Untangling the wires: development of sparse, distributed connectivity in the mushroom body calyx.

Appropriate perception and representation of sensory stimuli pose an everyday challenge to the brain. In order to represent the wide and unpredictable array of environmental stimuli, principle neurons of associative learning regions receive sparse, combinatorial sensory inputs. Despite the broad role of such networks in sensory neural circuits, the developmental mechanisms underlying their emergence are not well understood. As mammalian sensory coding regions are numerically complex and lack the accessibility of simpler invertebrate systems, we chose to focus this review on the numerically simpler, yet functionally similar, Drosophila mushroom body calyx. We bring together current knowledge about the cellular and molecular mechanisms orchestrating calyx development, in addition to drawing insights from literature regarding construction of sparse wiring in the mammalian cerebellum. From this, we formulate hypotheses to guide our future understanding of the development of this critical perceptual center.

Nephron sparing surgery for renal tumors-comparison of off-clamp partial nephrectomy with hilar clamping.

BACKGROUND AND OBJECTIVE: Open partial nephrectomy (PN) is still considered gold standard procedure for T1 localized renal tumors. Conventional technique involves clamping of the renal artery with or without vein however, renal ischemia produces a certain level of damage to the kidneys. This study aims to investigate potential effect of off-clamp vs. hilar clamping PN on renal function. METHODS: This is a retrospective cohort study of patients who underwent unilateral, open partial nephrectomy for renal tumors b/w January 2009 December 2016 at our institution. A total of 90 partial nephrectomies were performed of which 65 cases were eligible for analysis. Non clamping technique was used in 43 while clamp was applied in 22 patients. Variables studied were patients' demographics, clinical variables, the laterality, tumors size and location, R.E.N.A.L nephrometry score, blood loss, tumor histology and surgical margins. Patients' renal function (serum creatinine and eGFR) were determined pre-operatively, at 3 and 12 months follow up. Data was analyzed on SPSS v. 22. RESULTS: Both the groups were comparable with regards to pre-operative renal function. Mean radiological size of tumor was 4.71±1.31 and 3.81±1.0 (0.003) in two groups respectively. Mean R.E.N.A.L nephrometry score was 6.1±1.5 in off-clamp group compared to 7.05 ± 1.7 in clamp group (p=0.04). No statistically significant difference was found in operative duration, blood loss, positive surgical margins and intra/ peri-operative complications. At three months and one year, renal function was better preserved in non-clamp group compared to clamp group (p=0.001 and 0.007 respectively). CONCLUSION: Off clamp open partial nephrectomy is safe and feasible option leading to less decline in renal function.

Paediatric External Ventricular Drains: Experience from a tertiary care hospital of a Developing Country.

The aim of the study was to describe indications and complications of external ventricular drain (EVD) placement in children aged between 1 month and 16 years. This retrospective chart review was conducted at the Aga Khan University Hospital, Karachi, and comprised all children who underwent EVD placement from January 2007 to December 2014. Of the 177 patients identified, 117(66%) were males 60(34%) were girls. The overall mean age was 5.4±5.2 years. The median Glasgow Coma Scale score on presentation and discharge was 13 (interquartile range [IQR]: 7) and 15 (IQR: 4), respectively. Major diagnosis included intracranial tumour 60(34%), bacterial meningitis 34(19%), tuberculous meningitis 33(18.6%), and haemorrhage 23(13%). Clinical indications for EVD insertion were acute hydrocephalus secondary to infection 64(36.2%), tumour 54(30.5%), and haemorrhage 23(13%) ventriculoperitoneal shunt malfunction or infection 25(14.1%) and traumatic brain injury 11(6.2%). Complications were observed in 47(26%) patients including infections 25(14.1%), malfunction 11(6.2%), haemorrhage 6(3.4%), misplacement 3(1.7%) and obstruction 2(1.1%). Staphylococcus was the main organism isolated. Moreover, 25(14%) patients expired. Acute hydrocephalus was the major indication and EVD infection was the major complication.

Patient safety skills in primary care: a national survey of GP educators.

BACKGROUND: Clinicians have a vital role in promoting patient safety that goes beyond their technical competence. The qualities and attributes of the safe hospital doctor have been explored but similar work within primary care is lacking. Exploring the skills and attributes of a safe GP may help to inform the development of training programmes to promote patient safety within primary care. This study aimed to determine the views of General Practice Educational Supervisors (GPES) regarding the qualities and attributes of a safe General Practitioner (GP) and the perceived trainability of these 'safety skills' and to compare selected results with those generated by a previous study of hospital doctors. METHODS: This was a two-stage study comprising content validation of a safety skills questionnaire (originally developed for hospital doctors) (Stage 1) and a prospective survey of all GPES in Scotland (n = 691) (Stage 2). RESULTS: Stage 1: The content-validated questionnaire comprised 66 safety skills/attributes across 17 broad categories with an overall content validation index of 0.92. Stage 2: 348 (50%) GPES completed the survey. GPES felt the skills/attributes most important to being a safe GP were honesty (93%), technical clinical skills (89%) and conscientiousness (89%). That deemed least important/relevant to being a safe GP was leadership (36%). This contrasts sharply with the views of hospital doctors in the previous study. GPES felt the most trainable safety skills/attributes were technical skills (93%), situation awareness (75%) and anticipation/preparedness (71%). The least trainable were honesty (35%), humility (33%) and patient awareness/empathy (30%). Additional safety skills identified as relevant to primary care included patient advocacy, negotiation skills, accountability/ownership and clinical intuition ('listening to that worrying little inner voice'). CONCLUSIONS: GPES believe a broad range of skills and attributes contribute to being a safe GP. Important but subtle differences exist between what primary care and secondary care doctors perceive as core safety attributes. Educationalists, GPs and patient safety experts should collaborate to develop and implement training in these skills to ensure that current and future GPs possess the necessary competencies to engage and lead in safety improvement efforts.

The sustainable use of diverse plants accustomed by different ethnic groups in Sibi District, Balochistan, Pakistan.

The present study was conducted to analyze the utilization of medicinal plants (traditional as well as cultivated) and there recipes accustomed by different ethnic groups of Sibi District (SD), Balochistan, Pakistan. The study was carried out between 2018 and 2021 by using semi-structured and open-ended questionnaire.. The randomly selected methods applied for this study were mainly based on household surveys walk through and interview with indigenous communityage 40 to 80, a total of 75 plants, belonging to 63 genera and distributed among 33 plant families were recorded. The dominant Plant families were the Fabaceae (12%) of all studied taxa, followed by the Amaranthaceae (7%), Asteraceae (6%), Cucurbitaceae, Solanaceae, Poaceae (4% each), Rhamnaceae and Zygophyllaceae (3%). Thirty traditional Food Recipes (TFR) and Traditional Medicinal Recipes (TMR) were novel being first time reported from SD., which are utilized by the local communities in their daily routine. These ethnic TFR and TMR have a tremendous role in preservation and sustainable use of traditional food habits and culture. It was also documented that along with cultivated, the wild edible and medicinal plant preparations play a significant role in in the economic potential and primary health care system of the local communities. The study recommends the specific measures, such as small industries, improved export means, tourism and educational activities, to protect the traditional knowledge and biocultural heritage of the region before its erosion.

Spatial constraints and cell surface molecule depletion structure a randomly connected learning circuit.

The brain can represent almost limitless objects to "categorize an unlabeled world" (Edelman, 1989). This feat is supported by expansion layer circuit architectures, in which neurons carrying information about discrete sensory channels make combinatorial connections onto much larger postsynaptic populations. Combinatorial connections in expansion layers are modeled as randomized sets. The extent to which randomized wiring exists in vivo is debated, and how combinatorial connectivity patterns are generated during development is not understood. Non-deterministic wiring algorithms could program such connectivity using minimal genomic information. Here, we investigate anatomic and transcriptional patterns and perturb partner availability to ask how Kenyon cells, the expansion layer neurons of the insect mushroom body, obtain combinatorial input from olfactory projection neurons. Olfactory projection neurons form their presynaptic outputs in an orderly, predictable, and biased fashion. We find that Kenyon cells accept spatially co-located but molecularly heterogeneous inputs from this orderly map, and ask how Kenyon cell surface molecule expression impacts partner choice. Cell surface immunoglobulins are broadly depleted in Kenyon cells, and we propose that this allows them to form connections with molecularly heterogeneous partners. This model can explain how developmentally identical neurons acquire diverse wiring identities.

Operation debrief: a SHARP improvement in performance feedback in the operating room.

OBJECTIVES: To explore the current status of performance feedback (debriefing) in the operating room and to develop and evaluate an evidence-based, user-informed intervention termed "SHARP" to improve debriefing in surgery. BACKGROUND: Effective debriefing is a key educational technique for optimizing learning in surgical settings. However, there is a lack of a debriefing culture within surgery. Few studies have prospectively evaluated educational interventions to improve the quality and quantity of performance feedback in surgery. METHODS: This was a prospective pre- and post-study of 100 cases involving 22 trainers (attendings) and 30 surgical residents (postgraduate years 3-8). A trained researcher assessed the quality of debriefings provided to the trainee using the validated Objective Structured Assessment of Debriefing (OSAD) tool alongside ethnographic observation. Following the first 50 cases, an educational intervention termed "SHARP" was introduced and measures repeated for a further 50 cases. User satisfaction with SHARP was assessed via questionnaire. Twenty percent of the cases were observed independently by a second researcher to test interrater reliability. RESULTS: Interrater reliability for OSAD was excellent (ICC = 0.994). Objective scores of debriefing (OSAD) improved significantly after the SHARP intervention: median pre = 19 (range, 8-31); median post = 33 (range, 26-40), P < 0.001. Strong correlations between observer (OSAD) and trainee rating of debriefing were obtained (median ρ = 0.566, P < 0.01). Ethnographic observations also supported a significant improvement in both quality and style of debriefings. Users reported high levels of satisfaction in terms of usefulness, feasibility, and comprehensiveness of the SHARP tool. CONCLUSIONS: SHARP is an effective and efficient means of improving performance feedback in the operating room. Its routine use should be promoted to optimize workplace-based learning and foster a positive culture of debriefing and performance improvement within surgery.

Rosai Dorfman Disease With Extensive Bony Involvement- A Diagnostic Dilemma.

Previously classified as Non Langerhan cell histiocytosis by the Working Group of Histiocytic Society in 1987 Rosai Dorfman Destombes disease was first described by Destombes in 1965 and later in 1969 by Rosai and Dorfman as a rare histiocytic disorder with sinus histiocytosis and massive lymphadenopathy. They exist in both nodal and extranodal forms. Immunohistochemistry is an essential part of diagnosis to differentiate between Langerhans cell histiocytosis and another malignant histiocytosis. Some overlap has also been reported with IgG4-related diseases. We hereby reflect upon a patient who presented to our facility with pyrexia of unknown origin, the challenges faced to reach a diagnosis and the management offered.

Hacking brain development to test models of sensory coding.

Animals can discriminate myriad sensory stimuli but can also generalize from learned experience. You can probably distinguish the favorite teas of your colleagues while still recognizing that all tea pales in comparison to coffee. Tradeoffs between detection, discrimination, and generalization are inherent at every layer of sensory processing. During development, specific quantitative parameters are wired into perceptual circuits and set the playing field on which plasticity mechanisms play out. A primary goal of systems neuroscience is to understand how material properties of a circuit define the logical operations-computations--that it makes, and what good these computations are for survival. A cardinal method in biology-and the mechanism of evolution--is to change a unit or variable within a system and ask how this affects organismal function. Here, we make use of our knowledge of developmental wiring mechanisms to modify hard-wired circuit parameters in the Drosophila melanogaster mushroom body and assess the functional and behavioral consequences. By altering the number of expansion layer neurons (Kenyon cells) and their dendritic complexity, we find that input number, but not cell number, tunes odor selectivity. Simple odor discrimination performance is maintained when Kenyon cell number is reduced and augmented by Kenyon cell expansion.

Input density tunes Kenyon cell sensory responses in the Drosophila mushroom body.

The ability to discriminate sensory stimuli with overlapping features is thought to arise in brain structures called expansion layers, where neurons carrying information about sensory features make combinatorial connections onto a much larger set of cells. For 50 years, expansion coding has been a prime topic of theoretical neuroscience, which seeks to explain how quantitative parameters of the expansion circuit influence sensory sensitivity, discrimination, and generalization. Here, we investigate the developmental events that produce the quantitative parameters of the arthropod expansion layer, called the mushroom body. Using Drosophila melanogaster as a model, we employ genetic and chemical tools to engineer changes to circuit development. These allow us to produce living animals with hypothesis-driven variations on natural expansion layer wiring parameters. We then test the functional and behavioral consequences. By altering the number of expansion layer neurons (Kenyon cells) and their dendritic complexity, we find that input density, but not cell number, tunes neuronal odor selectivity. Simple odor discrimination behavior is maintained when the Kenyon cell number is reduced and augmented by Kenyon cell number expansion. Animals with increased input density to each Kenyon cell show increased overlap in Kenyon cell odor responses and become worse at odor discrimination tasks.

Objective structured assessment of debriefing: bringing science to the art of debriefing in surgery.

OBJECTIVE: : To identify the features of effective debriefing and to use this to develop and validate a tool for assessing such debriefings. INTRODUCTION: : Simulation-based training has become an accepted means of surgical skill acquisition. A key component of this is debriefing-yet there is a paucity of research to guide best practice. METHODS: : Phase 1-Identification of best practice and tool development. A search of the Medline, Embase, PsycINFO, and ERIC databases identified current evidence on debriefing. End-user input was obtained through 33 semistructured interviews conducted with surgeons (n = 18) and other operating room personnel (n = 15) from 3 continents (UK, USA, Australia) using standardized qualitative methodology. An expert panel (n = 7) combined the data to create the Objective Structured Assessment of Debriefing (OSAD) tool. Phase 2-Psychometric testing. OSAD was tested for feasibility, reliability, and validity by 2 independent assessors who rated 20 debriefings following high-fidelity simulations. RESULTS: : Phase 1: 28 reports on debriefing were retrieved from the literature. Key components of an effective debriefing identified from these reports and the 33 interviews included: approach to debriefing, learning environment, learner engagement, reaction, reflection, analysis, diagnosis of strengths and areas for improvement, and application to clinical practice. Phase 2: OSAD was feasible, reliable [inter-rater ICC (intraclass correlation coefficient) = 0.88, test-retest ICC = 0.90], and face and content valid (content validity index = 0.94). CONCLUSIONS: : OSAD provides an evidence-based, end-user informed approach to debriefing in surgery. By quantifying the quality of a debriefing, OSAD has the potential to identify areas for improving practice and to optimize learning during simulation-based training.

Junior doctors' reflections on patient safety.

AIM: To determine whether foundation year 1 (FY1) doctors reflect upon patient safety incidents (PSIs) within their portfolios and the potential value of such reflections for quality of care. METHODS: A cross-sectional retrospective review of every 'reflective practice' portfolio entry made by all FY1 doctors within an Acute Teaching Hospital Trust was conducted in February 2010. Entries were reviewed by two independent blinded researchers to determine whether they related to a PSI that is, any unintended or unexpected incident that could have or did lead to patient harm. For all entries rated positive by both reviewers, a content analysis approach was used to code PSI into incident type, contributing factors and patient outcome according to validated frameworks developed by the National Patient Safety Agency. RESULTS: 139 reflective practice entries were completed by 30 trainees (15 men, 15 women, mean age 24 years). Of the 139 entries, 49% reflected on a PSI. Of these, 22% were due to errors in clinical assessment; 22% were due to delayed access to care; 18% were due to infrastructure/staffing deficiencies; and 16% were due to medication errors. The most common contributing factors were team/social factors (23%), patient factors (22%), communication and task factors (both 17%). The majority of PSIs led to no harm. Six entries described PSIs resulting in patient death, the majority of which were attributable to diagnostic errors. CONCLUSIONS: FY1 doctors commonly reflect on PSIs within their professional portfolios. Such critical reflection can encourage learning but may also promote patient safety and the quality of healthcare across all medical specialties.

Pregnancy and Motherhood Challenges during Postgraduate Training in Pakistan.

In Pakistan, women have outnumbered men in medicine and many women now choose to start a family earlier in their careers. A 24-question survey was electronically distributed over social media. Female postgraduate trainees and consultants who had experienced pregnancy and motherhood during their training were included. Questions were asked about their experiences of pregnancy, news breaking, attitudes of colleagues and supervisors, maternity leaves, and lactational issues. A total of 320 responses were received; Internal Medicine (19.1%), Gynaecology and Obstetrics (15.0%), Surgery 46 (14.4%), and Pediatrics (11.9%) were major specialities. One hundred and nineteen (37.2%) respondents feared they would be considered 'uncommitted" if the news of their pregnancy broke. Breastfeeding was important to 77.5% mothers, but only 40% of the mothers could breastfeed, and 86.2% reported that lactation facilities were inadequate. 50% mothers thought to strongly reconsider their speciality. Postgraduate training programs in Pakistan should be tailored to address the needs of trainee mothers. Key Words: Motherhood, Postgraduate training, Lactation, Pregnancy.

Nodular Lymphocyte Predominant Hodgkin Lymphoma With Aberrant Immunophenotype or Variant Histopathology: Insights From Case Series of Three Patients.

BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) with variant histopathology or aberrant immunophenotype is exceedingly rare and there is paucity of data with regards to its clinical characteristics and course. CASE REPORT: Herein, we present three cases of NLPHL with aberrant immunophenotype or variant histopathological picture, which displayed distinct clinical and imaging findings. These case reports involved a patient with CD30 and CD20 positivity without Reed-Sternberg cells present, a NLPHL patient with aggressive, persistent disease activity with progressive transformation to germinal centres, and a patient with combined morphology of NLPHL and classical Hodgkin's lymphoma. CONCLUSION: Aberrant immunophenotype/variant NLPHL might represent a distinct form of NLPHL, sharing characteristics with classical Hodgkin, non-Hodgkin lymphomas or benign, progressive transformation of germinal centre lymphadenopathy.

Management of Allogeneic Stem Cell Transplantation for High-Risk AML following SARS-CoV-2 Associated Pancytopenia with Marked Bone Marrow Biopsy Alterations.

The present study describes a patient aged 70 with very high-risk AML who successfully received a nonmyeloablative matched unrelated donor allograft shortly following SARS-CoV-2 infection, which manifested with mild cough, interstitial abnormalities on chest CT, and pancytopenia with profound bone marrow biopsy histological alterations. In parallel, our study provides bone marrow biopsy data in a series of contemporary patients with serious haematological diseases who had a bone marrow biopsy performed within two weeks of PCR confirmation of SARS-CoV-2 infection. This study is notable because there are no published data describing the bone marrow biopsy changes observed in patients with haematological malignancies and SARS-CoV-2 infection. Finally, it is suggested that nonmyeloablative hematopoietic stem cell transplantation for very high-risk haematological malignancies can be successfully performed following recovery from SARS-CoV-2 infection.

Presynaptic developmental plasticity allows robust sparse wiring of the Drosophila mushroom body.

In order to represent complex stimuli, principle neurons of associative learning regions receive combinatorial sensory inputs. Density of combinatorial innervation is theorized to determine the number of distinct stimuli that can be represented and distinguished from one another, with sparse innervation thought to optimize the complexity of representations in networks of limited size. How the convergence of combinatorial inputs to principle neurons of associative brain regions is established during development is unknown. Here, we explore the developmental patterning of sparse olfactory inputs to Kenyon cells of the Drosophila melanogaster mushroom body. By manipulating the ratio between pre- and post-synaptic cells, we find that postsynaptic Kenyon cells set convergence ratio: Kenyon cells produce fixed distributions of dendritic claws while presynaptic processes are plastic. Moreover, we show that sparse odor responses are preserved in mushroom bodies with reduced cellular repertoires, suggesting that developmental specification of convergence ratio allows functional robustness.

Despite having a limited number of senses, animals can perceive a huge range of sensations. One possible explanation is that the brain combines several stimuli to make each specific sensation. The olfactory learning system in the fruit fly Drosophila melanogaster is in a part of the brain called the mushroom body. It allows fruit flies to associate a specific smell with a reward (e.g. food) or a punishment (e.g. poison) and behave accordingly. Two groups of neurons process stimuli from sensory receptors in the mushroom body: olfactory projection neurons carry information from the receptors and pass it on to neurons called Kenyon cells. The system relies on Kenyon cells receiving the combined input of multiple olfactory projection neurons, and therefore information from multiple receptors. The number of inputs each Kenyon cell receives is thought to determine the number of sensations that can be told apart, and thus, the number of signals that can be used for learning. While many mechanisms dictating the complexity of a neuron's shape have been described, the logic behind how two populations of neurons become connected to combine several inputs into a single sensation has not been addressed. A better understanding of how these connections are established during development can help explain how the brain processes information, and the D. melanogaster mushroom body is a good system to address these questions. Elkahlah, Rogow et al. manipulated the number of olfactory projection neurons and Kenyon cells in the mushroom body of fruit flies during development. They found that despite there being a varying number of cells, the number of connections into a post-synaptic cell remained the same. This indicates that the logic behind the combinations of inputs required for a sensation depends on the Kenyon cell, while olfactory projection neurons can adapt during their development to suit these input demands. Thus, if there are fewer Kenyon cells, the olfactory projection neurons will each provide connections to fewer cells to compensate, and if there are fewer olfactory projection neurons, each of them will input into more Kenyon cells. To show that the developing mushroom body could indeed adapt to different numbers of olfactory projection neurons and Kenyon cells, the modified flies were tested for olfactory perception: their responses to odor were largely normal. These results underline the robustness of neuronal circuits. During development, the mushroom body can compensate for missing or extra neurons by modifying the numbers of connections between two groups of neurons, thus allowing the olfactory system to work normally. This robustness may also predispose the system to evolutionary change, since it allows the system to continue working as it changes. These findings are relevant to any area of the brain where neurons rely on combined input from many sources.