Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer disease.

Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer Disease (AD). Given their essential role in neural communication, disruptions to these hubs have profound implications for overall brain network integrity and functionality. Hub disruption, or targeted impairment of functional connectivity at the hubs, is recognized in AD patients. Computational models paired with evidence from animal experiments hint at a mechanistic explanation, suggesting that these hubs may be preferentially targeted in neurodegeneration, due to their high neuronal activity levels-a phenomenon termed "activity-dependent degeneration". Yet, two critical issues were unresolved. First, past research hasn't definitively shown whether hub regions face a higher likelihood of impairment (targeted attack) compared to other regions or if impairment likelihood is uniformly distributed (random attack). Second, human studies offering support for activity-dependent explanations remain scarce. We applied a refined hub disruption index to determine the presence of targeted attacks in AD. Furthermore, we explored potential evidence for activity-dependent degeneration by evaluating if hub vulnerability is better explained by global connectivity or connectivity variations across functional systems, as well as comparing its timing relative to amyloid beta deposition in the brain. Our unique cohort of participants with autosomal dominant Alzheimer Disease (ADAD) allowed us to probe into the preclinical stages of AD to determine the hub disruption timeline in relation to expected symptom emergence. Our findings reveal a hub disruption pattern in ADAD aligned with targeted attacks, detectable even in pre-clinical stages. Notably, the disruption's severity amplified alongside symptomatic progression. Moreover, since excessive local neuronal activity has been shown to increase amyloid deposition and high connectivity regions show high level of neuronal activity, our observation that hub disruption was primarily tied to regional differences in global connectivity and sequentially followed changes observed in Aß PET cortical markers is consistent with the activity-dependent degeneration model. Intriguingly, these disruptions were discernible 8 years before the expected age of symptom onset. Taken together, our findings not only align with the targeted attack on hubs model but also suggest that activity-dependent degeneration might be the cause of hub vulnerability. This deepened understanding could be instrumental in refining diagnostic techniques and developing targeted therapeutic strategies for AD in the future.

Evaluating a handheld decision support device in pediatric intensive care settings.

OBJECTIVE: To evaluate end-user acceptance and the effect of a commercial handheld decision support device in pediatric intensive care settings. The technology, pac2, was designed to assist nurses in calculating medication dose volumes and infusion rates at the bedside. MATERIALS AND METHODS: The devices, manufactured by InformMed Inc., were deployed in the pediatric and neonatal intensive care units in 2 health systems. This mixed methods study assessed end-user acceptance, as well as pac2's effect on the cognitive load associated with bedside dose calculations and the rate of administration errors. Towards this end, data were collected in both pre- and postimplementation phases, including through ethnographic observations, semistructured interviews, and surveys. RESULTS: Although participants desired a handheld decision support tool such as pac2, their use of pac2 was limited. The nature of the critical care environment, nurses' risk perceptions, and the usability of the technology emerged as major barriers to use. Data did not reveal significant differences in cognitive load or administration errors after pac2 was deployed. DISCUSSION AND CONCLUSION: Despite its potential for reducing adverse medication events, the commercial standalone device evaluated in the study was not used by the nursing participants and thus had very limited effect. Our results have implications for the development and deployment of similar mobile decision support technologies. For example, they suggest that integrating the technology into hospitals' existing IT infrastructure and employing targeted implementation strategies may facilitate nurse acceptance. Ultimately, the usability of the design will be essential to reaping any potential benefits.

Wanting to Be Different Predicts Nonmotivated Change: Actual-Desired Self-Discrepancies and Susceptibility to Subtle Change Inductions.

Actual-desired discrepancies in people's self-concepts represent structural incongruities in their self-representations that can lead people to experience subjective conflict. Theory and research suggest that structural incongruities predict susceptibility to subtle influences like priming and conditioning. Although typically examined for their motivational properties, we hypothesized that because self-discrepancies represent structural incongruities in people's self-concepts, they should also predict susceptibility to subtle influences on people's active self-views. Across three studies, we found that subtle change inductions (self-evaluative conditioning and priming) exerted greater impact on active self-perceptions and behavior as actual-desired self-discrepancies increased in magnitude. Exploratory analyses suggested that these changes occurred regardless of the compatibility of the change induction with individuals' desired self-views.

Human memory CD4+ T cell response to the major dog allergen Can f 5, prostatic kallikrein.

BACKGROUND: Human CD4+ T cell responses to important animal allergens are still insufficiently understood. OBJECTIVE: To comprehensively characterize in vitro and ex vivo the peripheral blood memory CD4+ T cell responses of subjects with and without allergy to the major dog allergen Can f 5, the only known animal allergen in the kallikrein family of proteins. METHODS: Can f 5-specific memory CD4+ T cell lines (TCLs) were established from the peripheral blood of 12 subjects with and 12 subjects without allergy to Can f 5 and characterized for their functional and phenotypic properties. The results were evaluated with those obtained ex vivo with a novel CD154 enrichment method. The epitopes recognized by the Can f 5-specific TCLs were determined with 72 overlapping 16-mer peptides covering the sequence of the allergen. RESULTS: Can f 5-specific TCLs were obtained at about tenfold higher frequency from allergic than from non-allergic subjects. Functionally, the TCLs of allergic subjects displayed a Th2-biased cytokine phenotype and increased T cell receptor avidity, whereas the TCLs of non-allergic subjects displayed a Th1-/Th0-biased cytokine phenotype and lower TCR avidity. The higher frequency and the Th2 phenotype of Can f 5-specific memory CD4+ T cells in allergic subjects were confirmed by the CD154 enrichment method ex vivo. Six distinct T cell epitope regions of Can f 5 were predominantly recognized by the TCLs from allergic subjects. CONCLUSIONS AND CLINICAL RELEVANCE: Can f 5-specific memory CD4+ T cell responses differ considerably between subjects with and without allergy, as assessed by both in vitro and ex vivo approaches. Peptides containing the dominant T cell epitopes of Can f 5 can be employed for developing peptide-based immunotherapy for dog allergy.

Amount of weight loss or gain influences the severity of respiratory events in sleep apnea.

Severity of obstructive sleep apnea (OSA) is estimated based on respiratory events per hour [i.e., apnea-hypopnea index (AHI)]. The aim of this study was to investigate effects of weight change on the severity of respiratory events. Respiratory event severity, including duration and morphology, was estimated by determining parameters quantifying obstruction and desaturation event lengths and areas, respectively. Respiratory events of 54 OSA patients treated with dietary intervention were evaluated at baseline and after 5-year follow-up in subgroups with different levels of weight change. AHI, oxygen desaturation index (ODI) and obstruction event severities decreased during weight loss. In lower level weight loss, the decrease was milder in obstruction severity than in AHI and ODI, indicating that the decrease in the number of events is more focused on less severe events. In weight gain groups, parameters incorporating obstruction event severity, AHI and ODI increased, although increase was greater in parameters incorporating obstruction event severity. The number and severity of respiratory events were modulated differently by the level of weight change. AHI misses this change in the severity of respiratory events. Therefore, parameters incorporating information on the respiratory event severities may bring additional information on the health effects obtained with dietary treatment of OSA.

Weight loss alters severity of individual nocturnal respiratory events depending on sleeping position.

Weight loss is an effective treatment for obstructive sleep apnea (OSA). The mechanisms of how weight loss affects nocturnal breathing are not fully understood. The severity of OSA is currently estimated by the number of respiratory events per hour of sleep (i.e. apnea-hypopnea-index, AHI). AHI neglects duration and morphology of individual respiratory events, which describe the severity of individual events. In the current paper, we investigate the novel Adjusted-AHI parameter (incorporating individual event severity) and AHI after weight loss in relation to sleeping position. It was hypothesised that there are positional differences in individual event severity changes during weight loss. Altogether, 32 successful (> 5% of weight) and 34 unsuccessful weight loss patients at baseline and after 1 year follow-up were analysed. The results revealed that individual respiratory event severity was reduced differently in supine and non-supine positions during weight loss. During weight loss, AHI was reduced by 54% (p = 0.004) and 74% (p < 0.001), while Adjusted-AHI was reduced by 14% (p = 0.454) and 48% (p = 0.003) in supine and non-supine positions, respectively. In conclusion, the severity of individual respiratory events decreased more in the non-supine position. The novel Adjusted-AHI parameter takes these changes into account and might therefore contribute additional information to the planning of treatment of OSA patients.

Novel parameters reflect changes in morphology of respiratory events during weight loss.

Apnea-hypopnea-index (AHI), disregarding the respiratory event morphology, is currently used in estimation of severity of obstructive sleep apnea (OSA). The purpose of the current study was to evaluate the potential of novel parameters in estimation of changes in severity of OSA during weight loss. Polygraphic data of 67 patients, 37 in the control (no weight loss) and 30 in the weight loss (>5%) groups was evaluated at baseline and after two year follow-up. Changes in the values of novel parameters, incorporating detailed information of respiratory event characteristics, were evaluated and compared with changes in AHI. The median AHI in the weight loss group decreased significantly during the follow-up. The number of shorter respiratory events decreased in the weight loss group, while the longer ones remained, increasing the median durations of the respiratory events by 20-62%. For this reason the decrease of the values of the novel parameters were smaller compared to AHI in the weight loss group. This suggests that the severity of OSA might not fall as linearly during weight loss as AHI suggests. Moreover, the novel parameters containing more detailed information on the morphology characteristics may provide valuable supplementary information for the assessment of the severity of OSA.

Aspergillus fumigatus challenge increases cytokine levels in nasal lavage fluid.

Several studies have shown an association between exposure in moisture-damaged buildings and adverse health effects. There are several indicator microbes of moisture damage, but Aspergillus fumigatus is one of the best-documented molds provoking health problems in different occupational conditions. We assessed whether inhalation of a commercial A. fumigatus solution would affect cytokine levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-4, IL-6, interferon [IFN]-gamma) in nasal lavage fluid (NAL) compared with that evoked by placebo challenge. Twenty-seven subjects were studied: 13 had occupational exposure in a moisture-damaged building, 4 were atopic, and 10 were considered as controls. In all the subjects, the IL-1beta levels were increased significantly both at 6 (p = 0.013) and 24 h (p = .005) after the A. fumigatus challenge compared to placebo. In subjects with previous occupational exposure in a moisture-damaged building, IL-4 concentrations were increased significantly both at 6 (p =.046) and 24 h (p =.008) after the A. fumigatus challenge compared with placebo. Furthermore, in the control group, TNF-alpha levels were significantly increased at 6 h after the A. fumigatus challenge compared to placebo (p = .028). Thus, these data show a link between markers of inflammation in NAL and experimental A. fumigatus challenge.

The effects of Aspergillus fumigatus challenge on exhaled and nasal NO levels.

Several studies have previously shown that exposure to indoor air microbes from moisture-damaged buildings can cause adverse health effects. Aspergillus fumigatus is one of the best-documented moulds causing health problems to those exposed. In this study, inhalation of a commercial A. fumigatus solution was assessed, to establish if it would have effects on fractional exhaled (FeNO) and nasal (FnNO) nitric oxide levels and on lung function. The results were compared with placebo challenge. A total of 28 subjects were divided into three study groups: group 1 had been exposed to occupational mould; group 2 consisted of atopic subjects; and group 3 was a control group. Some 3 h after A. fumigatus challenge, there was a considerable increase in FeNO, and a significant difference was observed between the A. fumigatus and placebo inhalations. The difference was seen in all study groups. No such differences were found in the levels of FnNO or nitrite in nasal lavage fluid. Subjects reported significantly more frequent respiratory tract symptoms after the A. fumigatus inhalation compared with placebo challenge. In conclusion, it was shown here that inhalation challenge of Aspergillus fumigatus elevated fractional exhaled nitric oxide levels. An increase in fractional exhaled nitric oxide may serve as an indicator of respiratory inflammation of acute mould exposure.

Safety of formoterol after cumulative dosing via Easyhaler and Aerolizer.

This randomised, double-blind, double-dummy, cumulative dose, multicentre crossover study aimed to demonstrate non-inferiority in safety of formoterol delivered via Easyhaler versus Aerolizer. The secondary objective was to compare the efficacy of the devices. Thirty-three adult asthmatic subjects entered the study and 32 completed it. The study comprised screening and two study days, with each subject inhaling 96 microg (12, 12, 24 and 48 microg) cumulative dose of formoterol via the study inhalers. Serum potassium (S-K+), vital signs and spirometry were performed at baseline, 1h after each dose and additionally 4h after the last dose. The primary safety variable was S-K+. Secondary safety variables were heart rate, corrected QT interval, blood pressure, serum glucose and adverse events. Spirometry was assessed to evaluate efficacy. The results showed non-inferiority in safety of formoterol inhaled via Easyhaler compared to Aerolizer. The adjusted treatment difference in the S-K+ values after 96 microg cumulative dose of formoterol was 0.14 mmol/L being clearly above the pre-determined lower limit of the non-inferiority criterion of -0.2 mmol/L. There were dose-related changes in secondary efficacy variables after both treatments. The changes were comparable in most of the parameters but heart rate was statistically significantly higher and decrease in diastolic blood pressure greater after formoterol via Aerolizer than that via Easyhaler. The occurrence of adverse events was dose-related, the most common events being tremor, hypokalaemia, headache and palpitation. The spirometry results showed no statistically significant difference in efficacy between the treatments. In conclusion, formoterol delivered via Easyhaler was as safe as via Aerolizer.

Nitric oxide alone is an insufficient biomarker of exposure to microbes in a moisture-damaged building.

Several epidemiological studies have revealed a large variety of adverse health effects related to exposure to microbes in moisture damaged buildings. Recently some evidence has been reported for a biochemical linkage between microbial exposure and the respiratory symptoms suffered by the occupants. The objective of the current study was to evaluate the value of nitric oxide (NO) measurements in determining the inflammatory status of airways in inhabitants of problem buildings. NO was measured by a chemiluminescence analyzer from the exhaled air. In addition, NO was determined as its metabolite nitrite from nasal lavage (NL) and induced sputum (IS) samples and also via the expression of inducible nitric oxide synthase (iNOS) in the cells. Occupants of moisture-damaged and reference schools were studied. The sampling was performed at the end of the spring term, at the end of the summer vacation, during the winter term, and after a 1-wk winter holiday. No statistically significant differences in NO levels were detected between the studied groups or between exposure and vacation periods. iNOS was not detected from IS or NL samples of the exposed occupants. These results suggest that NO measurements alone are not sufficient to quantify airway inflammation when evaluating subjects exposed to microbes present in moisture-damaged buildings.

Comparison of inflammatory elements in nasal lavage and induced sputum following occupational exposure to moldy-building microbes.

Inflammatory processes in the nasal air passages may reflect corresponding processes in the lower airways due to the similarities in histology of nasal mucosa and bronchi. The objective of the current study was to determine whether the levels of inflammatory markers in nasal lavage fluid could be used as predictors of lower respiratory tract inflammation after exposure to microbes in indoor air of moisture-damaged buildings. Differential cell count, immunochemically measured concentrations of proinflammatory cytokines (Interleukins [IL] IL-1, IL-4, IL-6, and tumor necrosis factor alpha [TNFalpha]) and nitric oxide (NO), assessed as nitrite, were analyzed from nasal lavage (NL) and induced sputum (IS) samples of the occupants (n = 60) working in moisture-damaged and reference school buildings. The measurements of inflammation markers in NL and IS sample pairs, collected on the same day, were compared. Although the levels of NO (p =.026) and IL-4 (p =.014) in NL predicted their levels in IS in a statistically significant manner, their predictive values (6.9% and 7.8%, respectively) were low. There was no significant correlation between the concentrations of the studied proinflammatory cytokines or differential cell counts in NL and IS samples. Our results indicate that measurement of inflammatory mediators in NL is not per se a reliable method to evaluate the inflammatory status of the lower airways after exposure to indoor air pollutants of moisture damaged building. It is possible that NL is a more sensitive indicator of direct exposure to different irritants in inhaled air than is IS. This may be a reflection of the role of nasal mucosa as the primary physicochemical barrier to inhaled air.

Linear diffusion on DNA despite high-affinity binding by a DNA polymerase processivity factor.

The oligomeric "sliding clamp" processivity factors, such as PCNA, are thought to rely on a loose, topological association with DNA to slide freely along dsDNA. Unlike PCNA, the processivity subunit of the herpes simplex virus DNA polymerase, UL42, is a monomer and has an intrinsic affinity for dsDNA that is remarkably high for a sequence-independent DNA binding protein. Using a DNase footprinting assay, we demonstrate that UL42 translocates with the catalytic subunit of the polymerase during chain elongation. In addition, footprinting and electrophoretic mobility shift assays show that, despite its tight DNA binding, UL42 is capable of linear diffusion on DNA at a rate of between 17 and 47 bp/s. Our results thus suggest that, despite profound biochemical differences with the sliding clamps, UL42 can freely slide downstream with the catalytic subunit during DNA replication.

Changes in pro-inflammatory cytokines in association with exposure to moisture-damaged building microbes.

Several epidemiological studies have described an association between adverse health effects and exposure to mould and microbes present in the indoor air of moisture-damaged buildings. However, the biochemical linkage between microbial exposure and the large variety of reported respiratory symptoms is poorly understood. In the present study, the authors compared the respiratory symptoms, the production of inflammatory mediators interleukin (IL)-1, IL-4, IL-6, tumour necrosis factor-alpha (TNF-alpha) and cell count in nasal lavage fluid and induced sputum samples of subjects working in moisture-damaged and control school buildings. The sampling was performed and the questionnaires were completed at the end of the spring term, at the end of the summer vacation (2.5 months), during the winter term and after a 1-week winter holiday. The authors found a significant elevation of IL-1, TNF-alpha and IL-6 in nasal lavage fluid and IL-6 in induced sputum during the spring term in the subjects from the moisture-damaged school building compared to the subjects from the control building. The exposed workers reported sore throat, phlegm, eye irritation, rhinitis, nasal obstruction and cough in parallel with these findings. The present data suggests an association between microbial exposure, and symptoms as well as changes in pro-inflammatory mediators detected from both the upper and lower airways.

Reproducibility of measurements of exhaled NO, and cell count and cytokine concentrations in induced sputum.

Sputum induction is a noninvasive, well-tolerated method for studying airway inflammation. When induction with hypertonic saline is repeated at short time-intervals (<24 h), the cell profile of sputum has not been reproducible. To determine the proper interval between sampling cell profiles and cytokine contents of sputum samples that had been induced 48 h apart, were compared. In addition, the inducible nitric oxide synthase (iNOS) expression of sputum cells was compared to the levels of exhaled nitric oxide (NO). Sputum induction and measurement of exhaled NO was performed in 31 healthy nonatopic volunteers. Cell differentials were counted. Concentrations of interleukin (IL)-4, IL-6, tumour necrosis factor (TNF)alpha, eosinophil cationic protein (ECP) were measured in sputum supernatant, and iNOS was determined. Reproducibility of cell counts was high (r=0.836 total cells, r=0.762 neutrophils, r=0.966 eosinophils, r=0.742 macrophages). IL-4 (r=0.398), IL-6 (r=0.566), TNFalpha (r=0.658) and ECP (r=0.501) were also less reproducible in healthy volunteers. Consistent with the low levels of NO in the exhaled air (18.5+/-2.6 ppb and 19.3+/-2.8 parts per billion (ppb) on the two study days, r=0.976, p=0.0000), expression of iNOS was not detected. In conclusion, in healthy subjects, induced sputum cell counts are reproducible. Even though the success rate in nonatopic populations is relatively low, sputum induction appears to be a valid method for detecting inflammatory changes within the airways, when being performed 48 h apart.

Simple forced oscillatory technique and spirometry in assessment of bronchial responsiveness in non-asthmatic and asthmatic subjects.

Simple validity controlled forced oscillatory respiratory resistance (Rrsfo) at 8 Hz frequency was compared with flow-volume spirometry in detection of bronchial changes during induced bronchoconstriction. The methacholine provocation test was performed in subjects with mild asthma (n = 18) and in non-asthmatic subjects (n = 61) of which 44 were classified as responders (delta FEV1 > or = 15% in methacholine test). According to the index of maximal response/coefficient of variation for immediately repeated measurements (delta max/Coeffvar), Rrsfo was shown to be at least as sensitive indicator of bronchoconstriction as FEV1, and better than MMEF and FVC. The shape of the dose-response curves were similar for all parameters. In the non-asthmatic group, there were similar plateaux in Rrsfo, FEV1, and FVC at the same methacholine concentrations. In the asthmatic group, the provocative concentrations for Rrsfo and spirometric parameters correlated significantly (PC60-Rrsfo versus PC10-FEV1, P < 0.05; PC60-Rrsfo versus PC25-MMEF, P < 0.01). In the non-asthmatic responsive subjects, the correlations between PC60-Rrsfo and PC25-MMEF were significant (P < 0.05). Thus, Rrsfo at a fixed 8 Hz frequency and built-in validity control was shown to be at least as sensitive an indicator for changes in lung function in asthmatic and non-asthmatic responsive subjects as spirometry. Compared to spirometry, it may give additional information with fewer confounding factors during performance.

Short-term variations in oscillatory and spirometric lung function parameters of non-asthmatic adults.

Oscillatory respiratory resistance (Rrsfo) at 8 Hz was compared to flow-volume spirometry with regard to immediate, within-day, day-to-day and week-to-week variations in seven female and four male non-smoking, non-asthmatic volunteers. The lung functions were measured at 08:00, 12:00, 16:00 and 20:00 h on each of the four study days, i.e. two consecutive days in two consecutive weeks. During each visit there were three immediately repeated measurements of Rrsfo, followed by three spirometric recordings. The intra-subject coefficient of variation (Coeffvar) for the immediately repeated measurements was largest for Rrsfo (11.8%). When a simple reliability index (+/- 2 SD of the differences between the repeated measurements) was applied to the Rrsfo data, the Coeffvar reduced to 7.5%. In spirometry, the airflow parameters at defined lung volumes showed larger immediate variations (MEF50 = 5.6%, MEF25 = 8.3%, MMEF = 4.4%) than FEV1 (1.5%) and PEF (3.2%). The within-day variations were larger than the day-to-day or week-to-week variations, and the variations were largest in Rrsfo. A significant diurnal pattern was shown in spirometric parameters but not in Rrsfo. About 38% of the total variance in Rrsfo was due to variation within subjects, while the corresponding proportions in spirometric parameters were 1.8-18.4%. In conclusion, Rrsfo showed larger intrasubject variations than the spirometric parameters at all time intervals. Application of a simple reliability index and standardization of the time of day of the measurement reduced the variations and improved the quality of the Rrsfo data.

Short-term variations in oscillatory and spirometric lung function indices among school children.

The aim of this study was to compare immediate, daily and weekly variation in respiratory resistance measured by means of the forced oscillation technique (Rrs,FOT) to spirometric indices in 7-12 year old children with chronic respiratory symptoms. The lung function measurements were performed in 19 children on 4 days, i.e. two consecutive days during two consecutive weeks. On each day, the measurements were carried out at the same time of day and always repeated three times. In addition, Rrs,FOT and spirometric lung function indices were compared with an exercise challenge test in 12 children. Intrasubject coefficients of variation (CoVs) for Rrs,FOT were larger than those for spirometric indices. Only in the immediately repeated measurements was the CoV of maximal expiratory flow at 25% vital capacity larger than that of Rrs,FOT (16.6 vs 14.9%). At all time intervals, the smallest CoVs were observed in forced vital capacity (FVC) or in the ratio of forced expiratory volume in one second to FVC (2.0-2.6%). When excluding Rrs,FOT values which were not within 2 SD (0.11 kPa.L-1.s) of the differences between the immediately repeated measurements, the CoV of the immediately repeated measurements of Rrs,FOT was reduced to 9.1%, being smaller than that of maximal mid-expiratory flow (10.1%). However, even then the day-to-day variation in Rrs,FOT was clearly larger (16.0%) than those of the airflow indices at specified lung volumes (7.2-8.3%). This was also true for the weekly variation. In the exercise challenge test, there were larger changes in Rrs,FOT values than in the spirometric indices, but Rrs,FOT was the most sensitive index to detect changes in the respiratory system. In conclusion, the variation in Rrs,FOT values was larger than that of most spirometric indices. When a reliability index was applied, the immediate variation in Rrs,FOT values was comparable to those of the airflow indices at specified lung volumes. Rrs,FOT was also the most sensitive index in the exercise challenge test, and therefore it seems to be suitable for detection of short-term functional changes in the respiratory system. However, the relatively low repeatability of Rrs,FOT over days and weeks may limit its applicability to longer-term follow-ups.

Acute gonococcal arthritis: an unusual host and pathogen combination.

A 76 year old man was admitted for evaluation and treatment of acute oligoarticular arthritis having recently returned from India. He was diabetic on admission. Neisseria gonorrhoeae was isolated from pus collected by arthrocentesis of his right knee and was subsequently found to be chromosomally resistant to penicillin. The isolate required proline for growth and expressed the protein 1B-1 serovar. These characteristics of host and pathogen are atypical in that gonococcal arthritis usually occurs in young women and is usually caused by N gonorrhoeae isolates exhibiting hypersusceptibility to penicillin, the arginine, hypoxanthine and uracil requiring auxotype, and the protein 1A serotype. The patient responded well to therapy with oral ciprofloxacin and initial high dose penicillin.

Obstacles to the utilization of vocational services: an analysis of the literature.

While employment has been linked to positive clinical outcomes with drug abusers, research suggests that many treatment programs do not emphasize vocational services and under-utilize vocational resources. This article summarizes potential client-, program-, and societal-level obstacles to vocational rehabilitation service delivery identified in past studies with both substance abusers and other related client groups. Obstacles identified for related groups are integrated with issues relevant to drug treatment clients. This analysis is based on literature published over the last 20 years.