No association between the -308 polymorphism in the tumour necrosis factor alpha (TNFalpha) promoter region and polycystic ovaries

The tumour necrosis factor (TNF)2 allele appears to be linked with increased insulin resistance and obesity, conditions often found in overweight patients with polycystic ovary syndrome (PCOS). The significance of TNFalpha polymorphism in relation to the clinical and biochemical parameters associated with PCOS was investigated in 122 well-characterized patients with polycystic ovaries (PCO). Of these, 84 had an abnormal menstrual cycle and were classified as having PCOS, while the remaining 38 had a normal menstrual cycle and were classified as having PCO. There were a further 28 individuals without PCO (non-PCO) and 108 individuals whose PCO status was undetermined (reference population). The promoter region of the TNFalpha gene was amplified by polymerase chain reaction (PCR), and the presence or absence of the polymorphism at -308 was determined by single-strand conformational polymorphism (SSCP) analysis. The less common TNF allele (TNF2) was found as TNF1/2 or TNF2/2 in 11/38 (29%) of PCO subjects, 25/84 (30%) of PCOS subjects, 7/28 (25%) of non-PCO subjects, and 45/108 (42%) of the reference population. There was no significant difference in the incidence of the TNF2 allele between the groups. The relationship of TNF genotype to clinical and biochemical parameters was examined. In both the PCO group and the PCOS group, the presence of the TNF2 allele was significantly associated with lower glucose values obtained from the glucose tolerance testing (P<0.05). The TNF genotype was not significantly associated with any clinical or biochemical parameter measured in the PCO, PCOS or non-PCOS groups. Thus, the TNFalpha -308 polymorphism does not appear to strongly influence genetic susceptibility to polycystic ovaries.     

Stage, survival and delays in lung, colorectal, prostate and ovarian cancer: comparison between diagnostic routes

BACKGROUND: Very few studies have reported cancer outcomes of patients referred through different routes, despite the prominence of current UK cancer urgent referral guidance. AIM: This study aimed to compare outcomes of cancer patients referred through the urgent referral guidance with those who were not, with respect to stage at diagnosis, survival, and delays in diagnosis. Design of study: Analysis of hospital records. SETTING: One hospital trust in England. METHOD: The records of 889 patients diagnosed in 2000-2001 with one of four types of cancer were analysed: 409 with lung cancer; 239 with colorectal cancer; 146 with prostate cancer; and 95 with ovarian cancer. Outcome measures were diagnostic stage, survival, referral and secondary care delays. RESULTS: For lung cancer, urgent referrals had more advanced TNM (tumor, node, metastasis) stage than patients diagnosed through other routes (P = 0.035) and poorer survival (P = 0.020). There was no difference in stage or survival for the other cancers. For each cancer, a higher proportion of urgent referrals was seen within 2 weeks. Secondary care delays for lung and colorectal cancer were shorter for inter-specialty referrals. CONCLUSION: For patients with lung cancer, the guidance appears to be prioritising those in the more advanced stages of disease. This was not the case for the other three cancers. Referral delays were shorter for patients urgently referred, as is the intention of the guidance. The avoidance of delays in outpatient diagnostics probably accounts for shorter secondary care delays for inter-specialty referrals.     

Vertical gaze angle as a distance cue for programming reaching: insights from visual form agnosia II (of III)

It has been shown that a patient with visual form agnosia (DF) relies predominantly on vergence information when gauging target distance in an open-loop pointing task. This finding suggested that the programming of prehension might be severely disrupted if DF viewed target objects through ophthalmic prisms. An initial experiment showed that this prediction was not upheld; DF was able to programme reasonably accurate movements to objects located on a tabletop despite large changes in vergence angle. A second experiment, however, showed that placing the target objects at eye height whilst manipulating vergence angle caused gross disruption to prehension, with DF mis-programming the reach component in a predictable manner. Notably, the evidence for DF's reliance on vergence distance information was obtained in a task where the targets were viewed at eye height. These experiments indicate that DF uses vertical gaze angle to gauge target distance in normal prehension and suggest that this extra-retinal cue may be a useful source of distance information for the human nervous system, especially where pictorial cues are impoverished. Electronic Publication     

Inability to activate muscles maximally during cocontraction and the effect on joint stiffness

In order to determine the maximum joint stiffness that could be produced by cocontraction of wrist flexor and extensor muscles, experiments were conducted in which healthy human subjects stabilized a wrist manipulandum that was made mechanically unstable by using positive position feedback to create a load with the characteristics of a negative spring. To determine a subject's limit of stability, the negative stiffness of the manipulandum was increased by increments until the subject could no longer reliably stabilize the manipulandum in a 1° target window. Static wrist stiffness was measured by applying a 3° rampand-hold displacement of the manipulandum, which stretched the wrist flexor muscles. As the load stiffness was made more and more negative, subjects responded by increasing the level of cocontraction of flexor and extensor muscles to increase the stiffness of the wrist. The stiffness measured at a subject's limit of stability was taken as the maximum stiffness that the subject could achieve by cocontraction of wrist flexor and extensor muscles. In almost all cases, this value was as large or larger than that measured when the subject was asked to cocontract maximally to stiffen the wrist in the absence of any load. Static wrist stiffness was also measured when subjects reciprocally activated flexor or extensor muscles to hold the manipulandum in the target window against a load generated by a stretched spring. We found a strong linear correlation between wrist stiffness and flexor torque over the range of torques used in this study (20–80% maximal voluntary contraction). The maximum stiffness achieved by cocontraction of wrist flexor and extensor muscles was less than 50% of the maximum value predicted from the joint stiffness measured during matched reciprocal activation of flexor and extensor muscles. EMG recorded from either wrist flexor or extensor muscles during maximal cocontraction confirmed that this reduced stiffness was due to lower levels of activation during cocontraction of flexor and extensor muscles than during reciprocal contraction.     

Development of brain stimulation reward in the medial prefrontal cortex: Facilitation by prior electrical stimulation of the sulcal prefrontal cortex

Electrical stimulation of the medial prefrontal cortex (MC) in rats delivered daily for seven days causes a marked improvement in the rate of acquisition of a self-stimulation response. In the present experiment, we looked at whether we could get the same facilitatory effect on self-stimulation of the MC by delivering pre-training stimulation to other points in the brain anatomically related to the MC. Electrical stimulation of the lateral hypothalamus was without effect. However, electrical stimulation of the sulcal prefrontal cortex (SC) either contralateral or ipsilateral to the MC electrode did facilitate acquisition of self-stimulation of the MC. Thus the SC and MC would appear to be part of the same substrate controlling the development of positive reinforcement in the MC.     

Judgment and control of velocity in rapid voluntary movements

Summary Control of velocity in rapid flexion movements of the interphalangeal joint of the thumb was investigated by examining movement trajectories and patterns of activity in the extensor pollicis longus (EPL) and flexor pollicis longus (FPL) muscles. Although velocity was controlled with considerable accuracy, it was not sensed with the same precision. Consistent errors were made when subjects attempted to match the peak velocities under conditions in which the relationship between muscle activity and joint acceleration had been altered, i.e. changing the angle from which movement was initiated or varying the load. Rather than relying on afferent feedback from peripheral sensory receptors for information about velocity during rapid movements, it is suggested that subjects were more likely to base their judgment of velocity on sensations evoked by the voluntary motor command.     

Unilateral striatal dopamine denervation: Reduced motor inhibitory effects of dopamine antagonists revealed in models of asymmetric and circling behaviour

Summary Circling and asymmetric behaviours to apomorphine (dopamine agonist/antagonist) challenge were studied in rats with unilateral striatal electrolesions or 6-hydroxydopamine (6-OHDA) lesions, each induced by combined lesions at 3 striatal locations, to allow an assessment of drug action on normal receptors in the intact striatum or supersensitive receptors in the lesioned striatum respectively. The minimally effective dose of 6-OHDA (given in the presence of DMI and tranylcypromine) to cause functional change was 3×8 g, with 3×32 g providing maximal change. Electrolesions were shown histologically to be confined to striatal tissue, and dopamine depletions caused by 6-OHDA were selective for the striatum.Temporal differences were recorded for onset of asymmetry and circling behaviour, both between behaviours and between lesions. Thus, asymmetry developed during the 2nd–4th days after 6-OHDA lesion but circling developed more abruptly on postoperative days 10–12. In contrast, both asymmetry and circling behaviours were apparent from the first day following electrolesion. The dose-dependent effects of apomorphine were apparent at much lower doses in 6-OHDA lesioned than electrolesioned rats. This potency difference was also demonstrated for two further dopamine agonists, 2-di-n-propylamino-5,6-dihydroxytetralin and SK & F 38393. In contrast, the agonist-induced asymmetric and circling behaviours of electrolesioned rats were some 9–44 times more sensitive than those of 6-OHDA lesioned rats to antagonism by the neuroleptic agents haloperidol, -flupenthixol and oxiperomide, although tiapride antagonism was very similar in both the electrolesioned and 6-OHDA-lesioned rats. Thus, selective striatal denervation techniques are used to show that asymmetric and circling behaviours can be differentially induced and manipulated, and that the increased sensitivity (over electrolesions) of 6-OHDA lesioned rats to dopamine agonist action to induce these behavioural effects is associated with a reduced sensitivity to neuroleptic activity to reduce the asymmetric and circling responses.     

Evaluating Differences in Whole Blood,Serum, and Urine Screening Tests for Zika Virus,Puerto Rico,USA, 2016

We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015–2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens.     

The Impact of Dental Insurance and Medical Insurance on Dental Care Utilization During Pregnancy

Maternal and Child Health Journal - To measure the association between dental and medical insurance with the receipt of dental cleaning during pregnancy. We analyzed Pregnancy Risk Assessment...     

Building a Methodological Foundation for Impactful Urban Planetary Health Science

Anthropogenic environmental change will heavily impact cities, yet associated health risks will depend significantly on decisions made by urban leaders across a wide range of non-health sectors, including transport, energy, housing, basic urban services, and others. A subset of planetary health researchers focus on understanding the urban health impacts of global environmental change, and how these vary globally and within cities. Such researchers increasingly adopt collaborative transdisciplinary approaches to engage policy-makers, private citizens, and other actors in identifying and evaluating potential policy solutions that will reduce environmental impacts in ways that simultaneously promote health, equity, and/or local economies—in other words, maximising ‘co-benefits’. This report presents observations from a participatory workshop focused on challenges and opportunities for urban planetary health research. The workshop, held at the 16th International Conference on Urban Health (ICUH) in Xiamen, China, in November 2019, brought together 49 participants and covered topics related to collaboration, data, and research impact. It featured research projects funded by the Wellcome Trust’s Our Planet Our Health (OPOH) programme. This report aims to concisely summarise and disseminate participants’ collective contributions to current methodological practice in urban planetary health research.