The osteology of ‘Periptychus carinidens’: a robust, ungulate-like placental mammal (Mammalia: Periptychidae) from the Paleocene of North America

Periptychus is the archetypal genus of Periptychidae, a clade of prolific Paleocene 'condylarth' mammals from North America that were among the first placental mammals to radiate after the end-Cretaceous extinction, remarkable for their distinctive dental anatomy. A comprehensive understanding of the anatomy of Periptychus has been hindered by a lack of cranial and postcranial material and only cursory description of existing material. We comprehensively describe the cranial, dental and postcranial anatomy of Periptychus carinidens based on new fossil material from the early Paleocene (Torrejonian) of New Mexico, USA. The cranial anatomy of Periptychus is broadly concurrent with the inferred plesiomorphic eutherian condition, albeit more robust in overall construction. The rostrum is moderately elongate with no constriction, the facial region is broad, and the braincase is small with a well-exposed mastoid on the posterolateral corner and tall sagittal and nuchal crests. The dentition of Periptychus is characterized by strongly crenulated enamel, enlarged upper and lower premolars with a tall centralised paracone/protoconid. The postcranial skeleton of Periptychus is that of a robust, medium-sized (~20 Kg) stout-limbed animal that was incipiently mediportal and adopted a plantigrade stance. The structure of the fore- and hindlimb of Periptychus corresponds to that of a typically terrestrial mammal, while morphological features of the forelimb such as the low tubercles of the humerus, long and prominent deltopectoral crest, pronounced medial epicondyle, and hemispherical capitulum indicate some scansorial and/or fossorial ability. Most striking is the strongly dorsoplantarly compressed astragalus of Periptychus, which in combination with the distal crus and calcaneal morphology indicates a moderately mobile cruropedal joint. The anatomy of Periptychus is unique and lacks any extant analogue; it combines a basic early placental body plan with numerous unique specializations in its dental, cranial and postcranial anatomy that exemplify the ability of mammals to adapt and evolve following catastrophic environmental upheaval

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Optical coherence tomography-based contact indentation for diaphragm mechanics in a mouse model of transforming growth factor alpha induced lung disease

This study tested the utility of optical coherence tomography (OCT)-based indentation to assess mechanical properties of respiratory tissues in disease. Using OCT-based indentation, the elastic modulus of mouse diaphragm was measured from changes in diaphragm thickness in response to an applied force provided by an indenter. We used a transgenic mouse model of chronic lung disease induced by the overexpression of transforming growth factor-alpha (TGF-a), established by the presence of pleural and peribronchial fibrosis and impaired lung mechanics determined by the forced oscillation technique and plethysmography. Diaphragm elastic modulus assessed by OCT-based indentation was reduced by TGF-a at both left and right lateral locations (p < 0.05). Diaphragm elastic modulus at left and right lateral locations were correlated within mice (r = 0.67, p < 0.01) suggesting that measurements were representative of tissue beyond the indenter field. Co-localised images of diaphragm after TGF-a overexpression revealed a layered fibrotic appearance. Maximum diaphragm force in conventional organ bath studies was also reduced by TGF-a overexpression (p < 0.01). Results show that OCT-based indentation provided clear delineation of diseased diaphragm, and together with organ bath assessment, provides new evidence suggesting that TGF-a overexpression produces impairment in diaphragm function and, therefore, an increase in the work of breathing in chronic lung disease

Towards condom skills: a cross-sectional study of the association between condom proficiency, condom problems and STI risk amongst MSM

<p>Abstract</p> <p>Background</p> <p>Condom use problems are common amongst Scotland’s men who have sex with men (MSM). To date condom errors have been associated with the likelihood of sexually transmitted infections in heterosexual sexually transmitted infection (STI) clinic attendees but not in MSM and direct evidence of a link between condom problems and STI acquisition in MSM have been lacking. This study investigated the possibility of an independent association between condom proficiency, condom problems and STI acquisition in MSM in Scotland.</p> <p>Methods</p> <p>An exploratory observational design employed cross-sectional surveys in both STI clinic and community settings. Respondents completed self-report measures of socio-demographic variables, scales of condom proficiency and condom problems and numbers of different partners with whom men have had unprotected anal intercourse (UAI partners) in the preceding year. Self-report data was corroborated with clinical STI diagnosis where possible. Analysis included chi-squared and Mann–Whitney tests and multiple logistic regression.</p> <p>Results</p> <p>792 respondents provided data with an overall response rate of 70% (n = 459 clinic sample, n = 333 community sample). Number of UAI partners was the strongest predictor of self-reported STI acquisition over the previous 12 months (p < 0.001 in both clinic and community samples). Demographic characteristics were not associated with self-reported STI diagnosis. However, condom proficiency score was associated with self-reported STI acquisition (p < 0.05 in both samples). Condom problem score was also associated with self-reported STI diagnosis in the clinic (p = 0.001) but not the community sample. Condom problem score remained associated with self-reported STI diagnosis in the clinic sample after adjusting for number of UAI partners with logistic regression.</p> <p>Conclusions</p> <p>This exploratory study highlights the potential importance of targeted condom use skills interventions amongst MSM. It demands further research examining the utility of condom problem measures in wider populations, across prospective and experimental research designs, and a programme of research exploring their feasibility as a tool determining candidacy for brief interventions.</p

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Population Genetic Analysis of Propionibacterium acnes Identifies a Subpopulation and Epidemic Clones Associated with Acne

The involvement of Propionibacterium acnes in the pathogenesis of acne is controversial, mainly owing to its dominance as an inhabitant of healthy skin. This study tested the hypothesis that specific evolutionary lineages of the species are associated with acne while others are compatible with health. Phylogenetic reconstruction based on nine housekeeping genes was performed on 210 isolates of P. acnes from well-characterized patients with acne, various opportunistic infections, and from healthy carriers. Although evidence of recombination was observed, the results showed a basically clonal population structure correlated with allelic variation in the virulence genes tly and camp5, with pulsed field gel electrophoresis (PFGE)- and biotype, and with expressed putative virulence factors. An unexpected geographically and temporal widespread dissemination of some clones was demonstrated. The population comprised three major divisions, one of which, including an epidemic clone, was strongly associated with moderate to severe acne while others were associated with health and opportunistic infections. This dichotomy correlated with previously observed differences in in vitro inflammation-inducing properties. Comparison of five genomes representing acne- and health-associated clones revealed multiple both cluster- and strain-specific genes that suggest major differences in ecological preferences and redefines the spectrum of disease-associated virulence factors. The results of the study indicate that particular clones of P. acnes play an etiologic role in acne while others are associated with health