Does proximity to a fertility centre increase the chance of achieving pregnancy in Northeastern Ontario?

INTRODUCTION: Northern Ontario has a population of approximately 800,000 people distributed over 806,707 km2. Before 2018, the only fertility treatment centre in Northern Ontario was located in Thunder Bay; many patients travelled south for care. In 2018, the Northeastern Ontario Women's Health Network (NEOWHN) opened in Sudbury, providing fertility treatments to people living in Northeastern Ontario. The goal of this study was to determine if proximity to this new fertility centre increases one's chance of achieving pregnancy when undergoing fertility treatment. Secondary outcomes included the quantity and types of fertility investigations and treatments completed by patients. MATERIALS AND METHODS: A retrospective chart review was performed for all patients seeking fertility treatment at NEOWHN between January 2019 and December 2020. Traveling >100 km to access healthcare was considered to be a clinically significant determinant of health. RESULTS: Seven hundred and 5 patients were seen in consultation for fertility services at NEOWHN during the study period. One hundred eighty-one of 478 (37.9%) patients living <100 km from NEOWHN achieved pregnancy compared to 39 of 227 (17.2%) patients living >100 km from NEOWHN (P < 0.01). CONCLUSION: Living in proximity (<100 km) to NEOWHN increased the likelihood that individuals in Northeastern Ontario would seek fertility services and would achieve pregnancy. Financial constraints and inaccessibility likely play a role in this, but further studies are needed to explain this difference. INTRODUCTION: Le Nord de l'Ontario compte une population d'environ 800,000 personnes réparties sur 806,707 km2. Avant 2018, le seul centre de traitement de la fertilité du Nord de l'Ontario était situé à Thunder Bay; de nombreux patients SE rendaient dans le sud pour recevoir des soins. En 2018, le Northeastern Ontario Women's Health Network (NEOWHN-le Réseau de santé des femmes du Nord-Est de l'Ontario) a ouvert ses portes à Sudbury, offrant des traitements de fertilité aux personnes vivant dans le Nord-Est de l'Ontario. L'objectif de cette étude était de déterminer si la proximité de ce nouveau centre de fertilité augmente les chances d'obtenir une grossesse lors d'un traitement de fertilité. Les résultats secondaires comprenaient la quantité et les types d'examens et de traitements de fertilité effectués par les patients. MTHODES: Une étude rétrospective des dossiers a été réalisée pour tous les patients cherchant un traitement de fertilité au NEOWHN entre janvier 2019 et décembre 2020. Le fait de voyager >100 km pour accéder aux soins de santé a été considéré comme un déterminant de la santé cliniquement significatif. RSULTATS: Seven hundred and 5 patients ont été vus en consultation pour des services de fertilité au NEOWHN pendant la période d'étude. One hundred eighty-one des 478 (37.9%) patientes vivant à moins de 100 km du NEOWHN ont obtenu une grossesse, contre 39 des 227 (17.2%) patientes vivant à plus de 100 km du NEOWHN (P < 0.01). CONCLUSION: Le fait de vivre à proximité (<100 km) du NEOWHN augmente la probabilité que les habitants du Nord-Est de l'Ontario aient recours à des services de fertilité et obtiennent une grossesse. Les contraintes financières et l'inaccessibilité jouent probablement un rôle à cet égard, mais d'autres études sont nécessaires pour expliquer cette différence.

Epidemiology and risk factors for varicella zoster virus reactivation in heart transplant recipients.

Heart transplant (HT) recipients are at higher risk of varicella zoster virus (VZV) reactivation. Risk factors for VZV reactivation are currently not well defined, impeding the ability to design and implement strategies to minimize the burden of this illness in this population. Automated data extraction tools were used to retrieve data from the electronic health record (EHR) of all adult HT recipients at our center between 2010 and 2016. Information from the Organ Procurement and Transplantation Network Standard Analysis and Research Files was merged with the extracted data. Potential cases were manually reviewed and adjudicated using consensus definitions. Cumulative incidence and risk factors for VZV reactivation in HT recipients were assessed by the Kaplan-Meier method and Cox modeling, respectively. In 203 HT recipients, the cumulative incidence of VZV reactivation at 8-years post-transplantation was 26.4% (95% CI: 17.8-38.0). The median time to VZV reactivation was 2.1 years (IQR, 1.5-4.1). Half (14/28) of the cases experienced post-herpetic neuralgia (PHN). Post-transplant CMV infection (HR 9.05 [95% CI: 3.76-21.77) and post-transplant pulse-dose steroids (HR 3.19 [95% CI: 1.05-9.68]) were independently associated with a higher risk of VZV reactivation in multivariable modeling. Identification of risk factors will aid in the development of targeted preventive strategies.

Peptidoglycan Compositional Analysis of Enterococcus faecalis Biofilm by Stable Isotope Labeling by Amino Acids in a Bacterial Culture.

Peptidoglycan (PG) is a major component of the cell wall in Enterococcus faecalis. Accurate analysis of PG composition provides crucial insights into the bacterium's cellular functions and responses to external stimuli, but this analysis remains challenging because of various chemical modifications to PG-repeat subunits. We characterized changes to the PG composition of E. faecalis grown as planktonic bacteria and biofilm by developing "stable isotope labeling by amino acids in bacterial culture" (SILAB), optimized for bacterial cultures with incomplete amino acid labeling. This comparative analysis by mass spectrometry was performed by labeling E. faecalis in biofilm with heavy Lys (l-[13C6,2D9,15N2]Lys) and planktonic bacteria with natural abundance l-Lys, then mixing equal amounts of bacteria from each condition, and performing cell wall isolation and mutanolysin digestion necessary for liquid chromatography and mass spectrometry. An analytical method was developed to determine muropeptide abundances using correction factors to compensate for incomplete heavy Lys isotopic enrichment (98.33 ± 0.05%) and incorporation (83.23 ± 1.16%). Forty-seven pairs of PG fragment ions from isolated cell walls of planktonic and biofilm samples were selected for SILAB analysis. We found that the PG in biofilm showed an increased level of PG cross-linking, an increased level of N-deacetylation of GlcNAc, a decreased level of O-acetylation of MurNAc, and an increased number of stem modifications by d,d- and l,d-carboxypeptidases.

Boosting Social and Emotional Development In and Out of School.

(1) Illinois' state ESSA plan reflects the state's whole-child approach, adding references to the social, emotional and behavioral needs of students, along with high expectations for student achievement. (2) Massachusetts' state ESSA plan lists supporting socialemotional learning, health and safety as among the state's core educational strategies. (3) South Carolina's ESSA plan develops a framework identifying self-direction, perseverance, global perspective and interpersonal skills to be among the characteristics that every student should have when he or she graduates from high school.

Patients' Perspectives on the Impact of Genital Psoriasis: A Qualitative Study.

INTRODUCTION: Plaque psoriasis is a chronic skin disease where genital involvement is relatively common. Yet health care providers do not routinely evaluate psoriasis patients for genital involvement and patients do not readily initiate discussion of it. METHODS: A qualitative study of 20 US patients with dermatologist-confirmed genital psoriasis (GenPs) and self-reported moderate-to-severe GenPs at screening was conducted to identify key GenPs symptoms and their impacts on health-related quality of life (HRQoL). RESULTS: Patients had a mean age of 45 years, 55% were female, and patients had high rates of current/recent moderate-to-severe overall (65%) and genital (70%) psoriasis. Patients reported the following GenPs symptoms: genital itch (100%), discomfort (100%), redness (95%), stinging/burning (95%), pain (85%), and scaling (75%). Genital itching (40%) and stinging/burning (40%) were the most bothersome symptoms. Impacts on sexual health included impaired sexual experience during sexual activity (80%), worsening of symptoms after sexual activity (80%), decreased frequency of sexual activity (80%), avoidance of sexual relationships (75%), and reduced sexual desire (55%). Negative effects on sexual experience encompassed physical effects such as mechanical friction, cracking, and pain as well as psychosocial effects such as embarrassment and feeling stigmatized. Males reported a higher burden of symptoms and sexual impacts. Other HRQoL impacts were on mood/emotion (95%), physical activities (70%), daily activities (60%), and relationships with friends and family (45%). These impacts significantly affected daily activities. Physical activities were affected by symptoms and flares, and increased sweat and friction worsened symptoms. Patients reported daily practices to control outcomes. CONCLUSION: The high level of reported symptoms and sexual and nonsexual impacts reflects the potential burden of moderate-to-severe GenPs. GenPs can impact many facets of HRQoL and providers should evaluate their patients for the presence of genital psoriasis and its impact on their quality of life. FUNDING: Eli Lilly and Company.

Peptidoglycan O-acetylation increases in response to vancomycin treatment in vancomycin-resistant Enterococcus faecalis.

Vancomycin resistance is conferred upon vancomycin-resistant enterococci (VRE) through the replacement of peptidoglycan (PG) stem terminal d-Ala-d-Ala with d-Ala-d-Lac. The d-Ala-d-Lac incorporation can affect both the fitness and virulence of VRE. Here we comprehensively investigate the changes to PG composition in vancomycin-resistant Enterococcus faecalis following the growth in presence of vancomycin using liquid chromatography-mass spectrometry. Using high-resolution mass spectrometry, 104 unique muropeptides fragments were identified and the relative abundance of each fragment was accurately quantified by integrating the ion current of a selected ion using extracted-ion chromatogram. The analysis indicates reduced PG cross-linking, increased carboxypeptidase activities, increased N-deacetylation, and increased O-acetylation in VRE when grown in the presence of vancomycin. We found that O-acetylation preferentially occurred on muropeptides fragments with reduced cross-linking with a pentapeptide stem that terminated in d-Ala-d-Lac. These findings show that O-acetylation preferentially occurred in regions of the cell wall with reduced PG cross-linking on PG units that have stems terminating in d-Ala-d-Lac, serving as markers to prevent both the PG-stem modification by carboxypeptidases and the cell wall degradation by autolysins. Accurate quantitative PG composition analysis provided compositional insights into altered cell wall biosynthesis and modification processes in VRE that contribute to lysozyme resistance and enhanced virulence for VRE grown in the presence of vancomycin.

Released lipids regulate transient receptor potential channel (TRP)-dependent oral cancer pain.

BACKGROUND: Pain in the head neck area is an early symptom in oral cancer, supporting the hypothesis that cancer cells control the activities of surrounding nociceptors at the site of the tumor. Several reports implicate TRPV1 and TRPA1 in cancer pain, although there is a large gap in knowledge since the mechanisms for tumor-induced activation of these TRP receptors are unknown. Interestingly, TRP-active lipids such as linoleic acid, arachidonic acid, hydroxyoctadecadienoic acid and hydroxyeicosatetraenoic acid are significantly elevated in the saliva of oral cancer patients compared to normal patients, supporting a possible linkage between these lipids and oral cancer pain. We therefore hypothesize that oral squamous cell carcinomas release certain lipids that activate TRPV1 and/or TRPA1 on sensory neurons, contributing to the development of oral cancer pain. METHODS: Lipid extracts were made from conditioned media of three human oral squamous cell carcinoma (OSCC) cell lines as well as one normal human oral keratinocytes cell line. These were then injected intraplantarly into rat hindpaws to measure spontaneous nocifensive behavior, as well as thermal and mechanical allodynia. For interventional experiments, the animals were pretreated with AMG517 (TRPV1 antagonist) or HC030031 (TRPA1 antagonist) prior to extract injection. RESULTS: These studies demonstrate that lipids released from the three OSCC cell lines, but not the normal cell line, were capable of producing significant spontaneous nocifensive behaviors, as well as thermal and mechanical allodynia. Notably each of the cell lines produced a different magnitude of response for each of three behavioral assays. Importantly, pre-treatment with a TRPVI antagonist blocked lipid-mediated nocifensive and thermal hypersensitivity, but not mechanical hypersensitivity. In addition, pre-treatment with a TRPA1 antagonist only reversed thermal hypersensitivity without affecting lipid-induced nocifensive behavior or mechanical allodynia. CONCLUSIONS: These data reveal a novel mechanism for cancer pain and provide strong direction for future studies evaluating the cellular mechanism regulating the TRP-active lipids by OSCC tumors.

Probing peptide amphiphile self-assembly in blood serum.

There has been recent interest in designing smart diagnostic or therapeutic self-assembling peptide or polymeric materials that can selectively undergo morphological transitions to accumulate at a disease site in response to specific stimuli. Developing approaches to probe these self-assembly transitions in environments that accurately amalgamate the diverse plethora of proteins, biomolecules, and salts of blood is essential for creating systems that function in vivo. Here, we have developed a fluorescence anisotropy approach to probe the pH-dependent self-assembly transition of peptide amphiphile (PA) molecules that transform from spherical micelles at pH 7.4 to nanofibers under more acidic pH's in blood serum. By mixing small concentrations of a Ru(bipy)3(2+)-tagged PA with a Gd(DO3A)-tagged PA having the same lipid-peptide sequence, we showed that the pH dependence of self-assembly is minimally affected and can be monitored in mouse blood serum. These PA vehicles can be designed to transition from spherical micelles to nanofibers in the pH range 7.0-7.4 in pure serum. In contrast to the typical notion of serum albumin absorbing isolated surfactant molecules and disrupting self-assembly, our experiments showed that albumin does not bind these anionic PAs and instead promotes nanofibers due to a molecular crowding effect. Finally, we created a medium that replicates the transition pH in serum to within 0.08 pH units and allows probing self-assembly behavior using conventional spectroscopic techniques without conflicting protein signals, thus simplifying the development pathway from test tube to in vivo experimentation for stimuli-responsive materials.

Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats.

Current treatments for depression, including serotonin-specific reuptake inhibitors (SSRIs), are only partially effective, with a high incidence of residual symptoms, relapse, and treatment resistance. Loss of cognitive flexibility, a component of depression, is associated with dysregulation of the prefrontal cortex. Reversal learning, a form of cognitive flexibility, is impaired by chronic stress, a risk factor for depression, and the stress-induced impairment in reversal learning is sensitive to chronic SSRI treatment, and is mimicked by serotonin (5-HT) depletion. Vortioxetine, a novel, multimodal-acting antidepressant, is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, and inhibits the 5-HT transporter. Using adult male rats, we first investigated the direct effects of vortioxetine, acting at post-synaptic 5-HT receptors, on reversal learning that was compromised by 5-HT depletion using 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), effectively eliminating any contribution of 5-HT reuptake blockade. PCPA induced a reversal learning impairment that was alleviated by acute or sub-chronic vortioxetine administration, suggesting that post-synaptic 5-HT receptor activation contributes to the effects of vortioxetine. We then investigated the effects of chronic dietary administration of vortioxetine on reversal learning that had been compromised in intact animals exposed to chronic intermittent cold (CIC) stress, to assess vortioxetine's total pharmacological effect. CIC stress impaired reversal learning, and chronic vortioxetine administration prevented the reversal-learning deficit. Together, these results suggest that the direct effect of vortioxetine at 5-HT receptors may contribute to positive effects on cognitive flexibility deficits, and may enhance the effect of 5-HT reuptake blockade.

A rationally designed pyrrolysyl-tRNA synthetase mutant with a broad substrate spectrum.

Together with tRNA(CUA)(Pyl), a rationally designed pyrrolysyl-tRNA synthetase mutant N346A/C348A has been successfully used for the genetic incorporation of a variety of phenylalanine derivatives with large para substituents into superfolder green fluorescent protein at an amber mutation site in Escherichia coli. This discovery greatly expands the genetically encoded noncanonical amino acid inventory and opens the gate for the genetic incorporation of other phenylalanine derivatives using engineered pyrrolysyl-tRNA synthetase-tRNA(CUA)(Pyl) pairs.