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We present the case of a 65-year-old woman who presented with progressive dysphagia and was diagnosed with achalasia. She subsequently developed bilateral chylous pleural effusions, with no cause identified despite extensive investigations (including computed tomography (CT) scans, gastroscopy and medical thoracoscopy (MT)) and review at a dedicated pleural multidisciplinary team meeting.Despite optimal supportive management she deteriorated and was admitted to the intensive care unit, where she passed away due to sepsis and respiratory failure 10 months after initial presentation. A postmortem returned a diagnosis of epithelioid mesothelioma, encasing the carina, distal oesophagus and coeliac axis.Mesothelioma only very rarely presents with either chylous effusions or achalasia. Additionally while MT normally conveys excellent sensitivity for pleural malignancy, it was insufficient here. This case highlights how an unusually located mesothelioma can produce an unusual clinical picture. It also suggests a role for early video-assisted thoracoscopy to aid diagnosis.

Emerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.

There is a need for accurate quantitative non-invasive biomarkers to monitor myelin pathology in vivo and distinguish myelin changes from other pathological features including inflammation and axonal loss. Conventional MRI metrics such as T2, magnetization transfer ratio and radial diffusivity have proven sensitivity but not specificity. In highly coherent white matter bundles, compartment-specific white matter tract integrity (WMTI) metrics can be directly derived from the diffusion and kurtosis tensors: axonal water fraction, intra-axonal diffusivity, and extra-axonal radial and axial diffusivities. We evaluate the potential of WMTI to quantify demyelination by monitoring the effects of both acute (6weeks) and chronic (12weeks) cuprizone intoxication and subsequent recovery in the mouse corpus callosum, and compare its performance with that of conventional metrics (T2, magnetization transfer, and DTI parameters). The changes observed in vivo correlated with those obtained from quantitative electron microscopy image analysis. A 6-week intoxication produced a significant decrease in axonal water fraction (p<0.001), with only mild changes in extra-axonal radial diffusivity, consistent with patchy demyelination, while a 12-week intoxication caused a more marked decrease in extra-axonal radial diffusivity (p=0.0135), consistent with more severe demyelination and clearance of the extra-axonal space. Results thus revealed increased specificity of the axonal water fraction and extra-axonal radial diffusivity parameters to different degrees and patterns of demyelination. The specificities of these parameters were corroborated by their respective correlations with microstructural features: the axonal water fraction correlated significantly with the electron microscopy derived total axonal water fraction (ρ=0.66; p=0.0014) but not with the g-ratio, while the extra-axonal radial diffusivity correlated with the g-ratio (ρ=0.48; p=0.0342) but not with the electron microscopy derived axonal water fraction. These parameters represent promising candidates as clinically feasible biomarkers of demyelination and remyelination in the white matter. •We monitored de- and remyelination with compartment-specific diffusion MRI metrics.•Axonal water fraction decreased with patchy demyelination (6weeks of cuprizone).•Extra-axonal radial diffusivity increased with widespread demyelination (12weeks).•Correlations with electron microscopy supported each metric's specificity.•These metrics are promising candidates as clinical biomarkers of demyelination.

The PERIOD2 ( PER2 ) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2  variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.

Purpose The aim of this review is to determine the effect of ileal pouch-anal anastomosis (IPAA) on female fertility in ulcerative colitis (UC) and familial adenomatous polyposis (FAP), the mechanisms of this effect, strategies for prevention and management of infertility post-IPAA. Methods This paper is a systematic literature review of all articles investigating IPAA and fertility from 1966 onwards that were found searching the Medline and Embase databases. Meta-analysis was performed on relevant studies. Results Seventeen relevant studies were identified. Six studies were excluded (duplicate data, one; predominantly not IPAA patients, one; no control group, four). The control groups of the remaining 11 studies were too varied for comparison, and so the meta-analysis was limited to six studies that provided data on infertility both pre- and post-IPAA. Five of these involved predominantly UC patients and one FAP. Average infertility rates were 20% pre-IPAA and 63% post-IPAA. The relative risk of infertility after IPAA is 3.91 ([2.06, 7.44] 95% CI). The possibility of publication bias suggests that the risk may be lower. Any increased risk is probably due to tubal dysfunction secondary to adhesions. Various methods have been proposed to reduce pelvic adhesions, but there is no evidence they have any effect in preventing infertility. Infertility treatment post-IPAA is associated with good success rates. Conclusions Infertility is increased after IPAA in female patients in both UC and FAP. Both these disease processes affect patients during their reproductive years. This evidence emphasizes the need for careful consideration of fertility in the choice and timing of surgery.

The increasing kangaroo occurrence in expanding peri-urban areas can be problematic when kangaroos become aggressive towards people and present a collision risk to motor vehicles. An improved understanding on kangaroo spatial and temporal activity patterns in the peri-urban environment is essential to manage kangaroo–human conflict. In this study, we used GPS telemetry to determine activity patterns of male Eastern Grey Kangaroos (Macropus giganteus) in a peri-urban community on the north-coast of New South Wales, Australia. Two types of GPS devices were employed; collars and cheaper alternative glue-on units. Kangaroos moved on average 2.39 km a day, with an average movement rate of 1.89 m/min, which was greatest at dawn. The GPS glue-on devices had short deployment lengths of one to 12 days. Despite limitations in attachment time, the glue-on devices were viable in obtaining daily spatial and temporal activity data. Our results aid towards alleviating conflict with kangaroos by providing new insights into kangaroo movements and activity within a peri-urban environment and introduces a potential cheap GPS alternative for obtaining this data relative to more expensive collars.

This article defines and describes international services from the marketing perspective. A classification of four types of international services is proposed, and a theoretical model of one of these (contact-based services) is developed. With a rich literature on the nature of services, marketing scholars are in a strong position to make valuable contributions to the ongoing debate concerning international services, which has until now been dominated by international economists and trade statisticians.

To our astonishment, the patient retrieved his mobile phone from his undergarments and, while brandishing it with his mobile hand, asked whether he would be able to take the call.

Pulmonary hypertension (PH) is a cardiopulmonary disease manifesting in increased pulmonary arterial pressure and right ventricular dysfunction. PH pathogenesis involves extensive pulmonary vascular remodeling precipitated, at least in part, by endothelial reprogramming. Mounting evidence points to endothelial-to-mesenchymal transition (EndMT) as an important potentiator of endothelial reprogramming in PH, yet progress in dissecting these processes remains limited. Lung samples from pulmonary arterial hypertension (PAH) patients and two rodent models of PH were used. Expression of the scaffolding protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50, or NHERF1) was downregulated in PAH patient pulmonary arteries and isolated pulmonary arterial endothelial cells (PAECs), and in PH animal lung tissue and mouse isolated PAECs. In human PAECs in vitro, EBP50 was downregulated by PH-relevant stimuli, hypoxia and proinflammatory cytokine interleukin-1 beta (IL-1β). Phenocopy of EBP50 reduction in PAECs time-dependently increased expression and nuclear abundance of EndMT transcription factors Snail and Zeb1, and potentiated hypoxia-driven upregulation of Slug. Loss of EBP50 also drove expression of mesenchymal markers S100A4, fibronectin, N-cadherin, and transgelin (SM22), and inhibited cell proliferation and barrier function. In vivo studies on female EBP50+/- mice demonstrated that downregulation of EBP50 exacerbated the chronic hypoxia-induced rise in RV maximum pressure. These data identify EBP50 as a key regulator of EndMT in PH whose expression is downregulated in PH patient pulmonary endothelium and whose partial deletion exacerbates PH disease manifestations in rodents, opening doors for future therapeutic strategies to target EBP50 restoration to reverse PH.