Destruction, disruption and disaster: Sudan's health system amidst armed conflict.

The ongoing armed conflict in Sudan has resulted in a deepening humanitarian crisis with significant implications for the country's health system, threatening its collapse. This article examines the destruction, disruption, and disastrous consequences inflicted upon Sudan's health system. The conflict has led to the severe compromise of healthcare facilities, with only one-third of hospitals in conflict zones operational. Artillery attacks, forced militarization, power outages, and shortages of medical supplies and personnel have further crippled the health system. The exodus of health workers and escalating violence have exacerbated the crisis. Disrupted service delivery has resulted in the interruption of essential health services, including obstetric care, emergency services, and dialysis. Financial losses to the health system are estimated at $700 million, impacting an already underfunded sector. We identify that in addition to restoration of peace and mobilization of urgent aid, immediate prioritization of the reconstruction of the health system is crucial to mitigate the long-term consequences of the war. Rebuilding a resilient health system is sine qua non for Sudan's progress towards universal health.

The Association of Human Leukocyte Antigen Genotyping Among Sudanese Patients With Rheumatoid Arthritis: Reference to Ethnicity.

INTRODUCTION:  Human leukocyte antigens (HLA) account for up to one-half of the total genetic contribution to rheumatoid arthritis (RA) risk. The study investigated the association of HLA class II genotyping with RA susceptibility in Sudanese ethnic groups. METHODS:  The DRB1 and DQB1 alleles and haplotypes were determined in 122 RA patients (i.e., Gaalia = 54, Johayna = 24, Baggara = 17, Nile Nubian = 12, and others = 15) and 120 healthy controls of ethnic groups (i.e., Gaalia = 44, Johayna = 11, Baggara = 15, Nile Nubian = 9, and others = 21) using a polymerase chain reaction with sequence-specific primers method. RESULTS: Susceptibility to RA was associated with a high frequency of DRB1*04 (P = 0.04), DRB1*10 (P = 0.04), and DQB1*03 (P = 2.2 x 10-8/Pc = 6.6 x 10-8) between study ethnic groups, while protective effects were shown with DRB1*07 (P = 0.01), DQB1*02 (P = 0.02), and DQB1*06 (P = 2.2 x 10-6/Pc = 6.6 x 10-6), with an inconsistent frequency between study ethnic groups. The HLA haplotypes that were high in frequency among RA ethnic groups and showed susceptibility associations were DRB1*03-DQB1*03, DRB1*04-DQB1*03, DRB1*08-DQB1*03, DRB1*13-DQB1*02, and DRB1*13-DQB1*03 (P = 0.00003/Pc = 0.0003, P = 0.0001/Pc = 0.0001, P = 0.03, P = 0.004/Pc = 0.03, and P = 3.79x10-8/Pc = 3.3x10-9, respectively). On the contrary, DRB1*03-DQB1*02, DRB1*07-DQB1*02, and DRB1*13-DQB1*06 were lower in frequency in the ethnic groups with RA and may confer protection (P = 0.004/Pc = 0.032, P = 0.002/Pc = 0.02, and P = 0.01, respectively). CONCLUSIONS: Our findings indicate an association between HLA-DRB1 and DQB1 genotypes and the susceptibility to RA in the Sudanese population, with a moderate frequency between our ethnic groups.

BRCA 1/BRCA 2 Pathogenic/Likely Pathogenic Variant Patients with Breast, Ovarian, and Other Cancers.

The demographic and clinical characteristics of patients who have BRCA 1/BRCA 2 pathogenic/likely pathogenic variants may differ from their relatives who had BRCA-related cancer. In this study, we aimed to demonstrate the clinical and demographic findings of patients who had BRCA-related cancer and to assess the differences comparing their relatives who had BRCA-related cancer with breast, genital tract, prostate, and pancreas cancers as well. The results of sequencing analysis of 200 cancer patients (190 women, 10 men) who have been directed to genetic counseling with an indication of BRCA1/BRCA2 testing from different regions across 9 medical oncology centers were retrospectively analyzed. A total of 200 consecutive cancer patients who harbored the BRCA1/BRCA2 pathogenic/likely pathogenic variant (130 (65%) patients harbored BRCA 1 pathogenic/likely pathogenic variant, and 70 harbored BRCA 2 pathogenic/likely pathogenic variant) were included. Of these, 64.0% had breast cancer (43.8% of them had the triple-negative disease, and about 2.3% had only the HER-2 mutant), 31.5% had genital cancers (92.1% of them had ovarian cancer, 3.2% had endometrium, and 1.6% had peritoneum cancer as the primary site and mostly serous adenocarcinoma was the most common histopathology and 14.3% of the patients had endometrioid adenocarcinoma), 3.5% had prostate (median time from metastasis to castration-resistant status was 28 months) and 1.0% had pancreas cancer. Newly diagnosed cancer (breast and ovary) patients who had BRCA 1/BRCA 2 pathogenic/ likely pathogenic variant were younger than their previous cancer diagnosed (breast, ovary, and pancreas) parents who harbored BRCA pathogenic/likely pathogenic variant. We suggest that the genetic screening of BRCA 1/ BRCA 2 pathogenic/likely pathogenic variant is needed as a routine screening for those with a personal or family history of breast, ovarian, tubal, or peritoneal cancer. In addition, once BRCA 1 or BRCA 2 germline pathogenic variant has been identified in a family, testing of at-risk next-generation relatives earlier can identify those family members who also have the familial pathogenic variant, and thus need increased surveillance.

Beliefs and barriers of COVID-19 vaccination hesitancy among Sudanese healthcare workers in Sudan: A cross sectional study.

Vaccine hesitancy is one of the major global health impedances. Due to the unprecedented developing rate, the COVID-19 vaccine engendered a high level of hesitancy worldwide. The aim of this study is to assess hesitancy of COVID-19 vaccine among healthcare workers in Sudan. An online-based cross-sectional survey was conducted in Sudan between May and June 2021 using conventional sampling. An anonymous online questionnaire was distributed to healthcare workers (HCW) through different social media platforms and 930 healthcare workers agreed to participate. Data were cleaned in excel sheet and then statistically analyzed using R software version 4.0.2. Of total participants, 67.3% of them were females. Over three-fifths of the study participants agreed that COVID-19 vaccine is important and should be mandatory. A total of 570 (61.3%) agreed that COVID-19 vaccines are safe, whilst 584 (62.8%) had concerns regarding side effects of the vaccine and 533 (57.3%) believe insufficient trials were conducted. A total of 375 (40.3%) accept vaccination absolutely, while 292 (31.4%) accept with some hesitation and only 48 (5.2%) refuse absolutely. Insufficient information about side effects (42.6%) and the vaccine (39.9%) were the most common concerns regarding COVID-19 vaccination. Majority of Sudanese healthcare workers believed that COVID-19 vaccination should be mandatory. A high reliance on social media was observed among healthcare workers in Sudan for information on the COVID-19 pandemic.

Distribution, host range and toxicity assessment of different insecticides on Bactrocera diversa Coquillett, 1904 (Diptera: Tephritidae).

The present study was conducted to investigate the array of hosts, distribution and to evaluate the toxicity of four insecticides: imidacloprid, fipronil, cypermethrin and chlorpyrifos alone and in combination against 3rd instar maggot and adult stage of fruit fly Bactrocera diversa Coquillett, 1904 (Diptera: Tephritidae) during 2021. B. diversa maggots were found vigorously feeding inside the cucurbit hosts (pumpkin, cucumber, bitter gourd, watermelon, round melon, bottle gourd) collected from different localities of Poonch division of Azad Jammu & Kashmir, Pakistan, and this species is reported for the first time as new record to this region. Susceptibilities of B. diversa to insecticides were evaluated using topical method. Mortality was checked after 3, 6, 8 and 24h of exposure. Cypermethrin was most effective to kill 50% of both larval and adult stage with least LC50 [7.2(1.040±0.214), 17.4(0.748±0.193)], respectively followed by imidacloprid. Imidacloprid most effectively killed 90% of both larval and adult population with least LC90 value [73.2 (3.013±0.708) 16.9 (1.886±0.437)] respectively after 24 hours. Cypermethrin with chlorpyrifos most effectively killed 50 and 90 percent of both larval and adult stage of B. diversa with least LC50 value [11.3 (1.085±0.245), 2.5 (0.759±0.252)] and least LC90 value [171.3 (1.085±0.245), 121.9 (0.759±0.252)], respectively after 24h of exposure. Toxicity of each insecticide increased with exposure for longer time and increased dose. Cypermethrin is suggested as most effective against both larval and adult stages of B. diversa in combination with chlorpyrifos followed by imidacloprid.

Biosynthesis of tetrahydropapaverine and semisynthesis of papaverine in yeast.

Tetrahydropapaverine (THP) and papaverine are plant natural products with clinically significant roles. THP is a precursor in the production of the drugs atracurium and cisatracurium, and papaverine is used as an antispasmodic during vascular surgery. In recent years, metabolic engineering advances have enabled the production of natural products through heterologous expression of pathway enzymes in yeast. Heterologous biosynthesis of THP and papaverine could play a role in ensuring a stable supply of these clinically significant products. Biosynthesis of THP and papaverine has not been achieved to date, in part because multiple pathway enzymes have not been elucidated. Here, we describe the development of an engineered yeast strain for de novo biosynthesis of THP. The production of THP is achieved through heterologous expression of two enzyme variants with activity on nonnative substrates. Through protein engineering, we developed a variant of N-methylcoclaurine hydroxylase with activity on coclaurine, enabling de novo norreticuline biosynthesis. Similarly, we developed a variant of scoulerine 9-O-methyltransferase capable of O-methylating 1-benzylisoquinoline alkaloids at the 3' position, enabling de novo THP biosynthesis. Flux through the heterologous pathway was improved by knocking out yeast multidrug resistance transporters and optimization of media conditions. Overall, strain engineering increased the concentration of biosynthesized THP 600-fold to 121 µg/L. Finally, we demonstrate a strategy for papaverine semisynthesis using hydrogen peroxide as an oxidizing agent. Through optimizing pH, temperature, reaction time, and oxidizing agent concentration, we demonstrated the ability to produce semisynthesized papaverine through oxidation of biosynthesized THP.

Integrated Photocatalytic Reduction and Oxidation of Perfluorooctanoic Acid by Metal-Organic Frameworks: Key Insights into the Degradation Mechanisms.

The high porosity and tunability of metal-organic frameworks (MOFs) have made them an appealing group of materials for environmental applications. However, their potential in the photocatalytic degradation of per- and polyfluoroalkyl substances (PFAS) has been rarely investigated. Hereby, we demonstrate that over 98.9% of perfluorooctanoic acid (PFOA) was degraded by MIL-125-NH2, a titanium-based MOF, in 24 h under Hg-lamp irradiation. The MOF maintained its structural integrity and porosity after three cycles, as indicated by its crystal structure, surface area, and pore size distribution. Based on the experimental results and density functional theory (DFT) calculations, a detailed reaction mechanism of the chain-shortening and H/F exchange pathways in hydrated electron (eaq-)-induced PFOA degradation were revealed. Significantly, we proposed that the coordinated contribution of eaq- and hydroxyl radical (•OH) is vital for chain-shortening, highlighting the importance of an integrated system capable of both reduction and oxidation for efficient PFAS degradation in water. Our results shed light on the development of effective and sustainable technologies for PFAS breakdown in the environment.

Y Chromosome Material in Turner Syndrome.

Background Turner Syndrome (TS) is a frequently identified chromosomal disease in humans characterized by short stature, sexual infantilism, streak gonads, primary amenorrhea, and a number of somatic anomalies. Approximately 55% of TS individuals have a nonmosaic 45,X karyotype. In addition, a cell line with a Y chromosome is present in 5% of patients, which is undetectable by the standard cytogenetic analysis. The identification of Y chromatin in some TS individuals has been associated with the development of gonadoblastoma. Therefore, it is important to exclude the presence of Y chromatin in TS individuals. In this study, it was planned to detect cases with mosaicism in terms of Y chromatin with the help of Y whole chromosome probes (WCP) from individuals with TS by fluorescence in situ hybridization (FISH) analysis. Methodology Forty-four patients with Turner syndrome, who were being followed up in the Genetics Unit, were contacted and invited for the study. Of the 44 invited patients, 28 responded to the invitation. In this study, it was planned to detect TS patients with mosaicism in terms of Y chromatin with the help of the Y whole chromosome probe. Results The majority of the cases (71.42%) included in the study carried pure X monosomy, which is the classical Turner syndrome karyotype. Other structural X chromosome aberrations, in isolated or mosaic forms, were less frequently represented. Y chromosome sequences were searched in 28 cases with Turner syndrome by the FISH method using Y whole chromosome probe. Y chromosome sequence was detected in one (3.5%) case of 28 cases. Conclusions It is recommended that individuals with Turner syndrome be screened for Y chromatin. Detection of this will provide information and guidance to individuals with Turner syndrome, especially in terms of the risk of developing gonadoblastoma, with advanced clinical consultation. This study was conducted to emphasize the importance of this.

Heart failure with reduced ejection fraction due topolycythemia vera.

Polycythemia vera is a rare hematological disorder that can cause heart failure with reduced ejection fraction from chronic micro-vascular ischemia. Appropriately recognizing the underlying cause of cardiomyopathy is essential to decrease morbidity and mortality. Patients can present with elevated troponin level and have patent epicardial coronary arteries on coronary angiogram, hence presenting a diagnostic challenge for health care professionals. Furthermore, the presentation can mimic myocarditis. Herein, we report a case of a 61-year-old female who presented with heart failure due to microvascular thrombotic complication associated with polycythemia vera. Laboratory investigation and coronary angiogram were inconclusive. A high degree of clinical suspicion and utilizing non-invasive techniques, such as cardiac imaging, can describe myocardial pathology and aid with the diagnosis.

Polymerase-guided base editing enables in vivo mutagenesis and rapid protein engineering.

Random mutagenesis is a technique used to generate diversity and engineer biological systems. In vivo random mutagenesis generates diversity directly in a host organism, enabling applications such as lineage tracing, continuous evolution, and protein engineering. Here we describe TRIDENT (TaRgeted In vivo Diversification ENabled by T7 RNAP), a platform for targeted, continual, and inducible diversification at genes of interest at mutation rates one-million fold higher than natural genomic error rates. TRIDENT targets mutagenic enzymes to precise genetic loci by fusion to T7 RNA polymerase, resulting in mutation windows following a mutation targeting T7 promoter. Mutational diversity is tuned by DNA repair factors localized to sites of deaminase-driven mutation, enabling sustained mutation of all four DNA nucleotides at rates greater than 10-4 mutations per bp. We show TRIDENT can be applied to routine in vivo mutagenesis applications by evolving a red-shifted fluorescent protein and drug-resistant mutants of an essential enzyme.

A Comparison of Diagnostic Accuracy of Superior Semicircular Canal Dehiscence in MDCT and MRI, and Coexistence with Tegmen Tympani Dehiscence.

Objective Tegmen tympani dehiscence in temporal multidetector computed tomography (MDCT) and superior semicircular canal dehiscence may be seen together. We investigated superior semicircular canal dehiscence in temporal MDCT and temporal magnetic resonance imaging (MRI). Methods In this retrospective study, 127 temporal MRI and MDCT scans of the same patients were reviewed. In all, 48.8% ( n = 62) of cases were male, and 51.2% ( n = 65) of cases were female. Superior semicircular canal dehiscence and superior semicircular canal-temporal lobe distance were evaluated by both MDCT and MRI. Tegmen tympani dehiscence was evaluated by MDCT. Results Superior semicircular canal dehiscence was detected in 14 cases (5.5%) by temporal MDCT and 15 cases (5.9%) by temporal MRI. In 13 cases (5.1%), it was detected by both MDCT and MRI. In one case (0.4%), it was detected by only temporal MDCT, and in two cases (0.8%), it was detected by only temporal MRI. Median superior semicircular canal-to-temporal distance was 0.66 mm in both males and females in temporal MDCT and temporal MRI. In both temporal MDCT and temporal MRI, as superior semicircular canal-to-temporal lobe distance increased, the presence of superior semicircular canal dehiscence in temporal MDCT and temporal MRI decreased. Tegmen tympani dehiscence was detected in eight cases (6.3%) on the right side and six cases (4.7%) on the left side. The presence of tegmen tympani dehiscence in temporal MDCT and the presence of superior semicircular dehiscence in MDCT and MRI increased. Conclusion Superior semicircular canal dehiscence was detected by both MDCT and MRI. Due to the accuracy of the MRI method to detect superior semicircular dehiscence, we recommend using MRI instead of MDCT to diagnose superior semicircular canal dehiscence. Moreover, there is no radiation exposure from MRI.

Antenatal care and skilled delivery service utilisation in Somali pastoral communities of Eastern Ethiopia.

OBJECTIVE: To assess maternal health care service utilisation and associated factors in Somali pastoral communities of eastern Ethiopia. METHODS: Community-based cross-sectional study complemented by qualitative assessments in Adadle district, Somali region, eastern Ethiopia, among 450 women in six kebeles from August to September 2016. Logistic regression was used to assess factors associated with antenatal care use and skilled delivery care use, controlling for confounders. RESULTS: About 27% [95%CI 22.8-31.2%] of women used antenatal care, and 22.6% [95%CI 18.7-26.5%] received skilled delivery service. None of the respondents reported post-natal care. About 43% reported that they had no knowledge of antenatal care, and 46% did not perceive delivery at a health facility as important. Pastoral lifestyle, husband's educational status, women's attitude towards health care service and financial support from the husband were significantly associated with antenatal care utilisation. Health professionals' attitudes, perceptions of institutional delivery, antenatal care utilisation and information about exemptions from maternal health care fees were associated with skilled delivery service utilisation. CONCLUSION: Improving community awareness of antenatal care, employing female health professionals and culturally adapted guidelines could improve skilled delivery utilisation. In a patriarchal society, involving male partners in all maternal health issues is essential to increase use of maternal health services and to decrease maternal mortality.

OBJECTIF: Evaluer l'utilisation des services de soins de santé maternelle et les facteurs associés dans les communautés pastorales somaliennes dans l'est de l'Ethiopie. MÉTHODES: Etude transversale basée sur la communauté complétée par des évaluations qualitatives dans le district d'Adadle, région somalienne, dans l'est de l'Ethiopie, portant sur 450 femmes dans six kebeles d'août à septembre 2016. Une régression logistique a été utilisée pour évaluer les facteurs associés à l'utilisation des soins prénatals et à l'accouchement sous soins qualifiés, en ajustant pour les facteurs confusionnels. RÉSULTATS: 27% [IC95%: 22.8-31.2%] des femmes ont utilisé des soins prénatals et 22,6% [IC95%: 18.7-26.5%] ont reçu des services d'accouchement qualifiés. Aucune des répondantes n'a signalé des soins postnatals. 43% ont déclaré qu'elles n'avaient aucune connaissance des soins prénatals et 46% ne percevaient pas l'accouchement dans un établissement de santé comme important. Le mode de vie pastoral, le niveau d'éducation du mari, l'attitude des femmes à l'égard des services de santé et le soutien financier du mari étaient significativement associés à l'utilisation des soins prénatals. Les attitudes des professionnels de la santé, les perceptions de l'accouchement en établissement, l'utilisation des soins prénatals et les informations sur les exemptions des frais de soins de santé maternelle ont été associées à l'utilisation des services d'accouchement qualifiés. CONCLUSION: Améliorer la sensibilisation de la communauté aux soins prénatals, employer des professionnels de la santé féminins et des directives culturellement adaptées pourrait améliorer l'utilisation de l'accouchement qualifié. Dans une société patriarcale, la participation des partenaires masculins à toutes les questions de santé maternelle est essentielle pour accroître l'utilisation des services de santé maternelle et réduire la mortalité maternelle.

The thermally induced decarboxylation mechanism of a mixed-oxidation state carboxylate-based iron metal-organic framework.

Investigations into a thermally generated decarboxylation mechanism for metal site activation and the generation of mesopores in a carboxylate iron-based MOF, PCN-250, have been conducted. PCN-250 exhibits an interesting oxidation state change during thermal treatment under inert atmospheres or vacuum conditions, transitioning from an Fe(iii)3 cluster to a Fe(ii)Fe(iii)2 cluster. To probe this redox event and discern a mechanism of activation, a combination of thermogravimetric analysis, gas sorption, scanning electron microscopy, 57Fe Mössbauer spectroscopy, gas chromatography-mass spectrometry, and X-ray diffraction studies were conducted. The results suggest that the iron-site activation occurs due to ligand decarboxylation above 200 °C. This is also consistent with the generation of a missing cluster mesoporous defect in the framework. The resulting mesoporous PCN-250 maintains high thermal stability, preserving crystallinity after multiple consecutive high-temperature regeneration cycles. Additionally, the thermally reduced PCN-250 shows improvements in the total uptake capacity of methane and CO2.

Scurfy Mice Develop Features of Connective Tissue Disease Overlap Syndrome and Mixed Connective Tissue Disease in the Absence of Regulatory T Cells.

Due to a missense mutation in the Foxp3 gene, scurfy mice are deficient in functional regulatory T cells (Treg). The consequent loss of peripheral tolerance manifests itself by fatal autoimmune mediated multi-organ disease. Previous studies have outlined the systemic inflammatory disease and demonstrated production of anti-nuclear antibodies (ANA) in scurfy mice. However, specific autoantibody targets remained to be defined. ANA are immunological markers for several connective tissue diseases (CTD) and target a large number of intracellular molecules. Therefore, we examined scurfy sera for the presence of different ANA specificities and further assessed the organ involvement in these animals. Indirect immunofluorescence was used as a screen for ANA in the sera of scurfy mice and dilutions of 1/100 were considered positive. Addressable laser bead immunoassays (ALBIA) were used to detect specific autoantibody targets. Subsequent histological tissue evaluation was verified by hematoxylin and eosin (H&E) staining. In our study, we observed that nearly all scurfy mice produced ANA. The most prevalent pattern in scurfy sera was nuclear coarse speckled, also known as the AC-5 pattern according to the International Consensus on ANA Patterns. U1-ribonucleoprotein (U1RNP) was found to be the most common target antigen recognized by autoantibodies in scurfy mice. Additionally, scurfy mice exhibited a mild myositis with histological characteristics similar to polymyositis/dermatomyositis. Myopathy-specific autoantibody profile revealed significantly increased levels of anti-SMN (survival of motor neuron) as well as anti-Gemin3 antibodies in scurfy sera. Overall, we demonstrate that the impaired peripheral tolerance in the absence of regulatory T cells in scurfy mice is associated with features of mixed connective tissue disease (MCTD). This includes, along with our previous findings, very high titers of anti-U1RNP antibodies and an inflammatory myopathy.

Suspension Processing of Microporous Metal-Organic Frameworks: A Scalable Route to High-Quality Adsorbents.

Metal-Organic Frameworks (MOFs) have been intensively studied for applications such as gas storage, gas separation, catalysis, drug delivery, and more. Typically, the development of MOFs involves a post-synthetic solvent exchange process, which usually requires a significant investment of time, energy, labor, and resources. Herein, we propose a novel post-synthetic processing methodology for commercial and laboratory-scale MOFs called "Suspension Processing." Suspension processing is a non-destructive, agitation-based technique that provides efficient solvent exchange, pore cleaning, and surface defect removal in MOFs. Suspension processing has shown the capability to significantly improve the surface area and gas uptake properties of microporous MOFs, including PCN-250, UiO-66, and HKUST-1. Suspension processing displays improved time, energy, and labor efficiency, as well as considerably enhanced product quality. These findings confirm suspension processing as a straightforward methodology with applicability as a universal technique for the production of high-quality microporous materials.

Incorporating Heavy Alkanes in Metal-Organic Frameworks for Optimizing Adsorbed Natural Gas Capacity.

Metal-organic frameworks (MOFs) as methane adsorbents are highly promising materials for applications such as methane-powered vehicles, flare gas capture, and field natural gas separation. Pre- and post-synthetic modification of MOFs have been known to help improve both the overall methane uptake as well as the working capacity. Here, a post-synthetic modification strategy to non-covalently modify MOF adsorbents for the enhancement of the natural gas uptake for the MOF material is introduced. In this study, PCN-250 adsorbents were doped with C10 alkane and C14 fatty acid and their impact on the methane uptake capabilities was investigated. It was found that even trace amounts of heavy hydrocarbons could considerably enhance the raw methane uptake of the MOF while still being regenerable. The doped hydrocarbons are presumably located at the mesoporous defects of PCN-250, thus optimizing the framework-methane interactions. These findings reveal a general approach that can be used to modify the MOF absorbents, improving their ability to be sustainable and renewable natural gas adsorption platforms.

Regulatory T cell deficient scurfy mice exhibit a Th2/M2-like inflammatory response in the skin.

BACKGROUND: Scurfy mice have a functional defect in regulatory T cells (Treg), which leads to lethal multi-organ inflammation. The missing Treg function results in uncontrolled autoimmune cellular and humoral inflammatory responses. We and others have previously shown that during the course of disease scurfy mice develop severe skin inflammation and autoantibodies including anti-nuclear autoantibodies (ANA). OBJECTIVE: Autoimmune skin inflammation and ANA are hallmarks for the diagnosis of autoimmune connective tissue diseases; therefore we analyzed scurfy mice for typical signs of these diseases. METHODS: Indirect immunofluorescence was used to specify the ANA pattern in scurfy mice. Skin fibrosis was assessed by cutaneous collagen accumulation (Goldeners trichrome staining), collagen crosslinking/disorganization (Sirus red polarimetry) and quantitative PCR for fibrosis-related transcripts. The cellular components of the inflammatory infiltrates in scurfy skin were analyzed by flow cytometry and intracellular cytokine staining. RESULTS: The majority of scurfy mice developed ANA with a predominant AC-5 pattern typical for mixed connective tissue disease, especially scleroderma. Scurfy mice showed higher skin collagen content compared to WT controls with a significant tendency in upregulation of TIMP-1. CD3+CD4+ T cells in scurfy skin exhibited a strong Th2 deviation with a significant increase of IL-4, IL-5 and IL-13, and M2-polarized CD11b+MHCII+ macrophages compared to WT mice. CONCLUSION: We show that Scurfy mice show a predominant AC-5 ANA pattern typical for mixed connective tissue disease as in scleroderma. The autoimmune inflammation in scurfy skin mainly consists of CD4+ T cells with Th2 differentiation and alternatively-activated (M2) macrophages as it is found in scleroderma with advanced fibrosis.

Corrosion at the head-neck interface of current designs of modular femoral components: essential questions and answers relating to corrosion in modular head-neck junctions.

There is increasing global awareness of adverse reactions to metal debris and elevated serum metal ion concentrations following the use of second generation metal-on-metal total hip arthroplasties. The high incidence of these complications can be largely attributed to corrosion at the head-neck interface. Severe corrosion of the taper is identified most commonly in association with larger diameter femoral heads. However, there is emerging evidence of varying levels of corrosion observed in retrieved components with smaller diameter femoral heads. This same mechanism of galvanic and mechanically-assisted crevice corrosion has been observed in metal-on-polyethylene and ceramic components, suggesting an inherent biomechanical problem with current designs of the head-neck interface. We provide a review of the fundamental questions and answers clinicians and researchers must understand regarding corrosion of the taper, and its relevance to current orthopaedic practice. Cite this article: Bone Joint J 2016;98-B:579-84.