Central sensitization, chronic pain, and other symptoms: Better understanding, better management.

Central sensitization, a pathophysiologic process in which the central nervous system undergoes changes that alter its processing of pain and other sensory stimuli, may be the mechanism underlying various conditions in which patients have unexplained pain and fatigue. Patients frequently misunderstand the cause of their symptoms and pursue unnecessary evaluations and treatments. Clinicians have a pivotal role in decreasing this misunderstanding by providing patient education, which can affect perception, management, functional status, and quality of life.

Exploring the impact of elexacaftor-tezacaftor-ivacaftor treatment on opinions regarding airway clearance techniques and nebulisers: TEMPO a qualitative study in children with cystic fibrosis, their families and healthcare professionals.

BACKGROUND: Cystic fibrosis (CF) is a genetic condition caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that primarily impacts the lungs. Treatments historically have been symptomatic to improve airway clearance and treat infection. However, CFTR modulator drugs have recently been developed that target the underlying defect. The triple combination of elexacaftor-tezacaftor-ivacaftor (ETI) was approved in 2020 in England for over 80% of people with CF aged over 12 years and in 2022 extended to those over 6 years. ETI treatment is associated with substantial improvements in lung function. The experience of children with CF starting on ETI or their views regarding future treatments have not been well studied. This study aimed to explore the opinions of children with CF, their parents/carers and healthcare professionals (HCPs) on the impact of ETI, airway clearance techniques (ACTs) and nebulised treatments. METHODS: Semistructured qualitative interviews were performed with 10 children with CF, 7 parents/carers and 10 HCPs. Audio recordings were transcribed and analysed using reflexive thematic analysis. RESULTS: Four main themes were identified: 'Kaftrio changed my life', 'Your entire life is dictated by the CF timetable', 'Simplifying treatment-hopes and fears' and 'Kaftrio is a game-changer' along with several subthemes and an overarching theme of 'I still can't get my head around how three tablets can do what Kaftrio done'. CONCLUSIONS: Despite the highly positive impact of ETI on the health of children with CF some concerns remain about the longer-term outcomes of reducing ACTs or nebulised treatments. ETI has prompted a shift in treatment for many and offers an opportunity to personalise approaches.

Multi-host dispersal of known and novel carnivore amdoparvoviruses.

Amdoparvoviruses (family Parvoviridae) are ssDNA viruses that cause an immune complex-mediated wasting syndrome in carnivores. They are multi-host pathogens and cross-species infection is facilitated by the fact that viral entry is mediated by cellular Fc receptors recognizing antibody-coated viruses. We developed a pan-amdoparvovirus PCR and screened tissue samples from 666 wild carnivores (families Felidae, Canidae, and Mustelidae) from Newfoundland or Labrador (Canada) and molecularly characterized the identified strains. Fifty-four out of 666 (8.1%) animals were amdoparvovirus-positive. Infection rate was the highest in American mink (34/47, 72.3%), followed by foxes (Arctic and red foxes, 13/311, 4.2%), lynx (2/58, 3.5%), and American martens (5/156, 3.4%). No virus was detected in samples from 87 coyotes and 17 ermines. Viruses from Newfoundland were classified as Aleutian mink disease virus (AMDV). Mink harvested near AMDV-affected fur farms had higher prevalence (24/24, 100%) than other mink (10/23, 43.5%; P < 0.001) and their viruses were phylogenetically closely related to those from farms, while most viruses from other mink were in other clades. Strains from three foxes and two lynx were highly related to mink strains. This proves that farms disperse AMDV that subsequently spreads among wild mink (maintenance host) and transmits to other spillover carnivore hosts. In Labrador two novel viruses were identified, Labrador amdoparvovirus 1 (LaAV-1) found in foxes (9/261, 3.5%) and martens (5/156, 3.4%), and LaAV-2 found in one fox (0.4%). LaAV-1 fulfills all requirements to be classified as a novel species. LaAV-1 was most similar to viruses of mink and skunks (AMDV and skunk amdoparvovirus (SKAV)) while LaAV-2 was more closely related to other viruses infecting canids. LaAV-1 capsid proteins were almost indistinguishable from those of AMDV in some regions, suggesting that LaAV-1 could be a virus of mustelids that can infect foxes. While intensive farming practices provide occasions for inter-species transmission in farms, niche overlap or predation could explain cross-species transmission in the wild, but competition among sympatric species reduces the chances of direct contacts, making this an infrequent event. Pan-amdoparvovirus detection methods in wide epidemiological investigations can play a crucial role in defining amdoparvoviral ecology and evolution and discovering novel viruses.

Mortality of Little Brown Bats ( Myotis lucifugus carissima) Naturally Exposed to Microcystin-LR.

We describe a die-off of little brown bats ( Myotis lucifugus carissima) associated with acute intoxication with microcystin-LR in 2016 at Scofield Reservoir in Utah, US. High levels of this cyanotoxin in water from the reservoir and gastrointestinal content of bats supported this diagnosis.

Conceptualization and Assessment of Hypersexual Disorder: A Systematic Review of the Literature.

INTRODUCTION: Despite the rejection of hypersexual disorder (HD) as a new diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), clinical and research interest in HD continues. AIM: To systematically review the existing scientific literature on the conceptualization and assessment of HD and out-of-control sexual behavior. METHODS: Studies were identified from PsychInfo, PubMed, JSTOR, Google Scholar, and Scholar's Portal using an exhaustive list of key terms. Of 299 total articles identified and screened, 252 were excluded, and 47 are included in this review. MAIN OUTCOME MEASURES: To review two categories of articles: HD conceptualization and HD psychometric assessment. RESULTS: First, results of the review of theoretical conceptualizations of HD reflected a large proportion of the peer-reviewed literature devoted to discussing conceptualizations of HD without reaching consensus. Second, results of the review of HD psychometric assessments were analyzed using Hunsley and Mash's (2008) criteria to evaluate psychometric adequacy of evidence-based assessment measurements. The six most researched measurements of HD were evaluated, including the Hypersexual Disorder Screening Inventory, the Hypersexual Behavior Inventory, the Sexual Compulsivity Scale, the Sexual Addiction Screening Test, the Sexual Addiction Screening Test-Revised, and the Compulsive Sexual Behavior Inventory. Psychometric properties of the scales are reviewed, evaluated, and discussed. CONCLUSION: The Hypersexual Disorder Screening Inventory, the measurement proposed for the clinical screening of HD by the DSM-5 workgroup, currently has the strongest psychometric support. Future research and clinical directions are discussed in light of findings after the literature review and synthesis. Montgomery-Graham S. Conceptualization and Assessment of Hypersexual Disorder: A Systematic Review of the Literature. Sex Med Rev 2017;5:146-162.

Epidemiology and molecular characterization of protoparvoviruses infecting wild raccoons (Procyon lotor) in British Columbia, Canada.

Feline panleukopenia virus (FPV) and canine parvovirus 2 (CPV-2) belong to the species Carnivore protoparvovirus 1. While FPV has been endemic in cats for many years, CPV-2 emerged at the end of the 1970s and 3 antigenic variants (CPV-2a, b and c) are currently circulating in domestic and wild animals. Although raccoons played a fundamental role in the emergence of CPV-2a in dogs, knowledge about protoparvoviruses in these animals is still limited. We investigated 72 raccoons found dead or injured in southern British Columbia (BC), Canada, between 2009 and 2017. Among the 49 protoparvovirus-positive (66%) animals, 39 (80%) exhibited enteritis. Approximately 21% were FPV-positive and these were from Vancouver Island, while 79% were CPV-positive and found on the BC mainland, suggesting geographic separation of strains. Notably, one CPV-positive individual was FPV-vaccinated. The co-circulation of multiple FPV strains was observed, while the CPV-2 strain were all classified as CPV-2a, located in one unique clade, and likely originated from a single introduction. All BC CPV-2 sequences possessed a VP2-305His and therefore could represent one of the intermediate viruses that facilitated the emergence of CPV-2a in dogs. Like other raccoon viruses, all BC CPV-2 sequences possessed a VP2-300Asp but, differently, possessed a VP2-301Ala. Finally, two unique amino acid substitutions were identified in the NS1 of FPV (His554Gln and Gly573Cys). To our knowledge, this is the first molecular characterization of protoparvoviruses in wildlife from this region of North America and more studies are needed to elucidate the distribution of these viruses in wildlife outside the USA.

An automated method to assay locomotor activity in third instar Drosophila melanogaster larvae.

INTRODUCTION: The purpose of these studies was to describe a novel application of an automated data acquisition/data reduction system, DanioVision™ by Noldus. DanioVision™ has the ability to detect changes in locomotor activity in third instar Drosophila melanogaster larvae. The noncompetitive GABAA receptor antagonist picrotoxin (PTX), was used as a pharmacologic agent to decrease locomotor activity. METHODS: Two strains of Drosophila were used in these studies; wild-type flies and flies with a mutation in the Rdl gene (Rdl(MD-RR)). Rdl(MD-RR)Drosophila are naturally occurring mutants that express an aberrant form of the GABAA receptor, which has a lower affinity for PTX, but not GABA itself. Larvae, extracted from food in 20% sucrose, were randomly placed into vials containing vehicle or PTX (0.03-3mM). After incubation of 2-24h, individual larvae were put in each well of a 6-well culture plate previously coated with 2% agar, the plate was then placed in the DanioVision™ apparatus. The activity of individual larva was recorded for 5 min, digitized and analyzed using Ethovision® XT software. RESULTS: Incubation of third instar wild-type larvae in 1mM PTX for 4 or 24h decreased activity; whereas, a 2h incubation in PTX was without effect. PTX caused a concentration-dependent decrease in activity as demonstrated by consistently reduced locomotor activity with 1.0 and 3.0mM: 0.3mM resulted in variable decreases in locomotor activity and 0.03 mM yielded no effect. By contrast, PTX did not affect activity in Rdl(MD-RR) larvae even at the highest concentration, 3.0mM. DISCUSSION: Using an automated data acquisition system, it was found that PTX decreases activity in third instar Drosophila larvae due to a selective blockade of the GABAA receptor. The method will reduce the likelihood of human error and bias, as well as increase the speed and ease of data collection and analysis.

Sperm defects in mice lacking a functional Niemann-Pick C1 protein.

The Niemann-Pick C1 (NPC1) gene encodes for a multiple membrane spanning protein, which regulates the trafficking of low-density lipoprotein-mediated endocytosed cholesterol. Mutation of the human NPC1 gene causes Niemann-Pick type C (NPC) disease. The Npc1(NIH) mice, a model of human NPC disease, bear a spontaneous mutation of the Npc1 gene, and are infertile. In this study, we have performed sperm analysis to search for the cause of male infertility in the Npc1(NIH) mouse. The number of cauda sperms in Npc1(-/-) mice was decreased roughly three-and-half-fold of that in wild-type mice. The decreased sperm number in Npc1(-/-) mice is due, at least in part, to partial arrest of spermatogenesis in the testes, as revealed by histological analysis. Compared to wild-type sperm, Npc1(-/-) sperm displayed a high frequency of morphological abnormalities, including tailless heads and aberrant heads. In the in vitro fertilization (IVF) assay using cumulus-intact eggs, Npc1(-/-) sperm failed to produce two-cell embryos. In the IVF assay where zona-free eggs were used, Npc1(-/-) sperm bound normally but could not fuse with the egg. Further analysis indicated that Npc1(-/-) sperms are drastically impaired in the binding to the egg zona pellucida, only 14% of the level of wild-type sperm. Moreover, on Npc1(-/-) cauda sperm, one-third of the total cyritestin protein was not proteolytically processed, while fertilin beta was processed normally. Taken together, these results demonstrate that there are multiple defects in sperms from mice lacking a functional NPC1 protein, and these observed sperm defects may result in sterility.