4-Hydroxynonenal regulates mitochondrial function in human small airway epithelial cells

Prolonged exposure to oxidative stress causes Acute Lung Injury (ALI) and significantly impairs pulmonary function. Previously we have demonstrated that mitochondrial dysfunction is a key pathological factor in hyperoxic ALI. While it is known that hyperoxia induces the production of stable, but toxic 4-hydroxynonenal (4-HNE) molecule, it is unknown how the reactive aldehyde disrupts mitochondrial function. Our previous in vivo study indicated that exposure to hyperoxia significantly increases 4-HNE-Protein adducts, as well as levels of MDA in total lung homogenates. Based on the in vivo studies, we explored the effects of 4-HNE in human small airway epithelial cells (SAECs). Human SAECs treated with 25 μM of 4-HNE showed a significant decrease in cellular viability and increased caspase-3 activity. Moreover, 4-HNE treated SAECs showed impaired mitochondrial function and energy production indicated by reduced ATP levels, mitochondrial membrane potential, and aconitase activity. This was followed by a significant decrease in mitochondrial oxygen consumption and depletion of the reserve capacity. The direct effect of 4-HNE on the mitochondrial respiratory chain was confirmed using Rotenone. Furthermore, SAECs treated with 25 μM 4-HNE showed a time-dependent depletion of total Thioredoxin (Trx) proteins and Trx activity. Taken together, our results indicate that 4-HNE induces cellular and mitochondrial dysfunction in human SAECs, leading to an impaired endogenous antioxidant response.     

Short-term variability of cerebral blood flow velocity responses to arterial blood pressure transients

The time course of mean beat-to-beat changes in cerebral blood flow velocity changes induced by spontaneous transients in mean arterial blood pressure was studied in a group of 39 healthy subjects, ages 40 +/- 15 (SD) years. Continuous 10-min noninvasive recordings of cerebral blood flow velocity (CBFV) from both middle cerebral arteries (MCA) with Doppler ultrasound (US) and simultaneous beat-to-beat arterial blood pressure (ABP) were made. A total of 522 spontaneous positive transients of ABP and CBFV were extracted with a maximum of 15 transients for each subject. The CBFV transient amplitude was normalized by the corresponding ABP change and the area-under-the-curve (AUC) of the falling phase was used to classify the CBFV regulatory response as either weak, moderate or strong. The coherent average of ABP and CBFV of each category confirmed the consistency of this classification, reinforced by the agreement of separate averages for recordings from the right and left MCA. All 39 subjects showed at least two categories of transients, with all three categories present in 33 subjects (right MCA) and 29 subjects (left MCA), respectively. These results indicate a significant short-term variability of CBFV responses in healthy subjects whose origin remains unexplained.     

Validity of the neck disability index,Northwick Park neck pain questionnaire,and problem elicitation technique for measuring disability associated with whiplash-associated disorders

The Neck Disability Index (NDI) and Northwick Park Neck Pain Questionnaire (NPQ) were developed to measure self-perceived disability from neck pain, including that which may arise from whiplash injury. However, there is little data specifically concerning their validity for whiplash-associated disorders (WAD). The aim of this study was to assess the validity of the NDI and NPQ as measures of outcome in WAD by comparing them to a patient preference questionnaire, the problem elicitation technique (PET), which identifies problems that are of most importance to the individual patient. A cross-sectional study of 71 patients with varying severity and duration of WAD were recruited from a private physiotherapy practice. All patients completed a standardized self-administered questionnaire that included demographic and clinical details as well as self-perceived pain and severity of symptoms, NDI and NPQ. A trained interviewer administered the PET. Construct validity of the disability measures was examined by determining their correlation with each other and with pain and severity of symptoms by calculating Pearson's correlation coefficients. Content validity of the NDI and NPQ was assessed by comparing the items of both questionnaires to the problems identified by the PET. Participants' mean age was 40.1 years (SD=14.3) and 59 were women (83.1%). Most patients were in WAD category I (n=23, 32.1%), or II (n=42, 59.2%). Mean NDI, NPQ, and PET scores were 40.7 (SD=17.0), 38.7 (SD=15.8), and 160.2 (SD=92.0, range 6.0-509.5), respectively. Correlations between the NDI and PET, NPQ and PET, and NDI and NPQ were r=0.57, 0.56 and 0.88, respectively. The PET identified an average of 7.7 problems per patient (SD=4.2, range 1-17 problems). Problems most commonly identified were work for wages (52.1%), fatigued during the day (50.7%), participation in sports (47.9%), depression (43.7%), drive a car (43.7%), socialize with friends (33.8%), sleep through the night (31.0%), frustration (31.0%), and anger (28.2%). Only three of these problems are included in the NDI (work, driving, and sleeping) and only four are included in the NPQ (work, driving, sleeping, and social activities). While both the NDI and NPQ include some problems that are common in patients with WAD, frequently identified problems, such as emotional and social items are absent. In contrast to the PET, neither instrument captures the full spectrum of disabilities judged to be important by the patient.     

The Kaiser Permanente Shoulder Arthroplasty Registry: Results from 6,336 primary shoulder arthroplasties

Background and purpose

Shoulder arthroplasty is being performed in the United States with increasing frequency. We describe the medium-term findings from a large integrated healthcare system shoulder arthroplasty registry.

Patients and methods

Shoulder arthroplasty cases registered between January 2005 and June 2013 were included for analysis. The registry included patient characteristics, surgical information, implant data, attrition, and patient outcomes such as surgical site infections, venous thromboembolism, and revision procedures.

Results

During the study period, 6,336 primary cases were registered. Median follow-up time for all primaries was 3.3 years; 461 cases were lost to follow-up by ending of health plan membership. Primary cases were predominantly female (56%) and white (81%), with an average age of 70 years. The most common reason for surgery was osteoarthritis in 60% of cases, followed by acute fracture (17%) and rotator cuff tear arthropathy (15%). In elective shoulder arthroplasty procedures, 200 all-cause revisions (4%) were reported, with glenoid wear being the most common reason.

Interpretation

Most arthroplasties were elective procedures: over half performed for osteoarthritis. Glenoid wear was the most common reason for revision of primary shoulder arthroplasty in elective cases.In the period 2000 through 2010, over 200,000 shoulder arthroplasties were performed in the USA for osteoarthritis (Trofa et al. 2014). With the increasing use of shoulder arthroplasty (SA) over the past decade (Kim et al. 2011) and projections that future growth rates of SA may exceed those of hip and knee arthroplasty (Day et al. 2010), the need to track the outcomes of SA is becoming increasingly important.Arthroplasty registries provide an important mechanism for tracking surgical outcomes. In the fields of total hip arthroplasty and total knee arthroplasty, registries have demonstrated their importance in monitoring revisions, complications, and mortality, identifying outlier prostheses, and improving quality of care (Graves et al. 2004, Herberts and Malchau 2000, de Steiger et al. 2013, Paxton et al. 2010). SA registries have also provided critical information about demographics, survival, and outlier implants, though there have been considerably fewer publications from the younger national SA registries than from the more established hip and knee registries (Clitherow et al. 2014, Young et al. 2013, Rasmussen et al. 2012a, Rasmussen et al. 2014a and b, Fevang et al. 2009, Fevang et al. 2013). The lack of a national US registry emphasizes the need to use existing US registries to conduct international comparisons of SA patients, implants, surgical techniques, and outcomes. We present the medium-term findings of a large integrated healthcare system SA registry.     

Declines in violence and police arrest among female sex workers in Karnataka state,south India,following a comprehensive HIV prevention programme

Introduction

Female sex workers (FSWs) frequently experience violence, harassment and arrest by the police or their clients, but there is little evidence as to the impact that such factors may have on HIV risk or whether community interventions could mitigate this impact.

Methods

As part of the evaluation of the Avahan programme in Karnataka, serial integrated behavioural and biological assessment (IBBA) surveys (four districts) (2005 to 2011) and anonymous polling booth surveys (PBS) (16 districts) (2007 to 2011) were conducted with random samples of FSWs. Logistic regression analysis was used to assess 1) changes in reported violence and arrests over time and 2) associations between violence by non-partners and police arrest and HIV/STI risk and prevalence. Mediation analysis was used to identify mediating factors.

Results

5,792 FSWs participated in the IBBAs and 15,813 participated in the PBS. Over time, there were significant reductions in the percentages of FSWs reporting being raped in the past year (PBS) (30.0% in 2007, 10.0% in 2011, p<0.001), being arrested in the past year [adjusted odds ratio (AOR) 0.57 (0.35, 0.93), p=0.025] and being beaten in the past six months by a non-partner (clients, police, pimps, strangers, rowdies) [AOR 0.69 (0.49, 0.95), p=0.024)] (IBBA). The proportion drinking alcohol (during the past week) also fell significantly (32.5% in 2005, 24.9% in 2008, 16.8% in 2011; p<0.001). Violence by non-partners (being raped in the past year and/or beaten in the past six months) and being arrested in the past year were both strongly associated with HIV infection [AOR 1.59 (1.18, 2.15), p=0.002; AOR 1.91 (1.17, 3.12), p=0.01, respectively]. They were also associated with drinking alcohol (during the past week) [AOR 1.98 (1.54, 2.53), p<0.001; AOR 2.79 (1.93, 4.04), p<0.001, respectively], reduced condom self-efficacy with clients [AOR 0.36 (0.27, 0.47), p<0.001; AOR 0.62 (0.39, 0.98), p=0.039, respectively], symptomatic STI (during the past year) [AOR 2.62 (2.07, 3.30), p<0.001; AOR 2.17 (1.51, 3.13), p<0.001, respectively], gonorrhoea infection [AOR 2.79 (1.51, 5.15), p=0.001; AOR 2.69 (0.96, 7.56), p=0.060, respectively] and syphilis infection [AOR 1.86 (1.04, 3.31), p=0.036; AOR 3.35 (1.78, 6.28), p<0.001, respectively], but not with exposure to peer education, community mobilization or HIV testing uptake. Mediation analysis suggests that alcohol use and STIs may partially mediate the association between violence or arrests and HIV prevalence.

Discussion

Violence by non-partners and arrest are both strongly associated with HIV infection among FSWs. Large-scale, comprehensive HIV prevention programming can reduce violence, arrests and HIV/STI infection among FSWs.     

Longer hospital stay,more complications,and increased mortality but substantially improved function after knee replacement in older patients: A study of 3,144 primary unilateral total knee replacements

Background and purpose

Total knee replacement (TKR) is being increasingly performed in elderly patients, yet there is little information on specific requirements and complication rates encountered by this group. We assessed whether elderly patients undergoing TKR had different length of stay, requirements, complication rates, and functional outcomes compared to younger counterparts.

Patients and methods

We analyzed prospectively gathered data on 3,144 consecutive primary TKRs (in 2,092 patients aged less than 75 years, 694 patients aged between 75 and 80 years, and 358 patients aged over 80 years at the time of surgery).

Results

Incidence of blood transfusion, urinary catheterization, postoperative confusion, cardiac arrhythmia, and 1-year mortality increased with age, even after adjusting for confounding factors, whereas the incidences of chest infection and mortality at 1 month were highest in those aged 75–80. Rates of thromboembolism, prosthetic infection, and revision were similar in the 3 age groups. All groups showed similar substantial improvements in American Knee Society (AKS) knee scores, which were maintained at 5 years. Older patients had smaller improvements in AKS function score, which deteriorated between 3 and 5 years postoperatively, in contrast to the younger group.

Interpretation

Elderly people stand to gain considerably from TKR, particularly in terms of pain relief, and they should not be denied surgery based solely on age. However, they should be warned that they can expect a longer length of stay, a higher requirement for blood transfusion and/or urinary catheterization, and more medical complications postoperatively. Mortality was also higher in the older age groups. The risks have been quantified to assist in perioperative counselling, informed consent, and healthcare planning.Healthcare systems and medical professionals will need to cater for increasing numbers of total knee replacements (TKRs) in elderly people in the coming years (Carr et al. 2012), but little is known about inpatient requirements and the postoperative complications suffered by this particular patient group. Some studies have shown good joint-specific pain relief and functional benefits from TKR in the elderly (Anderson et al. 1996, Birdsall et al. 1999), although it has been suggested that elderly patients may attain lower global function than their younger counterparts (Clement et al. 2011, Kennedy et al. 2013). However, studies attempting to describe complications in the elderly undergoing TKR have been small (Zicat et al. 1993, Hosick et al. 1994, Joshi et al. 2003), have lacked comparator groups (Hosick et al. 1994, Joshi et al. 2003), or have failed to quantify the time scales within which complications have occurred (Clement et al. 2011, Kennedy et al. 2013). Other studies and registries have been based on discharge summary databases without specific patient follow-up (Kreder et al. 2005, Mahomed et al. 2005, Scottish Arthroplasty Project, 2012). They therefore relied on third-party coding of discharge summaries and reported only on mortality during the index admission (Kreder et al. 2005) or selected complications requiring hospital re-admission within 30 or 90 days (Kreder et al. 2005, Mahomed et al. 2005, Scottish Arthroplasty Project, 2012).The aim of this study was to determine whether elderly patients undergoing TKR had different postoperative length of stay, inpatient requirements (i.e. blood transfusion and urinary catheterization), complication rates, and mortality rates to those of their younger counterparts. Functional outcomes were assessed as a secondary outcome measure, to determine whether elderly patients gained benefit comparable to that of their younger counterparts, independently of recorded admission requirements and complications.