An exploratory qualitative study of the self-reported impact of female-perpetrated childhood sexual abuse

The limited findings on the impact of female-perpetrated sexual abuse of children are often contradictory, particularly in relation to males. In this exploratory qualitative study, a sample of nine men and five women who reported that they had been sexually abused by women in their childhood were recruited from the general community. They completed a questionnaire that asked them to describe various aspects of their abuse experiences and the perceived consequences. For both men and women, the abuse was associated with negative outcomes across a range of functional areas in both childhood and adulthood. Many impacts were similar to those reported by victims of male-perpetrated sexual abuse. It is argued that the consequences of female-perpetrated child sexual abuse are serious, and further research is required to bring these issues to the awareness of both the public and professionals working in the field of child protection and counseling.<br /

Forensic Use of the Five Domains Model for Assessing Suffering in Cases of Animal Cruelty

Conceptual frameworks for understanding animal welfare scientifically have become influential. An early “biological functioning” framework still influences expert opinions prepared for Courts hearing animal cruelty cases, despite deficiencies revealed by the emergence and wide scientific adoption of an “affective state” framework. According to “biological functioning” precepts, indices of negative welfare states should predominantly be physical and/or clinical and any reference to animals’ supposed subjective experiences, i.e., their “affective states”, should be excluded. However, “affective state” concepts, which have neuroscience and animal behaviour foundations, show that behavioural indices may be used to credibly identify negative welfare outcomes or affects. Acceptance of the “affective state” framework is entirely consistent with the current extensive international recognition that vertebrate animals are “sentient” beings. A long list of negative affects is discussed and each one is described as a prelude to updating the concept of “suffering” or “distress”, often referred to in animal welfare legislation and prosecutions for alleged ill-treatment of animals. The Five Domains Model for assessing and grading animal welfare compromise is then discussed using examples of severe-to-very-severe ill-treatment of dogs. It is concluded that experts should frame their opinions in ways that include negative affective outcomes

Acute knockdown of Kv4.1 regulates repetitive firing rates and clock gene expression in the suprachiasmatic nucleus and daily rhythms in locomotor behavior

AbstractRapidly activating and inactivating A-type K+currents (IA) encoded by Kv4.2 and Kv4.3 pore-forming (α) subunits of the Kv4 subfamily are key regulators of neuronal excitability. Previous studies have suggested a role for Kv4.1 α-subunits in regulating the firing properties of mouse suprachiasmatic nucleus (SCN) neurons. To test this, we utilized an RNA-interference strategy to knockdown Kv4.1, acutely and selectively, in the SCN. Current-clamp recordings revealed that thein vivoknockdown of Kv4.1 significantly (p&lt; 0.0001) increased mean ± SEM repetitive firing rates in SCN neurons during the day (6.4 ± 0.5 Hz) and at night (4.3 ± 0.6 Hz), compared with nontargeted shRNA-expressing SCN neurons (day: 3.1 ± 0.5 Hz; night: 1.6 ± 0.3 Hz). IAwas also significantly (p&lt; 0.05) reduced in Kv4.1-targeted shRNA-expressing SCN neurons (day: 80.3 ± 11.8 pA/pF; night: 55.3 ± 7.7 pA/pF), compared with nontargeted shRNA-expressing (day: 121.7 ± 10.2 pA/pF; night: 120.6 ± 16.5 pA/pF) SCN neurons. The magnitude of the effect of Kv4.1-targeted shRNA expression on firing rates and IAwas larger at night. In addition, Kv4.1-targeted shRNA expression significantly (p&lt; 0.001) increased mean ± SEM nighttime input resistance (Rin; 2256 ± 166 MΩ), compared to nontargeted shRNA-expressing SCN neurons (1143 ± 93 MΩ). Additional experiments revealed that acute knockdown of Kv4.1 significantly (p&lt; 0.01) shortened, by ∼0.5 h, the circadian period of spontaneous electrical activity, clock gene expression and locomotor activity demonstrating a physiological role for Kv4.1-encoded IAchannels in regulating circadian rhythms in neuronal excitability and behavior.</jats:p

Aspartame in conjunction with carbohydrate reduces insulin levels during endurance exercise

Gold OAAs most sport drinks contain some form of non-nutritive sweetener (e.g. aspartame), and with the variation in blood glucose regulation and insulin secretion reportedly associated with aspartame, a further understanding of the effects on insulin and blood glucose regulation during exercise is warranted. Therefore, the aim of this preliminary study was to profile the insulin and blood glucose responses in healthy individuals after aspartame and carbohydrate ingestion during rest and exercise. Each participant completed four trials under the same conditions (45 min rest + 60 min self-paced intense exercise) differing only in their fluid intake: 1) carbohydrate (2% maltodextrin and 5% sucrose (C)); 2) 0.04% aspartame with 2% maltodextrin and 5% sucrose (CA)); 3) water (W); and 4) aspartame (0.04% aspartame with 2% maltodextrin (A)). Insulin levels dropped significantly for CA versus C alone (43%) between pre-exercise and 30 min, while W and A insulin levels did not differ between these time points. Aspartame with carbohydrate significantly lowered insulin levels during exercise versus carbohydrate alone.Peer Reviewe

No Ifs, No Butts: Compliance with Smoking Cessation in Secondary Care Guidance (NICE PH48) by Providers of Cancer Therapies (Radiotherapy and Chemotherapy) in the UK.

Background: Legislation preventing smoking in public places was introduced in England in July 2007. Since then, smoke-free policies have been extended to the majority of hospitals including those providing cancer therapies. Whilst studies have been conducted on the impact and effectiveness of hospital smoke-free policy in the UK and other countries, there have not been any studies with a focus on cancer care providers. Cancer patients are a priority group for smoking cessation and support and this study aimed to examine implementation of the National Institute Clinical Excellence (NICE) guidance (PH48) in acute cancer care trusts in the UK. Methods: Participants were recruited from UK radiotherapy and chemotherapy departments (total 80 sites, 65 organisations) and asked to complete a 15 min online questionnaire exploring the implementation of NICE guidance at their hospital site. Results: Considerable variability in implementation of the NICE guidance was observed. A total of 79.1% trusts were smoke-free in theory; however, only 18.6% were described as smoke-free in practice. Areas of improvement were identified in information and support for patients and staff including in Nicotine Replacement Therapy (NRT) provision, staff training and clarity on e-cigarette policies. Conclusions: While some trusts have effective smoke-free policies and provide valuable cessation support services for patients, improvements are required to ensure that all sites fully adopt the NICE guidance

Modulation of the effects of class Ib antiarrhythmics on cardiac NaV1.5-encoded channels by accessory NaVβ subunits

Native myocardial voltage-gated sodium (NaV) channels function in macromolecular complexes comprising a pore-forming (α) subunit and multiple accessory proteins. Here, we investigated the impact of accessory NaVβ1 and NaVβ3 subunits on the functional effects of 2 well-known class Ib antiarrhythmics, lidocaine and ranolazine, on the predominant NaV channel α subunit, NaV1.5, expressed in the mammalian heart. We showed that both drugs stabilized the activated conformation of the voltage sensor of domain-III (DIII-VSD) in NaV1.5. In the presence of NaVβ1, the effect of lidocaine on the DIII-VSD was enhanced, whereas the effect of ranolazine was abolished. Mutating the main class Ib drug-binding site, F1760, affected but did not abolish the modulation of drug block by NaVβ1/β3. Recordings from adult mouse ventricular myocytes demonstrated that loss of Scn1b (NaVβ1) differentially affected the potencies of lidocaine and ranolazine. In vivo experiments revealed distinct ECG responses to i.p. injection of ranolazine or lidocaine in WT and Scn1b-null animals, suggesting that NaVβ1 modulated drug responses at the whole-heart level. In the human heart, we found that SCN1B transcript expression was 3 times higher in the atria than ventricles, differences that could, in combination with inherited or acquired cardiovascular disease, dramatically affect patient response to class Ib antiarrhythmic therapies

Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors

Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF). In spite of high homology, each of the iFGFs, iFGF11-iFGF14, as well as the individual iFGF splice variants, differentially regulates NaV channel gating, and the mechanisms underlying these differential effects remain elusive. Much of the work exploring iFGF regulation of NaV1.5 has been performed in mouse and rat ventricular myocytes in which iFGF13VY is the predominant iFGF expressed, whereas investigation into NaV1.5 regulation by the human heart-dominant iFGF12B is lacking. In this study, we used a mouse model with cardiac-specific Fgf13 deletion to study the consequences of iFGF13VY and iFGF12B expression. We observed distinct effects on the voltage-dependences of activation and inactivation of the sodium currents (INa), as well as on the kinetics of peak INa decay. Results in native myocytes were recapitulated with human NaV1.5 heterologously expressed in Xenopus oocytes, and additional experiments using voltage-clamp fluorometry (VCF) revealed iFGF-specific effects on the activation of the NaV1.5 voltage sensor domain in repeat IV (VSD-IV). iFGF chimeras further unveiled roles for all three iFGF domains (i.e., the N-terminus, core, and C-terminus) on the regulation of VSD-IV, and a slower time domain of inactivation. We present here a novel mechanism of iFGF regulation that is specific to individual iFGF isoforms and that leads to distinct functional effects on NaV channel/current kinetics

Kv12-encoded K+ channels drive the day-night switch in the repetitive firing rates of SCN neurons

Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations in the spontaneous firing rates of neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals. The K+ conductance(s) driving these daily rhythms in the repetitive firing rates of SCN neurons, however, have not been identified. To test the hypothesis that subthreshold Kv12.1/Kv12.2-encoded K+ channels play a role, we obtained current-clamp recordings from SCN neurons in slices prepared from adult mice harboring targeted disruptions in the Kcnh8 (Kv12.1-/-) or Kcnh3 (Kv12.2-/-) locus. We found that mean nighttime repetitive firing rates were higher in Kv12.1-/- and Kv12.2-/- than in wild type (WT), SCN neurons. In marked contrast, mean daytime repetitive firing rates were similar in Kv12.1-/-, Kv12.2-/-, and WT SCN neurons, and the day-night difference in mean repetitive firing rates, a hallmark feature of WT SCN neurons, was eliminated in Kv12.1-/- and Kv12.2-/- SCN neurons. Similar results were obtained with in vivo shRNA-mediated acute knockdown of Kv12.1 or Kv12.2 in adult SCN neurons. Voltage-clamp experiments revealed that Kv12-encoded current densities in WT SCN neurons are higher at night than during the day. In addition, the pharmacological block of Kv12-encoded currents increased the mean repetitive firing rate of nighttime, but not daytime, in WT SCN neurons. Dynamic clamp-mediated subtraction of modeled Kv12-encoded currents also selectively increased the mean repetitive firing rates of nighttime WT SCN neurons. Despite the elimination of the nighttime decrease in the mean repetitive firing rates of SCN neurons, however, locomotor (wheel-running) activity remained rhythmic in Kv12.1-/-, Kv12.2-/-, and Kv12.1-targeted shRNA-expressing, and Kv12.2-targeted shRNA-expressing animals