RESUMEN

Auditory processing is widely understood to occur differently in autism, though the patterns of brain activity underlying these differences are not well understood. The diversity of autism also means brain-wide networks may change in various ways to produce similar behavioral outputs. We used larval zebrafish to investigate auditory habituation in four genetic lines relevant to autism: fmr1 , mecp2 , scn1lab and cntnap2 . In free-swimming behavioral tests, we found each line had a unique profile of auditory hypersensitivity and/or delayed habituation. Combining the optical transparency of larval zebrafish with genetically encoded calcium indicators and light-sheet microscopy, we then observed brain-wide activity at cellular resolution during auditory habituation. As with behavior, each line showed unique alterations in brain-wide spontaneous activity, auditory processing, and adaptation in response to repetitive acoustic stimuli. We also observed commonalities in activity across our genetic lines that indicate shared circuit changes underlying certain aspects of their behavioral phenotypes. These were predominantly in regions involved in sensory integration and sensorimotor gating rather than primary auditory areas. Overlapping phenotypes include differences in the activity and functional connectivity of the telencephalon, thalamus, dopaminergic regions, and the locus coeruleus, and excitatory/inhibitory imbalance in the cerebellum. Unique phenotypes include loss of activity in the habenula in scn1lab , increased activity in auditory regions in fmr1, and differences in network activity over time in mecp2 and cntnap2 . Comparing these distinct but overlapping brain-wide auditory networks furthers our understanding of how diverse genetic factors can produce similar behavioral effects through a range of circuit- and network-scale mechanisms.

RESUMEN

Animals receive a constant stream of sensory input, and detecting changes in this sensory landscape is critical to their survival. One signature of change detection in humans is the auditory mismatch negativity (MMN), a neural response to unexpected stimuli that deviate from a predictable sequence. This process requires the auditory system to adapt to specific repeated stimuli while remaining sensitive to novel input (stimulus-specific adaptation). MMN was originally described in humans, and equivalent responses have been found in other mammals and birds, but it is not known to what extent this deviance detection circuitry is evolutionarily conserved. Here we present the first evidence for stimulus-specific adaptation in the brain of a teleost fish, using whole-brain calcium imaging of larval zebrafish at single-neuron resolution with selective plane illumination microscopy. We found frequency-specific responses across the brain with variable response amplitudes for frequencies of the same volume, and created a loudness curve to model this effect. We presented an auditory 'oddball' stimulus in an otherwise predictable train of pure tone stimuli, and did not find a population of neurons with specific responses to deviant tones that were not otherwise explained by stimulus-specific adaptation. Further, we observed no deviance responses to an unexpected omission of a sound in a repetitive sequence of white noise bursts. These findings extend the known scope of auditory adaptation and deviance responses across the evolutionary tree, and lay groundwork for future studies to describe the circuitry underlying auditory adaptation at the level of individual neurons.

RESUMEN

Contained electromechanical morcellation has emerged as a safety approach for laparoscopic myomatous tissue retrieval. This retrospective single-center analysis evaluated the bag deployment practicability and safety of electromechanical in-bag morcellation when used for big surgical benign specimens. The main age of patients was 39.3 years (range 21 to 71); 804 myomectomies, 242 supracervical hysterectomies, 73 total hysterectomies, and 1 retroperitoneal tumor extirpation were performed. A total of 78.7% of specimens weighed more than 250 g (n = 881) and 9% more than 1000 g. The largest specimens, weighing 2933 g, 3183 g, and 4780 g, required two bags for complete morcellation. Neither difficulties nor complications related to bag manipulation were recorded. Small bag puncture was detected in two cases, but peritoneal washing cytology was free of debris. One retroperitoneal angioleiomyomatosis and three malignancies were detected in histology (leiomyosarcoma = 2; sarcoma = 1); therefore, patients underwent radical surgery. All patients were disease-free at 3 years follow-up, but one patient presented multiple abdominal metastases of the leiomyosarcoma in the third year; she refused subsequent surgery and was lost from follow-up. This large series demonstrates that laparoscopic bag morcellation is a safe and comfortable method to remove large and giant uterine tumors. Bag manipulation takes only a few minutes, and perforations rarely occur and are easy to detect intraoperatively. This technique did not result in the spread of debris during myoma surgery, potentially avoiding the additional risk of parasitic fibroma or peritoneal sarcoma.

RESUMEN

Autism is a complex condition with many traits, including differences in auditory sensitivity. Studies in human autism are plagued by the difficulty of controlling for aetiology, whereas studies in individual rodent models cannot represent the full spectrum of human autism. This systematic review compares results in auditory studies across a wide range of established rodent models of autism to mimic the wide range of aetiologies in the human population. A search was conducted in the PubMed and Web of Science databases to find primary research articles in mouse or rat models of autism which investigate central auditory processing. A total of 88 studies were included. These used non-invasive measures of auditory function, such as auditory brainstem response recordings, cortical event-related potentials, electroencephalography, and behavioural tests, which are translatable to human studies. They also included invasive measures, such as electrophysiology and histology, which shed insight on the origins of the phenotypes found in the non-invasive studies. The most consistent results across these studies were increased latency of the N1 peak of event-related potentials, decreased power and coherence of gamma activity in the auditory cortex, and increased auditory startle responses to high sound levels. Invasive studies indicated loss of subcortical inhibitory neurons, hyperactivity in the lateral superior olive and auditory thalamus, and reduced specificity of responses in the auditory cortex. This review compares the auditory phenotypes across rodent models and highlights those that mimic findings in human studies, providing a framework and avenues for future studies to inform understanding of the auditory system in autism.

Asunto(s)

Trastorno Autístico , Animales , Percepción Auditiva/fisiología , Electroencefalografía/métodos , Potenciales Evocados Auditivos del Tronco Encefálico , Humanos , Ratones , Ratas , Roedores

RESUMEN

This study was conducted to provide information regarding the chemistry-including structure, synthesis, formulation, and mechanical properties-of two types of chemically modified anti-adhesion gels made of hyaluronic acid. Gel A (Hyalobarrier®) and gels B and C (HyaRegen® and MetaRegen®) that are used in postsurgical adhesion prevention. To date, little information is available on their physicochemical attributes. This information is necessary in order to understand the differences in their in vivo behavior. METHODS: Comparative analyses were conducted under laboratory-controlled conditions, including measuring the shear viscosity, storage modulus G', peel strength, and extrusion forces. RESULTS: All polymers exhibited viscoelastic behavior. Polymer A showed a shear viscosity approximately three times larger than both polymers B and C (114 Pa.s-1 vs. 36-38 Pa.s-1) over the shear-rate range measured, indicating a possible better ability to resist flows and potentially remain in place at the site of application in vivo. The results of storage modulus (G') measurements showed 100 Pa for polymer A and 16 Pa and 20 Pa for polymers B and C, respectively. This translated into a weaker elastic behavior for gels B and C, and a lower ability to resist sudden deformation. The peel test results showed a rupture strength of 72 mN (0.016 lbf) for polymer A, 39.6 mN (0.0089 lbf) for polymer B, and 38.3 mN (0.0086 lbf) for polymers C, indicating possible higher adhesive properties for polymer A. Tests measuring the extrudability of the hyaluronic acid gels in their commercial syringes showed an average extrusion force of 20 N (4.5 lbf) for polymer A, 28 N (6.33 lbf) for polymer B, and 17 N (3.79 lbf) for polymer C. CONCLUSIONS: Modified anti-adhesion gels made of hyaluronic acid differed in mechanical properties and concentration. Further clinical studies are needed to confirm whether these differences make one polymer easier to apply during surgery and more likely to stay in place longer after in vivo application, and to determine which is potentially superior in terms of preventing adhesions.

RESUMEN

Animals from insects to humans perform visual escape behavior in response to looming stimuli, and these responses habituate if looms are presented repeatedly without consequence. While the basic visual processing and motor pathways involved in this behavior have been described, many of the nuances of predator perception and sensorimotor gating have not. Here, we have performed both behavioral analyses and brain-wide cellular-resolution calcium imaging in larval zebrafish while presenting them with visual loom stimuli or stimuli that selectively deliver either the movement or the dimming properties of full loom stimuli. Behaviorally, we find that, while responses to repeated loom stimuli habituate, no such habituation occurs when repeated movement stimuli (in the absence of luminance changes) are presented. Dim stimuli seldom elicit escape responses, and therefore cannot habituate. Neither repeated movement stimuli nor repeated dimming stimuli habituate the responses to subsequent full loom stimuli, suggesting that full looms are required for habituation. Our calcium imaging reveals that motion-sensitive neurons are abundant in the brain, that dim-sensitive neurons are present but more rare, and that neurons responsive to both stimuli (and to full loom stimuli) are concentrated in the tectum. Neurons selective to full loom stimuli (but not to movement or dimming) were not evident. Finally, we explored whether movement- or dim-sensitive neurons have characteristic response profiles during habituation to full looms. Such functional links between baseline responsiveness and habituation rate could suggest a specific role in the brain-wide habituation network, but no such relationships were found in our data. Overall, our results suggest that, while both movement- and dim-sensitive neurons contribute to predator escape behavior, neither plays a specific role in brain-wide visual habituation networks or in behavioral habituation.

Asunto(s)

Visión Ocular , Pez Cebra , Animales , Humanos , Larva , Neuronas Motoras , Percepción Visual

RESUMEN

Uterine fibroids or uterine myomas are one of the most common benign diseases of the uterus. Symptoms associated with myomas can make surgical removal of myomas necessary. Besides the traditional abdominal route, laparoscopic myomectomy (LM) has gained more acceptances over the last few decades, and it is anticipated that laparoscopy is associated with lower adhesion development. Therefore, we conducted this review to analyze the evidence on adhesions after LM. The PubMed database was searched using the search terms "myomectomy" alone and in combination with "adhesions," "infertility OR fertility outcome," and "laparoscopy" among articles published in English and German. Although the well-known advantages of laparoscopy, for example, less pain, less blood loss, or shorter hospital stay, myomectomy belongs to high-risk operations concerning adhesion formation, with at least every fifth patient developing postsurgical adhesions. In laparoscopic surgery, surgeons´ experience as well tissue trauma, due to desiccation and hypoxia, are the underlying mechanisms leading to adhesion formation. Incisions of the posterior uterus may be associated with a higher rate of adhesions compared to anterior or fundal incisions. Adhesions can be associated with severe complications such as small bowel obstruction, chronic pelvic pain, complications in further operations, or impaired fertility. Tissue trauma and the experience of the surgeon in laparoscopic surgery are most of the influencing factors for adhesion formation after myomectomy. Therefore, every surgeon should adopt strategies to reduce adhesion development in daily routine, especially when it conducted to preserve or restore fertility.

RESUMEN

PURPOSE: Deep ovarian endometriosis surgery is likely to be associated with diffuse bleeding, intraoperative ovarian tissue destruction and perioperative adhesion formation. A new surgical approach is hereby proposed to avoid the negative short-term impact of classic laparoscopic cystectomy on ovarian reserve. RESULTS: The need for intraoperative periovarian coagulation after endometrioma excision was avoided by combining the gold standard minimal-access endometrioma stripping technique with a purely plant-based medical product with high-hemostatic and antiadhesion barrier properties. CONCLUSION: Endometrioma stripping followed by the application of a polysaccharide agent could avoid ovarian failure and at same time could reduce adhesion formation, thereby preserving tubo-ovarian function in endometrioma surgery. We encourage other surgically working groups to investigate middle- and long-term effects of this combined technique.

Asunto(s)

Endometriosis/cirugía , Infertilidad/cirugía , Enfermedades del Ovario/cirugía , Reserva Ovárica/fisiología , Adherencias Tisulares/cirugía , Femenino , Humanos

RESUMEN

Introduction: Genital injuries occur in half of cases of sexual assault through digital or penile penetration as well as the use of objects. Women aged >45 years are more likely to have physical injury and anogenital lesions, transmission of STI and HIV. This review focuses on the evidence about surgical reconstruction of the pelvic floor anatomy of adolescents and adult women sexually assaulted during adolescence or adulthood. Method: A systematic literature search was performed in PubMed and Orbis plus for articles published in English and German from June 2008 to June 2018. The literature search was performed in October 2018 by topic combining the following Medical Subject Headings: genital trauma, genital injuries, sexual assault, rape, surgical repair, treatment. Results: 34 records of descriptive studies were identified and 16 full-text articles were included in the present review. Due to the limited number of articles retrieved, articles were not excluded based on methodological design. Superficial genital lesions are common and usually left untreated. For deep vaginal or anal lacerations, intraperitoneal bleeding is usually assessed by means of and additional CT scan or diagnostic colposcopy, cystoscopy, rectoscopy and laparoscopy. Complete reconstruction of the injured is done after. To prevent rectovaginal fistula and uncomplicated primary wound healing a temporary colostomy can be performed. Conclusion: Although most of genital injuries due to sexual assault do not require any major surgical intervention, there is a lack of good quality evidence regarding the best diagnostic and surgical approach to restore deep lesions of genital organs as well lack evidence on contributors to poor wound healing. Therefore, clinical protocols that standardize examination as well as surgical management are encouraged to be developed.

RESUMEN

Minimally invasive surgery demands specific endoscopic psychomotor skills that are usually acquired outside the operating theatre. We present the results of a systematic analysis to identify how simulation is used during training and qualification in minimal access surgery to improve gynecologist's surgical skills. We found that despite the availability of simulation tools along with methods for training and testing specific endoscopic psychomotor and technical skills, there is no clear evidence of the superiority of one tool or method over the others in skill acquisition. However, prospective studies show that well-guided training courses combined with different trainers and methods improve significantly surgeon's laparoscopic skills and suturing ability, which are unforgettable over time. However, this proficiency could deteriorate over time when it is solely learned and executed on simulation trainers. Structured curricula including theory, simulation, and live-surgery seem to be the best option for trainees. More research in this field is needed.

Asunto(s)

Competencia Clínica , Ginecología , Laparoscopía , Procedimientos Quirúrgicos Mínimamente Invasivos , Simulación por Computador , Curriculum , Ginecología/educación , Humanos , Laparoscopía/educación , Laparoscopía/normas , Procedimientos Quirúrgicos Mínimamente Invasivos/educación , Procedimientos Quirúrgicos Mínimamente Invasivos/normas , Estudios Prospectivos

RESUMEN

PURPOSE: To evaluate the feasibility of using contained endobags (Morsafe®) in the retrieval of the specimen during laparoscopic surgeries in presumably benign myomatous pathology. MATERIAL AND METHODS: We conducted a retrospective single center case - control study on 239 patients, between 01.05.2014 and 31.12.2017 for uterine myomata, presumed to be benign. The analyzed parameters were the method for contained specimen retrieval, the time of bag manipulation, practicability of action and the perioperative complications rate. The present work has been reported in accordance with the STROCSS criteria and guidelines [1]. RESULTS: the main laparoscopic interventions were myomectomy (n = 148 cases) and LASH (laparoscopic supracervical hysterectomy) (n = 68 cases), LASH with bilateral salpingectomy (n = 7), LASH and bilateral adnexectomy (n = 3), LTH (laparoscopic total hysterectomy) (n = 3), LTH and bilateral adnexectomy (n = 1), radical LTH with lymphonodectomy (n = 2), LTH with bilateral salpingectomy (n = 1) and adenomyomectomy (n = 6). In 3 cases using contained closed bags, there was an evidence of malignancy in the pathological sections: leiomyosarcoma (n = 1) and endometrial carcinoma (n = 2). There were no adverse events and no intra - or postoperative bag - induced complications. Regarding the intraoperative duration, the time of bag introduction was about 7 min, and morcellation approximately 12 min. CONCLUSION: in - bag morcellation through endobag (Morsafe®) proved to be a safe laparoscopic method in retrieval of myomatous tissue, potentially reducing the risk of dissemination and thereby improving the patients' safety avoiding spreading of benign disease and malignancy, but preserving the benefits of minimally invasive surgery. The advantages concerned not only the operating time and costs, but also the safety aspects in case of malignancy. As the system can help to reduce risk of cell dissemination it could also reduce the risk in case of occult malignancy.

Asunto(s)

Leiomioma/cirugía , Morcelación/métodos , Miomectomía Uterina/métodos , Neoplasias Uterinas/cirugía , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Histerectomía/instrumentación , Histerectomía/métodos , Laparoscopía/efectos adversos , Laparoscopía/instrumentación , Laparoscopía/métodos , Leiomiosarcoma/cirugía , Persona de Mediana Edad , Morcelación/efectos adversos , Morcelación/instrumentación , Tempo Operativo , Estudios Retrospectivos , Miomectomía Uterina/efectos adversos , Miomectomía Uterina/instrumentación , Adulto Joven

RESUMEN

BACKGROUND: Uterine perforation is the most common complication of curettage and may result in bleeding. Therefore, urgent control of bleeding from the uterine wall perforation is necessary to avoid an emergency hysterectomy or blood transfusion, to prevent peritoneal adhesion formation, possible chronic pelvic pain, and infertility. In the present case, an active bleeding secondary to a perforation of the uterus during curettage, for diagnosis of endometrial carcinoma, was instantaneously and successfully treated with only the application of a novel modified polysaccharide powder. This is, to the best of our knowledge, the first time that the agent 4DryField® has been used for this purpose. CASE PRESENTATION: A 71-year-old German woman with serometra and endometrial hyperplasia suffered a perforation of the anterior wall of the uterus during the hysteroscopic resection of submucosal polyps and a fractional curettage. Subsequently, an immediate laparoscopy showed an active bleeding from the wound, which was promptly stopped with only the application of the hemostatic and anti-adhesion polysaccharide powder, 4DryField®. There were no postoperative complications. Nine weeks later, a laparoscopic hysterectomy with bilateral salpingoophorectomy for endometrial carcinoma (histology: stage IA, pT1a, cN0, L0 V0 M0/G2) was performed. The former injured area looked slightly prominent, was completely healed, and showed a shiny serosa. All her pelvic organs were free of adhesions, and there was one 0.5-mm calcified granuloma in the Douglas pouch. CONCLUSIONS: The efficient hemostasis combined with the adhesion prevention effect of 4DryField®, allowed a fast control of the uterine wall bleeding, saved operation time, avoided the risks of other procedures for bleeding control and contributed to the normal healing of the uterine wall without any adhesion formation.

Asunto(s)

Legrado/efectos adversos , Hemostáticos/administración & dosificación , Hemostáticos/uso terapéutico , Polisacáridos/administración & dosificación , Polisacáridos/uso terapéutico , Enfermedades Uterinas/cirugía , Hemorragia Uterina/terapia , Perforación Uterina/terapia , Anciano , Femenino , Hemostasis , Humanos , Laparoscopía , Pólipos/cirugía , Complicaciones Posoperatorias , Polvos , Adherencias Tisulares , Resultado del Tratamiento , Enfermedades Uterinas/patología , Hemorragia Uterina/etiología , Perforación Uterina/complicaciones , Perforación Uterina/etiología

RESUMEN

We conducted a prospective randomized single blind - subject study in the University Clinic of Gynecology of Pius-Hospital Oldenburg. The primary objective of the ADBEE study was to assess the safety and manageability of ADBLOCK when used as an adjunct to laparoscopic surgery for the primary of myomas in women wishing to improve pregnancy outcomes. The study population included 32 women aged between 18-45 years, in good general health condition, who have not completed their family planning and who are undergoing primary ('virgin') laparoscopic myomectomy with an aim to improve pregnancy outcomes. The patients were randomized in 2 groups, ADBLOCK arm with 21 patients and surgery only arm with 11 patients. The study was single blind - subject and the investigators were blinded to treatment group assignment until completion of uterine suturing and prior to removal of the endoscope. A vigorous follow-up of subjects was organized, focusing on its two critical characteristics: completeness and duration. Completeness represented the percentage of subjects who returned to every planed follow - up appointments. The patients were evaluated in a specific period of time, which defined the duration of follow-up. Safety of the ADBLOCK was estimated after analyzing and documentation of any adverse events occurred, clinical and physical examination of patients as well as evaluation of laboratory measures. There were 25 adverse events reported in ADBLOCK treatment group and 12 events in NO-ADBLOCK group over the 24-months treatment. All adverse events in both treatment arms were not anticipated, with all events in the ADBLOCK group being resolved. At 28 days, there was no significant difference in proportion of events between the two treatments (p = 0.440). Overall, the number of events reported was low and the severity of events was generally mild with an unlikely or no relationship to treatment. There were no unanticipated device related adverse events seen in both treatment groups over the immediate post-operative period or during the 24 months follow up period. By 12 weeks all patients reported their wound as healing well or healed and at 6 months all wounds were reported as healed. There were no differences between both treatment groups regarding the use of painkillers over 24 months follow up period. This clinical first - in - human study, sustained by a rigorous follow-up of the subjects has demonstrated that ADBLOCK is a safe product, presenting no additional safety risk or burden to the patients over surgery alone. The device was relatively easy to use, with a low device failure rate that had no impact on the surgical procedures.

Asunto(s)

Dextrinas/uso terapéutico , Infertilidad Femenina/cirugía , Leiomioma/cirugía , Polímeros/uso terapéutico , Adherencias Tisulares/prevención & control , Neoplasias Uterinas/cirugía , Adolescente , Adulto , Dextrinas/efectos adversos , Falla de Equipo , Femenino , Estudios de Seguimiento , Geles , Humanos , Infertilidad Femenina/etiología , Complicaciones Intraoperatorias/etiología , Laparoscopía/efectos adversos , Laparoscopía/instrumentación , Leiomioma/complicaciones , Persona de Mediana Edad , Dolor Postoperatorio/etiología , Cooperación del Paciente , Polímeros/efectos adversos , Embarazo , Índice de Embarazo , Estudios Prospectivos , Método Simple Ciego , Factores de Tiempo , Adherencias Tisulares/etiología , Neoplasias Uterinas/complicaciones , Cicatrización de Heridas , Adulto Joven

RESUMEN

Vaginal agenesis is a congenital anomaly that affects the life of one of each four thousand women around the world. There is a trend that patients request immediate surgical correction, instead of passive vaginal dilatation. Therefore a differentiated counselling should be provided. We present a comparative chart, based on published evidence, with aspect to the available techniques, which will facilitate the decision-making process in the clinical practice. From our point of view, the best results are achieved with techniques that combine the advantages of the minimal-invasive surgery with those derived of the use of peritoneum as covering tissue of the neovagina. Nevertheless there is a lack on interdisciplinary consensus about the best option to restore the physical and sexual quality of life.