Childhood idiopathic spinal cord infarction: Description of 7 cases and review of the literature

Publication date: Available online 31 May 2017
Source:Brain and Development
Author(s): Claire Bar, Emmanuel Cheuret, Pierre Bessou, Jean-Michel Pedespan
ObjectivesTo describe the clinical course, neuroimaging findings and functional outcome of idiopathic spinal cord infarction (SCI) in adolescents.MethodsRetrospective and descriptive analyses of seven patients with idiopathic SCI and 50 additional cases from the literature were included. Data collected concerned clinical presentation, MRI findings, initial diagnosis, treatments and functional outcome at the last medical visit.ResultsMean age at presentation was 13.2years (range 13–15). All patients presented a sudden and painful acute myelopathy with <24h time to maximal symptoms manifestation. A suspected trigger related to a minor effort was reported in 3/7 cases. Six patients presented with paraplegia, one with paraparesis. All had bladder dysfunction needing catheterization. Three patients had an initial misdiagnosis. Initial MRI was considered as normal in 2 cases. In the 5 other cases, T2-weighted-MR images showed hyperintensity within the thoracolumbar spinal cord, affecting mostly the anterior spinal artery territory. Evidence for associated spinal growth dystrophy were present in 6/7 cases. Mean follow-up time was 27.4months (range 3–46): 2 patients recovered autonomous ambulation, 4 patients regained walking ability with aids and one child (the shortest follow-up) remained wheelchair-dependent. A neurogenic bladder was still reported in 6/7 children at the last visit. Complementary analyses with literature cases were consistent with the findings obtained in our cohort.ConclusionIdiopathic SCI typically occurs in adolescence with a rapid onset and painful acute myelopathy. The MRI shows a T2-hyperintense signal within the spinal cord and provides evidence for an ischemic mechanism. Etiology remains unclear in most cases even though some specific risk factors for this age must play an important role in the pathogenesis, such as mechanical constraints on the immature spine.



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Three years’ experience with the first pediatric hospice in Asia

Publication date: Available online 31 May 2017
Source:Brain and Development
Author(s): Kohei Ando, Makoto Nabetani, Nobuyuki Yotani, Tatsushi Rin, Hiroyuki Sano
ObjectivePediatric hospice has been the adoption of several service provision models in highly developed countries such as UK, Germany, Australia or Canada for a few decades, yet it has seldom been the case in the Asian Continent. This study aimed to evaluate the newest challenge for the children with Life-threatening illness (LTI) and described the characteristic of pediatric palliative care at the first pediatric hospice in Japan.MethodsA retrospective review of all patients at our pediatric hospice in these three years was conducted. Of the 294 cases reviewed, 269 cases were eligible for analysis.ResultsWe reviewed 269 patients admitted during the first three years. Most patients required intensive medical intervention. Patients were hospitalized in our pediatric hospice not only for end-of-life care (EOL), but also for respite care. Only 7% of the patients were with cancer. To support children and family to make the most of their time together, we provided a range of medical and recreational care. It is expected that the pediatric hospice will extend and establish cooperation with other hospitals or community services.ConclusionThree years' experience of pediatric palliative care at the first pediatric hospice in the Asian Continent is encouraging. Further experience and improved communication with other pediatric service providers as well as their education in palliative care will enhance the recognition of the capacity of our hospice and support the needs of more children. Furthermore, we would like to introduce the idea of pediatric hospice and spread it throughout the Asian Continent in the future.



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Enhanced self-efficacy after a self-management programme in pituitary disease: a randomized controlled trial

Context

Patients with pituitary disease report impairments in Quality of Life (QoL) despite optimal biomedical care. Until now, the effects of a self-management intervention (SMI) addressing psychological and social issues for these patients and their partners have not been studied.

Objective

To examine the effects of a SMI i.e. Patient and Partner Education Programme for Pituitary disease (PPEP-Pituitary).

Design and subjects

A multicentre randomized controlled trial included 174 patients with pituitary disease, and 63 partners were allocated to either PPEP-Pituitary or a control group. PPEP-Pituitary included eight weekly sessions (90 min). Self-efficacy, bother and needs for support, illness perceptions, coping and QoL were assessed before the intervention (T0), directly after (T1) and after six months (T2). Mood was assessed before and after each session.

Results

Patients in PPEP-Pituitary reported improved mood after each session (except for session 1). In partners, mood only improved after the last three sessions. Patients reported higher self-efficacy at T1 (P = 0.016) which persisted up to T2 (P = 0.033), and less bother by mood problems directly after PPEP-Pituitary (P = 0.01), but more bother after six months (P = 0.001), although this increase was not different from baseline (P = 0.346). Partners in PPEP-Pituitary reported more vitality (P = 0.008) which persisted up to T2 (P = 0.034). At T2, partners also reported less anxiety and depressive symptoms (P ≤ 0.014).

Conclusion

This first study evaluating the effects of a SMI targeting psychosocial issues in patients with pituitary disease and their partners demonstrated promising positive results. Future research should focus on the refinement and implementation of this SMI into clinical practice.

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Association between estimated glomerular filtration rate and outcomes in patients with diabetic foot ulcers: a 3-year follow-up study

Objective

End-stage renal disease and dialysis have been proven to be associated with poor prognoses in diabetic foot ulcers (DFUs). However, it has rarely been reported whether and to what extent milder renal insufficiency affects the prognosis. The purpose of this study was to investigate the categorized impact of estimated glomerular filtration (eGFR) on the outcomes of patients with DFU.

Design and methods

Three hundred and sixty-six DFU patients hospitalized in a Chinese tertiary hospital were recruited and classified into 4 groups according to the eGFRs as follows: normal (≥90), mildly reduced (60–89), moderately reduced (30–59), and severely reduced (<30). These patients were followed-up for an average of 37 months to observe the outcomes, including ulcer healing, amputation, ulcer recurrence, cardiac or cerebrovascular events and death. The associations between eGFR and the outcomes were analysed by Cox proportional-hazards models.

Results

Compared to patients with normal eGFR, patients with moderately reduced eGFR had higher risk of healing failure (hazard ratio (HR) = 2.08, 95% confidence interval (CI): 1.13–3.82), cardiac events (HR = 5.25, 95% CI: 2.17–12.89) and death (HR = 3.54, 95% CI: 1.36–9.20). Severely reduced eGFR was associated with higher incidence of healing failure (HR = 2.84, 95% CI: 1.25–6.49) and death (HR = 4.45, 95% CI: 1.23–16.07). The impact of eGFR on ulcer recurrence and cerebrovascular events was not observed in all groups.

Conclusions

Moderately and severely reduced eGFR in patients with DFU were independent predictors for poor prognoses of both the limbs and the patients.

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Cardiovascular events in patients with mild autonomous cortisol secretion: analysis with artificial neural networks

Background

The independent role of mild autonomous cortisol secretion (ACS) in influencing the cardiovascular event (CVE) occurrence is a topic of interest. We investigated the role of mild ACS in the CVE occurrence in patients with adrenal incidentaloma (AI) by standard statistics and artificial neural networks (ANNs).

Methods

We analyzed a retrospective record of 518 AI patients. Data regarding cortisol levels after 1 mg dexamethasone suppression (1 mg DST) and the presence of obesity (OB), hypertension (AH), type-2 diabetes (T2DM), dyslipidemia (DL), familial CVE history, smoking habit and CVE were collected.

Results

The receiver-operating characteristic curve analysis suggested that 1 mg DST, at a cut-off of 1.8 µg/dL, had the best accuracy for detecting patients with increased CVE risk. In patients with 1 mg-DST ≥1.8 µg/dL (DST+, n = 223), age and prevalence of AH, T2DM, DL and CVE (66 years, 74.5, 25.9, 41.4 and 26.8% respectively) were higher than that of patients with 1 mg-DST ≤1.8 µg/dL (61.9 years, 60.7, 18.5, 32.9 and 10%, respectively, P < 0.05 for all). The CVE were associated with DST+ (OR: 2.46, 95% CI: 1.5–4.1, P = 0.01), regardless of T2DM, AH, DL, smoking habit, gender, observation period and age. The presence of at least two among AH, T2DM, DL and OB plus DST+ had 61.1% sensitivity in detecting patients with CVE. By using the variables selected by ANNs (familial CVE history, age, T2DM, AH, DL and DST+) 78.7% sensitivity was reached.

Conclusions

Cortisol after 1 mg-DST is independently associated with the CVE occurrence. The ANNs might help for assessing the CVE risk in AI patients.

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Brown adipose tissue is associated with systemic concentrations of peptides secreted from the gastrointestinal system and involved in appetite regulation

Objective

Brown adipose tissue (BAT) has been proposed as a potential therapeutic target against obesity and its related metabolic conditions. Data from studies in rodents support a cross talk between BAT and other distal tissues. The relation between BAT and peptide hormones secreted from the gastrointestinal system (GI) and involved in appetite regulation is not known in humans.

Design

We studied 18 men during thermoneutral conditions and mild non-shivering cold exposure (CE).

Methods

2-Deoxy-2-(¹⁸F)fluoro-d-glucose positron emission tomography-computed tomography scans were conducted after mild cold to measure BAT volume. Fasting serum concentration of GI-secreted peptides and peptides involved in appetite regulation were measured during thermoneutral conditions and mild CE.

Results

During thermoneutral conditions, BAT volume was associated with lower serum concentration of leptin (P = 0.006), gastric inhibitory polypeptide (P = 0.016) and glucagon (P = 0.048) after adjusting for age and body fat percent. CE significantly decreased serum leptin (P = 0.004) and glucagon concentration (P = 0.020), while cold-induced BAT activation was significantly associated with lower serum ghrelin concentration (P = 0.029).

Conclusions

BAT is associated with systemic concentrations of GI-secreted peptides and peptides involved in appetite regulation, suggesting a potential cross talk between BAT and the enteropancreatic axis. Further studies are needed to elucidate the potential link of BAT with the postprandial levels of appetite-regulating peptides and the putative role of BAT in appetite regulation in humans.

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Altered sleep patterns in patients with non-functional GHRH receptor

Objectives

GH-releasing hormone (GHRH) exerts hypnotic actions increasing the non-rapid eye movement (NREM) sleep. Conversely, GH stimulates the REM sleep. GH deficiency (GHD) often leads to sleep problems, daytime fatigue and reduced quality of life (QoL). GHD may be due to lack of hypothalamic GHRH or destruction of somatotroph cells. We have described a cohort with isolated GHD (IGHD) due to GHRH resistance caused by a homozygous null mutation (c.57 + 1G > A) in the GHRH receptor gene. They have normal QoL and no obvious complaints of chronic tiredness. The aim of this study was to determine the sleep quality in these subjects.

Methods

A cross-sectional study was carried out in 21 adult IGHD subjects, and 21 age- and gender-matched controls. Objective sleep assessment included polygraphic records of the awake, stages NREM [N1 (drowsiness), N2 and N3 (already sleeping)] and REM (R). Subjective evaluation included the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and the Epworth Sleepiness Scale.

Results

IGHD subjects showed a reduction in sleep efficiency (P = 0.007), total sleep time (P = 0.028), duration of N2 and R in minutes (P = 0.026 and P = 0.046 respectively), but had increased duration and percentage of N1 stage (P = 0.029 and P = 0.022 respectively), wake (P = 0.007) and wake-time after sleep onset (P = 0.017). There was no difference in N3 or in sleep quality questionnaire scores.

Conclusion

Patients with IGHD due to GHRH resistance exhibit objective reduction in the sleep quality, with changes in NREM and REM sleep, with no detectable subjective consequences. GHRH resistance seems to have a preponderant role over GHD in the sleep quality of these subjects.

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A Two-Phase Pilot Study to Evaluate the Safety and Tolerability of an In Situ Polymerizing Collagen.

BACKGROUND: Demand for collagen-based fillers has declined primarily because of limited long-term clinical benefit and the introduction of hyaluronic acid compositions. In situ polymerizing collagen is a noncrosslinked solution of porcine collagen containing a collagenase shield that undergoes fibrillogenesis on injected into tissues forming a natural matrix. OBJECTIVE: Conduct a prospective, single-center, dual-phase open-label study in 8 subjects to evaluate the safety, tolerability, and efficacy of the porcine collagen composition. METHODS: In Phase I, potential hypersensitivity of the collagen composition was evaluated after skin testing in the back (men) or forearms of subjects (women). In Phase II, subjects showing no signs of hypersensitivity received collagen injections into the nasolabial area followed by evaluation at 1, 4, 8, and 12 weeks using the Global Aesthetic Improvement Scale. RESULTS: None of the subjects had signs of hypersensitivity and all continued in Phase II. The treating physician(s) reported no post-treatment adverse events. Improvement of the nasolabial fold was observed by the physicians and confirmed by assessment of high-resolution photographs and Global Aesthetic Improvement Scale scores over the 12-week treatment were maintained. CONCLUSION: In this pilot clinical study in situ polymerizing collagen was shown to be safe and effective throughout the 3-month study period. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Platelet-Rich Plasma in Combination With 5% Minoxidil Topical Solution and 1 mg Oral Finasteride for the Treatment of Androgenetic Alopecia: A Randomized Placebo-Controlled, Double-Blind, Half-Head Study.

No abstract available

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Treatment of Actinic Keratoses: A Randomized Split-Site Approach Comparison of Sequential 5-Fluorouracil and 5-Aminolevulinic Acid Photodynamic Therapy to 5-Aminolevulinic Acid Photodynamic Monotherapy.

BACKGROUND: Actinic keratoses (AKs) are skin lesions resulting from sun exposure and carry a risk of developing into squamous cell carcinoma. Current therapies for AK eradication include topical 5-fluorouracil (5-FU) and photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA). However, sequential therapy with 5-FU-ALA-PDT may offer improved outcome compared to ALA-PDT alone. OBJECTIVE: The purpose of this study is to compare the long-term efficacy of AK clearance by sequential therapy with 5-FU-ALA-PDT versus ALA-PDT alone. MATERIALS AND METHODS: This is a single center, randomized split-site approach study on equivalent anatomical and clinical sites. Seventeen patients were enrolled with one half of the site randomized to receive sequential 5-FU-ALA-PDT and the other side with ALA-PDT monotherapy. Total AKs were counted at baseline, 6 and 12 months. RESULTS: Median percentage reduction in AK number at 6 months for 5-FU-ALA-PDT versus ALA-PDT was 100% for 5-FU-ALA-PDT (N = 21) and 66.7% for ALA-PDT (N = 21), p = .001. Median percentage reduction in AK number at 12 months for 5-FU-ALA-PDT versus ALA-PDT was 100% for 5-FU-ALA-PDT (N = 22) and 82.6% for ALA-PDT (N = 22), p = .0002. CONCLUSION: Sequential therapy with 5-FU-ALA-PDT is more effective at AK clearance at 6 and 12 months compared to ALA-PDT monotherapy. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Calcium Hydroxylapatite Dermal Filler for Treatment of Dorsal Hand Volume Loss: Results From a 12-Month, Multicenter, Randomized, Blinded Trial.

BACKGROUND: Calcium hydroxylapatite (CaHA) microspheres suspended in a carrier gel is an opaque dermal filler that has been used to provide immediate volume correction in the dorsal hands. OBJECTIVE: To assess the safety and effectiveness of CaHA for the correction of volume loss in the hands up to 12 months. MATERIALS AND METHODS: This multicenter, controlled, single-blind study (NCT01832090) included 114 subjects randomized 3:1 to CaHA treatment and untreated control groups. Effectiveness was assessed by blinded investigators using the validated Merz Hand Grading Scale (MHGS). Subject-reported improvement was assessed using the Global Aesthetic Improvement Scale. Effects of treatment on hand function were also assessed. RESULTS: A total of 75% of subjects achieved >=1-point improvement on the MHGS (p

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Comment on Double-Blind, Placebo-Controlled Pilot Study on the Use of Platelet-Rich Plasma in Women With Female Androgenetic Alopecia.

No abstract available

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Use of Skin Biopsies Among Dermatologists.

BACKGROUND: Skin biopsies are essential to establish a diagnosis in many skin diseases. Utilization has been increasing rapidly and represents a significant health care cost. There are no benchmarks or baselines to guide the practice of skin biopsies. OBJECTIVE: To create a reference data set of biopsy behavior among dermatologists. METHODS: Five hundred eighty-eight dermatologists belonging to the American Dermatological Association (ADA) were surveyed. Two hundred eighty-seven responded with 128 of those providing biopsy data. RESULTS: The mean percentage of biopsies that were malignant was 44.5%. This varied by subspecialty with a mean of 41.7%, 57.4%, and 4.1% of biopsies performed by general dermatologists, Mohs micrographic surgeons, and pediatric dermatologists, respectively. By category or diagnosis, the biopsies were 22.7% basal cell carcinoma, 12.0% SCC, 10.2% benign neoplasms, 10.0% nevi, 8.0% actinic keratosis, 7.6% seborrheic keratosis, 7.5% inflammatory disorders, 6.1% SCC in situ, 5.3% dysplastic nevus, 5.1% benign skin, 1.5% melanoma in situ, 1.4% melanoma, 0.9% lentigines, 0.8% other malignancies, 0.6% infectious, 0.2% not otherwise specified, and 0.1% atypical lesions. There was a statistically significant difference in biopsy results between different dermatological subspecialties. CONCLUSION: These results should help elucidate dermatologic practice patterns and thus create opportunities to improve dermatologic care and reduce health care costs. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Retrospective Evaluation of Topical Bimatoprost and Iris Pigmentation Change.

BACKGROUND: Topical bimatoprost is a topical prostaglandin analog originally used to treat glaucoma and more recently used to cosmetically induce hypertrichosis of the eyelashes. Iris pigmentation change has been noted in the treatment of glaucoma but has not been assessed with the cosmetic periorbital application of bimatoprost. OBJECTIVE: To evaluate for iris pigmentation change with the long-term cosmetic use of topical bimatoprost. MATERIALS AND METHODS: A retrospective chart review in a cosmetic dermatology practice of women (N = 50) who consistently purchased topical bimatoprost over an average of 4.59 years was compared with that of age-matched non-bimatoprost patients (N = 50). A blinded evaluator assessed each patient for iris pigmentary change. RESULTS: No iris pigmentation change was noted with the cutaneous application of bimatoprost. CONCLUSION: The cutaneous application of bimatoprost appears to be safe with minimal risk for iris pigmentation change. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Impact of Smoke Evacuation on Patient Experience During Mohs Surgery.

BACKGROUND: There have been several investigations into possible health risks of surgical smoke exposure, and it has previously been associated with harboring pathogens and carcinogens. Patients in the authors' practice have expressed that the odor from the smoke created by electrosurgical equipment is unpleasant. OBJECTIVE: The authors sought to determine if smoke evacuation decreases patient perception of smoke created by electrosurgery during Mohs surgery and if it subsequently improves patient satisfaction with their surgical experience by minimizing the associated odor. MATERIALS AND METHODS: Thirty patients were enrolled in this comparative trial. Smoke evacuation was used during closure but not during Mohs stages. Patients were queried regarding their experience and preferences during and at the end of the procedure. RESULTS: 100% of patients reported the perception of a burning odor during removal of Mohs stages, compared with 40% reporting the perception of a burning odor during closure. During the Mohs stages, 66.6% of patients reported the odor as unpleasant compared with 16.6% of patients during closure. There were no statistically significant differences in patient perceptions when stratified by age, sex, or surgical site. CONCLUSION: The authors believe that using a wall suction smoke evacuation system is simple and can result in a more pleasant experience for patients undergoing Mohs surgery. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Lacrimal Apparatus Defect Repair: Use of the Monocanalicular Silicone Stent.

No abstract available

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Forearm skin aging: characterization by instrumental measurements

Abstract

Background

The intrinsic aging and photoaged skin presents biomechanical and morphological differences, which are reflected in the appearance of roughness, superficial and deep wrinkles, atrophy, reduced elasticity, hypo and hyperpigmentation and actinic keratosis

Objective

To evaluate and compare the characteristics of the flexor (with a predominance of intrinsic aging) and extensor (chronically exposed to sunlight and other environmental factors, with a predominance of photoaging) skin surfaces of the forearms

Methods

Interventional, prospective, diagnostic study, including 23 females, aged over 60 years. The extensor and flexor faces of forearms were compared in relation to clinical parameters and non-invasive instrumental measurements, such as skin surface, elasticity, hydration as well as dermal thickness and echogenicity

Results

Regarding the water content of the stratum corneum, the flexor face presented an average value higher than the extensor face. The average of measures obtained through images of high frequency ultrasound demonstrated greater echogenicity of flexor face compared to the extensor face. The measurements of the skin surface showed significant differences between the faces. The roughness and scaliness were lower in the flexor face. Regarding the wrinkles depth, there was no significant difference between the faces. The average of the measurements was slightly higher in the flexor face, which demonstrated that wrinkles are present in the intrinsic aging and photoaging. The presence of elastosis and the reduction of elasticity in the clinical aspect of the photoaged face of forearms were according to results of the non-invasive measurements

Conclusion

Meaningful differences in the biophysical characteristics of the extensor and flexor faces of the forearms were detected. Because the non-invasive instrumental measurements correlated with clinical findings, they may represent useful tools to assess efficacy and safety of skin aging treatments in clinical research.

This article is protected by copyright. All rights reserved.

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Clinical and radiologic predictive factors of rib fractures in outpatients with chest pain

Publication date: Available online 30 May 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Liang Zhang, Colm J McMahon, Samir Shah, Jim S Wu, Ronald L. Eisenberg, Justin W. Kung
PurposeTo identify the clinical and radiologic predictive factors of rib fractures in stable adult outpatients presenting with chest pain and to determine the utility of dedicated rib radiographs in this population of patients.Method and MaterialsFollowing IRB approval, we performed a retrospective review of 339 consecutive cases in which a frontal chest radiograph and dedicated rib series had been obtained for chest pain in the outpatient setting. The frontal chest radiograph and dedicated rib series were sequentially reviewed in consensus by two fellowship-trained musculoskeletal radiologists blinded to the initial report. The consensus interpretation of the dedicated rib series was used as the gold standard. Multiple variable logistic regression analysis assessed clinical and radiological factors associated with rib fractures. Fisher's exact test was used to assess differences in medical treatment between the two groups.ResultsOf the 339 patients, 53 (15.6%) had at least one rib fracture. Only 20 of the 53 (37.7%) patients' fractures could be identified on the frontal chest radiograph. The frontal chest radiograph had a sensitivity of 38% and specificity of 100% when using the rib series as the reference standard. No pneumothorax, new mediastinal widening or pulmonary contusion was identified. Multiple variable logistic regression analysis of clinical factors associated with the presence of rib fractures revealed a significant association of trauma history [odds ratio 5.7 (p<0.05)] and age ≥40 [odds radio 3.1 (p<0.05)]. Multiple variable logistic regression analysis of radiographic factors associated with rib fractures in this population demonstrated a significant association of pleural effusion with rib fractures [odds ratio 18.9 (p<0.05)]. Patients with rib fractures received narcotic analgesia in 47.2% of cases, significantly more than those without rib fractures (21.3%, p<0.05). No patient required hospitalization.ConclusionIn the stable outpatient setting, rib fractures have a higher association with a history of minor trauma and age ≥40 in the adult population. Radiographic findings associated with rib fractures include pleural effusion. The frontal chest radiograph alone has low sensitivity in detecting rib fractures. The dedicated rib series detected a greater number of rib fractures. While no patient required hospitalization, those with rib fractures were more likely to receive narcotic analgesia.



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Shrimp TAB1 interacts with TAK1 and p38 and activates the host innate immune response to bacterial infection

Publication date: August 2017
Source:Molecular Immunology, Volume 88
Author(s): Sheng Wang, Mengqiao Li, Bin Yin, Haoyang Li, Bang Xiao, Kai Lǚ, Zhijian Huang, Sedong Li, Jianguo He, Chaozheng Li
Mammalian TAB1 has been previously identified as transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) binding protein, which functions as the activator of TAK1 and p38. This report, for the first time, identified and characterized the homolog of TAB1 in shrimp, to be specific, the homolog gene from Litopenaeus vannamei, containing a 1560-bp open reading frame (ORF) that encoded a putative protein of 519 amino acids with the conserved PP2Cc (Serine/threonine phosphatases, family 2C, catalytic) domain in N-terminal and a TAK1 binding motif in C-terminus, has been cloned and named LvTAB1. LvTAB1 was most abundant in gills and its expression could respond significantly to a series of stimuli, including LPS, Vibrio parahemolyticus and Staphylococcus aureus. Moreover, Co-immunoprecipitation (Co-IP) experiments showed that LvTAB1 could combine with LvTAK1 as well as Lvp38, two members of IMD-NF-κB/MAPK pathway, which meant LvTAB1 could have a role in regulating the activities of these kinases. Over-expression of LvTAB1 in drosophila S2 cells could improve the transcriptional levels of antimicrobial peptide genes (AMPs) such as Diptericin (Dpt), the hallmark of drosophila NF-κB activated genes, indicating its activation effect on NF-κB pathway. Furthermore, suppression of LvTAB1 expression in vivo by RNA-interference increased the sensibility of shrimps to V. parahaemolyticus infection, implying its protective role against bacterial infection. In conclusion, these results provide some insight into the function of LvTAB1 during bacterial infection.



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Complement in clinical medicine: Clinical trials, case reports and therapy monitoring

Publication date: Available online 31 May 2017
Source:Molecular Immunology
Author(s): Daniel Ricklin, Andreas Barratt-Due, Tom Eirik Mollnes
Research during past decades made it evident that complement is involved in more tasks than fighting infections, but has important roles in other immune surveillance and housekeeping functions. If the balance between complement activation and regulation is out of tune, however, complement can quickly turn against the host and contribute to adverse processes that result in various clinical conditions. Whereas clinical awareness was initially focused on complement deficiencies, excessive activation and insufficient regulation are frequently the dominant factors in complement-related disorders. The individual complement profile of a patient often determines the course and severity of the disease, and the pathophysiological involvement of complement may be highly diverse. As a consequence, complement assays have evolved as essential tools not only in initial diagnosis but also for following disease progression and for monitoring complement-targeted therapies, which become increasingly available in routine clinical use. We herein review the current state of complement-directed drug candidates in clinical evaluation and provide an overview of extended indications considered for the FDA-approved inhibitor eculizumab. Furthermore we review the literature describing cases reports and case series where eculizumab has been used "off-label". Finally, we give a summary of the currently available tests to measure complement profiles and discuss their suitability in diagnostics and treatment monitoring. With complement finally entering the clinical arena, there are intriguing opportunities for treating complement-mediated diseases. However, this progress also requires a new awareness about complement pathophysiology, adequate diagnostic tools and suitable treatment options among clinicians treating patients with such disorders.



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