Development of Concurrent Retinotopic Maps in the Fly Motion Detection Circuit.

Understanding how complex brain wiring is produced during development is a daunting challenge. In Drosophila, information from 800 retinal ommatidia is processed in distinct brain neuropiles, each subdivided into 800 matching retinotopic columns. The lobula plate comprises four T4 and four T5 neuronal subtypes. T4 neurons respond to bright edge motion, whereas T5 neurons respond to dark edge motion. Each is tuned to motion in one of the four cardinal directions, effectively establishing eight concurrent retinotopic maps to support wide-field motion. We discovered a mode of neurogenesis where two sequential Notch-dependent divisions of either a horizontal or a vertical progenitor produce matching sets of two T4 and two T5 neurons retinotopically coincident with pairwise opposite direction selectivity. We show that retinotopy is an emergent characteristic of this neurogenic program and derives directly from neuronal birth order. Our work illustrates how simple developmental rules can implement complex neural organization.

ICON 2020-International Scientific Tendinopathy Symposium Consensus: the development of a core outcome set for gluteal tendinopathy.

Gluteal tendinopathy (GT) is common and can be debilitating and challenging to manage. A lack of condition specific and appropriate outcome measures compromise evidence synthesis for treatment and limits clinical guideline development. Our objective was to develop a core outcome measurement set for GT (COS-GT). Participants were patients with GT and expert health professionals (HPs). A scoping review identified measures used in GT research, which were mapped to the nine International Scientific Tendinopathy Symposium Consensus core domains, and included in two surveys of HPs. The first survey identified the feasible and true measures for each domain. The second survey refined the list which a patient focus group then considered. Meeting online, HPs reached consensus (agreement ≥70%) on the most appropriate COS-GT measures. 34 HPs and seven patients were recruited. 57 measures were mapped to the nine core domains. Six measures did not proceed past survey one. Of those that progressed, none had adequate clinimetric properties for a COS-GT. Thus, participants decided on interim measures: the global rating of change, pain at night, time to pain onset with single limb stance, pain with stair walking, pain self-efficacy and hip abduction strength. HP participants additionally recommended that pain over the last week, the European Quality of Life-5 dimensions-5 levels and the Victorian Institute of Sport Assessment-Gluteal be considered in clinical trials, as they currently provide best easures of the relevant tendinopathy domains. In conclusion this interim COS-GT should guide outcome measure selection in clinical practice and future research trials in patients with GT.

Granulomatous cheilitis of Miescher: a rare entity.

BACKGROUND: Granulomatous cheilitis (GC) is a rare entity of unknown etiology. It is a chronic inflammatory disorder with a predilection for young females. It is characterized by asymptomatic unrelenting swelling of lips. It is a monosymptomatic form or an incomplete variant of Melkersson-Rosenthal syndrome (a triad of recurrent orofacial swelling, relapsing facial paralysis, and fissuring of the tongue). CASE PRESENTATION: We herewith report a case of a 27-year-old female, presenting with persistent upper lip swelling, for 3 months. Biopsy from the lesion revealed features of granulomatous cheilitis. CONCLUSION: GC should be considered in the differential diagnosis of unrelenting swelling in the lip. Spontaneous remission is rare, and recurrences are common. Corticosteroids used for treatment provide temporary improvement.

Cervical syringomyelia with caudal thoracic epidural lipomatosis: case report and literature review.

Syringomyelia associated with epidural lipomatosis is a rare finding. Only three published cases of epidural lipomatosis associated with syringomyelia exist in the literature.We report the case of a 46-year-old woman who presented with progressive myelopathy over an 18-month period. Imaging revealed significant thoracic spinal cord compression secondary to epidural lipomatosis from T3 to T8 with cephalad cervical syringomyelia extending from C7 to T1. Imaging was unremarkable for Chiari malformation or a craniospinal space-occupying lesion. A T2 to T8 laminoplasty was performed, removing excessive epidural adipose tissue to decompress the thoracic spinal cord. Postoperatively, the patient reported symptom improvement with complete symptom resolution at 3 months. Follow-up imaging at 3-months demonstrated thoracic spinal cord decompression with mild syrinx reduction. At two-year follow-up the patient remained asymptomatic with unchanged imaging.Syringomyelia in the setting epidural lipomatosis is a rare finding.

The Clinical Significance of Small Vessel Vasculitis on Temporal Artery Biopsies.

BACKGROUND: Giant cell arteritis (GCA) is the most common type of systemic vasculitis in the elderly. Untreated, it can lead to irreversible blindness. Its diagnosis relies on a temporal artery biopsy (TAB). However, a proportion of patients have small vessel vasculitis (SVV) on biopsy; the prognosis of which remains unclear. The aim of this study is to compare the clinical presentation and long-term outcomes of those with SVV with negative and positive biopsies to determine whether long-term corticosteroid therapy can be avoided in these patients. METHODS: Post hoc analysis of patients with suspected GCA who underwent TAB and fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan as part of a prospective GCA and PET cohort. Patients were divided in to 3 groups based on TAB result: positive (inflammation in the main artery wall), negative (no inflammation), and SVV (isolated vasa vasorum or periadventitial SVV). Clinical, serological, and PET/CT data of patients with SVV were compared with those with positive and those with negative biopsies. RESULTS: For the 58 eligible patients recruited between May 2016 and December 2017, 11 had SVV, 12 had positive, and 35 had negative biopsies. Patients with SVV had similar clinical, serological, and PET/CT findings to those with negative biopsies. Compared with those with positive biopsies, patients with SVV had lower erythrocyte sedimentation rate (25 vs 78 mm/hour; P = 0.02), platelet count (296 vs 385 ×109/L; P = 0.03), and a lower median total vascular score on PET/CT scan (1.0 vs 13.5; P = 0.01). Median prednisone dose was lower (4.8 vs 11.7 mg; P = 0.015) and fewer were on steroid-sparing agents (20% vs 67%; P = 0.043) at 6 months. The percentage of patients with a clinical diagnosis of GCA was similar between those with SVV (3/11, 27.3%) and those with negative biopsies (5/35, 14.3%; P = 0.374). CONCLUSIONS: Patients with SVV on TAB had similar clinical features, PET/CT findings, and 6-month outcomes to those with negative biopsies. Small vessel vasculitis can be treated as equivalent to a negative biopsy when being considered for diagnosis and treatment of GCA.

Molecular characterization of lung carcinomas: A study on diagnostic, predictive, and prognostic markers using immunohistochemical analysis at a Tertiary Care Center in Uttarakhand, India.

INTRODUCTION: Focused studies in different geographic regions would delineate the underlying biological differences and molecular alterations in non-small cell lung cancer (NSCLC) worldwide. Previous studies in literature have documented limited characterization by studying a minimal number of biological markers. This study was done to evaluate expression of multiple immunomarkers including diagnostic, prognostic, and predictive markers in NSCLC for its characterization. MATERIALS AND METHODS: This was an observational study conducted on 60 consecutive cases of NSCLC. Immunomarkers comprising of p63, p40, TTF-1, napsin A, B-Raf, c-Met, phospho-AKT (P-AKT), PTEN, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR) and K-Ras, synaptophysin, chromogranin and pan-cytokeratin were evaluated on paraffin-embedded tissue sections of NSCLC. RESULTS: Age of patients with NSCLC in our study ranged from 35 to 90 years, and 93.3% of them were chronic smokers. 93.3% of cases presented in late stages (Stages III and IV) and 78% of cases were squamous cell carcinoma (SCC). EGFR positivity was noted in 83.3% of cases. ALK was positive in one case while C-Met and PTEN immunopositivity was noted in only two cases. Ten cases showed positivity for K-Ras and 90% of these were SCC. Ten cases were positive for B-Raf and 80% of these were SCC. 30% of cases showed immunopositivity for P-AKT. None of the molecular markers was found to have statistically significant correlation with clinicopathological parameters. CONCLUSION: SCC is the predominant histological subtype of NSCLC in the region of Uttarakhand, India, with a high proportion of cases harboring EGFR mutation. Variable expression of K-Ras, P-AKT, ALK 1, and PTEN in NSCLC signifies that molecular profile of every case is individualistic and independent. We attribute this to ethnicity, influence of implicated substance or metabolite in tobacco, and variable mutations incurred in tumor cells over a period of time.

Short term biological variation of common hematological parameters in healthy subjects in a South Asian population.

There is no rigorous publication on the biological variation of common hematological parameters in South Asians to date. Also, there are few publications worldwide dealing with a variation of Reticulocyte parameters. Therefore, an attempt was made to estimate the short term within-subject and between-subject biological variation of common hematological and reticulocyte parameters. Twenty-eight healthy individuals (fifteen males and thirteen females) were selected after clinical and laboratory examination. Blood was collected in K3-EDTA vials in the morning for six consecutive days and analysed in triplicate on the Sysmex XN-1000 analyzer. Outliers were excluded and the within-subject, between-subject and analytical coefficient of variation calculated after statistical analysis by nested repeated measures ANOVA. The Reference change values (RCV), and estimates for desirable imprecision, bias, total error and index of individuality calculated. The within-subject biological variation for the studied subset belonging to South Asia closely followed published European and American studies and were similar for males and females. The between-subject variation showed differences from the published studies for white blood cells, platelets, red blood cells, hemoglobin, platelet indices and reticulocyte hemoglobin as well as between males and females for hemoglobin, red blood cell count and hematocrit. All the indices of individuality were low. This study supports the contention that the conclusions from within-subject biological variation for common hematological parameters are important and transportable to a South Asian population for short-term serial measurements. For quality specifications dependent on between-subject variation, the lower estimates from European and American studies should be used.

Short-term biological variation of differential count in healthy subjects in a South Asian population.

Estimates of Within-Subject and between subject biological variation for the white blood cell differential count (DC) have not been reported in South Asia. Therefore, we attempted to measure the short-term biological variation estimates for DC. The study was conducted on 28 healthy volunteers (15 males and 13 females). Blood from the volunteers was collected in the morning in K3-EDTA vials and analyzed in triplicate on the Sysmex XN-1000 analyzer, for six consecutive days. The Within subject, between subject and analytical coefficient of variation of the DC was calculated from the results by nested repeated measures ANOVA after outlier exclusion. The Reference change values (RCV) were also calculated. The within-subject variation for eosinophil Count and between subject variation for basophils in our study from South Asia was greater than the published European and American studies. Males and females showed similar biological variation for DC. The within-subject variation of other parameters (Neutrophils, Lymphocytes, Monocytes and Basophils) were similar or showed only mild differences to the published studies. The markedly different within-subject variation for Eosinophil counts suggest that the RCV for DC in South Asians need to be different from the published data in order to have clinical relevance. The Within-subject variation values of the other parameters seem transportable from the published European and American studies, but the small differences found mean that further regional estimates need to be reported for robust evidence of the same.

Foot measures in patients with pes cavus with and without charcot-marie-tooth disease: A pilot study.

INTRODUCTION: Pes cavus often signals the presence of Charcot-Marie-Tooth (CMT) in adult patients, although its prevalence in the general population makes it a finding of unclear significance. METHODS: We undertook a pilot double cohort study to investigate the feasibility of comparing preselected bedside and radiographic foot measures in pes cavus patients with and without CMT. RESULTS: A total of 16 CMT and 11 non-CMT patients were recruited. Although no findings consistently met statistical significance, recruitment was highly limiting. CONCLUSIONS: Formalized foot measurement comparisons of CMT and non-CMT pes cavus are feasible. Larger studies will be necessary to determine if there are differences in foot structure based on the presence of a hereditary neuropathy. Muscle Nerve 59:122-125, 2019.

Development of Charcot Neuroarthropathy in Diabetic Patients who Received Kidney or Kidney-Pancreas Transplants.

Only a small percentage of the general diabetic population develops Charcot neuroarthropathy. Charcot arthropathy greatly increases the risk of foot complications. At our academic institution, there appeared to be an increased incidence of Charcot arthropathy in transplant patients. We hypothesized that Charcot neuroarthropathy incidence is higher in the diabetic patients who had received kidney or kidney-pancreas transplants. The charts of 1000 patients were reviewed from January 2000 to January 2011. Four hundred and eighty-seven patients were included in the study. Of these diabetic patients, 249 had received a kidney transplant and 238 a kidney-pancreas transplant. The data were analyzed for the incidence of Charcot in each group. Other risk factors and sequelae were also evaluated and analyzed. The incidence of Charcot development in the diabetic patients who had a kidney-pancreas transplant was 18.4%, 44 of 238 patients. This was significantly higher than the incidence in kidney transplant patients, which was 11.2%, 28 of 249 patients (p < .05). Peripheral arterial disease was a statistically significant independent risk factor for developing ulceration, osteomyelitis, and subsequent amputation. Type 1 diabetic patients developed Charcot at a higher rate that was also statistically significant compared with type 2 diabetic patients. In our study, diabetic patients who had undergone kidney-pancreas transplants were associated with higher risk for development of Charcot neuroarthropathy than kidney transplants alone. The incidence of Charcot development in both these transplant groups was also much higher than in the general diabetic population. This is of particular interest to clinicians and surgeons as both transplant groups were found to be high risk for subsequent foot ulceration, infection, and amputation.

Update on giant cell arteritis.

PURPOSE OF REVIEW: Giant cell arteritis (GCA) is a challenging condition to manage because of the potential for acute irreversible vision loss and corticosteroid-related morbidity. Recent developments offer the potential to improve both the assessment and treatment of patients. RECENT FINDINGS: Vascular imaging is increasingly being used in the diagnostic algorithm for GCA. Results from recent vascular ultrasound and high-resolution cranial MRI studies have led some groups to suggest forgoing temporal artery biopsy (TAB) in selected patients. The treatment armamentarium has been enhanced with the addition of Tocilizumab, a monoclonal antibody that inhibits IL-6 and has been shown to be effective in sustaining glucocorticoid-free remission out to 52 weeks. New publications have provided guidance in how clinicians can interpret minimally inflamed biopsies and navigate the controversy about what role, if any, varicella zoster virus may play in the pathophysiology of GCA. Basic science developments have improved our understanding of the immunopathology of GCA including the role of Th1 and Th17 lymphocytes and mechanisms of arterial wall lymphocyte invasion. SUMMARY: There have been significant recent advances in GCA, particularly in relation to imaging and treatment options. Longer term outcome data will help clarify how best to utilize them in routine clinical practice.

Ringer's Lactate Versus Normal Saline in Urgent Cesarean Delivery in a Resource-Limited Setting: A Pragmatic Clinical Trial.

BACKGROUND: Crystalloids are used routinely for perioperative fluid management in cesarean delivery. Few studies have determined the crystalloid of choice in obstetric anesthesia. We compared the effects of Ringer's lactate (RL) versus 0.9% normal saline (NS) on maternal and neonatal blood pH and 24-hour postoperative morbidity in urgent cesarean delivery in a low-resource setting. Our hypothesis was that RL would result in 30% less acidosis than NS. METHODS: This was a pragmatic prospective double-blind randomized controlled trial in the Mulago National Referral Hospital Labor Ward Theater from September 2011 to May 2012. Five hundred parturients were studied; 252 were randomly assigned to NS and 248 to RL groups. Preoperative and postoperative maternal venous blood gases and placental umbilical arterial cord blood gases were analyzed. The primary outcome was incidence of maternal acidosis, as defined by a postoperative drop in venous pH below 7.32 or reduction in base excess below -3 in a previously normal parturient. Maternal 24-hour postoperative morbidity, neonatal pH, and neonatal base excess were the main secondary outcomes. The study was registered in ClinicalTrials.gov as NCT01585740. RESULTS: The overall incidence of maternal acidosis was 38% in NS and 29% in RL (relative risk, 1.29; 95% confidence interval, 1.01-1.66; P = .04). Thirty-two percent of parturients in NS experienced a drop in venous pH below 7.32 postoperatively, compared with 19% in RL (relative risk, 1.65; 95% confidence interval, 1.18-2.31; P = .003). The comparative drop in base excess postoperatively below -3 between the 2 groups was not statistically significant. There were no significant differences in the incidence of maternal 24-hour postoperative morbidity events and neonatal outcomes between the 2 groups. CONCLUSIONS: NS may be a safe choice for intraoperative fluid therapy in urgent cesarean delivery as RL, albeit with an increased incidence of metabolic acidosis.

Intravenous acetaminophen in bariatric surgery: effects on opioid requirements.

BACKGROUND: Opioids are commonly used after bariatric surgery for pain control because of their potent analgesic effects. Nevertheless, the morbidly obese patient has increased risk for developing adverse effects produced by opioids (such as sedation, apnea, hypoxemia, ileus, and vomiting). Intravenous acetaminophen (IVA) has been evaluated in some specialties showing a reduction in opioid consumption. The purpose of this study was to evaluate the effect on opioid consumption when IVA is administered in bariatric surgery patients. MATERIAL AND METHODS: A retrospective study was performed in patients who underwent bariatric surgery. Group A included those patients who received IVA perioperatively and group B those who did not. The amount of opioids administered was calculated and compared for each group. RESULTS: Group A included 38 cases (44.7%) and group B included 47 cases (55.3%). A comparison was performed in terms of age (P = 0.349), body mass index (P = 0.311), gender (P = 0.890), American Society of Anesthesiologist score (P = 0.438), total surgical time (P = 0.497), perioperative complications (P = 0.786), number of procedures per surgeon (P = 0.08), and type of surgical procedure (P ≤ 0.01). Group A had a mean 24-h total opioid dose of 99.5 mg, whereas group B of 164.6 mg (P = 0.018). Group A received 39.5% less opioids than group B. A post hoc analysis determined a statistical power of 0.74. CONCLUSIONS: IVA used perioperatively can decrease opioid consumption in patients after bariatric surgery. Randomized trials are needed to corroborate these results.

Cancer genomic research at the crossroads: realizing the changing genetic landscape as intratumoral spatial and temporal heterogeneity becomes a confounding factor.

The US National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) created the Cancer Genome Atlas (TCGA) Project in 2006. The TCGA's goal was to sequence the genomes of 10,000 tumors to identify common genetic changes among different types of tumors for developing genetic-based treatments. TCGA offered great potential for cancer patients, but in reality has little impact on clinical applications. Recent reports place the past TCGA approach of testing a small tumor mass at a single time-point at a crossroads. This crossroads presents us with the conundrum of whether we should sequence more tumors or obtain multiple biopsies from each individual tumor at different time points. Sequencing more tumors with the past TCGA approach of single time-point sampling can neither capture the heterogeneity between different parts of the same tumor nor catch the heterogeneity that occurs as a function of time, error rates, and random drift. Obtaining multiple biopsies from each individual tumor presents multiple logistical and financial challenges. Here, we review current literature and rethink the utility and application of the TCGA approach. We discuss that the TCGA-led catalogue may provide insights into studying the functional significance of oncogenic genes in reference to non-cancer genetic background. Different methods to enhance identifying cancer targets, such as single cell technology, real time imaging of cancer cells with a biological global positioning system, and cross-referencing big data sets, are offered as ways to address sampling discrepancies in the face of tumor heterogeneity. We predict that TCGA landmarks may prove far more useful for cancer prevention than for cancer diagnosis and treatment when considering the effect of non-cancer genes and the normal genetic background on tumor microenvironment. Cancer prevention can be better realized once we understand how therapy affects the genetic makeup of cancer over time in a clinical setting. This may help create novel therapies for gene mutations that arise during a tumor's evolution from the selection pressure of treatment.

The IUPAC aqueous and non-aqueous experimental pKa data repositories of organic acids and bases.

Accurate and well-curated experimental pKa data of organic acids and bases in both aqueous and non-aqueous media are invaluable in many areas of chemical research, including pharmaceutical, agrochemical, specialty chemical and property prediction research. In pharmaceutical research, pKa data are relevant in ligand design, protein binding, absorption, distribution, metabolism, elimination as well as solubility and dissolution rate. The pKa data compilations of the International Union of Pure and Applied Chemistry, originally in book form, have been carefully converted into computer-readable form, with value being added in the process, in the form of ionisation assignments and tautomer enumeration. These compilations offer a broad range of chemistry in both aqueous and non-aqueous media and the experimental conditions and original reference for all pKa determinations are supplied. The statistics for these compilations are presented and the utility of the computer-readable form of these compilations is examined in comparison to other pKa compilations. Finally, information is provided about how to access these databases.

Appendicular skeletal muscle in hospitalised hip-fracture patients: development and cross-validation of anthropometric prediction equations against dual-energy X-ray absorptiometry.

BACKGROUND: accurate and practical assessment methods for assessing appendicular skeletal muscle (ASM) is of clinical importance for the diagnosis of geriatric syndromes associated with skeletal muscle wasting. OBJECTIVES: the purpose of this study was to develop and cross-validate novel anthropometric prediction equations for the estimate of ASM in older adults post-surgical fixation for hip fracture, using dual-energy X-ray absorptiometry (DEXA) as the criterion measure. SUBJECTS: community-dwelling older adults (aged ≥65 years) recently hospitalised for hip fracture. SETTING: participants were recruited from hospital in the acute phase of recovery. DESIGN: validation measurement study. MEASUREMENTS: a total of 79 hip fracture patients were involved in the development of the regression models (MD group). A further 64 hip fracture patients also recruited in the early phase of recovery were used in the cross-validation of the regression models (CV group). Multiple linear regression analyses were undertaken in the MD group to identify the best performing prediction models. The linear coefficient of determination (R(2)) in addition to the standard error of the estimate (SEE) were calculated to determine the best performing model. Agreement between estimated ASM and ASMDEXA in the CV group was assessed using paired t-tests with the 95% limits of agreement (LOA) assessed using Bland-Altman analyses. RESULTS: the mean age of all the participants was 82.1 ± 7.3 years. The best two prediction models are presented as follows: ASMPRED-EQUATION_1: 22.28 - (0.069 * age) + (0.407 * weight) - (0.807 * BMI) - (0.222 * MAC) (adjusted R(2): 0.76; SEE: 1.80 kg); ASMPRED-EQUATION_2: 16.77 - (0.036 * age) + (0.385 * weight) - (0.873 * BMI) (adjusted R(2): 0.73; SEE: 1.90 kg). The mean bias from the CV group between ASMDEXA and the predictive equations is as follows: ASMDEXA - ASMPRED-EQUATION_1: 0.29 ± 2.6 kg (LOA: -4.80, 5.40 kg); ASMDEXA - ASMPRED-EQUATION_2: 0.13 ± 2.5 kg (LOA: -4.77, 5.0 kg). No significant difference was observed between measured ASMDEXA and estimated ASM (ASMDEXA: 16.4 ± 3.9 kg; ASMPRED-EQUATION_1: 16.7 ± 3.2 kg (P = 0.379); ASMPRED-EQUATION_2: 16.6 ± 3.2 kg (P = 0.670)). CONCLUSIONS: we have developed and cross-validated novel anthropometric prediction equations against DEXA for the estimate of ASM designed for application in older orthopaedic patients. Our equation may be of use as an alternative to DEXA in the diagnosis of skeletal muscle wasting syndromes. Further validation studies are required to determine the clinical utility of our equation across other settings, including hip fracture patients admitted from residential care, and also with a longer-term follow-up.

Increasing magic number and other trends in diagnostic radiology NRMP match data.

The magic number, or number of ranks needed to achieve a greater than 90 % chance of matching, has not been investigated for diagnostic radiology (DR). Somewhat reflective of a field's changing competitiveness, this individual metric can be useful for reassuring applicants or identifying a need to reach out to mentors. The NRMP's Charting Outcomes in the Match was accessed over the previous 10 cycles to assess changes to magic number and other match-related metrics. Over the last 10 cycles, there has been an increase in magic number for prospective radiologists. Based on the most 2022 recent report, the magic number was 14 compared to 5 and 2 in 2014 and 2016 respectively. Compared to the average US MD senior, those applying into DR were significantly more likely to match in 2014, 2016 and 2020 (p < 0.01 for all), and significantly less likely to match in 2018 and 2022 (p = 0.03 and p < 0.01, respectively). This trend has had important consequences for applicants and programs as the incentive to apply more widely grows. The increasing magic number demonstrates increasing competitiveness in the field, which might be due to a positive job market, changing medical student preferences, or increased access to radiology electives and mentors. The 2024 Charting Outcomes document will be the first to include data from a class almost entirely affected by the change to a pass/fail Step1 and the new preference signaling supplement. It is currently unclear how either change will affect the overall competitiveness of the field and the magic number.