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Anecdotal data suggest great variation in breadth and depth of skeletal muscle coverage between undergraduate human anatomy (HA) and anatomy and physiology (A&P) courses. This manuscript is the second in a series (Reynolds A, Goodwin M, O'Loughlin V. D. "Adv Physiol Educ" 46: 309-318, 2022. doi:https://doi.org/10.1152/advan.00084.2021) that methodically assesses skeletal muscle content coverage across undergraduate HA and A&P courses. The authors developed an online skeletal muscle coverage survey and collected 342 responses worldwide, 156 from instructors of HA courses and 186 from A&P course instructors. Demographic results showed that HA courses are primarily taught at 4-year baccalaureate institutions, have relatively larger class sizes, and are more likely to use human (vs. animal) prosections or dissections. In contrast, A&P courses are primarily taught at community colleges, have relatively smaller class sizes, and are more likely to use animal (vs. human) dissections. HA courses tend to require their students to learn all skeletal muscle aspects (i.e., identification, action, attachments, innervation), whereas A&P courses tend to focus on muscle identification or action only. The proportions of courses that require identification of large, superficial skeletal muscles are similar between the two course types. However, HA courses are more likely to require their students to identify deeper and smaller muscles, including more distal appendicular muscles and pelvic muscles. These differences likely are due, in part, to the more anatomical focus of HA courses and the slightly different student populations between these courses. These findings provide much-needed information about muscular system coverage between HA and A&P courses and may guide instructor discussions about curricula. [For the first article in the series, "General Trends in Skeletal Muscle Coverage in Undergraduate Human Anatomy and Anatomy and Physiology Courses," see EJ1347509.]

Belgium is 1 of the few countries where sequential oral contraceptives are still commercially available. The authors investigated the endometrial effect of Ortho-Novum SQ (14 tablets of 100 mcg mestranol and 7 tablets of 100 mcg mestranol + 2 mg norethisterone) in 222 biopsy specimens obtained from 184 asymptomatic Caucasian women (mean +or- s.d, age and parity, 34.6 +or- 6.7 and 2.0 +or- 1.0, respectively) who had used this sequential OC during an average of 52.5 months. Notwithstanding predominantly longterm use of Ortho-Novum SQ, 43% of the tissue samples had normal proliferative or luteal endometrium. The data suggest a positive correlation between the endometrial response and the duration of pill use. No premalignant or malignant changes were found. In 15 of 24 subjects for whom multiple biopsy specimens were available, the histological picture was static; 7 showed regression and only in 2 were the changes progressive, although never more severe than minor 'class 2' lesions. These results, which are at variance with those reported for users of other sequential brands (mainly Oracon), suggest that prolonged use of Ortho-Novum SQ does not enhance the risk of endometrial cancer in premenopausal women having no additional risk factors for the development of this type of neoplasia.

European sea bass were fed four low FM/FO (10%/6%) diets containing galactomannan oligosaccharides (GMOS), a mixture of garlic oil and labiatae plants oils (PHYTO), or a combination of both functional products (GMOSPHYTO) for 63 days before exposing the fish to an intestinal Vibrio anguillarum infection combined with crowding stress. In order to evaluate functional diets efficacy in terms of gut health maintenance, structural, cellular, and immune intestinal status were evaluated by optical and electron microscopy and gene expression analyses. A semi-automated software was adapted to determine variations in goblet cell area and mucosal mucus coverage during the challenge test. Feeding with functional diets did not affect growth performance; however, PHYTO and GMOS dietary inclusion reduced European sea bass susceptibility to V. anguillarum after 7 days of challenge testing. Rectum (post-ileorectal valve) showed longer (p = 0.001) folds than posterior gut (pre-ileorectal valve), whereas posterior gut had thicker submucosa (p = 0.001) and higher mucus coverage as a result of an increased cell density than rectum. Functional diets did not affect mucosal fold length or the grade of granulocytes and lymphocytes infiltration in either intestinal segment. However, the posterior gut fold area covered by goblet cells was smaller in fish fed GMOS (F = 14.53; p = 0.001) and PHYTO (F = 5.52; p = 0.019) than for the other diets. PHYTO (F = 3.95; p = 0.049) reduced posterior gut goblet cell size and increased rodlet cell density (F = 3.604; p = 0.068). Dietary GMOS reduced submucosal thickness (F = 51.31; p = 0.001) and increased rodlet cell density (F = 3.604; p = 0.068) in rectum. Structural TEM analyses revealed a normal intestinal morphological pattern, but the use of GMOS increased rectum microvilli length, whereas the use of PHYTO increased (p≤0.10) Ocln, N-Cad and Cad-17 posterior gut gene expression. After bacterial intestinal inoculation, posterior gut of fish fed PHYTO responded in a more controlled and belated way in terms of goblet cell size and mucus coverage in comparison to other treatments. For rectum, the pattern of response was similar for all dietary treatments, however fish fed GMOS maintained goblet cell size along the challenge test. [ABSTRACT FROM AUTHOR]

We here describe the first fossil remains of a green lizard of the Lacerta group from the late Miocene (MN 13) of the Solnechnodolsk locality in southern European Russia. This region of Europe is crucial for our understanding of the paleobiogeography and evolution of these middle-sized lizards. Although this clade has a broad geographical distribution across the continent today, its presence in the fossil record has only rarely been reported. In contrast to that, the material described here is abundant, consists of a premaxilla, maxillae, frontals, parietals, jugals, quadrate, pterygoids, dentaries and vertebrae. The comparison of these elements to all extant green lizard species shows that these fossils are indistinguishable from Lacerta trilineata. Thus, they form the first potential evidence of the occurrence of this species in the Miocene. This may be also used as a potential calibration point for further studies. Together with other lizard fossils, Solnechnodolsk shows an interesting combination of survivors and the dawn of modern species. This locality provides important evidence for the transition of an archaic Miocene world to the modern diversity of lizards in Europe. In addition, this article represents a contribution to the knowledge of the comparative osteological anatomy of the selected cranial elements in lacertids. This study gives special emphasis to the green lizards, but new data are also presented for related taxa, e.g., Timon lepidus, Podarcis muralis or Zootoca vivipara. Although the green lizards include several cryptic species for which determination based on isolated osteological material would be expected to be difficult, our comparisons show several important morphological differences, although a high degree of variability is present. [ABSTRACT FROM AUTHOR]

Background: Maternal iodine deficiency is related to high neonatal thyroid-stimulating hormone (TSH) values, with the threshold of 5 mIU/L recommended as an indicator of iodine nutrition status. The objective of this study was to analyse possible risk factors for increased TSH that could distort its validity as a marker of iodine status. The clinical relevance of this research question is that if the factors associated with iodine deficiency are known, iodine supplementation can be introduced in risk groups, both during pregnancy and in newborns. Methods: A case-control study was carried out in a sample of 46,622 newborns in 2002–2015 in Spain. Of these, 45,326 had a neonatal TSH value ≥5 mIU/L. The main variable was having TSH ≥5 mIU/L and the secondary variables were: sex, gestational age, day of sample extraction and maternal origin. Associated factors were analysed through a logistic regression model, calculating the odds ratio (OR). Results: The factors associated with this outcome were: male sex (OR = 1.34, 95% CI: 1.20–1.50, p<0.001), originating from an Asian/Oceanic country (OR = 0.80, 95% CI: 0.54–1.20, p = 0.536) or Europe (OR = 0.80, 95% CI: 0.66–0.96, p = 0.285) (including Spain, OR = 1) [p<0.001 for America (OR = 0.54, 95% CI: 0.44–0.68) and p = 0.025 for Africa (OR = 0.78, 95% CI: 0.62–0.97)] and fewer days from birth to sampling (OR = 0.80, 95% CI: 0.77–0.82, p<0.001). Conclusions: The risk of high neonatal TSH without congenital hypothyroidism is higher in males, decreases with a greater number of days from birth to extraction, and is dependent on maternal ethnicity but not on gestational age. [ABSTRACT FROM AUTHOR]

In fish, the circadian clock represents a key regulator of many aspects of biology and is controlled by combinations of abiotic and biotic factors. These environmental factors are frequently manipulated in fish farms as part of strategies designed to maximize productivity. The flatfish turbot, Scophthalmus maximus, represents one of the most important species within the aquaculture sector in Asia and Europe. Despite the strategic importance of this species, the function and regulation of the turbot circadian system remains poorly understood. Here, we have characterized the core circadian clock genes, clock1, per1, per2 and cry1 in turbot and have studied their daily expression in various tissues under a range of lighting conditions and feeding regimes. We have also explored the influence of light and feeding time on locomotor activity. Rhythmic expression of the four core clock genes was observed in all tissues studied under light dark (LD) cycle conditions. Rhythmicity of clock gene expression persisted upon transfer to artificial free running, constant conditions confirming their endogenous circadian clock control. Furthermore, turbot showed daily cycles of locomotor activity and food anticipatory activity (FAA) under LD and scheduled-feeding, with the activity phase as well as FAA coinciding with and being dependent upon exposure to light. Thus, while FAA was absent under constant dark (DD) conditions, it was still detected in constant light (LL). In contrast, general locomotor activity was arrhythmic in both constant darkness and constant light, pointing to a major contribution of light, in concert with the circadian clock, in timing locomotor activity in this species. Our data represents an important contribution to our understanding of the circadian timing system in the turbot and thereby the optimization of rearing protocols and the improvement of the well-being of turbot within fish farming environments. [ABSTRACT FROM AUTHOR]

Background: From 2014 to 2017, the number of migrants who came to Italy via the Mediterranean route has reached an unprecedented level. The majority of refugees and migrants were rescued in the Central Mediterranean and disembarked at ports in the Sicily region. Rapid on-spot active TB screening intervention at the point of arrival will cover most migrants arriving in EU and by detecting TB prevalent cases will limit further transmission of the disease. Material and methods: Between November 2016 and December 2017 newly arrived migrants at point of arrivals in Sicily, were screened for active Tuberculosis using a smartphone application, followed in symptomatic individuals by fast molecular test, Xpert MTB/RIF Ultra, on collected sputum samples. Results: In the study period 3787 migrants received a medical evaluation. Eight hundred and ninety-one (23.5%) reported at least one protocol-defined Tuberculosis symptom. Fifteen (2.7%) were positive to at least one microbiological test revealing a post-entry screening prevalence rate of 396 per 100.000 individuals screened (95% CI: 2.22–6.53). In logistic regression analysis, those with cough and at least one other symptom had an increased probability of testing positive compared to persons with symptoms other than cough. Whole-genome-sequencing demonstrate two separate cases of transmission. Discussion: To our knowledge this study reports first-time results of an active TB case finding strategy based on on-spot symptom screening using a smartphone application, followed by fast molecular test on collected sputum samples. Our preliminary findings reveal a post-entry screening prevalence rate of 396 per 100.000 individuals screened (95% CI: 2.22–6.53). [ABSTRACT FROM AUTHOR]

Human T-cell lymphotropic virus (HTLV) belongs to a larger group of primate T-cell lymphotropic viruses (PTLVs) within the family Retroviridae. It is estimated that 10 to 20 million people worldwide may be infected with HTLV-1. Although most of them are asymptomatic, around 5% of infected individuals may develop either HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or Adult T-cell Leukaemia/Lymphoma (ATLL). Public Health authorities in many countries have implemented routine blood-donor tests for HTLV-specific antibodies; but this is not the case for Germany since the reported prevalence is very low (7/100,000). With the aim to evaluate retrospectively the presence of HTLV-1 among oncology patients in this country, samples stored at the Universitätsklinikum Freiburg, were analyzed. For this purpose, two different nested-PCR (n-PCR) protocols have been modified and set up for HTLV-1 detection. One positive case was detected by n-PCR among 406 samples (0,25%) in a period of 5 years (2008–2012) corresponding to a T-Cell Lymphoma. Despite the low prevalence, this virus is circulating in Germany, probably due to the increasing numbers of immigrants in these last years. Physicians should consider HTLV-1 infection and suspect it taking in account the ethnic and relation to endemic regions regardless the patient's residence. [ABSTRACT FROM AUTHOR]

Background: Image-based blood flow simulations have been increasingly applied to investigate intracranial aneurysm (IA) hemodynamics. However, the acceptance among physicians remains limited due to the high variability in the underlying assumptions and quality of results. Methods: To evaluate the vessel segmentation as one of the most important sources of error, the international Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH) was announced. 26 research groups from 13 different countries segmented three datasets, which contained five IAs in total. Based on these segmentations, 73 time-dependent blood flow simulations under consistent conditions were carried out. Afterwards, relevant flow and shear parameters (e.g., neck inflow rate, parent vessel flow rate, spatial mean velocity, and wall shear stress) were analyzed both qualitatively and quantitatively. Results: Regarding the entire vasculature, the variability of the segmented vessel radius is 0.13 mm, consistent and independent of the local vessel radius. However, the centerline velocity shows increased variability in more distal vessels. Focusing on the aneurysms, clear differences in morphological and hemodynamic parameters were observed. The quantification of the segmentation-induced variability showed approximately a 14% difference among the groups for the parent vessel flow rate. Regarding the mean aneurysmal velocity and the neck inflow rate, a variation of 30% and 46% was observed, respectively. Finally, time-averaged wall shear stresses varied between 28% and 51%, depending on the aneurysm in question. Conclusions: MATCH reveals the effect of state-of-the-art segmentation algorithms on subsequent hemodynamic simulations for IA research. The observed variations may lead to an inappropriate interpretation of the simulation results and thus, can lead to inappropriate conclusions by physicians. Therefore, accurate segmentation of the region of interest is necessary to obtain reliable and clinically helpful flow information. [ABSTRACT FROM AUTHOR]

Vaginal lubricants are commonly used by couples trying-to-conceive. However, most vaginal lubricants are sperm toxic and therefore should not be used by couples trying-to-conceive. Despite this, lubricant sperm toxicity is insufficiently reported and guidance for healthcare professionals (HCPs) is absent. In this study, lubricant-related practices of fertility-based HCPs in Scotland were sampled via an online survey. Lubricants identified as being utilised in the fertility setting were subsequently incubated with prepared sperm samples to establish effects on sperm motility. HCP recommendations (n = 32) on lubricant use were varied although knowledge related to sperm toxicity was generally poor. HCPs infrequently asked about lubricant use and were unaware of guidance in this area. Aquagel, the only prescribed lubricant identified in this study, reduced sperm progressive motility to 49% of control after 10 minutes, even at concentrations as low as 5%. Vitality testing suggested the deterioration in progressive motility with Aquagel was not as a result of cell death. Conversely, Pré Vaginal Lubricant, a ‘sperm-safe’ lubricant, did not significantly affect any markers of sperm function assessed. Development of clinical guidance in this area is recommended to ensure HCPs deliver informed advice as lubricant use in couples trying-to-conceive may inadvertently contribute to delay in conception. [ABSTRACT FROM AUTHOR]

Objective: To compare the differences in the use of healthcare services: visits to the doctor and hospitalisation, performance of routine tests, and preventive influenza vaccination, between users and non-users of homeopathic products. Methods: We used the microdata for adults over 15 years old from three waves of the Spanish National Health Survey, corresponding to the years 2011, 2014 and 2017. We proposed a comparative design of a quasi-experimental type, considering as the treatment group the respondents who said that they had used homeopathic products in the past two weeks; and another group, for control, comprising respondents who said that they had not used this type of products, but only conventional medicines, with observable characteristics similar to those of the treatment group. We used a model for rare events logistics regression (relogit) to estimate the probability of using homeopathy. From the propensity score and a vector of control variables, we used techniques of genetic matching to match individuals from the treatment group with similar individuals belonging to the control group. Results: There are no statistically significant differences between users and non-users of homeopathy in visits to the general practitioner (P>|z| 0.387), to the specialist (P>|z| 0.52), in hospitalisations (P>|z| 0.592) or in the use of emergency services (P>|z| 0.109). Nor were there any statistically significant differences in the performance of routine tests, except for the faecal occult blood test, which is more prevalent in users of homeopathic products. 20.9% of users of homeopathy had done this test compared with 15.3% of non-users (P>|z| 0.022). There are also significant differences in vaccination against influenza with 12.6% of homeopathy users stating that they had been vaccinated in the last influenza campaign, against 21.0% of non-users (P>|z| <0.001). The health conditions which homeopathy users reported were constipation (OR: 1.65 CI: 1.16–2.36), malignant tumour (OR: 1.60 CI: 1.09–2.36) osteoporosis (OR: 1.49 CI: 1.05–2.10), varicose veins (OR: 1.35 CI: 1.05–1.74) and allergy (OR: 1.35 CI: 1.06–1.72). Conclusions: Differences in the use of healthcare resources between users and non-users of homeopathic products have not been found to be statistically significant in Spain. It has been shown that most homeopathic products are used as a complement to treatment with conventional medicine. Nevertheless, our results highlight some warning signs which should raise the attention of healthcare authorities. The use of these therapies in patients with malignant tumours and the rejection of vaccines are warning signs of a possible health hazard in the long term. [ABSTRACT FROM AUTHOR]

Hantaan virus (HTNV) and Puumala virus (PUUV) are rodent-borne hantaviruses that are the primary causes of hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. The development of well characterized animal models of HTNV and PUUV infection is critical for the evaluation and the potential licensure of HFRS vaccines and therapeutics. In this study we present three animal models of HTNV infection (hamster, ferret and marmoset), and two animal models of PUUV infection (hamster, ferret). Infection of hamsters with a ~3 times the infectious dose 99% (ID99) of HTNV by the intramuscular and ~1 ID99 of HTNV by the intranasal route leads to a persistent asymptomatic infection, characterized by sporadic viremia and high levels of viral genome in the lung, brain and kidney. In contrast, infection of hamsters with ~2 ID99 of PUUV by the intramuscular or ~1 ID99 of PUUV by the intranasal route leads to seroconversion with no detectable viremia, and a transient detection of viral genome. Infection of ferrets with a high dose of either HTNV or PUUV by the intramuscular route leads to seroconversion and gradual weight loss, though kidney function remained unimpaired and serum viremia and viral dissemination to organs was not detected. In marmosets a 1,000 PFU HTNV intramuscular challenge led to robust seroconversion and neutralizing antibody production. Similarly to the ferret model of HTNV infection, no renal impairment, serum viremia or viral dissemination to organs was detected in marmosets. This is the first report of hantavirus infection in ferrets and marmosets. [ABSTRACT FROM AUTHOR]

Background: Previous ischemic stroke is a predictor of recurrent ischemic stroke after an acute myocardial infarction (AMI). Dual antiplatelet therapy, including a P2Y12-inhibitor, is important in secondary prevention after AMI. Ticagrelor, a P2Y12-inhibitor, is more potent than the commonly used clopidogrel. Here, we evaluated the impact of ticagrelor on the risk of ischemic stroke following AMI in patients with previous ischemic stroke. Methods: Data for patients with AMI that had a previous ischemic stroke were obtained from the Swedish Registry of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients were assigned to early and late cohorts, each covering a two-year time period before and after, respectively, the introduction of ticagrelor prescriptions (20 Dec 2011). Patients in the early cohort (n = 1633) were treated with clopidogrel (100%); those in the late cohort (n = 1642) were treated with either clopidogrel (66.3%) or ticagrelor (33.7%). We assessed the risk of ischemic stroke and intracranial bleeding over time with Kaplan-Meier analyses. We identified predictors of ischemic stroke with multivariable Cox regression analyses. Results: Of 3275 patients, 311 experienced ischemic stroke after AMI. Cumulative Kaplan-Meier incidence estimates of ischemic stroke within one year after AMI were 12.1% versus 8.6% for the early and late cohorts, respectively (p<0.01). Intracranial bleeding incidences (1.2% versus 1.5%) were similar between the two cohorts. Conclusions: Ticagrelor introduction was associated with a lower rate of ischemic stroke, with no increase in intracranial bleeding, in an AMI population with a history of ischemic stroke. [ABSTRACT FROM AUTHOR]

The fibularis tertius muscle (FTM) is a rare anatomic variation. The prevalence of this exclusively human structure, which is found in the anterior compartment of the leg, is often underestimated, and it is believed that foot and ankle conditions are more difficult to manage in patients with an FTM. The aim of this study was to assess the presence of the FTM palpation and determine whether its presence is associated with an individual’s sex, because the exact prevalence in males and females is unclear. An observational cross-sectional study was carried out. The study included 481 people (23.49% men and 76.51% women) with a mean age of 23.51±5.369 years, who were recruited from a Podiatric Medicine and Surgery Clinic (Spain). Data on routine demographic and clinical factors were recorded, and the presence or absence of the FTM was determined based on surface visual or palpated localization of the tendon (using a consistent protocol). The FTM was present in 38.25% (184/481) of the participants. Furthermore, FTM were present in 38.6% (142/481) of females and 37.2% (42/481) of males. The study revealed that the presence of the FTM varies between individuals and does not depend on an individual’s sex. Significant differences in the prevalence of the FTM between countries should be carefully evaluated rather than generalizing the results of this Spanish study to other non-Spanish populations. Larger numbers of participants should be enrolled in future studies in order to meet the statistical criteria. [ABSTRACT FROM AUTHOR]

Background: Folate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis. Objectives: The aim of this study was to assess the relationship between folate/homocysteine concentrations, the functional polymorphisms of folate/homocysteine genes and lung cancer risk among cigarette smokers. Study design: The study included 132 lung cancer patients and 396 controls from northern Poland, matched by sex, age and smoking status. The median cigarette pack-years of smoking among both cases and controls was 30.0. Serum, red blood cell (RBC) folates and serum homocysteine concentrations were measured. The genotypes in selected polymorphic sites of the MTHFR, CBS, SHMT1, MTHFD1, MTRR, MTR, TYMS DHFR, TCN2, and SLC19A1 genes were determined. All study participants underwent scanning with low-dose computed tomography. Results: Serum folate concentrations above the median (> 17.5 nmol/l among the healthy controls) were associated with an increased lung cancer risk (odds ratio [OR], 1.54, 95% confidence intervals [CI], 1.04–2.29, P = 0.031). An analogous trend was observed when the population was analysed after subdivision according to RBC folate concentrations, that is, above a value of 506.5 nmol/l (OR, 1.53; 95% CI, 0.95–2.47; P = 0.084). Additionally, in a subset of women, an increased risk of lung cancer development was associated with the SLC19A1 c.80AA genotype (c.80AA versus GG OR, 3.14; 95% CI, 1.32–7.46; P = P = 0.010). Conclusion: These results suggest that, in the population consisting of heavy smokers, high folate levels add to the cancerogenic effect of smoking. [ABSTRACT FROM AUTHOR]

Little is known of the resources that limit or promote the rapidly expanding golden jackal (Canis aureus) population in Europe. We hypothesised that in an area of intensive big game hunting, a reduction of the main food resource (human subsidised big game viscera) would result in dietary switching. We used multivariate analyses to test whether the dietary composition of 200 jackal stomachs varied between two 2-yearly survey occasions, the first without big game viscera removal (availability of 68 kg viscera/year/km2) followed by a period with viscera removal (minimum of 50 kg of viscera/year/km2 removed). The proportion of empty stomachs and the stomach wet content weight did not differ between the two periods. Even after the reduction of food subsidies, the primary food of jackals was viscera and carrion from wild ungulates (frequency of occurrence: 45% vs. 30%; wet weight: 55% vs. 29%, respectively), and scavenging was not affected by season or sex. Log-linear analysis of frequency data revealed no significant differences between survey occasions in consumption of either food type. MANCOVA of wet weight data revealed that in the first period with food subsidies jackals consumed a higher proportion of adult wild boar (11.6% vs. 1.3%; from predation or scavenging), while juvenile wild boar (0 vs. 11.8%; from predation or scavenging), domestic animals (0.8% vs. 6.2%; mostly from scavenging) and invertebrates (2.6% vs. 4.1%) increased in the second period. The stomachs in the second survey occasion contained more varied food items, but the trophic niche was not significantly wider. The feeding responses of this mesopredator to the reduction of food subsidies were less pronounced than expected. Because in high big game density areas, wild ungulate carrion from different mortality causes are available in high quantities throughout the year, predator populations can be maintained despite the high amount of viscera removal. [ABSTRACT FROM AUTHOR]

Background: Fundamental measures of control of tuberculosis are early detection and timely treatment of the affected. The aim of this study was to identify factors associated with patient-related and health system-related delays among patients with tuberculosis in the Republic of Montenegro. Methods: A cross-sectional study included 130 tuberculosis patients older than 15 years of age. The inclusion criteria were diagnosis of tuberculosis based on clinical, pathohistological and microbiological findings. Patient delay referred to the number of days between the onset of symptoms and the first consultation with general practitioner (GP). Health system delay represented the number of days between the first consultation with GP and the initiation of tuberculosis treatment.We classified delays longer than median delay length as 'prolonged delays'. Delays greater than 75th percentile of the maximum length of delay were classified as 'extreme delays'. Results: Distribution of patient and health system delay in the overall delay was apprioximately equal (49% vs. 51%). Being married (OR = 2.54, p = 0.026) and having more negative attitudes towards tuberculosis (OR = 4.00, p = 0.045) were associated with extreme patient delay. Greater knowledge on tuberculosis was associated with lower likelihood of prolonged (OR = 0.24, p = 0.031) and extreme (OR = 0.30, p = 0.012) patient delay. Persons with negative sputum smear were more likely to experience prolonged (OR = 7.01, p<0.001) and extreme (OR = 4.40, p = 0.032) health system delay. Persons older than 47 years of age were more likely to experience prolonged health system delay (OR = 2.61, p = 0.042). Specialist consultation delay was associated with prolonged (OR = 1.08, p = 0.001) and extreme (OR = 1.05, p<0.001) health system delay. Conclusion: Contribution to overall delay is equally distributed between the patients and the health care system. Improvement of knowledge in the general population and continuing medical education of the health care workers on tuberculosis could lead to reduction in patient and health system delays in treatment of tuberculosis. [ABSTRACT FROM AUTHOR]

The split of our own clade from the Panini is undocumented in the fossil record. To fill this gap we investigated the dentognathic morphology of Graecopithecus freybergi from Pyrgos Vassilissis (Greece) and cf. Graecopithecus sp. from Azmaka (Bulgaria), using new μCT and 3D reconstructions of the two known specimens. Pyrgos Vassilissis and Azmaka are currently dated to the early Messinian at 7.175 Ma and 7.24 Ma. Mainly based on its external preservation and the previously vague dating, Graecopithecus is often referred to as nomen dubium. The examination of its previously unknown dental root and pulp canal morphology confirms the taxonomic distinction from the significantly older northern Greek hominine Ouranopithecus. Furthermore, it shows features that point to a possible phylogenetic affinity with hominins. G. freybergi uniquely shares p4 partial root fusion and a possible canine root reduction with this tribe and therefore, provides intriguing evidence of what could be the oldest known hominin. [ABSTRACT FROM AUTHOR]

Background: Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.Methods and Findings: The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed.Conclusions: These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer. [ABSTRACT FROM AUTHOR]

The widely studied and invasive earthworm, Lumbricus terrestris L., 1758 has been the subject of nomenclatural debate for many years. However these disputes were not based on suspicions of heterogeneity, but rather on the descriptions and nomenclatural acts associated with the species name. Large numbers of DNA barcode sequences of the cytochrome oxidase I obtained for nominal L. terrestris and six congeneric species reveal that there are two distinct lineages within nominal L. terrestris. One of those lineages contains the Swedish population from which the name-bearing specimen of L. terrestris was obtained. The other contains the population from which the syntype series of Enterion herculeum Savigny, 1826 was collected. In both cases modern and old representatives yielded barcode sequences allowing us to clearly establish that these are two distinct species, as different from one another as any other pair of congeners in our data set. The two are morphologically indistinguishable, except by overlapping size-related characters. We have designated a new neotype for L. terrestris. The newly designated neotype and a syntype of L. herculeus yielded DNA adequate for sequencing part of the cytochrome oxidase I gene (COI). The sequence data make possible the objective determination of the identities of earthworms morphologically identical to L. terrestris and L. herculeus, regardless of body size and segment number. Past work on nominal L. terrestris could have been on either or both species, although L. herculeus has yet to be found outside of Europe. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Fractional Flow Reserve is a Useful Reference Standard for Myocardial Perfusion Studies with Limitations" in the previous issue.