Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

BACKGROUND: Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy. OBJECTIVES: To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction. SEARCH METHODS: We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods. MAIN RESULTS: We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor. AUTHORS' CONCLUSIONS: Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.

Texture Analysis to Detect Cerebral Degeneration in Amyotrophic Lateral Sclerosis.

BACKGROUND: Evidence of cerebral degeneration is not apparent on routine brain MRI in amyotrophic lateral sclerosis (ALS). Texture analysis can detect change in images based on the statistical properties of voxel intensities. Our objective was to test the utility of texture analysis in detecting cerebral degeneration in ALS. A secondary objective was to determine whether the performance of texture analysis is dependent on image resolution. METHODS: High-resolution (0.5×0.5 mm2 in-plane) coronal T2-weighted MRI of the brain were acquired from 12 patients with ALS and 19 healthy controls on a 4.7 Tesla MRI system. Image data sets at lower resolutions were created by down-sampling to 1×1, 2×2, 3×3, and 4×4 mm2. Texture features were extracted from a slice encompassing the corticospinal tract at the different resolutions and tested for their discriminatory power and correlations with clinical measures. Subjects were also classified by visual assessment by expert reviewers. RESULTS: Texture features were different between ALS patients and healthy controls at 1×1, 2×2, and 3×3 mm2 resolutions. Texture features correlated with measures of upper motor neuron function and disability. Optimal classification performance was achieved when best-performing texture features were combined with visual assessment at 2×2 mm2 resolution (0.851 area under the curve, 83% sensitivity, 79% specificity). CONCLUSIONS: Texture analysis can detect subtle abnormalities in MRI of ALS patients. The clinical yield of the method is dependent on image resolution. Texture analysis holds promise as a potential source of neuroimaging biomarkers in ALS.

Stimuli-responsive peptide-based ABA-triblock copolymers: unique morphology transitions with pH.

We report the synthesis and solution characterization of poly(L-lysine)-b-poly(propylene oxide)-b-poly(L-lysine) (KPK) triblock copolymers with high lysine weight fractions (>75 wt%). In contrast to PK diblock copolymers in this composition range, KPK triblock copolymers exhibit morphology transitions as a function of pH. Using a combination of light-scattering and microscopy techniques, we demonstrate spherical micelle-vesicle and spherical micelle-disk micelle transitions for different K fractions. We interpret these morphology changes in terms of the energy penalty associated with folding the core P block to form a spherical micelle in relation to the interfacial curvature associated with different charged states of the K block.

Temperature- and pH-responsive self-assembly of poly(propylene oxide)-b-poly(lysine) block copolymers in aqueous solution.

A series of poly(propylene oxide)-b-poly(L-lysine) (PPO-PK) block copolymers were synthesized using Huisgen's 1,3-dipolar cycloaddition, and the solution self-assembly was studied using transmission electron microscopy, circular dichroism spectroscopy, and dynamic and static light scattering techniques. In contrast to previous studies of poly(lysine)-based block copolymers, PPO-PK exhibits a significant shift in the pH associated with the helix-coil transition of the poly(lysine) block, potentially a result of decreased hydrophobicity in the core PPO block. Given the proximity of the lower critical solution temperature of the PPO block, these materials exhibit both pH and temperature-responsive (i.e., "schizophrenic") self-assembly, the latter of which was interpreted in terms of changes in the second osmotic virial coefficient. Finally, the vesicle morphology obtained from these polymers was studied for the propensity in drug encapsulation and passive release.

Acute Prevertebral Calcific Tendinitis.

We present a case of neck pain in a middle-aged woman, initially attributed to a retropharyngeal infection and treated with urgent intubation. With the help of computed tomography, the diagnosis was later revised to acute prevertebral calcific tendinitis, a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the longus colli muscles. It is critical to differentiate between these two disease entities due to dramatic differences in management. A discussion of acute prevertebral calcific tendinitis and its imaging findings is provided below.

First report of Schistosoma mekongi infection with brain involvement.

We describe, to our knowledge, the first reported case of Schistosoma mekongi infection with brain involvement. S. mekongi is a distinct species most closely related to Schistosoma japonicum that is endemic in a defined area of the Mekong River in Laos and Cambodia and characteristically associated with hepatosplenic disease. The patient had an excellent response to praziquantel therapy but required repeated courses of corticosteroid therapy to suppress recrudescent neurological symptoms.

Prolonged Delirium Secondary to Hypoxic-ischemic Encephalopathy Following Cardiac Arrest.

Hypoxic-ischemic brain injury encompasses a complex constellation of pathophysiological and cellular brain injury induced by hypoxia, ischemia, cytotoxicity, or combinations of these mechanisms and can result in poor outcomes including significant changes in personality and cognitive impairments in memory, cognition, and attention. We report a case of a male patient with normal premorbid functioning who developed prolonged delirium following hypoxic-ischemic brain insults subsequent to cardiac arrest. The case highlights the importance of adopting a multidisciplinary treatment approach involving the coordinated care of medical and nursing teams to optimise management of patients suffering from such a debilitating organic brain syndrome.

Persistent, severe hypoglycemia-induced organic brain syndrome with neurological sequelae: a case report.

Hypoglycemia is a biochemical abnormality and often the rate-limiting step in the treatment of both type 1 and type 2 diabetes mellitus. Left uncorrected and prolonged, hypoglycemia can result in neuronal dysfunction and death, with deficits ranging from measurable cognitive impairments to aberrant behavior, seizures and coma. In this case report, hypoglycemia resulted in severe and persistent neurological (slurred speech and gait abnormalities), cognitive (inattention, disorientation and memory deficits) and behavioral manifestations (verbal hostility and irritability). It highlights the potentially severe neuropsychiatric sequelae following hypoglycemia and is timely for clinicians to be reminded that hypoglycemia prevention needs to be more of a focus of diabetes care in general.