Evaluation of a panel of furochromenones as the activator and inhibitor of tyrosinase.

Tyrosinase is a copper-containing enzyme involved in the biosynthesis of melanin pigment. While the excess production of melanin causes hyperpigmentation of human skin, hypopigmentation results in medical conditions like vitiligo. Tyrosinase inhibitors could be used as efficient skin whitening agents and tyrosinase agonists could be used for enhanced melanin synthesis and skin protection from UV exposure. Among a wide range of tyrosinase-regulating compounds, natural and synthetic derivatives of furochromenones, such as 8-methoxypsoralen (8-MOP), are known to both activate and inhibit tyrosinase. We recently reported a synthetic approach to generate a variety of dihydrofuro[3,2-c]chromenones and furo[3,2-c]chromenones in a metal-free condition. In the present study, we investigated these compounds for their potential as antagonists or agonists of tyrosinase. Using fungal tyrosinase-based in vitro biochemical assay, we obtained one compound (3k) which could inhibit tyrosinase activity, and the other compound (4f) that stimulated tyrosinase activity. The kinetic studies revealed that compound 3k caused 'mixed' type tyrosinase inhibition and 4f stimulated the catalytic efficiency. Studying the mechanisms of these compounds may provide a basis for the development of new effective tyrosinase inhibitors or activators.

Do integrative approaches to health contribute to self-reliance in primary healthcare? reflections from a community case study in Kerala, India.

A pluralistic Health system provides options for people to choose appropriate healthcare approach. However, the ability to make informed decision is infleuenced by many factors. An informed decision is one of the attributes of self-reliance. In this study, through the interactions with smallholder farmers, we tried to travel through the realm of communities' integrative practices and perceptions with a specific focus on traditional medicine concerning animal and human health. We aimed to understand what influences healthcare choices, mainly traditional medicine among people and how it contributes to self-reliance in primary healthcare. We conducted this case study in Aluva taluk of Ernakulam district in Kerala, India. Study participants were selected using the purposive sampling method and the data collected through 22 in-depth interviews and participant observation. Integrative healthcare practice is fragmented due to variations in the evidence perception by the people. Personal experiences, social and cultural factors, and health literacy influence health decisions in practicing integrative healthcare. Therefore, while investigating a concept like self-reliance, there is a need for analytical methods to embrace experiential, textual, inherited, and incorporated forms of learning. This further helps researchers and policymakers to recommend context-specific and sustainable solutions to create self-reliant communities in primary healthcare.

Nanocomposite fibrous scaffold mediated mandible reconstruction and dental rehabilitation: An experimental study in pig model.

Mandible reconstruction and dental rehabilitation after trauma or tumor resection represent a serious challenge for maxillofacial surgeons. This study aimed to investigate the bone formation potential of nanocomposite fibrous scaffold (silica-nanohydroxyapatite-gelatin reinforced with poly L-lactic acid yarns - CSF) for delayed Titanium (Ti) implantation, which was compared to autograft (AG) taken from the iliac crest. The grafts were placed in critical-sized mandibular defects in an adult pig model for 6 months followed by dental implant placement for another 3 months. There was complete union and vascularised lamellar bone formation within 6 months. Moreover, the biological processes associated with angiogenesis, bone maturation and remodelling were seen in CSF, which was comparable to AG. Later, when Ti dental implant was placed on newly formed bone, CSF group demonstrated better osseointegration. In short, nanocomposite fibrous scaffold promoted quality bone formation in mandible defect that leads to successful osseointegration, suggesting as a potential candidate for implant-based rehabilitation in clinics in future.

Proximal femoral replacement in non-neoplastic revision hip arthroplasty : five-year results.

AIMS: With increasing burden of revision hip arthroplasty (THA), one of the major challenges is the management of proximal femoral bone loss associated with previous multiple surgeries. Proximal femoral arthroplasty (PFA) has already been popularized for tumour surgeries. Our aim was to describe the outcome of using PFA in these demanding non-neoplastic cases. METHODS: A retrospective review of 25 patients who underwent PFA for non-neoplastic indications between January 2009 and December 2015 was undertaken. Their clinical and radiological outcome, complication rates, and survival were recorded. All patients had the Stanmore Implant - Modular Endo-prosthetic Tumour System (METS). RESULTS: At mean follow-up of 5.9 years, there were no periprosthetic fractures. Clearance of infection was achieved in 63.6% of cases. One hip was re-revised to pseudo arthroplasty for deep infection. Instability was noted in eight of the hips (32%), of which seven needed further surgery. Out of these eight hips with instability, five had preoperative infection. Deep infection was noted in five of the hips (20%), of which four were primarily revised for infection. One patient had aseptic loosening of the femoral component and awaits revision surgery. The Kaplan-Meier survivorship free of revision of any component for any reason was 72% (95% confidence interval (CI) 51.3% to 92.7%), and for revisions of only femoral component for any reason was 96% (95% CI 86.3% to 105.7%) at five years. CONCLUSION: Dislocation and infection remain the major cause for failure, particularly in patients with pre-existing infection. The use of dual mobility cups, silver-coated implants, and less aggressive postoperative rehabilitation regimens would possibly aid in the reduction of complications. PFA performed in patients with periprosthetic fracture seem to fair better. This study supports the judicious use of PFA in non-oncological revision hip arthroplasties, and that they be performed by experienced revision arthroplasty surgeons. Cite this article: Bone Jt Open 2022;3(3):229-235.

Taxane-induced acute interstitial pneumonitis in patients with breast cancer and outcome of taxane rechallenge.

Background: Although rare, taxane-induced interstitial pneumonitis is a well-recognized toxicity following chemotherapy. Data on taxane rechallenge in patients who developed taxane-induced interstitial pneumonitis following chemotherapy are limited. Here, we share our experience of acute interstitial pneumonitis following taxane chemotherapy for breast cancer and its clinical outcome following steroids and subsequent rechallenge with taxanes in selected patients without residual lung abnormalities on imaging following steroid treatment. Objectives: To study the taxane-induced acute interstitial pneumonitis in patients with breast cancer receiving chemotherapy and outcome of taxane rechallenge in these patients. Materials and Methods: Patients with breast cancer who developed taxane-induced acute interstitial pneumonitis following chemotherapy either with paclitaxel or docetaxel were included. Results: Among 1240 patients with breast cancer, who received chemotherapy with either docetaxel or paclitaxel, 41 patients developed taxane-induced acute interstitial lung disease (ILD) during the study period. The interstitial pneumonitis was more seen with docetaxel. Among paclitaxel regimens, weekly schedules showed more cases of ILD than 2 weekly paclitaxel. After steroid pulse/maintenance treatment, complete resolution of lung abnormalities was seen in 76%, but residual interstitial pattern on imaging was noted in 24% of patients. Taxane rechallenge was done in 20 (49%) patients. Agents used were paclitaxel, nab-paclitaxel, or docetaxel. All rechallenged patients received short-course oral steroids for one week following taxane rechallenge as a safety measure. Rechallenge was not done in 51% either due to patient unwillingness for rechallenge (27%) or patient with residual interstitial pattern on imaging (24%). None of the patients experienced any recurrence of pneumonitis or any mortality following taxane rechallenge. Conclusion: Acute interstitial pneumonitis is a well-known toxicity following taxanes in breast cancer and taxane rechallenge is an option in those patients without any residual pneumonitis following steroid pulse/maintenance. We also advise short-course oral steroids for 1 week following taxane rechallenge as a safety measure. We strongly do not recommend rechallenge in patients with residual lung abnormalities after steroids.

Maggot Debridement Therapy for Chronic Leg and Foot Ulcers: A Review of Randomized Controlled Trials.

OBJECTIVE: To critically analyze the existing randomized controlled trials (RCTs) on the clinical, economic, and psychological implications of maggot debridement therapy (MDT). DATA SOURCES: An exhaustive literature search for English-language publications was conducted using MEDLINE, EMBASE, and PubMed. STUDY SELECTION: Keywords used for the search were based on the PICO (Population, Intervention, Comparison, Outcome) framework. The titles, abstracts, and relevant full-text articles were screened. Seven RCTs were selected after applying the inclusion and exclusion criteria. DATA EXTRACTION: Data pertaining to the primary and secondary outcomes of each study were extracted. DATA SYNTHESIS: The data extracted were evaluated and categorized into clinical, economic, and psychological outcomes pertaining to MDT. A judicious evaluation of these outcomes was made, and the following conclusions were drawn. CONCLUSIONS: There exists heterogeneity in the extant RCTs, but MDT appears to be effective for a quick early debridement. For diabetic foot ulcers, MDT improves debridement, controls infection, and enhances wound healing. In chronic peripheral vascular disease ulcers, it aids in early debridement, but the final outcome is equivocal. Further robust integrated health economic and parallel qualitative assessment studies are recommended to understand the cost-effectiveness and patient acceptability and experience.

Missed Lisfranc injuries-surgical vs conservative treatment.

INTRODUCTION: Lisfranc injuries form a distinct group of rare but severe injury. Literature suggests a low incidence, but failure to diagnose these injuries early and its subsequent delay in management will affect the patient's mobility and quality of life significantly. The preferred mode of management is said to be surgical. Conversely, the method of intervention for patients not suitable for surgery is less clear. AIM: This study aims to evaluate the effect of delayed diagnosis and the treatment provided on the overall functional outcome for the patients with missed Lisfranc injury. METHODOLOGY: The study was conducted at a specialist centre in the North-West of UK between January 2011 and November 2016. All patients with acute Lisfranc injuries were included in this study. Patient data was collected through electronic notes and analysed to ascertain missed diagnosis. It was also used to evaluate functional and radiological outcome. RESULTS: In our series, 58.8% of Lisfranc injuries were missed on their initial presentation. We report better results for the surgical group when compared with the non-operated group, in spite of the delay in diagnosis. CONCLUSION: We believe that definitive treatment in the form of surgical fixation and anatomical reduction has more influence on the functional outcome than the timing of the surgical fixation in case of subtle Lisfranc injuries.

Validity of direct magnetic resonance arthrogram in patients with femoroacetabular impingement and their outcome post hip arthroscopy.

Femoroacetabular Impingement is an established cause of labral tears and chondral delamination. The aim was to test the validity of direct magnetic resonance arthrogram [dMRA] in the diagnosis of the same. We also looked at the short term functional outcome in these patients post hip arthroscopy. The dMRA is valuable in diagnosing labral tears nevertheless poor in detecting cartilage delamination. Hip arthroscopic intervention provided a good short-term functional outcome; however, should be offered with caution in patients over 40 years. To our knowledge, this is the single largest series published with similar methodology.

Bilateral hamstring origin calcification: rare presentation of Gitelman syndrome.

This case report is the first case to our knowledge of intratendinous or peritendinous calcification reported in Gitelman syndrome (GS) patients. GS represents the clinical manifestations of inactivation of the Slc12a3 genes encoding the thiazide-sensitive sodium chloride cotransporter and the Trpm6-Mg genes encoding the magnesium transporters in the distal convoluted tubule. Hence, the biochemical findings resemble those with thiazide diuretics such as hypokalaemia, hypomagnesaemia, hypocalciuria, metabolic alkalosis and low normal blood pressure. Serum calcium and phosphate levels are usually unaffected in GS unless associated with hyperparathyroidism or other hypercalcaemic aetiologies. We report a 69-year-old male patient with a history of GS who presented with bilateral ischial tuberosity tenderness. Further investigations confirmed the calcification of bilateral hamstring origin. Chondrocalcinosis is a known association of GS; however, extra-articular calcification is rare. Literature review illustrates sclerochoroidal calcification as the only reported soft tissue calcification apart from chondrocalcinosis.

A Mysterious Case of Spontaneous Cervical Epidural Hematoma and Bilateral Primary Spontaneous Pneumothorax Caused by a Rare Etiology.

Spontaneous spinal epidural hematoma (SSEH) is a rare disorder that can present as an acute onset of pain and radicular symptoms that mimic disc herniation. Primary spontaneous pneumothorax (PSP) can be defined as the presence of air in the pleural space without apparent underlying lung disease or trauma. We describe a rare case of SSEH in the cervical spine (C5-7) presenting with a novel association, a bilateral PSP, which has never been documented before. Both SSEH and spontaneous pneumothorax, though rare, can be associated with vasculopathy and our patient had signs of vasculopathy of intracranial vessels and pulmonary vasculature. Vasculopathy also needs to be considered while evaluating a case of PSP without emphysema-like changes (ELC) and if diagnosed as the cause, pleurodesis could be considered as a part of the management to avoid the sequel of recurrent pneumothorax and prolonged ICU stay in this subset of patients. HOW TO CITE THIS ARTICLE: Thakkar K, Ajayan N, Unnikrishnan P, Sethuraman M, Hrishi AP. A Mysterious Case of Spontaneous Cervical Epidural Hematoma and Bilateral Primary Spontaneous Pneumothorax Caused by a Rare Etiology. Indian Journal of Critical Care Medicine, January 2019;23(1):51-53.

Distortion of aortic valve from mechanical traction imposed by the mitral valve prosthesis: The three-dimensional transesophageal echocardiographic perception.

Iatrogenic injury to the aortic valve is a rare but frequently reported complication during mitral valve surgeries. Intraoperative 2-dimensional transesophageal echocardiography (2D TEE) has a major impact in diagnosing these injuries, so that timely intervention is possible. However, 2D TEE has lot of limitations during the perioperative period, which can be overcome by the three dimensional echocardiography (3D-TEE). We report a case where 3D TEE has undoubtedly delineated the cause for distortion of aortic sinus after mitral valve replacement and helped in the successful outcome.

Wrist Arthroscopy in Children and Adolescent With Chronic Wrist Pain: Arthroscopic Findings Compared With MRI.

BACKGROUND: Wrist arthroscopy is a dynamic diagnostic procedure and its indications are growing as a treatment modality in the adult population. The aim of the study was to retrospectively report our series of pediatric and adolescence with chronic wrist pain, with or without wrist instability who underwent wrist arthroscopy after failing at least 4 months of conservative management. Our secondary aim was to report the sensitivity and specificity of clinical examination and magnetic resonance imaging evaluation for various injury subgroups against the gold standard of the arthroscopic findings. Technical challenges, complications, and outcomes are also discussed. METHODS: A retrospective review of the medical records of 32 pediatric and adolescent patients who underwent wrist arthroscopy was conducted. Preoperative clinical diagnosis, radiographic, and intraoperative findings including classifications of triangular fibrocartilage complex (TFCC) and interosseous ligaments were obtained. Patients were followed up to 1 year postoperatively and were discharged if symptom free. RESULTS: Thirty-three wrist arthroscopies in 32 patients were performed from 1996 to 2004. There were 2 male and 30 female patients. At arthroscopy 16 wrists were found to have TFCC injuries, 11 wrists had scapholunate injuries, and 8 had lunotriquetral (LT) injuries. Clinical examination for diagnosis of TFCC injury was too sensitive and nonspecific; however, clinical diagnosis of scapholunate injury was sensitive and specific. LT injury was under diagnosed clinically. Magnetic resonance imaging was found to have a low sensitivity for diagnosis of LT injury but diagnosis of TFCC was sensitive and specific. CONCLUSIONS: The sex ratio of 2 males:30 females was startling. Nevertheless, this therapeutic level 3 study supports a thorough search for pathology in any patient with persistent wrist symptoms because pathology was identified in 32 of the 33 wrists at arthroscopy. LEVEL OF EVIDENCE: Level III-Therapeutic.

Development of Health Parameter Model for Risk Prediction of CVD Using SVM.

Current methods of cardiovascular risk assessment are performed using health factors which are often based on the Framingham study. However, these methods have significant limitations due to their poor sensitivity and specificity. We have compared the parameters from the Framingham equation with linear regression analysis to establish the effect of training of the model for the local database. Support vector machine was used to determine the effectiveness of machine learning approach with the Framingham health parameters for risk assessment of cardiovascular disease (CVD). The result shows that while linear model trained using local database was an improvement on Framingham model, SVM based risk assessment model had high sensitivity and specificity of prediction of CVD. This indicates that using the health parameters identified using Framingham study, machine learning approach overcomes the low sensitivity and specificity of Framingham model.

Alpha-amylase Inhibition and Antioxidant Activity of Marine Green Algae and its Possible Role in Diabetes Management.

AIM: In the continuing search for safe and efficient antidiabetic drug, marine algae become important source which provide several compounds of immense therapeutic potential. Alpha-amylase, alpha-glucosidase inhibitors, and antioxidant compounds are known to manage diabetes and have received much attention recently. In the present study, four green algae (Chaetomorpha aerea, Enteromorpha intestinalis, Chlorodesmis, and Cladophora rupestris) were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro. MATERIALS AND METHODS: The phytochemical constituents of all the extracts were qualitatively determined. Antidiabetic activity was evaluated by inhibitory potential of extracts against alpha-amylase and alpha-glucosidase by spectrophotometric assays. Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide (H2O2), and nitric oxide scavenging assay. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out to determine the major compound responsible for its antidiabetic action. RESULTS: Among the various extracts screened, chloroform extract of C. aerea (IC50 - 408.9 µg/ml) and methanol extract of Chlorodesmis (IC50 - 147.6 µg/ml) showed effective inhibition against alpha-amylase. The extracts were also evaluated for alpha-glucosidase inhibition, and no observed activity was found. Methanol extract of C. rupestris showed notable free radical scavenging activity (IC50 - 666.3 µg/ml), followed by H2O2 (34%) and nitric oxide (49%). Further, chemical profiling by GC-MS revealed the presence of major bioactive compounds. Phenol, 2,4-bis (1,1-dimethylethyl) and z, z-6,28-heptatriactontadien-2-one were predominantly found in the methanol extract of C. rupestris and chloroform extract of C. aerea. CONCLUSION: Our results demonstrate that the selected algae exhibit notable alpha-amylase inhibition and antioxidant activity. Therefore, characterization of active compounds and its in vivo assays will be noteworthy. SUMMARY: Four green algae were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro C. aerea and Chlorodesmis showed significant inhibition against alpha-amylase, and C. rupestris showed notable free radical scavenging activityNo observed activity was found against alpha-glucosidaseGC-MS analysis of the active extracts reveals the presence of major compounds which gives an insight on the antidiabetic and antioxidant activity of these algae. Abbreviations used: DPPH: 2,2-diphenyl-1-picrylhydrazyl, BHT: Butylated hydroxytoluene, GC-MS: Gas chromatography-mass spectrometry.

Inhibitory potential of Turbinaria ornata against key metabolic enzymes linked to diabetes.

One of the therapeutic approaches in treating diabetes is to reduce postprandial hyperglycemia by inhibiting major carbohydrate hydrolyzing enzymes. In the present study, crude extracts of marine seaweed, Turbinaria ornata, were tested for their antidiabetic potential using enzyme inhibitory assays (α-amylase, α-glucosidase, and dipeptidyl peptidase-IV). Among the tested extracts, methanol and acetone extracts showed significant inhibitory effects on α-amylase (IC50 250.9 µg/mL), α-glucosidase (535.6 µg/mL), and dipeptidyl peptidase-4 (55.2 µg/mL), respectively. Free radical scavenging activity of these extracts was analyzed using DPPH assay (65%). Extracts were tested for in vitro toxicity using DNA fragmentation assay, haemolytic assay, and MTT assay. None of the extracts showed toxicity in tested models. Furthermore, GC-MS analysis of lead extracts showed the presence of major compounds, hentriacontane, z, z-6, 28-heptatriactontadien-2-one, 8-heptadecene, and 1-heptacosanol. Our findings suggest that Turbinaria ornata can be used as a potential source for further in vivo studies in controlling hyperglycemia.

16-Oxa-penta-cyclo-[6.6.5.0(1,18).0(2,7).0(9,14)]nona-deca-2,4,6,9,11,13,18-heptaen-15-one.

In the title compound, C18H12O2, the benzene rings are inclined to one another by 66.79 (7)°. The five-membered ring is almost planar with a maximum deviation of 0.014 (1) Å. In the crystal, the mol-ecules are linked by pairs of weak C-H⋯O interactions into centrosymmetric dimers. These dimers are linked by C-H⋯π interactions, forming a three-dimensional structure.