Pre-frailty factors in community-dwelling 40-75 year olds: opportunities for successful ageing.

BACKGROUND: There is little known about pre-frailty attributes or when changes which contribute to frailty might be detectable and amenable to change. This study explores pre-frailty and frailty in independent community-dwelling adults aged 40-75 years. METHODS: Participants were recruited through local council networks, a national bank and one university in Adelaide, Australia. Fried frailty phenotype scores were calculated from measures of unintentional weight loss, exhaustion, low physical activity levels, poor hand grip strength and slow walking speed. Participants were identified as not frail (no phenotypes), pre-frail (one or two phenotypes) or frail (three or more phenotypes). Factor analysis was applied to binary forms of 25 published frailty measures Differences were tested in mean factor scores between the three Fried frailty phenotypes and ROC curves estimated predictive capacity of factors. RESULTS: Of 656 participants (67% female; mean age 59.9 years, SD 10.6) 59.2% were classified as not frail, 39.0% pre-frail and 1.8% frail. There were no gender or age differences. Seven frailty factors were identified, incorporating all 25 frailty measures. Factors 1 and 7 significantly predicted progression from not-frail to pre-frail (Factor 1 AUC 0.64 (95%CI 0.60-0.68, combined dynamic trunk stability and lower limb functional strength, balance, foot sensation, hearing, lean muscle mass and low BMI; Factor 7 AUC 0.55 (95%CI 0.52-0.59) comprising continence and nutrition. Factors 3 and 4 significantly predicted progression from pre-frail to frail (Factor 3 AUC 0.65 (95% CI 0.59-0.70)), combining living alone, sleep quality, depression and anxiety, and lung function; Factor 4 AUC 0.60 (95%CI 0.54-0.66) comprising perceived exertion on exercise, and falls history. CONCLUSIONS: This research identified pre-frailty and frailty states in people aged in their 40s and 50s. Pre-frailty in body systems performance can be detected by a range of mutable measures, and interventions to prevent progression to frailty could be commenced from the fourth decade of life.

Health assessments and screening tools for adults experiencing homelessness: a systematic review.

BACKGROUND: Homelessness is increasing globally. It results in poorer physical and mental health than age matched people living in permanent housing. Better information on the health needs of people experiencing homelessness is needed to inform effective resourcing, planning and service delivery by government and care organisations. The aim of this review was to identify assessment tools that are valid, reliable and appropriate to measure the health status of people who are homeless. METHODS: Data sources: A systematic literature search was conducted in PubMed (and Medline), PsychInfo, Scopus, CINAHL and ERIC from database inception until September 2018. Key words used were homeless, homelessness, homeless persons, vagrancy, health status, health, health issues, health assessment and health screening. The protocol was registered with PROSPERO. The National Health and Medical Research Council of Australia (NHMRC) hierarchy of evidence was applied; methodological quality of included articles was assessed using the McMaster critical appraisal tools and psychometric properties of the tools were appraised using the International Centre for Allied Health Evidence Ready Reckoner. RESULTS: Diverse tools and measures (N = 71) were administered within, and across the reviewed studies (N = 37), with the main focus being on general health, oral health and nutrition. Eleven assessment tools in 13 studies had evidence of appropriate psychometric testing for the target population in domains of quality of life and health status, injury, substance use, mental health, psychological and cognitive function. Methodological quality of articles and tools were assessed as moderate to good. No validated tools were identified to assess oral health, chronic conditions, anthropometry, demography, nutrition, continence, functional decline and frailty, or vision and hearing. However, assessments of physical constructs (such as oral health, anthropometry, vision and hearing) could be applied to homeless people on a presumption of validity, because the constructs would be measured with clinical indicators in the same manner as people living in permanent dwellings. CONCLUSIONS: This review highlighted the need to develop consistent and comprehensive health assessment tools validated with, and tailored for, adults experiencing homelessness.

Prevalence of Streptococcus dysgalactiae subsp. equisimilis and S. equi subsp. zooepidemicus in a sample of healthy dogs, cats and horses.

AIMS: To estimate the prevalence of ß-haemolytic Lancefield group C streptococci in healthy dogs, cats and horses; to determine if frequent contact with horses was associated with isolation of these species from dogs and cats; and to characterise recovered S. equi subsp. zooepidemicus isolates by multilocus sequence typing. METHODS: Oropharyngeal swabs were collected from 197 dogs and 72 cats, and nasopharyngeal swabs from 93 horses. Sampling was carried out at the Massey University Veterinary Teaching Hospital, on sheep and beef farms or on premises where horses were present. All animals were healthy and were categorised as Urban dogs and cats (minimal contact with horses or farm livestock), Farm dogs (minimal contact with horses) and Stable dogs and cats (frequent contact with horses). Swabs were cultured for ß-haemolytic Streptococcus spp. and Lancefield group C streptococcal subspecies were confirmed by phenotypic and molecular techniques. RESULTS: Of the 197 dogs sampled, 21 (10.7 (95% CI= 4.0-25.4)%) tested positive for S. dysgalactiae subsp. equisimilis and 4 (2.0 (95% CI=0.7-5.5)%) tested positive for S. equi subsp. zooepidemicus. All these isolates, except for one S. dysgalactiae subsp. equisimilis isolate in an Urban dog, were from Stable dogs. S. dysgalactiae subsp. equisimilis was isolated from one Stable cat. Of the 93 horses, 22 (23.7 (95% CI=12.3-40.6)%) and 6 (6.5 (95% CI=2.8-14.1)%) had confirmed S. dysgalactiae subsp. equisimilis and S. equi subsp. zooepidemicus isolation respectively. Isolation of S. dysgalactiae subsp. equisimilis from dogs was associated with frequent contact with horses (OR=9.8 (95% CI=2.6-72.8)). Three different multilocus sequence type profiles of S. equi subsp. zooepidemicus that have not been previously reported in dogs were recovered. CONCLUSIONS AND CLINICAL RELEVANCE: Subclinical infection or colonisation by S. equi subsp. zooepidemicus and S. dysgalactiae subsp. equisimilis occurs in dogs and further research on inter-species transmission and the pathogenic potential of these Lancefield group C streptococci is needed. Complete speciation of ß-haemolytic streptococci should be recommended in clinical cases and the possible exposure to horses and their environment should be considered in epidemiological investigations.

Distal aortic aneurysm presumed to be secondary to an infected umbilical artery in a foal.

CASE HISTORY: A 3-month-old female Warmblood foal was presented after displaying signs of colic with pyrexia for 5 days. CLINICAL AND PATHOLOGICAL FINDINGS: The foal continued to show signs of colic, frequently passed urine, and was pyrexic with an elevated white blood cell count. The umbilical stalk was thickened but there was no evidence of purulent material. Exploratory laparotomy revealed an enlarged left umbilical artery remnant tightly adhered to the bladder wall. The left umbilical artery continued to an aneurysm involving the distal aorta. The foal was subject to euthanasia and post-mortem examination confirmed a spherical aortic aneurysm, in the dorsal midline caudal to the kidneys that contained a large thrombus. Histopathological examination revealed inflammation and necrosis of the tunica intima and tunica media of the left umbilical artery with suppuration and bacterial colonies evident in the periarterial tissues. DIAGNOSIS: Infected aortic aneurysm presumably caused by an umbilical artery infection. CLINICAL RELEVANCE: A previously undetected umbilical infection appears to have resulted in an unusual delayed complication causing signs of colic in a foal. Veterinarians should be aware of this condition, and the possibility that it may be a cause of signs of colic in foals. Diagnosis based on ultrasonography should be possible, but may require sedation, visceral analgesia and careful examination.

Use of the CEEA stapler to avoid ultra-low segmental resection of a full-thickness rectal endometriotic nodule.

A woman with a history of numerous surgical episodes for treatment of aggressive endometriosis experienced rectal symptoms. She was prepared for the possibility of laparotomy with or without colostomy to relieve her symptoms. After extensive laparoscopic dissection of the rectovaginal septum, a circular stapling device (Premium Plus CEEA; Autosuture, Melbourne, Victoria, Australia) was used to excise completely an anterior rectal lesion that otherwise would have resulted in ultra-low rectal resection and anastomosis. Morbidity associated with the latter procedure was avoided; the patient was discharged within 72 hours and experienced no early or late complications. Postoperative barium enema was obviated by rapid return to normal bowel habits and complete resolution of dyschezia and dyspareunia.

Impaired transition state complementarity in the hydrolysis of O-arylphosphorothioates by protein-tyrosine phosphatases.

The hydrolysis of O-arylphosphorothioates by protein-tyrosine phosphatases (PTPases) was studied with the aim of providing a mechanistic framework for the reactions of this important class of substrate analogues. O-arylphosphorothioates are hydrolyzed 2 to 3 orders of magnitude slower than O-aryl phosphates by PTPases. This is in contrast to the solution reaction where phosphorothioates display 10-60-fold higher reactivity than the corresponding oxygen analogues. Kinetic analyses suggest that PTPases utilize the same active site and similar kinetic and chemical mechanisms for the hydrolysis of O-arylphosphorothioates and O-aryl phosphates. Thio substitution has no effect on the affinity of substrate or product for the PTPases. Bronsted analyses suggest that like the PTPase-catalyzed phosphoryl transfer reaction the transition state for the PTPase-catalyzed thiophosphoryl transfer is highly dissociative, similar to that of the corresponding solution reaction. The side chain of the active-site Arg residue forms a bidentate hydrogen bond with two of the terminal phosphate oxygens in the ground state and two of the equatorial oxygens in a transition state analog complex with vanadate [Denu et al. (1996) Proc. Natl. Acad. Sci. USA 93, 2493-2498; Zhang, M. et al. (1997) Biochemistry 36, 15-23; Pannifer et al. (1998) J. Biol. Chem. 273, 10454-10462]. Replacement of the active-site Arg409 in the Yersinia PTPase by a Lys reduces the thio effect by 54-fold, consistent with direct interaction and demonstrating strong energetic coupling between Arg409 and the phosphoryl oxygens in the transition state. These results suggest that the large thio effect observed in the PTPase reaction is the result of inability to achieve precise transition state complementarity in the enzyme active site with the larger sulfur substitution.

The incidence and management of failed Pipelle sampling in a general outpatient clinic.

A prospective audit was performed on 100 consecutive patients who underwent Pipelle endometrial sampling in a general outpatient clinic setting. The indications for sampling were abnormal menstrual bleeding (AMB, 65), intermenstrual or postcoital bleeding (IMB/PCB, 7), postmenopausal bleeding (PMB, 28). An insufficient sample was obtained in 33 women: (AMB 14, 21.5%); IMB/PCB, (0); PMB 19,68%). In 3 women the Pipelle was unable to be introduced through the cervix; in the remainder an insufficient sample for histological diagnosis was obtained. Registrars and resident doctors were more likely to sample insufficiently. In the AMB group all but 1 woman with an insufficient sample had further investigations or treatment but 7 of 19 (37%) of PMB patients had no further investigations. Where definitive histology was available, endometrial polyps or submucous fibroids were found in half of the cases with an inadequate Pipelle sample. Pipelle sampling detected only 1 of the 2 cases of endometrial cancer in this study.

Molecular basis for substrate specificity of protein-tyrosine phosphatase 1B.

Protein-tyrosine phosphatases can exhibit stringent substrate specificity in vivo, although the molecular basis for this is not well understood. The three-dimensional structure of the catalytically inactive protein-tyrosine phosphate 1B (PTP1B)/C215S complexed with an optimal substrate, DADEpYL-NH2, reveals specific interactions between amino acid residues in the substrate and PTP1B. The goal of this work is to rigorously evaluate the functional significance of Tyr46, Arg47, Asp48, Phe182, and Gln262 in substrate binding and catalysis, using site-directed mutagenesis. Combined with structural information, kinetic analysis of the wild type and mutant PTP1B using p-nitrophenyl phosphate and phosphotyrosine-containing peptides has yielded further insight into PTP1B residues, which recognize general features, as well as specific properties, in peptide substrates. In addition, the kinetic results suggest roles of these residues in E-P hydrolysis, which are not obvious from the structure of PTP1B/peptide complex. Thus, Tyr46 and Asp48 recognize common features of peptide substrates and are important for peptide substrate binding and/or E-P formation. Arg47 acts as a determinant of substrate specificity and is responsible for the modest preference of PTP1B for acidic residues NH2-terminal to phosphotyrosine. Phe182 and the invariant Gln262 are not only important for substrate binding and/or E-P formation but also important for the E-P hydrolysis step.

Toxicity of single-day high-dose vincristine, melphalan, etoposide and carboplatin consolidation with autologous bone marrow rescue in advanced neuroblastoma.

16 unselected patients with advanced neuroblastoma were given high-dose consolidation chemotherapy with vincristine, melphalan, etoposide and carboplatin over 5 h followed by autologous bone marrow rescue. 3 patients died from treatment-related toxicity, 2 from disease, 1 is alive with disease and 10 are alive and disease-free a median of 12.5 months (range 2-38 months) after bone marrow rescue. All had bone marrow toxicity, most mucositis and 6 had seizures. Renal failure was unexpectedly severe. In the last 3 patients, administration of carboplatin was delayed by 18 h in an attempt to reduce renal damage. The results show that this regimen produces significant morbidity and has a high mortality. Although the overall outcome is encouraging, too few patients have been studied to gauge its efficacy. Whether such aggressive consolidation is necessary in heavily pretreated children with neuroblastoma remains unknown.

Successful shock-wave lithotripsy of bile duct stones using ultrasound guidance.

Eighteen patients with 41 gallstones in the common bile duct, common hepatic, cystic, and intrahepatic ducts underwent shock-wave lithotripsy using the electrohydraulic Sonolith 3000 lithotripter. Lithotripsy was performed using ultrasound guidance alone under intravenous analgesia/sedation. All patients previously had failed stone extraction via retrograde endoscopy, T-tube, or cholecystostomy. Lithotripsy was performed according to an FDA-approved protocol allowing a maximum of two 2500 shock-wave treatments at a 48 hr interval. Following the final lithotripsy or cholangiographic evidence of stone fragmentation, residual fragments were removed via endoscopic or percutaneous route within 24-72 hr. Ultrasound localization of gallstones was aided by continuous infusion of the common bile duct with saline solution. In 15 of the 18 patients, complete fragmentation of the stones was accomplished, two had minimal fragmentation, and one with an encysted stone had no fracturing. No serious complications were encountered. Overall nonsurgical stone-free success rate was 17 of 18 patients, indicating biliary duct stones can be successfully treated using an ultrasound-guided lithotripter and intravenous sedation alone.

Transhepatic laser lithotripsy of choledocholithiasis: initial clinical experience.

Three patients with symptomatic intra- and extrahepatic choledocholithiasis who were not good candidates for retrograde endoscopy, surgery, or extracorporeal shock wave lithotripsy (ESWL) were treated successfully with endoscopically guided tunable dye laser lithotripsy via a 12-F transhepatic sheath. There were no complications secondary to the use of the laser. On the basis of this initial experience, transhepatic laser lithotripsy is a technically feasible and safe alternative when choledocholithiasis cannot be managed with retrograde endoscopy, ESWL, or surgery. Its role in the management of choledocholithiasis relative to other transhepatic techniques remains to be determined.

Mechanism of disc rupture. A preliminary report.

Lumbar intervertebral disc herniation is thought to be related to senescent changes in the nucleus pulposus except in rare instances of trauma. This investigation provides the first in vitro model of disc prolapse that reliably ruptures discs under physiologically reasonable stress. Fourteen vertebral motion segments with intact posterior elements were loaded repetitively at 1.5 Hz in a combination of flexion (7 degrees), rotation (less than 3 degrees), and compression (1,334 N) for an average of 6.9 hours (range, 3.0-13.0 hours) in a materials testing machine. Loading was terminated when reaction force leveled off for more than 1 hour. Ten discs failed through annular protrusions, and four failed by nuclear extrusion through annular tears, supporting the hypothesis that intervertebral disc prolapse is peripheral in origin. The annulus fibrosus is the site of primary pathologic change.

Assessment of cardiac function by M-mode echocardiography in selenium-deficient phenylketonuric children.

Selenium (Se) deficiency is associated with cardiac and skeletal muscle dysfunction. Twenty well children aged 2-16 years (10 male) attending the Phenylketonuria (PKU) Clinic at the Royal Children's Hospital, Brisbane, had low Se levels (mean 0.29 +/- 0.02 s.e.m. mumol/L; normal range 0.56-1.16 mumol/L). Their myocardial function was assessed at rest and after exercise provocation by M-mode echocardiography in order to exclude occult left ventricular dysfunction. At rest, fractional shortening (FS) was normal (mean 38.1 +/- 1.1 s.e.m. %, n = 20). After exercise, FS increased significantly (P less than 0.001) from 37.6 +/- 1.4% to 44.3 +/- 1.2%, n = 12). This was associated with a significant rise (P less than 0.001) in heart rate (HR) from 77.3 +/- 3.1 beats/min to 125.8 +/- 5.2 beats/min (n = 12). The normal resting FS and normal increase in FS and HR with exercise is evidence against significant cardiac impairment in this group of Se-deficient children.