Perceptual-Auditory and Acoustic Analysis of Breathiness in Cis and Transgender Men and Women.

OBJECTIVE: To verify breathiness in the cisgender and transgender men and women's voices, compare values of acoustic and perceptual indicators of breathiness and fundamental frequency (f0) between groups, and compare them between the voices attributed as female and male. STUDY DESIGN: Cross sectional retrospective study. METHODS: The study was approved by the Research Ethics Committee (4,937,140). Sustained vowel /a/ and continuous speech recordings of 21 cisgender men (CISM), 31 transgender men (TM), 32 cisgender women (CISW), and 31 transgender women (TW) were analyzed. Three judges conducted a perceptive-auditory analysis regarding the degree breathiness, using a visual analog scale, and attributed gender (female or male). The ABI (Acoustic Breathiness Index) was extracted using the PRAAT software (6.1.16). The f0, Harmonic-Noise Ratio (HNR), Voice Turbulence Index (VTI), and Soft Phonation Index (SPI) were analyzed using the Multi-Dimensional Voice Program (KayPentax). RESULTS: The ABI value for CISM was lower than for TM and CISW. CISW had a higher f0 than; TM had a higher f0 than CISM; and TW had a higher f0 than CISM. The groups did not differ for HNR and VTI. Regarding the SPI, CISM had higher values than CISW. Regarding the auditory perception, TM presented more intense breathiness than CISM in the vowel. Regarding gender attribution by voice, the voices CISM and CISW were 100% identified as male and female. On the other hand, in the vowel analysis, 45.2% of the TM voices were perceived as female, and 59.4% of TW voices as male. CONCLUSION: Breathiness occurs differently between groups and the voices perceived as male and female. Even when TM is submitted to the use of testosterone and undergoes vocal changes, the transglottal airflow remains, which is a female characteristic of phonation.

Fifty years after its discharge, methylation of legacy mercury trapped in the Penobscot Estuary sustains high mercury in biota.

Fifty years ago, the Penobscot Estuary was contaminated by mercury discharged from the chlor-alkali plant located in Orrington, Maine, USA. Almost all of the mercury was discharged from the plant during the late 1960s and early 1970s. Despite the much lower mercury discharges in recent decades, present-day concentrations in surface sediment remain high (averaging 350-1100 ng/g dw) and are still high in blood of marsh birds (up to 10.5 µg/g), black duck muscle (0.8 µg/g), and lobster muscle (0.4 µg/g). Methyl mercury (MeHg) concentrations in marsh birds exceed levels that impair reproduction. There are health advisories for duck hunters and closures of shellfish fisheries. These continuing high mercury concentrations are caused by the trapping of legacy mercury in a mobile pool of sediment that is retained in the upper estuary above a tidally forced salinity front, which travels up and down the estuary each tidal cycle - slowing the transport of particulate mercury to Penobscot Bay. The trapped legacy mercury continues to be available for methylation 50 years after it first entered the estuary. This is demonstrated by the fact that rates of MeHg production are positively related to the inorganic mercury concentration in parts of the estuary with elevated concentrations of legacy mercury. Thus, remediation measures that would lower the THg concentration in surface sediment would lower the MeHg in birds, fish and shellfish. All of this new information leads us to recommend two remediation options. Addition of mercury binding agents may lower mercury concentrations in birds in some wetland areas. System-wide, we also recommend Enhanced Natural Recovery (ENR), a novel approach that involves the partial removal of the contaminated mobile sediment pool followed by replacement with clean-clay particulates to dilute inorganic mercury concentrations, which would lower methylation rates and mercury concentrations in biota.

Cortical map plasticity as a function of vagus nerve stimulation rate.

BACKGROUND: Repeatedly pairing a brief train of vagus nerve stimulation (VNS) with an external event can reorganize the sensory or motor cortex. A 30 Hz train of sixteen VNS pulses paired with a tone significantly increases the number of neurons in primary auditory cortex (A1) that respond to tones near the paired tone frequency. The effective range of VNS pulse rates for driving cortical map plasticity has not been defined. OBJECTIVE/HYPOTHESIS: This project investigated the effects of VNS rate on cortical plasticity. We expected that VNS pulse rate would affect the degree of plasticity caused by VNS-tone pairing. METHODS: Rats received sixteen pulses of VNS delivered at a low (7.5 Hz), moderate (30 Hz), or high (120 Hz) rate paired with 9 kHz tones 300 times per day over a 20 day period. RESULTS: More A1 neurons responded to the paired tone frequency in rats from the moderate rate VNS group compared to naïve controls. The response strength was also increased in these rats. In contrast, rats that received high or low rate VNS failed to exhibit a significant increase in the number of neurons tuned to sounds near 9 kHz. CONCLUSION: Our results demonstrate that the degree of cortical plasticity caused by VNS-tone pairing is an inverted-U function of VNS pulse rate. The apparent high temporal precision of VNS-tone pairing helps identify optimal VNS parameters to achieve the beneficial effects from restoration of sensory or motor function.

The effect of vitamin D levels on the assessment of disease activity in rheumatoid arthritis.

Disease activity in rheumatoid arthritis (RA) is assessed by a combination of objective and subjective tests, combined to produce a disease activity score in 28 joints (DAS28). There is some evidence that RA disease activity, as assessed by DAS28, can be influenced by vitamin D levels. It is difficult to know whether this is due to a true immunomodulatory effect of vitamin D or a more subjective effect of low vitamin D on pain perception. We addressed this issue by comparing vitamin D levels with disease activity, analysing each component of the DAS28 score separately. We measured 25-hydroxy vitamin D levels in 176 outpatients with RA at two different centres and recorded a DAS28 score using an ESR checked at the same time. We calculated DAS28 both with and without the patient's rating of their symptoms on the visual analogue score (VAS) to assess the effect of VAS on DAS28. The vitamin D results were expressed as nanomole per litre with 50 nmol/l taken as the lower limit of normal. We calculated mean levels of vitamin D and undertook a multivariate regression analysis to assess correlations between vitamin D levels and DAS28 (and its individual components), corrected for centre, age and gender. The overall mean DAS28 score was 3.66 (SE ± 0.11) using all four criteria and 3.43 (SE ± 0.10) using just three criteria (omitting VAS). The mean vitamin D level was 39.42 nmol/l (SE ± 1.55). There was no significant correlation between vitamin D and DAS28 scores with or without the inclusion of VAS. However, there was a significant inverse relationship between vitamin D and VAS itself (coefficient = 0.249, p = 0.013). The mean DAS28 score was greater in vitamin D-deficient patients and this was explained by their higher VAS scores. Our data confirms that vitamin D deficiency is common in RA. This paper provides evidence that the VAS component, assessing patient perception of symptoms, is inversely related to vitamin D, with lower levels producing higher VAS values. Although there was no overall correlation between vitamin D levels and DAS28, patients may perceive themselves or be perceived by assessors as having responded less well to disease modification in the presence of vitamin D deficiency. This could have major implications for subsequent management, and clinicians need to be aware of the potential confounding effect of vitamin D deficiency in assessing RA disease activity using the full DAS28 tool.

Urinary tract infections in patients with rheumatoid arthritis.

Co-morbidity from rheumatoid arthritis (RA) has recently focussed on outcomes of cardiovascular and pulmonary disease, but serious infections are an increasingly well-recognised complication of RA. Recent work has demonstrated how the incidence of pneumonia can be reduced in RA, but little attention has been paid to the incidence of urinary tract infection (UTI) in RA or to the associated co-morbidity. The aim of this study was to describe the incidence of UTI leading to hospitalisation in a large cohort of patients with RA and investigate which factors contributed to this. This study assessed all patients with RA hospitalised over a 12-month period with a discharge diagnosis including UTI. Patients were identified through a PAS records search in a single large centre. Historical case controls without RA matched for age and gender were identified from the literature. Clinical notes were manually examined by two observers. We recorded: age, gender, duration of RA, number of UTI, all RA therapy, co-morbidity, results of urine and blood cultures with antimicrobial sensitivities, readmission rates, treatment and outcome. We calculated the relative risk (RR) of developing UTI in patients with RA and the factors influencing this. From a population of 2,200 RA patients, the overall annual incidence of hospitalisation with UTI amongst RA patients was 2.09 %, as against 0.97 and 0.91 % for two control groups (RR = 2.16 and 2.29). Most patients (90 %) were female, and the group mean age was 76 years. The use of long-term oral steroids as sole therapy was associated with a RR of 6.8 for UTI (p = 0.002) while failure to take disease-modifying anti-rheumatic drugs (DMARDs) was associated with a similar RR of 6.7 (p = 0.001). Positive cultures for Escherichia coli were found in 51 % of RA patients. Relevant co-morbidities included permanent catheters, vaginal prolapse, cancer and diabetes. Recurrence of UTI within a year was common. RA was associated with a higher-than-expected incidence of UTI, particularly among older females. This was associated with the use of long-term oral steroids and the absence of DMARDs. Other factors included female gender, greater age and long disease duration. We recommend avoidance of long-term oral steroids but consideration of low-dose prophylactic antibiotics in those patients with recurrent UTI.

Anaemia in rheumatoid arthritis: can we afford to ignore it?

INTRODUCTION Anaemia is common in rheumatoid arthritis (RA). Clinicians may focus on rheumatological issues and assume anaemia of chronic disease (ACD). This study challenged this assumption and investigated the causes of anaemia in a large cohort of RA patients to assess its implications. METHODS The hospital where the study was conducted monitors regular full blood count and erythrocyte sedimentation rate (ESR) monthly in all RA patients on disease modifying drugs to assess efficacy and safety. A computerised system identifies and records abnormal results. The database for 2009 was interrogated to find all patients with two consecutive haemoglobin values <11 g/dl. Using a proforma, patients were defined as having iron deficiency anaemia (IDA), ACD, macrocytic anaemia (MCA) or another cause. All results of further tests investigating the anaemia were recorded. RESULTS Among 2000 RA patients on the system, 199 (10%) were identified as having anaemia over a year. Of these, 90 had IDA, 78 had ACD, 25 had MCA, and 6 had postoperative anaemia. Among 90 patients with IDA, investigations were performed in 53, with 23 normal. An explanation for IDA was found in 30: gastrointestinal bleeding in 25, gynaecological blood loss in 3, and urinary bleeding in 2. Among 78 patients with ACD, response to intensification of RA treatment occurred in 45, but erythropoietin therapy was required in 9. Within the 25 patients with MCA, 12 had unrecognised vitamin B(12) deficiency, 4 drug induced changes, 3 myeloid malignancy, 2 hypothyroidism, and 2 alcoholism. CONCLUSIONS Anaemia in RA is common, multifactorial, and potentially both serious and correctable. Established malignancy was present in 10 patients and premalignancy in a further 10 (10% of total). Treatable causes were commonly identified. Clinicians need to investigate the nature and cause of persistent anaemia, and must not assume it to be simply ACD without evidence.

How to reduce morbidity and mortality from chest infections in rheumatoid arthritis.

Morbidity and mortality from pneumonia is increased in patients with rheumatoid arthritis. Factors contributing to this have been recently identified and a number of recommendations have been implemented in an attempt to reverse this trend. The present paper shows that these measures have combined to produce a fourfold reduction in both admissions and case fatality rates. In the study population, immunisation rates against influenza and pneumococcus have improved to 86% and 65%, oral steroid consumption has halved and disease modifying drugs were usually appropriately suspended during acute infection. These measures may now merit more widespread adoption.

The importance of postpartum glucose tolerance testing after pregnancies complicated by gestational diabetes.

AIMS: To review postpartum glucose tolerance in women with gestational diabetes and evaluate the role of formal 75 g oral glucose tolerance testing vs. fasting plasma glucose in screening for persistent abnormalities. METHODS: Retrospective study of 985 pregnancies over a 10 year period in a mixed ethnic cohort of women who underwent follow-up glucose tolerance testing at 6 weeks postpartum. Diagnosis obtained by oral glucose tolerance test was tested against that from the fasting plasma glucose value. RESULTS: There were 272 abnormal postpartum oral glucose tolerance test results (27.6%), with 109 women identified as having frank diabetes. Eleven of these (10%) had fasting plasma glucose < or =6.0 mmol/l, as did 62 of 114 cases of impaired glucose tolerance. A fasting plasma glucose concentration of > or =6.1 mmol/l correctly identified abnormal glucose tolerance in 199 of 272 cases (sensitivity 0.73). South Asian women were much more likely to have persistent abnormalities of glucose tolerance than were Europeans (32 vs. 15%, chi(2)P < 0.0001). CONCLUSIONS: A postpartum fasting plasma glucose measurement alone is not sensitive enough in our population to classify glucose tolerance status accurately. A formal postpartum oral glucose tolerance test is therefore needed to facilitate early detection and treatment.

Sustained release hGH microsphere formulation produced by a novel supercritical fluid technology: in vivo studies.

Novel sustained release formulations of hGH prepared by supercritical fluid processing of PLGA/PLA (the CriticalMix process) were produced in the form of microparticles for subcutaneous injection. The basis of the process is that PLGA/PLA polymers liquefy when exposed to supercritical CO(2), thereby allowing the hGH to be mixed efficiently into the polymers at an ambient temperature and in the absence of solvents. The CO(2) was removed from the mixture by depressurisation through a nozzle, resulting in the production of microparticles containing the hGH, which were collected in a cyclone. The best microparticle formulations showed an initial in vitro burst of around 35% and a sustained release over 14 days. When tested in the rat model, which displays a faster clearance rate of hGH than other animal models, two formulations showed prolonged release over 2-3 days with sustained plasma levels at 1-5 ng/ml whereas the soluble hGH formulation was cleared within 24h. Two selected sustained release formulations were tested in cynomolgus monkeys and compared to a single injection of soluble hGH. The burst release from the sustained release formulations was similar in magnitude to a daily dose of hGH and serum hGH levels were maintained for a seven day period. It is probable from the data that the sustained release would have continued for up to 14 days if sampling had been continued. The IGF-1 results showed there was no significant difference between the levels obtained for once daily injection of soluble hGH and the two sustained release formulations.

Gross synovial fluid analysis in the differential diagnosis of joint effusion.

AIMS: To develop an objective and easy to complete standardised questionnaire for documentation of synovial fluid (SF) gross appearance and use it in the assessment of patients presenting to the rheumatology service with a joint effusion. METHODS: A standardised questionnaire to record the gross appearance of SF was developed. Interobserver error in recorded observations and direct gross analysis of synovial fluid between four observers was calculated in a pilot study. In a prospective study over 8 months, SF gross analysis and cell count were documented in all patients presenting with a joint effusion. Fusch Rosenthal manual counting chamber was used for calculating SF cell counts. RESULTS: There was good interobserver agreement on direct gross analysis and between questionnaire assessors (mean kappa 0.889). 80 SF samples were collected. Gross analysis was performed in all samples and cell count in 72. Of the specimens thought to be inflammatory on gross analysis, 31% were found to be non-inflammatory based on cell count; however, 12 of these patients had an established inflammatory arthritis. Gross analysis had a sensitivity of 94% and specificity of 58% when used to determine whether SF is inflammatory or non-inflammatory. The positive and negative predictive values were 0.69 and 0.91 respectively. CONCLUSIONS: SF cell count did not add any information when SF gross analysis suggested a non-inflammatory process. Gross analysis was better than cell count to determine a potentially septic joint fluid. Further work needs to be done on the value of SF cell counts if gross analysis suggests the fluid to be inflammatory.

O ruído em sala de aula e a percepção dos professores de uma escola de ensino fundamental de Piracicaba / Classroom noise and the perception of the teachers in a school of Piracicaba city

Os professores estão entre os profissionais sujeitos às alterações de saúde devido às condições de trabalho inadequadas, como ruído ambiental (alunos, rua, ventiladores), acústica ruim e organização do trabalho (cargas extensas). Essas condições podem ocasionar efeitos auditivos e extra-auditivos nesse profissional, resultando em estresse e cansaço, além de possibilitar a ocorrência de problemas na comunicação, como a disfonia. Objetivo: analisar as percepções dos professores sobre os efeitos do ruído em sala de aula na sua saúde. Método: participaram desta pesquisa, 36 professores do ensino fundamental de uma escola Pública de Piracicaba. Foram realizadas mensurações do ruído em sala de aula, entrevistas sobre efeitos auditivos e extra-auditivos causados pela exposição ao ruído e exames audiométricos. Resultado: 75 por cento dos professores consideraram o ruído em sala de aula alto; na mensuração do ruído, encontrou-se variação de 55 a 102 dB(A). A maioria dos professores (86 por cento) relatou sintomas extra-auditivos (tontura, problemas digestivos e no sistema cirulatório), 95 por cento deles apresentaram queixas vocais (cansaço e ardor na laringe após a aula) e efeitos do ruído sobre comunicação oral em sa1a de aula (precisam falar mais alto, têm dificuldade de se fazer entender e compreender o que lhes falam). Conclusão: o ruído encontrado nas salas de aula dessa escola pode ter relação direta com os efeitos na saúde do professor, porém, há necessidade de outros estudos que aprofundem o tema. Percebe-se, então, neste estudo, a urgência em alertar a sociedade, especialmente os profissionais da saúde, sobre os efeitos prejudiciais decorrentes da exposição ao ruído

An unusual cause of fitting in a 20 year old girl.

Native renal artery stenosis resulting in hypertensive encephalopathy is exceptionally rare, with only 3 previous case reports in adults. We report such a case in a previously well 20 year old female.

Influence of diabetes on peripheral bone mineral density in men: a controlled study.

The aims of the study were to (1) compare peripheral bone mineral density (BMD) in men with diabetes to peripheral BMD in non-diabetic men, and (2) explore factors which may predict BMD in diabetic men. Ninety men with type 2 diabetes and 35 men with type 1 diabetes were randomly selected for participation via a computerised database. Fifty healthy males were also recruited. All patients had peripheral BMD measured by dual energy Xray absorptiometry (DEXA) at the non-dominant distal radius. Information on a number of clinical parameters was obtained by direct questioning, and from patient case notes. The mean age (95% confidence interval (CI)) of the type 1 diabetic group, type 2 diabetic group and control group were, respectively: 49.3 years (44.6-53.9), 62.8 years (60.7-64.8) and 38.5 (34.9-42.1) years. Median (95% CI) Z-scores for the three groups were: -0.18 (-0.68 to +0.32), +0.19 (-0.14 to +0.49) and -0.02 (-0.4 to +0.31), respectively (p=not significant). Only body mass index (BMI) was correlated with BMD in the type 1 diabetic group, and only BMI and age were correlated with BMD in type 2 diabetics. There was no correlation between BMD and glycosylated haemoglobin concentration (HbA(1)c), disease duration or presence of microvascular or macrovascular complications in either of the diabetic groups. We did not find any significant difference in peripheral BMD between patients with type 1 diabetes, type 2 diabetes and controls.

The pattern and significance of abnormal liver function tests in community-acquired pneumonia.

BACKGROUND: The pattern of liver function tests (LFTs) in community-acquired pneumonia has not been investigated in detail. Although abnormal tests are thought to be more frequent in patients with atypical pneumonia, the prognostic value of LFTs have not been clearly established. METHODS: We assessed 96 consecutive patients admitted to one hospital with a chest infection over a period of 6 weeks. The infection was classified as bronchitis or lobar pneumonia on clinical and radiological criteria. The site and severity of the infection were assessed and correlated with LFTs and standard British Thoracic Society prognostic criteria. Mortality and length of stay in survivors were used as major outcome measures. RESULTS: There were 17 deaths (18%) overall and patients with abnormal LFTs were significantly more likely to die than those with normal tests (25% vs. 5%; p=0.026). Length of stay was significantly longer in survivors with abnormal liver function than in those with normal tests (9.7 vs. 5.8 days; p=0.006). A low albumin was the most useful predictor of poor outcome and carried a relative risk of dying of 1.8, comparable to the predictive value of tachypnoea. ALT was increased threefold in those succumbing to their disease, but alkaline phosphatase levels were not predictive of outcome and an increase in gamma GT appeared to be protective. CONCLUSIONS: Abnormal LFTs are common in community-acquired pneumonia and are of prognostic value. Patients with a low albumin or raised ALT are significantly more likely to die from their disease or to stay in hospital for a prolonged period. However, other LFTs are of less value in predicting prognosis.

Electrocardiogram and cardiovascular changes in thioridazine and chlorpromazine poisoning.

OBJECTIVES: To examine the effects of anti-psychotic medications on cardiovascular parameters in overdose. Specifically, to examine dose-response relationships for thioridazine and chlorpromazine. METHODS: A retrospective study of case records of patients presenting to the Edinburgh poisons treatment unit over 3 years (2000-2002). Information--including that on stated dose ingested, ECG parameters, and pulse and blood pressure--was extracted from case notes. RESULTS: A total of 224 chlorpromazine, 96 thioridazine and 99 patients ingesting other anti-psychotics were evaluated. Full data on all aspects, both dose and cardiovascular change, was available in 96 chlorpromazine, 36 thioridazine and 27 of the other anti-psychotic cases. For thioridazine, there was a significant dose-response relationship for increasing heart rate and increasing QTc but not other cardiovascular changes. For chlorpromazine, there was no dose-response relationship for ECG changes, but there was a significant dose-response relationship for increasing heart rate and reduction in mean blood pressure. CONCLUSIONS: We have confirmed a relationship between increasing dose of thioridazine and prolongation of QTc in overdose patients. No such change was observed with chlorpromazine. Both of these agents are reported to cause QT prolongation, but this study suggests that the nature of these effects is different for each agent. Poisoned patients may offer ways of exploring in more detail, and at a larger dose range, the effects of potentially cardiotoxic drugs in humans.

Are selective serotonin re-uptake inhibitors associated with an increased risk of self-harm by antidepressant overdose?

OBJECTIVE: To investigate likelihood of self-harm by overdose with antidepressant drugs of different types by examining hospital admission data and poisons inquiries and relating them to prescribing. DESIGN: Retrospective analysis of prospectively collected data on overdose admissions, poisons inquiries and prescribing of antidepressants in Edinburgh and Scotland. SETTING: Poisons treatment unit of the Royal Infirmary of Edinburgh and its surrounding catchment for overdose cases and Scotland for poisons inquiries. PARTICIPANTS: All patients admitted to the Royal Infirmary of Edinburgh between 1 January 2000 and 31 December 2002 with an overdose involving an antidepressant. MAIN OUTCOME MEASURES: Overdose admissions (patients) in relation to prescribing in Edinburgh and poisons inquiries in relation to prescription rates in Scotland. RESULTS: There were 1656 admissions involving 1343 patients. The likelihood of admission for an individual patient in relation to volume of prescribing (likelihood ratio: 95%CI) in the catchment was somewhat smaller for amitriptyline (0.83:0.74-0.92) and sertraline (0.79:0.63-0.99), and somewhat greater for mirtazapine (1.99:1.57-2.51), trazadone (1.30:1.09-1.54) and venlafaxine (0.97:1.81-1.16) [corrected] For poisons inquiries in Scotland, the excess for venlafaxine and mirtazapine was confirmed and likelihood of an inquiry lowest for selective serotonin re-uptake inhibitors (SSRIs). CONCLUSIONS: There was no evidence of an excess likelihood of presentation with overdose with SSRIs, and the likelihood was reduced with sertraline. There was a small excess of both admissions and poisons inquiries for mirtazapine and venlafaxine. This is a concern in view of the increased toxicity of venlafaxine in overdose in comparison with SSRIs.

Comparative toxicity of citalopram and the newer antidepressants after overdose.

OBJECTIVE: To compare the toxicity of citalopram, venlafaxine, mirtazapine, and nefazadone after overdose. METHODS: Two-year retrospective review of consecutive patients admitted to the toxicology unit of Edinburgh Royal Infirmary. Outcome measure included physiological variables, ECG recordings, peak creatine kinase, development of arrhythmias, seizure, tremor or agitation, and the need for admission to a critical care facility. RESULTS: A total of 225 patients were studied. Venlafaxine was associated with a significantly higher pulse rate (p < 0.0001) and tremor (p = 0.007) than other antidepressants. Citalopram was associated with a significantly longer QT interval on ECG recording (p < 0.0001) but mean QTc durations were not significantly different between all drugs studied. No arrhythmias were recorded. Only venlafaxine and citalopram caused seizures and were associated with the need for admission to Intensive Care, but there was no significant difference between them. CONCLUSIONS: Mirtazapine and nefazadone appear safe in overdose and were associated with minimal features of neurological or cardiovascular toxicity. Citalopram is more likely to cause QT prolongation but other features of cardiovascular toxicity were uncommon. Both citalopram and venlafaxine are proconvulsants. Venlafaxine also causes more frequent features of the serotonin syndrome.