Breast cancer treatment and ovarian function

The aim of this study was to provide an update on ovarian function and the mechanisms of gonadal damage after exposure to chemotherapy in breast cancer survivors. The alkylating agents are toxic to both primordial and growing follicles. However, anti-metabolite drugs are more likely to destroy preantral and antral follicles. Younger patients are more likely to have a higher ovarian reserve, and therefore, more likely to retain some residual ovarian function after exposure to gonadotoxic regimens. However, there can be significant variability in ovarian reserve among patients of the same age. Furthermore, patients with critically diminished ovarian reserve may continue to menstruate regularly. Therefore age and menstrual status are not reliable indicators of good ovarian reserve and might give a false sense of security and result in an adverse outcome if the patient is consulted without considering more reliable quantitative markers of ovarian reserve (antral follicle count and anti-Müllerian hormone) and fertility preservation is not pursued. In contrast to well-documented ovarian toxicity of older chemotherapy regimens, data for newer taxane-containing protocols have only accumulated in the last decade and data are still very limited regarding the impact of targeted therapies on ovarian function.     

Processing of modulation frequency in the dorsal cochlear nucleus of the guinea pig: Amplitude modulated tones

The modulation frequency (Fm), particularly high Fm (> 200 Hz), in amplitude modulated (AM) tones can elicit the perception of the periodicity pitch (Langner, 1992). In this study, single unit responses to the Fms of the sinusoidal AM tones were investigated at 50 to 90 dB SPL. The recordings were made from the dorsal cochlear nucleus (DCN) of neuroleptic anesthetized guinea pigs with an intact cerebellum. The DCN units show a good capability of phase-locking to Fm at 400–1200 Hz. On-S-type II and Pauser/Buildup (P/B) units have a high modulation gain (7.2–8.3 dB). P/B units can preserve the high modulation gain (5–9 dB) up to 90 dB SPL. The modulation gain exponentially increases with decreasing modulation depth (Dm) and the phase-locking is detectable even at the Dm as low as 2–5%. The ‘central skipping’ of the phase-locking peak has been found at deep Dms in a few cases. The synchronization is independent of the discharge rate and can remain high even when the responses to AM tones are inhibited below the spontaneous activity. Such encoding behaviors over the unit's response area show that the Fm phase-locking is strong near or at its characteristic frequency (CF). The synchronization index (SI) versus carrier frequency (Fc) curve is similar to the inverse shape of tuning curve but more narrowly tuned than the iso-intensity function of pure tones at moderate to high intensity levels. The phase-locking is related to the unit's spontaneous rate (SR). The average modulation gain of the lower SR (≤ 2 spikes/s) units is 5 dB higher than that of the higher SR (> 2 spikes/s) units (8.16 and 2.92 dB, respectively) at 70 dB SPL. These results suggest that AM information is temporally encoded over broad ranges of modulation parameters in the DCN and is conveyed by the Fc channel. Such a timing mechanism can play an important role in processing of complex sounds under normal acoustic conditions.     

Volitional consumption of ethanol by fawn-hooded rats: Effects of alternative solutions and drug treatments

Behavioral and neurochemical measures of brain 5-hydroxytryptamine (5-HT) function in the Fawn-Hooded rat are abnormal relative to outbred strains of rats. Fawn-Hooded rats freely drink large amounts of 10% ethanol in the presence of water and have been proposed to be an animal model for studies related to alcoholism. In this study, Fawn-Hooded rats were given solutions of ethanol increasing in concentration from 3% to 30% (w/v in tap water) over 10 days with tap water in a second drinking tube and a third tube left empty. The solutions of ethanol that produced maximal drinking with a preference (ml ethanol/ml total fluid) near 50% ranged from 5% to 13%, which became: the fixed individual concentrations for each rat. After a 5-day baseline period the rats were offered a solution in the third drinking tube of either 0.5% aspartame or chocolate Ultra SlimFast (diluted with water 2: 1). The chocolate drink, but not aspartame, significantly reduced the consumption of alcohol by 73%. For the drug experiments, the rats were given successive 4-day periods of: baseline drinking; drug or saline injections b.i.d.; and a posttreatment period. Neither ipsapirone, a 5-HT_1a partial agonist, nor naltrexone injected inhibited the intakes of ethanol solutions. Treatment with 2.5 mg/kg of amperozide, a 5-HT₂ antagonist, decreased the consumption of ethanol by 38%, but also caused a decrease in consumption of food. These results show a pattern of drinking of increasing concentrations of ethanol different than other strains of rats. Because ethanol intakes of the Fawn-Hooded rat decline precipitously when offered palatable chocolate drink and fail to respond to drugs known to decrease human ethanol intake, this strain may not be a valid model for testing the effects of centrally acting drugs on the consumption of ethanol.     

Oxidation of substituted 4-fluorobenzaldehydes: Application to the no-carrier-added syntheses of 4-[18F]fluoroguaiacol and 4-[18F]fluorocatechol

The synthesis of 4-[¹⁸F]fluoroguaiacol (4-[¹⁸F]fluoro-2-methoxyphenol) has been achieved in no-carrier-added form starting from 2-methoxy-4-nitrobenzaldehyde, using nucleophilic aromatic substitution by [¹⁸F]fluoride followed by Baeyer-Villiger oxidation of the benzaldehyde to the phenol. Demethylation with boron tribromide gave 4-[¹⁸F]fluorocatechol (1,2-dihydroxy-4-[¹⁸F]fluorobenzene) with an overall yield of 18–28% (EOB) in less than 2 h synthesis time. The fluorine-18 labeled intermediates and products were identical to standards of 4-fluoroguaiacol and 4-fluorocatechol prepared by the same methods. This represents a new approach to the synthesis of fluorinated phenols in fluorine-19 and fluorine-18 forms.     

Neurotensin stimulates cyclic AMP formation in CHO-rNTR-10 cells expressing the cloned rat neurotensin receptor

Recently, we reported that the rat neurotensin receptor expressed in transfected Chinese hamster ovary cells (CHO-rNTR-10) mediates the hydrolysis of polyphosphoinositides. In this study, we show that neurotensin stimulated cyclic AMP formation in CHO-rNTR-10 cells in a dose-dependent manner (EC₅₀ = 34 nM). Neurotensin also stimulated cyclic AMP formation in membranal preparations under Ca²⁺-free conditions. These results suggest that this cyclic AMP formation occurs from direct coupling of the neurotensin receptor to a type of GTP binding protein, mediating synthesis of cyclic AMP, and not from an increase in intracellular Ca²⁺ concentration from polyphosphoinositide hydrolysis.     

Without insight accompanied with deteriorated brain functional alterations in healthy individuals with auditory verbal hallucinations: a pilot study

Brain Imaging and Behavior - Few studies have reported on brain functional differences between healthy individuals with auditory verbal hallucinations (Hi-AVH) with and without insight, so we...     

Exploring clinicians’ decision-making processes about end-of-life care after burns: A qualitative interview study

IntroductionLittle is known about treatment decision-making experiences and how/why particular attitudes exist amongst specialist burn clinicians when faced with patients with potentially non-survivable burn injuries. This exploratory qualitative study aimed to understand clinicians’ decision-making processes regarding end-of-life (EoL) care after a severe and potentially non-survivable burn injury.MethodsEleven clinicians experienced in EoL decision-making were interviewed via telephone or video conferencing in June-August 2021. A thematic analysis was undertaken using a framework approach.ResultsDecision-making about initiating EoL care was described as complex and multifactorial. On occasions when people presented with ‘unsurvivable’ injuries, decision-making was clear. Most clinicians used a multidisciplinary team approach to initiate EoL; variations existed on which professions were included in the decision-making process. Many clinicians reported using protocols or guidelines that could be personalised to each patient. The use of pathways/protocols might explain why clinicians did not report routine involvement of palliative care clinicians in EoL discussions.ConclusionThe process of EoL decision-making for a patient with a potentially non-survivable burn injury was layered, complex, and tailored. Processes and approaches varied, although most used protocols to guide EoL decisions. Despite the reported complexity of EoL decision-making, palliative care teams were rarely involved or consulted.