Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease.

BACKGROUND: Falls are a common complication of Parkinson's disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson's disease. METHODS: This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson's motor and non-motor symptoms, quality of life and cost-effectiveness. DISCUSSION: This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson's disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population. TRIAL REGISTRATION: REC reference: 19/SW/0043. EudraCT: 2018-003219-23. ISCRTN: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 PROTOCOL AT TIME OF PUBLICATION: Version 7.0, 20th January 2021.

The Lombard effect in singing humpback whales: Source levels increase as ambient ocean noise levels increase.

Many animals increase the intensity of their vocalizations in increased noise. This response is known as the Lombard effect. While some previous studies about cetaceans report a 1 dB increase in the source level (SL) for every dB increase in the background noise level (NL), more recent data have not supported this compensation ability. The purpose of this study was to calculate the SLs of humpback whale song units recorded off Hawaii and test for a relationship between these SLs and background NLs. Opportunistic recordings during 2012-2017 were used to detect and track 524 humpback whale encounters comprised of 83 974 units on the U.S. Navy's Pacific Missile Range Facility hydrophones. Received levels were added to their estimated transmission losses to calculate SLs. Humpback whale song units had a median SL of 173 dB re 1 µPa at 1 m, and SLs increased by 0.53 dB/1 dB increase in background NLs. These changes occurred in real time on hourly and daily time scales. Increases in ambient noise could reduce male humpback whale communication space in the important breeding area off Hawaii. Since these vocalization changes may be dependent on location or behavioral state, more work is needed at other locations and with other species.

Lombard effect: Minke whale boing call source levels vary with natural variations in ocean noise.

Minke whales were acoustically detected, localized, and tracked on the U.S. Navy's Pacific Missile Range Facility from 2012 to 2017. Animal source levels (SLs) were estimated by adding transmission loss estimates to measured received levels of 42 159 individual minke whale boings. Minke whales off Hawaii exhibited the Lombard effect in that they increased their boing call intensity in increased background noise. Minke whales also decreased the variance of the boing call SL in higher background noise levels. Although the whales partially compensated for increasing background noise, they were unable or unwilling to increase their SLs by the same amount as the background noise. As oceans become louder, this reduction in communication space could negatively impact the health of minke whale populations. The findings in this study also have important implications for acoustic animal density studies, which may use SL to estimate probability of detection.

A multicentre, clinical evaluation of a hydro-responsive wound dressing: the Glasgow experience.

OBJECTIVE: Our aim was to assess the effectiveness of hydro-responsive wound dressing (HRWD) in debridement and wound bed preparation of a variety of acute and chronic wounds that presented with devitalised tissue needing removal so that healing may proceed. METHOD: This was a non-comparative evaluation of acute and chronic wounds that required debridement as part of their normal treatment regimen. Clinicians recorded wound changes including a subjective assessment level of devitalised tissue and wound bed preparation, presence of pain, wound status (e.g., wound size) and periwound skin condition. Data was also collected from clinicians and patients to provide information on clinical performance of the dressing. RESULTS: We recruited 100 patients with a variety of wound types into the study. Over 90% of the clinicians reported removal of devitalised tissue to enable a healing response in both chronic and acute wounds. Specifically, over the course of the evaluation period, levels of devitalised tissue (necrosis and slough) reduced from 85.5% to 26.3%, and this was accompanied by an increase in wound bed granulation from 12.0% to 33.7%. Correspondingly, there was a 40% reduction in wound area, hence a clinically relevant healing response was seen upon treatment with HRWD. It is also noteworthy that this patient population included a significant proportion of chronic wounds (51.4%) that showed no signs of wound progression within <4 weeks before study inclusion. Of these chronic wounds, 93% demonstrated wound progression upon treatment with HRWD. Despite reported pain levels being low pre- and post-dressing change, overall wound pain improved (reduced) in 48% of patients. Periwound skin condition showed a tendency towards improvement, and the fluid management capabilities of the HRWD was reported as good to excellent in the majority of cases. Wound infections were reduced by at least 60% over the evaluation period. A simple cost-effective analysis demonstrated significant savings using HRWD (£6.33) over current standard practice regimens of a four-step debridement process (£8.05), larval therapy (£306.39) and mechanical pad debridement (£11.46). CONCLUSION: HRWD was well tolerated and was demonstrated to be an efficient debridement tool providing rapid, effective and pain free debridement in a variety of wound types.

Comparing the epidemiology of hospital-acquired methicillin-resistant Staphylococcus aureus clone groups in Alberta, Canada.

Patients with methicillin-resistant Staphylococcus aureus (MRSA) clones, which were traditionally seen in the community setting (USA400/CMRSA7 and USA300/CMRSA10), are often identified as hospital-acquired (HA) infections using Infection Prevention and Control (IPC) surveillance definitions. This study examined the demographics and healthcare risk factors of patients with HA-MRSA to help understand if community MRSA clones are from a source internal or external to the hospital setting. Despite USA300/CMRSA10 being the predominant clone in Alberta, hospital clones (USA100/CMRSA2) still dominated in the acute care setting. In the Alberta hospitalized population, patients with USA400/CMRSA7 and USA300/CMRSA10 clones were significantly younger, had fewer comorbidities, and a greater proportion had none or ambulatory care-only healthcare exposure. These findings suggest that there are two distinct populations of HA-MRSA patients, and the patients with USA400/CMRSA7 and USA300/CMRSA10 clones identified in hospital more greatly resemble patients affected by those clones in the community. It is possible that epidemiological assessment overidentifies HA acquisition of MRSA in patients unscreened for MRSA on admission to acute care.

Swim track kinematics and calling behavior attributed to Bryde's whales on the Navy's Pacific Missile Range Facility.

Time difference of arrival methods for acoustically localizing multiple marine mammals have been applied to recorded data from the Navy's Pacific Missile Range Facility in order to localize and track calls attributed to Bryde's whales. Data were recorded during the months of August-October 2014, and 17 individual tracks were identified. Call characteristics were compared to other Bryde's whale vocalizations from the Pacific Ocean, and locations of the recorded signals were compared to published visual sightings of Bryde's whales in the Hawaiian archipelago. Track kinematic information, such as swim speeds, bearing information, track duration, and directivity, was recorded for the species. The intercall interval was also established for most of the tracks, providing cue rate information for this species that may be useful for future acoustic density estimate calculations.

Minke whales (Balaenoptera acutorostrata) respond to navy training.

Minke whales (Balaenoptera acutorostrata) were acoustically detected and localized via their boing calls using 766 h of recorded data from 24 hydrophones at the U.S. Navy's Pacific Missile Range Facility located off Kauai, Hawaii. Data were collected before, during, and after naval undersea warfare training events, which occurred in February over three consecutive years (2011-2013). Data collection in the during periods were further categorized as phase A and phase B with the latter being the only period with naval surface ship activities (e.g., frigate and destroyer maneuvers including the use of mid-frequency active sonar). Minimum minke whale densities were estimated for all data periods based upon the numbers of whales acoustically localized within the 3780 km(2) study area. The 2011 minimum densities in the study area were: 3.64 whales [confidence interval (CI) 3.31-4.01] before the training activity, 2.81 whales (CI 2.31-3.42) for phase A, 0.69 whales (CI 0.27-1.8) for phase B and 4.44 whales (CI 4.04-4.88) after. The minimum densities for the phase B periods were highly statistically significantly lower (p < 0.001) from all other periods within each year, suggesting a clear response to the phase B training. The phase A period results were mixed when compared to other non-training periods.

Delphinid behavioral responses to incidental mid-frequency active sonar.

Opportunistic observations of behavioral responses by delphinids to incidental mid-frequency active (MFA) sonar were recorded in the Southern California Bight from 2004 through 2008 using visual focal follows, static hydrophones, and autonomous recorders. Sound pressure levels were calculated between 2 and 8 kHz. Surface behavioral responses were observed in 26 groups from at least three species of 46 groups out of five species encountered during MFA sonar incidents. Responses included changes in behavioral state or direction of travel, changes in vocalization rates and call intensity, or a lack of vocalizations while MFA sonar occurred. However, 46% of focal groups not exposed to sonar also changed their behavior, and 43% of focal groups exposed to sonar did not change their behavior. Mean peak sound pressure levels when a behavioral response occurred were around 122 dB re: 1 µPa. Acoustic localizations of dolphin groups exhibiting a response gave insight into nighttime movement patterns and provided evidence that impacts of sonar may be mediated by behavioral state. The lack of response in some cases may indicate a tolerance of or habituation to MFA sonar by local populations; however, the responses that occur at lower received levels may point to some sensitization as well.

Why go online when you have pain? A qualitative analysis of teenagers' use of the Internet for pain management advice.

BACKGROUND: Adolescents are routinely recognized as native to online technologies. However, we know from previous research that this familiarity does not often translate into its use for help-seeking around health. We designed this study to examine the experience of adolescents in using the Internet to access pain management information, specifically why some adolescents may be reluctant to use these resources. METHODS: Twenty-six healthy, school attending, adolescents aged between 14 and 17 years old were recruited to a qualitative study of focus groups. Seventeen participants were female and nine were male. Participation was limited to those who self-selected as frequent users of the Internet, but who were loath to use it as a resource for health information as we wished to explore reasons for non-use. All data were thematically analysed. RESULTS: Most participants reported using the Internet to seek health information at least once. Experiences with online content were typically negative and drawn on only when all other sources of information and pain coping were exhausted. Three themes emerged, Drivers of Internet use, Barriers, and Anxiety around use. Adolescent health websites were reported to be confusing, anxiety provoking and hard to negotiate. The Internet was judged to be less accessible than other forms of pain and health coping information. Secondary themes related to topic embarrassment, the strive for independence and reassurance, preferred information source failure, curiosity, website design, availability of OTC analgesics, effort, fear-provoking narratives, mistrust of quality of online content and pain-related anxiety. CONCLUSIONS: Counter to many positive reports of the health benefits of Internet use during information seeking, its value is questionable to some adolescents. Typical experience was anxiety provoking, unlikely to yield helpful results, and wasteful comparative to off-line resources for pain.

Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population.

IMPORTANCE: Latino populations have one of the highest prevalences of type 2 diabetes worldwide. OBJECTIVES: To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships. DESIGN, SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013. One variant was further tested for allele frequency and association with type 2 diabetes in large multiethnic data sets of 14,276 participants and characterized in experimental assays. MAIN OUTCOME AND MEASURES: Prevalence of type 2 diabetes. Secondary outcomes included age of onset, body mass index, and effect on protein function. RESULTS: A single rare missense variant (c.1522G>A [p.E508K]) was associated with type 2 diabetes prevalence (odds ratio [OR], 5.48; 95% CI, 2.83-10.61; P = 4.4 × 10(-7)) in hepatocyte nuclear factor 1-α (HNF1A), the gene responsible for maturity onset diabetes of the young type 3 (MODY3). This variant was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it. In multiethnic replication data sets, the p.E508K variant was seen only in Latino patients (n = 1443 with type 2 diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16; 95% CI, 1.75-9.92; P = .0013). In experimental assays, HNF-1A protein encoding the p.E508K mutant demonstrated reduced transactivation activity of its target promoter compared with a wild-type protein. In our data, carriers and noncarriers of the p.E508K mutation with type 2 diabetes had no significant differences in compared clinical characteristics, including age at onset. The mean (SD) age for carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P = .49) and the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P = .19). CONCLUSIONS AND RELEVANCE: Using whole-exome sequencing, we identified a single low-frequency variant in the MODY3-causing gene HNF1A that is associated with type 2 diabetes in Latino populations and may affect protein function. This finding may have implications for screening and therapeutic modification in this population, but additional studies are required.

Survival of current production tumor endoprostheses: complications, functional results, and a comparative statistical analysis.

BACKGROUND AND OBJECTIVES: Retrospectively analyze outcomes of current-generation Global Modular Replacement System (GMRS) modular tumor endoprosthesis for the lower limb in primary and secondary implantation procedures. METHODS: Two hundred ninety five prostheses were implanted, 197 were primary implants, 98 were for revision surgery; revision procedures included 84 failed tumor reconstructions and 14 failed non-tumor reconstructions. Anatomic sites included: distal femur 199; proximal tibia 60; proximal femur 32;total femur 4. Endoprosthesis failures were classified as soft-tissue failures (Type 1), aseptic loosening (Type 2), structural fracture (Type 3), infection (Type 4), and tumor recurrence (Type 5). MSTS functional scores were measured. RESULTS: The overall failure rate was 28.8% and failure occurred at a median of 1.7 years (range, 1 month to 7 years). At a mean oncologic follow up of 4.2 years (range, 2-8 years), 195 patients are continuously NED, 43 NED after treatment of relapse, 10 AWD, 33 DWD. There was a significant difference in implant survival of all modes of failure between primary and revision implants (P = 0.03). No prosthetic fracture occurred. The average functional score was 81.6% (24.5). CONCLUSIONS: Mid-term results with GMRS are promising, with good functional results and low incidence of complications for primary implants. LEVEL OF EVIDENCE: Therapeutic study, level IV-1 (case series).

Tracking dolphin whistles using an autonomous acoustic recorder array.

Dolphins are known to produce nearly omnidirectional whistles that can propagate several kilometers, allowing these sounds to be localized and tracked using acoustic arrays. During the fall of 2007, a km-scale array of four autonomous acoustic recorders was deployed offshore of southern California in a known dolphin habitat at ~800 m depth. Concurrently with the one-month recording, a fixed-point marine mammal visual survey was conducted from a moored research platform in the center of the array, providing daytime species and behavior visual confirmation. The recordings showed three main types of dolphin acoustic activity during distinct times: primarily whistling during daytime, whistling and clicking during early night, and primarily clicking during late night. Tracks from periods of daytime whistling typically were tightly grouped and traveled at a moderate rate. In one example with visual observations, traveling common dolphins (Delphinus sp.) were tracked for about 10 km with an average speed of ~2.5 m s(-1) (9 km h(-1)). Early night recordings had whistle localizations with wider spatial distribution and slower travel speed than daytime recordings, presumably associated with foraging behavior. Localization and tracking of dolphins over long periods has the potential to provide insight into their ecology, behavior, and potential response to stimuli.

Offshore killer whale tracking using multiple hydrophone arrays.

To study delphinid near surface movements and behavior, two L-shaped hydrophone arrays and one vertical hydrophone line array were deployed at shallow depths (<125 m) from the floating instrument platform R/P FLIP, moored northwest of San Clemente Island in the Southern California Bight. A three-dimensional propagation-model based passive acoustic tracking method was developed and used to track a group of five offshore killer whales (Orcinus orca) using their emitted clicks. In addition, killer whale pulsed calls and high-frequency modulated (HFM) signals were localized using other standard techniques. Based on these tracks sound source levels for the killer whales were estimated. The peak to peak source levels for echolocation clicks vary between 170-205 dB re 1 µPa @ 1 m, for HFM calls between 185-193 dB re 1 µPa @ 1 m, and for pulsed calls between 146-158 dB re 1 µPa @ 1 m.

Cemented versus cementless endoprostheses for lower limb salvage surgery.

PURPOSE: To determine the survival and failures of cemented vs cementless endoprostheses. METHODS: We retrospectively studied 232 patients treated with lower limb salvage surgery and reconstruction using cementless and cemented endoprostheses from 2002 to 2007. We compared survival and failures of the endoprostheses regarding age, gender, body mass index (BMI), diagnosis, site of reconstruction, radiation therapy, chemotherapy, and stem fixation. RESULTS: The mean patient follow-up was 28 months (median 24; range 12-84). The overall survival of cemented and cementless endoprostheses at 60 months was 64 and 78%, respectively (p=0.0078). Survival at 60 months of cemented and cementless endoprostheses to infection was 68 and 82%, respectively (p=0.0248). Survival of cemented and cementless endoprostheses to aseptic loosening at 60 months was 94 and 96%, respectively (p=0.1493). The only significant univariate and multivariate predictor of survival was the cementless type of stem fixation. CONCLUSION: Cementless endoprostheses have higher overall survival and survival to infection compared to cemented endoprostheses. Survival to aseptic loosening is not different. Stem fixation is the only significant variable for survival.

Surgical Site Infection in Patients Managed with an Endoprosthesis for the Treatment of Cancer: Evaluation of Patient, Disease, and Index Surgical Factors.

BACKGROUND: Surgical site infection (SSI) after segmental endoprosthetic reconstruction in patients treated for oncologic conditions remains both a devastating and a common complication. The goal of the present study was to identify variables associated with the success or failure of treatment of early SSI following the treatment of a primary bone tumor with use of a segmental endoprosthesis. METHODS: The present study used the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) data set to identify patients who had been diagnosed with an SSI after undergoing endoprosthetic reconstruction of a lower extremity primary bone tumor. The primary outcome of interest in the present study was a dichotomous variable: the success or failure of infection treatment. We defined failure as the inability to eradicate the infection, which we considered as an outcome of amputation or limb retention with chronic antibiotic suppression (>90 days or ongoing therapy at the conclusion of the study). Multivariable models were created with covariates of interest for each of the following: surgery characteristics, cancer treatment-related characteristics, and tumor characteristics. Multivariable testing included variables selected on the basis of known associations with infection or results of the univariable tests. RESULTS: Of the 96 patients who were diagnosed with an SSI, 27 (28%) had successful eradication of the infection and 69 had treatment failure. Baseline and index procedure variables showing significant association with SSI treatment outcome were moderate/large amounts of fascial excision ≥1 cm2) (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.001), use of local muscle/skin graft (OR,11.88 [95% CI, 1.83 to 245.83]; p = 0.031), and use of a deep Hemovac (OR, 0.24 [95% CI, 0.05 to 0.85]; p = 0.041). In the final multivariable model, excision of fascia during primary tumor resection was the only variable with a significant association with treatment outcome (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.018). CONCLUSIONS: The results of this secondary analysis of the PARITY trial data provide further insight into the patient-, disease-, and treatment-specific associations with SSI treatment outcomes, which may help to inform decision-making and management of SSI in patients who have undergone segmental bone reconstruction of the femur or tibia for oncologic indications. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Prone Positioning of Older Adults with COVID-19: A Brief Review and Proposed Protocol.

COVID-19 disproportionately affects older people, with higher rates of infection and a higher risk of adverse outcomes. A brief review of literature was undertaken to inform development of a protocol describing the indications and process of prone positioning to aid the management of COVID-19 infection in non-mechanically ventilated, awake older adults. PubMed was searched up to 14th January 2021 to identify English language papers that described prone positioning procedures used in non-mechanically ventilated patients. Data were pooled to inform the development of a prone positioning protocol for use in hospital ward environments. The protocol was trialled and refined during routine clinical practice. Screening of 146 articles yielded five studies detailing a prone positioning protocol. Prone positioning is a potentially feasible and tolerated treatment adjunct for hypoxaemia in older adults with COVID-19. Future studies should further establish the efficacy, safety, and tolerability in respiratory illnesses in non-intensive care settings.

Classification of behavior using vocalizations of Pacific white-sided dolphins (Lagenorhynchus obliquidens).

Surface behavior and concurrent underwater vocalizations were recorded for Pacific white-sided dolphins in the Southern California Bight (SCB) over multiple field seasons spanning 3 years. Clicks, click trains, and pulsed calls were counted and classified based on acoustic measurements, leading to the identification of 19 key call features used for analysis. Kruskal-Wallis tests indicated that call features differ significantly across behavioral categories. Previous work had discovered two distinctive click Types (A and B), which may correspond to known subpopulations of Pacific white-side dolphins in the Southern California Bight; this study revealed that animals producing these different click types also differ in both their behavior and vocalization patterns. Click Type A groups were predominantly observed slow traveling and milling, with little daytime foraging, while click Type B groups were observed traveling and foraging. These behavioral differences may be characteristic of niche partitioning by overlapping populations; coupled with differences in vocalization patterns, they may signify that these subpopulations are cryptic species. Finally, random forest decision trees were used to classify behavior based on vocalization data, with rates of correct classification up to 86%, demonstrating the potential for the use of vocalization patterns to predict behavior.

Public attitudes to the use of remote data collection in clinical research.

BACKGROUND/AIMS: Coronavirus Disease 2019 (COVID-19) has presented an unprecedented challenge for delivering clinical research. The use of technology-assisted data collection for clinical research is desirable for many practitioners, but the acceptability of use in the general population has not been assessed. The aim of the study was to assess attitudes towards using technology-assisted remote methods in the delivery of clinical research in the UK and to understand the barriers to taking part in research with respect to both remote assessments and traditional research methods across different age ranges. METHODS: The study was conducted as an online anonymous survey with a 4-part questionnaire, between August 2020 and December 2020. Participants living in the UK aged 18 years and above were eligible to take part. RESULTS: A total 351 completed the survey and are included in the data analysis. In all age groups, participants identified that use of online assignments, video calls and telephone calls would make them more likely to take part in clinical research. Overall, the largest barrier to taking part in research was time commitments and timing of the appointment. COVID-19 has had a small, positive influence on the confidence of using technology in the general population. CONCLUSIONS: The study found that there is a large interest in taking part in research using online, telephone and video call appointments, which could facilitate research delivery in light of ongoing COVID-19-related restrictions and also improve the accessibility and inclusivity of research.

An in vitro study of the effect of the optimal irrigation solution conditions during canine articular surgery.

OBJECTIVES: To establish whether chondrocyte viability, matrix degradation and the induction of proteolytic gene expression in canine cartilage is independent of irrigation fluid osmolality and time following exposure to the irrigation fluid. METHODS: Canine cartilage explants were exposed to one of three different solution types i) Culture medium (270-280 mOsmol/kg) ii) NaCl 0.9% (302 mOsmol/kg) iii) NaCl 0.9% with sucrose (600 mOsmol/kg). Chondrocyte viability and selected proteolytic gene expression were measured at two time points; immediately following exposure and 24 h following exposure. The media samples at 24 h following exposure were assessed for sulphated glycosaminoglycan (sGAG) release. RESULTS: In all samples, no cell death was observed across the superficial or deeper layers of the cartilage. When adjusting for time, gene expression was not shown to be dependent on solution type. However for all solution types, Matrix Metalloproteinase 13 (MMP13) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS5) expression was significantly decreased in cartilage samples at 24 h post exposure comparatively to samples tested immediately post exposure. No significant differences were identified in the relative sGAG release between the solution types. CLINICAL SIGNIFCANCE: Arthroscopic solution irrigation of cartilage explants had no effect on cell viability or proteinase production. At present there is no indication to optimise irrigation fluid osmolarity, as conventional arthroscopic solution was not deleterious to healthy cartilage in this model.

Developmental regulation of Dictyostelium discoideum plasma membrane proteins.

Developmental changes in the plasma membrane proteins of Dictyostelium discoideum have been studied using metabolic labeling with [35S]methionine and two-dimensional electrophoresis. Pulse labeling for 1 h at the early interphase, late interphase, aggregation, and tip formation stages of development showed that the profile of newly synthesized plasma membrane proteins changed dramatically over this interval. Only 14% of the polypeptide species were synthesized at all four stages at detectable levels; 86% of the species changed over this developmental interval according to the criterion that they were synthesized at some but not all of the four stages tested. Long-term labeling during vegetative growth followed by initiation of development showed that the "steady-state" levels of the plasma membrane proteins changed very little over the same period. The only changes were in minor species (33% overall change). Similar analyses of whole cell proteins showed 27 and 20% change, respectively. Cell surface radioiodination revealed 52 external proteins in the plasma membrane. Comparison with the uniform methionine labeling results showed that these proteins were, with one notable exception, minor membrane components. In these external proteins, also, developmental changes were limited and were observed in the less abundant species. These results demonstrate the existence of two general classes of plasma membrane proteins. The first is a population of high-abundance proteins that are present in vegetative cells and are largely conserved through development. These possibly serve "housekeeping" functions common to all stages. The second class consists of low-abundance species that are expressed in a highly stage-specific manner and which presumably participate in developmentally important functions.