Prevalence of post-traumatic neuropathic pain after digital nerve repair and finger amputation.

INTRODUCTION: Post-traumatic neuropathic pain is a major factor affecting the quality of life after finger trauma and is reported with considerable variance in the literature. This can partially be attributed to the different methods of determining neuropathic pain. The Douleur Neuropathique 4 (DN4) has been validated to be a reliable and non-invasive tool to assess the presence of neuropathic pain. This study investigated the prevalence of neuropathic pain after finger amputation or digital nerve repair using the DN4 questionnaire. METHODS: Patients with finger amputation or digital nerve repair were identified between 2011 and 2018 at our institution. After a minimal follow-up of 12 months, the short form DN4 (S-DN4) was used to assess neuropathic pain. RESULTS: A total of 120 patients were included: 50 patients with 91 digital amputations and 70 patients with 87 fingers with digital nerve repair. In the amputation group, 32% of the patients had pain, and 18% had neuropathic pain. In the digital nerve repair group, 38% of the patients had pain, and 14% had neuropathic pain. Secondly, of patient-, trauma-, and treatment-specific factors, only the time between trauma and surgery had a significant negative influence on the prevalence of neuropathic pain in patients with digital nerve repair. CONCLUSION: This study shows that persistent pain and neuropathic pain are common after finger trauma with nerve damage. One of the significant prognostic factors in developing neuropathic pain is treatment delay between trauma and time of digital nerve repair, which is of major clinical relevance for surgical planning of these injuries.

Surgical Treatment Outcome of de Quervain's Disease: A Systematic Review and Meta-analysis.

Background: Surgical release of the extensor retinaculum is performed as a treatment for de Quervain's (DQ) disease when conservative treatment fails. In the literature, there is no consensus about the effectiveness of a surgical release in patients with DQ, the complication rate, or which type of incision is superior. Therefore, a systematic review and meta-analysis were conducted. Methods: A systematic search was performed in Embase, Medline Ovid, Web of Science Core Collection, Cochrane, and Google Scholar. Articles regarding surgical treatment of DQ disease that reported outcome and complications were included. We extracted exact values of visual analog scale scores and percentages of patients who experienced pain at follow-up. Complications assessed were (sub) luxation, superficial radial nerve injuries, wound infections, and scar problems. Results: Twenty-one studies with a total of 939 patients were included. Five percent of these patients (95% CI 1%-18%) did not show complete remission of pain at follow-up. When pooled, the mean reduction in visual analog scale scores was 5.7 (95% CI 5.3-6.1) on a 0-10 scale. No difference in outcome between different types of surgery or incisions was seen. Based on the meta-analysis, the pooled complication rate was 11% (95% CI 5%-22%). Conclusions: Five percent of patients still have residual pain after surgical release of the first extensor compartment. Surgery type, as well as the type of incision, did not affect outcome or complication. Thus, surgical release of the extensor retinaculum for DQ disease is an effective treatment, regardless of the type of surgery.

Prevention is better than cure: Surgical methods for neuropathic pain prevention following amputation - A systematic review.

BACKGROUND: Pain after amputation can be known as residual limb pain (RLP) or phantom limb pain (PLP); however, both can be disabling in daily life with reported incidences of 8% for finger amputations and up to 85% for major limb amputations. The current treatment is focused on reducing the pain after neuropathic pain occurs. However, surgical techniques to prevent neuropathic pain after amputation are available and effective, but they are underutilized. The purpose of the review is to investigate the effects of techniques during amputation to prevent neuropathic pain. METHODS: A systematic review was performed in multiple databases (Embase, Medline, Web of Science, Scopus, Cochrane, and Google Scholar) and following the PRISMA guidelines. Studies that reported surgical techniques to prevent neuropathic pain during limb amputation were included. RESULTS: Of the 6188 selected studies, 13 eligible articles were selected. Five articles reported techniques for finger amputation: neurovascular island flap, centro-central union (CCU), and epineural ligatures, and flaps. For finger amputations, the use of prevention techniques resulted in a decrease of incidences from 8% to 0-3% with CCU being the most beneficial. For major limb amputations, the incidences for RLP were decreased to 0 to 55% with TMR and RPNI and compared to 64-91% for the control group. Eight articles reported techniques for amputations on major limbs: targeted muscle reinnervation (TMR), targeted nerve implantation, concomitant nerve coaptation, and regenerative peripheral nerve interface (RPNI). CONCLUSIONS: Based on the current literature, we state that during finger and major limb amputation, the techniques to prevent neuropathic pain and PLP should be performed.

Proteomics of sea bass skin-scales exposed to the emerging pollutant fluoxetine compared to estradiol.

Teleost fish skin-scales are essential for protection and homeostasis and the largest tissue in direct contact with the environment, but their potential as early indicators of pollutant exposure are hampered by limited knowledge about this model. This study evaluated multi-level impacts of in vivo exposure of European sea bass to fluoxetine (FLX, a selective serotonin-reuptake inhibitor and an emerging pollutant) and 17ß-estradiol (E2, a natural hormone and representative of diverse estrogenic endocrine-disrupting pollutants). Exposed fish had significantly increased circulating levels of FLX and its active metabolite nor-FLX that, in contrast to E2, did not have estrogenic effects on most fish plasma and scale indicators. Quantitative proteomics using SWATH-MS identified 985 proteins in the scale total proteome. 213 proteins were significantly modified 5 days after exposure to E2 or FLX and 31 were common to both treatments and responded in the same way. Common biological processes significantly affected by both treatments were protein turnover and cytoskeleton reorganization. E2 specifically up-regulated proteins related to protein production and degradation and down-regulated the cytoskeleton/extracellular matrix and innate immune proteins. FLX caused both up- and down-regulation of protein synthesis and energy metabolism. Multiple estrogen and serotonin receptor and transporter transcripts were altered in sea bass scales after E2 and/or FLX exposure, revealing complex disruptive effects in estrogen/serotonin responsiveness, which may account for the partially overlapping effects of E2 and FLX on the proteome. A large number (103) of FLX-specifically regulated proteins indicated numerous actions independent of estrogen signalling. This study provides the first quantitative proteome of the fish skin-scale barrier, elucidates routes of action and biochemical and molecular signatures of E2 or FLX-exposure and identifies potential physiological consequences and candidate biomarkers of pollutant exposure, for monitoring and risk assessment.

Metabarcoding the Antarctic Peninsula biodiversity using a multi-gene approach.

Marine sediment communities are major contributors to biogeochemical cycling and benthic ecosystem functioning, but they are poorly described, particularly in remote regions such as Antarctica. We analysed patterns and drivers of diversity in metazoan and prokaryotic benthic communities of the Antarctic Peninsula with metabarcoding approaches. Our results show that the combined use of mitochondrial Cox1, and 16S and 18S rRNA gene regions recovered more phyla, from metazoan to non-metazoan groups, and allowed correlation of possible interactions between kingdoms. This higher level of detection revealed dominance by the arthropods and not nematodes in the Antarctic benthos and further eukaryotic diversity was dominated by benthic protists: the world's largest reservoir of marine diversity. The bacterial family Woeseiaceae was described for the first time in Antarctic sediments. Almost 50% of bacteria and 70% metazoan taxa were unique to each sampled site (high alpha diversity) and harboured unique features for local adaptation (niche-driven). The main abiotic drivers measured, shaping community structure were sediment organic matter, water content and mud. Biotic factors included the nematodes and the highly abundant bacterial fraction, placing protists as a possible bridge for between kingdom interactions. Meiofauna are proposed as sentinels for identifying anthropogenic-induced changes in Antarctic marine sediments.

Vertebrate SLRP family evolution and the subfunctionalization of osteoglycin gene duplicates in teleost fish.

BACKGROUND: Osteoglycin (OGN, a.k.a. mimecan) belongs to cluster III of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). In vertebrates OGN is a characteristic ECM protein of bone. In the present study we explore the evolution of SLRP III and OGN in teleosts that have a skeleton adapted to an aquatic environment. RESULTS: The SLRP gene family has been conserved since the separation of chondrichthyes and osteichthyes. Few gene duplicates of the SLRP III family exist even in the teleosts that experienced a specific whole genome duplication. One exception is ogn for which duplicate copies were identified in fish genomes. The ogn promoter sequence and in vitro mesenchymal stem cell (MSC) cultures suggest the duplicate ogn genes acquired divergent functions. In gilthead sea bream (Sparus aurata) ogn1 was up-regulated during osteoblast and myocyte differentiation in vitro, while ogn2 was severely down-regulated during bone-derived MSCs differentiation into adipocytes in vitro. CONCLUSIONS: Overall, the phylogenetic analysis indicates that the SLRP III family in vertebrates has been under conservative evolutionary pressure. The retention of the ogn gene duplicates in teleosts was linked with the acquisition of different functions. The acquisition by OGN of functions other than that of a bone ECM protein occurred early in the vertebrate lineage.

A review of 10 years of scapula injuries sustained by UK military personnel on operations.

BACKGROUND: Scapula fractures are relatively uncommon injuries, mostly occurring due to the effects of high-energy trauma. Rates of scapula fractures are unknown in the military setting. The aim of this study is to analyse the incidence, aetiology, associated injuries, treatment and complications of these fractures occurring in deployed military personnel. METHODS: All UK military personnel returning with upper limb injuries from Afghanistan and Iraq were retrospectively reviewed using the Royal Centre for Defence Medicine database and case notes (2004-2014). RESULTS: Forty-four scapula fractures out of 572 upper limb fractures (7.7%) were sustained over 10 years. Blast and gunshot wounds (GSW) were leading causative factors in 85%. Over half were open fractures (54%), with open blast fractures often having significant bone and soft tissue loss requiring extensive reconstruction. Multiple injuries were noted including lung, head, vascular and nerve injuries. Injury Severity Scores (ISS) were significantly higher than the average upper limb injury without a scapula fracture (p<0.0001). Brachial plexus injuries occurred in 17%. While military personnel with GSW have a favourable chance of nerve recovery, 75% of brachial plexus injuries that are associated with blast have poorer outcomes. Fixation occurred with either glenoid fractures or floating shoulders (10%); these were as a result of high velocity GSW or mounted blast ejections. There were no cases of deep soft tissue infection or osteomyelitis and all scapula fractures united. CONCLUSION: Scapula fractures have a 20 times higher incidence in military personnel compared with the civilian population, occurring predominantly as a result of blast and GSW, and a higher than average ISS. These fractures are often associated with multiple injuries, including brachial plexus injuries, where those sustained from blast have less favourable outcome. High rates of union following fixation and low rates of infection are expected despite significant contamination and soft tissue loss.

Thyroid function of steatitis-affected Mozambique tilapia Oreochromis mossambicus from a sub-tropical African reservoir.

Thyroid function and nutritional indicators were measured in obese, steatitis-affected Mozambique tilapia Oreochromis mossambicus from Loskop Reservoir (LR), South Africa. Plasma thyroid hormones (especially T3) and thyroid follicle histomorphology revealed high levels of activity in every aspect of the thyroid cascade measured in fish from LR compared to a reference population of steatitis-free fish. Concurrent measurements of nutritional state including plasma lipids, liver lipid content and hepatocyte size showed that fish from LR had significant energy stores indicative of abundant nutritional intake. There were distinct sex and seasonal differences, with the highest plasma lipids and T3 levels observed in steatitis-affected females during spring and summer. Positive correlations were observed between plasma lipids (especially cholesterol) and T3 concentrations in fish from both populations, indicating a link between lipid metabolism and thyroid function. There was no direct evidence of thyroid disruption, but this cannot be ruled out until further research determines the factors that underlie the homeostatic shift leading to elevated plasma and liver lipids and T3 levels in steatitis-affected tilapia.

Duplication of Dio3 genes in teleost fish and their divergent expression in skin during flatfish metamorphosis.

Deiodinase 3 (Dio3) plays an essential role during early development in vertebrates by controlling tissue thyroid hormone (TH) availability. The Atlantic halibut (Hippoglossus hippoglossus) possesses duplicate dio3 genes (dio3a and dio3b). Expression analysis indicates that dio3b levels change in abocular skin during metamorphosis and this suggests that this enzyme is associated with the divergent development of larval skin to the juvenile phenotype. In larvae exposed to MMI, a chemical that inhibits TH production, expression of dio3b in ocular skin is significantly up-regulated suggesting that THs normally modulate this genes expression during this developmental event. The molecular basis for divergent dio3a and dio3b expression and responsiveness to MMI treatment is explained by the multiple conserved TREs in the proximal promoter region of teleost dio3b and their absence from the promoter of dio3a. We propose that the divergent expression of dio3 in ocular and abocular skin during halibut metamorphosis contributes to the asymmetric pigment development in response to THs.

Characterization of the peripheral thyroid system of gilthead seabream acclimated to different ambient salinities.

Thyroid hormones are involved in many developmental and physiological processes, including osmoregulation. The regulation of the thyroid system by environmental salinity in the euryhaline gilthead seabream (Sparus aurata) is still poorly characterized. To this end seabreams were exposed to four different environmental salinities (5, 15, 40 and 55ppt) for 14days, and plasma free thyroid hormones (fT3, fT4), outer ring deiodination and Na+/K+-ATPase activities in gills and kidney, as well as other osmoregulatory and metabolic parameters were measured. Low salinity conditions (5ppt) elicited a significant increase in fT3 (29%) and fT4 (184%) plasma concentrations compared to control animals (acclimated to 40ppt, natural salinity conditions in the Bay of Cádiz, Spain), while the amount of pituitary thyroid stimulating hormone subunit ß (tshb) transcript abundance remained unchanged. In addition, plasma fT4 levels were positively correlated to renal and branchial deiodinase type 2 (dio2) mRNA expression. Gill and kidney T4-outer ring deiodination activities correlated positively with dio2 mRNA expression and the highest values were observed in fish acclimated to low salinities (5 and 15ppt). The high salinity (55ppt) exposure caused a significant increase in tshb expression (65%), but deiodinase gene expression (dio1 and dio2) and activity did not change and were similar to controls (40ppt). In conclusion, acclimation to different salinities led to changes in the peripheral regulation of thyroid hormone metabolism in seabream. Therefore, thyroid hormones are involved in the regulation of ion transport and osmoregulatory physiology in this species. The conclusions derived from this study may also allow aquaculturists to modulate thyroid metabolism in seabream by adjusting culture salinity.

Transcriptomics provides insight into Mytilus galloprovincialis (Mollusca: Bivalvia) mantle function and its role in biomineralisation.

The mantle is an organ common to all molluscs and is at the forefront of the biomineralisation process. The present study used the Mediterranean mussel (Mytilus galloprovincialis) as a model species to investigate the structural and functional role of the mantle in shell formation. The transcriptomes of three regions of the mantle edge (umbo to posterior edge) were sequenced using Illumina technology which yielded a total of 61,674,325 reads after adapter trimming and filtering. The raw reads assembled into 179,879 transcripts with an N50 value of 1086bp. A total of 1363 transcripts (321, 223 and 816 in regions 1, 2 and 3, respectively) that differed in abundance in the three mantle regions were identified and putative function was assigned to 54% using BLAST sequence similarity searches (cut-off less than 1e(-10)). Morphological differences detected by histology of the three mantle regions was linked to functional heterogeneity by selecting the top five most abundant Pfam domains in the annotated 1363 differentially abundant transcripts across the three mantle regions. Calcium binding domains dominated region two (middle segment of the mantle edge). Candidate biomineralisation genes were mined and tested by qPCR. This revealed that Flp-like, a penicillin binding protein potentially involved in shell matrix maintenance of the Pacific oyster (Crassostrea gigas), had significantly higher expression in the posterior end of the mantle edge (region one). Our findings are intriguing as they indicate that the mantle edge appears to be a heterogeneous tissue, displaying structural and functional bias.

Orchestrating change: The thyroid hormones and GI-tract development in flatfish metamorphosis.

Metamorphosis in flatfish (Pleuronectiformes) is a late post-embryonic developmental event that prepares the organism for the larval-to-juvenile transition. Thyroid hormones (THs) play a central role in flatfish metamorphosis and the basic elements that constitute the thyroid axis in vertebrates are all present at this stage. The advantage of using flatfish to study the larval-to-juvenile transition is the profound change in external morphology that accompanies metamorphosis making it easy to track progression to climax. This important lifecycle transition is underpinned by molecular, cellular, structural and functional modifications of organs and tissues that prepare larvae for a successful transition to the adult habitat and lifestyle. Understanding the role of THs in the maturation of organs and tissues with diverse functions during metamorphosis is a major challenge. The change in diet that accompanies the transition from a pelagic larvae to a benthic juvenile in flatfish is associated with structural and functional modifications in the gastrointestinal tract (GI-tract). The present review will focus on the maturation of the GI-tract during metamorphosis giving particular attention to organogenesis of the stomach a TH triggered event. Gene transcripts and biological processes that are associated with GI-tract maturation during Atlantic halibut metamorphosis are identified. Gene ontology analysis reveals core biological functions and putative TH-responsive genes that underpin TH-driven metamorphosis of the GI-tract in Atlantic halibut. Deciphering the specific role remains a challenge. Recent advances in characterizing the molecular, structural and functional modifications that accompany the appearance of a functional stomach in Atlantic halibut are considered and future research challenges identified.

Transcriptome of the Atlantic halibut (Hippoglossus hippoglossus).

Although the Atlantic halibut (Hippoglossus hippoglossus) is an important commercial species, there is still a deficit with regard to the number of transcripts in the databases, which can be accessed and exploited for targeted candidate gene and pathway studies. In this study, the RNAs from head, skin and GI tract from different developmental stages were sequenced to generate 22,272 contigs of 500 base pairs or greater as a molecular resource for this species.

Waterborne exposure of zebrafish embryos to micromole concentrations of ioxynil and diethylstilbestrol disrupts thyrocyte development.

The herbicide ioxynil (IOX) and synthetic estrogen diethylstilbestrol (DES) are common aquatic contaminants with an endocrine disrupting action. In juvenile teleost fish IOX and DES disrupt the hypothalamic-pituitary-thyroid (HPT) axis. To assess how IOX and DES influence the developing HPT axis prior to establishment of central regulation of thyroid hormones, zebrafish embryos were exposed to low concentrations of the chemicals in water. IOX and DES (1 and 0.1 µM) exposure failed to modify hypothalamic development but had a negative effect on thyrocyte development. Specifically, IOX and DES caused a significant (p<0.05) reduction in the size of the thyroid anlagen by decreasing the mRNA expression field of both nk2.1a and thyroglobulin (Tg) genes. Inhibition of thyroid gland development by IOX and DES (0.1 µM) was strongly associated with altered heart morphology. To test if the effect of IOX and DES on the thyroid was a consequence of altered cardiac development a morpholino (MO) against zebrafish cardiac troponin I (zcTnI) was microinjected. The zcTnI morphants had modified heart function, a small thyroid anlagen and a reduction in the mRNA expression of nk2.1a and Tg genes similar to that of zebrafish exposed to IOX (1 and 0.1 µM) and DES (0.1 µM). Collectively the data indicate that IOX and DES alter thyroid development in zebrafish and chemicals that alter heart development and function can have an indirect endocrine disrupting action on the thyroid in teleosts.