Distal Limb Research Articles

Prevalence of radiographic changes in forelimb digits and metacarpophalangeal joints of South African endurance racehorses.

If the number of events alone is considered, endurance riding is the fastest growing and the second-most popular Fédération Equestre Internationale (FEI) discipline. Lameness is the most common cause of elimination from endurance races worldwide. To the authors' knowledge, no studies have been published investigating the prevalence of radiographic changes in the forelimb digits and metacarpophalangeal joints (MCP) of endurance racehorses in South Africa. Investigate the prevalence of radiographic changes in the forelimb digits and MCP joints of South African endurance racehorses. One hundred endurance racehorses registered with ERASA were volunteered by their owners to partake in the current study. Radiographs were obtained from horses competing in endurance races during the 2018-2019 endurance racing season. Radiographs included seven standard views of each distal forelimb. Radiographic images were independently evaluated by three observers, point prevalence and inter-rater reliability (IRR) was calculated. Data analysis of the forelimb digits revealed a large proportion of horses with bilateral signs of dorsopalmar hoof imbalance (95%); a diversion from a straight digital axis (91%), with an extended (broken back) proximal interphalangeal joint (67%) being the most common abnormality. Osteoarthritis of the proximal (16%) and distal (7%) interphalangeal joints was only observed in a low percentage of horses. Interestingly, the hoof-distal-phalanx-ratio of the majority (86%) of horses was more than 25% but none of these horses showed any other signs of chronic laminitis, indicating that hoof-distal-phalanx-ratio might not be a reliable indicator of chronic laminitis in this population of horses. Ossification of the ungular cartilages was observed in the majority (69%) of horses, either affecting one or both distal phalanges. Descriptive data analysis of the MCP joints showed that a large proportion of horses displayed radiological signs of MCP joint osteoarthritis (28%), with 10% being bilateral. The current study provides insight into radiographic changes and their prevalence in the distal front limbs of South African endurance racehorses. Knowledge about the prevalence of specific radiographic changes would enable equine practitioners to better evaluate and manage horses that are affected. Although no correlations were made with age, speed or number of competitive kilometres competed, the current study may serve as a basis for future research.

En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration.

The mouse digit tip regenerates following amputation. How the regenerate is patterned is unknown, but a long-standing hypothesis proposes developmental patterning mechanisms are re-used during regeneration. The digit tip bone exhibits dorsal-ventral (DV) polarity, so we focus on En1 and Lmx1b, two factors necessary for DV patterning during limb development. We investigate whether they are re-expressed during regeneration in a developmental-like pattern and whether they direct DV morphology of the regenerate. We find that both En1 and Lmx1b are expressed in the regenerating digit tip epithelium and mesenchyme, respectively, but without DV polarity. Conditional genetics and quantitative analysis of digit tip bone morphology determine that genetic deletion of En1 or Lmx1b in adult digit tip regeneration modestly reduces bone regeneration but does not affect DV patterning. Collectively, our data suggest that, while En1 and Lmx1b are re-expressed during mouse digit tip regeneration, they do not define the DV axis during regeneration.

The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.

In the field of hereditary spastic paraplegia (HSP), progress in molecular diagnostics needs to be translated into robust phenotyping studies to understand genetic and phenotypic heterogeneity and to support interventional trials. ZFYVE26-associated hereditary spastic paraplegia (HSP-ZFYVE26, SPG15) is a rare, early-onset complex HSP, characterized by progressive spasticity and a variety of other neurological symptoms. While prior reports, often in populations with high rates of consanguinity, have established a general phenotype, there is a lack of systematic investigations and a limited understanding of age-dependent manifestation of symptoms. Here we delineate the clinical, neuroimaging and molecular features of 44 individuals from 36 families, the largest cohort assembled to date. Median age at last follow-up was 23.8 years covering a wide age range (11-61 years). While symptom onset often occurred in early childhood [median: 24 months, interquartile range (IQR) = 24], a molecular diagnosis was reached at a median age of 18.8 years (IQR = 8), indicating significant diagnostic delay. We demonstrate that most patients present with motor and/or speech delay or learning disabilities. Importantly, these developmental symptoms preceded the onset of motor symptoms by several years. Progressive spasticity in the lower extremities, the hallmark feature of HSP-ZFYVE26, typically presents in adolescence and involves the distal lower limbs before progressing proximally. Spasticity in the upper extremities was seen in 64%. We found a high prevalence of extrapyramidal movement disorders including cerebellar ataxia (64%) and dystonia (11%). Parkinsonism (16%) was present in a subset and showed no sustained response to levodopa. Cognitive decline and neurogenic bladder dysfunction progressed over time in most patients. A systematic analysis of brain MRI features revealed a common diagnostic signature consisting of thinning of the anterior corpus callosum, signal changes of the anterior forceps and non-specific cortical and cerebellar atrophy. The molecular spectrum included 45 distinct variants, distributed across the protein structure without mutational hotspots. Spastic Paraplegia Rating Scale scores, SPATAX Disability Scores and the Four Stage Functional Mobility Score showed moderate strength in representing the proportion of variation between disease duration and motor dysfunction. Plasma neurofilament light chain levels were significantly elevated in all patients (Mann-Whitney U-test, P < 0.0001) and were correlated inversely with age (Spearman's rank correlation coefficient r = -0.65, P = 0.01). In summary, our systematic cross-sectional analysis of HSP-ZFYVE26 patients across a wide age-range, delineates core clinical, neuroimaging and molecular features and identifies markers of disease severity. These results raise awareness to this rare disease, facilitate an early diagnosis and create clinical trial readiness.

Environmental signal in the evolutionary diversification of bird skeletons.

Characterizing how variation in the tempo and mode of evolution has structured the phenotypic diversity of extant species is a central goal of macroevolution1-3. However, studies are typically limited to a handful of traits4-6, providing incomplete information. We analyse morphological diversification in living birds, an ecologically diverse group7, documenting structural scales from 'pan-skeletal' proportions down to the localized three-dimensional shape changes of individual bones. We find substantial variation in evolutionary modes among avian subgroups and among skeletal parts, indicating widespread mosaicism and possible differences in the structure of the macroevolutionary landscape across Earth's main environments. Water-linked groups, especially Aequorlitornithes (waterbirds), have repeatedly explored a large portion of their total morphospace, emphasizing variation in body proportions and in the shape of bones close to the body core, which are functionally related to the mechanics of locomotion8. By contrast, landbirds (Inopinaves) evolved distinct, group-specific body forms early in the aftermath of the K-Pg and subsequently emphasized local shape variation, especially in the head and distal limb bones, which interact more directly with the environment. Passerines, which comprise more than half of all bird species, show a conservative evolutionary dynamic that resulted in low disparity across all skeletal parts. Evidence for early establishment of the morphospace of living birds is clear for some skeletal parts, including beaks and the combined skeletal morphology. However, we find little evidence for early partitioning of that morphospace, contrary to more specific predictions of 'niche-filling' models1,9. Nevertheless, early divergence among broad environmental types may have caused an early divergence of evolutionary modes, suggesting an important role for environmental divergence in structuring the radiation of crown-group birds.

Functional connectivity of proximal and distal lower limb muscles and impact on gait variability in stroke

BackgroundHigher gait variability after stroke increases risk of falls and compromises safe community ambulation. Corticomotor connectivity plays an important role in walking after stroke, however, its relation to gait variability remains unknown. Research questionDo corticomotor characteristics of the proximal and distal lower limb muscles predict gait variability in individuals with chronic stroke? MethodsRetrospective analysis of data from 30 individuals with chronic stroke was conducted. Corticomotor characteristics were measured in the paretic and non-paretic tibialis anterior (TA, distal muscle) and rectus femoris (RF, proximal muscle) using transcranial magnetic stimulation. We calculated corticomotor excitability ratio of paretic TA and RF (CMETA/RF), corticomotor excitability symmetry (CMEsym) between hemispheres for the TA and RF, and ipsilateral corticomotor excitability (ICE) of the paretic TA. Gait variability was quantified as the coefficient of variation of the paretic step length (spatial) and step time (temporal) during comfortable walking. Relations between corticomotor characteristics and gait variability were tested with multiple linear regression. ResultsCMETA/RF and CMEsym of RF were significant predictors of spatial gait variability. Greater corticomotor input to the paretic RF compared to the paretic TA and greater symmetry of RF were related to higher spatial gait variability. There were no significant predictors of temporal gait variability. SignificanceCorticomotor inputs to the proximal RF may be important for spatial gait variability, reflecting a compensatory role of RF in walking after stroke. Stroke survivors with relatively greater corticomotor input to the paretic RF may adopt compensatory strategy to enhance propulsion and achieve foot clearance, but it may also increase spatial gait variability, particularly when combined with impaired motor control of the paretic TA. These findings may provide novel rehabilitative targets to decrease gait variability and promote safe ambulation in individuals with stroke.

First clinical applications for the NIR-II imaging with ICG in microsurgery.

In microsurgery, it is always difficult to accurately identify the blood supply with ease, such as vascular anastomosis, digit replantation, skin avulsion reconstruction and flap transplantation. Near-infrared window I (NIR-I, 700-900nm) imaging has many clinical applications, whereas near-infrared window II (NIR-II, 1,000-1700nm) imaging has emerged as a highly promising novel optical imaging modality and used in a few clinical fields recently, especially its penetration distance and noninvasive characteristics coincide with the needs of microsurgery. Therefore, a portable NIR-II imaging instrument and the Food and Drug Administration (FDA) approved indocyanine green (ICG) were used to improve the operation efficiency in microsurgery of 39 patients in this study. The anastomotic vessels and the salvaged distal limbs were clearly visualized after intravenous injection of ICG. The technique enabled identification of perforator vessels and estimation of perforator areas prior to the flap obtention and made it easier to monitor the prognosis. Overall, this study highlights the use of the portable NIR- II imaging with ICG as an operative evaluation tool can enhance the safety and accuracy of microsurgery.

The effect of different socio-economic and working conditions on body size and proportions: A case study on adults from Samsun, Turkey.

Conditions in the early stages of life shape body size and proportions. This study includes individuals who came from different socio-economic conditions and worked in physically demanding jobs in childhood. By determining the body sizes of these individuals and evaluating the proportional relationships between several groups, the goal was to understand the effect levels of socio-economic levels and working conditions on the body. For this purpose, an anthropometric study was conducted on 623 males and females between the ages of 20 and 45 living in Samsun, Turkey. The study sample consisted of four different groups. It was divided into two main groups of high and low socio-economic level, and the low socio-economic group was divided into two subgroups of heavy-worker and nonheavy-worker. The results demonstrated that socio-economic differences in the size and proportions of the individuals were statistically significant (p<0.05). The high socio-economic group had the highest values in all measures. External factors affected the lower limbs more than the upper limbs. The measurement most affected by these factors was leg length. Longer legs characterized the high socio-economic group, while longer arms characterized both low socio-economic groups. The relative differences observed can be said to derive from the distal limbs. This finding was valid for both sexes. The average values were close to each other in the low socio-economic group, for which the aim was to comprehend the effects of heavy working conditions. However, differences in proportional relationships were more significant. In this context, it was seen that heavy labour also affected growth, in addition to the well-known factors encountered during the growth period, such as nutrition, health, and illness. The observed changes were more significant in males than in females. Thus, it can be said that males were more affected by physiological and physical conditions.

Robotic Fingers in Reach-to-Grasp Tasks of Rehabilitation

The REHAROB robotic upper limb rehabilitation system was improved with a custom-designed and developed hand/finger therapy module. The new module extends the scope of the applicable motion therapy from passive to active reach-to-grasp activities of daily living tasks, and the range of treated anatomical joints was also extended to every proximal and distal upper limb anatomical joint. Finger exercising and object grasping are supported with a pair of two degree-of-freedom (DOF) robotic fingers. One of the robotic fingers moves the index/middle/ring fingers together, whereas the other robotic finger moves the thumb. A novel hypothesis was established, analyzed, and tested for setting the orientation of the robotic finger moving the thumb. The robotic thumb is not aligned with the patient's thumb; its orientation is optimized in the patient's hand reference system to maximize the efficiency in the opposite grasping task. While most concurrent systems utilize virtual objects for grasping tasks, the REHAROB system exercises five carefully selected reach-and-grasp type activities of daily living (ADL) with real objects. Actuating the human finger phalanges through custom development finger orthoses is described. An advanced feature of the hand/finger therapy module is the left-right hand side changeover by only alternating the orientation of the robotic fingers and exchanging the finger orthoses.

Body distribution of impetigo and association with host and pathogen factors

Background Impetigo or skin sores are estimated to affect &gt;162 million people worldwide. Detailed descriptions of the anatomical location of skin sores are lacking. Methods We used prospectively collected data from a randomised control trial of treatments for impetigo in Aboriginal children in Australia. We generated heat-map distributions of skin sores on the human body from 56 predefined anatomical locations and stratified skin sore distribution by sex, age, causative pathogen and co-infection with scabies, tinea and head lice. We compared the distribution of sores between males and females, between sores with only Streptococcus pyogenes and sores with only Staphylococcus aureus; and across age groups with a Fisher’s exact test. Results There were 663 episodes of impetigo infections among 508 children enrolled in the trial. For all 663 episodes, the lower limbs were the most affected body sites followed by the distal upper limbs, face and scalp. On the anterior surface of the body, the pre-tibial region was the most affected while on the posterior surface, the dorsum of the hands and calves predominated. There was no observable difference between males and females in distribution of sores. Children up to 3 years of age were more likely to have sores on the upper posterior lower limbs and scalp than older age groups, with the distribution of sores differing across age groups (p = 3 × 10−5). Sores from which only Staphylococcus aureus was cultured differed in distribution to those with only Streptococcus pyogenes cultured (p = 3 × 10−4) and were more commonly found on the upper posterior lower limbs. Conclusions Skin sores were predominantly found on exposed regions of the lower leg and distal upper limbs. The distribution of sores varied by age group and pathogen. These results highlight key areas of the body for clinicians to pay attention to when examining children for skin sores.

Post-fracture serum cytokine levels are not associated with a later diagnosis of complex regional pain syndrome: a case-control study nested in a prospective cohort study

BackgroundComplex Regional Pain Syndrome (CRPS) is a disabling pain disorder that is most common after a distal limb fracture. While the acute systemic immune response to the injury is thought to play a role in the development of CRPS, this hypothesis has never been tested directly. Thus, we evaluated whether elevated levels of circulating pro-inflammatory cytokines early after a fracture were associated with the development of CRPS.MethodsWe conducted a case-control study nested within a prospective cohort study. Individuals with wrist and/or hand fractures were recruited from specialist hand units. Baseline clinical data were obtained from participants within 28 days of fracture. CRPS status was determined 16 weeks after the fracture using a two-stage diagnostic process. Cytokine assays were obtained from all cases (defined using the Budapest criteria) and a random sample of those who did not have CRPS at 16 weeks. We calculated odds ratios with 95% confidence intervals to determine the risk of CRPS associated with the expression of each of 25 cytokines.ResultsBaseline data were collected for 702 consenting participants, of whom 535 provided blood samples. Follow-up at 16 weeks was 97.2%. 15 (2.2% of the cohort) met the Budapest CRPS criteria and 69 (including those who met the Budapest criteria; 9.8%) met the International Association for the Study of Pain (IASP) CRPS criteria. In all of the primary analyses (using Budapest criteria) and 49/50 secondary analyses (using IASP criteria), 95% confidence intervals for the association between cytokine levels and the risk of subsequently developing CRPS included the null value (OR = 1). However, the confidence intervals were wide.ConclusionThere was no evidence that early post-injury expression of systemic cytokines was associated with a CRPS diagnosis 16 weeks after injury. This study does not provide support for the hypothesis that innate immune activation has a determinative role in the development of CRPS.

ERI1: A case report of an autosomal recessive syndrome associated with developmental delay and distal limb abnormalities.

ERI1 is an evolutionary conserved 3'-5' exonuclease with an important function in multiple RNA processing pathways. Although the molecular mechanisms in which ERI1 is involved have been studied extensively in model organisms, the pathology associated with ERI1 variants in humans has remained elusive because no case has been reported so far. Here, we present a case of a female patient with a homozygous nonsense variant in ERI1 gene. The patient exhibits mild intellectual disability, eyelid ptosis, and anomalies in her hands and feet (brachydactyly, clinodactyly, dysplastic/short nail of halluces, brachytelephalangy, short metacarpals, and toe syndactyly). This case report is the first of its kind and is invaluable for understanding ERI1 pathology in humans.

Save the Leg: Utilization of Distal Perfusion Catheter With Impella CP® May Prevent Morbidity of Limb.

Leg ischemia is a potential complication of percutaneous left ventricular assist device (Impella CP®) placement. To avoid leg ischemia in at-risk patients, a distal perfusion catheter (DPC) should be placed. In utilizing a passive distal perfusion system from the contralateral femoral artery, we optimized blood flow to the distal limb mitigating leg ischemia. A 65-year-old female with dilated cardiomyopathy complicated by hemodynamic instability was placed on an Impella CP via the right femoral artery. A DPC was placed to the right distal femoral artery and connected to the wire re-access port of the Impella CP. Despite this, the leg became ischemic shortly after admission to the ICU. A contralateral femoral arterial line was placed in standard fashion, and it was connected to the DPC while the wire re-access port was capped. Shortly after placement of the new DPC system, the right lower extremity distal pulses returned, and distal leg ischemia was resolved. Another patient, a 67-year-old male with acute myocardial infarction, was placed on an Impella CP via the left femoral artery for cardiogenic shock. His hemodynamics continued to deteriorate, requiring initiation of veno-arterial extracorporeal membrane oxygenation (VA ECMO) via the right femoral artery and vein with associated DPC placement. Shortly after the initiation of VA ECMO, the Impella CP-related extremity (left leg) became ischemic. A left femoral DPC was placed and connected to the side port of the right femoral arterial cannula. After initiation of the additional DPC system, the left leg ischemia resolved. Distal leg ischemia with Impella CP is not a rare event. Utilization of a DPC to Impella CP may decrease the morbidity of limb malperfusion.

Retrospective study on clinical manifestation, thigh MRI and electrophysiology characteristics of immune-mediated necrotizing myopathy

Objective: To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM). Methods: A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP+) group, anti-HMGCR antibody positive (HMGCR+) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result: (1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP+, 8 (25.0%) with HMGCR+, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP+group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb (P<0.01). The axial muscle score was lower than the distal limb score (P<0.05).(3) Extramuscular manifestations of HMGCR+ group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups (P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP+ group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR+ group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion: IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP+ group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR+group were more prone to myotonia potential and CRDs.

Ischemic Monomelic Neuropathy

Ischemic monomelic neuropathy is a rare complication associated with arteriovenous fistula creation for hemodialysis. It is an acutely developing ischemic neuropathy involving multiple nerves of a single limb. The pathogenesis is thought to be decreased blood flow to the distal axons, due to the shunting of blood away from the distal limb. It is characterized by severe pain and muscle weakness along with multiple nerve distributions, confined to the limb. It is different from steal syndrome in that there is no muscle or skin necrosis. It is often a debilitating condition warranting immediate closure of the fistula. Hence, prompt recognition of this entity is essential. Hereby, we report the case of a 60-year-old male with chronic kidney disease, who underwent a brachiocephalic fistula creation in the left upper limb and developed features of ischemic monomelic neuropathy.

Thinking Out of the Box: Use of the Radial Artery Distally to the Snuffbox as Recipient Vessel.

Background:The use of the radial artery (RA) as a recipient vessel in the hand is mainly described in the snuffbox. However, we believe that employing the RA distally to the extensor pollicis longus (EPL) tendon may provide remarkable advantages.Methods:We conducted a prospective study from June 2019 until December 2021, which included all patients who underwent reconstructive procedures with the RA distally to the snuffbox as the recipient vessel. We reviewed patients’ medical records: demographics, type of trauma, defect characteristics, microsurgical procedure, reoperations, and short- and long-term complications.Results:We found 23 patients eligible for this study; 22 patients required a reconstructive procedure due to a trauma and one for a congenital malformation. RA distal to snuffbox was always identified and judged reliable and apt as a recipient vessel. There were no issues with the anastomosis and no total flap failure in all cases. The morbidity in the recipient area was also minimal, with no mobility deficits, loss of sensation, or neuroma development.Conclusions:The RA is the primary vessel in the dorsum of the distal upper limb; performing the anastomosis distally to the EPL tendon may offer various advantages, making the surgery safer and less invasive.

Hirayama Disease: A Case Report and Review of Literature

Hirayama disease is a rare disorder seen in young patients in their second or third decade of life with slowly progressive self-limiting distal upper limb muscle weakness with seldom symmetrical involvement. It is a peculiar anterior horn cell disease that is managed conservatively with limited surgical options available as per literature.

Cryoglobulinaemia in a Thoroughbred gelding with multicentric lymphoma

SummaryA 17‐year‐old Thoroughbred gelding was presented to the hospital with epistaxis, multiple alopecic skin lesions, firm swelling in the masseter region and acute cellulitis of the right hind distal limb. Epistaxis originated from ulcerative lesions within the nasal passages and nasopharynx. Histopathology results of a skin biopsy revealed necrotising dermatitis. Initial laboratory evaluation included severe leucocytosis with marked hyperproteinaemia and adequate coagulation times. A cryoprecipitate was noted in a refrigerated blood sample in the absence of lipemia. Serum protein electrophoresis yielded inconsistent results depending on sample preparation, suggestive of the presence of cryoglobulins. Evaluation of an uncentrifuged sample revealed a gammopathy, with a peak in the beta 2 globulin fraction. Treatment for vasculitis and dermatitis resulted in little clinical improvement, and the gelding was euthanised. Necropsy revealed multicentric lymphoma with a tropism for perivascular spaces and skeletal muscles.

A novel approach to alpha-lipoic acid therapy in the treatment of diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a heterogenic disorder prevalent amongst patients suffering from diabetes mellitus (DM), with symptoms comprising neuropathic pain, paresthesia, and numbness in distal lower limbs. Alpha-lipoic acid (ALA) is proposed as a pathogenesis-oriented treatment option, targeting underlying causes of neural lesions such as hyperglycemia, metabolic and microvascular dysfunctions, and cellular oxidative stress. We performed a comprehensive review of controlled clinical trials demonstrating the clinical usefulness of ALA in the treatment of DPN, published in the last 5 years to determine the benefits of ALA monotherapy and combined treatments with other known antioxidants. We also investigated the differential efficacy of oral versus intravenous ALA administration. Clinical trials show the efficacy of ALA treatment, attributed to its anti-inflammatory, anti-hyperglycemic, and antioxidant properties, as well as its function in the endothelial activation and lipid metabolism parameters. ALA supplementation is associated with amelioration in nerve conduction velocity scores, clinically significant reduction of reported neuropathic pain, burning and paresthesia, as well as a decrease in serum triglycerides, improved insulin sensitivity, and quality of life.

Ancient DNA confirmation of lepromatous leprosy in a skeleton with concurrent osteosarcoma, excavated from the leprosarium of St. Mary Magdalen in Winchester, Hants., UK

To establish a biological profile and disease aetiologies for one of four burials recovered during a Time Team dig at the St. Mary Magdalen leprosarium, Winchester, UK in AD 2000. Osteological techniques were applied to estimate age at death, biological sex, stature and pathology. Visual assessment of the material was supplemented by radiographic examination. Evidence for leprosy DNA was sought using ancient DNA (aDNA) analysis. The remains are those of a male individual excavated from a west-east aligned grave. The skeleton shows signs of two pathologies. Remodelling of the rhino-maxillary area and degenerative changes to small bones of the feet and reactive bone on the distal lower limbs suggest a multibacillary form of leprosy, whereas the right tibia and fibula show the presence of a primary neoplasm identified as an osteosarcoma. The aDNA study confirmed presence of Mycobacterium leprae in several skeletal elements, and the strain was genotyped to the 3I lineage, one of two main SNP types present in mediaeval Britain and ancestral to extant strains in America. This is a rare documentation of leprosy in association with a primary neoplasm.

A geometric morphometric evaluation of equid tooth shape at Natural Trap Cave, Wyoming

Natural Trap Cave is an enigmatic site in Wyoming that has been accumulating fossils for tens of thousands of years from animals falling into it. One of the more common taxa present at this site are horses. North American equids have been separated into two main groups: caballine “stout legged” horses, which include the modern Equus ferus caballus; and the extinct non-caballine so-called “New World Stilt Legged” horses, which possess more gracile distal limb elements than modern horses. Genetic evidence has shown that both taxa are present at the Natural Trap Cave site. While post-cranial elements of both have been found, the most common horse specimens recovered have been isolated teeth, which have historically been difficult to identify to a specific taxon, though recent studies have been successful using geometric morphometrics on the occlusal surfaces of cheek teeth to differentiate equid taxa and populations. This study also uses geometric morphometrics to attempt to differentiate upper cheek tooth specimens between caballine and non-caballine stilt legged horses from Natural Trap Cave. Two landmark schemes were employed, one with fewer landmarks, and one with greater coverage, including sliding semi-landmarks. These schemes were used first on a dataset of only known specimens that had been taxonomically identified, and then unknown specimens from Natural Trap Cave were added. These analyses showed that the two taxa do indeed occupy statistically significant different areas of morphospace, as do premolars and molars. Surprisingly, the smaller landmark scheme produced better resolution on the Principal Components Analysis plots, possibly because the larger landmark scheme introduced ontogenetic variation due to different levels of tooth wear. While definitive identification does not seem advisable with this methodology, the unknown specimens grouped more with the known stilt legged specimens, suggesting that this taxon was more prevalent at Natural Trap Cave than the caballine Equus.