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.

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.

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.

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.

Response of Bortezomib Chemotherapy in Hepatic Amyloidosis.

Amyloidosis is a rare disorder with a wide spectrum of presentations and anomalies. It is subdivided into 2 broad categories based on protein deposition; primary and secondary amyloidosis. It can present as a single-organ involvement or as a diffuse infiltrative multi-organ process. Isolated hepatic amyloidosis presentation is a rare phenomenon that develops due to insoluble amyloid deposition in liver. Its clinical presentation is usually vague and ranges from mild hepatomegaly with elevated liver enzymes to acute liver failure and hepatic rupture. Currently, there are scarce data available regarding treatment options for biopsy-proven hepatic amyloidosis. In this review article, we present an interesting case of hepatic amyloidosis and its poor outcome to new molecular targeted chemotherapy. Furthermore, we aim to review current and future diagnostic tools for early detection and advancements in targeted chemotherapeutics options available for hepatic amyloidosis.

Measuring Healthy Lifestyle and Mental Health Indicators in South Asian Women Using the "Your Health: Quality of Life and Well-Being" Questionnaire.

INTRODUCTION: Health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. A literature review has revealed that there is no specific questionnaire available to assess well-being within the community. METHODS: Fifty South Asian women were randomly selected to complete the "Your Health: Quality of Life and Well-being Questionnaire" assessing diet, lifestyle, and mental health among others. Data from the questionnaires was extracted and participants were categorised based on these findings. RESULTS: This tool has positively identified a number of key risk factors for poor health, symptoms associated with mental illness, and the burden of comorbidities within the assessed cohort. Sixty-three percent of the women had an unhealthy body mass index (BMI), over half did not know the maximum limit of salt per day, and almost one-fourth had multiple health conditions. CONCLUSIONS: This questionnaire is an effective tool to use within the community. There is a significant burden of obesity, complicated by poor lifestyle habits and significant mood and anxiety symptoms within the studied South Asian population.

Crush Deformation of a Balloon-Expandable Stent Implanted in an Infrainguinal Bypass Graft.

A 59-year-old man with critical claudication underwent left femoro-anterior bypass grafting, which was uneventful. The graft was tunneled medially across the knee, then anterior to the tibia. His symptoms recurred 1 year later and he was found to have critical stenosis of the vein graft just proximal to the anterior tibial arterial anastomosis. This was treated with scaffolded balloon angioplasty and implantation of a coronary, zotarolimus-eluting balloon-expandable stent, which was also uneventful. However, his claudication again recurred 1 year later. Diagnostic angiography revealed crush, deformation and restenosis of the balloon-expandable stent requiring surgical revision of the bypass graft.

Gefitinib as first line therapy in Malaysian patients with EGFR mutation-positive non-small-cell lung cancer: A single-center retrospective study.

The present retrospective, single-center study evaluated the objective response rate (ORR) and progression-free survival (PFS) of epidermal growth factor receptor (EGFR) mutation-positive Malaysian patients with advanced lung adenocarcinoma treated with gefitinib. During May 2008 to July 2013, 33 patients with Stage IV, EGFR mutation-positive non-small-cell lung cancer (NSCLC) were identified and received gefitinib (250 mg) as first line treatment. The primary and secondary end points were ORR, PFS and safety, respectively. A total of 18 (54.5%) and 2 (6.1%) patients achieved partial response (PR) and complete response (CR) to gefitinib therapy, respectively, yielding an ORR of 60.6% (95% CI, 42.1-77.1%). Patients with exon 20 or 21 mutations (n=6, 66.7%) tended to have better ORR compared with exon 19 (n=22, 59.1%). The median PFS was 8.9 months in Malaysian patients with EGFR mutation-positive NSCLC, treated with gefitinib. The majority of treatment-related toxicity was mild in nature. The most frequently reported adverse events included dry skin (39.4%), skin rash (27.2%), and dermatitis acneiform (15.2%). In conclusion, Malaysian patients with locally advanced and metastatic EGFR mutation-positive NSCLC responded favorably to gefitinib therapy in terms of ORR, median PFS, and tolerability, the results of which were consistent with those of the IPASS study conducted in an Asian population. Considering the efficacy and safety profile of gefitinib, it is a favorable option for the first-line treatment of Malaysian patients with EGFR mutation-positive NSCLC. However, future long-term studies in a larger population of Malaysian patients are required to support whether the prolonged PFS conferred by gefitinib will translate into prolonged overall survival.

Nodal expression in triple-negative breast cancer: Cellular effects of its inhibition following doxorubicin treatment.

Triple-negative breast cancer (TNBC) represents an aggressive cancer subtype characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The independence of TNBC from these growth promoting factors eliminates the efficacy of therapies which specifically target them, and limits TNBC patients to traditional systemic neo/adjuvant chemotherapy. To better understand the growth advantage of TNBC - in the absence of ER, PR and HER2, we focused on the embryonic morphogen Nodal (associated with the cancer stem cell phenotype), which is re-expressed in aggressive breast cancers. Most notably, our previous data demonstrated that inhibition of Nodal signaling in breast cancer cells reduces their tumorigenic capacity. Furthermore, inhibiting Nodal in other cancers has resulted in improved effects of chemotherapy, although the mechanisms for this remain unknown. Thus, we hypothesized that targeting Nodal in TNBC cells in combination with conventional chemotherapy may improve efficacy and represent a potential new strategy. Our preliminary data demonstrate that Nodal is highly expressed in TNBC when compared to invasive hormone receptor positive samples. Treatment of Nodal expressing TNBC cell lines with a neutralizing anti-Nodal antibody reduces the viability of cells that had previously survived treatment with the anthracycline doxorubicin. We show that inhibiting Nodal may alter response mechanisms employed by cancer cells undergoing DNA damage. These data suggest that development of therapies which target Nodal in TNBC may lead to additional treatment options in conjunction with chemotherapy regimens - by altering signaling pathways critical to cellular survival.

Single-incision versus conventional laparoscopic adjustable gastric banding.

BACKGROUND AND OBJECTIVES: Laparoscopic adjustable gastric banding is an effective and popular bariatric surgery for weight loss in obese patients that traditionally involves up to 5 incisions. Recently, a more minimally invasive single-incision technique has been developed. In this retrospective study, we compare conventional and single-incision laparoscopic adjustable gastric banding with regard to weight loss and complication rates in a cohort of demographically similar patients. METHODS: From February 2009 to February 2010, 59 patients underwent laparoscopic adjustable gastric banding by one surgeon at an outpatient surgery center. All patients were compared by age, sex, preoperative body mass index, 30-day complication rates, and excess weight loss. Thirty-seven operations were performed by a conventional, 5-incision technique, whereas 22 patients underwent the single-incision technique. The success of these techniques was determined by comparing complication rates and average percentage excess weight loss at 6-month follow-up intervals. RESULTS: Patients who underwent conventional laparoscopic adjustable gastric banding had a mean age of 41.2 years and preoperative body mass index of 48.2 kg/m(2) compared with 43.9 years and 40.3 kg/m(2), respectively, for the single-incision patients. The mean operative time in the single-incision group was longer than that in the conventional group: 47.1 minutes versus 37.4 minutes (P = .0027). The overall percentage excess weight loss was not statistically different between the 2 groups for each follow-up period. There were no complications or deaths in either group. CONCLUSION: Although patients undergoing bariatric surgery may choose the single-incision technique for cosmetic purposes, this retrospective review comparing single-incision and conventional laparoscopic adjustable gastric banding shows longer operative times with equivalent weight loss and morbidity.

Desmoid tumour of lower abdomen.

A desmoid tumour is slow growing fibromatosis with aggressive infiltration of adjacent tissue and extremely unusual systemic metastases. We report on a female patient aged 25 years who had a mass in lower abdomen for 2 years. There was no previous history of any surgical intervention. Preoperative evaluation included ultrasound and computed tomography. Patient underwent primary resection with wide margins. Histology revealed a desmoid tumour.