The role of Allied Health Professions and Nursing Research Internships in developing a research culture: a mixed-methods exploration of stakeholder perspectives.

BACKGROUND: Developing research capability and capacity within the healthcare professions is a challenge throughout diverse international settings. Within England, the National Institute for Health Research aimed to address these challenges through the Integrated Clinical Academic (ICA) research careers escalator for nurses, midwives and allied health professionals. Poor academic progression has been identified in the advanced stages of the pathway, though progression from the earlier entry point (Internship) has not previously been investigated. A national evaluation of four completed Internship cohorts was undertaken to explore stakeholder perspectives and progression beyond the Internship programme. METHODS: A mixed methods project used sequential qualitative and quantitative data collection phases commencing with two stakeholder focus groups (n = 10); the findings informed the development of an online survey distributed to previous cohorts of interns (n = 104), their managers (n = 12) and academic mentors (n = 36). Eight semi-structured interviews subsequently explored the challenges and opportunities afforded by the internships. Thematic analysis was used to review qualitative data from focus groups and interviews, with survey data analysed and displayed using descriptive statistics. Synthesis of data from each phase is displayed within the four level evaluation framework outlined within the New World Kirkpatrick® Training Evaluation Model. RESULTS: Important regional differences exist yet the internships are highly valued by all stakeholders. Representation varied between different professions, with nursing and some service-based professions poorly represented. All interns successfully completed the programme (n = 104), with evidence of positive impacts on interns, colleagues and patient care. Balancing research commitments with clinical activity was challenging; middle managers were seen as gatekeepers to programme success. Progression to the next stage of the ICA pathway is highly competitive and was achieved by only a quarter of interns; access to mentors outside of the funded programme is vital for a successful transition. CONCLUSIONS: The Internship programme succeeds in providing a range of important early experiences in research, though progression beyond the programme is challenging due, in part, to a widening gap between Internship and the next level of the ICA framework. Vital mentorship support to bridge this gap is threatened by a lack of time and funding; therefore, the pursuit of a clinical-academic career will continue to be elusive for many nurses and allied health professionals. A partnership approach to clinical academic support at institutional level is needed with several international models offering alternative strategies for consideration.

Y chromosome microdeletions and varicocele as aetiological factors of male infertility: A cross-sectional study.

The pathogenic mechanisms by which varicocele disrupt spermatogenesis are not clearly understood. Over 30% of male infertility cases resulting from spermatogenic problems are associated with genetic abnormalities, and Y chromosome microdeletions are the second most frequent genetic cause. Here, we aimed to evaluate the frequency of Y chromosome microdeletion in infertile men with varicocele. A cross-sectional study comprising 51 infertile men with varicocele presenting spermatogenesis failures was performed. Y chromosome microdeletion research was made using polymerase chain reaction. Of the 51 men with infertility and varicocele, 35.3% (18/51) had nonobstructive azoospermia and 64.7% had severe oligozoospermia. Y chromosome microdeletion was found in two cases (3.9%): one patient had nonobstructive azoospermia and complete microdeletion of the AZFb and AZFc regions, and another patient had severe oligozoospermia and complete microdeletion of the AZFc region. Although in recent years, a genetic aetiology related to Y chromosome microdeletions has become a major cause of infertility in males with spermatogenesis failures, in this study, the varicocele was the clinical cause of seminal abnormalities that could lead to infertility, suggesting that both varicocele and Y chromosome microdeletion aetiologies can present, alone or combined, as factors of male infertility.

Histopathologic features in actinic cheilitis by the comparison of grading dysplasia systems.

OBJECTIVE: This study aimed to determine the histopathologic findings in actinic cheilitis (AC) and lip squamous cell carcinomas (LSCC) diagnosed at Federal University of Santa Catarina in order to attempt to predict the evolution from AC to LSCC based on the comparison of two dysplasia classification systems. METHODS: Histopathologic features were evaluated according to the World Health Organization classification of dysplasia and binary system of classification. Also, in LSCC, pattern, stage of invasion, and degree of keratinization were evaluated. A total of 58 cases of AC and 70 cases of LSCC were studied, and data correlation was performed using statistical analysis. RESULTS: The presence of dyskeratosis and keratin pearls was found to be strongly associated with severe dysplasia and could represent higher proximity between the severe dysplasia in AC and LSCC. Also, changes related to the nuclei, such as hyperchromasia, nuclear pleomorphism, anisonucleosis, increase in the number and size of nucleoli, increased number of mitoses, and atypical mitoses, indicate progression in dysplasia spectrum. CONCLUSION: Knowledge of clinical and histological features of AC and LSCC leads to better understanding of factors possibly associated with malignant transformation of epithelial dysplasia.

The influence of inflammatory cytokines in physiopathology of suicidal behavior.

BACKGROUND: Based on the urgent need for reliable biomarkers in relation to suicide risk both for more accurate prediction as well as for new therapeutic opportunities, several researchers have been studied evidences of the potential participation of inflammatory processes in the brain, in particular cytokines, in suicide. The purpose of this review was to analyze the associations between inflammation markers and suicide. METHODS: To achieve this goal, a systematic review of literature was conducted via electronic database Scopus using the Medical Subject Headings (MeSH) terms: "cytokines", "suicide" and "inflammation". Through this search it was found 54 articles. After analyzing them 15 met the eligibility criteria and were included in the final sample. RESULTS: One of the most mentioned inflammatory markers was Interferon-α (IFN-α), a pro-inflammatory cytokine which has been shown to increase serum concentrations of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-a (TNF- α) and IFN-ϒ, which are factors increased suicide victims and attempters. In this line, IL-6 is not only found to be elevated in the cerebrospinal fluid of suicide attempters, even its levels in the peripheral blood have been proposed as a biological suicide marker. Another study stated that increased levels of IL-4 and IL-13 transcription in the orbitofrontal cortex of suicides suggest that these cytokines may affect neurobehavioral processes relevant to suicide. LIMITATIONS: A lack of studies and great amount of cross-sectional studies. CONCLUSION: Inflammation may play an important role in the pathophysiology of suicide, especially, levels of some specific inflammatory cytokines.

AMH: An ovarian reserve biomarker in assisted reproduction.

Ovarian reserve tests provide knowledge of a possible response to controlled ovarian hyperstimulation in patients undergoing assisted reproduction treatment, allowing management and alteration of treatment protocol with the appropriate dose of gonadotrophin. Several parameters have been used as predictors of ovarian response. The basal FSH serum level on the third day of the menstrual cycle seemed to be the best predictor, but with significant intraindividual variability from one cycle to another. Thus, the anti-Müllerian hormone (AMH) emerges as a new ovarian test marker. AMH is produced exclusively in the gonads, by the granulosa cells, and plays an important role in folliculogenesis, acting on the modulation of follicular recruitment in the granulosa cells in order to limit the number of recruited oocytes and to regulate the number of growing follicles and their selection for ovulation. It has been suggested that AMH is strongly associated with oocyte yield after ovarian stimulation and could therefore be capable of predicting the ovarian response and the quality of oocytes and embryos. In this review, we discuss the role of AMH in assisted reproduction outcomes.

Promoter -817C>T variant of B lymphocyte stimulator gene (BLyS) and susceptibility to endometriosis-related infertility and idiopathic infertility in Brazilian population.

Many theories have been proposed to explain the development of endometriosis, and recently, autoimmune aetiology has been suggested. Besides, it is well known that endometriosis, especially the advanced disease, may impair fertility. B lymphocyte stimulator (BLyS) is a cytokine produced by macrophages and is necessary for normal B cell development. One of the most studied polymorphisms is the -817C/T in the promoter region of the gene. We aimed to assess the association between endometriosis-related infertility and idiopathic infertility and the BLyS -817C/T polymorphism in a Brazilian population. We performed a case-control study comprising 165 infertile women with endometriosis, 83 with idiopathic infertility and 145 fertile and assessed the association with BLys -817C/T polymorphism. BLyS -817C/T polymorphism was detected using TaqMan PCR. The results were analysed statistically, and a P-value < 0.05 was considered significant. The results disclosed similar genotype and allelic frequencies between endometriosis-related infertility (P = 0.225) and control group, regardless of the disease stage (P = 0.213 and P = 0.462, respectively). However, a statistically significant difference was observed regarding idiopathic infertile group (P = 0.048) compared with controls. Considering the dominant and recessive inheritance models, no significant differences in both endometriosis and idiopathic infertility group were found. The genotype frequencies were in Hardy-Weinberg equilibrium in all studied groups. The results point to a possible association between BLyS -817C/T polymorphism and idiopathic infertility in Brazilian population.

The effect of hormones on endometriosis development.

Endometriosis is a common gynecological condition in which tissue that is histologically similar to the endometrium with glands and/or stroma grows outside the uterine cavity and can lead to pelvic pain, dysmenorrhea and infertility. Many aspects of female reproductive function are strongly influenced by genetic factors and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as endometriosis. The importance of steroid hormones on endometriosis is unquestionable. The disease is most prevalent in women of reproductive age and regresses after menopause and its occurrence before menarche has not been reported. Sex steroids, estrogen and progesterone, are mainly produced in the ovaries and they regulate the growth of endometrial tissue, basically by stimulating and inhibiting cell proliferation, respectively. In addition, estrogen plays an important role in the regulation of cyclic gonadotropin release and in folliculogenesis. Numerous studies have been conducted to demonstrate the interaction of hormone and their receptors with endometriosis with conflict results. Besides, environmental chemicals, known as endocrine disruptors, have the capacity to mimic, block or modulate the endocrine system through the interaction with steroidal receptors. Recently evidences have proposed a putative role for ubiquitous environmental contaminants in the occurrence of endometriosis. Here, we reviewed significant articles regarding the interaction among endometriosis, hormones and genetic polymorphic variants.

Analysis of CTLA4 gene variant in infertile Brazilian women with and without endometriosis.

An autoimmune aetiology has been suggested for endometriosis mostly on the basis of an increased prevalence of autoimmune diseases in affected women. Cytotoxic T lymphocyte antigen (CTLA) 4 gene is recognized as a primary determinant for autoimmunity, since specific polymorphisms have been associated with predisposition to most autoimmune disorders. Thus, the objective of the study was to evaluate CTLA4 polymorphism (+49A/G) in a group of infertile women with and without endometriosis and controls. Case-control study comprising 244 infertile women (177 with endometriosis and 67 without endometriosis) and 172 fertile women as controls. CTLA4 polymorphism was identified by qPCR. The results were analysed statistically and a P-value <0.05 was considered significant. We found relatively similar CTLA4 polymorphisms genotype frequencies in women with and without endometriosis and controls (P=0.158 and P=0.262, respectively). When the patients with minimal/mild endometriosis and moderate/severe endometriosis were studied separately, no difference was also found related to controls (P=0.560 and P=0.11, respectively). The data suggest that the CTLA4 polymorphism is not associated with endometriosis and/or infertility in Brazilian women.

Severe oligospermia associated with a unique balanced reciprocal translocation t(6;12)(q23;q24.3): male infertility related to t(6;12).

The prevalence of chromosome abnormalities is increased in infertile men, the incidence of a chromosomal factor being estimated to be about 8%. We report two brothers, a 38-year-old man with 10 years' primary infertility and severe oligospermia, but otherwise healthy, and a 35-year-old man with primary infertility and a history of mumps during puberty. Semen and karyotype analysis, and investigation of Y-chromosome microdeletions were performed. An apparently unique reciprocal translocation t(6;12)(q23;q24.3) was found in both infertile brothers. Semen analyses showed severe oligospermia. No Y-chromosome microdeletions were found. These two cases support the relationship between both environmental and chromosomal abnormalities, combined or separated, with male infertility. Investigation of genetic alterations in infertile males has to be performed prior to performing any assisted reproduction technique.

PTPN22 polymorphism is related to autoimmune disease risk in patients with Turner syndrome.

Individuals with Turner syndrome (TS) clearly have an increased risk for autoimmune diseases. Recently, an allelic variation (C1858T) of the PTPN22 gene was revealed to be associated with the development of autoimmunity. Thus, the aim of this study was to determine the frequency of the PTPN22 C1858T polymorphism in women with Turner syndrome (TS) compared to controls. Case-control study comprises 142 women with TS (cases) and 180 healthy and fertile women without a history of autoimmune disease (controls). Detection of the PTPN22 C1858T polymorphism (rs2476601) was performed by TaqMan real-time PCR. The chi-square test was used to compare allele and genotype frequencies between groups and to estimate the Hardy-Weinberg equilibrium. All P-values were two-tailed, and 95% confidence intervals (CIs) were calculated. A P-value <0.05 was considered statistically significant. Genotypes CC, CT and TT of the PTPN22 C1858T polymorphism presented frequencies of, respectively, 67.6%, 28.2% and 4.2% in the TS, and 82.8%, 16.1% and 1.1% in the control group (P = 0.0043). Alleles C and T were present in, respectively, 81.7% and 18.3% of the patients with TS (P = 0.001, OR = 2.22, 95% CI = 1.39-3.54) and in 90.8% and 9.2%, respectively, of the controls. The data suggest that in Brazilian patients with TS, the PTPN22 C1858T polymorphism may be an important genetic factor predisposing to autoimmune disease risk.

[Helical CT without contrast media as alternative to other methods in urolithiasis]. / La Tc spirale senza mdc in alternativa alle altre metodiche nella urolitiasi.

PURPOSE: During the last five years the use of unenhanced helical CT (HTC) has been proposed as a preliminary diagnostic approach in patients with typical renal colics or with nonspecific flank pain. The aim of this study was to describe our experience in this field. MATERIAL AND METHODS: 130 consecutive patients (82 men and 48 women, with an average age of 54 years) were studied; 94 of them presented typical renal colics, while 36 presented acute flank pain. The parameters used were: 5-mm-thick sections, a pitch of 1.6, a reconstruction interscan spacing at 3 mm, an examination area extending from the kidneys to the base of the bladder. Depending on the case, examinations were carried out using urography in the instrumental or surgical pretreatment phase, ultrasonography to check urinary dilatation and juxtavesical calculi, pyeloMR, ureteroscopic extraction, surgical operation, extracorporeal lithotripsy, and finally the expulsion of the calculi was checked. RESULTS: 81 cases of urolithiasis, 6 cases of renal abnormalities and other renal pathologies, 23 cases of extraurinary pathologies correlated to the symptoms, 5 cases of extraurinary pathologies not correlated to the symptoms and 15 normal cases, were diagnosed. The results obtained were a) a sensitivity of 96.8%, a specificity of 98.4% and a diagnostic accuracy of 97.6% in identifying ureteral calculi; b) a diagnostic accuracy of 100% in identifying urinary tract dilatation; c) a sensitivity of 100% and a specificity of 96.7% in determining the level of obstruction; d) a sensitivity of 92.9% and a specificity of 100% in determining the cause of obstruction. CONCLUSIONS: Confirming the data in the medical literature, helical CT has yielded for more reliable results than the other procedures in identifying the following: calculi, acute obstruction of the urinary tract and other urinary and extraurinary pathologies correlated to the symptoms. Therefore helical CT, where available, must be accepted as the method of preliminary evaluation in all patients with typical renal colics or with nonspecific flank pain.

Zeeman-Stark modeling of the RF EMF interaction with ligand binding.

The influence of radiofrequency electromagnetic exposure on ligand binding to hydrophobic receptor proteins is a plausible early event of the interaction mechanism. A comprehensive quantum Zeeman-Stark model has been developed which takes into account the energy losses of the ligand ion due to its collisions inside the receptor crevice, the attracting nonlinear endogenous force due to the potential energy of the ion in the binding site, the out of equilibrium state of the ligand-receptor system due to the basal cell metabolism, and the thermal noise. The biophysical "output" is the change of the ligand binding probability that, in some instances, may be affected by a suitable low intensity exogenous electromagnetic "input" exposure, e.g., if the depth of the potential energy well of a putative receptor protein matches the energy of the radiofrequency photon. These results point toward both the possibility of the electromagnetic control of biochemical processes and the need for a new database of safety standards.

DC-ELF characterization of random mixtures of piecewise nonlinear media.

Biological tissues are ensembles of linear and nonlinear, symmetric and asymmetric constituents. As far as their electromagnetic characterization is concerned, they can be modeled as microscopic mixtures of the corresponding material media. Any medium volume can be properly discretized in a finite number of cells which can be modeled as an equivalent three dimensional network of lumped components, in order to characterize its electromagnetic behavior at wavelengths much longer than the relevant average linear size of the constitutive cells. Therefore, any mixture and the corresponding tissue can be characterized in terms of its effective conductance at extremely low frequency, with respect to a reference set of electrodes (ports of the equivalent network). When the above procedure is implemented for evaluating any of the aforesaid conductances, a resulting nonlinear characteristic should be expected. In reality, it may happen that the effect of the constitutive nonlinearities and the related asymmetries are smeared out by the randomness of the interconnections of the lumped components, leading at a macroscopic level to an isotropic constant equivalent conductance, i.e., to an isotropic constant equivalent conductivity of the mixture. The closed form analysis of a random network of nonlinear (piecewise linear) resistors offers a simple but clear cut example of such a property. This result, if extrapolated to biological media, suggests a new hint for explaining why there is no inconsistency between the typical electric characterization of biological tissues as almost linear macroscopic media, by means of their effective conductivity and permittivity, and the nonlinearities of the biochemical processes occurring in the tissue cells. In fact, the nonlinearities may not be observable by means of macroscopic electrical measurements because of the randomized spatial orientation and location of the processes.

Computational methods for ultrasonic bone assessment.

Ultrasound has been proposed as a means to noninvasively assess bone and, particularly, bone strength and fracture risk. Although there has been some success in this application, there is still much that is unknown regarding the propagation of ultrasound through bone. Because strength and fracture risk are a function of both bone mineral density and architectural structure, this study was carried out to examine how architecture and density interact in ultrasound propagation. Due to the difficulties inherent in obtaining fresh bone specimens and associated architectural and density features, simulation methods were used to explore the interactions of ultrasound with bone. A sample of calcaneal trabecular bone was scanned with micro-CT and subjected to morphological image processing (erosions and dilations) operations to obtain a total of 15 three-dimensional (3-D) data sets. Fifteen two-dimensional (2-D) slices obtained from the 3-D data sets were then analyzed to evaluate their respective architectures and densities. The architecture was characterized through the fabric feature, and the density was represented in terms of the bone volume fraction. Computer simulations of ultrasonic propagation through each of the 15 2-D bone slices were carried out, and the ultrasonic velocity and mean frequency of the received waveforms were evaluated. Results demonstrate that ultrasound propagation is affected by both density and architecture, although there was not a simple linear correlation between the relative degree of structural anisotropy with the ultrasound measurements. This study elucidates further aspects of propagation of ultrasound through bone, and demonstrates as well as the power of computational methods for ultrasound research in general and tissue and bone characterization in particular.

[A case of peritoneal tuberculosis. Contribution of mini-endoscopy]. / Un caso di tubercolosi peritoneale. Contributo della miniendoscopia.

BACKGROUND: Tuberculosis in the genital and peritoneal region is increasing in last years. For this reason, the high value and efficacy of laparoscopy using a small caliber endoscope for the diagnosis of this disease, which often presents no specific and heterogeneous clinical features, is underlined. METHODS: A case of peritoneal tuberculosis in a young female presenting fever, asthenia and peritoneal effusion, is reported. Blood tests, X-ray and cytological examination of the peritoneal fluid all failed to point out the right diagnosis. Then multiple biopsies of the peritoneum and the external surface of uterus and ovaries were made using laparoscopy. RESULTS: Laparoscopy clearly showed the miliary nodules. The histology showed multiple granulomas composed by inner caseous necrosis and outer layer of epithelioid histiocytes and Langhans cells, leading thus to the diagnosis of peritoneal tuberculosis. The patient, treated with streptomycin and rifampicin, five months after diagnosis, did not show any feature of tubercular disease. CONCLUSIONS: Because of its safety, laparoscopy is a very useful and powerful diagnostic technique especially in those young women presenting with painful abdominal symptoms without any clear evident cause.