Neglected alkaptonuric patient presented with low back pain and radiculopathy: A case report

Background: Alkaptonuria (AKU) is a rare hereditary disorder in which excess homogentisic acid (HGA) deposits in connective tissues (ochronosis). Here, we report the unusual presentation of a lumbar disc herniation occurring in a patient with AKU warranting surgical intervention. Case Description: A 28-year-old male presented with 1 year of low back pain. The lumbar magnetic resonance imaging showed an extruded disc at the L4-L5 level accompanied extensive disc space narrowing and osteophyte formation. At surgery, the interspinous ligaments, facet joints, and disc herniation were black. In addition, the postoperative re-examination revealed a black discoloration of the nasal and ear cartilage. Finally, the diagnosis of AKU was confirmed when the urine specimen was positive for HGA. Conclusion: Rarely, younger patients with AKU who develop excess black deposits of HGA in connective tissues (i.e., ochronosis) may present with lumbar disc herniations and spondylosis.

Transglutaminase mediated asprosin oligomerization allows its tissue storage as fibers

Asprosin, the C-terminal furin cleavage product of profibrillin-1, was reported to act as a hormone that circulates at nanomolar levels and is recruited to the liver where it induces G protein-coupled activation of the cAMP-PKA pathway and stimulates rapid glucose release into the circulation. Although derived from profibrillin-1, a multidomain extracellular matrix glycoprotein with a ubiquitous distribution in connective tissues, little is known about the tissue distribution of asprosin. In the current view, asprosin is mainly produced by white adipose tissue from where it is released into the blood in monomeric form. Here, by employing newly generated specific asprosin antibodies we monitored the distribution pattern of asprosin in human and murine connective tissues such as placenta, and muscle. Thereby we detected the presence of asprosin positive extracellular fibers. Further, by screening established cell lines for asprosin synthesis we found that most cells derived from musculoskeletal tissues render asprosin into an oligomerized form. This oligomerization is facilitated by transglutaminase activity and requires an intact fibrillin fiber network for proper linear deposition. Our data suggest a new extracellular storage mechanism of asprosin in oligomerized form which may regulate its cellular bioavailability in tissues.

Nature-Based Solutions for Water Security and the Role of Education for Enhancing the Implementation of the 2030 Agenda

Water security is a central sustainable development challenge. Billions of people lack access to clean and reliable water, while global hydrological changes and increasingly common extreme weather events pose serious risks. However, current issues are mainly driven by unsustainable management and ensuing ecological degradation. Nature-based solutions restore, enhance and safeguard ecosystems that provide water for people and the rest of nature. They also buffer the impacts of natural hazards and provide other critical benefits. Global policy frameworks on sustainable development, disaster prevention, climate change, biodiversity, wetlands and desertification offer holistic objectives toward water security. Education and capacity development is one of their central connective tissues, and as a mean to enhance their implementation. In spite of this, major gaps remain that require novel approaches. This chapter explores these and discusses strategic considerations and innovative approaches that can leverage existing knowledge and foster context specific innovation for transformative solutions.

Eudesmol-A promising inhibitor for glucosyltransferase: Docking and Molecular dynamics study

The loss of natural teeth can be avoided by invoking the molecular signal behind teeth regeneration. The destruction of the connective tissues is mainly due to bacterial origin which reacts to dental caries, a multifactorial disease. Glycosyl transferase is the enzyme which is involved in the glycosidic linkage. Glucosyltransferase inactivation reduces dental caries. This enzyme is a crucial virulence factor of Streptococcus mutans, a major pathogen that causes dental caries. In this present work, screening was done with library of anti-oxidant and anti-inflammatory molecules against the crystal structure of the target protein. Based on the predicted binding affinities, small molecules were selected and evaluated for their activity. Further, attempts were done to evaluate the toxicity of the lead compounds and compounds with no toxicity and good binding affinity were subjected for simulation and compared with reference complex. The potential energy of Glycosyl transferase-Eudesmol (proposed compound) (-1500 kj/mol) indicates its higher stability as compared to Glycosyl tranferase-G43 (reference) complex (-1100kj/mol). The inactives and actives compound for Glycosyl transferase was predicted from DeepScreening server.

LTBP1 promotes fibrillin incorporation into the extracellular matrix

LTBP1 is a large extracellular matrix protein and an associated ligand of fibrillin-microfibrils. Knowledge of LTBP1 functions is largely limited to its role in targeting and sequestering TGFβ growth factors within the extracellular matrix, thereby regulating their bioavailability. However, the recent description of a wide spectrum of phenotypes in multiple tissues in patients harboring LTBP1 pathogenic variants suggests a multifaceted role of the protein in the homeostasis of connective tissues. To better understand the human pathology caused by LTBP1 deficiency it is important to investigate its functional role in extracellular matrix formation. In this study, we show that LTBP1 coordinates the incorporation of fibrillin-1 and -2 into the extracellular matrix in vitro. We also demonstrate that this function is differentially exerted by the two isoforms, the short and long forms of LTBP1. Thereby our findings uncover a novel TGFβ-independent LTBP1 function potentially contributing to the development of connective tissue disorders.

High-Definition Liposuction Body Scale: Expanding Indications for High-Definition Liposuction

Introduction: Performing optimal gluteal augmentation using traditional methods in moderate to severe weight-loss patients poses a surgical challenge as such patients typically present with (1) severe skin redundancy, (2) soft tissues containing high-density connective tissues than fat content, and (3) ptotic buttock cheeks. Materials and Methods: This procedure uses a modified lateral thigh and buttock tuck excision not only to lift the buttock cheek complex but also to create a dermal fat flap that is transposed into the upper buttock pole to achieve upper buttock fullness. The remainder of the excised tissue undergoes novel ex vivo liposuction while remaining sterile, which allows for simultaneous repair of the created excision line. Results: This novel ex vivo liposuction technique provides several advantages that include (1) limiting operative time, (2) allowing for maximal fat removal while avoiding unnecessary trauma to the patient, and (3) providing improved quality with less blood and fat volumes. This ex vivo fat is then transferred to the mid- and lower buttock to complete buttock augmentation for the Brazilian buttock lift. Discussion: Excess skin redundancy and buttock check ptosis require consideration of supplemental excisional tucking to achieve optimal results. In addition, subcutaneous tissues that maintain more connective tissue pose difficulty with fat removal using traditional liposuction techniques. As such, we present a novel surgical technique to optimally augment and shape the buttock in patients who have undergone weight loss. Conclusion: In summary, we present a novel Brazilian buttock lift technique to augment the buttock in weight-loss patients that maximizes both patient safety and efficacy.

Alkaptonuria: clinical manifestations and an updated approach to treatment of a rare disease

Alkaptonuria (AKU) is a rare autosomal recessive disorder with a global incidence of 1 in 250 000 to 1 million people worldwide. It results from a deficiency of the enzyme homogentisic acid (HGA) oxidase which when absent, leads to an accumulation of HGA. Without this enzymatic degradation, HGA deposits in connective tissues resulting in pigmentation (ochronosis), plaque formation and accelerated cartilage destruction. With this, many patients who suffer from AKU develop ochronotic arthropathies, tendon ruptures, fractures, and chronic joint pain. Similarly, patients can develop cardiac valvular dysfunction and interstitial renal disease. Our two cases highlight the array of pathologies seen in AKU and, in light of newly published research, give us a platform from which we can discuss the developments in management of this rare disease.

A CASE OF NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS (NPSLE) PRESENTED WITH NEGATIVE SYMPTOMS OF SCHIZOPHRENIA

Systemic lupus erythematosus is an autoimmune chronic inflammatory disorder affecting connective tissues of body organs. It is more common in female. Neuropsychiatric manifestations like headache, cerebrovascular events like stroke, seizures, psychosis, cognitive impairment, which is termed as neuropsychiatric systemic lupus erythematosus 1,2,3 (NPSLE)

Pediatric hallux valgus: An overview of history, examination, conservative, and surgical management

Pediatric hallux valgus (PHV), while relatively rare, is still often encountered by general pediatricians. Herein, we concisely summarize the existing literature regarding the pathogenesis, associated conditions, clinical diagnosis, radiographic characteristics, conservative management, and surgical management of PVH. Though PHV is generally considered benign, the progression of hallux valgus can result in complications. The presence of an open physis in the pediatric age group delineates first line treatment choices, whenever possible, as nonoperative. The general exception to this recommendation is for children with neuromuscular and connective tissues disease who may benefit from earlier surgical management. If conservative approaches fail prior to skeletal maturity, the risk of recurrence and need for revision surgery should be discussed with patients and their families before surgical referral is made. The current review was conducted to aid primary care providers in better understanding the pathogenesis, associated conditions, and intervention options available to manage PHV.