"We were leery of going": qualitatively exploring Canadian international retirement migrants' travel-related decisions during the COVID-19 pandemic.

BACKGROUND: International retirement migration, which is the seasonal or permanent relocation of older people to another country, has grown in popularity in recent years. These retirees are motivated by the promise of warmer winter climates that are conducive to participating in health-promoting recreational and social activities. Ease of cross-border travel facilitates this transnational practice when undertaken seasonally. However, border closures and other travel-related measures put in place to manage the spread of COVID-19, disrupted travel, including for older Canadians who typically winter in the United States (US). During the 2020-21 winter season, for example, Canadians were advised not to engage in non-essential international travel and the land border between Canada and the US was closed to all but essential travellers. Nonetheless, retirement migration remained a significant draw for many Canadian retirees. Here, we qualitatively explore the factors that Canadian international retirement migrants considered when deciding whether or not to travel to the US for the 2020-21 winter during the COVID-19 pandemic. METHODS: Guided by case study methodology, semi-structured interviews were conducted with 31 Canadian international retirement migrants who had wintered in the US prior to the COVID-19 pandemic and were in the US at the outset of the pandemic in late winter 2020. Interviews were transcribed verbatim and thematically analyzed to decipher what factors were most important to their travel-related decision-making during the pandemic. We structure the thematic results around four factors previously identified to motivate older people to become international retirement migrants and thus inform decision-making: the destination, the people, the cost, and the movement. RESULTS: The previously identified factors that motivate older people to participate in international retirement migration include: the destination (e.g., climate and amenities), the people (e.g., social networks), the cost (e.g., health insurance and living costs), and the movement (e.g., ease of travel). These factors informed how international retirement migrants made decisions to travel abroad or not in the 2020-21 winter season. For example, destination-based factors included a lack of public health measures and high case counts, people-based factors comprised of less opportunities to engage in social activities, cost-based factors involved maintaining property investments and the lack of COVID-19 treatment coverage in available travel health insurance plans, and movement-based factors included challenges in ease of access when travel was viewed as essential or non-essential. These factors disincentivized or motivated international retirement migrants to travel abroad in the 2020-21 winter season during the COVID-19 pandemic. CONCLUSIONS: The results of this study support the need to create tailored decision-support tools for international retirement migrants to make informed travel-related decisions during crisis events so as to protect their health and wellbeing. More research is needed to explore perceptions of risk, especially health risks, among international retirement migrants and how they differently affect their travel-related decisions.

Systematic assessment of the brown tree frog (Anura: Pelodryadidae: Litoria ewingii) reveals two endemic species in South Australia.

The brown tree frog (Litoria ewingii) is a relatively widespread, commonly encountered pelodryadid frog from south-eastern Australia, known for its characteristic whistling call. The distribution of Litoria ewingii spans over more than 350,000 km2, encompassing a range of moist temperate habitats, and is fragmented by well-known biogeographic barriers. A preliminary analysis of mitochondrial DNA sequences revealed evidence for deep phylogenetic structure between some of these fragmented populations. In this study, we sought to re-evaluate the systematics and taxonomy of Litoria ewingii sensu lato by analysing variation in nuclear and mitochondrial DNA, adult morphology and male advertisement calls throughout the species range. Our analyses reveal two additional, deeply divergent and allopatric lineages in South Australia. We herein re-describe Litoria ewingii from Tasmania, southern New South Wales, Victoria and south-eastern South Australia, resurrect the name Litoria calliscelis for a species occurring in the Mount Lofty Ranges and Fleurieu Peninsula in South Australia, and describe a new species, Litoria sibilus sp. nov., endemic to Kangaroo Island.

Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor.

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TETRAS) and 68% (BF-ADL) of 'severe' or 'moderate' patients improving to 'mild' or 'slight'. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.

The Ectodomain of the Vaccinia Virus Glycoprotein A34 Is Required for Cell Binding by Extracellular Virions and Contains a Large Region Capable of Interaction with Glycoprotein B5.

An interaction between the orthopoxvirus glycoproteins A34 and B5 has been reported. The transmembrane and ectodomain of A34 are sufficient for interaction with B5, localization of B5 to the site of intracellular wrapping, and subsequent incorporation into the envelope of released extracellular virions. Several mutagenic approaches were undertaken to better define the B5 interaction domain on A34. A set of C-terminal truncations in A34 identified residues 1 to 80 as sufficient for interaction with B5. Additional truncations identified residues 80 to 130 of A34 as sufficient for interaction with B5. To better understand the function of this region, a set of recombinant viruses expressing A34 with the full, partial, or no B5 interaction site (residues 1 to 130, 1 to 100, and 1 to 70, respectively) was constructed. All the recombinants expressing truncations of A34 incorporated B5 into extracellular virions but had a small-plaque phenotype similar to that of a virus with the A34R gene deleted (vΔA34R). Further characterization indicated that the small-plaque phenotype exhibited by these viruses is due to a combination of abrogated actin tail formation, reduced cell binding, and a defect in polyanion-induced nonfusogenic dissolution. Taken together, these results suggest that residues 80 to 130 of A34 are not necessary for the proper localization and incorporation of B5 into extracellular virions and, furthermore, that the C-terminal residues of A34 are involved in cell binding and dissolution.IMPORTANCE Previous studies have shown that the vaccinia virus glycoproteins A34 and B5 interact, and in the absence of A34, B5 is mislocalized and not incorporated into extracellular virions. Here, using a transient-transfection assay, residues 80 to 130 of the ectodomain of A34 were determined to be sufficient for interaction with B5. Recombinant viruses expressing A34 with a full, partial, or no B5 interaction site were constructed and characterized. All of the A34 truncations interacted with B5 as predicted by the transient-transfection studies but had a small-plaque phenotype. Further analysis revealed that all of the recombinants incorporated detectable levels of B5 into released virions but were defective in cell binding and extracellular virion (EV) dissolution. This study is the first to directly demonstrate that A34 is involved in cell binding and implicate the ectodomain in this role.

Pearls & Oy-sters: The critical role of histopathology in diagnosing cancer-associated necrotizing CNS vasculitis.

OBJECTIVE: To highlight the importance of a broad differential and histopathologic confirmation in patients with newly diagnosed cancer with brain lesions atypical for CNS metastasis. METHODS: We report 2 cases of biopsy-proven CNS vasculitis in patients undergoing treatment for a newly diagnosed nonmetastatic cancer. Comprehensive medical record review was performed to identify the clinical presentation, representative neuroimaging, histopathologic features, and response to treatment. RESULTS: Patient 1 presented 1 month into induction therapy of malignant vaginal squamous cell carcinoma (stage 3, T2N1M0) with acute episodic left-sided hemiparesis due to seizure activity progressing to severe encephalopathy. Imaging revealed a right frontoparietal lesion while systemic workup was unrevealing. Biopsy demonstrated necrotizing vasculitis. Patient 2 presented 6 months after diagnosis of right breast invasive ductal carcinoma (stage IIa, T2N0M0, estrogen receptor-positive, progesterone receptor-positive, human epidermal growth factor receptor-2 positive) with subacute bifrontal headaches with associated phonophobia. Imaging showed hyperintense lesions involving the right temporoparietal region and systemic workup was unrevealing. Brain biopsy showed a necrotizing vasculitis. Patient 1 was treated with methyprednisolone and plasmapheresis and patient 2 was treated with prednisone. Both patients showed complete resolution of symptoms shortly after treatment and improvement on imaging. CONCLUSIONS: These cases highlight the importance of comprehensive evaluation of new brain lesions in patients with nonmetastatic solid tumors. Characteristics of new brain lesions in patients with cancer that should raise suspicion of diagnoses other than brain metastasis include (1) primary malignancy without regional or distant metastasis, (2) imaging without discrete mass-like enhancement, and (3) cortically based location of lesions not at the gray-white matter junction.

Biochemical analysis of the multifunctional vaccinia mRNA capping enzyme encoded by a temperature sensitive virus mutant.

Prior biochemical analysis of the heterodimeric vaccinia virus mRNA capping enzyme suggests roles not only in mRNA capping but also in early viral gene transcription termination and intermediate viral gene transcription initiation. Prior phenotypic characterization of Dts36, a temperature sensitive virus mutant affecting the large subunit of the capping enzyme was consistent with the multifunctional roles of the capping enzyme in vivo. We report a biochemical analysis of the capping enzyme encoded by Dts36. Of the three enzymatic activities required for mRNA capping, the guanylyltransferase and methyltransferase activities are compromised while the triphosphatase activity and the D12 subunit interaction are unaffected. The mutant enzyme is also defective in stimulating early gene transcription termination and intermediate gene transcription initiation in vitro. These results confirm that the vaccinia virus mRNA capping enzyme functions not only in mRNA capping but also early gene transcription termination and intermediate gene transcription initiation in vivo.

Association between subthalamic nucleus deep brain stimulation and weight gain: Results of a case-control study.

OBJECTIVE: To evaluate whether weight change in patients with Parkinson's disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS. PATIENTS AND METHODS: A retrospective case-control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain. RESULTS: Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9 kg (+4.65%) while controls lost 1.8 kg (-3.05%, p<0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain. CONCLUSION: In this case-control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain.

The role of vaccinia termination factor and cis-acting elements in vaccinia virus early gene transcription termination.

Vaccinia virus early gene transcription termination requires the virion form of the viral RNA polymerase (vRNAP), Nucleoside Triphosphate Phosphohydrolase I (NPHI), ATP, the vaccinia termination factor (VTF), and a U5NU termination signal in the nascent transcript. VTF, also the viral mRNA capping enzyme, binds U5NU, and NPHI hydrolyzes ATP to release the transcript. NPHI can release transcripts independent of VTF and U5NU if vRNAP is not actively elongating. However, VTF and U5NU are required for transcript release from an elongating vRNAP, suggesting that the function of VTF and U5NU may be to stall the polymerase. Here we demonstrate that VTF inhibits transcription elongation by enhancing vRNAP pausing. Hence VTF provides the connection between the termination signal in the RNA transcript and viral RNA polymerase to initiate transcription termination. We also provide evidence that a second cis-acting element downstream of U5NU influences the location and efficiency of early gene transcription termination.

Host factor SAMHD1 restricts DNA viruses in non-dividing myeloid cells.

SAMHD1 is a newly identified anti-HIV host factor that has a dNTP triphosphohydrolase activity and depletes intracellular dNTP pools in non-dividing myeloid cells. Since DNA viruses utilize cellular dNTPs, we investigated whether SAMHD1 limits the replication of DNA viruses in non-dividing myeloid target cells. Indeed, two double stranded DNA viruses, vaccinia and herpes simplex virus type 1, are subject to SAMHD1 restriction in non-dividing target cells in a dNTP dependent manner. Using a thymidine kinase deficient strain of vaccinia virus, we demonstrate a greater restriction of viral replication in non-dividing cells expressing SAMHD1. Therefore, this study suggests that SAMHD1 is a potential innate anti-viral player that suppresses the replication of a wide range of DNA viruses, as well as retroviruses, which infect non-dividing myeloid cells.

Role of forward translocation in nucleoside triphosphate phosphohydrolase I (NPH I)-mediated transcription termination of vaccinia virus early genes.

Termination of transcription of vaccinia virus early genes requires the virion form of the viral RNA polymerase (RNAP), a termination signal (UUUUUNU) in the nascent RNA, vaccinia termination factor, nucleoside triphosphate phosphohydrolase I (NPH I), and ATP. NPH I uses ATP hydrolysis to mediate transcript release, and in vitro, ATPase activity requires single-stranded DNA. NPH I shows sequence similarity with the DEXH-box family of proteins, which includes an Escherichia coli ATP-dependent motor protein, Mfd. Mfd releases transcripts and rescues arrested transcription complexes by moving the transcription elongation complex downstream on the DNA template in the absence of transcription elongation. This mechanism is known as forward translocation. In this study, we demonstrate that NPH I also uses forward translocation to catalyze transcript release from viral RNAP. Moreover, we show that NPH I-mediated release can occur at a stalled RNAP in the absence of vaccinia termination factor and U(5)NU when transcription elongation is prevented.

Pregnancy and stroke risk in women.

Stroke, the sudden onset of brain dysfunction from a vascular cause, is one of the most common causes of long-term disability. Although rare during childbearing years, stroke is even more devastating when it occurs in a young woman trying to start a family. Pregnancy and the postpartum period are associated with an increased risk of ischemic stroke and intracerebral hemorrhage, although the incidence estimates have varied. There are several causes of stroke that are in fact unique to pregnancy and the postpartum period, such as preeclampsia and eclampsia, amniotic fluid embolus, postpartum angiopathy and postpartum cardiomyopathy. Data regarding these individual entities are scant. Most concerning is the lack of data regarding both prevention and acute management of pregnancy-related stroke. The purpose of this article is to summarize existing data regarding incidence, risk factors and potential etiologies, as well as treatment strategies for stroke in pregnancy.

Number of immunoreactive GnRH-containing neurons is heritable in a wild-derived population of white-footed mice (Peromyscus leucopus).

The evolution of mammalian brain function depends in part on levels of natural, heritable variation in numbers, location, and function of neurons. However, the nature and amount of natural genetic variation in neural traits and their physiological link to variation in function or evolutionary change are unknown. We estimated the level of within-population heritable variation in the number of gonadotropin-releasing hormone (GnRH) neurons, which play a major role in reproductive regulation, in an unselected outbred population recently derived (<10 generations) from a single natural population of white-footed mice (Peromyscus leucopus, Rafinesque). Young adult male mice exhibited an approximately threefold variation in the number of neurons immunoreactive for GnRH in the brain areas surveyed, as detected using SMI-41 antibody with a single-label avidin-biotin complex method. Consistent with earlier findings of selectable variation in GnRH neurons in this population, the level of genetic variation in this neuronal trait within this single population was high, with broadsense heritability using full-sib analysis estimated at 0.72 (P<0.05). Either weak selection on this trait or environmental variation that results in inconsistent selection on this trait might allow a high level of variation in this population.