Functional differences between human NKp44- and NKp44+ RORC+ innate lymphoid cells

Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC+ innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC+ innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44+ IL-22 producing cells are present in tonsils while NKp44- IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44+ ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44+ ILC are the main ILC subset producing IL-22. NKp44- ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses

Research priorities in regional anaesthesia: an international Delphi study

Background: Regional anaesthesia use is growing worldwide, and there is an increasing emphasis on research in regional anaesthesia to improve patient outcomes. However, priorities for future study remain unclear. We therefore conducted an international research prioritisation exercise, setting the agenda for future investigators and funding bodies. Methods: We invited members of specialist regional anaesthesia societies from six continents to propose research questions that they felt were unanswered. These were consolidated into representative indicative questions, and a literature review was undertaken to determine if any indicative questions were already answered by published work. Unanswered indicative questions entered a three-round modified Delphi process, whereby 29 experts in regional anaesthesia (representing all participating specialist societies) rated each indicative question for inclusion on a final high priority shortlist. If ≥75% of participants rated an indicative question as ‘definitely’ include in any round, it was accepted. Indicative questions rated as ‘definitely’ or ‘probably’ by <50% of participants in any round were excluded. Retained indicative questions were further ranked based on the rating score in the final Delphi round. The final research priorities were ratified by the Delphi expert group. Results: There were 1318 responses from 516 people in the initial survey, from which 71 indicative questions were formed, of which 68 entered the modified Delphi process. Eleven ‘highest priority’ research questions were short listed, covering themes of pain management; training and assessment; clinical practice and efficacy; technology and equipment. Conclusions: We prioritised unanswered research questions in regional anaesthesia. These will inform a coordinated global research strategy for regional anaesthesia and direct investigators to address high-priority areas

Clinical and molecular consequences of disease-associated de novo mutations in SATB2

Purpose: To characterize features associated with de novo mutations affecting SATB2 function in individuals ascertained on the basis of intellectual disability. Methods: Twenty previously unreported individuals with 19 different SATB2 mutations (11 loss-of-function and 8 missense variants) were studied. Fibroblasts were used to measure mutant protein production. Subcellular localization and mobility of wild-type and mutant SATB2 were assessed using fluorescently tagged protein. Results: Recurrent clinical features included neurodevelopmental impairment (19/19), absent/near absent speech (16/19), normal somatic growth (17/19), cleft palate (9/19), drooling (12/19), and dental anomalies (8/19). Six of eight missense variants clustered in the first CUT domain. Sibling recurrence due to gonadal mosaicism was seen in one family. A nonsense mutation in the last exon resulted in production of a truncated protein retaining all three DNA-binding domains. SATB2 nuclear mobility was mutation-dependent; p.Arg389Cys in CUT1 increased mobility and both p.Gly515Ser in CUT2 and p.Gln566Lys between CUT2 and HOX reduced mobility. The clinical features in individuals with missense variants were indistinguishable from those with loss of function. Conclusion: SATB2 haploinsufficiency is a common cause of syndromic intellectual disability. When mutant SATB2 protein is produced, the protein appears functionally inactive with a disrupted pattern of chromatin or matrix association

Analisis Location Quotient dalam penentuan sektor unggulan pada 4 Kota di Propinsi Sulawesi Utara

Penelitian ini bertujuan untuk mengetahui sektor apa saja yang menjadi sektor unggulan di 4 Kota yang ada di Propinsi Sulawesi Utara. Metode yang digunakan dalam penelitian ini adalah pendekatan kuantitatif dengan teknik analisis location quotient dan menggunakan data sekunder yang di publikasikan oleh BPS Sulawesi Utara tahun 2022. Banyaknya sektor yang dianalisis adalah 17 Sektor dengan tahun amatan 2019,2020 dan 2021. Berdasarkan hasil perhitungan Location Quotient ( LQ) pada 4 Kota di Propinsi Sulawesi Utara, untuk Kota Manado dengan 10 sektor unggulan yaitu : perdagangan besar dan eceran, transportasi dan pergudangan, penyediaan akomodasi dan makan minum, informasi dan komunikasi, jasa keuangan dan asuransi, jasa perusahaan, administrasi pemerintah, jasa pendidikan, jasa kesehatan dan jasa lainnya. Kota Kotamobagu dengan 9 sektor unggulan yaitu : pengadaan listrik dan gas, pengadaan air, konstruksi, perdagangan besar dan eceran, jasa keuangan dan asuransi, administrasi pemerintah, jasa pendidikan, jasa kesehatan, dan jasa lainnya. Kota Tomohon dengan 7 sektor unggulan yaitu : pertambangan, konstruksi, penyediaan akomodasi dan makan, minum, real estat, jasa kesehatan, jasa pendidikan dan jasa lainnya. Kota Bitung dengan 3 sektor unggulan yaitu : industri pengolahan, pengadaan air dan transportasi pengolahan. Kata kunci : Sektor Unggulan, Location Quotient, Propinsi Sulawesi Utar

Australian Cardiovascular Health and Rehabilitation Association (ACRA) core components of cardiovascular disease secondary prevention and cardiac rehabilitation 2014.

Background: Research on Australian cardiovascular disease secondary prevention and cardiac rehabilitation to guide practice needs updating to reflect current context of practice. It is timely therefore to review the core components that underpin effective services that deliver maximum benefits for participants.Methods: The Australian Cardiovascular Health and Rehabilitation Association (ACRA) convened an inter-agency, multidisciplinary, nationally representative expert panel of Australia's leading cardiac rehabilitation clinicians, researchers and health advocates who reviewed the research evidence.Results: Five core components for quality delivery and outcomes of services were identified and are recommended: 1) Equity and access to services, 2) Assessment and short-term monitoring, 3) Recovery and longer term maintenance, 4) Lifestyle/behavioural modification and medication adherence, and 5) Evaluation and quality improvement.Conclusions: ACRA seeks to provide guidance on the latest evidence in cardiovascular disease secondary prevention and cardiac rehabilitation. Clinicians should use these core components to guide effective service delivery and promote high quality evidence based care. Directors of hospitals and health services should use these core components to aid decision-making about the development and maintenance of these services

Functional differences between human NKp44- and NKp44+ RORC+ innate lymphoid cells

Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC+ innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC+ innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44+ IL-22 producing cells are present in tonsils while NKp44- IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44+ ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44+ ILC are the main ILC subset producing IL-22. NKp44- ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses

The CRIOAc healthcare network in France: A nationwide Health Ministry program to improve the management of bone and joint infection

International audienceBackground: Bone and joint infections (BJIs) have a major clinical and economic impact in industrialized countries. Its management requires a multidisciplinary approach, and a great experience for the most complicated cases to limit treatment failure, motor disability and amputation risk. To our best knowledge there is not currently national specific organization dedicated to manage BJI. Is it possible to build at a national level, a network involving orthopaedic surgeons, infectiologists and microbiologists performing locally multidisciplinary meetings to facilitate the recruitment and the management of patients with complex bone and joint infection in regional centers?Hypothesis: A national healthcare network with regional labeled centers creates a dynamic that improves the recruitment, the management, the education, and the clinical research in the field of complex BJI.Patients and methods: We describe the history of this unique national healthcare network and how it works, specify the missions confided to the CRIOAcs, evaluate the activity of the network over the first decade, and finally discuss perspectives.Results: The labelling of 24 centers in the CRIOAc network allowed for a meshing of the territory, with the possibility of management of complex BJI in each region of France. A dedicated secure national online information system was designed and used to facilitate decision-making during multidisciplinary consultation meetings. Since October 2012 to June 2017, 4553 multidisciplinary consultation meetings have been performed in the structures belonging to the network, with 34,607 cases discussed in 19,961 individual. Prosthetic joint infections represented 38% (7585/19,961) of all BJIs. Among all the cases discussed, the rate of complexity was of 61% (21,110/34,607) (related to antibiotic resistance, infection recurrence, patient co morbidities). A national scientific meeting was created and a national postgraduate diploma in the field of BJI was launched in 2014. The promotion of education, clinical research and interactivity between each academic discipline and between each labeled centers across the country has synergized the strengths and have greatly facilitated the management of patients with BJI.Discussion: The setting up of the CRIOAc network in France took time, and has a cost for the French Ministry of Health. However, this network has greatly facilitated the management of BJI in France, and allowed to concentrate the management of complex BJI in centers that have significantly gained skills. There is, to our knowledge, no other exemple of such nationwide network in the field of BJI