Barriers to advance care planning: a qualitative study of seriously ill Chinese patients and their families.

BACKGROUND: Advance care planning (ACP) facilitates identification and documentation of patients' treatment preferences. Its goal aligns with that of palliative care - optimizing quality of life of seriously ill patients. However, concepts of ACP and palliative care remain poorly recognized in Chinese population. This study aims at exploring barriers to ACP from perspective of seriously ill patients and their family caregivers. METHODS: This is a qualitative study conducted in a Palliative Day Care Centre of Hong Kong between October 2016 and July 2017. We carried out focus groups and individual interviews for the seriously ill patients and their family caregivers. A semi-structured interview guide was used to explore participants' experiences and attitudes about ACP. Qualitative content analysis was adopted to analyze both manifest content and latent content. RESULTS: A total of 17 patients and 13 family caregivers participated in our study. The qualitative analysis identified four barriers to ACP: 1) limited patients' participation in autonomous decision making, 2) cognitive and emotional barriers to discussion, 3) lack of readiness and awareness of early discussion, and 4) unprepared healthcare professionals and healthcare system. CONCLUSIONS: Participations of seriously ill patients, family caregivers and healthcare workers in ACP initiation are lacking respectively. A series of interventions are necessary to resolve the barriers.

About the Accuracy and Problems of Consumer Devices in the Assessment of Sleep.

Commercial sleep devices and mobile-phone applications for scoring sleep are gaining ground. In order to provide reliable information about the quantity and/or quality of sleep, their performance needs to be assessed against the current gold standard, i.e., polysomnography (PSG; measuring brain, eye, and muscle activity). Here, we assessed some commercially available sleep trackers, namely an activity tracker; Mi band (Xiaomi, Beijing, China), a scientific actigraph: Motionwatch 8 (CamNTech, Cambridge, UK), and a much-used mobile phone application: Sleep Cycle (Northcube, Gothenburg, Sweden). We recorded 27 nights in healthy sleepers using PSG and these devices and compared the results. Surprisingly, all devices had poor agreement with the PSG gold standard. Sleep parameter comparisons revealed that, specifically, the Mi band and the Sleep Cycle application had difficulties in detecting wake periods which negatively affected their total sleep time and sleep-efficiency estimations. However, all 3 devices were good in detecting the most basic parameter, the actual time in bed. In summary, our results suggest that, to date, the available sleep trackers do not provide meaningful sleep analysis but may be interesting for simply tracking time in bed. A much closer interaction with the scientific field seems necessary if reliable information shall be derived from such devices in the future.

The neuropsychology of cluster headache: cognition, mood, disability, and quality of life of patients with chronic and episodic cluster headache.

BACKGROUND: Cluster headache (CH) is commonly regarded as one of the most disabling headache conditions, and referred to as one of the most painful conditions known to humankind. Although there has been some research indicating the severe impact of CH, there is little comprehensive evidence of its impact on quality of life, disability, mood, and cognitive function in both its episodic (ECH) and chronic (CCH) variants. METHODS: This cross-sectional study investigates various aspects of cognitive function including intelligence, executive function, and memory, and mood, disability, and quality of life in 22 patients with ECH and CCH compared with age-matched healthy controls. RESULTS: The results showed that intelligence and executive functions are intact in patients with CH, but that patients with CH perform significantly worse than healthy controls on tests of working memory and (all P < .05) report greater cognitive failures (P < .05). Around one third of both the ECH and CCH groups achieved "caseness" for depression, while self-reported anxiety was higher in those with CCH than the ECH patients, with 75% of the former compared with 38% of the latter groups achieving "caseness" on the measure of anxiety. Patients with CH reported high levels of disability, which was not significantly different between the 2 groups (P > .05). The patients with CH reported poor quality of life compared with healthy controls; however, this difference was not statistically significant. CONCLUSION: Patients with CH show worse working memory, disturbance of mood, and poorer quality of life compared with healthy controls. The differences between patients with ECH and CCH, and the implications of these findings for the management of CH are discussed.

An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models.

A pan-sarbecovirus or pan-betacoronavirus vaccine that can prevent current and potential future beta-coronavirus infections is important for fighting possible future pandemics. Here, we report a mucosal vaccine that cross-protects small animal models from sarbecoviruses including SARS-CoV-1, SARS-CoV-2 and its variants. The vaccine comprises a live-but-defective SARS-CoV-2 virus that is envelope deficient and has the orf8 segment replaced by interferon-beta, hence named Interferon Beta Integrated SARS-CoV-2 (IBIS) vaccine. Nasal vaccination with IBIS protected mice from lethal homotypic SARS-CoV-2 infection and hamsters from co-housing-mediated transmission of homotypic virus. Moreover, IBIS provided complete protection against heterotypic sarbecoviruses, including SARS-CoV-2 Delta and Omicron variants, and SARS-CoV-1 in both mice and hamsters. Besides inducing a strong lung CD8 + T cell response, IBIS specifically heightened the activation of mucosal virus-specific CD4 + T cells compared to the interferon-null vaccine. The direct production of interferon by IBIS also suppressed virus co-infection of SARS-CoV-2 in human cells, reducing the risk of genetic recombination when using as live vaccines. Altogether, IBIS is a next-generation pan-sarbecovirus vaccine and warrants further clinical investigations.

Coastal Transient Niches Shape the Microdiversity Pattern of a Bacterioplankton Population with Reduced Genomes.

Globally dominant marine bacterioplankton lineages are often limited in metabolic versatility, owing to their extensive genome reductions, and thus cannot take advantage of transient nutrient patches. It is therefore perplexing how the nutrient-poor bulk seawater sustains the pelagic streamlined lineages, each containing numerous populations. Here, we sequenced the genomes of 33 isolates of the recently discovered CHUG lineage (~2.6 Mbp), which have some of the smallest genomes in the globally abundant Roseobacter group (commonly over 4 Mbp). These genome-reduced bacteria were isolated from a transient habitat: seawater surrounding the brown alga, Sargassum hemiphyllum. Population genomic analyses showed that: (i) these isolates, despite sharing identical 16S rRNA genes, were differentiated into several genetically isolated populations through successive speciation events; (ii) only the first speciation event led to the genetic separation of both core and accessory genomes; and (iii) populations resulting from this event are differentiated at many loci involved in carbon utilization and oxygen respiration, corroborated by BiOLOG phenotype microarray assays and oxygen uptake kinetics experiments, respectively. These differentiated traits match well with the dynamic nature of the macroalgal seawater, in which the quantity and quality of carbon sources and the concentration of oxygen likely vary spatially and temporally, though other habitats, like fresh organic aggregates, cannot be ruled out. Our study implies that transient habitats in the overall nutrient-poor ocean can shape the microdiversity and population structure of genome-reduced bacterioplankton lineages. IMPORTANCE Prokaryotic species, defined with operational thresholds, such as 95% of the whole-genome average nucleotide identity (ANI) or 98.7% similarity of the 16S rRNA gene sequences, commonly contain extensive fine-grained diversity in both the core genome and the accessory genome. However, the ways in which this genomic microdiversity and its associated phenotypic microdiversity are organized and structured is poorly understood, which disconnects microbial diversity and ecosystem functioning. Population genomic approaches that allow this question to be addressed are commonly applied to cultured species because linkages between different loci are necessary but are missing from metagenome-assembled genomes. In the past, these approaches were only applied to easily cultivable bacteria and archaea, which, nevertheless, are often not representative of natural communities. Here, we focus on the recently discovered cluster, CHUG, which are representative in marine bacterioplankton communities and possess some of the smallest genomes in the globally dominant marine Roseobacter group. Despite being over 95% ANI and identical in the 16S rRNA gene, the 33 CHUG genomes we analyzed have undergone multiple speciation events, with the first split event predominantly structuring the genomic diversity. The observed pattern of genomic microdiversity correlates with CHUG members' differential utilization of carbon sources and differential ability to explore low-oxygen niches. The available data are consistent with the idea that brown algae may be home to CHUG, though other habitats, such as fresh organic aggregates, are also possible.

Streamlining the Diagnosis of Atypical Facial Palsies: A 5-year Review of 805 Patients.

BACKGROUND: Currently, there are no definitive guidelines in the investigation and management of atypical facial palsies (AFPs). Our aim was to determine the etiology of AFPs presenting to a tertiary facial palsy center and to review the current spectrum of diagnostic and management approaches to these conditions. METHODS: A retrospective cohort analysis of attendees at the Queen Victoria Hospital multidisciplinary facial palsy clinic over a 5-year period from 2016 to 2020 was conducted. Demographic data were collated from the QVH Research and Governance team. Those presenting with classic Bell's palsy or Ramsay-Hunt syndrome were excluded. Anyone with atypical presentations (including multiple recurrences, focal neurological deficits, polycranial neuropathies, autoimmune conditions, hemifacial spasms, hearing/balance issues, weight loss, segmental facial palsies, and gradual onset presentations) were included under the AFP category. These patients were subjected to standard serological and radiological investigations and their follow-ups were reviewed. RESULTS: A total of 849 patients were identified, and 805 had actual facial palsy presentations. Of these, 172 patients had AFP. The majority of these patients had MRI imaging tests, which were useful, but the remaining serological tests were found to correlate more with symptom clusters and specific questions rather than with random tests for all AFPs. CONCLUSIONS: Although serological and radiological investigations help in the diagnosis of AFP, specific questions and presentations help streamline the diagnosis, without affecting its accuracy whilst reducing unnecessary tests and, thereby, cost and time. We present an algorithm organized by specific questions of presentations in those with AFPs.

The Impact of Reassurance on Musculoskeletal (MSK) Pain: A Qualitative Review.

BACKGROUND: The reassurance provided during patient-therapist interactions is significantly associated with psychosocial outcomes, including fear and increased confidence. Currently, there are no available reviews that discuss the impact of reassurance for patients with musculoskeletal (MSK) pain. The aim of the present review was to qualitatively synthesize themes around reassurance mechanisms, and the impact during the interaction between patients with MSK pain and therapists. A systematic search strategy was undertaken. Studies were included if they were qualitative or mixed methods studies, examining the patient-therapist consultation, in any MSK clinical setting, with any health care professional, for adult patients with acute to chronic MSK pain. A thematic synthesis was conducted and supported by a particular assessment using CERQual. RESULTS: Twenty-four studies were included (451 patients). Certain themes that related to both positive and negative outcomes of reassurance were identified as well as themes that illustrate the mechanisms causative of the outcomes. Using CerQual, we identified the most supported outcomes. CONCLUSIONS: Effective reassurance includes affectionate interactions such as therapeutic relationship building and interpersonal skills, an individualized patient-centered approach, education and the provision of self-management strategies. It should be noted that some interactions that use pathoanatomic models led patients to misinterpret the information provided, this created feelings of fear.

Ulnar nerve compression secondary to migration of pyrocarbon implant following right wrist arthroplasty.

A 50-year-old, right-hand dominant woman presented with a seven-month history of stiffness, pain and swelling on the ulnar side of her right wrist. She had undergone right wrist arthroplasty with a Pyrocarbon Amandys implant seven months previously for post-traumatic degenerative arthritis. She had an uneventful initial recovery until developing carpal tunnel syndrome, for which she underwent carpal tunnel release 5 months after her arthroplasty. Examination revealed a painful and limited range of movement in the affected wrist, with weakness of the first dorsal interosseous muscle and altered sensation in the ring finger. A hard swelling was visible and palpable on the palmar-ulnar aspect of the wrist. X-rays showed that the swelling was due to the dislocated Amandys implant (which was thought to be causing compression neuropathy of the ulnar nerve). The patient underwent removal of the pyrocarbon implant (through a palmar approach) and total wrist fusion one month later, following which the wrist successfully united and all symptoms of ulnar nerve compression resolved. Although some studies have reported migration of pyrocarbon implant following total wrist arthroplasty, to our knowledge, this is the first reported case of ulnar compression neuropathy from a migrated pyrocarbon wrist implant.

Characterization of PFOS toxicity on in-vivo and ex-vivo mouse pancreatic islets.

Considerable human data have shown that the exposure to perfluorooctane sulfonate (PFOS) correlates to the risk of metabolic diseases, however the underlying effects are not clearly elucidated. In this study, we investigated the impacts of PFOS treatment, using in-vivo, ex-vivo and in-vitro approaches, on pancreatic ß-cell functions. Mice were oral-gavage with 1 and 5 µg PFOS/g body weight/day for 21 days. The animals showed a significant increase in liver triglycerides, accompanied by a reduction of triglycerides in blood sera and glycogen in livers and muscles. Histological examination of pancreases showed no noticeable changes in the size and number of islets from the control and treatment groups. Immunohistochemistry showed a reduction of staining intensities of insulin and the transcriptional factors (Pdx-1, islet-1) in islets of pancreatic sections from PFOS-treated groups, but no changes in the intensity of Glut2 and glucagon were noted. Transcriptomic study of isolated pancreatic islets treated ex vivo with 1 µM and 10 µM PFOS for 24 h, underlined perturbations of the insulin signaling pathways. Western blot analysis of ex-vivo PFOS-treated islets revealed a significant reduction in the expression levels of the insulin receptor, the IGF1 receptor-ß, Pdk1-Akt-mTOR pathways, and Pdx-1. Using the mouse ß-cells (Min-6) treated with 1 µM and 10 µM PFOS for 24 h, Western blot analysis consistently showed the PFOS-treatment inhibited Akt-pathway and reduced cellular insulin contents. Moreover, functional studies revealed the inhibitory effects of PFOS on glucose-stimulated insulin-secretion (GSIS) and the rate of ATP production. Our data support the perturbing effects of PFOS on animal metabolism and demonstrate the underlying molecular targets to impair ß-cell functions.

Development and validation of an ultra high-performance liquid chromatographic method for the determination of a diastereomeric impurity in (+)-pinoresinol diglucoside chemical reference substance.

(+)-Pinoresinol 4,4'-di-O-beta-D-glucopyranoside ((+)-PDG) is one of the major lignans with various pharmacological activities which could be isolated from Duzhong and other plant species. In this study, a diastereomeric impurity, (-)-pinoresinol 4,4'-di-O-beta-D-glucopyranoside ((-)-PDG), the main impurity was identified in (+)-PDG chemical reference substance (CRS) and a reliable chromatographic method for rapid purity determination of (+)-PDG CRS was firstly developed. The optimal chromatographic condition was found to be using ACN/1,4-dioxane-water (2.5:6:91.5, v/v/v) as mobile phase on a Waters Acquity UPLC HSS T3 column (2.1 mm x 100 mm, 1.8 microm) with column temperature of 37 degrees C. The method was validated and applied to determine the chromatographic purity of five (+)-PDG CRS samples. The content of (-)-PDG in four commercial (+)-PDG CRS was 8.47-20.30%, whereas no (-)-PDG was detected in our in-house prepared (+)-PDG CRS in which purity was confirmed to be 99.80%. The above results confirmed that this method is fast and highly efficient for purity determination of the (+)-PDG CRS.

The effects of Scutellaria baicalensis extract on embryonic development in mice.

BACKGROUND: Scutellaria baicalensis is a perennial herbaceous plant widely distributed in Oriental areas. Its roots, a commonly used medicinal source, reputedly calm fetuses in pregnant women; however, there is no sufficient evidence to date to assess its safety during pregnancy. This study aims to evaluate the effects of S. baicalensis aqueous extract on embryonic development in ICR mice. METHODS: Aqueous extract of S. baicalensis roots was prepared in accordance with clinical application. Pregnant mice were randomly divided into four groups, i.e., mice treated by gavage with water as negative control, with aqueous extract of 2 (1.8 times of human daily dose), 8 or 32 g/kg/day from gestation day (Gd) 6 to 15 as low-, middle-, and high-dose groups, respectively. The parameters of live and dead fetuses, resorptions, external and skeletal malformed fetuses, maternal body weight, maternal liver, kidneys, and heart weights were evaluated on Gd 18. RESULTS: There was no significant difference in fetal parameters among four groups. Maternal absolute liver and kidneys weights in the high-dose group were significantly higher than those in negative control (p<0.05). Relative liver and kidneys weights in this group were significantly higher than those in any other group (p<0.05). CONCLUSIONS: Oral administration of aqueous extract of S. baicalensis roots at or below 32 g/kg/day to ICR mice during organogenesis did not cause significant fetal external or skeletal malformations. However, 32 g/kg/day presented potential maternal toxicity.

THM, HAA and CNCl formation from UV irradiation and chlor(am)ination of selected organic waters.

The formation of disinfection by-products (DBPs), including chloroform, dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and cyanogen chloride (CNCl) after sequential exposure of four organic waters to UV irradiation via either low- or medium-pressure lamps and free chlorine (or preformed monochloramine) under practical conditions was simulated. Statistically significant changes in the DBP formation from chlorination due to the additional UV irradiation are commonly observed under testing conditions, although some of these changes are not practically significant. The impacts from UV exposure were found to be most significant in chloroform formation (up to 40 microg/L) among the four tested DBPs. Organics from rivers were more sensitive to UV alteration than was the organic drawn from soil. This difference could not be explained by the specific UV absorbance (SUVA) values. In most cases, irradiation with the medium-pressure UV lamp gave similar or slightly larger changes in DBP yields, compared with the corresponding trials using the low-pressure lamp. Different application sequences could significantly change the relative quantities of DBPs but no general trend was identified. Case-specific evaluation of the formation of chloroform and CNCl is necessary.