Fine needle aspiration cytology of the thyroid: a cytohistologic study with evaluation of discordant cases

OBJECTIVE: To analyze the diagnostic efficacy of fine needle aspiration cytology (FNAC) in the initial evaluation of thyroid nodules, with special emphasis on discrepant cytologic diagnoses. STUDY DESIGN: A total of 192 thyroid fine needle aspirates with subsequent histopathologic follow-up were analyzed. The cytologic diagnoses were divided into 4 categories: positive for malignancy, negative for malignancy, indeterminate for diagnosis and nondiagnostic. The detailed cytologic features were studied along with histopathology sections in all these cases by 2 observers (S.J. and P.D) independently. RESULTS: Cytohistologic correlation was seen in 78.1% of cases and discordance in 21.9%. Indeterminate diagnoses accounted for 15.1% of cases. The majority of these were "follicular neoplasms." The overall sensitivity was 84.44% and specificity 99.11 %. A false positive diagnosis was made in 1 case (0.5%), proven a follicular adenoma on histopathologic examination. A false negative diagnosis was seen in 3.6% of cases. These were cases of papillary microcarcinoma. CONCLUSION: FNAC is a safe, sensitive and specific technique in the initial evaluation of thyroid nodules. A correct cytologic diagnosis can be achieved in a majority of cases, thus obviating the need for a second surgical intervention. A careful and diligent search for various cytologic features and accurate sampling can help in reducing the number of indeterminate, false positive and false negative diagnoses.     

Diel timing of nest predation changes across breeding season in a subtropical shorebird

Predation is the most common cause of nest failure in birds. While nest predation is relatively well studied in general, our knowledge is unevenly distributed across the globe and taxa, with, for example, limited information on shorebirds breeding in subtropics. Importantly, we know fairly little about the timing of predation within a day. Here, we followed 444 nests of the red‐wattled lapwing (Vanellus indicus), a ground‐nesting shorebird, for a sum of 7,828 days to estimate a nest predation rate, and continuously monitored 230 of these nests for a sum of 2,779 days to reveal how the timing of predation changes over the day and season in a subtropical desert. We found that 312 nests (70%) hatched, 76 nests (17%) were predated, 23 (5%) failed for other reasons, and 33 (7%) had an unknown fate. Daily predation rate was 0.95% (95%CrI: 0.76% – 1.19%), which for a 30‐day long incubation period translates into ~25% (20% – 30%) chance of nest being predated. Such a predation rate is low compared to most other avian species. Predation events (N = 25) were evenly distributed across day and night, with a tendency for increased predation around sunrise, and evenly distributed also across the season, although night predation was more common later in the season, perhaps because predators reduce their activity during daylight to avoid extreme heat. Indeed, nests were never predated when midday ground temperatures exceeded 45℃. Whether the diel activity pattern of resident predators undeniably changes across the breeding season and whether the described predation patterns hold for other populations, species, and geographical regions await future investigations.     

Nanocell targeting using engineered bispecific antibodies

There are many design formats for bispecific antibodies (BsAbs), and the best design choice is highly dependent on the final application. Our aim was to engineer BsAbs to target a novel nanocell (EnGeneIC Delivery Vehicle or EDV^TMnanocell) to the epidermal growth factor receptor (EGFR). EDV^TMnanocells are coated with lipopolysaccharide (LPS), and BsAb designs incorporated single chain Fv (scFv) fragments derived from an anti-LPS antibody (1H10) and an anti-EGFR antibody, ABX-EGF. We engineered various BsAb formats with monovalent or bivalent binding arms and linked scFv fragments via either glycine-serine (G4S) or Fc-linkers. Binding analyses utilizing ELISA, surface plasmon resonance, bio-layer interferometry, flow cytometry and fluorescence microscopy showed that binding to LPS and to either soluble recombinant EGFR or MDA-MB-468 cells expressing EGFR, was conserved for all construct designs. However, the Fc-linked BsAbs led to nanocell clumping upon binding to EDV^TMnanocells. Clumping was eliminated when additional disulfide bonds were incorporated into the scFv components of the BsAbs, but this resulted in lower BsAb expression. The G4S-linked tandem scFv BsAb format was the optimal design with respect to EDV binding and expression yield. Doxorubicin-loaded EDV^TMnanocells actively targeted with tandem scFv BsAb in vivo to MDA-MB-468-derived tumors in mouse xenograft models enhanced tumor regression by 40% compared to passively targeted EDV^TMnanocells. BsAbs therefore provide a functional means to deliver EDV^TMnanocells to target cells.     

Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy

In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04–3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098–4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR).     

TULIP study: Trail of Lurasidone in bipolar disorder in Pakistan

BackgroundThis study examined usefulness and efficiency of Lurasidone in appraisal with the placebo as for the treatment of Bipolar Disorders.MethodsSeven treatment centers in Pakistan were selected for the purpose of starting a six week-long control trial (randomized and double-blind placebo). 76 subjects, already diagnosed with Bipolar I or II based on DSM 5 diagnosis, were selected after randomization. Patients were allocated in one of the two groups. Primary efficacy of the drug was measured using Young Mania Rating Scale. Positive response of the drug was defined as 50% reduction in symptoms from the baseline/13 point less than the baseline score on Young Mania Rating Scale. Efficacy and safety of the drug was assessed using variety of markers such as administering extra-pyramidal symptoms rating scale, adverse side effects reported, electrocardiograms, body weight, vital signs changes, and laboratory investigations.ResultsPatients treated with Lurasidone showed enhanced improvement in their overall health and symptoms manifestation in comparison to patients who were given placebo. Lurasidone treated patients showed a better response to the drug (66%), in comparison with the placebo treated patients (42%).LimitationsStudy was conducted on small scale due to complexity.ConclusionPatients treated with Lurasidone showed reduction in bipolar symptoms and tolerate the drug well.     

Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

Background

Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.

Results

Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay. KA was found to be non-cytotoxic against HUVECs with IC₅₀ 40.97 ± 0.37 μg/ml. KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.

Conclusions

The non-cytotoxic compound, KA, may be a potent antiangiogenic agent; its activity may be attributed to inhibition of endothelial cells migration and differentiation as well VEGF suppression.     

Phytohormones and microRNAs as sensors and regulators of leaf senescence: Assigning macro roles to small molecules

Ageing or senescence is an intricate and highly synchronized developmental phase in the life of plant parts including leaf. Senescence not only means death of a plant part, but during this process, different macromolecules undergo degradation and the resulting components are transported to other parts of the plant. During the period from when a leaf is young and green to the stage when it senesces, a multitude of factors such as hormones, environmental factors and senescence associated genes (SAGs) are involved. Plant hormones including salicylic acid, abscisic acid, jasmonic acid and ethylene advance leaf senescence, whereas others like cytokinins, gibberellins, and auxins delay this process. The environmental factors which generally affect plant development and growth, can hasten senescence, the examples being nutrient dearth, water stress, pathogen attack, radiations, high temperature and light intensity, waterlogging, and air, water or soil contamination. Other important influences include carbohydrate accumulation and high carbon/nitrogen level. To date, although several genes involved in this complex process have been identified, still not much information exists in the literature on the signalling mechanism of leaf senescence. Now, the Arabidopsis mutants have paved our way and opened new vistas to elucidate the signalling mechanism of leaf senescence for which various mutants are being utilized. Recent studies demonstrating the role of microRNAs in leaf senescence have reinforced our knowledge of this intricate process. This review provides a comprehensive and critical analysis of the information gained particularly on the roles of several plant growth regulators and microRNAs in regulation of leaf senescence.