A comparative study between cryo-laser cryo-sclerotherapy and sclerotherapy in the treatment of telangiectasia and reticular veins: A randomized controlled trial.

OBJECTIVE: Telangiectasias, characterized by dilated venules, are frequently observed in the lower extremities. Sclerotherapy stands out as the predominant treatment of these vascular lesions. The integration of laser therapy with a mild sclerosing agent, serving as an osmotic sclerosant, presents an enhanced cosmetic treatment approach, aiming to optimize outcomes and minimize potential adverse effects. This study sought to evaluate the feasibility, efficacy, and safety of cryo-laser and cryo-sclerotherapy (CLaCS) and compare it with injection sclerotherapy for the treatment of telangiectasia and reticular veins. METHODS: In this randomized controlled trial, individuals expressing concerns about telangiectasia and reticular veins were recruited for aesthetic treatment. The enrolled patients were prospectively randomized according to the chosen treatment technique. Group A included patients undergoing CLaCS with 70% dextrose, focusing on a single area measuring 20 cm by 20 cm. Group B included patients receiving polidocanol injection sclerotherapy for a single area of the same dimensions. RESULTS: Group A comprised 195 patients and group B comprised 197 patients. The rates of complete lesion elimination after the first, second, and third treatment sessions were 64.6%, 86.2%, and 100% in group A and 50.3%, 74.1%, and 85.3% in group B, respectively. Group A exhibited a significantly higher complete elimination rate compared with group B at the conclusion of the study (P < .001). Furthermore, group A demonstrated a statistically significant lower incidence of postprocedural pigmentation and other complications compared with group B (P < .001). These findings underscore the enhanced efficacy and safety profile associated with the CLaCS technique using 70% dextrose compared with injection sclerotherapy with polidocanol. CONCLUSIONS: CLaCS, combining cryo-laser and cryo-sclerotherapy, demonstrated superior efficacy and safety compared with traditional polidocanol sclerotherapy for treating telangiectasia and reticular veins.

The outcome of sharp recanalization of chronic central venous occlusions in patients undergoing hemodialysis.

BACKGROUND: Patients on hemodialysis are particularly vulnerable to central venous occlusion (CVO). Endovascular treatment has gained wide acceptance for the treatment of CVO. However, difficulties in crossing the occluded segment can be encountered during conventional endovascular management. Sharp recanalization has been adopted when conventional endovascular methods could not recanalize the obstructed region. This study aimed to assess the outcome of the sharp venous recanalization technique with angioplasty and stenting in the treatment of CVO in Egyptian patients undergoing hemodialysis. METHODS: This retrospective study is based on data from a prospectively maintained department database of patients under regular hemodialysis who underwent the sharp venous recanalization technique for CVO. Routinely, the patients were followed up at 3, 6, and 12 months with a clinical examination. The primary outcomes were technical success and primary patency. Secondary outcomes included complication rates and clinical success. RESULTS: This study included 40 patients. Thirty-six patients (90%) achieved technical and clinical success. Seven patients (17.5%) had immediate postoperative complications. Four cases had minor complications (10%) and three patients had major complications (7.5%): hemothorax in two patients (5.1%) and pneumothorax in one patient (2.6%). At the 1-year follow-up, reintervention was required in nine patients (22.5%), with primary patency rate of 77.5% and a secondary patency rate of 100%. CONCLUSIONS: Sharp recanalization offers a solution for patients undergoing hemodialysis who developed CVO and failed to be recanalized using the conventional endovascular method. It offered promising technical success, clinical improvement, and good primary patency rates.

Diet composition of the Pharaoh eagle owl, Bubo ascalaphus, across agricultural and natural areas in Saudi Arabia.

The diet of the Pharaoh eagle owl, Bubo ascalaphus, inhabiting agricultural and natural areas in Saudi Arabia, was studied. Pellet analysis for B. ascalaphus in the agricultural area contained a high percentage (61.3%) of the house mouse, Mus musculus, while pellets collected from natural habitats were void of M. musculus, however, with a high proportion of wild rodents (Meriones crassus (28.6%) and Jaculus loftusi (41.6%). This suggests the importance of this owl as a biological control agent in agricultural areas.

Local production of 17ß-oestradiol in the endometrium during the implantation window: a pilot study.

Abstract: Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17ß-oestradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/intracytoplasmic sperm injection (ICSI). Endometrial biopsies were obtained from IVF/ICSI patients 5-8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n = 15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n = 15). Formation of 17ß-oestradiol (oxidative 17ß-hydroxysteroid dehydrogenases (HSDs)), oestrone (reductive HSD17Bs) and inhibition of HSD17B1 activity were determined by high-performance liquid chromatography. The endometrial transcriptome was profiled using RNA sequencing followed by principal component analysis and differentially expressed gene analysis. The false discovery rate-adjusted P < 0.05 and log fold change >0.5 were selected as the screening threshold. Formation and inactivation of 17ß-oestradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n = 12) were considered (27.1%, n = 5 vs 16.2%, n = 7, P = 0.04). Gene expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolising enzymes in the endometrium. In the primary infertile subgroup (n = 10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid-metabolising enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups. Lay summary: Sex hormones are produced and broken down by enzymes that can be found in the endometrium (the inner lining of the womb). This enzyme activity might influence the chances of becoming pregnant. We compared (i) enzyme activity in the endometrium of 15 women who did and 15 women who did not become pregnant in their second in vitro fertilisation attempt, (ii) how enzyme activity can be blocked by an inhibitor, and (iii) differences in gene expression (the process by which instructions in our DNA are converted into a product). Enzyme activity was similar between groups. We found that in women who have never been pregnant in the past, inhibition of enzyme activity was higher and found differences in a gene that has been linked to the implantation of the embryo, but future studies should be performed in larger, well-defined patient groups to confirm these findings.

Clinical supervision in medical education: A citation analysis.

PURPOSE: Medical education relies on clinical supervision for critical functions, including trainee assessment and ensuring patient safety. Yet, there is substantial variance in supervision, which has led to calls for a shared definition of the concept and guidelines to inform practice. AMEE Guide No. 27 provided these desired elements and is highly cited, suggesting that translation and utilization of the Guide's knowledge is suboptimal. This study investigates utilization by systematically characterizing citations to the Guide and by describing translation of its recommendations in relation to supervision. MATERIALS AND METHODS: Citations were identified using Web of Science, Scopus, and Google Scholar. The authors coded all citations and conducted a subanalysis of studies specific to supervision. RESULTS: 583 studies were identified; 268 met inclusion criteria for general analysis of which 167 studies were further analyzed. Most studies reiterated the Guide's characterization of effective supervision, but few demonstrate how these recommendations inform innovations in supervisory practice. CONCLUSION: Translation of the Guide's recommendations regarding clinical supervision appears limited. Future research should consider the extent of knowledge translation occurring in clinical supervision literature as well as AMEE Guides. Increased attention to knowledge translation in medical education may benefit the distribution of similar knowledge products.

Autoimmune epilepsy, retrospective case series of clinical features, management, and outcomes.

OBJECTIVES: To evaluate the clinical and electrographic features of patients with autoimmune epilepsy and assess the influence of early diagnosis and treatment on reducing seizure frequency. METHODS: A retrospective observational case series was conducted utilizing medical records from King Abdullah Medical Hospital between 2017 and 2022. Cases of newly diagnosed seizures were chosen based on laboratory-proven autoimmunity. RESULTS: Five female inpatients were identified, primarily presenting with seizures suggestive of an autoimmune origin. Autoimmune antibodies were detected in all patients as follows: GAD (3), NMDA-R (2). One patient exhibited unilateral temporal lobe onset while three displayed bilateral onset. One patient had an associated malignancy. Rituximab was administered as an immunomodulatory therapy to four patients, resulting in successful seizure reduction post-immunotherapy initiation. CONCLUSION: Autoimmune epilepsy is recognized as a distinct condition. The clinical presentation can be complex and antibody testing may warrant repetition if initial results are negative or if specific antibodies are not detected. Early initiation of immunosuppression, coupled with prompt treatment escalation when required, is vital for achieving optimal patient outcomes.

Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival.

Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96® aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases.

Fatty Acid Conjugated Chalcones as Tubulin Polymerization Inhibitors: Design, Synthesis, QSAR, and Apoptotic and Antiproliferative Activity.

Cancer is often associated with an aberrant increase in tubulin and microtubule activity required for cell migration, invasion, and metastasis. A new series of fatty acid conjugated chalcones have been designed as tubulin polymerization inhibitors and anticancer candidates. These conjugates were designed to harness the beneficial physicochemical properties, ease of synthesis, and tubulin inhibitory activity of two classes of natural components. New lipidated chalcones were synthesized from 4-aminoacetophenone via N-acylation followed by condensation with different aromatic aldehydes. All new compounds showed strong inhibition of tubulin polymerization and antiproliferative activity against breast and lung cancer cell lines (MCF-7 and A549) at low or sub-micromolar concentrations. A significant apoptotic effect was shown using a flow cytometry assay that corresponded to cytotoxicity against cancer cell lines, as indicated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Decanoic acid conjugates were more potent than longer lipid analogues, with the most active being more potent than the reference tubulin inhibitor, combretastatin-A4 and the anticancer drug, doxorubicin. None of the newly synthesized compounds caused any detectable cytotoxicity against the normal cell line (Wi-38) or hemolysis of red blood cells below 100 µM. It is unlikely that the new conjugates described would affect normal cells or interrupt with cell membranes due to their lipidic nature. A quantitative structure-activity relationship analysis was performed to determine the influence of 315 descriptors of the physicochemical properties of the new conjugates on their tubulin inhibitory activity. The obtained model revealed a strong correlation between the tubulin inhibitory activity of the investigated compounds and their dipole moment and degree of reactivity.

Varicose veins as a risk factor for venous thromboembolism in arthroplasty patients: Meta-analysis.

OBJECTIVE: A meta-analysis to determine if patients with varicose veins are at an increased risk of venous thromboembolism (VTE) when undergoing major lower limb arthroplasty. METHODS: Medline, Embase, and Cochrane Library databases were searched using appropriate terms for studies that reported post-operative VTE in patients who had lower limb arthroplasty with any history of varicose veins. Methodological quality of included studies was quantified using the Risk of Bias (ROB) assessment tools. Findings were reported using the meta-analysis of observational studies in epidemiology (MOOSE) checklist. RESULTS: A total of 129 studies were identified with 11 observational studies being eligible for inclusion. This consisted of 265,194 patients who underwent lower limb arthroplasty, 2188 of which had pre-existing varicose veins. Overall, VTE occurred in 1845 patients, and 122 cases had varicose veins present at time of arthroplasty. Meta-analysis indicates that patients undergoing lower limb arthroplasty with varicose veins are at increased risk of having a VTE, OR 2.37, 95% CI 1.54-3.63, (p < 0.001). One study evaluated if previous varicose veins surgery influenced the risk of VTE in arthroplasty patients, OR 0.96 (95% CI 0.7-1.28), p = 0.429. CONCLUSIONS: Varicose veins and lower limb arthroplasty are known independent risk factors for VTE. There is a paucity of data regarding the risk of VTE in patients undergoing lower limb arthroplasty who have co-existing varicose veins. This meta-analysis shows that patients with varicose veins are at an increased risk of VTE when undergoing major lower limb arthroplasty. Further studies are required in order to determine if such patients should undergo varicose vein surgery before undertaking major lower limb joint replacement.

Dust, Sand, and Winds Within an Active Martian Storm in Jezero Crater.

Rovers and landers on Mars have experienced local, regional, and planetary-scale dust storms. However, in situ documentation of active lifting within storms has remained elusive. Over 5-11 January 2022 (LS 153°-156°), a dust storm passed over the Perseverance rover site. Peak visible optical depth was ∼2, and visibility across the crater was briefly reduced. Pressure amplitudes and temperatures responded to the storm. Winds up to 20 m s-1 rotated around the site before the wind sensor was damaged. The rover imaged 21 dust-lifting events-gusts and dust devils-in one 25-min period, and at least three events mobilized sediment near the rover. Rover tracks and drill cuttings were extensively modified, and debris was moved onto the rover deck. Migration of small ripples was seen, but there was no large-scale change in undisturbed areas. This work presents an overview of observations and initial results from the study of the storm.

Chemical composition and anticholinesterase activity of Lepisanthes rubiginosa (Roxb.) Leenh. essential oil.

Essential oils obtained from medicinal plants show high therapeutic potential against several types of pathologies, including Alzheimer's disease. The purpose of this work was to study the chemical composition and anticholinesterase inhibitory activity of the essential oil obtained from Lepisanthes rubiginosa leaves collected from Malaysia. Twenty-four components were identified using gas chromatography-flame ionization detection (GC-FID) and gas chromatography/mass spectrometry (GC-MS), which represent 99.5% of the essential oil. The identified major components include α-cadinol (40.0%), safrole (12.6%), α-amorphene (9.5%), (E)-isosafrole (5.0%), δ-cadinene (4.2%), and t-muurolol (4.1%). Anticholinesterase activity was assessed using Ellman method, and the essential oil demonstrated a moderate inhibitory activity against acetylcholinesterase (I%: 75.2%) and butyrylcholinesterase (I%: 70.2%) at conconcetration of 1000 µg/mL. The current study is the first to report chemical composition and anticholinesterase activity of the essential oil obtained from L. rubiginosa, which may have implications on the characterization, pharmaceutical, and therapeutic applications of Lepisanthes genus essential oils.

Knowledge, attitudes, and experiences in suicide assessment and management: a qualitative study among primary health care workers in southwestern Uganda.

BACKGROUND: Suicide is one of the leading causes of death globally, with over 75% of all suicides occurring in low-and middle-income Countries. Although 25% of people have contact with their health care workers before suicide attempts, most never receive proper suicide assessment and management. We explored primary care health workers' knowledge, attitudes, and experiences in evaluating and managing suicidality in structured primary healthcare services in Uganda. METHODS: This was a cross-sectional qualitative study among health workers in southwestern Uganda from purposively selected health facilities. A semi-structured interview guide was used, and data were analyzed using thematic analysis. RESULTS: The in-depth interviews were conducted with 18 individuals (i.e., five medical doctors, two clinical officers, two midwives, and nine nurses) from 12 health facilities in the five selected districts. Four themes emerged from the discussions: a) Knowledge and attitudes of primary healthcare workers in the assessment and management of suicidality, b) Experiences in the assessment and management of suicidality, c) challenges faced by primary healthcare workers while assessing and managing suicidality, and d) Recommendations for improving assessment and management of suicidality in PHC. Most participants were knowledgeable about suicide and the associated risk factors but reported challenges in assessing and managing individuals with suicide risk. The participants freely shared individual experiences and attitudes in the assessment and management of suicide. They also proposed possible ways to improve the evaluation and management of suicidality in PHC, such as setting up a system of managing suicidality, regularizing community sensitization, and training health workers. CONCLUSION: Suicidality is commonly encountered by primary health care workers in Uganda who struggle with its assessment and management. Improving the knowledge and attitudes of primary health care workers would be a big step towards ensuring equitable services.

Lack of association between gestational age adjusted TSH percentiles and neurodevelopmental outcomes among preterm infants.

BACKGROUND: Limited evidence exists on whether subclinical hypothyroidism suggested by mildly elevated TSH levels affect neurodevelopment and growth in preterm infants. The objective of this study was to determine the association between gestational age adjusted TSH percentiles and neurodevelopmental outcomes among preterm infants. METHODS: Univariate linear regression analysis was conducted to determine, in infants born less than thirty-two weeks gestational age, the correlation between the TSH percentile on the last newborn screen and neurodevelopmental assessment scores and growth outcomes at eighteen to twenty-two months of corrected age. RESULTS: Seventy-four patients were enrolled in the study with a mean gestational age of 28.8 weeks. There was no correlation between the last TSH percentile value and Bayley-III cognitive composite score or other neurodevelopmental or growth outcomes. CONCLUSION: In a cohort of preterm infants, higher TSH percentiles suggesting potential subclinical hypothyroidism did not predict any adverse effect on neurodevelopmental or growth outcomes.

The landscape of neurophysiological outcome measures in ALS interventional trials: A systematic review.

OBJECTIVE: We collated all interventional clinical trials in amyotrophic lateral sclerosis (ALS), which utilised at least one neurophysiological technique as a primary or secondary outcome measure. By identifying the strengths and limitations of these studies, we aim to guide study design in future trials. METHODS: We conducted and reported this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight databases were searched from inception. In total, 703 studies were retrieved for screening and eligibility assessment. RESULTS: Dating back to 1986, 32 eligible interventional clinical trials were identified, recruiting a median of 30 patients per completed trial. The most widely employed neurophysiological techniques were electromyography, motor unit number estimation (including motor unit number index), neurophysiological index and transcranial magnetic stimulation (including resting motor threshold and short-interval intracortical inhibition). Almost 40% of trials reported a positive outcome with respect to at least one neurophysiological measure. The interventions targeted either ion channels, immune mechanisms or neuronal metabolic pathways. CONCLUSIONS: Neurophysiology offers many promising biomarkers that can be utilised as outcome measures in interventional clinical trials in ALS. When selecting the most appropriate technique, key considerations include methodological standardisation, target engagement and logistical burden. SIGNIFICANCE: Future trial design in ALS would benefit from a standardised, updated and easily accessible repository of neurophysiological outcome measures.

Novel Amiloride Derivatives That Inhibit Bacterial Motility across Multiple Strains and Stator Types.

The bacterial flagellar motor (BFM) is a protein complex that confers motility to cells and contributes to survival and virulence. The BFM consists of stators that are ion-selective membrane protein complexes and a rotor that directly connects to a large filament, acting as a propeller. The stator complexes couple ion transit across the membrane to torque that drives rotation of the motor. The most common ion gradients that drive BFM rotation are protons (H+) and sodium ions (Na+). The sodium-powered stators, like those in the PomA/PomB stator complex of Vibrio spp., can be inhibited by sodium channel inhibitors, in particular, by phenamil, a potent and widely used inhibitor. However, relatively few new sodium motility inhibitors have been described since the discovery of phenamil. In this study, we characterized two possible motility inhibitors, HM2-16F and BB2-50F, from a small library of previously reported amiloride derivatives. We used three approaches: effect on rotation of tethered cells, effect on free-swimming bacteria, and effect on rotation of marker beads. We showed that both HM2-16F and BB2-50F stopped rotation of tethered cells driven by Na+ motors comparable to phenamil at matching concentrations and could also stop rotation of tethered cells driven by H+ motors. Bead measurements in the presence and absence of stators confirmed that the compounds did not inhibit rotation via direct association with the stator, in contrast to the established mode of action of phenamil. Overall, HM2-16F and BB2-50F stopped swimming in both Na+ and H+ stator types and in pathogenic and nonpathogenic strains. IMPORTANCE Here, we characterized two novel amiloride derivatives in the search for antimicrobial compounds that target bacterial motility. These compounds were shown to inhibit flagellar motility at 10 µM across multiple strains: from nonpathogenic Escherichia coli with flagellar rotation driven by proton or chimeric sodium-powered stators, to proton-powered pathogenic E. coli (enterohemorrhagic E. coli or uropathogenic E. coli [EHEC or UPEC, respectively]), and finally, sodium-powered Vibrio alginolyticus. Broad antimotility compounds such as these are important tools in our efforts to control virulence of pathogens in health and agricultural settings.

Ketorolac-fluconazole: A New Combination Reverting Resistance in Candida albicans from Acute Myeloid Leukemia Patients on Induction Chemotherapy: In vitro Study.

BACKGROUND AND OBJECTIVES: Candida albicans is a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML). Prolonged use of fluconazole as empirical antifungal prophylaxis in AML patients leads to overexpression of efflux pump genes that resulted in the emergence of azole-resistant species. Consequently, the introduction of a new strategy to improve the management of C. albicans infections is an urgent need. Nonsteroidal anti-inflammatory drug (NSAID) ketorolac is associated with a reduction in cancer relapses. The present study was performed to investigate the use of ketorolac-fluconazole combination to reverse fluconazole resistance in C. albicans isolated from AML patients on induction chemotherapy. PATIENTS AND METHODS: One hundred and seventy AML patients were evaluated. Fifty C. albicans were isolated and subjected to disc diffusion assay and broth microdilution for fluconazole alone and combined with different concentrations of ketorolac. Efflux pump gene (CDR1, CDR2, and MDR1) expressions were quantified by real-time PCR. RESULTS: The tested ketorolac acted synergistically with fluconazole against resistant C. albicans with the minimum inhibitory concentration (MIC) of fluconazole decreased from >160 µg/mL to 0.3-1.25 µg/mL in (93.8%) of resistant isolates with fractional inhibitory concentration index (FICI) value of 0.25. The majority of the resistant isolates overexpressed CDR1 (71.1%) and MDR1 (60%). CONCLUSION: Ketorolac-fluconazole in vitro combination would be a promising strategy for further clinical in vivo trials to overcome fluconazole resistance in AML patients on induction chemotherapy.

Nuclear heterogeneity is prevalent in high-quality fractionated human sperm cells typically used for assisted conception.

STUDY QUESTION: What is the nuclear heterogeneity of high-density purified human spermatozoa typically used for IVF purposes. SUMMARY ANSWER: The data show that while density gradient separation has improved the overall sperm population, there is still a large degree of nuclear heterogeneity within these cells. WHAT IS KNOWN ALREADY: Chromomycin A3 (CMA3) is an important DNA binding fluorochrome for the assessment of male-factor fertility. It is typically used to predict IVF outcomes on entire sperm ejaculates with very high receiver operating characteristic. Here we used CMA3 to characterise typical populations of human spermatozoa that would be used for IVF purposes after density gradient separation. STUDY DESIGN, SIZE, DURATION: We compared the intensity of CMA3 binding within high-dense sperm populations obtained from men. Binding heterogeneity was confirmed through fluorescence microscopy and FACS analysis independently. We also looked at CMA3 staining directly with head morphology in this sperm population. Finally, we looked at electron micrographs of nuclear heterogeneity (vacuoles, chromatin compaction) of spermatozoa following density gradient sorting of CMA3-stained cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used sperm donors who had fathered one or more children. Semen was collected after 2 days abstinence and purified over Percoll gradients. Only the high-quality spermatozoa, the same used for assisted conception, were then used. Cells were stained with CMA3 and sorted using FACS. Following this, electron micrographs were used to assess nuclear heterogeneity of CMA3-dependent sorted spermatozoa. MAIN RESULTS AND THE ROLE OF CHANCE: CMA3 staining occurs within morphologically normal as well as abnormal spermatozoa. High-intensity CMA3-stained sperm possessed large vacuoles that were not seen in the low-CMA3 population. In addition, the high-CMA3 stained cells possess higher amounts of nuclear granulation. LIMITATIONS, REASONS FOR CAUTION: The present study only describes the issues within the chromatin of these cells and does not suggest an alternate selection technique. WIDER IMPLICATIONS OF THE FINDINGS: CMA3 is one of the better reported prognostic assays in predicting pregnancy outcomes, especially in cases where the male is at fault. However, it is clear that even in fractionated populations of human spermatozoa, there are sperm cells that are morphologically normal yet possess high levels of CMA3 staining and chromatin granulation. The implication of this is that the embryologist, whom selects on the basis of sperm morphology, may choose a cell with poor chromatin, which may lead to poor embryo outcomes. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the National Health and Medical Research council, APP1118943. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Pushing the super-resolution limit: recent improvements in microscopy below the diffraction limit.

Super-resolution microscopy has revolutionised the way we observe biological systems. These methods are now a staple of fluorescence microscopy. Researchers have used super-resolution methods in myriad systems to extract nanoscale spatial information on multiple interacting parts. These methods are continually being extended and reimagined to further push their resolving power and achieve truly single protein resolution. Here, we explore the most recent advances at the frontier of the 'super-resolution' limit and what opportunities remain for further improvements in the near future.

Please be upstanding - A narrative review of evidence comparing upright to supine lumbar spine MRI.

OBJECTIVES: The objective of the review was to examine the evidence comparing upright to supine MRI of the lumbar spine. KEY FINDINGS: A literature search identified 14 articles comparing data where subjects had been scanned in both supine and upright positions on the same scanner. Lumbar spine anatomy is dynamic and therefore subject to morphological changes when transitioning from the supine to the upright position. There is strong evidence to suggest structural changes in spinal morphology due to radiographic positioning, and that upright positioning is better for evaluating spondylolisthesis. CONCLUSION: It has been demonstrated that the scanning position is important in the outcome of the MRI examination of the lumbar spine. With this in mind, it would be beneficial for guidance to be written and adopted to improve the consistency and quality of scanning. IMPLICATIONS FOR PRACTICE: As upright MRI occupies a niche in the scanning sector, many professionals are unaware of its capabilities. This article aims to increase awareness of the use of upright MRI in evaluating the lumbar spine.

Vibrational spectroscopic analysis of blood for diagnosis of infections and sepsis: a review of requirements for a rapid diagnostic test.

Infections and sepsis represent a growing global burden. There is a widespread clinical need for a rapid, high-throughput and sensitive technique for the diagnosis of infections and detection of invading pathogens and the presence of sepsis. Current diagnostic methods primarily consist of laboratory-based haematology, biochemistry and microbiology that are time consuming, labour- and resource-intensive, and prone to both false positive and false negative results. Current methods are insufficient for the increasing demands on healthcare systems, causing delays in diagnosis and initiation of treatment, due to the intrinsic time delay in sample preparation, measurement, and analysis. Vibrational spectroscopic techniques can overcome these limitations by providing a rapid, label-free and low-cost method for blood analysis, with limited sample preparation required, potentially revolutionising clinical diagnostics by producing actionable results that enable early diagnosis, leading to improved patient outcomes. This review will discuss the challenges associated with the diagnosis of infections and sepsis, primarily within the UK healthcare system. We will consider the clinical potential of spectroscopic point-of-care technologies to enable blood analysis in the primary-care setting.