Diversity and host specificity of Borrelia burgdorferi's outer surface protein C (ospC) alleles in synanthropic mammals, with a notable ospC allele U absence from mixed infections.

Interactions among pathogen genotypes that vary in host specificity may affect overall transmission dynamics in multi-host systems. Borrelia burgdorferi, a bacterium that causes Lyme disease, is typically transmitted among wildlife by Ixodes ticks. Despite the existence of many alleles of B. burgdorferi's sensu stricto outer surface protein C (ospC) gene, most human infections are caused by a small number of ospC alleles ["human infectious alleles" (HIAs)], suggesting variation in host specificity associated with ospC. To characterize the wildlife host association of B. burgdorferi's ospC alleles, we used metagenomics to sequence ospC alleles from 68 infected individuals belonging to eight mammalian species trapped at three sites in suburban New Brunswick, New Jersey (USA). We found that multiple allele ("mixed") infections were common. HIAs were most common in mice (Peromyscus spp.) and only one HIA was detected at a site where mice were rarely captured. ospC allele U was exclusively found in chipmunks (Tamias striatus), and although a significant number of different alleles were observed in chipmunks, including HIAs, allele U never co-occurred with other alleles in mixed infections. Our results suggest that allele U may be excluding other alleles, thereby reducing the capacity of chipmunks to act as reservoirs for HIAs.

Cortistatin as a Novel Multimodal Therapy for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a complex disorder characterized by the impairment of the dopaminergic nigrostriatal system. PD has duplicated its global burden in the last few years, becoming the leading neurological disability worldwide. Therefore, there is an urgent need to develop innovative approaches that target multifactorial underlying causes to potentially prevent or limit disease progression. Accumulating evidence suggests that neuroinflammatory responses may play a pivotal role in the neurodegenerative processes that occur during the development of PD. Cortistatin is a neuropeptide that has shown potent anti-inflammatory and immunoregulatory effects in preclinical models of autoimmune and neuroinflammatory disorders. The goal of this study was to explore the therapeutic potential of cortistatin in a well-established preclinical mouse model of PD induced by acute exposure to the neurotoxin 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine (MPTP). We observed that treatment with cortistatin mitigated the MPTP-induced loss of dopaminergic neurons in the substantia nigra and their connections to the striatum. Consequently, cortistatin administration improved the locomotor activity of animals intoxicated with MPTP. In addition, cortistatin diminished the presence and activation of glial cells in the affected brain regions of MPTP-treated mice, reduced the production of immune mediators, and promoted the expression of neurotrophic factors in the striatum. In an in vitro model of PD, treatment with cortistatin also demonstrated a reduction in the cell death of dopaminergic neurons that were exposed to the neurotoxin. Taken together, these findings suggest that cortistatin could emerge as a promising new therapeutic agent that combines anti-inflammatory and neuroprotective properties to regulate the progression of PD at multiple levels.

Cortistatin deficiency reveals a dysfunctional brain endothelium with impaired gene pathways, exacerbated immune activation, and disrupted barrier integrity.

BACKGROUND: Brain activity governing cognition and behaviour depends on the fine-tuned microenvironment provided by a tightly controlled blood-brain barrier (BBB). Brain endothelium dysfunction is a hallmark of BBB breakdown in most neurodegenerative/neuroinflammatory disorders. Therefore, the identification of new endogenous molecules involved in endothelial cell disruption is essential to better understand BBB dynamics. Cortistatin is a neuroimmune mediator with anti-inflammatory and neuroprotective properties that exerts beneficial effects on the peripheral endothelium. However, its role in the healthy and injured brain endothelium remains to be evaluated. Herein, this study aimed to investigate the potential function of endogenous and therapeutic cortistatin in regulating brain endothelium dysfunction in a neuroinflammatory/neurodegenerative environment. METHODS: Wild-type and cortistatin-deficient murine brain endothelium and human cells were used for an in vitro barrier model, where a simulated ischemia-like environment was mimicked. Endothelial permeability, junction integrity, and immune response in the presence and absence of cortistatin were evaluated using different size tracers, immunofluorescence labelling, qPCR, and ELISA. Cortistatin molecular mechanisms underlying brain endothelium dynamics were assessed by RNA-sequencing analysis. Cortistatin role in BBB leakage was evaluated in adult mice injected with LPS. RESULTS: The endogenous lack of cortistatin predisposes endothelium weakening with increased permeability, tight-junctions breakdown, and dysregulated immune activity. We demonstrated that both damaged and uninjured brain endothelial cells isolated from cortistatin-deficient mice, present a dysregulated and/or deactivated genetic programming. These pathways, related to basic physiology but also crucial for the repair after damage (e.g., extracellular matrix remodelling, angiogenesis, response to oxygen, signalling, and metabolites transport), are dysfunctional and make brain endothelial barrier lacking cortistatin non-responsive to any further injury. Treatment with cortistatin reversed in vitro hyperpermeability, tight-junctions disruption, inflammatory response, and reduced in vivo BBB leakage. CONCLUSIONS: The neuropeptide cortistatin has a key role in the physiology of the cerebral microvasculature and its presence is crucial to develop a canonical balanced response to damage. The reparative effects of cortistatin in the brain endothelium were accompanied by the modulation of the immune function and the rescue of barrier integrity. Cortistatin-based therapies could emerge as a novel pleiotropic strategy to ameliorate neuroinflammatory/neurodegenerative disorders with disrupted BBB.

Multiple piroplasm parasites (Apicomplexa: Piroplasmida) in northeastern populations of the invasive Asian longhorned tick, Haemaphysalis longicornis Neumann (Ixodida: Ixodidae), in the United States.

Piroplasms, which include the agents of cattle fever and human and dog babesiosis, are a diverse group of blood parasites of significant veterinary and medical importance. The invasive Asian longhorned tick, Haemaphysalis longicornis, is a known vector of piroplasms in its native range in East Asia and invasive range in Australasia. In the USA, H. longicornis has been associated with Theileria orientalis Ikeda outbreaks that caused cattle mortality. To survey invasive populations of H. longicornis for a broad range of piroplasms, 667 questing H. longicornis collected in 2021 from 3 sites in New Jersey, USA, were tested with generalist piroplasm primers targeting the 18S small subunit rRNA (395­515 bp, depending on species) and the cytochrome b oxidase loci (1009 bp). Sequences matching Theileria cervi type F (1 adult, 5 nymphs), an unidentified Theileria species (in 1 nymph), an undescribed Babesia sensu stricto ('true' Babesia, 2 adults, 2 nymphs), a Babesia sp. Coco (also a 'true Babesia', 1 adult, 1 nymph), as well as Babesia microti S837 (1 adult, 4 nymphs) were recovered. Babesia microti S837 is closely related to the human pathogen B. microti US-type. Additionally, a 132 bp sequence matching the cytochrome b locus of deer, Odocoileus virginanus, was obtained from 2 partially engorged H. longicornis. The diverse assemblage of piroplasms now associated with H. longicornis in the USA spans 3 clades in the piroplasm phylogeny and raises concerns of transmission amplification of veterinary pathogens as well as spillover of pathogens from wildlife to humans.

The first alongside midwifery unit in Spain: A retrospective cohort study of maternal and neonatal outcomes.

BACKGROUND: Midwife-led units have been shown to be safer and reduce interventions for women at low risk of complications at birth. In 2017, the first alongside birth center was opened in Spain. The aim of this study was to compare outcomes for women with uncomplicated pregnancies giving birth in the Midwife-led unit (MLU) and in the Obstetric unit (OU) of the same hospital. METHODS: Retrospective cohort study comparing birth outcomes between low-risk women, depending on their planned place of birth. Data were analyzed with an intention-to-treat approach for women that gave birth between January 2018 and December 2020. RESULTS: A total of 878 women were included in the study, 255 women chose to give birth in the MLU and 623 in the OU. Findings showed that women in the MLU were more likely to have a vaginal birth (91.4%) than in the OU (83.8%) (aOR 2.98 [95%CI 1.62-5.47]), less likely to have an instrumental delivery, 3.9% versus 11.2% (0.25 [0.11-0.55]), to use epidural analgesia, 19.6% versus 77.9% (0.15 [0.04-0.17]) and to have an episiotomy, 7.4% versus 15.4% (0.27 [0.14-0.53]). There were no differences in rates of postpartum hemorrhage, retained placenta, or adverse neonatal outcomes. Intrapartum and postpartum transfer rates from the MLU to the OU were 21.1% and 2.4%, respectively. CONCLUSIONS: The high rate of obstetric interventions in Spain could be reduced by implementing midwife-led units across the whole system, without an increase in maternal or neonatal complications.

Novel Therapeutic Opportunities for Neurodegenerative Diseases with Mesenchymal Stem Cells: The Focus on Modulating the Blood-Brain Barrier.

Neurodegenerative disorders encompass a broad spectrum of profoundly disabling situations that impact millions of individuals globally. While their underlying causes and pathophysiology display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, is a common feature among them. Consequently, targeting the BBB has emerged as an innovative therapeutic strategy for addressing neurological disorders. Within this review, we not only explore the neuroprotective, neurotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will investigate the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological conditions like Alzheimer's disease, Parkinson's disease, and stroke, as well as immune-mediated diseases such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological contexts.

Risk prediction of CMV reactivation after allogeneic stem cell transplantation using five non-HLA immunogenetic polymorphisms.

Despite advances in the understanding of the pathophysiology of cytomegalovirus (CMV) infection, it remains as one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to determine the genotype of cytokines and chemokines in donor and recipient and their association with CMV reactivation. Eighty-five patients receiving an allo-HSCT from an HLA-identical sibling donor were included in the study. Fifty genes were selected for their potential role in the pathogenesis of CMV infection. CMV DNAemia was evaluated until day 180 after allo-HSCT. CMV reactivation was observed in 51/85 (60%) patients. Of the 213 genetic variants selected, 11 polymorphisms in 7 different genes (CXCL12, IL12A, KIR3DL1, TGFB2, TNF, IL1RN, and CD48) were associated with development or protection from CMV reactivation. A predictive model using five of such polymorphisms (CXCL12 rs2839695, IL12A rs7615589, KIR3DL1 rs4554639, TGFB2 rs5781034 for the recipient and CD48 rs2295615 for the donor) together with the development of acute GVHD grade III/IV improved risk stratification of CMV reactivation. In conclusion, the data presented suggest that the screening of five polymorphisms in recipient and donor pre-transplantation could help to predict the individual risk of CMV infection development after HLA-identical allo-HSCT.

Cost-Consequence Analysis of Single-Dose Dalbavancin Versus Standard of Care for the Treatment of Acute Bacterial Skin and Skin Structure Infections in a Multisite Healthcare System.

BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSIs) are common infectious diseases that cause a significant economic burden on the healthcare system. This study aimed to compare the cost-effectiveness of dalbavancin vs standard of care (SoC) in the treatment of ABSSSI in a community-based healthcare system. METHODS: This was a retrospective study of adult patients with ABSSSI treated with dalbavancin or SoC during a 27-month period. Patients were matched based on age and body mass index. The primary outcome was average net cost of care to the healthcare system per patient, calculated as the difference between reimbursement payments and the total cost to provide care to the patient. The secondary outcome was proportion of cases successfully treated, defined as no ABSSSI-related readmission within 30 days after the initiation of treatment. RESULTS: Of the 418 matched patients, 209 received SoC and 209 received dalbavancin. The average total cost of care per patient was greater with dalbavancin vs SoC ($4770 vs $2709, P < .0001). The average reimbursement per patient was $3084 with dalbavancin vs $2633 SoC (P = .527). The net cost, calculated as revenue minus total cost, was $1685 with dalbavancin vs $75 with SoC (P = .013). The overall treatment success rate was 74% with dalbavancin vs 85% with SoC (P = .004). CONCLUSIONS: Dalbavancin was more costly than SoC for the treatment of ABSSSI, with a higher 30-day readmission rate. Dalbavancin does not offer an economic or efficacy advantage.

Body composition and body mass index in Duchenne muscular dystrophy: Role of dietary intake.

INTRODUCTION: In Duchenne muscular dystrophy (DMD) muscle is replaced by adipose tissue. The role of dietary intake (DI) in DMD has not been evaluated. In this study we examined body composition, body mass index (BMI), and adequacy of DI in patients with DMD and evaluated the influence of DI on body composition. METHODS: Patients (n = 101; age 3-18 years; BMI 11.8-29.5 kg/m2 ) completed a dietary recall to determine DI and then underwent dual-energy X-ray absorptiometry to determine body composition. RESULTS: Preschool-age and school-age boys with DMD had high total energy intake. Protein intake per kilogram exceeded recommendations. As age increased, the percentage of boys with abnormal BMI and fat mass increased, while lean mass decreased. Dietary intake did not predict body fat or lean mass. DISCUSSION: Age-dependent changes in BD in boys with DMD may be due to endogenous metabolic factors related to the underlying disease process and to disease-related mobility impairments. Muscle Nerve 59:295-302, 2019.

Seroprevalence of HPV serotypes 6, 11, 16 and 18 in unvaccinated children from Mexico City.

Data regarding humoral immunity against HPV infection are scarce. Most analyses focus on the identification of viruses on mucous membranes and primarily refer to women of reproductive age. The aim of this work was to estimate the seroprevalence of antibodies against HPV serotypes 6, 11, 16 and 18 among unvaccinated boys living in Mexico City. A cross-sectional study of 257 male students from 48 public primary schools in Mexico City, whose ages fluctuated between 9 and 14 years, was carried out. Immunological status was assessed by applying the competitive Luminex Immunoassay of HPV (cLIA). Among the study population, we initially found that 38.52% (n = 99) of the children tested positive against one or more of the HPV 6, 11, 16 and/or 18 serotypes. The most commonly found serotype was isolated HPV 18 or in combination with other serotypes (22% and 31%, respectively), followed by HPV 6 with frequencies of 4.7% and 11%, respectively; however, lower frequencies were estimated for HPV 16 (2%; 6%) and isolated HPV 11, 4%. If a second set of cut-off points for seropositivity is applied, the overall prevalence for any serotype is reduced to 15.2%. As it appears that a significant sector of the study population has had basal contact with an HPV serotype, we recommend considering the possibility of vaccination against HPV at earlier ages.

Incidence of Acute Kidney Injury in Intermittent Versus Continuous Infusion of Polymyxin B in Hospitalized Patients.

Background: Studies evaluating the risk of developing acute kidney injury (AKI) with different dosing strategies of polymyxin B are limited. Objectives: To compare the incidence of AKI in patients treated with intermittent versus continuous polymyxin B therapy. Secondary objectives included time to onset of AKI, hospital length of stay (LOS), and all-cause hospital mortality. Variables associated with an increased risk of AKI were evaluated. Methods: A retrospective record review was conducted at a single center in Puerto Rico. Adult patients (≥18 years old) treated with polymyxin B (first course) for at least 48 hours from 2013-2015 were evaluated. Patients with a creatinine clearance <10 mL/min and/or on renal replacement were excluded. Results: A total of 69 patients were included: 42 in the continuous infusion and 27 in the intermittent dosing group. Incidence of AKI was not significantly different between the groups (intermittent 41% vs continuous 31%, P = 0.4). No difference was found in the onset of nephrotoxicity, hospital LOS, or all-cause hospital mortality. Variables associated with increased risk of AKI were baseline serum creatinine, age, and intensive care unit admission. Patients with a body mass index (BMI) >25 kg/m2 on polymyxin B via continuous infusion had a significantly higher cumulative incidence of AKI (P = 0.016). Conclusion and Relevance: No difference in the risk of polymyxin B nephrotoxicity was found between intermittent and continuous infusion administration. Administration of polymyxin B via a continuous infusion may result in a higher risk of AKI in patients with a BMI >25 kg/m2.

Familial low phospholipid-associated cholelithiasis resulting from an autosomal dominant ABCB4 mutation.

Low phospholipid-associated cholelithiasis (LPAC) syndrome is characterized by early intrahepatic and symptomatic gallstones leading to cholangitis, acute pancreatitis and biliary colic. It has been associated with loss of function variants in the ABCB4 gene. ABCB4 encodes for a phospholipid translocator at the canalicular membrane of the hepatocyte, which "flops" phosphatidylcholine into bile. The autosomal recessive form is the most common, although autosomal dominant forms have also been described. We report the first family with autosomal dominant LPAC syndrome due to heterozygosity of the loss of function mutation c.2932T>C in ABCB4, identified by targeted next generation sequencing.

Donor Cell-Derived Hematologic Neoplasms after Hematopoietic Stem Cell Transplantation: A Systematic Review.

Development of de novo hematologic malignancies in donor cells after allogeneic stem cell transplantation (allo-SCT) provides a useful in vivo model to study the process of leukemogenesis. A systematic analysis of the cases reported in the literature was performed to identify risk factors and mechanisms involved in the pathogenesis of donor cell-derived hematologic neoplasms (DCHN) and leukemogenic transformation. Relevant data were extracted from 137 cases. Cases of DCHN show a wide heterogeneity with regard to recipient/donor age, sex mismatch, and conditioning regimen. Some characteristics, such as the type of primary disease, the type of hematologic malignancy of the DCHN, and the stem cell source used in the transplant procedure, differ from those expected. Mechanisms involved in the pathogenesis of DCHN are complex, and several hypotheses have been proposed, such as pre-existing hematologic neoplasms or premalignant clones in the donor, decreased immune surveillance, and damage to bone marrow microenvironment in the recipient. Most likely several if not all these mechanisms play a role in DCHN development. Novel approaches, such as next-generation sequencing to study consecutive samples after allo-SCT in these patients, appear to be promising to decipher the mechanisms of leukemogenesis.

Effect of intravenous and intracoronary melatonin as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: Results of the Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty trial.

The MARIA randomized trial evaluated the efficacy and safety of melatonin for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI). This was a prespecified interim analysis. A total of 146 patients presenting with STEMI within 6 hours of chest pain onset were randomized to receive intravenous and intracoronary melatonin (n=73) or placebo (n=73) during primary percutaneous coronary intervention (PPCI). Primary endpoint was myocardial infarct size as assessed by magnetic resonance imaging (MRI) at 6 ± 2 days. Secondary endpoints were changes in left ventricular volumes and ejection fraction (LVEF) at 130 ± 10 days post-PPCI and adverse events during the first year. No significant differences in baseline characteristics were observed between groups. MRI was performed in 108 patients (86.4%). Myocardial infarct size by MRI evaluated 6 ± 2 days post-PPCI, did not differ between melatonin and placebo groups (P=.63). Infarct size assessed by MRI at 130 ± 10 days post-PPCI, performed in 91 patients (72.8%), did not show statistically significant differences between groups (P=.27). The recovery of LVEF from 6 ± 2 to 130 ± 10 days post-PPCI was greater in the placebo group (60.0 ± 10.4% vs 53.1 ± 12.5%, P=.008). Both left ventricular end-diastolic and end-systolic volumes were lower in the placebo group (P=.01). The incidence of adverse events at 1 year was comparable in both groups (P=.150). Thus, in a nonrestricted STEMI population, intravenous and intracoronary melatonin was not associated with a reduction in infarct size and has an unfavourable effect on the ventricular volumes and LVEF evolution. Likewise, there is lack of toxicity of melatonin with the doses used.

Influence of environmental temperature and humidity on questing ticks in central Spain.

Ticks are important ectoparasites and vectors of the pathogens that cause disease in humans and animals. At a natural reserve in Ciudad Real (Spain), an uncontrollable infestation of wild animals with Hyalomma lusitanicum (Koch) has been reported by some game reserve owners. Many questions about distribution, abundance, and phenology of this tick in this area remain unanswered. The aim of this study was to determine if temperature and relative humidity affect the questing tick's activity in four species of ticks in a meso-Mediterranean area, especially that of H. lusitanicum. Data for tick populations in six selected sampling sites every month, between January 2007 and December 2013 were used. Temperature and humidity values (ground and environmental) were recorded. The sampling effort, the similarity between sites, and the phenology of the species were analyzed. Effects of environmental variables on tick's activity were assessed by general linear models (GLM) whereas the comparative importance of variables was measured by hierarchical variance partitioning. Hyalomma lusitanicum represented 96.3% of the four species of ticks collected. Spring and summer months presented a higher activity of ticks, than autumn and winter months. In general, humidity variables were negatively related to the activity of ticks, whereas temperature variables were positively related. Our results suggest that the highest activity in the area is produced by biological characteristics of H. lusitanicum; being temperature and humidity the most important environmental factors influencing the abundance of this species in the region.

Cytogenetic and dosimetric effects of (131)I in patients with differentiated thyroid carcinoma: comparison between stimulation with rhTSH and thyroid hormone withdrawal treatments.

A study directed to the cytogenetic and dosimetric aspects of radionuclides of medical interest is very valuable, both for an accurate evaluation of the dose received by the patients, and consequently of the genetic damage, and for the optimization of therapeutic strategies. Cytogenetic and dosimetric effects of (131)I in lymphocytes of thyroidectomized differentiated thyroid cancer (DTC) patients were evaluated through chromosome aberration (CA) technique: Euthyroid patients submitted to recombinant human thyroid-stimulating hormone (rhTSH) therapy (group A) were compared with hypothyroid patients left without levothyroxine treatment (group B). CA analysis was carried out prior to and 24 h, 1 week, 1 month and 1 year after radioiodine administration (4995-7030 MBq) in both groups. An activity-response curve of (131)I (0.074-0.740 MBq/mL) was elaborated, comparing dicentric chromosomes in vivo and in vitro in order to estimate the absorbed dose through Monte Carlo simulations. In general, radioiodine therapy induced a higher total CA rate in hypothyroid patients as compared to euthyroid patients. The frequencies of dicentrics obtained in DTC patients 24 h after treatment were equivalent to those induced in vitro (0.2903 ± 0.1005 MBq/mL in group A and 0.2391 ± 0.1019 MBq/mL in group B), corresponding to absorbed doses of 0.65 ± 0.23 Gy and 0.53 ± 0.23 Gy, respectively. The effect on lymphocytes of internal radiation induced by (131)I therapy is minimal when based on the frequencies of CA 1 year after the treatment, maintaining a higher quality of life for DTC patients receiving rhTSH-aided therapy.

Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles.

In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particles (VLPs). Our results further confirmed the differential antigenic properties exhibited by RHDV and RHDV2, highlighting the need of using RHDV2-specific diagnostic assays to monitor the spread of this new virus.

The impact of frailty in older patients with non-ischaemic cardiomyopathy after implantation of cardiac resynchronization therapy defibrillator.

AIMS: Frailty status impacts the prognosis in older patients with heart disease. However, frailty status impact is unknown in patients with non-ischaemic cardiomyopathy after cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Functional measures of baseline frailty and clinical data were collected for all patients with non-ischaemic cardiomyopathy before CRT defibrillator (CRT-D) implantation. The level of frailty was assessed using the Fried and Walston definition. Cox proportional hazard regression models were used to examine the association between baseline frailty and decompensated heart failure (HF) at the 12 months follow-up. The cohort study consisted of 102 patients with a mean age of 73 ± 4 years, 53% of which were male patients. Twenty-nine patients (28%) were classified as frail before CRT-D implantation. Twenty-seven patients experienced decompensated HF after CRT-D implantation at the 12-month follow-up. In the non-frail group, 12 of 73 patients (16.4%) experienced episodes of decompensated HF. In contrast, 15 of 29 (55.6%) frail patients experienced higher proportions of decompensated HF (P < 0.001). Patients who were frail (hazard ratio 4.55, 95% confidence interval 1.726-12.013) were at increased risk for the decompensated HF (P for trend = 0.002) compared with those who were not frail. CONCLUSION: Frailty is a strong predictor of adverse post-implantation outcome in patients with non-ischaemic cardiomyopathy undergoing CRT-D.

Effect of short photoperiod on the development of Haemaphysalis longicornis (Ixodida: Ixodidae).

The invasive tick, Haemaphysalis longicornis Neumann, is now present across most of the mid-Atlantic States in the eastern United States. This tick ends its seasonal activity in late October to early November, with larvae being the last life-stage observed questing. Previous research has revealed that the activity of H. longicornis is influenced by photoperiod: short daylight lengths trigger diapause in nymphs, marking it as the primary overwintering stage. However, whether engorged larvae can enter diapause or are affected by short daylight is unclear. In this study, we tested in the laboratory whether the photoperiod Affects the development of H. longicornis engorged larvae and engorged nymphs under constant temperature and humidity. The results showed that engorged larvae molted significantly faster (3 days faster) when the photoperiod was 9 h of light as opposed to 14 h. In contrast, changes in the photoperiod did not affect the molting of engorged nymphs. Our results demonstrate that engorged larvae respond to short daylight length, by molting faster. These results suggest that engorged larvae are unlikely to overwinter under field conditions and support the expectation that nymphs are the primary overwintering stage for H. longicornis in the United States.