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Background: Epidermolysis bullosa (EB) is a complex and heterogeneous dermatological disease. Four main types of EB have been described, each of them with distinct characteristics: EB simplex (EBS), dystrophic EB (DEB), junctional EB (JEB) and Kindler EB (KEB). Each main type varies in its manifestations, severity, and genetic abnormality. Methods: We sought mutations in 19 genes known to cause EB and 10 genes associated with other dermatologic diseases in 35 Peruvian pediatric patients of a rich Amerindian genetic background. Whole exome sequencing and bioinformatics analysis was performed. Results: Thirty-four of 35 families revealed an EB mutation. Dystrophic EB was the most frequently diagnosed type, with 19 (56%) patients, followed by EBS (35%), JEB (6%), and KEB (3%). We found 37 mutations in seven genes; 27 (73%) were missense mutations; 22 (59%) were novel mutations. Five cases changed their initial diagnosis of EBS. Four were reclassified as DEB and one as JEB. Inspection into other non-EB genes revealed a variant, c.7130C>A, in the gene FLGR2, which was present in 31 of the 34 patients (91%). Conclusion: We were able to confirm and identify pathological mutations in 34 of 35 patients.

Myiasis is infestation of live human tissue by larva. It usually involves immunocompromised people or people living in unsanitary conditions. The cutaneous myiasis is most common type and can enter the skin with a pre-existing wound. Herein we present a case of an 18-year-old girl known case of Dystrophic Epidermolysis Bullosa with cutaneous myiasis affecting the knee managed surgically with full recovery. Such case has not reported previously in the literature, and detailed management plan is described. [ABSTRACT FROM AUTHOR]

Type-1 neurofibromatosis (NF1) is a neurocutaneous syndrome classically known as peripheral NF to distinguish it from type-2 NF (central NF). Its main characteristic is the high predisposition to the growth of multiple tumors, which specially arouses the interest of spinal surgeons due to the presence of spinal cord compression and spinal deformities. Considering this, we have performed a comprehensive review, with illustrative cases of the main manifestations of NF1, focusing on the perspective of the spine surgeon. Articles were grouped according to the following subjects: diagnosis, skeletal complications, spinal deformity, and spinal tumors. For all of them, a detailed discussion on pearls for practice was presented. The diagnosis of NF1 is based on the presence of at least two out of seven criteria. Cutaneous findings are very common in NF1, and the most usual tumor is cutaneous neurofibroma (NFB). Plexiform neurofibromas are also found and present a high risk of becoming malignant peripheral nerve sheath tumors (MPNSTs), reducing life expectancy. Astrocytomas, especially pilocytic astrocytomas, are the most common central nervous system tumor, including in the spinal cord. Surgery is necessary to resect as much as possible without adding new neurological deficits. Spinal deformities are also commonly found (in 30–70% of the cases), potentially associated with dystrophic changes, which may result in acute and rapid progression. In the present review, we discuss specific characteristics found in this group of patients which are of paramount importance to properly manage this challenging disease.

Early studies (1976-1982) of the Drizzle Lake Ecological Reserve on Haida Gwaii, British Columbia focussed on the endemic Giant Threespine Stickleback (Gasterosteus aculeatus) and their predators. These surveys showed daily visits to the small lake (110 ha) by up to 59 adult non-breeding Common Loon (Gavia immer), an important stickleback predator and up to 19 breeding and non-breeding adult Red-throated Loon (Gavia stellata), which leave daily to forage in nearby marine waters. We continued loon surveys for 17 additional years (1983-1989, 2011-2020) and found that aggregations of nonbreeding Common Loons occurred annually on the lake during July with maximum daily numbers of 78-83 individuals in 1987, 2018, and 2020 and a large increase from 2011 to 2020. We did not detect any relationship of these differences with the Pacific Decadal Oscillation but a significant inverse correlation with average wind speed. Average yearly numbers of Redthroated Loons declined by 50% from 1976 to 1989 and have remained low, with lowest numbers (<2) occurring in 2017. Two Red-throated Loon nesting territories on the lake were occupied from 1976 to 1995, with chicks occurring in 24 of 36 nests, but no successful nesting was observed on the lake over the last decade. The relative decline of Red-throated Loon in this reserve is similar to that reported in Arctic and Subarctic surveys of the species in the north Pacific and northern Europe. We discuss the implications for the evolutionary ecology of the sticklebacks and the conservation of the ecological reserve. [ABSTRACT FROM AUTHOR]

Microglia are dynamic cells that have roles in neuronal plasticity as well as in recovery responses following neuronal injury. Although many hypothesize that hyperactivation of microglia contributes to alcohol-induced neuropathology, in other neurodegenerative conditions disruption of normal microglial processes also contributes to neuronal loss, particularly as microglia become dystrophic or dysfunctional. Based on the observation of a striking, abnormal morphology in microglia during binge-like ethanol exposure, the present study investigated the impact of excessive ethanol exposure on microglia number and dystrophic morphology in a model of alcohol dependence that includes neurodegeneration in both adult and adolescent rats. Following 2- and 4-day binge ethanol exposure, the number of microglia was decreased in the hippocampus and the perirhinal and entorhinal cortices of both adult and adolescent rats. Furthermore, a significant number of microglia with a dystrophic morphology were observed in ethanol-exposed tissue, accompanied by a significant decrease in brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Together these findings suggest another means by which microglia may contribute to alcohol-induced neurodegeneration, specifically dystrophic microglia and/or loss of microglia may disrupt homeostatic and recovery mechanisms. These results demonstrate that microglia also degenerate with excessive alcohol exposure, which has important implications for understanding the role of microglia—and specifically their contributions to plasticity and neuronal survival—in neurodegenerative disease.

Abstract Background Abnormal deposition of calcium in the skin or subcutaneous tissue is termed calcinosis cutis. Idiopathic calcinosis cutis of the scrotum is an uncommon entity. The pathogenesis of idiopathic calcinosis cutis of the scrotum is debatable. The condition presents as several brown to yellowish nodules on the scrotum, gradually progressive, and mostly asymptomatic. Here we report a case of idiopathic calcinosis cutis of the scrotum with a brief review of the literature and a discussion on pathogenesis. Case presentation A healthy looking, 50-year-old Nepali man presented with multiple growths on his scrotum for 15 years, which were mostly asymptomatic with an occasional complaint of itching. On physical examination, multiple pink to brown nodules ranging in size from 0.5 × 0.5 × 0.5 cm to 3 × 3 × 1 cm, which were painless and firm in consistency, were noted. On laboratory examinations the following were found to be within normal limits: serum calcium, phosphorus, parathyroid hormone, and vitamin D hormone levels; uric acid; alkaline phosphatase; and lipid profile. Based on clinical features and laboratory reports, a diagnosis of idiopathic calcinosis cutis of the scrotum was made. The nodules were excised under local anesthesia in several sittings, which gave a good cosmetic result with no evidence of recurrence in 1-year follow-up period. A histopathological examination revealed dermis with areas of fibrosis and calcification along with numerous multinucleated giant cells and an absence of any cystic structure. Conclusions Idiopathic calcinosis cutis of the scrotum is a benign condition, which remains mostly asymptomatic. It presents as progressive multiple nodules of varying numbers and sizes. A histopathological evaluation reveals areas of calcification. The cause is either dystrophic calcification of cysts or idiopathic. Excision is the treatment of choice.

Microglia are dynamic cells that have roles in neuronal plasticity as well as in recovery responses following neuronal injury. Although many hypothesize that hyperactivation of microglia contributes to alcohol-induced neuropathology, in other neurodegenerative conditions disruption of normal microglial processes also contributes to neuronal loss, particularly as microglia become dystrophic or dysfunctional. Based on the observation of a striking, abnormal morphology in microglia during binge-like ethanol exposure, the present study investigated the impact of excessive ethanol exposure on microglia number and dystrophic morphology in a model of alcohol dependence that includes neurodegeneration in both adult and adolescent rats. Following 2- and 4-day binge ethanol exposure, the number of microglia was decreased in the hippocampus and the perirhinal and entorhinal cortices of both adult and adolescent rats. Furthermore, a significant number of microglia with a dystrophic morphology were observed in ethanol-exposed tissue, accompanied by a significant decrease in brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Together these findings suggest another means by which microglia may contribute to alcohol-induced neurodegeneration, specifically dystrophic microglia and/or loss of microglia may disrupt homeostatic and recovery mechanisms. These results demonstrate that microglia also degenerate with excessive alcohol exposure, which has important implications for understanding the role of microglia—and specifically their contributions to plasticity and neuronal survival—in neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Calcification and ossification are uncommon in schwannomas; however, when present these findings may cause diagnostic confusion with other mesenchymal tumors which more frequently harbor these features. We sought to better characterize the type and rate of calcification and ossification in schwannomas. Cases of schwannoma diagnosed at our institution from 2005 to 2019 were reviewed to determine the type and amount of calcification and ossification present. Of 2116 total cases of schwannoma reported during the study period, 38 cases harbored calcification or ossification per the pathology report. Thirty‐two of the 38 cases had slides available for review, of which 27 (84.3%) showed calcification, nine showed ossification (28.1%), and four (12.5%) cases demonstrated both. Foci of ossification typically occurred adjacent to large vessels. Of the 27 cases showing calcification, coarse dystrophic calcification was seen in 22 cases, psammomatous calcification in nine cases, and combined dystrophic and psammomatous calcification was seen in four cases. Cases with psammomatous calcification predominantly occurred in spinal roots and cerebellopontine angle of a younger age group with almost equal gender distribution. All four cases tested for protein kinase cyclic adenosine monophosphate‐dependent type I regulatory subunit alpha immunohistochemical stain demonstrated retained expression. We confirm that calcification and ossification are rare findings in schwannoma. Awareness that these features may be present in these tumors will prevent misdiagnosis and ensure appropriate clinical management. [ABSTRACT FROM AUTHOR]

The single largest risk factor for etiology of neurodegenerative diseases like Alzheimer's disease is increased age. Therefore, understanding the changes that occur as a result of aging is central to any possible prevention or cure for such conditions. Microglia, the resident brain glial population most associated with both protection of neurons in health and their destruction is disease, could be a significant player in age related changes. Microglia can adopt an aberrant phenotype sometimes referred to either as dystrophic or senescent. While aged microglia have been frequently identified in neurodegenerative diseases such as Alzheimer's disease, there is no conclusive evidence that proves a causal role. This has been hampered by a lack of models of aged microglia. We have recently generated a model of senescent microglia based on the observation that all dystrophic microglia show iron overload. Iron‐overloading cultured microglia causes them to take on a senescent phenotype and can cause changes in models of neurodegeneration similar to those observed in patients. This review considers how this model could be used to determine the role of senescent microglia in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Dominant dystrophic epidermolysis bullosa (DDEB), an inherited disorder due to type VII collagen mutations, is characterized by blisters and erosions that heal with scarring, atrophy, and milia. There is no established role for laser in the management of patients with DDEB. Pulsed dye laser (PDL) is most often used to target vascular skin lesions. We describe a patient with DDEB with marked improvement in erythema as well as fewer and less symptomatic episodes of blistering following treatment with PDL. [ABSTRACT FROM AUTHOR]

Dystrophic epidermolysis bullosa (DEB), a rare form of EB, is characterized by defects in Type VII collagen which is encoded by COL7A1 gene located on chromosome 3p21. A 12-year-old female with low intelligent quotient presented with intensely pruritic multiple violaceous papules which were coalescent at areas on both the shins. Histopathological examination showed epidermis displaying focal thinning. A subepidermal cleft was seen beneath the basement membrane zone. The dermis showed a linear array of keratinous cysts with intervening diffuse lymphohistiocytic infiltrate. Features were suggestive of pretibial DEB. Since it was associated with intense itching, the lesion was termed as pretibial DEB pruriginosa which has combined elements of exclusive pretibial lesions and intense itching. An appropriate clinical history and increased awareness of histopathological features will enable earlier diagnosis and suitable management.

We report a case of an uncommon adverse effect of insulin injection resulting in hard subcutaneous swelling in the lower abdomen of a 47-year-oldfemale with type 1 diabetes. Extensive dystrophic calcification and fat necrosis was revealed on histopathological examination.

Forests have been expanding over typical savanna sites for the past 3000 years in the Neotropics. Such invasion can produce a series of environmental modifications on typical savanna; however, it remains unclear how modifications in soil properties, caused by the encroachment of woody species, facilitate the expansion of forest ecosystems under dystrophic conditions. Here we examined chemical and microbiological changes associated with tree encroachment in oxisols of a Neotropical Savanna at Assis Ecological Station, Southeastern Brazil. We predicted that tree encroachment caused by typical forest species would cause significant changes in the chemical and microbiological properties of savanna soils. Soils were sampled at Assis Ecological Station, from savanna sites differing in tree encroachment (typical, dense and forested savanna) caused by decades of fire exclusion. We analysed vegetation leaf area index and leaf litter volume deposited in the studied plots and chemical (pH, organic matter, P, K, Ca, Mg, Al, NO , NH ) and microbiological (microbial C biomass and dehydrogenase activity) properties of soils under distinct encroachment conditions. Most soil chemical properties did not change along the tree encroachment gradient; however, total P, soil organic matter, soil microbial C and dehydrogenase activity increased from typical savanna to forested savanna. The changes in soil organic matter and dehydrogenase activity were correlated with the values of leaf area index and litter volume along the encroachment gradient. Our results demonstrate that forest species can increase carbon and phosphorus supplies in tropical savanna soils. [ABSTRACT FROM AUTHOR]

Neurofilaments are major protein constituents of the brain, but are particularly abundant in specific subpopulations of neurons and likely have a key role in the regulation of axonal calibre. Neurofilament proteins may also be involved in the transformation of the neuronal cytoskeleton leading to substantial tau pathology in axons damaged by Aβ, subsequently leading to neurofibrillary pathology in their cell bodies of origin. An understanding of neurofilamentous changes in axons and subsequent tau pathology may provide insight into how Aβ pathology may stimulate an aberrant plasticity-related response of damaged neurons, leading to the progressive and degenerative changes in the neuronal cytoskeleton that result in synapse loss and neuronal degeneration. [ABSTRACT FROM AUTHOR]

The mouse model of Duchenne muscular dystrophy, the mdx mouse, displays changes in Ca2+ homeostasis that may lead to the pathology of the muscle. Here we examine the activation of store overload-induced Ca2+ release (SOICR) in mdx muscle. The activation of SOICR is associated with the depolymerization of the sarcoplasmic reticulum (SR) Ca2+ buffer calsequestrin and the reduction of SR Ca2+ buffering power (BSR). The role of SOICR in healthy and dystrophic muscle is unclear. Using skinned fibers we show that lowering the Mg2+ concentration can activate discrete Ca2+ release events that did not necessarily lead to activation of SOICR. However, SOICR waves could propagate into these fiber segments. The average delay to activation of SOICR in mdx fibers was longer than in wild-type (WT) fibers. In the lowered Ca2+-buffered environment following large SOICR events, brief waves in mdx fibers displayed a low amplitude and propagation rate, in contrast to WT fibers that showed a range of amplitudes correlated with wave propagation rate. The distinct properties of SOICR in mdx fibers were consistent with a ryanodine receptor (RyR) that was leakier to Ca2+ than in WT. The consequence of delayed SOICR and leaky RyRs is prolonged high BSR and a reduction in free Ca2+ concentration inside the SR as total SR calcium drops. We present a hypothesis that SOICR activation is required in healthy muscle and that this mechanism works suboptimally in mdx fibers to fail to limit the activation of store-operated Ca2+ entry. [ABSTRACT FROM AUTHOR]

Duchenne's and Becker's muscular dystrophy (DMD & BMD) is a X linked disease caused by mutations in the dystrophic gene. DMD is the malign form of the disease, which significantly shortens the lifetime of the patient, while BMD has late onset with slow progression. Sixty five percent of DMD and BMD cases are caused by deletion of one or more exons in the dystrophic gene, while duplications cause these diseases in 6 to 7% of the cases. There are two hot spots for deletions and duplications. These are exons in the proximal part of the gene (3rd to 18th) and exons of a distal part of the gene (45th to 52nd). The remaining 30% of DMD and BMD cases are caused by point mutations, small deletions or inversions in the dystrophic gene. The correlation between School of Medicine, University of Belgrade, Belgrade the severity of the disease and the position of deletion shows that most of the out of frame deletions cause DMD phenotype, while in frame deletions result in BMD pheno-type. We report on the results of 28 non-related DMD and BMD patients. In 57% of cases deletions were detected and all were found in the distal hot spot of the gene. These results suggest that in most of the cases, out of frame deletions produce DMD phenotype while in frame deletions result in BMD phenotype. This is in compliance with data from literature.

Background:Calcinosis cutis is a very rare condition where in calcium deposits form in the skin. It occurs in four forms: metastatic, dystrophic, idiopathic and as a subepidermalnodule. Aim:This study was done to analyse the clinical and histological features of calcinosis cutis which have an influence on patientmanagement. Material:A retrospective study of cases diagnosed in the Department of Pathology over a period of six years. Results: Six cases were found during this period,which includedtwo cases of idiopathic calcinosis cutis, two of scrotal calcinosis, one case of calcinosis cutissecondary to systemic sclerosis, and one subepidermal calcified nodule. Conclusion:In the types in which there is an underlying systemic disease it is important to recognise thiscondition promptly for the proper management of the patient. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) is a group of rare inherited skin and mucous membrane disorders in which blister formation may arise spontaneously or following a minor friction. Various patterns of inheritance are explicated for the disease. The disease has a profound effect on oral mucosa and may result in high prevalence of dental caries. General anesthesia is sometimes the only choice for dental treatments in patients with EB. The following case report describes the dental and anesthetic management of an 12.5 -year-old girl with dystrophic type of EB. The patient was followed up every 6 months. New carious lesions were detected one year after the treatment, on the last visit. Presenting a perfect dental care to children with this disorder can be challenging for the in charge specialist, both pediatric dentist and anesthesiologist. [ABSTRACT FROM AUTHOR]

Calcific myonecrosis is a rare late complication of limb trauma characterized by liquefaction and dystrophic calcification of muscles in the single compartment, usually in the leg. This occurs many years after the trauma and is probably due to chronic compartment syndrome. We report 2 cases of calcific myonecrosis involving the anterior compartment of the leg that presented to us in an advanced stage of multiple sinuses discharging calcific material. Incision and drainage had been attempted at a local hospital prior to presentation at our hospital resulting in a non healing wound. Both patients had a history of antecedent trauma to the leg a few years ago. Patients were treated by thorough debridement of the involved muscles in the anterior compartment. Limited access dressing (LAD) was used to manage the dead space left after debridement. After application of the LAD, the wound was covered with split skin grafting. In both patients, healing of the cavity following debridement was facilitated by application of limited access dressing. While the wound completely healed, the disability due to extensive debridement of anterior compartment of the leg persisted. At the latest follow-up, the patients were asymptomatic without any recurrence. Thorough debridement of the compartment involved and application of LAD may be another option of treating calcific myonecrosis of the leg, which was initially considered a “do not touch” lesion. Morbidity due to surgery and need of repeated surgeries for recurrences should be kept in mind and regular follow-up should be considered. [ABSTRACT FROM PUBLISHER]

Brain calcifications are a common radiographic finding. The pathogenesis is diverse and ranges from benign physiological calcifications to a variety of pathological disorders. Whereas certain calcifications are considered an incidental finding, their presence can sometimes be crucial in making a specific diagnosis. Several pathological conditions affecting the brain parenchyma are associated with calcifications and their recognition and location might help in narrowing the differential. Knowledge of physiological calcifications is essential to avoid misinterpretation. This review illustrates a broad spectrum of CNS disorders associated with calcifications, and tries to highlight the salient radiological findings. [ABSTRACT FROM AUTHOR]

The article discusses a study on the effects of exercise in Duchenne muscular dystrophy (DMD). Exercise has been proven to have a positive effect on non-diseased persons but scientific studies have not yet established if such activity can have a therapeutic effect on patients with DMD. Clinical studies have been applied on mdx mice only and they are far from being conclusive due to differences between a dystrophic mouse and a dystrophic human and the lack of studies concerning the use of exercise as a prescription to DMD.

Dystrophic epidermolysis bullosa (DEB), a rare form of EB, is characterized by defects in Type VII collagen which is encoded by COL7A1 gene located on chromosome 3p21. A 12‑year‑old female with low intelligent quotient presented with intensely pruritic multiple violaceous papules which were coalescent at areas on both the shins. Histopathological examination showed epidermis displaying focal thinning. A subepidermal cleft was seen beneath the basement membrane zone. The dermis showed a linear array of keratinous cysts with intervening diffuse lymphohistiocytic infiltrate. Features were suggestive of pretibial DEB. Since it was associated with intense itching, the lesion was termed as pretibial DEB pruriginosa which has combined elements of exclusive pretibial lesions and intense itching. An appropriate clinical history and increased awareness of histopathological features will enable earlier diagnosis and suitable management. [ABSTRACT FROM AUTHOR]

Injured axons of the adult CNS undergo lengthy retraction from the initial site of axotomy after spinal cord injury. Macrophage infiltration correlates spatiotemporally with this deleterious phenomenon, but the direct involvement of these inflammatory cells has not been demonstrated. In the present study, we examined the role of macrophages in axonal retraction within the dorsal columns after spinal cord injury in vivo and found that retraction occurred between days 2 and 28 after lesion and that the ends of injured axons were associated with ED-1+ cells. Clodronate liposome-mediated depletion of infiltrating macrophages resulted in a significant reduction in axonal retraction; however, we saw no evidence of regeneration.Weused time-lapse imaging of adult dorsal root ganglion neurons in an in vitro model of the glial scar to examine macrophage—axon interactions and observed that adhesive contacts and considerable physical interplay between macrophages and dystrophic axons led to extensive axonal retraction. The induction of retraction was dependent on both the growth state of the axon and the activation state of the macrophage. Only dystrophic adult axons were susceptible to macrophage "attack." Unlike intrinsically active cell line macrophages, both primary macrophages and microglia required activation to induce axonal retraction. Contact with astrocytes had no deleterious effect on adult dystrophic axons, suggesting that the induction of extensive retraction was specific to phagocytic cells. Our data are the first to indicate a direct role of activated macrophages in axonal retraction by physical cell—cell interactions with injured axons. [ABSTRACT FROM AUTHOR]

Nodes of Ranvier are specialized axonal domains, at which voltage-gated sodium channels cluster. How axons cluster molecules in discrete domains is mostly unknown. Both axons and glia probably provide constraining mechanisms that contribute to domain formation. Proper sodium channel clustering in peripheral nerves depends on contact from Schwann cell microvilli, where at least one molecule, gliomedin, binds the sodium channel complex and induces its clustering. Furthermore, mice lacking Schwann cell dystroglycan have aberrant microvilli and poorly clustered sodium channels. Dystroglycan could interact at the basal lamina or at the axon--glial surface. Because dystroglycan is a laminin receptor, and laminin 2 mutations [merosin-deficient congenital muscular dystrophy (MDC1A)] cause reduced nerve conduction velocity, we asked whether laminins are involved. Here, we show that the composition of both laminins and the dystroglycan complex at nodes differs from that of internodes. Mice defective in laminin 2 have poorly formed microvilli and abnormal sodium clusters. These abnormalities are similar, albeit less severe, than those of mice lacking dystroglycan. However, mice lacking all Schwann cell laminins show severe nodal abnormalities, suggesting that other laminins compensate for the lack of laminin 2. Thus, although laminins are located at a distance from the axoglial junction, they are required for proper clustering of sodium channels. Laminins, through their specific nodal receptors and cytoskeletal linkages, may participate in the formation of mechanisms that constrain clusters at nodes. Finally, abnormal sodium channel clusters are present in a patient with MDC1A, providing a molecular basis for the reduced nerve conduction velocity in this disorder. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Neurofibromatosis is an autosomal-dominant hereditary disorder with two subtypes: NF-1 (type I) and NF-2 (type II). NF-1 is a complex disorder with a constellation of manifestations that can also entail skeletal abnormalities, including spinal deformity of a noncongenital nature with early age onset. The short, sharp, angular curve usually present in the thoracic region, as exhibited in NF-1, presents a quandary in its surgical management. Various studies have reported on the efficacy of anterior correction as opposed to posterior alone, whereas others have advocated a sequential, combined approach to diminish the degree of deformity and achieve solid arthrodesis. However, despite solid arthrodesis, curve progression may still ensue. Nonetheless, a simultaneous anterior-posterior approach to treat such a condition of NF-1 with severe dystrophic kyphoscoliosis is a rare occurrence. Purpose: To describe the presentation and operative management of a patient with NF-1 and severe dystrophic kyphoscoliosis. Study design: A case report and review of the literature. Methods: A clinical and radiographic review of a 51-year-old male patient who presented with NF-1, a 165-degree thoracic kyphotic deformity, associated scoliosis, varied degree of vertebral destruction of T9–T11, and paraparesis below T10. Results: Operative intervention of the deformity consisted of a simultaneous anterior-posterior approach and entailed posterior cord exposure, anterior vertebrectomy of T9–T11, cord decompression, posterior osteotomy (posterior elements were auto-fused), anterior distraction and kyphosis correction, anterior strut grafting, anterior rod instrumentation, and posterior compression instrumentation and fusion from T6–L2. The deformity was reduced, sold fusion was noted, and the patient was asymptomatic. Conclusions: A simultaneous anterior-posterior approach for the surgical treatment of severe dystrophic kyphoscoliosis in neurofibromatosis type I is an avenue to properly visualize the spinal cord, achieve solid arthrodesis, and to minimize as well as prevent the progression of deformity. [Copyright &y& Elsevier]

We have developed a novel in vitro model of the glial scar that mimics the gradient of proteoglycan found in vivo after spinal cord injury. In this model, regenerated axons from adult sensory neurons that extended deeply into the gradient developed bulbous, vacuolated endings that looked remarkably similar to dystrophic endings formed in vivo. We demonstrate that despite their highly abnormal appearance and stalled forward progress, dystrophic endings are extremely dynamic both in vitro and in vivo after spinal cord injury. Time-lapse movies demonstrated that dystrophic endings continually send out membrane veils and endocytose large membrane vesicles at the leading edge, which were then retrogradely transported to the rear of the "growth cone." This direction of movement is contrary to membrane dynamics that occur during normal neurite outgrowth. As further evidence of this motility, dystrophic endings endocytosed large amounts of dextran both in vitro and in vivo. We now have an in vitro model of the glial scar that may serve as a potent tool for developing and screening potential treatments to help promote regeneration past the lesion in vivo. [ABSTRACT FROM AUTHOR]

The differentiation of both original muscle fibres and the regenerated muscle fibres following necrosis in mdx muscles was investigated using immunoblotting and immunocytochemical procedures. Before the onset of necrosis, postnatal skeletal muscles in mdx mouse differentiated well with only a slight delay in differentiation indicated by the level of developmental isoforms of troponin T. Prior to the onset of apparent myopathic change, both fast and slow skeletal muscle fibre types in mdx leg muscles also differentiated well when investigated by analysis of specific myosin heavy chain expression pattern. While the original muscle fibres in mdx leg muscles developed well, the differentiation of regenerated myotubes into both slow and distinct fast muscle fibre types, however, was markedly delayed or inhibited as indicated by several clusters of homogeneously staining fibres even at 14 weeks of age. The number of slow myosin heavy chain-positive myotubes amongst the regenerated muscle clusters was quite small even in soleus. This study thus established that while muscle fibres initially develop normally with only a slight delay in the differentiation process, the differentiation of regenerated myotubes in mdx muscles is markedly compromised and consequently delayed. [ABSTRACT FROM AUTHOR]

Monitoring of key water quality parameters in Laguna de Bay was carried out from 1986 to 1996 to determine trends in water quality and the trophic state of the lake. Monthly sampling and field analyses were made at randomly selected sites of the lake. Three-year trend analysis of the annual mean values of some key water quality parameters showed the worsening condition of the lake. Ammonia-nitrogen, nitrate-nitrogen, ortho-phosphate, total phosphorus, chemical oxygen demand, turbidity, conductivity, and chlorides increased while alkalinity, clarity, and dissolved oxygen decreased. The lake is judged to be extremely trophic or dystrophic. Uses of the lake as a fishery resource and as a source of domestic water supply are briefly discussed. [ABSTRACT FROM AUTHOR]

Duchenne’s muscular dystrophy (DMD) is a fatal disease caused by mutations in the DMD gene that lead to quantitative and qualitative disturbances in dystrophin expression. Dystrophin is a member of the spectrin superfamily of proteins. Dystrophin itself is closely related to three proteins that constitute a family of dystrophin-related proteins (DRPs): the chromosome 6-encoded DRP or utrophin, the chromosome-X encoded, DRP2 and the chromosome-18 encoded, dystrobrevin. These proteins share sequence similarity and functional motifs with dystrophin. Current attempts at somatic gene therapy of DMD face numerous technical problems. An alternative strategy for DMD therapy, that circumvents many of these problems, has arisen from the demonstration that the DRP utrophin can functionally substitute for the missing dystrophin and its overexpression can rescue dystrophin-deficient muscle. Currently, a promising avenue of research consists of identifying molecules that would increase the expression of utrophin and the delivery of these molecules to dystrophin-deficient tissues as a means of DMD therapy. In this review, we will focus on DRPs from the perspective of strategies and issues related to upregulating utrophin expression for DMD therapy. Additionally, we will address the techniques used for anatomical, biochemical and physiological evaluation of the potential benefits of this and other forms of DMD therapy in dystrophin-deficient animal models. [ABSTRACT FROM AUTHOR]

(1) Background. Scoliosis is the most common musculoskeletal manifestation of Neurofibromatosis type 1 (NF1), and it might be dystrophic (D) or non-dystrophic (ND) depending on the presence of dysplastic changes of the spine. The aim of our study was to describe the characteristics and natural history of patients with NF1 and scoliosis. (2) Methods. We retrospectively reviewed records from patients with NF1 and scoliosis. Scoliosis was classified as D if at least two dystrophic changes were documented at imaging. (3) Results. Of the 438 patients reviewed, 43 fulfilled inclusion criteria; 17 were classified in D group and 26 in ND. The groups did not differ in age and localization of scoliosis curvature. Surgery was needed more often in D group, but the between-group difference was not significant. Male-to-female ratios of 3:1 and 4:1 were reported in surgically treated NF1 patients with ND and D scoliosis, respectively. (4) Conclusions. Our data suggests independently by the presence of dysplastic changes affecting the spine that males with NF1 are more often affected by scoliosis that requires surgery. [ABSTRACT FROM AUTHOR]

Empirical models used to predict thermocline depths of lakes have typically been based on physical and morpho-metric variables. However, lakes with appreciable levels of dissolved organic material, including those found on the Canadian Precambrian Shield (DOC levels 1.4-12.41 mg/l), have seldom been included in these models. Our analysis suggests that for such lakes, thermocline depth is linked strongly to light penetration (Secchi depth r = 0.83, light extinction r = 0.85) which is strongly related to DOC concentration (Secchi depth r = 0.91, light extinction r = 0.97). A multivariate regression based on small Canadian Shield lakes suggests that DOC is the most important predictor of thermocline depth. Maximum effective length, maximum depth, and chlorophyll a contribute significantly to the prediction power of the regression model, but are of secondary importance in the presence of DOC. [ABSTRACT FROM AUTHOR]

In order to study the osteogenic action of hydroxylapatite (HA) on the dental pulp, a pulp capping experiment was designed using the rat upper molar. Under general anesthesia, molar teeth in 14 male Sprague-Dawley rats were pulp capped with Osteogen (HA) or with Dycal as a control material. After pulp capping, the maxillary molars cavities were restored with amalgam and a pedodontic steel crown was adjusted and sealed over the molar teeth on either side of the maxilla. After 7 days, the areas of necrosis and acute inflammation were more evident in the pulps treated with Dycal than with Osteogen. Hard tissue formation began to appear around dentinal chips in the pulp and extended from the cavity walls into the pulp regardless of the material that was used. Furthermore, this calcified material was scattered throughout the pulp when Osteogen was used, but was not observed in the Dycal treated pulps. The hard tissue formation was thought to be due to the putative fibroblasts and odontoblasts found in the pulp. After 28 days dense dentinal tissue was observed bridging the exposure site when Dycal was used. The dentinal tissues formed with Osteogen was always of a globular type, and showed an irregular distribution. Since Osteogen tends to cause areas of dystrophic calcification in the pulp, its use is not be recommended for pulp capping purposes in humans, because these areas of calcification would make future endodontic treatment difficult. [ABSTRACT FROM AUTHOR]