Artificial oocyte activation improves ICSI outcomes following unexplained fertilization abnormalities.

RESEARCH QUESTION: Is artificial oocyte activation (AOA) effective for patients with unexplained low or no fertilization following IVF/intracytoplasmic sperm injection (ICSI)? DESIGN: All IVF/ICSI cases resulting in total fertilization failure or fertilization rate ≤25% at Ninewells Assisted Conception Unit, Dundee between January 2014 and December 2021 (n = 231) were reviewed contemporaneously. After exclusion of obvious stimulation, egg, sperm and/or assisted reproductive technology laboratory factors, patients with at least one cycle of IVF/ICSI resulting in apparently unexplained fertilization abnormalities were offered research investigations, including sperm immunocytochemistry for phospholipase C zeta (PLCζ) protein expression. This retrospective case-control cohort study evaluated laboratory and clinical outcomes for 39 couples (15 attended for sperm studies research) that subsequently undertook ICSI-AOA with Ca2+ ionophore. RESULTS: Comparing preceding IVF/ICSI and subsequent ICSI-AOA for each patient, the number of eggs collected was similar; however, ICSI-AOA resulted in a significantly improved fertilization rate (57.2% versus 7.1%; P < 0.0001). The uplift for a subset of 10 patients identified with PLCζ deficiency was 66.3% versus 4.6% (P < 0.0001). Overall, ICSI-AOA resulted in a higher number of fresh embryo transfers (94.6% versus 33.3%; P < 0.0001), a significantly higher clinical pregnancy rate (CPR) and live birth rate (LBR; 18.9% versus 2.6%; P = 0.02), a significant increase in cycles with surplus embryos suitable for cryostorage (43.6% versus 0%; P < 0.0001), and increased cumulative CPR (41.0% versus 2.6%; P < 0.0001) and LBR (38.5% versus 2.6%; P < 0.0001). CONCLUSION: AOA is a powerful tool that can transform clinical outcomes for couples experiencing apparently unexplained fertilization abnormalities. PLCζ assays have the potential to be valuable diagnostic tools to determine patient selection for ICSI-AOA, and research efforts should continue to focus on their development.

Assessment of inter-rater reliability of clinical hidradenitis suppurativa outcome measures using ultrasonography.

BACKGROUND: Hidradenitis suppurativa (HS) staging and severity is typically based upon physical examination findings, which can result in misclassification of severity based on subclinical disease activity and significant variation between healthcare providers. Ultrasonography (US) is an objective tool to help evaluate subclinical disease and to more accurately classify disease severity. AIM: To evaluate inter-rater reliability in HS disease severity assessment using clinical and US techniques. METHODS: In total, 20 subjects underwent clinical evaluation of HS, independently by two physicians, using clinical outcome measures, including Hurley, Sartorius, HS Physician Global Assessment (HS-PGA) and Hidradenitis Suppurativa Clinical Response (HiSCR). US was subsequently performed, and clinical assessments were repeated. Intraclass correlation coefficients (ICC) were obtained to evaluate inter-rater agreement of each outcome measure before and after US. RESULTS: Pre-US to post-US improvement in ICC was seen with the Sartorius, HiSCR nodule and abscess count, and the HiSCR draining fistula count. The scores went from having 'good' rater agreement for Sartorius and HiSCR nodule and abscess count, to 'poor' rater agreement for HiSCR draining fistula count, to 'excellent' rater agreement among these scores. CONCLUSION: US improved inter-rater agreement and should be used in conjunction with physical examination findings to evaluate disease severity to ensure uniform staging of HS.

Synergistic effects of long-wavelength ultraviolet A1 and visible light on pigmentation and erythema.

BACKGROUND: Visible light (VL) induces multiple cutaneous effects. Sunscreen testing protocols recommended by regulatory bodies throughout the world require the use of solar simulators with spectral output in the ultraviolet (UV) domain only. However, sunlight contains VL and infrared radiation also. OBJECTIVES: This study aimed to evaluate the contributions of VL and UVA on pigmentation and erythema, and optimize parameters for in vivo testing. METHODS: Ten subjects with Fitzpatrick skin phototype IV-VI were enrolled. Subjects were irradiated on their back with VL using two light sources: one containing pure VL and one containing VL with less than 0·5% UVA1 (VL+UVA1). Four different irradiances were administered to investigate reciprocity behaviour. Assessments, including photography, Investigator's Global Assessment, colorimetry and spectroscopy, were performed immediately, 24 h, 7 days and 14 days post-irradiation. RESULTS: Pigmentation was observed with both light sources; however, pigment intensity was greater with VL+UVA1 than with pure VL. Reciprocity was observed in pure VL sites, but not VL+UVA1. Variation in spectral output had greater impact on pigment intensity than irradiance. Clinical erythema was observed on the VL+UVA1 side, but not on the pure VL side. A protocol for testing photoprotection product efficacy against VL-induced effects has been proposed. CONCLUSIONS: The findings suggest a synergistic relationship between VL and UVA1 and emphasize the need for developing means of photoprotection against VL.

Influence of Exercise and Intra-articular Site on Canals in Articular Calcified Cartilage of Equine Third Carpal Bones.

The third carpal bone (C3) responds to exercise by adaptive modeling of bone and articular calcified cartilage along the dorsal load path. Canals penetrating articular calcified cartilage, thought to contain vascular tissue, are reported in numerous species. Their significance remains unclear. Our objective was to determine if the number of canals was significantly different in strenuously exercised and control young horses and in a site of intermittent high loading compared to sites sustaining lower habitual loads. Volumetric bone mineral density in the radial facet of C3 of strenuously exercised and gently exercised (control) 19-month-old thoroughbred horses (n= 6/group) was determined by peripheral quantitative computed tomography. The hyaline cartilage was corroded to expose the surface of articular calcified cartilage. The number of canals penetrating the articular calcified cartilage surface in en face scanning electron microscopy images was compared in 4 regions. Volumetric bone mineral density of C3 was significantly greater (P= .004) in strenuously exercised horses. There were 2 morphologically distinct groups of canals and significantly fewer (P= .006) large canals in the dorsal than in the palmar aspect of C3 in control but not in exercised horses. Roughly circular depressions in the articular calcified cartilage surface around apparently forming canals were visible in some samples and have not been previously described in the literature. The canals may be evidence of chondroclastic activity reaching the interface of hyaline and calcified cartilage. Further work is needed to elucidate the relationships between presence of canals and the responses to exercise and to joint disease.

Assessment of bone response to conditioning exercise in the radius and tibia of young thoroughbred horses using pQCT.

OBJECTIVES: To assess the effect of conditioning exercise on bone parameters at multiple sites in the radius and tibia of young Thoroughbred horses. METHODS: The left and right radius and tibia were obtained from twelve horses, six of which had received conditioning exercise and six which formed the control group. Each bone was scanned at 5% intervals along its entire length using pQCT. RESULTS: Bone strength, bone area and periosteal circumference were significantly greater for the group of conditioned horses in both the radius and tibia. Volumetric bone mineral density was lower while bone mineral content, endocortical circumference and polar moment of inertia were higher in the conditioned group of horses but the significance of these differences varied between the two bones. Cortical thickness was not significantly different between the groups in either bone. CONCLUSIONS: Conditioning exercise stimulated a significant increase in the strength of both bones that could be attributed mainly to an increase in bone size, rather than differences in bone mineral content or density. The radius and tibia exhibited differences in the significance of changes in several bone parameters suggesting that not all bones respond in an identical fashion to imposed exercise.

Dentate nucleus as target for deep brain stimulation in dystono-dyskinetic syndromes.

PURPOSE: To discuss the potential of deep brain stimulation (DBS) of the dentate nucleus as a treatment for dystono-dyskinetic syndromes. METHODS: An extensive literature review covered the anatomy and physiology of the dentate nucleus and the experimental evidence for its involvement in the pathophysiology of dystonia and dyskinesia. RESULTS: Evidence from animal models and from functional imaging in humans is strongly in favor of involvement of the dentate nucleus in dystono-dyskinetic syndromes. Results from previous surgical series of dentate nucleus stimulation were promising but precise description of movement disorders being treated were lacking and outcome measures were generally not well defined. CONCLUSIONS: In the light of new evidence regarding the involvement of the dentate nucleus in dystono-dyskinetic syndromes, we present a review of the current literature and discuss why the question of dentate nucleus stimulation deserves to be revisited.

Spinal cord stimulation for failed back surgery syndrome and other disorders.

Chronic pain is a complex condition that requires a multi-disciplinary approach to management. Spinal cord stimulation (SCS) has evolved into a relatively easily implemented, reversible technique with low morbidity for the management of chronic, intractable pain in selected patients. Percutaneous placement of electrode arrays, under local anaesthesia. supported by programmable, implanted electronics has been a major technical advance. Multicenter prospective studies were conducted and demonstrated that SCS. as a neuromodulation procedure, is indeed a superior method for treatment of chronic pain if the patients are selected with caution and a proper strategy. Future development of innovative electrodes and pulse generation systems will continue to improve this therapy.

Vagus nerve stimulation for intractable epilepsy: outcome in two series combining 90 patients.

Vagus nerve stimulation (VNS) is the most widely used non-pharmacological treatment for medically intractable epilepsy and has been in clinical use for over a decade. It is indicated in patients who are refractory to medical treatment or who experience intolerable side effects, and who are not candidates for resective surgery. VNS used in the acute setting can both abort seizures and have an acute prophylactic effect. This effect increases over time in chronic treatment to a maximum at around 18 months. The evidence base supporting the efficacy of VNS is strong, but its exact mechanism of action remains unknown. A vagus nerve stimulator consists of two electrodes embedded in a silastic helix that is wrapped around the cervical vagus nerve. The stimulator is always implanted on the left vagus nerve in order to reduce the likelihood of adverse cardiac effects. The electrodes are connected to an implantable pulse generator (IPG) which is positioned subcutaneously either below the clavicle or in the axilla. The IPG is programmed by computer via a wand placed on the skin over it. In addition, extra pulses of stimulation triggered by a hand-held magnet may help to prevent or abort seizures. VNS is essentially a palliative treatment and the number of patients who become seizure free is very small. A significant reduction in the frequency and severity of seizures can be expected in about one third of patients and efficacy tends to improve with time. Vagus nerve stimulation is well tolerated and has few significant side effects. We describe our experience on the use of VNS on drug-resistant epilepsy in 90 patients treated in two departments (in Athens, Greece and Newcastle, England).

E-cadherin in the developing mouse gonad.

Expression of the cell adhesion molecule E-cadherin in the developing mouse has been investigated by immunocytochemistry and disaggregated organ culture. The principal aims were firstly, to determine whether E-cadherin is expressed in the indifferent gonad and if so with which cell population(s) it is associated. Secondly, to investigate the pattern of expression in the mesonephros, especially in relation to ventral mesonephric tubule cells, which contribute to the somatic cell population of the gonad. Thirdly, to discover whether there are any sex differences in expression of E-cadherin in differentiating gonads. Germ cells in the indifferent gonad showed strong immunoreactivity whereas somatic cells were unstained unless their membranes were in contact with those of germ cells. Positive staining for E-cadherin was found in epithelial cells of the mesonephric duct and tubules. Staining was weak at the ventral margins of the ventral mesonephric tubules. At later stages, germ cell immunoreactivity could be correlated with stages of ovarian differentiation, being reduced or absent between germ cells at 16 days post coitum, when ovigerous cords become dissociated as a prelude to follicle formation. Stronger staining reappeared briefly at 17 days post coitum, the time of follicular cell attachment to oocytes, before waning again 2 days later. Similarly, immunoreactivity in the differentiating testis was initially restricted to the germ cell population but pre-Sertoli cells were strongly positive between 16 and 19 days post coitum. The most striking sex difference was seen in the somatic cell population, where Leydig cells of the testis became strongly positive for E-cadherin from 17 days post coitum onwards. At this time, unlike controls, dissociated cells from gonads of either sex were unable to reform their initial contacts when cultured in the presence of the antibody to E-cadherin, confirming its functional importance.

Side errors in neurosurgery.

Eight cases of neurosurgical operations being performed on the wrong side were studied. Safeguards of confidentiality were used. In seven cases side marking was not done and the surgeons felt that had it been done, the mistake would have or may have been prevented. In all but one case the surgeon's normal side check was omitted. Distracting circumstances contributed to the checks being omitted in these seven cases. In the one case where the check was carried out the mistake was made because the patient had been marked on the wrong side. In no case was the mistake made because of ambiguous or absent site data in the imaging or notes. It is concluded that to prevent these mistakes emphasis should be placed on ensuring that the preoperative site check is completed more than on ensuring that unambiguous side information is available in the notes and imaging.