Novel missense mutations and a 288-bp exonic insertion in PAX9 in families with autosomal dominant hypodontia

We describe the molecular analysis of three families with hypodontia involving primarily molar teeth and report two novel mutational mechanisms. Linkage analysis of two large families revealed that the hypodontia was linked to the PAX9 locus. These two families revealed missense mutations consisting of a glutamic acid substitution for lysine and a proline substitution for leucine within the paired domain of PAX9. A pair of identical twins affected with hypodontia in a third family demonstrated a 288-bp insertion within exon 2 that resulted in a putative frameshift mutation and a premature stop codon. The insertion was associated with the loss of 7-bp from exon 2. A block of 256-bp of sequence within the insertion was completely identical to downstream sequence from the second intron of the PAX9 gene. These studies extend the spectrum of mutations in PAX9 associated with hypodontia to include heretofore undescribed categories, including missense mutations.     

Simultaneous differentiation and typing of Entamoeba histolytica and Entamoeba dispar

Sequences corresponding to some of the polymorphic loci previously reported from Entamoeba histolytica have been detected in Entamoeba dispar. Comparison of nucleotide sequences of two loci between E. dispar strain SAW760 and E. histolytica strain HM-1:IMSS revealed significant differences in both repeat and flanking regions. The tandem repeat units varied not only in sequence but also in number and arrangement between the two species at both the loci. Using the sequences obtained, primer pairs aimed at amplifying species-specific products were designed and tested on a variety of E. histolytica and E. dispar samples. Amplification results were in complete agreement with the original species classification in all cases, and the PCR products displayed discernible size and pattern variations among the isolates.     

Ten years of Pan-InfORM: modelling research for public health in Canada

Modelling and simulation methods can play an important role in guiding public health responses to infectious diseases and emerging health threats by projecting the plausible outcomes of decisions and interventions. The 2003 SARS epidemic marked a new chapter in disease modelling in Canada as it triggered a national discussion on the utility and uptake of modelling research in local and pandemic outbreaks. However, integration and application of model-based outcomes in public health requires knowledge translation and contextualization. We reviewed the history and performance of Pan-InfORM (Pandemic Influenza Outbreak Research Modelling), which created a national infrastructure in Canada with a mandate to develop innovative knowledge translation methodologies to inform policy makers through modelling frameworks that bridge the gaps between theory, policy, and practice. This review demonstrates the importance of a collaborative infrastructure as a “Community of Practice” to guide public health responses, especially in the context of emerging diseases with substantial uncertainty, such as the COVID-19 pandemic. Dedicated resources to modelling and knowledge translation activities can help create synergistic strategies at the global scale and optimize public health responses to protect at-risk populations and quell socioeconomic and health burden.     

Myiasis in Kuwait: nosocomial infections caused by lucilia sericata and Megaselia scalaris

Myiasis, the invasion of live human tissue by larvae of Diptera, is reported in the nasopharynx and a leg wound in two patients who were hospitalized for more than 72 hours in Mubarak Al-Kabeer Teaching Hospital in Kuwait City, Kuwait. On the fourth and fifth days after a 10-year-old Kuwaiti boy was admitted to the hospital intensive care unit in a bloodied and comatose state following a traffic accident, 'worms' that came out of his nostrils were fixed, cleared, and identified as second and third instar of Lucilia sericata (Diptera: Calliphoridae). After 14 days, 'worms' were seen in the original dressing of a 35-year-old Iranian man admitted to the Orthopedic Unit of the hospital with multiple lacerations and fractures. The larvae, in various stages of development, were identified as those of Megaselia scalaris (Diptera: Phoridae). Since the presence of larvae in both patients was recorded after a stay of at least 3-4 days in the hospital, by definition, these infestations are considered nosocomial.     

Clinical and biochemical characteristic features of metastatic cancer to the sella turcica: an analytical review

Background and objectives

Sellar metastasis is uncommon and poorly characterized as published data include small series of subjects. This study’s goal is to identify unique features that differentiate this entity from other sellar masses such as pituitary macroadenomas.

Methods

Published cases of pathologically-confirmed sellar metastasis along with our experience in such patients over a 6-years period were reviewed (total = 129). As a control group, we reviewed similar data on 55 patients with pituitary macroadenomas managed over the same time-period. Presenting symptoms, pituitary dysfunction were analyzed using univariate, multivariate and receiver operating characteristic (ROC) analyses.

Results

Sellar metastasis has equal gender distribution with a median patient-age of 56 years. The most common primary malignancy was breast cancer (29 %) in women and lung cancer (30 %) in men. Sellar metastasis was the first manifestation of cancer in over 40 % of patients. Common presenting symptoms included headaches, visual field deficits, abnormal eye motility and diabetes insipidus. These symptoms were less frequent among patients with pituitary macroadenomas. Univariate regression analyses showed that headaches, abnormal eye motility, visual field deficits and diabetes insipidus were each predictive of metastatic disease. ROC analysis combining all 4 features revealed an AUC of 0.953 with a sensitivity of 0.818 and a specificity of 0.935. Using the multivariate regression, abnormal eye motility and/or diabetes insipidus independently predicted metastatic disease.

Conclusions

Sellar metastasis should be suspected in patients presenting with sellar masses, abnormal eye motility and/or diabetes insipidus even those without known malignancy since pituitary metastasis can often be the first manifestation of cancer.     

Foveal vasculature changes and nonperfusion in patients with diabetes types I and II with no evidence of diabetic retinopathy

Graefe's Archive for Clinical and Experimental Ophthalmology - To analyze the foveal avascular zone (FAZ) in patients with diabetes and no retinopathy vs. controls using OCT angiography...     

Unsymmetrical 1,3-disubstituted urea derivatives as α-chymotrypsin inhibitors

The objective of this study was to synthesize potent and/or novel inhibitors for α-chymotrypsin activity. Eighteen derivatives of N-methylphenyl-N′-(alkyl/aryl) urea (1–18) were synthesized, and their inhibitory effects on α-chymotrypsin enzyme were evaluated. Two compounds exhibited potent inhibitory activities. The most potent, N-(2-methylphenyl)-2-oxo-1-pyrrolidinecarboxamide (15) having a methyl group at ortho position was the most active inhibitor with an IC₅₀ value of 8.10 ± 0.14 μM, which was comparable to standard chymostatin (IC₅₀ = 8.24 ± 0.11 μM). A slightly less potent, N-(2-acetylphenyl)-N′-(3-methylphenyl) urea (10), exhibited an IC₅₀ of 13.6 ± 0.23 μM. Compounds 3, 4, 7, 11, and 13 exhibited moderate activities. The results demonstrated that α-chymotrypsin inhibition is related to the position of the methyl group and the presence of substituent at the nitrogen of the urea bridge. The inhibitory trend suggests that α-chymotrypsin inhibitory activity declines with ortho > meta > para substitution order. In conclusion, our data suggest that the compound 15 may serve as a lead compound for further designing of other potent or novel α-chymotrypsin inhibitors.     

Theoretical and Experimental in vitro Antifungal and Antitumor Activities of Organotin(IV) Derivatives of 3-(4-nitrophenyl)-2-methylacrylic acid

Pharmaceutical Chemistry Journal - Di- and triorganotin(IV) derivatives of 3-(4-nitrophenyl)-2-methylacrylic acid (HL), i.e., [n-Bu2SnL2] (1), [Me2SnL2] (2), [n-Bu3SnL]n (3) [Me3SnL]n (4) and...