Potential Efficacy of 68Ga-Trivehexin PET/CT and Immunohistochemical Validation of αvß6 Integrin Expression in Patients With Head and Neck Squamous Cell Carcinoma and Pancreatic Ductal Adenocarcinoma.

PURPOSE: αvß6 integrin is exclusively expressed in epithelial cells and is upregulated in many carcinomas, such as pancreatic ductal adenocarcinomas (PDACs) and head and neck squamous cell carcinomas (H&NSCCs). Trivehexin is a recently synthesized trimerized αvß6 integrin selective nonapeptide, which can be labeled with a positron emitter like 68Ga. This is a pilot study to assess the potential role of 68Ga-Trivehexin PET/CT in patients with H&NSCC and PDAC and their correlation with αvß6 integrin expression by the tumor tissue on immunohistochemistry (IHC). PATIENTS AND METHODS: Thirty-two patients with suspected H&NSCC (n = 20) or PDAC (n = 12) underwent whole-body 68Ga-Trivehexin PET/CT and 18F-FDG PET/CT scans on 2 separate days. All 32 patients underwent biopsy from the tumor site for histopathological diagnosis and IHC for αvß6 integrin expression. The degree of αvß6 integrin expression on IHC was scored using the immunoreactive score and modified 4-point immunoreactive score classification. RESULTS: The 68Ga-Trivehexin PET images demonstrated increased tracer uptake (mean SUVmax 5.9 ± 3.3) in the primary and metastatic lesions with good lesion delineation in 8 out of the 9 cases of PDACs. However, FDG PET showed increased tracer uptake in 7 cases (6.2 ± 2.6). Among various cases of H&NSCC, increased uptakes of 68Ga-Trivehexin (6.6 ± 4.5) and 18F-FDG (12.7 ± 6.7) were seen in 17 out of the 18 patients. The 2 cases of inflammatory changes with suspected disease recurrence showed increased tracer uptake in 18F-FDG PET (7.98 ± 3.1) and no significant uptake in 68Ga-Trivehexin PET (2.2 ± 0.34).IHC showed higher expression of αvß6 integrins in lesions with higher uptake of 68Ga-Trivehexin. A higher sensitivity, specificity, and accuracy of 68Ga-Trivehexin PET over 18F-FDG PET was seen for detection of primary and metastatic lesions. CONCLUSIONS: 68Ga-Trivehexin is a promising noninvasive molecular imaging agent for tumors expressing αvß6 integrin, especially in cases where 18F-FDG PET/CT scan may be suboptimal due to its low uptake, or due to its nonspecific uptake around tumor sites.

Successful Pregnancy Outcome in an Operated Case of Budd-Chiari Syndrome Having Fetal Growth Restriction: A Twisted Tale of Gravid.

Budd-Chiari Syndrome (BCS) primarily affects women in the reproductive age group, with an ever-increasing incidence in the general population. Due to its rarity, it is not known precisely how a pregnancy progresses in a woman with BCS and what can happen to the baby. A rare condition known as Budd-Chiari syndrome causes the hepatic veins in the liver to constrict and become blocked. The challenges in pregnancy, such as decreasing hepatic function, a rise in thrombotic and bleeding events, or ascites, have historically made pregnancy inappropriate in these people. Here, we present a case of an unbooked 24-year-old female, a known case of treated BCS with 36 weeks and three days gestation period. She was referred from a peripheral hospital to our hospital's emergency department because of having fetal growth restriction. By presenting this rare case, we expect more extensive studies will be conducted on the effect of pregnancy on BCS and the effect of BCS on pregnancy which will help obstetricians to turn this rare possibility of conception into a fair possibility.

1,3-thiazole Derivatives: A Scaffold with Considerable Potential in the Treatment of Neurodegenerative Diseases.

1,3-thiazoles, which contain nitrogen and a sulfur atom is an unsaturated five-membered heterocyclic ring, have achieved a unique significant place in drug design and development because of their versatile structure and a variety of pharmacological activities, viz. anticancer, antiviral, antimicrobial, anticonvulsant, antioxidant, antidiabetic, etc. They have inspired researchers to design novel thiazole with different biological activities. The presence of the thiazole moiety has resulted in a large number of clinically useful drugs with a wide range of activities, such as Ritonavir (antiviral), Sulfathiazole (antimicrobial antibiotic), Abafungin, Ravuconazole (antifungal), Meloxicam (NSAID), etc., that further verify this statement. The prevalence of neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's is increasing at a rapid pace but existing treatments mainly provide symptomatic relief and are associated with undesired effects. Consequently, designing novel compounds with more effectiveness and reduced toxicity are required. 1,3-thiazole derivatives have emerged as excellent candidate in this regard and have an important role for the treatment of neurodegenerative diseases. In the current review, we have gathered all the appropriate literature which demonstrate the remarkable role of 1,3-thiazole and its derivatives in these diseases that may help design new compounds with more desired characteristics. The literature was assessed through worldwide scientific databases like GOOGLE, SCOPUS, and PUBMED using different keywords, and only relevant information published in English was evaluated.

Immunohistochemical expression of Ki-67 and Glypican-3 to distinguish aggressive from nonaggressive benign odontogenic tumors.

Background: The benign neoplasms are normally slow growing, indolent with no invasive potential. However, there exist a few locally aggressive benign odontogenic tumors that have a tendency to invade and deform the surrounding structures. The exact reason for the aggressiveness of these benign neoplasms remained an enigma. Their biology and clinical expression can often be destructive and ominous. An appropriate treatment protocol needs to be followed to combat the high recurrence rate and aggressiveness of these entities. Aggressive and noniaggressive epithelial odontogenic tumors were analyzed immunohistochemically with Ki-67 and glypican 3 (GPC3). Materials and Methods: Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, and 28 keratocystic odontogenic tumors) and nonaggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic itumors). Results: Statistical analysis using Pearson correlation showed Ki-67 to be a better marker for differentiating aggressive from nonaggressive odontogenic tumor as compared to GPC3 (P < 0.001, highly significant), whereas among aggressive tumors, GPC3 turned out to be more useful as compared to Ki-67 (P < 0.001, highly significant). Conclusion: The present study provides an insight into the different biological behavior of odontogenic tumors, which can thus be helpful in determining the therapy strategies for more aggressive odontogenic tumors.

Migraine: An Underestimated Neurological Condition Affecting Billions.

The second most prevalent cause of years of disability worldwide is migraine, a neurological condition that causes a persistent headache that is lifelong. This condition affects more than a billion people globally. Its widespread prevalence and concomitant impairment have several adverse effects. Migraines are brought on by numerous behavioural, ecological, and genetic factors. There are various types of migraines, of which migraine without aura is the most common. The objective of this article is to determine the causes of migraine headaches, review the appropriate diagnosis of migraine, and describe the migraine headache management alternatives that are available. Various treatments for migraine are available on the market. Among the many types of headaches, migraines are neurological in nature and are inherited in some people. It has four phases: prodromal phase, aura, attack phase, and postdrome phase. Stress, anxiety, changes in the female endocrine system, bright lights, loud noises, foul odour, excessive or insufficient sleep, changes in the environment or the climate, flashes of light or intense lighting, overexertion, missing meals, drinking alcohol and smoking, quitting caffeine, and taking too many migraine drugs are some of the triggering factors for migraine. Diagnosis of migraine mainly relies on a good history. Appropriate prevention can be done for specific indications. Treatment mainly revolves around medications like analgesics, triptans, ergot derivatives, and newly derived biologics. Lifestyle modifications are also essential as many daily life factors contribute to migraine. Migraine can be well-managed if sufficient attention and care are given along with proper medications and guidance. The patient should not ignore symptoms and report to the physician at the earliest so that correct management can be done.

Once-Daily Oral Semaglutide Versus Injectable GLP-1 RAs in People with Type 2 Diabetes Inadequately Controlled on Basal Insulin: Systematic Review and Network Meta-analysis.

INTRODUCTION: The relative efficacy and safety of once-daily oral semaglutide vs. injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in subjects with type 2 diabetes (T2D) inadequately controlled on basal insulin were assessed using network meta-analysis (NMA). METHODS: A systematic literature review (SLR) was performed to identify randomised controlled trials of GLP-1 RAs in this population. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA1c), weight and blood pressure; HbA1c target levels (< 7.0% and ≤ 6.5%); composite endpoint; incidence of nausea, vomiting or diarrhoea. Comparators of interest were all licensed doses of dulaglutide, exenatide, liraglutide, lixisenatide and once-weekly injectable semaglutide. RESULTS: The NMA included seven trials. Once-daily oral semaglutide 14 mg was associated with significantly greater HbA1c reductions vs. most comparators (treatment differences: - 0.42 to - 1.32%); differences vs. once-weekly injectable semaglutide (0.5 mg and 1 mg doses) were not statistically significant. Once-daily oral semaglutide 14 mg was associated with significantly greater weight reductions vs. exenatide 2 mg and lixisenatide 20 µg (- 2.21 and - 2.39 kg respectively); non-statistically significant weight reductions in favour of once-daily oral semaglutide 14 mg were observed vs. all other comparators except once-weekly injectable semaglutide 1 mg. Similar trends were observed for the proportion of subjects achieving HbA1c < 7.0% and ≤ 6.5% and the composite endpoint. Once-daily oral semaglutide 14 mg was associated with similar odds of experiencing nausea, vomiting or diarrhoea vs. all comparators. CONCLUSION: Once-daily oral semaglutide 14 mg, as an add-on to basal insulin, is an efficacious treatment for reducing HbA1c and weight and meeting glycaemic targets at 26 ± 4 weeks. Once-daily oral semaglutide 14 mg also offers the option of an oral treatment with similar or better efficacy and similar tolerability vs. most injectable GLP-1 RAs.

Efficacy and safety of front-line treatments for advanced Hodgkin lymphoma: a systematic literature review.

OBJECTIVE: To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and A+AVD (brentuximab vedotin, with doxorubicin, vinblastine, and dacarbazine) for advanced-stage Hodgkin lymphoma (HL). METHODS: A systematic literature review (SLR) was conducted on 29 July 2016 (updated 26 July 2018) to identify randomized controlled trials (RCTs) and non-RCTs assessing the treatment of newly-diagnosed advanced-stage HL with ABVD and BEACOPP (and their variants), and A+AVD. RESULTS: The SLR identified 62 RCTs and 42 non-RCTs. Five-year overall survival rates for ABVD and BEACOPP were 60-97% and 84-99%, and 5-year progression-free survival rates were 58-81% and 83-96%, respectively. Both regimens were associated with tolerability issues and side effects. Discontinuation or dose reduction of bleomycin resulted in fewer adverse events, without significantly affecting efficacy. A head-to-head trial demonstrated improved efficacy for A+AVD vs ABVD, with an acceptable tolerability profile. No data from head-to-head trials comparing A+AVD with BEACOPP were available, and an indirect treatment comparison was not feasible. CONCLUSION: New therapies, such as A+AVD, maintain the efficacy observed with current treatments, and may provide a more tolerable treatment option for patients with advanced-stage HL.

Orally Administered Semaglutide Versus GLP-1 RAs in Patients with Type 2 Diabetes Previously Receiving 1-2 Oral Antidiabetics: Systematic Review and Network Meta-Analysis.

INTRODUCTION: Orally administered semaglutide is the first glucagon-like peptide 1 receptor agonist (GLP-1 RA) for oral administration. As head-to-head trials assessing orally administered semaglutide as an add-on to 1-2 oral antidiabetic drugs (OADs) vs other GLP-1 RAs are limited, a network meta-analysis (NMA) was performed to assess the relative efficacy and safety of orally administered semaglutide 14 mg once-daily (QD) vs injectable GLP-1 RAs in patients with type 2 diabetes inadequately controlled on 1-2 OADs. METHODS: A systematic literature review was conducted to identify randomised controlled trials of GLP-1 RAs in patients inadequately controlled on 1-2 OADs. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA1c), weight, HbA1c target levels (< 7.0% and ≤ 6.5%), blood pressure, and any gastrointestinal adverse events specified in system organ class. Data were synthesised using NMA and a Bayesian framework. RESULTS: In total, 27 studies were included in the analyses. Orally administered semaglutide 14 mg QD was associated with significantly greater reductions in HbA1c vs most comparators, and numerically greater reductions vs semaglutide 0.5 mg once-weekly (QW), dulaglutide 1.5 mg QW and liraglutide 1.8 mg QD. HbA1c reductions with semaglutide 1 mg QW were numerically greater than those with orally administered semaglutide 14 mg QD. Reductions in body weight for orally administered semaglutide 14 mg QD were significantly greater than all comparators except semaglutide QW (both doses). Orally administered semaglutide QD 14 mg was associated with statistically similar odds of experiencing gastrointestinal adverse events vs injectable GLP-1 RAs. CONCLUSION: Orally administered semaglutide 14 mg QD as an add-on to 1-2 OADs is one of the most efficacious GLP-1 RAs for reducing HbA1c and body weight at 26 ± 4 weeks. Orally administered semaglutide 14 mg QD is well tolerated, with a safety profile in line with the GLP-1 RA class. FUNDING: Novo Nordisk.

Comparison of different stains in exfoliated oral mucosal cell micronucleus of potentially malignant disorders of oral cavity.

BACKGROUND: Micronucleus (MN) has been proved to be an important biomarker of genomic damage. Leishman Giemsa (LG) cocktail, being a relatively new staining technique, has not been used in exfoliative cytology. The aim of this study is to observe and compare the micronuclei (MN) frequency in potentially malignant disorders (PMDs) and also to compare the staining efficacy of May-Grünwald Giemsa (MGG), LG cocktail, and Papanicolaou (PAP) for micronuclei in exfoliated oral mucosal cells. MATERIALS AND METHODS: Three smears were prepared from each 30 controls (buccal mucosa) and 120 patients (40 oral submucous fibrosis, 40 lichen planus, and 40 leukoplakia) clinically diagnosed with having one of the PMDs of the oral cavity stained with PAP, MGG, and LG cocktail stains. MN frequency (No. of MN/1000 cells) was evaluated and compared between the cases and the controls. Comparison between the three different stained smears was also made to determine the clarity and efficacy of the stains. RESULTS: LG cocktail gave comparatively better results followed by PAP and MGG. Statistically significant results (P < 0.05) were obtained, using Mann-Whitney test for comparison of MN frequency between cases and controls. CONCLUSION: LG cocktail is an easy, cost- effective, and one step technique comparable to PAP staining; however, it warrants further study in its potential application in screening of oral cancer.

Partitioning a reaction-diffusion ecological network for dynamic stability.

The loss of dispersal connections between habitat patches may destabilize populations in a patched ecological network. This work studies the stability of populations when one or more communication links is removed. An example is finding the alignment of a highway through a patched forest containing a network of metapopulations in the patches. This problem is modelled as that of finding a stable cut of the graph induced by the metapopulations network, where nodes represent the habitat patches and the weighted edges model the dispersal between habitat patches. A reaction-diffusion system on the graph models the dynamics of the predator-prey system over the patched ecological network. The graph Laplacian's Fiedler value, which indicates the well-connectedness of the graph, is shown to affect the stability of the metapopulations. We show that, when the Fiedler value is sufficiently large, the removal of edges without destabilizing the dynamics of the network is possible. We give an exhaustive graph partitioning procedure, which is suitable for smaller networks and uses the criterion for both the local and global stability of populations in partitioned networks. A heuristic graph bisection algorithm that preserves the preassigned lower bound for the Fiedler value is proposed for larger networks and is illustrated with examples.

Prevalence of tobacco in Darbhanga district: A hospital-based cross-sectional study.

INTRODUCTION: Chewing tobacco, smoking, and consumption of alcoholic beverages have become common social habits in India. No study has been conducted so far in this part of Bihar regarding the prevalence of tobacco. The aim of this study was to estimate the prevalence of tobacco use, its influences, triggers, and associated oral lesions. MATERIALS AND METHODS: A hospital-based cross-sectional study was conducted. Patients who consume tobacco in any form were selected and were interviewed through a pretested structured questionnaire in relation to their tobacco habits, its influences, and triggers. In addition, clinical examination was carried out to check for any tobacco-related oral lesions. RESULTS: The overall prevalence of tobacco use was 16.69%, out of which 14.48% were males and 2.21% were females. The most affected age group was from 19 to 50 years. 13.45% were below 18 years of age. 43.40% males and 77.42% females having the tobacco habit were illiterates. The majority of individuals were addicted due to peer pressure and friends, some acquired it, due to loneliness, stress, and for adapting themselves in the work place. Females frequently used smokeless for cleaning teeth. The most common oral mucosal lesion in both males (53.26%) and females (18.55%) was tobacco hyperkeratosis. CONCLUSION: The present study reflects the high prevalence rates of tobacco use among various sections of society. Apart from mass against tobacco products, authorities should focus on strict enforcement of law and promote research for creating new and harmless replacement products.

Design and evaluation of antibiotic releasing self- assembled scaffolds at room temperature using biodegradable polymer particles.

Biodegradable polymer-based drug-eluting implants offer many advantages such as predictable drug release kinetics, safety, and acceptable drug loading under ambient conditions. Herein, we describe fabrication and evaluation of antibiotic loaded scaffolds for localized delivery and tissue engineering applications. PDLLA particles entrapping gentamycin were formulated using solvent evaporation method and used for scaffold fabrication. Optimization of formulation parameters such as pH of the internal aqueous phase and combination of excipients like glycerol, polyvinyl alcohol (PVA) resulted in high entrapment efficiencies up to 96% of gentamicin in particles with drug load of 16-18µg/mg of polymer particles. These microparticles were fused in presence of methanol at ambient temperatures to form scaffolds of different geometry having reasonable mechanical strength. Porosity of these scaffolds was found to be more than 80%. Antibiotic released from the scaffolds was found to be bioactive as tested against Staphylococcus aureus and the release pattern was biphasic over a period of one week. The scaffolds were found to be non-toxic to murine fibroblasts cultures in vitro as well as to mice upon subcutaneous implantation. This method provides a novel and easy way of fabricating antibiotic loaded polymer scaffolds for varieties of applications.

Evaluation of stromal myofibroblasts in oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma--an immunohistochemical study.

BACKGROUND: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are the main potentially malignant disorders and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Myofibroblasts (MFs) secrete numerous growth factors and inflammatory mediators that stimulate epithelial cell proliferation and play an important role in tumoral invasion and use a combination of different factors in the course of neoplastic growth and development. Hence the present study was undertaken to evaluate and compare the distribution of MFs using alpha smooth muscle actin (α-SMA) in OL, OSMF, and various histopathological grades OSCC. MATERIALS AND METHODS: Sixty formalin-fixed paraffin-embedded tissue blocks consisting of histopathologically diagnosed cases of normal mucosa (n = 10), OL (n = 14) hyperkeratosis with various grades of dysplasia, OSMF (n = 11), and OSCC (n = 25) were subjected to immunohistochemistry using α-SMA antibody for detection of MFs. RESULTS: MFs were not detected in normal oral mucosa. On comparison of frequency of mean scores in OL, OSMF, and OSCC the values were 0.6 ± 0.2 (0-2), 1.2 ± 0.68 (1-2), and 2.6 ± 1.34 (0-4), respectively. The results were statistically significant (P < 0.001). CONCLUSION: These findings are suggestive of role of MFs with the creation of a permissive environment for tumor invasion in OSCC. Hence the presence of MF is a prognostic marker and evaluation of the frequency in the stroma can be used as therapeutic targets.

Corelation between machines assisted endodontic irrigant agitation and apical extrusion of debris and irrigant: a laboratory study.

AIMS: To compare amount of root canal debris and irrigant extruded apically after irrigants agitation using closed and open chambers. METHODS AND MATERIAL: Sixty maxillary central incisors were selected, decoronated, and mounted in preweighed glass vials filled with distilled water. Biomechanical preparation was completed using ProTaper rotary files until number F4 and 1 mL of 3% NaOCl solution after each file use. Samples were randomly divided into closed or open chamber sets which were further subdivided into 6 groups, based on the agitation techniques: no agitation (control), canalBrush, lentulospiral, passive ultrasonic agitation (PUA), EndoActivator, and EndoVac. Canals were irrigated with 1 mL of 17% EDTA and agitated for 30 s and then flushed with 2 mL of distilled water. Apically extruded irrigant was measured and vials were kept in incubator for 5 days at 68 °C for drying for weight calculation. Statistical Analysis. Analysis was done using Student's t-test, one-way ANOVA, and post-hoc. RESULTS: All agitation techniques showed apical extrusion of the debris and irrigant. The closed chamber apparatus showed significantly less extrusion of debris and irrigant than open chamber (P < 0.05). CONCLUSIONS: EndoVac was found to be the safest agitation system among all test groups with regard to apical extrusion of debris and irrigant.