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BACKGROUND: Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone or as a bivalent preparation with the prototype vaccine (NVX-CoV2373) to assess antibody responses to SARS-CoV-2. METHODS: Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or the bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed. RESULTS: Of participants who received trial vaccine (N = 829), those administered NVX-CoV2515 (n = 286) demonstrated a superior neutralizing antibody response to BA.1 vs NVX-CoV2373 (n = 274) at day 14 (geometric mean titer ratio, 1.6; 95% CI, 1.33-2.03). Seroresponse rates were 73.4% (91/124; 95% CI, 64.7-80.9) for NVX-CoV2515 vs 50.9% (59/116; 95% CI, 41.4-60.3) for NVX-CoV2373. All formulations were similarly well tolerated. CONCLUSIONS: NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant as compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT05372588).
Sujet(s)
Anticorps neutralisants , Anticorps antiviraux , Vaccins contre la COVID-19 , COVID-19 , Rappel de vaccin , Immunogénicité des vaccins , SARS-CoV-2 , Glycoprotéine de spicule des coronavirus , Humains , Vaccins contre la COVID-19/immunologie , Vaccins contre la COVID-19/administration et posologie , Vaccins contre la COVID-19/effets indésirables , Adulte , SARS-CoV-2/immunologie , SARS-CoV-2/génétique , Anticorps antiviraux/sang , Anticorps antiviraux/immunologie , Glycoprotéine de spicule des coronavirus/immunologie , Glycoprotéine de spicule des coronavirus/génétique , Mâle , Femelle , COVID-19/prévention et contrôle , COVID-19/immunologie , Anticorps neutralisants/sang , Anticorps neutralisants/immunologie , Jeune adulte , Adulte d'âge moyen , Adolescent , Vaccins synthétiques/immunologie , Vaccins synthétiques/administration et posologie , Vaccins synthétiques/effets indésirablesRÉSUMÉ
Objectives: Revision hip arthroplasty is a major surgical challenge and is even more difficult in cases with a deficient proximal femur. Modular uncemented cone body revision femoral stems were introduced as a solution. They have the advantage of optimising joint kinematics by allowing the variable degrees of version, offset and leg length. However, we noticed cantilever failure of such stems, particularly in patients with deficient proximal femoral support. Fatigue fracture of the revision femoral stems should raise questions about its use in patients with insufficient proximal femoral bone support. Methods: We present a case series of five patients with the cantilever failure of Stryker restoration modular stem conical distal femur prosthesis. These cases were identified during a retrospective review of revision hip surgeries performed at our trust. Results: The stem failed after an average of 22.6 months post-revision surgery. Primarily, poor proximal femur bone support with a well-fixed distal stem and secondarily high BMI led to this catastrophic failure in the absence of trauma. All five cases were re-revised to Stanmore proximal femoral replacement and achieved good functional outcomes after an average follow-up of seven years. Conclusion: Proximal femoral bone support should be restored to prevent early cantilever failure of distally fixed proximal modular revision femoral stems. Consider a proximal femoral replacement if we cannot ensure proximal bone support.
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BACKGROUND: SARS-CoV-2 variants evade immunity despite vaccination with prototype COVID-19 vaccines or previous infection. The 2019nCoV-311 (part 2) study is evaluating immune responses after two booster doses of a vaccine containing the omicron BA.5 subvariant spike protein in adults previously vaccinated with a prototype mRNA vaccine. This interim analysis reports on day 28 immunogenicity and safety outcomes after one booster dose. METHODS: In this phase 3, randomised, observer-blinded study conducted at 35 sites in Australia, medically stable, previously COVID-19-vaccinated (mRNA-based; ≥three doses) adults aged 18 years or older were enrolled and randomly allocated (1:1:1; via an interactive web response system) to receive two doses of bivalent (NVX-CoV2373 + NVX-CoV2540; bivalent group), authorised prototype (NVX-CoV2373; prototype group), or BA.5 (NVX-CoV2540; BA.5 group) vaccine. Only blinded personnel performed study assessments or had participant contact to collect data after study vaccination. Participants received vaccines containing 5 µg SARS-CoV-2 recombinant spike protein and 50 µg Matrix-M adjuvant, administered via a 0·5 mL intramuscular injection (2·5 µg of NVX-CoV2373 plus 2·5 µg of NVX-CoV2540 for the bivalent vaccine, prepared on-site as a 1:1 mixture). The coprimary endpoints include day 28 neutralising antibody geometric mean titre (GMT) ratios (GMTRs) to omicron BA.5 and the ancestral strain, and seroresponse rates to BA.5, in the bivalent and prototype groups. These endpoints were calculated in the per-protocol analysis set, which was defined as participants who had received a vaccine dose, had baseline and day 28 immunogenicity data, and were PCR-negative for SARS-CoV-2, with no major protocol deviations. The primary objective was to determine the primary outcome (antibody responses), which consisted of three comparisons: superiority of the bivalent versus prototype vaccine for neutralising antibody GMT to BA.5 (ie, lower bound of the GMTR 95% CI >1·0); non-inferiority of neutralising antibody seroresponse rate to BA.5 (ie, lower bound of the seroresponse rate 95% CI >-5%); and non-inferiority of neutralising antibody GMT to the ancestral strain (ie, lower bound of GMTR 95% CI >0·67). This trial was registered at ClinicalTrials.gov, number NCT05372588. FINDINGS: Between March 22, 2023 and May 2, 2023, 837 participants were screened for eligibility and 766 were randomly allocated to receive the BA.5 (n=255), prototype (n=252), or bivalent (n=259) vaccine. After accounting for exclusions due to participants being baseline SARS-CoV-2-positive, having previous infection, or protocol deviations, the per-protocol analysis set included 694 participants (236 in BA.5 group, 227 in prototype group, and 231 in bivalent group). In this interim analysis (maximum follow-up 35 days after the first dose), the bivalent group, compared with the prototype group, had superior neutralising antibody responses to BA.5 (GMT 1017·8 [95% CI 891·0-1162·6] vs 515·1 [450·4-589·0]; GMTR 2·0 [1·69-2·33]) and a non-inferior seroresponse rate to BA.5 at day 28 (39·8% [33·5-46·5] vs 12·3% [8·4-17·3]; difference 27·5% [19·8-35·0]). The bivalent group also had non-inferior neutralising antibody responses to the ancestral strain (GMTR 1·0 [0·84-1·20]), compared with the prototype group. All vaccines were similarly well tolerated. INTERPRETATION: All three coprimary endpoints were met in part 2 of the ongoing 2019nCoV-311 study. These data support the development of monovalent and/or bivalent vaccines for the most currently circulating variants, to optimise protection. With no new safety findings, further investigation of omicron-based subvariant vaccines is supported by the evidence. FUNDING: Novavax.
Sujet(s)
Anticorps neutralisants , Anticorps antiviraux , Vaccins contre la COVID-19 , COVID-19 , Rappel de vaccin , Immunogénicité des vaccins , SARS-CoV-2 , Glycoprotéine de spicule des coronavirus , Humains , Vaccins contre la COVID-19/immunologie , Vaccins contre la COVID-19/administration et posologie , Glycoprotéine de spicule des coronavirus/immunologie , Mâle , COVID-19/prévention et contrôle , COVID-19/immunologie , SARS-CoV-2/immunologie , Femelle , Rappel de vaccin/méthodes , Adulte d'âge moyen , Adulte , Anticorps antiviraux/sang , Anticorps neutralisants/sang , Anticorps neutralisants/immunologie , Vaccins synthétiques/immunologie , Vaccins synthétiques/administration et posologie , Sujet âgé , Australie , Jeune adulteRÉSUMÉ
Tuberculosis (TB), an infection caused by Mycobacterium tuberculosis, accounts for significant morbidity and mortality worldwide. While primary TB predominantly involves the respiratory system, approximately 10-19% patients have musculoskeletal involvement. We present a case of a 54-year-old year gentleman with insidious onset of anterior knee pain. Imaging demonstrated a soft tissue lesion involving the patellar tendon and eroding the inferior pole of the patella. The imaging features, particularly ultrasound, resembled those that are typically seen with gout. Ultrasound guided biopsy revealed this to be TB of the patella. The patient was successfully treated with antitubercular therapy. Musculoskeletal TB, while usually not a primary form of TB, is an important consideration particularly in patients with risk factors for the disease. Its imaging features can mimic other forms of arthropathy such as gout. Moreover, while the knee is a relatively common site for TB infection, isolated involvement of the patella and patellar tendon is extremely rare. The case highlights the possibility of rare musculoskeletal manifestation of TB as a well as a potential imaging pitfall of TB infection mimicking gout, which is an important consideration in clinical practice.
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BACKGROUND: Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone, or as a bivalent preparation in combination with the prototype vaccine (NVX-CoV2373), to assess antibody responses to SARS-CoV-2. METHODS: Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed. RESULTS: Of participants who received trial vaccine (N = 829), those administered NVX-CoV2515 (n = 286) demonstrated superior neutralizing antibody response to BA.1 versus NVX-CoV2373 (n = 274) at Day 14 (geometric mean titer ratio [95% CI]: 1.6 [1.33, 2.03]). Seroresponse rates [n/N; 95% CI] were 73.4% [91/124; 64.7, 80.9] for NVX-CoV2515 versus 50.9% [59/116; 41.4, 60.3] for NVX-CoV2373. All formulations were similarly well-tolerated. CONCLUSIONS: NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373.
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Historically, cannabis has been valued for its pain-relieving, anti-inflammatory, and calming properties. Ancient civilizations like the Egyptians, Greeks, and Chinese medicines recognized their therapeutic potential. The discovery of the endocannabinoid system, which interacts with cannabis phytoconstituents, has scientifically explained how cannabis affects the human immune system, including the central nervous system (CNS). This review explores the evolving world of cannabis-based treatments, spotlighting its diverse applications. By researching current research and clinical studies, we probe into how cannabinoids like Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) help to manage conditions ranging from chronic pain, persistent inflammation, cancer, inflammatory bowel disease, and neurological disorders to even viral diseases such as Human Immunodeficiency virus (HIV), SARS-CoV-2. and the emerging monkeypox. The long-term recreational use of cannabis can develop into cannabis use disorder (CUD), and therefore, understanding the factors contributing to the development and maintenance of cannabis addiction, including genetic predisposition, neurobiological mechanisms, and environmental influences, will be timely. Shedding light on the adverse impacts of CUD underscores the importance of early intervention, effective treatment approaches, and public health initiatives to address this complex issue in an evolving landscape of cannabis policies and perceptions.
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Background: The gold standard treatment for Anterior Cruciate Ligament injury is reconstruction (ACL-R). Graft failure is the concern and ensuring a durable initial graft with rapid integration is crucial. Graft augmentation with implantable devices (internal brace reinforcement) is a technique purported to reduce the risk of rupture and hasten recovery. Few studies have examined these techniques, in particular when compared to non-augmented grafts. This study assesses the short-term outcome of ACL-R using augmented and non-augmented hamstring tendon autografts. Methods: This was a retrospective cohort study comparing augmented and non-augmented ACL-R. All procedures were performed in a single centre using the same technique. The Knee injury and Osteoarthritis Outcome Score [KOOS] was used to assess patient-reported outcomes. Results: There were 70 patients in the augmented and 111 patients in the control group. Mean graft diameter in the augmented group was 8.82 mm versus 8.44 mm in the non-augmented. Six strand graft was achievable in 73.5% of the augmented group compared to 33% in the non-augmented group. Two graft failures were reported in the non-augmented group and none in the augmented group. Patient satisfaction rates were higher in the augmented group. There was a statistically insignificant improvement in the postoperative KOOS in the augmented group compared to the non-augmented group (p 0.6). Irrespective of augmentation status, no correlation was found between the functional score and age, or femoral tunnel width. Conclusion: No statistically significant difference was demonstrated in the short-term functional outcome of ACL reconstruction using an augmented or non-augmented hamstring graft. Augmented ACL-R may achieve superior graft diameters, failure rates and patient reported outcomes when compared to nonaugmented ACL-R. Prospective trials are needed to examine this further.
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Sea ice variability patterns are highly influenced by several large-scale ocean-atmospheric oscillations. We analysed both statistical and wavelet coherence methods to examine sea ice's interannual and interdecadal variability. During the past 42-year, the total Southern Ocean sea ice extent (SIE) has expanded, while the Amundsen-Bellingshausen Sea SIE has decreased. A wavelet coherence analysis (WCA) of El Niño Southern Oscillation (ENSO) and the SIE in various sectors revealed an out-of-phase correlation between the Indian Ocean and the Ross Sea. There are significant out-of-phase correlations between sea ice variability and Indian Ocean Dipole (IOD) on an interannual scale. A consistent phase relationship was seen between SIE and Southern Annular Mode (SAM) over the past decade, with in-phase relationships advancing to out-of-phase relationships. The Interdecadal Pacific Oscillation (IPO) shifted from positive to negative after the 1990s. In recent years, SAM has had a stronger impact on sea ice variability than ENSO.
Sujet(s)
El Nino-oscillation australe , Couche de glace , Régions antarctiques , Océan IndienRÉSUMÉ
Oceanic calcifying plankton such as coccolithophores is expected to exhibit sensitivity to climate change stressors such as warming and acidification. Observational studies on coccolithophore communities along with carbonate chemistry provide important perceptions of possible adaptations of these organisms to ocean acidification. However, this phytoplankton group remains one of the least studied in the northern Indian Ocean. In 2017, the biogeochemistry group at the Council for Scientific and Industrial Research-National Institute of Oceanography (CSIR-NIO) initiated a coccolithophore monitoring study in the eastern Arabian Sea (EAS). Here, we document for the first time a detailed spatial and seasonal distribution of coccolithophores and their controlling factors from the EAS, which is a well-known source of CO2 to the atmosphere. To infer the seasonality, data collected at three transects (Goa, Mangalore, and Kochi) during the Southwest Monsoon (SWM) of 2018 was compared with that of the late SWM of 2017. Apart from this, the abundance of coccolithophores was studied at the Candolim Time Series (CaTS) transect, off Goa during the Northeast Monsoon (NEM). The most abundant coccolithophore species found in the study region was Gephyrocapsa oceanica. A high abundance of G. oceanica (1800 × 103cells L-1) was observed at the Mangalore transect during the late SWM despite experiencing low pH and can be linked to nitrogen availability. The high abundance of G. oceanica at Mangalore was associated with high dimethylsulphide (DMS). Particulate inorganic carbon (PIC) and scattering coefficient retrieved from satellites also indicated a high abundance of coccolithophores off Mangalore during the late SWM of 2017. Interestingly, G. oceanica showed malformation during the late SWM in low pH waters. Malformation in coccolithophores could have a far-reaching impact on the settling fluxes of organic matter and also on the emissions of climatically important gases such as DMS and CO2, thus influencing atmospheric chemistry. The satellite data for PIC in the EAS indicates a high abundance of coccolithophore in recent years, especially during the warm El Nino years (2015 and 2018). This warrants the need for a better assessment of the fate of coccolithophores in high-CO2 and warmer oceans.
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Haptophyta , Eau de mer , Carbone , Dioxyde de carbone/composition chimique , Concentration en ions d'hydrogène , Océan Indien , Océans et mers , Phytoplancton/composition chimique , Eau de mer/composition chimiqueRÉSUMÉ
Non-tuberculous Mycobacteria (NTM), previously classified as environmental microbes, have emerged as opportunistic pathogens causing pulmonary infections in immunocompromised hosts. The formation of the biofilm empowers NTM pathogens to escape from the immune response and antibiotic action, leading to treatment failures. NF1001 is a novel thiopeptide antibiotic first-in-class compound with potent activity against planktonic/replicating and biofilm forms of various NTM species. It is potent against both drug-sensitive and -resistant NTM. It has demonstrated a concentration-dependent killing of replicating and intracellularly growing NTM, and has inhibited and reduced the viability of NTM in biofilms. Combination studies using standard-of-care (SoC) drugs for NTM exhibited synergetic/additive effects, but no antagonism against both planktonic and biofilm populations of Mycobacterium abscessus and Mycobacterium avium. In summary, the activity of NF1001 alone or in combination with SoC drugs projects NF1001 as a promising candidate for the treatment of difficult-to-treat NTM pulmonary diseases (NTM-PD) and cystic fibrosis (CF) in patients.
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Genome-wide association studies provide a powerful means of identifying loci and genes contributing to disease, but in many cases, the related cell types/states through which genes confer disease risk remain unknown. Deciphering such relationships is important for identifying pathogenic processes and developing therapeutics. In the present study, we introduce sc-linker, a framework for integrating single-cell RNA-sequencing, epigenomic SNP-to-gene maps and genome-wide association study summary statistics to infer the underlying cell types and processes by which genetic variants influence disease. The inferred disease enrichments recapitulated known biology and highlighted notable cell-disease relationships, including γ-aminobutyric acid-ergic neurons in major depressive disorder, a disease-dependent M-cell program in ulcerative colitis and a disease-specific complement cascade process in multiple sclerosis. In autoimmune disease, both healthy and disease-dependent immune cell-type programs were associated, whereas only disease-dependent epithelial cell programs were prominent, suggesting a role in disease response rather than initiation. Our framework provides a powerful approach for identifying the cell types and cellular processes by which genetic variants influence disease.
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Trouble dépressif majeur , Étude d'association pangénomique , Trouble dépressif majeur/génétique , Prédisposition génétique à une maladie , Génétique humaine , Humains , Polymorphisme de nucléotide simple/génétique , ARN , Acide gamma-amino-butyriqueRÉSUMÉ
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or therapeutic development. Here, we construct a high-resolution molecular landscape of the cellular subtypes and spatial communities that compose PDAC using single-nucleus RNA sequencing and whole-transcriptome digital spatial profiling (DSP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment naive. We uncovered recurrent expression programs across malignant cells and fibroblasts, including a newly identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities with distinct contributions from malignant, fibroblast and immune subtypes: classical, squamoid-basaloid and treatment enriched. Our refined molecular and cellular taxonomy can provide a framework for stratification in clinical trials and serve as a roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions.
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Carcinome du canal pancréatique , Tumeurs du pancréas , Marqueurs biologiques tumoraux/génétique , Carcinome du canal pancréatique/génétique , Carcinome du canal pancréatique/anatomopathologie , Carcinome du canal pancréatique/thérapie , Analyse de profil d'expression de gènes , Humains , Traitement néoadjuvant , Tumeurs du pancréas/traitement médicamenteux , Tumeurs du pancréas/génétique , Pronostic , Transcriptome/génétique , Tumeurs du pancréasRÉSUMÉ
Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts. Methods: Patients were evaluated in the hepatology clinic, and 29 patients agreed to undergo liver biopsy. The liver histology was scored by the meta-analysis of histological data in viral hepatitis scoring system and was assessed by hepatopathologists. The fibrosis score was compared between patients who initiated direct-acting antiviral (DAA) within 6 wk (n = 6) and after 6 wk (n = 29). Results: Eighty-nine aviremic patients were transplanted with HCV-infected grafts between March 2018 and October 2019. All patients developed HCV infection and were treated with DAA treatment after kidney transplantation (median, 70 d; interquartile range, 55-85 d). All patients (n = 89) achieved sustained virologic response with DAA. The median follow-up time from kidney transplant to liver biopsy was 28 mo (interquartile range, 26-30 mo). Twenty-five patients (86%) had F0, and 4 patients (14%) had F1 fibrosis. No patient had advanced fibrosis (F3-F4). Grade 1 inflammation was present in 6 (21%) patients, whereas 26 (90%) patients had iron accumulation in the hepatocytes and reticuloendothelial cells. There was no difference in the fibrosis score between patients who received treatment within 6 wk versus after 6 wk (P = 0.55). Conclusions: Kidney transplantation of HCV-infected graft to HCV-negative recipients is safe and has no long-term liver-related complications with successful eradication of HCV. In our cohort, delayed treatment did not affect sustained virologic response or liver histology.
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Antarctic sea ice variability is primarily associated with ocean-atmospheric forcing driven by anomalous conditions over the tropical regions of the Pacific and Indian Oceans. The ice-ocean-atmosphere dynamics in the Indian Ocean Sector (IOS) of Antarctica have been studied using monthly satellite and reanalysis observations over four decades (1979-2019). In this study, we revealed that the annual sea ice extent (SIE) in the IOS increases at a rate of 0.7 ± 0.9% decade-1, with a maximum increase in austral summer (5.9 ± 3.7% decade-1). The wavelet approach was used to determine the variability in IOS sea ice caused by the El Niño/Southern Oscillation (ENSO) and southern annular mode (SAM). The SIE has a significant association with both indices during the summer and autumn. In comparison to ENSO, the sea ice variability associated with SAM is typically seasonal in nature and lacks distinct patterns. The wavelet coherence analysis revealed a relatively weak relationship between ENSO and SAM but a highly significant coherence between climatic indices and SIE. We observed that sea ice in the IOS is influenced significantly by climatic oscillations during their negative SAM/El Niño or positive SAM/La Niña phases. Furthermore, the study demonstrated a substantial impact of climatic disturbances in determining the sea ice variability in the IOS.
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El Nino-oscillation australe , Couche de glace , Régions antarctiques , Océan Indien , SaisonsRÉSUMÉ
Genome-wide association studies (GWAS) provide a powerful means to identify loci and genes contributing to disease, but in many cases the related cell types/states through which genes confer disease risk remain unknown. Deciphering such relationships is important for identifying pathogenic processes and developing therapeutics. Here, we introduce sc-linker, a framework for integrating single-cell RNA-seq (scRNA-seq), epigenomic maps and GWAS summary statistics to infer the underlying cell types and processes by which genetic variants influence disease. We analyzed 1.6 million scRNA-seq profiles from 209 individuals spanning 11 tissue types and 6 disease conditions, and constructed gene programs capturing cell types, disease progression, and cellular processes both within and across cell types. We evaluated these gene programs for disease enrichment by transforming them to SNP annotations with tissue-specific epigenomic maps and computing enrichment scores across 60 diseases and complex traits (average N= 297K). Cell type, disease progression, and cellular process programs captured distinct heritability signals even within the same cell type, as we show in multiple complex diseases that affect the brain (Alzheimerâ™s disease, multiple sclerosis), colon (ulcerative colitis) and lung (asthma, idiopathic pulmonary fibrosis, severe COVID-19). The inferred disease enrichments recapitulated known biology and highlighted novel cell-disease relationships, including GABAergic neurons in major depressive disorder (MDD), a disease progression M cell program in ulcerative colitis, and a disease-specific complement cascade process in multiple sclerosis. In autoimmune disease, both healthy and disease progression immune cell type programs were associated, whereas for epithelial cells, disease progression programs were most prominent, perhaps suggesting a role in disease progression over initiation. Our framework provides a powerful approach for identifying the cell types and cellular processes by which genetic variants influence disease.
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Hallux varus is a rare foot deformity due to iatrogenic, post-traumatic, idiopathic, inflammatory, spontaneous, or congenital pathologies. Acquired hallux varus, in particular, iatrogenic type, is the commonest. The primary pathology is the abnormal musculotendinous forces secondary to soft tissue or bony imbalance exerting varus deforming force. Understanding the anatomy of the hallux stabilisers and the pathophysiology of hallux varus is vital in its management. It would be helpful to understand the potential surgical pitfalls leading to iatrogenic hallux varus. This literature review summarises all the published facts about hallux varus, focussing on anatomy, pathophysiology, clinical and radiological assessment, and management.
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Hallux valgus , Hallux varus , Hallux , Hallux valgus/imagerie diagnostique , Hallux valgus/chirurgie , Hallux varus/imagerie diagnostique , Hallux varus/étiologie , Humains , Transposition tendineuseRÉSUMÉ
Many anaesthetists are hesitant to perform epidural blood patch in patients with cancer because of the potential risk of seeding the CNS with malignant cells. Recent evidence suggests that anaesthetists may view malignancy as a relative contraindication to epidural blood patch rather than an absolute contraindication. This review article summarises the clinical dilemma, reviews the existing literature, and proposes a treatment algorithm that includes the utilisation of for the management of post-dural puncture headache in the oncology population.
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Colmatage sanguin épidural , Tumeurs/complications , Céphalée post-ponction durale/thérapie , Adolescent , Adulte , Facteurs âges , Colmatage sanguin épidural/effets indésirables , Enfant , Prise de décision clinique , Contre-indications aux procédures , Techniques d'aide à la décision , Femelle , Humains , Mâle , Adulte d'âge moyen , Essaimage tumoral , Tumeurs/diagnostic , Céphalée post-ponction durale/complications , Céphalée post-ponction durale/diagnostic , Appréciation des risques , Facteurs de risque , Résultat thérapeutique , Jeune adulteRÉSUMÉ
The reduction in Arctic sea-ice in recent decades has been a significant indicator of climate change and is related to weather pattern changes across the Arctic regions. In this study, for the period 1979-2018, we addressed the processes controlling the sea-ice cover in the Barents-Kara Sea (BKS). The inter-annual variability of the sea-ice extent (SIE) in BKS was analyzed using passive microwave satellite observations. The ocean-atmospheric forcing variables which including air temperature (AT), sea surface temperature (SST) and outgoing long-wave radiation (OLR) were derived from ERA-Interim reanalysis data. The spatial correlation analysis was performed for the year 2016 and 1998, where sea ice concentration (SIC) in BKS is recorded as a minimum and maximum respectively. The long-term analysis (1979-2018) shows negative trends of the Arctic SIE (-4.7 ± 0.3% decade-1) with the largest decrease in the Barents Sea (-23 ± 2.5% decade-1) and Kara Sea (-7.3 ± 0.9% decade-1). However, the sea-ice decline in the Barents Sea was recorded very high during the winter (-17.6 ± 2.2% decade-1) compared to the Kara Sea (-0.8 ± 0.2% decade-1). Sea-ice cover in the Barents Sea is more likely to recede during the summers -4.1 ± 0.7 x 103 km2yr-1 due to warm inflow of Atlantic waters. Correlation analysis using statistically significant trend values with p-values ≤ 0.01 was performed from 1982 to 2018, the SIC of BKS showing significant negative correlation analyses with SST (-0.75; p-value = 0.01), SAT (-0.84; p-value = 0.00) and OLR (-0.76; p-value = 0.00). In recent years, Atlantic Multi-decadal Oscillation (AMO) index has become positive due to an increase in SST anomalies, while, AMO does not reflect the cooling events in the BKS. During recent Arctic climate change, caused by atmospheric heat transport, the loss of sea-ice at BKS is becoming a major factor. In this study, new perspectives of the complex processes associated with Arctic warming and the declining sea-ice in the BKS region are demonstrated.