The association between neurodegeneration and local complement activation in the thalamus to progressive multiple sclerosis outcome.

The extent of grey matter demyelination and neurodegeneration in the progressive multiple sclerosis (PMS) brains at post-mortem associates with more severe disease. Regional tissue atrophy, especially affecting the cortical and deep grey matter, including the thalamus, is prognostic for poor outcomes. Microglial and complement activation are important in the pathogenesis and contribute to damaging processes that underlie tissue atrophy in PMS. We investigated the extent of pathology and innate immune activation in the thalamus in comparison to cortical grey and white matter in blocks from 21 cases of PMS and 10 matched controls. Using a digital pathology workflow, we show that the thalamus is invariably affected by demyelination and had a far higher proportion of active inflammatory lesions than forebrain cortical tissue blocks from the same cases. Lesions were larger and more frequent in the medial nuclei near the ventricular margin, whilst neuronal loss was greatest in the lateral thalamic nuclei. The extent of thalamic neuron loss was not associated with thalamic demyelination but correlated with the burden of white matter pathology in other forebrain areas (Spearman r = 0.79, p < 0.0001). Only thalamic neuronal loss, and not that seen in other forebrain cortical areas, correlated with disease duration (Spearman r = -0.58, p = 0.009) and age of death (Spearman r = -0.47, p = 0.045). Immunoreactivity for the complement pattern recognition molecule C1q, and products of complement activation (C4d, Bb and C3b) were elevated in thalamic lesions with an active inflammatory pathology. Complement regulatory protein, C1 inhibitor, was unchanged in expression. We conclude that active inflammatory demyelination, neuronal loss and local complement synthesis and activation in the thalamus, are important to the pathological and clinical disease outcomes of PMS.

Impact of STIMUlant and osmotic LAXatives (STIMULAX trial) on gastrointestinal recovery after colorectal surgery: randomized clinical trial.

BACKGROUND: Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. METHODS: This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. RESULTS: Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5-4) versus 3 (2-5.5) days; 95 per cent c.i. -1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. CONCLUSION: Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au).

The Thermosynechococcus Genus: Wide Environmental Distribution, but a Highly Conserved Genomic Core.

Cyanobacteria thrive in diverse environments. However, questions remain about possible growth limitations in ancient environmental conditions. As a single genus, the Thermosynechococcus are cosmopolitan and live in chemically diverse habitats. To understand the genetic basis for this, we compared the protein coding component of Thermosynechococcus genomes. Supplementing the known genetic diversity of Thermosynechococcus, we report draft metagenome-assembled genomes of two Thermosynechococcus recovered from ferrous carbonate hot springs in Japan. We find that as a genus, Thermosynechococcus is genomically conserved, having a small pan-genome with few accessory genes per individual strain as well as few genes that are unique to the genus. Furthermore, by comparing orthologous protein groups, including an analysis of genes encoding proteins with an iron related function (uptake, storage or utilization), no clear differences in genetic content, or adaptive mechanisms could be detected between genus members, despite the range of environments they inhabit. Overall, our results highlight a seemingly innate ability for Thermosynechococcus to inhabit diverse habitats without having undergone substantial genomic adaptation to accommodate this. The finding of Thermosynechococcus in both hot and high iron environments without adaptation recognizable from the perspective of the proteome has implications for understanding the basis of thermophily within this clade, and also for understanding the possible genetic basis for high iron tolerance in cyanobacteria on early Earth. The conserved core genome may be indicative of an allopatric lifestyle-or reduced genetic complexity of hot spring habitats relative to other environments.

Octopamine neuron dependent aggression requires dVGLUT from dual-transmitting neurons.

Neuromodulators such as monoamines are often expressed in neurons that also release at least one fast-acting neurotransmitter. The release of a combination of transmitters provides both "classical" and "modulatory" signals that could produce diverse and/or complementary effects in associated circuits. Here, we establish that the majority of Drosophila octopamine (OA) neurons are also glutamatergic and identify the individual contributions of each neurotransmitter on sex-specific behaviors. Males without OA display low levels of aggression and high levels of inter-male courtship. Males deficient for dVGLUT solely in OA-glutamate neurons (OGNs) also exhibit a reduction in aggression, but without a concurrent increase in inter-male courtship. Within OGNs, a portion of VMAT and dVGLUT puncta differ in localization suggesting spatial differences in OA signaling. Our findings establish a previously undetermined role for dVGLUT in OA neurons and suggests that glutamate uncouples aggression from OA-dependent courtship-related behavior. These results indicate that dual neurotransmission can increase the efficacy of individual neurotransmitters while maintaining unique functions within a multi-functional social behavior neuronal network.

Clinical course and prognostic factors across different musculoskeletal pain sites: A secondary analysis of individual patient data from randomised clinical trials.

BACKGROUND: Previous research has identified similar prognostic factors in patients with musculoskeletal (MSK) conditions regardless of pain presentation, generating opportunities for management based on prognosis rather than specific pain presentation. METHODS: Data from seven RCTs (2483 participants) evaluating a range of primary care interventions for different MSK pain conditions were used to investigate the course of symptoms and explore similarities and differences in predictors of outcome. The value of pain site for predicting changes in pain and function was investigated and compared with that of age, gender, social class, pain duration, widespread pain and level of anxiety/depression. RESULTS: Over the initial three months of follow-up, changes in mean pain intensity reflected an improvement, with little change occurring after this period. Participants with knee pain due to osteoarthritis (OA) showed poorer long-term outcome (mean difference in pain reduction at 12 months -1.85, 95% CI -2.12 to -1.57, compared to low back pain). Increasing age, manual work, longer pain duration, widespread pain and increasing anxiety/depression scores were significantly associated with poorer outcome regardless of pain site. Testing of interactions showed some variation between pain sites, particularly for knee OA, where age, manual work and pain duration were most strongly associated with outcome. CONCLUSIONS: Despite some differences in prognostic factors for trial participants with knee OA who were older and had more chronic conditions, similarity of outcome predictors across regional MSK pain sites provides evidence to support targeting of treatment based on prognostic factors rather than site of pain. SIGNIFICANCE: Individual patient data analysis of trials across different regional musculoskeletal pain sites was used to evaluate course and prognostic factors associated with pain and disability. Overall, similarity of outcome predictors across these different pain sites supports targeting of treatment based on prognostic factors rather than pain site alone.

Audiologic characteristics in a sample of recently-separated military Veterans: The Noise Outcomes in Servicemembers Epidemiology Study (NOISE Study).

Military Service Members are often exposed to high levels of occupational noise, solvents, and other exposures that can be damaging to the auditory system. Little is known about hearing loss and how it progresses in Veterans following military service. This epidemiology study is designed to evaluate and monitor a cohort of Veterans for 20 years or more to determine how hearing loss changes over time and how those changes are related to noise exposure and other ototoxic exposures encountered during military service. Data reported here are from baseline assessments of the first 100 study participants (84 males; 16 females; mean age 33.5 years; SD 8.8; range 21-58). Each participant was asked to complete a comprehensive audiologic examination and self-report questionnaires regarding sociodemographic characteristics, noise and solvent exposures, health conditions common among post-deployment Veterans, and the social and emotional consequences of hearing loss. For this relatively young cohort, 29% exhibited hearing loss, defined as average hearing threshold >20 dB HL in the conventional audiometric range. Forty-two percent exhibited hearing loss in the extended-high-frequency audiometric range using the same criterion (average hearing threshold >20 dB HL). Certain factors were found to be associated with poorer hearing in both conventional and extended-high-frequency ranges, including age, type of military branch, years of military service, number of military deployments, noise exposure, tinnitus, and a positive screen for post-traumatic stress disorder. Although the majority of participants had hearing within normal limits, 27% reported a self-perceived mild/moderate hearing handicap and 14% reported a significant handicap. Further research is needed to identify a cause for this discrepancy in audiologic results versus self-report. The information obtained from this longitudinal study could be used in future resource planning with the goal of preventing, as much as possible, the development of hearing loss during military service, and the exacerbation of prevalent hearing loss after military service and over Veterans' lifetimes.

A comparison of two digital mammography systems: are there any differences?

AIM: To compare the performance of two newly introduced digital mammography technologies (Sectra and Hologic) to the Welsh breast-screening service; specifically, whether there are differences in the number, type, size, and grade of tumour identified. MATERIALS AND METHODS: This was a retrospective study of a prospectively collected database of 50,000 consecutive screening episodes from 2012; clients were aged 49-88 years (mean 61.9 years). All studies were double-blind read by two readers. All tumours identified in the two arms of the study were detailed and compared specifically with regards to type (ductal or lobular) size, grade, and whether invasive or non-invasive. Performance was analysed for any statistically significant differences. RESULTS: Twenty-five thousand consecutive women were screened with Hologic (recall rate 5.9% of which 18% were cancer) and 25,000 were screened with Sectra digital mammography (recall rate 4.3% and 22% were cancer). Five hundred tumours were found with no significant difference in invasive cancer detection or between ductal or lobular subtypes. The Hologic system detected 267 tumours; of which 81 (30.33%) were non-invasive (3.24 per 1000), compared to the Sectra system with 233 cancers overall including 36 non-invasive (15.45%, 1.44 per 1000). The difference in non-invasive lesions (mainly ductal carcinoma in situ [DCIS]) detection was significant (p<0.001); 38% of which were high nuclear grade (HNG) using Hologic and 50% HNG lesions using Sectra. There was no significant difference in non-invasive size between the two technologies. The mean glandular dose received using the Sectra system was significantly less (0.7 mGy) compared to the Hologic system (1.6 mGy) for a 50-60 mm breast thickness. CONCLUSIONS: Population breast screening is frequently criticised for identifying lesions irrelevant to long-term outcomes or life expectancy and although the two systems seem comparable in terms of invasive cancer detection, a statistically significant difference in the detection of non-invasive lesions was seen, not reported in previous studies. This is a contentious issue, as identifying more DCIS has the potential to over-diagnose screened women leading to increased morbidity, higher "cancer detection rates", longer cancer waiting times, and reduced patient psychological wellbeing. The Sectra system is able to deliver a similar invasive detection cancer delivering a much lower dose mammogram, which is important in limiting overall population radiation dose. Further study as to whether the differences in tumour detection rates are clinically significant long term are now required.

Potential sources of mouth drying in beverages fortified with dairy proteins: A comparison of casein- and whey-rich ingredients.

Oral nutritional supplement drinks (ONS) are beverages high in dairy proteins that are prescribed to individuals at risk of malnutrition. Consumption of ONS is poor in elderly care facilities, with patients commenting that the sensory attributes of these drinks reduce their enjoyment and willingness to consume. Mouth drying is an attribute of ONS found to build with repeated consumption, which may further limit liking of these products. This study investigated the sources of drying sensations by sequential profiling, with a trained sensory panel rating a range of model milk systems and ONS over repeated sips and during after-effects. Sequential profiling found that fortification of milk with both caseinate and whey protein concentrate significantly increased the perception of mouth drying over repeated consumption, increasing by between 35 and 85% over consumption of 40mL. Enrichment of ONS with either whey protein concentrate or milk protein concentrate to a total protein content of 8.7% (wt/wt) resulted in whey and casein levels of 4.3:4.4% and 1.7:7.0% respectively. The product higher in whey protein was substantially more mouth drying, implying that whey proteins may be the most important contributor to mouth drying in ONS. However, efforts to mask mouth drying of protein-fortified milk by increasing sweetness or fat level were unsuccessful at the levels tested. Increasing the viscosity of protein-fortified milk led to a small but significant reduction in mouth drying. However, this approach was not successful when tested within complete ONS. Further analysis is required into the mechanism of protein-derived mouth drying to mask negative sensations and improve the enjoyment and consumption of protein-rich ONS.

Heat stability of milk supplemented with calcium chloride.

Calcium chloride (0-25 mM) was added to skim milk powder that was reconstituted to 9% total solids. Heat stability was evaluated between 60 and 120°C for different times by observing whether samples had coagulated, and by measuring the amount of sediment and residual protein in the centrifuged supernatant. Milk samples were also dialyzed during their respective heat treatments to recover the soluble phase at different temperatures to measure pH and ionic calcium. The transition conditions between good and poor heat stability were established for different calcium chloride concentrations and temperatures. As temperature increased, coagulation occurred at lower levels of added calcium chloride. The transition was quite distinct at higher temperatures but less so at lower temperatures; it was initiated by an increase in sediment formation before a firm coagulum was formed. Both pH and ionic calcium decreased in dialysates as temperature increased. No coagulation was observed if Ca(2+) was <0.5 mM and pH was >6.3 in dialysates taken at their respective coagulation temperatures. Being able to measure pH and ionic calcium at high temperatures will allow better understanding of factors affecting heat stability. Electrophoresis of the supernatants permitted identification of the protein fractions participating in the coagulation process. When coagulation was observed below 80°C, substantial amounts of undenatured ß-lactoglobulin and α-lactalbumin were found in the supernatant, as well as some soluble casein fractions. All the major whey protein and casein fractions were found in the sediment.

Feasibility of using dialysis for determining calcium ion concentration and pH in calcium-fortified soymilk at high temperature.

Dialysis was performed to examine some of the properties of the soluble phase of calcium (Ca) fortified soymilk at high temperatures. Dialysates were obtained while heating soymilk at temperatures of 80 and 100 °C for 1 h and 121 °C for 15 min. It was found that the pH, total Ca, and ionic Ca of dialysates obtained at high temperature were all lower than in their corresponding nonheated Ca-fortified soymilk. Increasing temperature from 80 to 100 °C hardly affected Ca ion concentration ([Ca²âº]) of dialysate obtained from Ca chloride-fortified soymilk, but it increased [Ca²âº] in dialysates of Ca gluconate-fortified soymilk and Ca lactate-fortified soymilk fortified with 5 to 6 mM Ca. Dialysates obtained at 100 °C had lower pH than dialysate prepared at 80 °C. Higher Ca additions to soymilk caused a significant (P≤ 0.05) reduction in pH and an increase in [Ca²âº] of these dialysates. When soymilk was dialyzed at 121 °C, pH, total Ca, and ionic Ca were further reduced. Freezing point depression (FPD) of dialysates increased as temperature increased but were lower than corresponding soymilk samples. This approach provides a means of estimating pH and ionic Ca in soymilks at high temperatures, in order to better understand their combined role on soymilk coagulation.

Self-injurious behaviour: limbic dysregulation and stress effects in an animal model.

BACKGROUND: Self-injurious behaviour (SIB) is prevalent in neurodevelopmental disorders, but its expression is highly variable within, and between diagnostic categories. This raises questions about the factors that contribute to aetiology and expression of SIB. Expression of SIB is generally described in relation to social reinforcement. However, variables that predispose vulnerability have not been as clearly characterised. This study reports the aetiology and expression of self-injury in an animal model of pemoline-induced SIB. It describes changes in gross neuronal activity in selected brain regions after chronic treatment with pemoline, and it describes the impact that a history of social defeat stress has on the subsequent expression of SIB during pemoline treatment. METHODS: Experiment 1--Male Long-Evans rats were injected on each of five consecutive days with pemoline or vehicle, and the expression of SIB was evaluated using a rating scale. The brains were harvested on the morning of the sixth day, and were assayed for expression of cytochrome oxidase, an index of sustained neuronal metabolic activity. Experiment 2--Male Long-Evans rats were exposed to a regimen of 12 daily sessions of social defeat stress or 12 daily sessions of handling (i.e. controls). Starting on the day after completion of the social defeat or handling regimen, each rat was given five daily injections of pemoline. The durations of self-injurious oral contact and other stereotyped behaviours were monitored, and the areas of tissue injury were quantified. RESULTS: Experiment 1--Neuronal metabolic activity was significantly lower in a variety of limbic and limbic-associated brain structures in the pemoline-treated rats, when compared with activity in the same regions of vehicle-treated controls. In addition, neuronal activity was low in the caudate-putamen, and in subfields of the hypothalamus, but did not differ between groups for a variety of other brain regions, including nucleus accumbens, substantia nigra, ventral tegmentum, thalamus, amygdala, and cortical regions. Experiment 2--All the pemoline-treated rats exhibited SIB, and whereas the social defeat regimen did not alter the total amount of self-injurious oral contact or other stereotyped behaviours, it significantly increased the severity of tissue injury. CONCLUSIONS: A broad sampling of regional metabolic activity indicates that the pemoline regimen produces enduring changes that are localised to specific limbic, hypothalamic and striatal structures. The potential role of limbic function in aetiology of SIB is further supported by the finding that pemoline-induced self-injury is exacerbated by prior exposure to social defeat stress. Overall, the results suggest brain targets that should be investigated further, and increase our understanding of the putative role that stress plays in the pathophysiology of SIB.

The role of health literacy on African American and Hispanic/Latino perspectives on cancer clinical trials.

Although cancer clinical trials are important for discovering lifesaving therapies, participation remains low among racial/ethnic minorities, and little research explores the role of health literacy in racial/ethnic minority perceptions of cancer clinical trials (CCTs). Five focus groups (n = 50) with African American and Hispanic participants explored CCT perceptions using a multidimensional health literacy framework. We found poor scientific literacy including misconceptions of scientific information, perceptions of clinical trials as uncertain and fear; limited civic literacy around topics of trust, perceptions of participants as guinea pigs, and concerns about of IRB protections; and cultural literacy challenges regarding the importance of home remedies for health, use of native language, and the importance of race/ethnicity matching to health care professionals. Results highlight the importance of attending to scientific literacy, cultural literacy, and civic literacy. Future educational interventions regarding cancer clinical trials should address the importance of health literacy in understanding cancer clinical trial decision making.

Vaccination of dairy cows with recombinant Streptococcus uberis adhesion molecule induces antibodies that reduce adherence to and internalization of S. uberis into bovine mammary epithelial cells.

Streptococcus uberis is an important environmental mastitis pathogen that causes subclinical and clinical mastitis in lactating and nonlactating cows and heifers throughout the world. Previous work from our laboratory suggests that S. uberis adhesion molecule (SUAM) is involved in S. uberis pathogenesis and may be an excellent target for vaccine development. The objective of this study was to evaluate the antibody response of cattle vaccinated with recombinant SUAM (rSUAM). Uninfected primiparous dairy cows (n=30) in late lactation were divided randomly into three groups of 10 cows each: control, 200 µg rSUAM, and 400 µg rSUAM. Cows in groups vaccinated with 200 µg and 400 µg rSUAM received an emulsion containing adjuvant, phosphate-buffered saline (PBS) and affinity purified rSUAM. Cows in the control group received an emulsion containing adjuvant and PBS. Cows were vaccinated subcutaneously in the neck region at drying off (D-0), 28 d after drying off (D+28) and within 7 d after calving. Serum was collected at D-0, D+28, at calving (C-0), calving vaccination (CV), and during early lactation (CV+14). Serum antibody responses were measured by an ELISA against rSUAM. Following the first vaccination a significant increase in anti-rSUAM antibodies was detected at D+28 in cows from groups vaccinated with 200 µg and 400 µg rSUAM when compared to the control group. This increase in anti-rSUAM antibodies continued following the second immunization at D+28; reaching the highest levels in the post-parturient sampling period (C0), after which antibodies appeared to plateau. S. uberis UT888 pretreated with several dilutions of heat-inactivated serum from cows vaccinated with rSUAM, affinity purified antibodies against rSUAM, and to a 17 amino acid long peptide from the N terminus of SUAM (pep-SUAM) were co-cultured with bovine mammary epithelial cells and adherence to and internalization of S. uberis into epithelial cells was measured. Compared to untreated controls, opsonization of two strains of S. uberis with sera from cows vaccinated with rSUAM, with affinity purified rSUAM antibodies, or with affinity purified pep-SUAM antibodies significantly reduced adherence to and internalization of this pathogen into bovine mammary epithelial cells. In conclusion, subcutaneous vaccination of dairy cows with rSUAM during physiological transitions of the mammary gland either from or to a state of active milk synthesis induced antibodies in serum and milk and these antibodies reduced adherence to and internalization of S. uberis into mammary epithelial cells under in vitro conditions. SUAM appears to be an excellent candidate for vaccine development.

Antimicrobial activity of Citrox bioflavonoid preparations against oral microorganisms.

BACKGROUND: Citrox is a formulation of soluble bioflavonoids obtained from citrus fruits. The non-toxic and antimicrobial properties of natural bioflavonoids are well documented, and consequently there has been interest in the therapeutic application of these substances. OBJECTIVE: To determine the antimicrobial activity of two Citrox formulations (BC30 and MDC30) with different bioflavonoid combinations against a range of oral microorganisms. METHODS: The antimicrobial activity of both formulations was tested against 14 bacterial species and six Candida species. The two Citrox formulations (dilution range 0.007-8% v/v) were firstly evaluated by determining the in vitro Minimal Inhibitory Concentration (MIC) against planktonic microorganisms in a broth microdilution assay. Secondly, the ability of the same serial dilutions to inhibit microbial growth was assessed in a modified microtitre biofilm assay. RESULTS: Both Citrox formulations exhibited antimicrobial activity. The BC30 formulation demonstrated greater activity than MDC30 and significantly inhibited growth of all bacterial species and most candidal species tested at a concentration of 1% (v/v) in both the broth and the biofilm assay. CONCLUSION: Bioflavonoid preparations of Citrox have a broad-spectrum of antimicrobial activity against oral microorganisms, and as such have the potential to be used within therapeutic preparations for the control of the oral microflora.

Differential involvement of striato- and cerebello-thalamo-cortical pathways in tremor- and akinetic/rigid-predominant Parkinson's disease.

Parkinson's disease (PD) presents clinically with varying degrees of resting tremor, rigidity, and bradykinesia. For decades, striatal-thalamo-cortical (STC) dysfunction has been implied in bradykinesia and rigidity, but does not explain resting tremor in PD. To understand the roles of cerebello-thalamo-cortical (CTC) and STC circuits in the pathophysiology of the heterogeneous clinical presentation of PD, we collected functional magnetic resonance imaging (fMRI) data from 17 right-handed PD patients [nine tremor predominant (PDT) and eight akinetic-rigidity predominant (PDAR)] and 14 right-handed controls while they performed internally-guided (IG) sequential finger tapping tasks. The percentage of voxels activated in regions constituting the STC and CTC [divided as cerebellar hemisphere-thalamo-cortical (CHTC) and vermis-thalamo-cortical (CVTC)] circuits was calculated. Multivariate analysis of variance compared the activation patterns of these circuits between study groups. Compared to controls, both PDAR and PDT subjects displayed an overall increase in the percentage of voxels activated in both STC and CTC circuits. These increases reached statistical significance in contralateral STC and CTC circuits for PDT subjects, and in contralateral CTC pathways for PDAR subjects. Comparison of PDAR and PDT subjects revealed significant differences in ipsilateral STC (P=0.005) and CTC (P=0.043 for CHTC and P=0.003 for CVTC) circuits. These data support the differential involvement of STC and CTC circuits in PD subtypes, and help explain the heterogeneous presentation of PD symptoms. These findings underscore the importance of integrating CTC circuits in understanding PD and other disorders of the basal ganglia.

A pilot study of bioaerosol reduction using an air cleaning system during dental procedures.

BACKGROUND: Bioaerosols are defined as airborne particles of liquid or volatile compounds that contain living organisms or have been released from living organisms. The creation of bioaerosols is a recognized consequence of certain types of dental treatment and represents a potential mechanism for the spread of infection. OBJECTIVES: The aims of the present study were to assess the bioaerosols generated by certain dental procedures and to evaluate the efficiency of a commercially available Air Cleaning System (ACS) designed to reduce bioaerosol levels. METHODS: Bioaerosol sampling was undertaken in the absence of clinical activity (baseline) and also during treatment procedures (cavity preparation using an air rotor, history and oral examination, ultrasonic scaling and tooth extraction under local anaesthesia). For each treatment, bioaerosols were measured for two patient episodes (with and without ACS operation) and between five and nine bioaerosol samples were collected. For baseline measurements, 15 bioaerosol samples were obtained. For bioaerosol sampling, environmental air was drawn on to blood agar plates using a bioaerosol sampling pump placed in a standard position 20 cm from the dental chair. Plates were incubated aerobically at 37°C for 48 hours and resulting growth quantified as colony forming units (cfu/m³). Distinct colony types were identified using standard methods. Results were analysed statistically using SPSS 12 and Wilcoxon signed rank tests. RESULTS: The ACS resulted in a significant reduction (p = 0.001) in the mean bioaerosols (cfu/m³) of all three clinics compared with baseline measurements. The mean level of bioaerosols recorded during the procedures, with or without the ACS activated respectively, was 23.9 cfu/m³ and 105.1 cfu/m³ (p = 0.02) for cavity preparation, 23.9 cfu/m³ and 62.2 cfu/m³ (p = 0.04) for history and oral examination; 41.9 cfu/m³ and 70.9 cfu/m³ (p = 0.01) for ultrasonic scaling and 9.1 cfu/m³ and 66.1 cfu/m³ (p = 0.01) for extraction. The predominant microorganisms isolated were Staphylococcus species and Micrococcus species. CONCLUSION: These findings indicate potentially hazardous bioaerosols created during dental procedures can be significantly reduced using an air cleaning system.

Should there be an expanded role for palliative care in end-stage renal disease?

PURPOSE OF REVIEW: In this review, we outline the rationale for expanding the role of palliative care in end-stage renal disease (ESRD), describe the components of a palliative care model, and identify potential barriers in implementation. RECENT FINDINGS: Patients receiving chronic dialysis have reduced life expectancy and high rates of chronic pain, depression, cognitive impairment, and physical disability. Delivery of prognostic information and advance care planning are desired by patients, but occur infrequently. Furthermore, although hospice care is associated with improved symptom control and lower healthcare costs at the end of life, it is underutilized by the ESRD population, even among patients who withdraw from dialysis. A palliative care model incorporating communication of prognosis, advance care planning, symptom assessment and management, and timely hospice referral may improve quality of life and quality of dying. Resources and clinical practice guidelines are available to assist practitioners with incorporating palliative care into ESRD management. SUMMARY: There is a large unmet need to alleviate the physical, psychosocial, and existential suffering of patients with ESRD. More fully integrating palliative care into ESRD management by improving end-of-life care training, eliminating structural and financial barriers to hospice use, and identifying optimal methods to deliver palliative care are necessary if we are to successfully address the needs of an aging ESRD population.

An integrative approach to advanced kidney disease in the elderly.

Chronic kidney disease (CKD) has increasingly become a "geriatric" disease, with a dramatic rise in incidence in the aging population. Patients aged >75 years have become the fastest growing population initiating dialysis. These patients have increased comorbid diseases and functional limitations which affect mortality and quality of life. This review describes the challenges of dialysis initiation and considerations for management of the elderly subpopulation. There is a need for an integrative approach to care, which addresses management issues, health-related quality of life, and timely discussion of goals of care and end-of-life issues. This comprehensive approach to patient care involves the integration of nephrology, geriatric, and palliative medicine practices.

Dynamic changes in cerebello-thalamo-cortical motor circuitry during progression of Parkinson's disease.

Both the basal ganglia and cerebellum are known to influence cortical motor and motor-associated areas via the thalamus. Whereas striato-thalamo-cortical (STC) motor circuit dysfunction has been implicated clearly in Parkinson's disease (PD), the role of the cerebello-thalamo-cortical (CTC) motor circuit has not been well defined. Functional magnetic resonance imaging (fMRI) is a convenient tool for studying the role of the CTC in vivo in PD patients, but large inter-individual differences in fMRI activation patterns require very large numbers of subjects in order to interpret data from cross-sectional, case control studies. To understand the role of the CTC during PD progression, we obtained longitudinal fMRI 2 years apart from 5 PD (57+/-8 yr) and five Controls (57+/-9 yr) performing either externally- (EG) or internally-guided (IG) sequential finger movements. All PD subjects had unilateral motor symptoms at baseline, but developed bilateral symptoms at follow-up. Within-group analyses were performed by comparing fMRI activation patterns between baseline and follow-up scans. Between-group comparisons were made by contrasting fMRI activation patterns generated by the more-affected and less-affected hands of PD subjects with the mean of the dominant and non-dominant hands of Controls. Compared to baseline, Controls showed changes in CTC circuits, but PD subjects had increased recruitment of both cortical motor-associated and cerebellar areas. Compared to Controls, PD subjects demonstrated augmented recruitment of CTC circuits over time that was statistically significant when the IG task was performed by the hand that transitioned from non-symptomatic to symptomatic. This longitudinal fMRI study demonstrates increased recruitment of the CTC motor circuit concomitant with PD progression, suggesting a role of the CTC circuit in accommodation to, or pathophysiology of, PD.

Probabilistic neural networks modeling of the 48-h LC50 acute toxicity endpoint to Daphnia magna.

Two modeling experiments based on the maximum likelihood estimation paradigm and targeting prediction of the Daphnia magna 48-h LC50 acute toxicity endpoint for both organic and inorganic compounds are reported. The resulting models computational algorithms are implemented as basic probabilistic neural networks with Gaussian kernel (statistical corrections included). The first experiment uses strictly D. magna information for 971 structures as training/learning data and the resulting model targets practical applications. The second experiment uses the same training/learning information plus additional data on another 29 compounds whose endpoint information is originating from D. pulex and Ceriodaphnia dubia. It only targets investigation of the effect of mixing strictly D. magna 48-h LC50 modeling information with small amounts of similar information estimated from related species, and this is done as part of the validation process. A complementary 81 compounds dataset (involving only strictly D. magna information) is used to perform external testing. On this external test set, the Gaussian character of the distribution of the residuals is confirmed for both models. This allows the use of traditional statistical methodology to implement computation of confidence intervals for the unknown measured values based on the models predictions. Examples are provided for the model targeting practical applications. For the same model, a comparison with other existing models targeting the same endpoint is performed.