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Fertility and Sterility Aug 2022Climate change is a major risk factor for overall health, including reproductive health, and well-being. Increasing temperatures, due mostly to increased greenhouse... (Review)
Review
Climate change is a major risk factor for overall health, including reproductive health, and well-being. Increasing temperatures, due mostly to increased greenhouse gases trapping excess heat in the atmosphere, result in erratic weather patterns, wildfires, displacement of large communities, and stagnant water resulting in vector-borne diseases that, together, have set the stage for new and devastating health threats across the globe. These conditions disproportionately affect disadvantaged and vulnerable populations, including women, pregnant persons, young children, the elderly, and the disabled. This review reports on the evidence for the adverse impacts of air pollution, wildfires, heat stress, floods, toxic chemicals, and vector-borne diseases on male and female fertility, the developing fetus, and obstetric outcomes. Reproductive health care providers are uniquely positioned and have an unprecedented opportunity to educate patients and policy makers about mitigating the impact of climate change to assure reproductive health in this and future generations.
Topics: Air Pollution; Climate Change; Female; Humans; Male; Reproductive Health; Vulnerable Populations; Weather
PubMed: 35878942
DOI: 10.1016/j.fertnstert.2022.06.005 -
Drugs May 2020Posaconazole is typically used for preventing invasive yeast and mold infections such as invasive aspergillosis in high-risk immunocompromised patients. The oral... (Review)
Review
Posaconazole is typically used for preventing invasive yeast and mold infections such as invasive aspergillosis in high-risk immunocompromised patients. The oral suspension was the first released formulation and many pharmacokinetic and pharmacodynamic studies of this formulation have been published. Erratic absorption profiles associated with this formulation were widely reported. Posaconazole exposure was found to be significantly influenced by food and many gastrointestinal conditions, including pH and motility. As a result, low posaconazole plasma concentrations were obtained in large groups of patients. These issues of erratic absorption urged the development of the subsequently marketed delayed-release tablet, which proved to be associated with higher and more stable exposure profiles. Shortly thereafter, an intravenous formulation was released for patients who are not able to take oral formulations. Both new formulations require a loading dose on day 1 to achieve high posaconazole concentrations more quickly, which was not possible with the oral suspension. So far, there appears to be no evidence of increased toxicity correlated to the higher posaconazole exposure achieved with the regimen for these formulations. The higher systemic availability of posaconazole for the delayed-release tablet and intravenous formulation have resulted in these two formulations being preferable for both prophylaxis and treatment of invasive fungal disease. This review aimed to integrate the current knowledge on posaconazole pharmacokinetics, pharmacodynamics, major toxicity, existing resistance, clinical experience in special populations, and new therapeutic strategies in order to get a clear understanding of the clinical use of this drug.
Topics: Administration, Oral; Animals; Antifungal Agents; Aspergillosis; Drug Compounding; Humans; Injections, Intravenous; Triazoles
PubMed: 32323222
DOI: 10.1007/s40265-020-01306-y -
Behavioural Brain Research Dec 2009The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress...
The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and high-throughput model of stress and affective disorders.
Topics: Animals; Antidepressive Agents, Second-Generation; Anxiety; Behavior, Animal; Caffeine; Central Nervous System Depressants; Central Nervous System Stimulants; Disease Models, Animal; Ethanol; Female; Fluoxetine; Hydrocortisone; Male; Motor Activity; Phenotype; Pheromones; Species Specificity; Stress, Psychological; Zebrafish
PubMed: 19540270
DOI: 10.1016/j.bbr.2009.06.022 -
Cell Metabolism Nov 2015A diurnal rhythm of eating-fasting promotes health, but the eating pattern of humans is rarely assessed. Using a mobile app, we monitored ingestion events in healthy...
A diurnal rhythm of eating-fasting promotes health, but the eating pattern of humans is rarely assessed. Using a mobile app, we monitored ingestion events in healthy adults with no shift-work for several days. Most subjects ate frequently and erratically throughout wakeful hours, and overnight fasting duration paralleled time in bed. There was a bias toward eating late, with an estimated <25% of calories being consumed before noon and >35% after 6 p.m. "Metabolic jetlag" resulting from weekday/weekend variation in eating pattern akin to travel across time zones was prevalent. The daily intake duration (95% interval) exceeded 14.75 hr for half of the cohort. When overweight individuals with >14 hr eating duration ate for only 10-11 hr daily for 16 weeks assisted by a data visualization (raster plot of dietary intake pattern, "feedogram") that we developed, they reduced body weight, reported being energetic, and improved sleep. Benefits persisted for a year.
Topics: Adult; Body Weight; Eating; Energy Intake; Feeding Behavior; Female; Humans; Male; Smartphone
PubMed: 26411343
DOI: 10.1016/j.cmet.2015.09.005 -
Journal of Diabetes and Its... Jan 2021"Brittle diabetes" was first used to describe a life "disrupted by episodes of hypoglycemia or hyperglycemia." Early descriptions focused on small case reports of mostly... (Review)
Review
"Brittle diabetes" was first used to describe a life "disrupted by episodes of hypoglycemia or hyperglycemia." Early descriptions focused on small case reports of mostly young women with psycho-social instability, recurrent diabetic ketoacidosis, poor patient compliance or maladaptation. We redefine "brittle diabetes" as occurring in four specific life stages each with distinct characteristics and associated conditions resulting in severely erratic glycemic control and poor outcomes. Once identified however these factors can often be reversed or significantly mitigated. The first group includes younger patients with associated psychiatric diseases such as bulimia and depression which require specific therapy and are treatable. A second group includes individuals who have another underlying medical condition resulting in disruption of insulin sensitivity or glucose utilization which must be sought. A third group, the largest we believe, has "geriatric type 1 diabetes" and develops severe glycemic instability due to frailty, chronic renal failure, dementia, vision loss, loss of counterregulation and other diseases of aging which lead to unintentional omission of insulin, insulin dosing errors and increasing insulin sensitivity. The fourth group, now seen around the world, suffers lack of insulin access and associated food insecurity. All four of these groups are described.
Topics: Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Hypoglycemia; Insulin; Insulin Resistance; Insulin, Regular, Human
PubMed: 32620472
DOI: 10.1016/j.jdiacomp.2020.107646 -
The Plant Cell Apr 1990We attempted to overexpress chalcone synthase (CHS) in pigmented petunia petals by introducing a chimeric petunia CHS gene. Unexpectedly, the introduced gene created a...
We attempted to overexpress chalcone synthase (CHS) in pigmented petunia petals by introducing a chimeric petunia CHS gene. Unexpectedly, the introduced gene created a block in anthocyanin biosynthesis. Forty-two percent of plants with the introduced CHS gene produced totally white flowers and/or patterned flowers with white or pale nonclonal sectors on a wild-type pigmented background; none of hundreds of transgenic control plants exhibited such phenotypes. Progeny testing of one plant demonstrated that the novel color phenotype co-segregated with the introduced CHS gene; progeny without this gene were phenotypically wild type. The somatic and germinal stability of the novel color patterns was variable. RNase protection analysis of petal RNAs isolated from white flowers showed that, although the developmental timing of mRNA expression of the endogenous CHS gene was not altered, the level of the mRNA produced by this gene was reduced 50-fold from wild-type levels. Somatic reversion of plants with white flowers to phenotypically parental violet flowers was associated with a coordinate rise in the steady-state levels of the mRNAs produced by both the endogenous and the introduced CHS genes. Thus, in the altered white flowers, the expression of both genes was coordinately suppressed, indicating that expression of the introduced CHS gene was not alone sufficient for suppression of endogenous CHS transcript levels. The mechanism responsible for the reversible co-suppression of homologous genes in trans is unclear, but the erratic and reversible nature of this phenomenon suggests the possible involvement of methylation.
PubMed: 12354959
DOI: 10.1105/tpc.2.4.279 -
Canadian Journal of Public Health =... Mar 2016Risky sexual behaviour associated with sexually transmitted infections (STI) and sexual harassment are important topics in university environments and public health.... (Comparative Study)
Comparative Study
OBJECTIVES
Risky sexual behaviour associated with sexually transmitted infections (STI) and sexual harassment are important topics in university environments and public health. This article compares these behaviours between student cohorts in 2005 and 2012 from a Western Canadian university. The sexual habits of young adults with multiple partners are also examined.
METHODS
Researchers conducted a comparative study of sexual behaviour among approximately 400 students per cohort. Estimates of prevalence and adjusted odds for age group and sex were used to analyze associations between the two cohorts and their sexual behaviours.
RESULTS
Trends in sexual behaviour of young adults are maintained with respect to the proportion of those who are sexually active and their number of partners. A reduction in sexual harassment is observed, especially towards women. The condom remains the most frequently used method of contraception, but its use is erratic, particularly among respondents with multiple sexual partners. Drinking and the use of drugs predisposes to unplanned sexual relations and to non-use of means to prevent STIs and pregnancy, particularly among respondents with multiple sexual partners.
CONCLUSIONS
The postsecondary student population should be informed of the risks associated with multiple sexual partners and alcohol and drug consumption leading to unplanned sexual acts. A sexual harassment policy contributes to reduction of incidents of harassment within a postsecondary institution.
Topics: Adolescent; Canada; Cohort Studies; Female; Humans; Male; Risk-Taking; Sexual Behavior; Sexual Harassment; Sexual Partners; Sexually Transmitted Diseases; Students; Universities; Young Adult
PubMed: 26986909
DOI: 10.17269/cjph.106.4968 -
International Journal of Surgery... Dec 2016Cryoablation (CA) has been broadly used mostly in the treatment of small renal masses (SRMs). The present review aims to define the current role of CA in the treatment... (Review)
Review
INTRODUCTION
Cryoablation (CA) has been broadly used mostly in the treatment of small renal masses (SRMs). The present review aims to define the current role of CA in the treatment of SRMs by assessing clinical indications and outcomes.
METHOD
A comprehensive review on patient selection, procedural details, perioperative complications, and short/long-term oncological and functional outcomes was conducted. For each section, a take-home message was formulated with level of evidence (LoE) according to Cochrane collaboration.
RESULTS
Age and comorbidity drive the choice of ablation in SRMs, although hospital setting also influences the decision. Technically in adequate CA or first post-CA control occurs in 3-5% of laparoscopic cryoablation (LCA) or percutaneous cryoablation (PCA) series. Meta-analysis does not evidence differences in the rate of residual tumor per person-year between the approaches (0.033 LCA vs. 0.046 PCA, p = 0.25). Perioperative complications (8-25%) are erratically reported. LCA has significantly lower likelihood of complications than minimally invasive partial nephrectomy (MIPN). Systematic reviews indicate 30-month local tumor progression rate of 8.5% for LCA in renal cell carcinoma but low metastatic progression (1-4.4%). Few LCA long-term follow-up series (mean/media 48-98 months) report recurrence-free survival (RFS) and cancer-specific survival (CSS) ranges of 80-100%. For PCA, Kaplan-Meier local disease-free survival (DFS) of 95.6% at 3-5 years [32] and 5-year overall survival and local RFS of 86.3% were reported. The decrease in renal function after CA is minimal, and the only risk factor associated is the basal estimated glomerular filtration rate (eGFR).
CONCLUSION
LoE 3a/b confirms lower CA perioperative complication rate and higher local progression rate than those for MIPN. CA preserves postoperative renal functional, without any evidence of differences in mid-/long-term follow-up compared to nephron sparing surgery.
Topics: Age Factors; Aged; Carcinoma, Renal Cell; Catheter Ablation; Cryosurgery; Disease Progression; Disease-Free Survival; Female; Humans; Kidney; Kidney Neoplasms; Laparoscopy; Male; Middle Aged; Nephrectomy; Patient Selection; Risk Factors; Treatment Outcome
PubMed: 27500963
DOI: 10.1016/j.ijsu.2016.06.049 -
Science Advances Apr 2022Stress is the most common trigger among episodic neurologic disorders. In episodic ataxia type 2 (EA2), physical or emotional stress causes episodes of severe motor...
Stress is the most common trigger among episodic neurologic disorders. In episodic ataxia type 2 (EA2), physical or emotional stress causes episodes of severe motor dysfunction that manifest as ataxia and dystonia. We used the (tg/tg) mouse, a faithful animal model of EA2, to dissect the mechanisms underlying stress-induced motor attacks. We find that in response to acute stress, activation of α-adrenergic receptors (α1-Rs) on Purkinje cells by norepinephrine leads to their erratic firing and consequently motor attacks. We show that norepinephrine induces erratic firing of Purkinje cells by disrupting their spontaneous intrinsic pacemaking via a casein kinase 2 (CK2)-dependent signaling pathway, which likely reduces the activity of calcium-dependent potassium channels. Moreover, we report that disruption of this signaling cascade at a number of nodes prevents stress-induced attacks in the mouse. Together, our results suggest that norepinephrine and CK2 are required for the initiation of stress-induced attacks in EA2 and provide previously unidentified targets for therapeutic intervention.
PubMed: 35442745
DOI: 10.1126/sciadv.abh2675 -
JACS Au Apr 2023The autocatalysis of epoxide-opening ether cyclizations on the aromatic surface of anion-π catalysts stands out as a leading example of emergent properties expected...
The autocatalysis of epoxide-opening ether cyclizations on the aromatic surface of anion-π catalysts stands out as a leading example of emergent properties expected from the integration of unorthodox interactions into catalysis. A working hypothesis was proposed early on, but the mechanism of anion-π autocatalysis has never been elucidated. Here, we show that anion-π autocatalysis is almost independent of peripheral crowding in substrate and product. Inaccessible asymmetric anion-π autocatalysis and sometimes erratic reproducibility further support that the origin of anion-π autocatalysis is more complex than originally assumed. The apparent long-distance communication without physical contact calls for the inclusion of water between substrate and product on the catalytic aromatic surface. Efficient anion-π autocatalysis around equimolar amounts but poor activity in dry solvents and with excess water indicate that this inclusion of water requires high precision. Computational models suggest that two water molecules transmit dual substrate activation by the product and serve as proton shuttles along antiparallel but decoupled hydrogen-bonded chains to delocalize and stabilize evolving charge density in the transition state by "anion-π double bonds". This new transition-state model of anion-π autocatalysis provides a plausible mechanism that explains experimental results and brings anion-π catalysis to an unprecedented level of sophistication.
PubMed: 37124310
DOI: 10.1021/jacsau.2c00656