deficit of active extension of the knee (A). Standard radiographs of the left knee showed avulsion of the anterior tibial tuberosity (B). The treatment was surgical with reduction of the fragment and osteosynthesis by two cortical screws through the median approach (C). With a follow-up of 6 months, the knee mobility was normal and the fracture consolidated. Osgood-Schlatter disease, a pathology of growth, is generally of good prognosis, resolving spontaneously with skeletal maturity. However, if the young athlete does not change his practice, he may seriously aggravate it  and therefore with much more serious consequences for its sporting recovery.


The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed. Premenstrual dysphoric disorder (PMDD) affects 2%–5% of women in their reproductive years, and is characterized by affective, behavioral and somatic symptoms that recur monthly in the luteal phase of the menstrual cycle and resolve during menstruation. The affective symptoms, which are the most debilitating in the syndrome, include marked irritability or anger, depressed mood, anxiety, tension, mood lability, difficulty concentrating, and feeling overwhelmed or out of control ,2.Behavioral and somatic symptoms contribute to impairment, and can include decreased interest, sleep and appetite disturbances, fatigue, lethargy, poor concentration, swelling, and pain . PrecediWhile constituting only 10% of brain volume, the cerebellum contains the majority of neurons in the brain, about 3.6 times the number in the cerebral cortex. This ratio of cerebellar to neocortical neurons is conserved across mammalian species, indicating a co-evolution that is consistent with a coordinated integrative functioning of the two structures . MoreoveConsistent with this link to the cerebral cortex, the historical view of the cerebellum as a motor machine has been expanded to encompass a more comprehensive role, including the modulation of cognitive and affective behavior. Based in part on observations of Harry Harlow’s socially-deprived monkeys , James PEarly clinical support for this idea came from studies in which the deep cerebellar regions were stimulated in patients with behavioral disorders, including psychosis, aggression, and epilepsy –12. StimIn 1998, damage to the posterior but not the anterior cerebellar lobe was shown to result in a cerebellar cognitive affective syndrome (CCAS), characterized by executive, visuospatial, linguistic and affective deficits . FurtherThe Dysmetria of Thought Theory ,19 postuThe prediction of topographic organization of function within the cerebellum was evaluated in a 2009 meta-analysis of neuroimaging studies reporting cerebellar activation during tasks that could be considered to involve one primary category of processing . EmotionA study of neural response to emotional faces, measured with functional magnetic resonance imaging (fMRI), found activation in lobules VI, VII and the posterior vermis of the cerebellum . BecauseIn another consensus paper, 16 experts on cerebellar physiology agreed that the cerebellum serves as a “supervised learning machine” that automates sequences of behaviors, thoughts and affects through the evolutionary adaptation and expansion of more primitive motoric internal control models . The autThis view fits well with a modification of earlier hypotheses of cognitive aging (reviewed by West ), which Using source-based morphometry, it was shown that age-related changes in processing speed were best predicted by structural changes both in the frontal lobe and in cerebellar networks . The preOver the past 15 years, a variety of brain imaging techniques have been applied to the study of PMDD and related disorders . The tecMRS has been used in relevant preliminary studies of brain metabolites, and the neurotransmitters γ-aminobutyric acid (GABA) and glutamate. In the first study , MRS wasAnother small MRS study quantified GABA, a neurotransmitter that had been implicated in anxiety and depressive disorders, including PMDD . Within In another MRS study, there was a decline in glutamate levels from the follicular to the luteal phase, measured as the ratio of glutamate to creatinine, and the change was equivalent in 12 women with and 13 women without PMDD . The finPrompted by the clinical response of PMDD patients to selective serotonin reuptake inhibitors –52, posi11C-labeled 5-hydroxytryptophan, the immediate biosynthetic precursor of serotonin, in whole brain, dorsolateral and medial prefrontal cortices, putamen and caudate in women with PMDD -hexamethylpropylene amine oxime (HMPAO). Changes in regional cerebral blood flow (rCBF) from the asymptomatic follicular phase to the symptomatic late luteal phase were quantified in seven women with PMS and matched healthy controls. Regions of interest were drawn on the images to measure radioactivity in frontal, temporal and a region including both parietal and occipital cortices, the thalamus, and the basal ganglia of each hemisphere. Radioactivity in the regions was normalized to counts in the cerebellum. There were marked decreases in this normalized measure of rCBF in the temporal lobes on the premenstrual compared to the postmenstrual scan in PMS patients but not in controls, and the temporal lobe rCBF changes were correlated with the changes in self-reports of depressive symptoms in the PMS patients fluorodeoxyglucose (FDG) to assess regional brain glucose metabolism and self-rated mood during performance of an affectively neutral vigilance task in women with PMDD and healthy controls H2O and PET while the fMRI blood-oxygen level dependent (BOLD) signal was also quantified. The paradigm was repeated during ovarian suppression, and two subsequent conditions in which estrogen (mid follicular levels) or progesterone , randomized for order, were replaced. As before [In 1998, ovarian suppression induced by a gonadotropin-releasing hormone analog was used to show that PMS symptoms are an abnormal response to normal hormonal changes . The invs before , premensAcross all three hormone conditions, working memory generated greater PET activation in women with PMDD than controls in nine regional clusters. The largest cluster, comprising 53% of the voxels in all of the nine clusters, was in the cerebellum. Notably, the cerebellar effect was stronger in the PET assessment. Task-related activation in PMDD patients was correlated with a measure of psychosocial/somatic impairment, serving as an index of disease severity, in 10 clusters that overlapped with the areas of greater activation in PMDD patients. Frontal cortex and cerebellum represented, respectively, 62% and 32% of the voxels where impairment was correlated with activation related to working memory. PMDD duration and age of onset also were correlated with task-related activation and the extent to which activation was greater in PMDD patients than controls bilaterally in both structures  . All fivIt is unfortunate that in the initial SPECT study, the cerebellum was chosen as the reference region, preventing evaluation of abnormalities in cerebellar rCBF, and possibly influencing the measures of perfusion in other structures . The menIn summary, SPECT/PET studies of PMDD point to differences in cerebral blood flow and glucose metabolism as functional indices in women with PMDD. The evidence is that the differences are predominantly in the cerebellum, and specifically in anatomical regions associated with emotional processing and control.The first fMRI study of premenstrual dysphoria presented emotionally positive, negative and neutral words to women with PMDD and healthy controls, using a Go/NoGo paradigm designed to probe emotional and inhibitory processing . AnalyseAnother group used a Go/NoGo task paired with fMRI to explore brain activity during response inhibition in 14 women with PMDD and 13 healthy controls . ParticiAmygdala reactivity was contrasted in women with and without PMDD by pairing fMRI with an emotional face-matching task . ContrarIn another fMRI study, women with and without PMDD were evaluated during valence-cued anticipation and presentation of emotional images in 14 regions of interest in both hemispheres : amygdalIn the above-mentioned study of Baller and associates, the working memory task generated greater activation in women with PMDD than controls, assessed with fMRI across the one asymptomatic and the two symptomatic hormone conditions, in 8 regional clusters . The larAcross the fMRI studies, the most consistent abnormality associated with premenstrual dysphoria was greater frontal activation, particularly in the dorsolateral prefrontal cortex, in PMDD patients as compared to controls. This was measured when patients were symptomatic in response to affectively negative words , or antin = 12) and without (n = 13) PMDD, tissue composition in three compartments  was compared in the two groups within medial prefrontal cortex using a double-inversion recovery one-dimensional projection method [As part of one of the MRS studies of women with  of high-resolution structural MRI scans was used to compare regional gray matter in the brains of 15 PMDD patients and 15 healthy women . The PMDOur group also has used optimized VBM with structural MRI to study PMDD . The onlThere are several possible reasons for different results of the two structural brain studies. Notably both studies were of small sample size, and Jeong and associates used a version of the VBM software (VBM2), which did not include the high-dimensional DARTEL normalization designed to improve registration in the version we used (VBM8). This may be important because prior procedures for normalization to whole-brain MRI templates produce inaccuracies especially in the cerebellum ,60. JeonThe finding of preserved cerebellar structure with aging in PMDD warrants replication, but has some interesting implications which will now be discussed. The aforementioned whole-brain structural studies found a greater proportion of voxels with higher rather than lower gray matter in women with PMDD than in healthy controls  ,49. ThisA positive correlation between the duration of bipolar illness and the degree of bilateral cerebellar GM deficits was observed in medication-naive patients , and oneBecause cognitive complaints are common in PMDD, but have been difficult to quantify, we suggested that most women with PMDD exert greater effort, or other compensatory mechanisms that increase cerebellar activity, in order to maintain cognitive functioning during symptomatic periods, which can total over 3000 days over the lifetime . Since rCerebellar hyperactivity also may contribute to the higher serum levels of several neuroprotective factors that have been reported in women with PMDD relative to healthy controls ,72, and The cerebellum also contains the highest density of brain receptors for the neuroprotective hormone leptin . Leptin n = 21) were reported to have higher plasma leptin than healthy subjects (n = 22) in both follicular (P < 0.001) and to a lesser extent luteal (P < 0.08) assessments [Woman with PMS , this suggests the possibility of different age trajectories for the ability of BOLD measurement to index neural activity in the two structures.An interesting question is why cerebellar abnormalities in PMDD are more prominent for PET-assessed measures of activation, where they represent the largest and strongest differences in both glucose metabolism and blood flow, as compared to abnormalities accessed via the BOLD signal, a more indirect measure of neural activity that depends on neurovascular coupling. The origins of the BOLD fMRI response are complex, and not completely understood , but by This notion is supported by studies of age-related variability in the moment-to-moment BOLD signal. The mean BOLD signal is currently the most utilized measure of brain function in neuroimaging, including all of the fMRI studies reviewed here. It has been reported, however, that over five times as much of the variability in participants’ age can be predicted by the standard deviation of the BOLD signal (BOLD-SD) than can be predicted by the mean, and that BOLD-SD is also a better predictor than BOLD-mean of performance on cognitive tasks ,102. In Combined with strong PET evidence for greater activation of “emotional” cerebellum in women with PMDD than controls ,54, sparTaken as a whole, brain imaging studies best support the hypothesis that premenstrual dysphoria is associated with increased activity of the dorsolateral prefrontal cortex and lobules VI and VII of the posterior cerebellum. Both brain regions have been associated with emotional processing and mood disorders, working memory and executive functions. Combined with the above discussed recent expansion of current understanding of cerebellar physiology to include the modulation and fine-tuning of all forms of brain computation, this suggests that increased activity within these two regions in PMDD patients probably represents coactivation of both regions within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Future brain imaging studies of premenstrual dysphoria should explore the functioning of this cerebro-cerebellar circuit.


Optimal maternal body composition during pregnancy is a public health priority due to its implications on maternal health and infant development. We therefore aimed to conduct a systematic review of randomised, controlled trials, and case–control and cohort studies using lifestyle interventions to improve body composition in developing countries. Of the 1 708 articles that were searched, seven studies, representing three countries , were included in the review. Two articles suggested that intervention with physical activity during pregnancy may significantly reduce maternal weight gain, and five studies were scored as being of poor quality. This systematic review highlights the lack of research within developing countries on lifestyle interventions for the management of excessive weight gain during pregnancy. Similar reviews from developed countries demonstrate the efficacy of such interventions, which should be confirmed using well-designed studies with appropriate intervention methods in resource-limited environments. Both developed and developing countries are experiencing a rapid increase in the prevalence of obesity, which places affected individuals at an increased risk for a number of different diseases, including hypertension, diabetes, heart disease, asthma and cancer.3Especially alarming is the high prevalence of overweight and obesity among women of childbearing age in both developed and developing countries. Around 12 to 38% of pregnant women in developed countries,Obesity during pregnancy is associated with an increased risk for maternal and neonatal complications. The associated adverse maternal effects of obesity during pregnancy include miscarriage, pre-eclampsia, gestational diabetes mellitus, infection, venous thromboembolism and haemorrhage.9Both under- and overweight pose a risk to the mother and child during and after birth.The health risks of maternal obesity and excessive gestational weight gain to the mother and baby pose significant demands on the healthcare system, with an increased need for additional resources in both primary and secondary care settings.Five electronic databases were searched; these included Public/ Publisher MEDLINE (PubMed), SCOPUS, a bibliographic database containing abstracts and citations for academic journal articles, Biomed Central, the Cochrane Library and the Cumulative Index to Nursing and Allied Health (CINHAL). Twenty-four search terms, with varying combinations, encompassing pregnancy, obesity/overweight, diet/nutrition, physical activity and developing countries , were usRandomised, controlled trials (RCTs), case–control studies and cohort studies that were performed in developing countries and which investigated overweight/obesity in pregnant women and/or lifestyle interventions during pregnancy were considered eligible. Investigations performed in developing countries and the following types of studies were not eligible for inclusion: reviews, position statements/guidelines, reports, epidemiological studies, observational studies and prevalence studies.The literature search was performed independently by two authors, Shelley Macaulay (SM) and Estelle Watson (EW). The search results obtained from each of the five electronic databases were pooled and duplicates were removed. At the first step, titles were screened for eligibility. Following this, the abstracts of those that were considered eligible were then obtained and read. Fulltext articles of the abstracts that fulfilled the inclusion criteria were then obtained and read. In addition, the reference lists of appropriate full-text articles were hand-searched for further relevant articles.Data were extracted from the full-text articles by four of the reviewers: Phillipe Gradidge (PG), Elena Libhaber (EL), EW and SM. For each included article, data were extracted for country, region, sample size, gestational age, BMI, intervention details and outcomes.The quality of each included article was assessed by three authors  using the Cochrane Risk of Bias Tool . In accordance with the risk-assessment checklist, each study was assessed on: sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other threats to validity.The studies were classified as being good, average or poor quality based on how many of the above criteria were met. Good-quality articles met five or more of the above criteria, average-quality articles met three to four of the above criteria, and poor-quality ones met less than three of the above criteria.A total of 6 988 records were identified from the five databases, after which 5 280 duplicates were removed. The title screen therefore involved 1 708 articles, of which 73 were considered appropriate, and their abstracts were obtained and reviewed. After reviewing the abstracts, 23 full-text articles were obtained and read. In addition, the bibliography of the full-text articles were hand-searched for further appropriate articles. Six additional articles were obtained through hand-searching. Together with the hand-searched articles, a final total of seven articles were considered eligible for this systematic review. Articles that were excluded at this stage were those conducted in high-income countries and articles involving women post delivery of their babies .The results of the Cochrane Risk of Bias Tool are displayed in The articles comprised five RCTs from Brazil and Iran and two non-RCTs from Argentina and Iran, as shown in A study by Prevedel et al.A study by Cavalcante et al.18 also used an intervention of aquatic exercise during pregnancy to determine its effectiveness on maternal outcomes. No differences were noted between control and intervention groups for weight gain during pregnancy, body fat percentage, fat-free mass or body mass index (BMI).The effects of supervised aerobic exercise on the maternal outcomes of overweight pregnant women were evaluated by Santos et al.Two Iranian interventionsThe intervention that aimed to determine the possibility of improving maternal outcomes using fortified foods11 found that the prevalence of folic acid and serum retinol deficiency decreased, while vitamin A deficiency remained the same post intervention. No differences were noted for body composition, and the proportions of overweight and obesity in the groups were at a moderate level of 20 and 26.3%, respectively, post intervention.Pregnancy appears to be a pivotal time for both maternal and foetal health. Emerging research has highlighted the profound effects of the in utero environment on the lifelong health of the baby. More specifically, both underweight and overweight babies are at risk of obesity later on in life.Maternal obesity is perhaps one of the major causes of intrauterine over-nutrition during pregnancy, and can lead to largefor- gestational-age deliveries. In addition, excessive gestational weight gain in both overweight and normal-weight women has been shown to increase obesity in the offspring in both childhoodDue to the potential health consequences of maternal obesity, pregnancy is a pivotal period to implement health interventions,The type of interventions used to limit weight gain during pregnancy appears to vary widely between studies. In their systematic review of lifestyle interventions in pregnancy, Oteng-Ntim et al.Although previous systematic reviews have analysed the literature dealing with interventions during pregnancy for limiting excessive weight gain,29Although there have been calls to focus interventions on maternal nutrition in order to reduce the risk of obesity later on in life,Despite the growing prevalence of obesity in developing countries and the well-recognised detrimental effects of maternal obesity on both maternal and foetal outcomes, this review demonstrates the lack of pertinent research in this area within developing countries. Two of the studies in our review found an increase in weightKey messages:Lifestyle interventions may be a cost-effective and useful way to manage maternal overweight and obesity as well as gestational weight gainFew good-quality studies assessing the efficacy of lifestyle interventions on maternal body composition have been conducted in developing countriesIn this systematic review of seven studies, two suggested that a physical activity intervention during pregnancy may significantly reduce maternal weight gain; and five were scored as being of poor qualityFuture, well-designed lifestyle-intervention studies aimed at managing maternal body composition are much needed in developing countriesVery few studies exist to address the issues of intervention for obesity and weight gain during pregnancy in developing countries. This review summarises the existing literature, of which 71% were of poor quality. Although our review focused on lifestyle interventions for overweight and obesity during pregnancy, the search yielded only one study that aimed the intervention at overweight women, and 50% of the studies were not primarily measuring weight gain as an outcome. In addition, the studies varied significantly from type of intervention to outcome measure, and additionally, the methodology was often poorly described, making comparative and accumulative analysis difficult.Dietary and lifestyle interventions during pregnancy may well be the key to addressing the prevention of obesity in future generations.This review has highlighted the need for further research, and in particular, carefully designed randomised, controlled trials, addressing primarily the issues of weight gain and obesity in pregnancy. Such studies are essential to determine the effectiveness and safety of appropriate lifestyle interventions during pregnancy in resource-limited settings.


Actinomycosis of the larynx has been rarely reported in the literature and usually occurs in patients with a history of laryngeal carcinoma and radiation therapy. However, its co-existence with chondroradionecrosis due to radiotherapy is even rarer. The most common site of infection is the cervicofacial region, especially in the submandibular area.Here we report a 63-year-old male with a history of chemoradiotherapy because of laryngeal cancer 1 year earlier who presented with laryngeal actinomycosis. After prolonged penicillin-based treatment, the patient underwent thyroid cartilage defect reconstructive surgery because of a laryngocutaneous fistula due to chondroradionecrosis. The diagnosis, work-up, and management of the case are discussed, as well as a review of the literature.Although actinomycotic infection of the larynx is rare, it should be considered in the differential diagnosis of laryngeal complaints, especially in immunocompromised patients. Actinomycosis has rarely been reported to involve the larynx, and usually occurs in patients with a history of laryngeal carcinoma and radiation therapy . The mosA 63-year-old male who first presented with dysphonia with a diagnosis of early-stage glottic cancer  refused to give consent for surgery and instead underwent chemoradiation. The chemoradiation therapy consisted of six chemotherapy and 33 radiotherapy sessions, with a total dose of 70 Gy (at 2.0 Gy/fraction). One year after treatment, the patient complained of neck swelling with mild dysphagia as well as fever and chills, accompanied by a suppurative malodorous discharge from three neighboring fistulas, located at the anterior of the neck.A thorough work-up was conducted to exclude vascular disorders or recurrence of malignancy. Direct laryngoscopy showed swelling of true and false vocal cords on both sides, and a biopsy was taken. Debridement was performed under anesthesia, and cultures and pathology specimens were sent to the laboratory, in addition to fungus smears from the fistula. Pathological examinations of all samples were negative for recurrence of malignancy. Microbiological specimens were also negative. The patient underwent empiric therapy based on consultations with infectious diseases specialists. Histological examination of biopsies revealed actinomycotic colonies in the biopsy specimen with sulfur granuloma. The patient was treated with intravenous penicillin following by long-term oral penicillin therapy for 6 months. The anterior cervical infection and malodorous discharge showed a good response to antibiotic treatment and the inflammation gradually resolved with long-term antibiotic therapy.However, due to incomplete closure of the fistulas and an 8-mm defect in the thyroid cartilage, laryngoscopy and multiple biopsies of the stoma were performed to rule out malignancy. Radiologic and clinical signs were consistent with a diagnosis of laryngeal chondroradionecrosis. Because of laryngo- cutaneous fistula due to chondroradionecrosis, the patient underwent thyroid cartilage defect reconstructive surgery using nasal septum cartilage graft, and the cutaneous defect was repaired with pectoralis major myocutaneous flap transposition. Under general anesthesia, and after appropriate preparation of the surgery sites, the margins of the skin were removed by a senior surgeon . The skin was notably thickened and normal surgical plans were unidentifiable due to previous radiotherapy and long-term infection. The site of the fistula and marginal skin was debrided until bleeding occurred. Fibrotic tissue and necrotic cartilage were also resected .Endolaryngeal mucosa was normal. True vocal cord remnants, surviving after radiation and multiple biopsies, were visible on both sides. Arytenoids were sutured to the lateral sides in order to prevent mucosal prolapse. By measuring the size of the cartilage and skin defect, reconstructions were planned. A cartilage and its attached bony part from perpendicular plate of ethmoid bone, harvested from the nasal septum, were placed on the defect, sutured and fixed to the lateral sides . To assure its survival, the bony part of the graft was covered by the rotated sternocleidomastoid muscle flap from the same side , and a tThe patient stayed in hospital for 6 days and was discharged in a well condition. He was further admitted for monthly follow-up visits. In less than 3 months, the tracheostomy site was closed. Six months after reconstructive surgery, the patient’s airway was patent and video stroboscopy showed normal true vocal cords, false vocal cords, and arytenoid movement, and small granulation tissue on the endolaryngeal mucosa.Actinomycosis is characterized by a subacute or chronic suppurative and granulomatous process caused by anaerobic or microaerophilic/capnophilic bacteria, mainly within the Actinomyces species . Many orClinical observation is the start of the diagnostic process. For instance, cervicofacial actinomycosis should be suspected in patients with persistent or recurrent head and neck swelling, especially in the presence of poor dental hygiene and fistulas (sinus tracts) yielding sulfur granules . DiagnosMost patients, as in our case, have a history of laryngeal carcinoma and radiotherapy and present with an ulceration mimicking a laryngeal cancer relapse, with neither abscess nor sinus tract . A revieThe key principle in the therapy of actinomycosis is to use high doses of antibiotics for a prolonged period  due to induration of infected tissue, a lack of adequate blood supply, and the resulting poor antibiotic penetration into the tissue ,12. AntiActinomycosis of the larynx represents an unusual presentation for a common bacterium comprising the oral and oropharyngeal florae ,15. ManyAn important point is to differentiate chondroradionecrosis from tumor recurrence since the symptoms of necrosis can mimic the recurrence of cancer. The computed tomography (CT) appearance of laryngeal chondroradio- necrosis is nonspecific. Despite repeated negative biopsies, it may be necessary to perform total laryngectomy when there is concern about malignant remnants or when the larynx is nonfunctional. Rowley et al. reported seven cases of laryngectomy due to chondroradionecrosis in whom histology revealed residual or recurrent carcinoma in two cases . SalvageReconstructive surgery with pectoralis major muscle transposition after excision of the necrotic skin of the neck and destroyed thyroid cartilage has been reported to have acceptable outcomes in terms of laryngeal function and cosmetic appearance , 18. To Although actinomycotic infection of the larynx is rare, it should be considered in the differential diagnosis of laryngeal complaints, especially in immunocompromised patients. Management of chondroradionecrosis as a complication of chemoradiation therapy in a patient with laryngeal carcinoma can be challenging for ear, nose, and throat (ENT) and head and neck surgeons. Thyroid cartilage defect reconstructive surgery using a nasal septum cartilage graft and myocutaneous flap transposition may be considered acceptable surgical management.


Head and neck squamous cell carcinoma is the sixth leading cause of cancer worldwide. The most common risk factors are carcinogens , and infection of the human papilloma virus. Surgery is still considered as the treatment of choice in case of head and neck cancer, followed by a reconstructive surgery to enhance the quality of life in the patients. However, the widespread use of artificial implants does not provide appropriate physiological activities and often cannot act as a long-term solution for the patients. Here we review the applicability of multiple stem cell types for tissue engineering of cartilage, trachea, vocal folds and nerves for head and neck injuries. The ability of the cells to self-renew and maintain their pluripotency state makes them an attractive tool in tissue engineering. Head and neck cell carcinoma (HNSCC), the sixth leading cause of cancer worldwide, represents approx. 4 % of all malignant tumors and 5 % mortality  and chemotherapy are commonly used. Such proceedings provide the best chance to cure the patients and increase their overall survival rate  and induced pluripotent stem cells (Murry and Keller One of the procedures to obtain embryonic cells (ES) is the nuclear transfer of the somatic cell into an oocyte with previously removed nuclear genetic material. The mechanism of parthenogenesis, i.e. transformation of the oocyte in the embryo without fertilization using a defined chemical protocol, is also used Condic . In 2006With advancement in technologies, there is a growing potential for using iPSC and ES cells in tissue engineering as a component of constructs engineered at the cellular and basic tissue levels  , which results in decreased differentiation capacity and increased proliferation rate. Moreover, changes in culture conditions in vitro could contribute to epigenetic instability, and long-term culture may increase the risk of these anomalies. Another concern is the process of reprogramming, which may lead to the creation of genetically unstable induced pluripotent stem cells. High costs of reprogramming and increase risk of teratoma formation are also an important issues , biocompatibility, and sterility. The mechanical requirements such as plasticity, stability or flexibility are also important. The aim of tissue engineering is to restore, defend (avoid disease progression) and/or improve the function of the damaged tissues and organs. The material must allow for cell adhesion, supplying the growth factors, and excretion of the metabolic products  are highly expressed in the MSCs cells. However no expression of haematopoietic lineage markers such as CD14, CD34, and CD45 was confirmed  from the bone marrow. MSCs play a pivotal role as support cells for haematopoiesis. They function as a reservoir of cells to regenerate various types of mesenchymal tissues Gerson . The numCsaki et al.  summarizTissue engineering combined with gene therapy results in a modified and novel tissue engineering technology. Guo et al.  achievedBesides cartilage, other tissues are also an attractive target for tissue engineering. In the head and neck area, primary cancers of the trachea are rare but are characterized by a high mortality rate. The gold standard of treatment for these tumors is surgical resection with primary reconstruction  guarantees increasing host stem cells deployment inside the implanted biopolymers -co-poly-(3-caprolactone)/collagen (PLCL/Coll) nanofibrous scaffolds. The authors suggested the potential application of mesenchymal stem cells towards nerve regeneration. Both MSC and iPSC have the potential for treatment of traumatic injury of the nervous system. Kuo and Chen . Prabhakaran et al.  investigand Chen  performeand Chen . The preand Chen  demonstrand Chen  who indiN-terminus LDLK-12 core with the KLPGWSG peptide self-assembling peptides) scaffold enhances the neuronal differentiation of neural stem cells. These indications make KLPGWSG and the Ac-KLP peptide promising candidates to be used in stem cell therapies for nervous regeneration  nerve conduits containing bioactive acidic fibroblast growth factor 1 could be fabricated by micropatterning techniques, open plasma activation, and immobilization, which, combined with aligned stem cells, may synergistically contribute to the regeneration of the severely damaged peripheral nerve.Neural stem cells (NSCs) hold great promise for cell therapies and tissue engineering. NSCs occurs in the nervous system and can differentiate into neurons, astrocytes, and glial cells. They were used in tissue-engineered studies due to their multipotent capacity, high immigration ability, and low immunogenicity. Caprini et al.  synthesiThe hESCs, iPSCs and other types of stem cells have great potential in tissue engineering. These cells can differentiate between a variety of cell types like cartilage, neural, or muscle cells. This unlimited source, and introduced improvements of the use of stem cells with a proper scaffold component, increases the chances of for greater usage in the future. Promising results indicate that stem cells have therapeutic potential for tissue engineering applications. However, further studiessss are required to estimate the safety of the therapeutic use of stem cells in humans.


Dear Editor,A 55-year-old male presented with dysuria, polyuria, nocturia, and decreased urinaryflow. The physical examination revealed a large left-sided inguinoscrotal hernia thatwas irreducible, together a slightly enlarged prostate. Laboratory tests showed mildanemia and pyuria, as well as elevated concentrations of urea and creatinine. Ultrasoundshowed a left-sided inguinoscrotal hernia that had insinuated itself into the bladder,with dilation of the distal ureteral segment and two calculi, one measuringapproximately 2.2 cm, at the ureterovesical junction, and the other, of similardiameter, free within the bladder .Compute. Inthe past, inguinoscrotal hernias of the bladder were diagnosed intraoperatively orthrough excretory urography and produced complications such as urinary tract infectionand obstructive uropathy-4. The preoperative diagnosis of a herniainsinuating itself into the bladder is very important for the urologist, guiding thesurgical planning.Bladder hernias, which are not uncommon, protrude into the femoral canal in women andinto the inguinal canal in men. Ultrasound is anoninvasive test, useful for identifying a herniated bladder and its components, as wellas the continuity of the bladder with the non-herniated portion within the pelvis, andcan be used in emergency settings. The use of multidetector CT facilitates the diagnosisand in traumatic cases can show other herniations in the abdominal wall, through coronaland sagittal reconstructions. Because of its high resolution, multidetector CT allowsbetter visualization of the relationship between the bladder and the inferior epigastricvessels, thus facilitating the differentiation among direct inguinal, indirect inguinal,and femoral hernias. Magneticresonance imaging can be used in place of CT. The combination of ultrasound and magneticresonance imaging is useful for the noninvasive, nonradiative evaluation of alterationsin the scrotum.The examinations most commonly performed in order to diagnose inguinoscrotal hernias areultrasound and CTIn the case presented here, we have described the importance of ultrasound for thediagnosis of a calculus within the lumen of the bladder and another at theureterovesical junction, with upstream dilation of the renal excretory pathway, and forconfirmation of the CT findings, which showed a calculus in the bladder and another atthe left ureterovesical junction, contributing to the selection of appropriate practiceand the success of the surgical procedure. In our review of the literature, we found noother reports of a ureteral calculus in a patient with inguinoscrotal hernia of thebladder.