Biochemical synthesis of taxanes from mevalonate.

Taxanes are kinds of diterpenoids with important bioactivities, such as paclitaxel (taxol®) is an excellent natural broad-spectrum anticancer drug. Attempts to biosynthesize taxanes have made with limited success, mainly due to the bottleneck of the low efficiency catalytic elements. In this study, we developed an artificial synthetic system to produce taxanes from mevalonate (MVA) by coupling biological and chemical methods, which comprises in vitro multi-enzyme catalytic module, chemical catalytic module and yeast cell catalytic module. Through optimizing in vitro multienzyme catalytic system, the yield of taxadiene was increased to 946.7 mg/L from MVA within 8 h and the productivity was 14.2-fold higher than microbial fermentation. By incorporating palladium catalysis, the conversion rate of Taxa-4(20),11(12)-dien-5α-yl acetate (T5α-AC) reached 48 %, effectively addressing the product promiscuity and the low yield rate of T5αOH. Finally, we optimized the expression of T10ßOH in yeast resulting in the biosynthesis of Taxa-4(20),11(12)-dien-5α-acetoxy-10ß-ol(T5α-AC-10ß-ol) at a production of 15.8 mg/L, which displayed more than 2000-fold higher than that produced by co-culture fermentation strategy. These technologies offered a promising new approach for efficient synthesis of taxanes.

Examining the Backpack Weight Relative to Students' Body Weight Among Urban and Rural Schoolchildren: A Cross-Sectional Study.

Background Schoolbags or backpacks have been an essential part of the education system for a long time. However, a hefty backpack causes the child to arch the back excessively or bend their head and trunk forward to withstand the weight of the schoolbag. If the student carries the backpack on one shoulder, he/she bends to the opposite side to compensate for the extra weight, which may damage the shoulders and spine. Considering these factors, the main aim of this study was to investigate the percentage of backpack weight in proportion to the student's body weight regarding the new guidelines among urban and rural schoolchildren aged 12 to 15 years in Bangalore, Karnataka. Methodology In southern India, over a year, a cross-sectional study was conducted with 500 students who voluntarily participated after providing written consent. They completed a questionnaire, underwent vital and anthropometric measurements, and had their weights measured, including the weights of their backpacks. Sample bags were inspected to determine contributing weight factors and evaluate adherence to timetables. Results The average weight carried by children of all ages was 6.53 kg, averaging 13.53% of their body weight. Among males, the percentage carrying backpacks weighing over 10% of their body weight was 80.9%, while among females, it was 85.7%. Of all the males carrying bags weighing more than 10% of their body weight, 67.7% attended government schools, while 32.3% attended private schools. Among females studying in government schools, 63.6% carried backpacks weighing more than 10% of their body weight, while among those in private schools, 36.4% carried bags exceeding that weight. Conclusions The study concluded that despite regulations being implemented on backpack weight for children, a significant number still carry bags exceeding 10% of their body weight among both urban and rural school children. This could elevate pressure on neck and back muscles, leading to excessive fatigue and potential damage to the skeletal system, ultimately contributing to spinal deformities.

Versatility of Titanium Mesh in Comminuted Maxillofacial Fractures. A Retrospective Study.

Background: Titanium mesh provides three-dimensional stability, it is easier and quick in placement, highly malleable and adaptable hence, proved to be worth in restoring the function and form in cases of comminuted maxillofacial fractures. Materials and Methods: A total of 12 patients were included in this retrospective study at Department of Oral and maxillofacial surgery, Sri Rajiv Gandhi College of Dental Science and Hospital, from December 2015 to June 2020. Out of 12 patients, 7 reported with frontal bone fracture and 5 reported with mandibular fracture. Patients were followed up for upto 18 months to evaluate efficacy of titanium mesh on postoperative long-term healing, aesthetic outcomes and return to normal function were evaluated. Results: The results have shown that titanium mesh has low complication rates and the ability to maintain occlusion and chewing postoperatively. Union occurred without complication in 90% of fractures, and patients treated for frontal bone fracture had excellent cosmetic results. Conclusion: The semi rigid nature of the titanium mesh fixation allows micro movement at the healing bone ends, reduces stress shielding effect which may improve functional bone healing. Bony continuity of the mandible can be restored providing three-dimensional morphology and stability. The versatile placement of screws is the principal advantage.

Know DBS: patient perceptions and knowledge of deep brain stimulation in Parkinson's disease.

Introduction: Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD) that can significantly improve motor symptoms and quality of life. Despite its effectiveness, little is known about patient perceptions of DBS. Objectives: To evaluate patient perceptions of DBS for PD, focusing on understanding, satisfaction, and factors influencing their outlook. This study aims to enhance patient education and counseling by identifying key determinants of patient perceptions. Design: A patient survey. Methods: We surveyed 77 PD patients who had undergone DBS at multiple centers using a comprehensive questionnaire. The questionnaire included questions on demographic information, disease history, and detailed understanding about the indications for DBS, side effects, outlook, and other common misconceptions. We summarize data using measures of central tendency and dispersion appropriate to the data type (categorical, continuous, proportional) and model relationships among variables using fractional and linear regression methods. Results: Participants had a median age of 66 years, were predominantly male (66%), Caucasian (90%), well-educated (79% with at least college degrees), and had a disease duration of greater than 5 years (97%). They conveyed good understanding of the signs and symptoms addressed by DBS across the motor and non-motor domains and associated side effects. Regression analysis identified age, disease duration, and education level as key determinants of patient understanding and outlook of DBS. Conclusion: Our study provides a detailed understanding of patient perceptions of DBS for PD, including the benefits, challenges, and misconceptions. Our findings underscore the importance of identifying the causes of disparities in patient knowledge and perceptions regarding DBS to tailor patient counseling and ensure optimal treatment outcomes.

Comparison of the Glenoid Index by Computed Tomography With Magnetic Resonance Imaging.

Introduction Anterior shoulder instability results in labral and osseous glenoid injuries. With a large osseous defect, there is a risk of recurrent dislocation of the joint, and therefore the patient has to undergo surgical correction. An MRI evaluation of the patient helps to assess the soft tissue injury. Currently, the volumetric three-dimensional (3D) reconstructed CT image is the standard for measuring glenoid bone loss and the glenoid index. However, it has the disadvantage of exposing the patient to radiation and additional expenses. This study aims to compare the values of the glenoid index using MRI and CT. Methodology The present study was a two-year cross-sectional study of patients with shoulder pain, trauma, and dislocation in a tertiary hospital in Karnataka. The sagittal proton density (PD) section of the glenoid and enface 3D reconstructed images of the scapula were used to calculate glenoid bone loss and the glenoid index. The baseline data were analyzed using descriptive statistics, and the Chi-square test was used to test the association of various complications with selected variables of interest. Results The glenoid index calculated in the current study using 3D volumetric CT images and MR sagittal PD images was 0.95±0.01 and 0.95±0.01, respectively. The CT and MRI glenoid bone loss was 5.41±0.65% and 5.38±0.65%, respectively. When compared, the glenoid index and bone loss calculated by MRI and CT revealed a high correlation and significance with a p-value of <0.001. Conclusions The study concluded that MRI is a reliable method for glenoid measurement. The sagittal PD sequence combined with an enface glenoid makes it possible to identify osseous defects linked to glenohumeral joint damage and dislocation. The values derived from 3D CT are identical to the glenoid index and bone loss determined using the sagittal PD sequence in MRI.

Cyclization mechanism of monoterpenes catalyzed by monoterpene synthases in dipterocarpaceae.

Monoterpenoids are typically present in the secretory tissues of higher plants, and their biosynthesis is catalyzed by the action of monoterpene synthases (MTSs). However, the knowledge about these enzymes is restricted in a few plant species. MTSs are responsible for the complex cyclization of monoterpene precursors, resulting in the production of diverse monoterpene products. These enzymatic reactions are considered exceptionally complex in nature. Therefore, it is crucial to understand the catalytic mechanism of MTSs to elucidate their ability to produce diverse or specific monoterpenoid products. In our study, we analyzed thirteen genomes of Dipterocarpaceae and identified 38 MTSs that generate a variety of monoterpene products. By focusing on four MTSs with different product spectra and analyzing the formation mechanism of acyclic, monocyclic and bicyclic products in MTSs, we observed that even a single amino acid mutation can change the specificity and diversity of MTS products, which is due to the synergistic effect between the shape of the active cavity and the stabilization of carbon-positive intermediates that the mutation changing. Notably, residues N340, I448, and phosphoric acid groups were found to be significant contributors to the stabilization of intermediate terpinyl and pinene cations. Alterations in these residues, either directly or indirectly, can impact the synthesis of single monoterpenes or their mixtures. By revealing the role of key residues in the catalytic process and establishing the interaction model between specific residues and complex monoterpenes in MTSs, it will be possible to reasonably design and engineer different catalytic activities into existing MTSs, laying a foundation for the artificial design and industrial application of MTSs.

A Case Series of Dengue Myocarditis: A Complication Observed in Dengue Patients.

Dengue is a prevalent arthropod-born viral disease with a wide spectrum of clinical presentations ranging from undifferentiated fever to a more severe form of the disease, dengue hemorrhagic fever, and dengue shock syndrome. However, atypical manifestations such as hepatic, neurological, cardiac, and kidney involvement are increasingly being reported, thus the term "expanded dengue syndrome". We report a series of cases with an atypical presentation of dengue fever marked by various cardiac manifestations, including cardiogenic shock secondary to myocardial involvement.

Complications of Conventional Sinus Augmentation Techniques Versus Modified Osteotome Techniques in Dental Implant Surgery: A 3-Year Retrospective Clinical Study.

Introduction: Sinus Augmentation has proven to be a predictable and popular approach to overcome bone volume deficiency in the posterior maxilla for patients seeking dental implants. The most common surgical methods utilized for maxillary sinus augmentations are the lateral window approach and crestal osteotome technique, which may cause many complications like sinus membrane tear, bleeding, sinusitis, etc. the purpose of this study is to compare complications rates of different sinus lift techniques in dental implant surgery. Aims and Objective: To assess the intraoperative and postoperative complications between the conventional direct or indirect method with alternative sinus lift techniques using Modified Crestal and Lateral (CAS & LAS KIT) ®method (Osstem/Hiossen). Materials and Methods: This is a retrospective study where in all the sinus lift cases done during 3year duration in the center data was collected and analyzed a total of 61 sinus lift procedure was done and all the data is tabulated and analyzed. Results: Results show of the total 61 cases 25 (40%) male patients and 36(59%)female patients traditional techniques like summers osteotome and conventional direct or indirect method had 7 cases (33.3%-37.5%) complication rates compared to Modified Lateral osteotome had 2 complications (14.2%) & Modified Crestal osteotome had only 3 case(3.7%) infections, wound dehiscence, membrane tear etc. Conclusion: Modified Crestal & Lateral Osteotome (CAS KIT & LAS KIT) ® technique does reduce the incidence of complications like sinus membrane tear compared to conventional Direct and Indirect techniques, because of stopper system used in hydraulic lift and the special design of drill head of these instruments.

Cone-beam computed tomography (CBCT) analysis of maxillary sinus septa in Indians.

It is of interest to assess the presence of maxillary sinus septae in patients undergoing implant treatment using Cone Beam Computed Tomography (CBCT).This retrospective study evaluated CBCT scans of 99 patients who opted for implant placement. A total of 198 sinuses were analyzed. The cases were divided into two group's namely edentulous group and non-edentulous groups. The location of septa was divided for analysis into 3 regions namely, the anterior (1st and 2nd premolar), middle (1st and 2nd molar) and posterior (behind 2nd molar) regions. Out of 198 sinuses assessed 15 sinuses had septa. It was more common in males. Mean height of septa was 7.7mm. It was more commonly seen in the middle region (1st and 2nd molar). All of the septa were partial in nature. Septa were common on the right side. It was absent in the edentulous group. To conclude this study showed low prevalence of septa in patients who were assessed as a part of pre-operative planning for implant placement. Modified sinus lift procedures were completed for placement of bone grafts in patients with septa,. This reduced the chances of membrane perforation and increases the chances of better outcomes. CBCT with its low cost and high resolution is useful for assessing the sinus.

Synthetic biology of plant natural products: From pathway elucidation to engineered biosynthesis in plant cells.

Plant natural products (PNPs) are the main sources of drugs, food additives, and new biofuels and have become a hotspot in synthetic biology. In the past two decades, the engineered biosynthesis of many PNPs has been achieved through the construction of microbial cell factories. Alongside the rapid development of plant physiology, genetics, and plant genetic modification techniques, hosts have now expanded from single-celled microbes to complex plant systems. Plant synthetic biology is an emerging field that combines engineering principles with plant biology. In this review, we introduce recent advances in the biosynthetic pathway elucidation of PNPs and summarize the progress of engineered PNP biosynthesis in plant cells. Furthermore, a future vision of plant synthetic biology is proposed. Although we are still a long way from overcoming all the bottlenecks in plant synthetic biology, the ascent of this field is expected to provide a huge opportunity for future agriculture and industry.

A Rare Entity of Undifferentiated Pleomorphic Sarcoma of the Mandible - A Case Report.

THE RATIONALE: Undifferentiated pleomorphic sarcoma originally known as malignant fibrous histiocytoma was declassified by the World Health Organization in 2002 as a formal diagnostic entity and renamed as an undifferentiated pleomorphic sarcoma. It accounts for <1% of malignant tumours of the long bone. PATIENT CONCERNS: A 33-year-old male patient reported with swelling and pain in the lower left posterior jaw region for 3 months with a history of fall on the floor 3 months back. DIAGNOSIS: On examination, diffuse solitary swelling was present on the left lower third of the face and was diagnosed radiographically and histopathologically as undifferentiated pleomorphic sarcoma of the mandible. TREATMENT AND OUTCOMES: Selective neck dissection, followed by reconstruction with fibula osteomyocutaneous flap and then referred for adjuvant radiotherapy. TAKE-AWAY LESSONS: Vimentin staining plays a substantial role in the diagnosis of undifferentiated pleomorphic sarcoma. A long-term follow-up after treatment is required to increase the chances of disease-free survival for the patients.

Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis.

BACKGROUND: Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR). OBJECTIVES: This study identified clinical characteristics and outcomes of AS-CA compared with lone AS. METHODS: Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality. RESULTS: A total of 407 patients (age 83.4 ± 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n = 16]; grade 2/3: 7.9% [n = 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p < 0.001). Decisions by the heart team (DPD-blinded) resulted in TAVR (333 [81.6%]), surgical AVR (10 [2.5%]), or medical management (65 [15.9%]). After a median of 1.7 years, 23% of patients died. One-year mortality was worse in all patients with AS-CA (grade: 1 to 3) than those with lone AS (24.5% vs. 13.9%; p = 0.05). TAVR improved survival versus medical management; AS-CA survival post-TAVR did not differ from lone AS (p = 0.36). CONCLUSIONS: Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA.

Efficacy of Various Routes of Dexamethasone Administration in Reducing Postoperative Sequelae Following Impacted Third Molar Surgery.

AIM: To compare the efficacy of intravenous (IV), intramassetric (IM) submucosal (SM) routes & oral routes of dexamethasone administration post impacted third molar removal surgery. TYPE OF STUDY: Prospective randomized comparative clinical study. MATERIALS AND METHOD: This prospective comparative study included 60 patients with Class II and position B type of impaction (according to Pell and Gregory's classification). Patients were randomly divided into 4 groups. Group A, B, C & D patients received 8mg dexamethasone immediately post-surgical tooth removal via the IV, SM and IM route & oral respectively. Assessment of swelling, mouth opening and pain was done at intervals of 1st, 3rd and 7th post-op days. RESULTS: The average age of the patients was 27 years. The mean time taken was 20 mins 40 seconds. The IV group showed minimal swelling and better pain control on the 3rd post op day (statistically significant). All 4 routes showed comparable mouth opening results. CONCLUSION: IV administration of dexamethasone post third molar surgery has been the traditional way because of its faster onset of action and increased efficacy; IM and SM routes are also comparably effective although oral route had the best patient acceptance.

Removal of Displaced Maxillary Third Molar Using Modified Gillie's Temporal Approach.

Tooth impaction is a pathological situation where a tooth is unable to achieve its normal functional position within the expected time span. The removal may be associated with intra-operative or post-operative complications. The Le Fort I osteotomy is a procedure used by maxillofacial surgeons to correct a wide range of dentofacial deformities. Due to its versatility and simplicity, it has gained popularity for a wide range of uses. This case report describes the location and surgical removal of a right maxillary third molar which was accidentally displaced into the infratemporal fossa in a 26-year-old female while performing Le Fort I osteotomy. The patient underwent a second surgery for the retrieval of tooth using modified Gillie's temporal approach. The important role of the cone beam computed tomography in determining the localization of the displaced tooth is demonstrated.

Acute Limb Ischemia Due to Arterial Thrombosis Associated With Coronavirus Disease 2019.

OBJECTIVES: To describe a case of acute limb ischemia caused by arterial thrombosis due to coronavirus disease 2019. DESIGN: Clinical observation of a patient. SETTING: Academic medical center. PATIENT: A 59-year-old female with history of hypertension, hyperlipidemia, and prior smoking. INTERVENTION: Clinical observation and data extraction from electronic medical records. MEASUREMENTS AND MAIN RESULTS: We report a case of peripheral arterial thrombosis associated with coronavirus disease 2019, resulting in acute limb ischemia of the right lower extremity. This event was heralded by a sudden and significant elevation in d-dimer levels. At the time of surgery, a long, gelatinous clot was retrieved from the right popliteal artery. Perioperatively, she continued to have absent pedal Doppler signals and after multiple embolectomy attempts, required distal arterial cut down with removal of additional thrombi and resultant improvement of distal arterial flow. CONCLUSIONS: This case demonstrates the importance of regularly checking d-dimer levels and vigilant monitoring for arterial thrombotic events, as they can rapidly become catastrophic.

Apps and Online Platforms for Patients with Heart Failure.

The use of the internet for health advice and information has burgeoned over recent years. This corresponds with an increasing number of people living with heart failure and, in the context of a greater focus on patient engagement, producing accurate online health information is becoming vitally important. To help meet this need, major cardiology societies have designed dedicated, patient-specific areas on their websites. This article aims to provide an overview of the patient information resources from three main professional societies: the European Society of Cardiology, American Heart Association and American College of Cardiology. A summary of the content of these dedicated websites and two smartphone apps is provided, along with a brief look into the future role of these technologies and resources in supporting both patients and their clinicians in the management of heart failure.

Lessons of the month 5: Cardiac tamponade after an acute myocardial infarction: the clinical diagnosis.

We present the case of a late presenting ST-elevation myocardial infarction with a coronary dissection. After primary percutaneous coronary intervention, the patient went on to develop pericardial effusion with tamponade. Despite only a small volume of fluid, we demonstrate how it can have significant clinical consequences in the diseased heart. We also highlight the value of being able to carry out bedside echocardiography in the acutely unwell post-myocardial infarction patient.