Comments on Marken and Shaffer: The power law of movement: an example of a behavioral illusion.

Many researchers who have studied movements along curved paths, under a variety of conditions, by different organisms, mostly human but a couple with non-human organisms, have found a consistent form of relation between the tangential (along-track) instantaneous velocity V and the local radius of curvature R. The consistent relation is that V ≈ cR k , where k is a constant less than unity, often near 0.33 but sometimes far from 0.33, and c is a proportionality constant appropriate to the organism and the situation (see Zago, Matic, Flash, et al. (2017) for many examples in which the power law holds with widely varying values of the power, as well as cases of simple systems for which everything can be calculated exactly and in which the power law fails badly). Marken and Shaffer (Exp Brain Res 235:1835-1842; 2017), following a challenge by Gomez-Marin to see whether it is possible to use Perceptual Control Theory (Powers 1973/2005) to explain the power law results (Alex Gomez-Marin posting to CSGnet@lists.illinois.edu 2016.05.03), claim to have found a mathematical argument that proves the true exponent of the power relating velocity and radius of curvature always to be 1/3. They say that deviations from this value occur because researchers have omitted a critical correction "cross-product" factor that the authors label "D". This note questions the logic of the analysis offered by Marken and Shaffer, and argues that even had the analysis been correct, it would not affect future research into the reasons why and when the power law is observed and the circumstances that determine the value of the power found when it is observed.

HIV status and viral loads among men testing positive for rectal gonorrhoea and chlamydia, Maricopa County, Arizona, USA, 2011-2013.

OBJECTIVES: Men diagnosed with rectal gonorrhoea (GC) and chlamydia (CT) have engaged in unprotected receptive anal intercourse. We reviewed the HIV positivity and HIV viral loads (VLs) of men who had rectal GC and CT testing to evaluate potential HIV acquisition and transmission risk. METHODS: Rectal GC and CT testing data for men attending the Maricopa County STD clinic during the period from 1 October 2011 to 30 September 2013 were cross-matched with HIV surveillance data to identify men with HIV coinfection. We examined HIV status, HIV diagnosis date, and the values of VL collected nearest to the date of reported rectal infection. RESULTS: During the 2-year time period, 1591 men were tested for rectal GC and CT. Of the men tested, 506 (31.8%) were positive for GC (13.2%), CT (12.2%) or both (6.4%); 119 (23.5%) of those with rectal GC or CT were coinfected with HIV. Among the 275 men with HIV at the time of rectal testing, 54 (19.6%) had no reported VL; 63 (22.9%) had an undetectable VL (< 20 HIV-1 RNA copies/mL) and 158 (57.4%) had a detectable VL collected within 1 year of rectal diagnosis. Mean VL was higher among HIV and rectal GC/CT coinfected cases compared with men with HIV alone (174 316 vs. 57 717 copies/mL, respectively; P = 0.04). CONCLUSIONS: Approximately one-third of men undergoing rectal testing were positive for GC or CT and one-quarter of men with rectal GC or CT also had HIV infection. Of the HIV-infected men tested for rectal GC or CT, more than half had a detectable VL collected near the time of rectal testing, demonstrating a risk for transmitting HIV.

Selective cognitive deficits in adult rats after prenatal exposure to inhaled ethanol.

Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by inhalation, the most likely route of exposure from gasoline-ethanol fuel blends. We evaluated the potential cognitive consequences of ethanol inhalation by exposing pregnant Long Evans rats to clean air or ethanol vapor from gestational days 9-20, a critical period of neuronal development. Concentrations of inhaled ethanol (5000, 10,000, or 21,000 ppm for 6.5h/day) produced modeled peak blood ethanol concentrations (BECs) in exposed dams of 2.3, 6.8, and 192 mg/dL, respectively. In offspring, no dose-related impairments were observed on spatial learning or working memory in the Morris water maze or in operant delayed match-to-position tests. Two measures showed significant effects in female offspring at all ethanol doses: 1) impaired cue learning after trace fear conditioning, and 2) an absence of bias for the correct quadrant after place training during a reference memory probe in the Morris water maze. In choice reaction time tests, male offspring (females were not tested) from the 5000 and 10,000 ppm groups showed a transient increase in decision times. Also, male offspring from the 21,000 ppm group made more anticipatory responses during a preparatory hold period, suggesting a deficit in response inhibition. The increase in anticipatory responding during the choice reaction time test shows that inhaled ethanol yielding a peak BEC of ~200mg/dL can produce lasting effects in the offspring. The lack of a dose-related decrement in the effects observed in females on cue learning and a reference memory probe may reflect confounding influences in the exposed offspring possibly related to maternal care or altered anxiety levels in females. The surprising lack of more pervasive cognitive deficits, as reported by others at BECs in the 200mg/dL range, may reflect route-dependent differences in the kinetics of ethanol. These data show that response inhibition was impaired in the offspring of pregnant rats that inhaled ethanol at concentrations at least 5 orders of magnitude higher than concentrations observed during normal automotive transport and fueling operations, which rarely exceed 100 ppb.

Prevalence of urease in Vibrio parahaemolyticus from the Mississippi Sound.

UNLABELLED: Vibrio parahaemolyticus is a pathogenic marine bacterium that causes food-borne gastroenteritis and, less commonly, wound infections. As is the case for many pathogens, all V. parahaemolyticus strains possess at least one erythrocyte-lysing haemolysin. In addition, many V. parahaemolyticus also possess the enzyme urease. We tested 206 environmental V. parahaemolyticus isolates from Mississippi coastal waters for urease and haemolytic activity using urea agar with added salt and Wagatsuma agar, respectively. The relative abundance of haemolysin-producing V. parahaemolyticus was consistently high throughout the sampling period. In contrast, the number of urease-positive organisms increased from 36% in 2006 to 80% in 2007 and 97% in 2009. We then tested the ability of four strains representing each of the three sample years along with seven other bacterial strains for their ability to grow in seawater urea and raise the pH of this seawater broth. Finally, one of the 4 strains was tested for its ability to form an alkaline microhabitat immediately above its biofilm. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study illustrate that V. parahaemolyticus has the ability to create alkaline microhabitats that could enhance virulence, including virulence from haemolysins. This finding could have both clinical and ecological impact as to how V. parahaemolyticus can modify its habitat.

Targeting platinum resistant disease in ovarian cancer.

Ovarian cancer is an extremely aggressive disease in which the vast majority of patients face a very poor prognosis. Although most patients initially respond to current chemotherapeutic regimens that include a combination of platinum- based therapy (cisplatin/carboplatin) and paclitaxel, the vast majority of them quickly relapse and develop increased resistance to available treatments. Thus, intrinsic and acquired chemotherapy resistance is a major obstacle in the treatment of ovarian cancer patients. Consequently, the priorities for basic and translational ovarian cancer research need to include the identification of novel therapies directed against key molecular targets and signaling pathways in platinum resistant disease. At the same time, we need to develop novel systems for drug delivery aimed at increasing the efficacy and reducing the toxicity of platinum-based treatments. Improving the current responses to platinum chemotherapy is critical not only for achieving a better outcome clinically, including a longer survival, but also for allowing patients to have a better quality of life while in treatment.

Use of expedited partner therapy among chlamydia cases diagnosed at an urban Indian health centre, Arizona.

Chlamydia cases diagnosed in the women's clinic were more likely to receive expedited partner therapy (EPT) and to be re-tested as compared with urgent and emergent care settings. Fewer re-infections occurred among patients who received EPT. Disproportionate rates of chlamydia occur among American Indian (AI) populations. To describe use of EPT among chlamydia cases diagnosed at an urban Indian Health Service (IHS) facility in Arizona, health records were used to extract confirmed cases of chlamydia diagnosed between January 2009 and August 2011. Medical records of 492 patients diagnosed with chlamydia were reviewed. Among the 472 cases who received treatment, 246 (52%) received EPT. Receipt of EPT was significantly associated with being female (odds ratio (OR) 2.1, 1.03-4.4, P < 0.001) and receipt of care in the women's clinic (OR 9.9, 95% CI 6.0-16.2) or in a primary care clinic (OR 2.4, 95% CI 1.1-5.1). Compared with those receiving care in the women's clinic, the odds of receipt of EPT were significantly less in those attending the urgent/express care clinic (OR 0.1, 95% CI 0.06-0.2), and the emergency department (OR 0.1, 95% CI 0.05-0.2). Among treated patients who underwent re-testing (N = 323, 68% total treated) re-infection was less common among those that received EPT (13% versus 27%; OR 0.5, 95% CI 0.3-0.9). In this IHS facility, EPT was protective in preventing chlamydia re-infection. Opportunities to expand the use of EPT were identified in urgent and emergent care settings.

Examining self and partners for syphilis among men who have sex with men: five US cities, 2009-2011.

To increase self-examination for syphilis among men who have sex with men (MSM), we developed educational materials to increase knowledge of primary and secondary syphilis manifestations. Materials were piloted in five cities' infectious disease or MSM clinics. Self- and partner-examination behaviour was assessed with an anonymous questionnaire. Of 1459 participants, 914 men had had sex with a man in the previous three months; the 171 MSM who reported having read the materials were significantly more likely to examine themselves (anus, adjusted prevalence ratio [aPR] 1.3, 95% confidence interval [CI] 1.15-1.52), mouth, penis and skin, and their partners' anus (aPR 1.3, 95% CI 1.03-1.73) and mouth (aPR 1.6, 95% CI 1.1-2.26). Further research is needed to determine whether educational materials affect early detection and treatment of primary and secondary syphilis and reduce transmission.

Reticence to prescribe: utilization of expedited partner therapy among obstetrics providers in Arizona.

Expedited partner therapy (EPT) is the practice of providing an extra dose or prescription of antibiotic to patients diagnosed with chlamydia or gonorrhoea to deliver to their sexual partner(s). Obstetrical providers who delivered more than 20 infants in Maricopa County, Arizona, USA, during the year 2008 were surveyed by telephone regarding their use of EPT. A total of 142 eligible respondents completed the survey, representing 34% (142/421) of the delivering providers, 67 (47%) of whom reported the use of EPT in their clinics. Having received information about EPT was significantly associated with its use (67% versus 41%) (P = 0.008). The most common reasons for not using EPT included the inability to obtain allergy history in partners (24%) and concern for liability (11%). Additional education regarding the use of EPT may increase the use of this personal and public health tool among some obstetrics providers in Maricopa County; however, concerns for liability may limit broad utilization.

Circuit parties: sexual behaviors and HIV disclosure practices among men who have sex with men at the White Party, Palm Springs, California, 2003.

The syphilis epidemic among men who have sex with men (MSM) in major US cities and concomitant increases in high-risk sexual behavior, have raised concerns of increased HIV transmission in this population. Therefore, to provide information for health promotion and disease awareness efforts, we investigated sexual behaviors, partner selection preferences and HIV serostatus disclosure practices of MSM at the White Party in Palm Springs, California. Circuit party attendees reported engaging in unprotected anal sex, however, a high proportion reported disclosing their HIV status. These findings suggest that some gay men are serosorting as a risk reduction strategy or implementing sexual risk reduction strategies to protect themselves and their partners. In our study, HIV-negative men were nine times more likely to report a preference for a seroconcordant sexual partner. The self-protecting attitudes of HIV-negative men in our sample outweighed the partner-protecting attitudes of HIV-positive men. This suggests that prevention interventions focusing on HIV-positive persons are warranted.

Central neuropeptide B administration activates stress hormone secretion and stimulates feeding in male rats.

Neuropeptide B (NPB) was identified to be an endogenous, peptide ligand for the orphan receptors GPR7 and GPR8. Because GPR7 is expressed in rat brain and, in particular, in the hypothalamus, we hypothesized that NPB might interact with neuroendocrine systems that control hormone release from the anterior pituitary gland. No significant effects of NPB were observed on the in vitro releases of prolactin, adrenocorticotropic hormone (ACTH) or growth hormone (GH) when log molar concentrations ranging from 1 pM to 100 nM NPB were incubated with dispersed anterior pituitary cells harvested from male rats. In addition NPB (100 nM) did not alter the concentration response stimulation of prolactin secretion by thyrotropin-releasing hormone, ACTH secretion by corticotropin-releasing factor (CRF) and GH secretion by GH-releasing hormone. However, NPB, when injected into the lateral cerebroventricle (i.c.v.) of conscious, unrestrained male rats, elevated prolactin and corticosterone, and lowered GH levels in circulation. The threshold dose for the effect on corticosterone and prolactin levels was 1.0 nmol, while that for the effect on GH release was 3.0 nmol NPB. Pretreatment with a polyclonal anti-CRF antiserum completely blocked the ability of NPB to stimulate ACTH release and significantly inhibited the effect of NPB on plasma corticosterone levels. NPB administration i.c.v. did not significantly alter plasma vasopressin and oxytocin levels in conscious rats. It did stimulate feeding (minimum effective dose 1.0 nmol) in sated animals in a manner similar to that of the other endogenous ligand for GPR7, neuropeptide W. We conclude that NPB can act in the brain to modulate neuroendocrine signals accessing the anterior pituitary gland, but does not itself act as a releasing or inhibiting factor in the gland, at least with regard to prolactin, ACTH and GH secretion.

Schedule-controlled behavior in rats exposed perinatally to the PCB mixture Aroclor 1254.

Exposure to polychlorinated biphenyls (PCBs) has been shown to detrimentally affect learning and memory in children as well as schedule-controlled behavior in experimental animals. The objective of the present series of experiments was to extend research into the effects of PCBs on behavior maintained under both short (30 s) and long (5 min) fixed-interval (FI) schedules as well as an FI 3-min with reinforcement omission. Long-Evans rats were exposed to 0 or 6 mg/kg/day Aroclor 1254 (A1254) via oral gavage from Gestation Day 6 (GD 6) through Postnatal Day 21 (PND 21). At approximately PND 90, acquisition and steady-state performance were assessed under a series of FI reinforcement schedules consisting of FI 30-s, FI 5-min, and FI 3-min with 33% of the scheduled reinforcers omitted. Performance measures included index of curvature (IOC), response rate, and postreinforcement pause (PRP). There were no effects of A1254 on the acquisition of behavior under the FI 30-s schedule. Subsequently, there was an initial decrease in response rate and IOC and an increase in PRP following the transition from FI 30-s to the FI 5-min; there were, however, no treatment-related effects on any measure. During the reinforcement-omission procedure, there was an increase in the rate of responding and a decrease in IOC and PRP following omission intervals irrespective of treatment. These data are inconsistent with previous findings and suggest that perinatal A1254 exposure in the rat does not disrupt temporally organized behavior.

The prolactin releasing peptides: RF-amide peptides.

Although dopamine is considered the major hypothalamic controller of prolactin release from the anterior pituitary gland, there is evidence that a yet to be discovered prolactin releasing factor (PRF) also exists in brain. Recently, two peptides were isolated, products of the same prohormone, that were reported to have significant prolactin-releasing activity. These peptides, called prolactin releasing peptides, are not accepted by all investigators to be in fact PRFs. Instead, it appears that their widespread distribution in brain and the presence of receptors for the peptides in sites unrelated to neuroendocrine function are the basis for a variety of central nervous system action including activation of the autonomic nervous system. Thus, these peptides may not be PRFs, but instead neuroactive agents that are involved in many brain circuits with divergent functions.

Hypocretin/orexin suppresses corticotroph responsiveness in vitro.

The hypocretin/orexins (Hcrts/ORXs) are peptides produced in neurons in the lateral hypothalamic area that project to neuroendocrine centers in the hypothalamus. Hcrt/ORX receptors are present in the hypothalamus and anterior pituitary gland. We examined the possibility that the Hcrts/ORXs, which we have demonstrated previously to act in the brain to stimulate sympathetic function, could alter stress hormone secretion by a direct pituitary action. In vitro studies revealed a dose-related inhibitory effect of the Hcrts/ORXs on corticotropin-releasing hormone-stimulated ACTH secretion that appeared to be mediated via the orexin-1 receptor and to be expressed at doses (threshold dose 1 nM orexin A) similar to the affinity constant for the receptor. The effect was not due to abrogation of the cAMP response of the corticotroph to corticotropin-releasing hormone and was not pertussis toxin sensitive, suggesting a non-G(i)-mediated mechanism. Instead, a G(q)-mediated signaling mechanism was indicated by the ability of protein kinase C blockade with calphostin C to reverse the inhibitory action of orexin A. Orexin A and orexin B did not significantly alter basal ACTH secretion in vitro and did not alter basal or releasing factor-stimulated secretion of luteinizing hormone, prolactin, thyroid-stimulating hormone or growth hormone from cells harvested from male or random-cycle female donors. Our data suggest a direct, pituitary action of the Hcrts/ORXs to modulate the endocrine response to stress and identify the potential cellular mechanism of a unique biological action of the peptides in the anterior pituitary gland.

Adrenomedullin and central cardiovascular regulation.

Adrenomedullin gene products have been localized to neurons in brain that innervate sites known to be important in the regulation of cardiovascular function. Those sites also have been demonstrated to possess receptors for the peptide and central administrations of adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) elevate blood pressure and heart rate in both conscious and anesthetized animals. The accumulated evidence points to a role of the sympathetic nervous system in these cardiovascular effects. These sympathostimulatory actions of AM and PAMP have been hypothesized to be cardioprotective in nature and to reflect the central nervous system (CNS) equivalent of the direct cardiostimulatory effects of the peptides in the periphery. This review summarizes the most recent data on the CNS actions of the adrenomedullin gene-derived peptides and suggests future strategies for the elucidation of the physiologic relevance of the already demonstrated, pharmacologic actions of these peptides.

Generation of mutant murine cytomegalovirus strains from overlapping cosmid and plasmid clones.

We have developed a cosmid and plasmid system to generate mutant strains of murine cytomegalovirus (MCMV). The system is based on a series of seven overlapping cosmid clones that regenerate MCMV when cotransfected into mouse cells. The unaltered cosmids produce MCMV that is indistinguishable from wild-type MCMV based on restriction enzyme digest patterns of virus DNA and growth rates both in vitro and in vivo. Analysis of viral DNA from plaque-purified recombinant isolates taken from in vitro and in vivo stocks indicated that regeneration did not introduce novel mutations in the recombinant viral genomes. Isolation of specific genes and subsequent generation of specific mutant MCMVs was accomplished by replacement of cosmids with overlapping plasmid subclones. A new vector, PmeSUB, featuring a multiple cloning site and a stringent origin of replication, was constructed to make large subclones for use with smaller subclones containing the gene of interest. The utility of this system was demonstrated by the generation of two different mutant MCMVs from different combinations of overlapping plasmid subclones of one cosmid. The advantages of this system are that (i) target genes are maintained as small clones making them amenable to standard in vitro mutagenesis manipulations and that (ii) no reporter or selection genes are necessary to identify mutants.

A different function for a critical tryptophan in c-Raf and Hck.

The similarity of the catalytic domains of Raf and Src family members suggests that functions of homologous residues may be similar in both kinase families. A tryptophan residue, W260, in the WEI region of the Src family kinase Hck has an important role in regulating ATP binding. We tested the hypothesis that the tryptophan, W342, in the WEI region of c-Raf may have a similar role to the W260 of Hck. Mutation of W260 to A in Hck activates kinase activity, but we found that mutation of W342 to A in c-Raf inactivates the kinase activity. Mutating W342 to aspartate (D), lysine (K) or histidine (H) also inactivated c-Raf whether assayed as a purified immunoprecipitate or when recruited to the plasma membrane. A constitutively active c-Raf can be generated by mutating two regulatory tyrosines to aspartate. When placed into this active c-Raf mutant, mutation of W342 to D, K or H enabled phosphorylation and activation of the c-Raf substrate MEK at the plasma membrane but not in an immunoprecipitation assay. We conclude that (1) Tryptophan has a different role in the WEI regions of c-Raf and Hck, (2) W342 is not directly involved in MEK binding as both positive and negative residues at 342 are permissive for MEK activation at the membrane in a constitutively active c-Raf mutant, (3) Factors at the membrane are capable of potentiating activation of c-Raf containing mutated W342 in a hyperactivated c-Raf, but not in a wild type c-Raf and (4) There is a stringent structural requirement for W at residue 342 in c-Raf.

Reasons for tooth extraction in Scotland.

OBJECTIVES: A 1984 study investigated the reasons underlying the extraction of teeth in Scotland. The survey described in this paper, used a similar methodology and aimed to determine the reasons for the extraction of permanent teeth by general dental practitioners and investigate changes in the influences on tooth extraction over a 10 year period. METHODS: During a 1 week period in November 1994, 139 general dental practitioners working throughout Scotland, recorded the reasons for all permanent tooth extractions. RESULTS: A total of 917 permanent teeth were extracted from 613 patients, the reason for extraction being stated as dental caries (51%), periodontal disease (21%), orthodontics (11%) and failed endodontics (4%). Trauma, pericoronitis and other reasons accounted for 5.5% of extractions whilst, in 7.5% of cases, patients requested extraction in preference to other treatments. The proportion of extractions attributed to periodontal disease increased from age 31-60 years, but declined thereafter. CONCLUSIONS: Comparing the results with those obtained in the 1984 study, whilst the mean number of teeth extracted by each practitioner had reduced, the overall relative contribution of different reasons for extraction was similar.

Prioritisation of research recommendations from a national needs assessment programme.

OBJECTIVE: To gain consensus on and rank research and development recommendations from a series of Scottish Needs Assessment Programme (SNAP) reports. DESIGN: A two stage Delphi questionnaire was used and participants were asked to rank the recommendations in terms of potential health gain, practicality and priority. SUBJECTS: Views were sought from all consultants in dental public health in Scotland and from non-consultant members of the SNAP oral health steering group. RESULTS: Of the 17 individuals eligible, 16 participated in the study. Fifty four recommendations for research and development were identified in seven SNAP reports. Recommendations relating to the prevention of dental caries in young children, the organisation and delivery of dental care to disadvantaged groups and increased understanding of the aetiology and pathogenesis of oral cancer in younger people were seen as of highest priority. CONCLUSIONS: This study has drawn together and prioritised a series of recommendations, and will help inform future oral health research needs in Scotland.