Der p 23 sensitisation in patients with house dust mite respiratory allergy.

Summary: Background. The sensitization profile of patients allergic to house dust mites (HDM) and its molecular diagnosis may determine treatment and evolution of the disease. The present study investigates the prevalence of Der p 23 sensitization and its relation to asthma in a population of HDM-allergic patients. Methods. We conducted a cross-sectional study of 891 patients with HDM allergy with symptoms of rhinitis and 52.1% of them with asthma. Total and specific IgE (sIgE) was measured against Dermatophagoides pteronyssinus and its molecular components (Der p 1, Der p 2 and Der p 23) and the storage mite Lepidoglyphus destructor using ImmunoCAP. Prevalence of sensitization and levels of sIgE were analysed according to asthma diagnosis and asthma severity. Results. Der p 23 was the predominant allergen in this population (83.7%) but IgE levels were lower than those of sIgE to Der p 1 and Der p 2. A good correlation was found between sIgE to Der p 23 and the other allergens. A total of 8.2% patients were monosensitized to Der p 23. Asthma was more frequent in patients with positive sIgE against Der p 23 than in patients without this sensitization (52.8% vs 42.8%, p = 0.027). A tendency to increase both total IgE and sIgE was observed in relation to the severity of asthma from intermittent mild asthma to persistent moderate asthma but a substantial decrease in total IgE and sIgE was detected in more severe asthmatics. Conclusions. Der p 23 might be a prevalent allergen in regions with high rates of HDM exposure. Even though sIgE levels against this allergen are usually low, its presence could increase the risk of asthma.

Analysis of outcomes of emergency general and gastrointestinal surgery during the COVID-19 pandemic.

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.

Transanal total mesorectal excision for rectal cancer with indocyanine green fluorescence angiography.

BACKGROUND: The aim of this study was to evaluate the impact of fluorescence angiography (FA) on any change in proximal resection margin and/or anastomotic leak (AL) following transanal total mesorectal excision (TaTME) for rectal cancer (RC). METHODS: This retrospective cohort study was conducted at two centers by three senior surgeons. Both institutions' prospectively maintained Institutional Review Board-approved databases were retrospectively queried for all consecutive patients between July 2015 and May 2017 who had laparoscopic hybrid trans-abdominal total mesorectal excision (TME) and TaTME for RC with colorectal or coloanal anastomosis < 10 cm from the anal verge. All patients had intraoperative FA to assess colonic perfusion of the planned proximal resection margin before bowel transection and after construction of the anastomosis. Primary outcomes measured any changes in proximal resection margins and AL rates. RESULTS: Fifty-four patients (31 males; mean age 63 ± 12 years) were included; 30 (55%) of whom received neoadjuvant chemoradiation. The average anastomotic height was 3.6 cm from the anal verge and 8 (14.5%) patients required intersphincteric dissection. Forty-six patients (85%) had loop ileostomy. FA led to a change in the proximal resection margin in 10 patients (18.5%), one of whom had AL on postoperative day 3 requiring diagnostic laparoscopy and loop ileostomy. A second patient, without a change in the proximal resection margin, also had an AL. The overall AL rate was 3.7%. CONCLUSIONS: FA changed the planned proximal resection margin in 18.5% of patients, possibly accounting for the relatively low AL rate. FA is imperfect, and subjective but does have the potential to improve outcomes.

Estimated prevalence of dementia based on analysis of drug databases in the Region of Madrid (Spain).

INTRODUCTION: The progressive rise in dementia prevalence increases the need for rapid methods that complement population-based prevalence studies. OBJECTIVE: To estimate the prevalence of dementia in the population aged 65 and older based on use of cholinesterase inhibitors and memantine. METHODS: Descriptive study of use and prescription of cholinesterase inhibitors and/or memantine in 2011 according to 2 databases: Farm@drid (pharmacy billing records for the Region of Madrid) and BIFAP (database for pharmacoepidemiology research in primary care, with diagnosis and prescription records). We tested the comparability of drug use results from each database using the chi-square test and prevalence ratios. The prevalence of dementia in Madrid was estimated based on the dose per 100 inhabitants/day, adjusting the result for data obtained from BIFAP on combination treatment in the general population (0.37%) and the percentage of dementia patients undergoing treatment (41.13%). RESULTS: Cholinesterase inhibitors and memantine were taken by 2.08% and 0.72% of Madrid residents aged 65 and older was respectively. Both databases displayed similar results for use of these drugs. The estimated prevalence of dementia in individuals aged 65 and older is 5.91% (95% CI%, 5.85-5.95) (52 287 people), and it is higher in women (7.16%) than in men (4.00%). CONCLUSIONS: The estimated prevalence of dementia is similar to that found in population-based studies. Analysing consumption of specific dementia drugs can be a reliable and inexpensive means of updating prevalence data periodically and helping rationalise healthcare resources.

Aii20J, a wide-spectrum thermostable N-acylhomoserine lactonase from the marine bacterium Tenacibaculum sp. 20J, can quench AHL-mediated acid resistance in Escherichia coli.

Acyl homoserine lactones (AHLs) are produced by many Gram-negative bacteria to coordinate gene expression in cellular density dependent mechanisms known as quorum sensing (QS). Since the disruption of the communication systems significantly reduces virulence, the inhibition of quorumsensing processes or quorum quenching (QQ) represents an interesting anti-pathogenic strategy to control bacterial infections. Escherichia coli does not produce AHLs but possesses an orphan AHL receptor, SdiA, which is thought to be able to sense the QS signals produced by other bacteria and controls important traits as the expression of glutamate-dependent acid resistance mechanism, therefore constituting a putative target for QQ. A novel AHL-lactonase, named Aii20J, has been identified, cloned and over expressed from the marine bacterium Tenacibaculum sp. strain 20 J presenting a wide-spectrum QQ activity. The enzyme, belonging to the metallo-ß-lactamase family, shares less than 31 % identity with the lactonase AiiA from Bacillus spp. Aii20J presents a much higher specific activity than the Bacillus enzyme, maintains its activity after incubation at 100 ºC for 10 minutes, is resistant to protease K and α-chymotrypsin, and is unaffected by wide ranges of pH. The addition of Aii20J (20 µg/mL) to cultures of E. coli K-12 to which OC6-HSL was added resulted in a significant reduction in cell viability in comparison with the acidresistant cultures derived from the presence of the signal. Results confirm the interaction between AHLs and SdiA in E. coli for the expression of virulence-related genes and reveal the potential use of Aii20J as anti-virulence strategy against important bacterial pathogens and in other biotechnological applications.

Parathyroid hormone response to two levels of vitamin D deficiency is associated with high risk of medical problems during hospitalization in patients with hip fracture.

BACKGROUND: Vitamin D and the parathyroid hormone (PTH) response play an important role in hip fracture patients. This study was carried out to determine the factors associated with the PTH response to different levels of vitamin D deficiency during hospitalization. METHODS: This was a cross-sectional study of patients over 64 years of age admitted with an acute fragility hip fracture between March 1st 2009 and November 30th 2012. Demographic, clinical, functional, and cognitive function were evaluated at admission and during hospitalization. Levels of 25-hydroxyvitamin D (25-OHD) and PTH were analyzed. Two 25-OHD cut-off points were considered, <12 ng/ml and 12-20 ng/ml. Multivariate logistic regression analysis was used. RESULTS: Mean age of the 607 patients included was 84.7 years (SD 7.10), and 81.9 % were women. The mean 25-OHD level in the total sample was 13.2 (SD 11.1) ng/ml. Levels of 25-OHD <12 ng/ml were present in 347 patients (57.2 %), of whom 158 (45.5 %) had secondary hyperparathyroidism (SHPT) (PTH >65 pg/ml). 25-OHD levels of 12-20 ng/ml were present in 168 (27.7 %) patients, of whom 47 (28 %) had SHPT. Following logistic regression, SHPT was associated in both groups (25-OHD <12 and 12-20 ng/ml) with a greater number of medical problems during hospitalization. In the 25-OHD group <12 ng/ml, SHPT was also associated with poorer glomerular filtration rates. CONCLUSION: The PTH response to vitamin D deficiency in hip fracture patients may be a marker for patients with higher risk of developing multiple medical problems, both when considering severe (<12 ng/ml) and moderate (12-20 ng/ml) vitamin D deficiency.

Consumption trends for specific drugs used to treat dementia in the region of Madrid (Spain) from 2002 to 2012.

INTRODUCTION: Analysing drug consumption in large population groups lets us observe consumption trends and compare them between different settings. OBJECTIVE: to analyse the time trends for consumption and costs of specific drugs used to treat dementia in the region of Madrid (Spain) and compare trends by sex and age cohort. METHODS: Descriptive study of cholinesterase inhibitors (N06DA) and memantine (N06DX01) dispensed in Madrid between 2002 and 2012 and covered by the Spain's national health system. Consumption was calculated by analysing changes in DDD (defined daily doses) to find total and yearly increases. The cost was estimated based on DDD price. To compare consumption rates by age and sex, we calculated DDD per 100 inhabitants/day. RESULTS: Between 2002 and 2012, consumption of drugs used to treat dementia increased sixfold. During this period, cholinesterase inhibitors accounted for 76.70% of the drugs consumed and memantine, 23.30%. The estimated cost rose by a by a factor of 5.7 over 11 years (or by a factor of 4 taking into account the use of generic drugs). In 2012, 2.42% of the patients aged 65 or over consumed cholinesterase inhibitors (women 2.82%, men 1.83%) and 0.90% consumed memantine (women 1.10%, men 0.61%). Consumption increased in age cohorts up to 86 to 90 (5.84% for cholinesterase inhibitors and 2.33% for memantine) and declined thereafter. CONCLUSIONS: Consumption of cholinesterase inhibitors and memantine gradually increased, but consumption in 2012 did not reach levels equivalent to dementia prevalence figures. Pharmaceutical expenditure restraint measures may temporarily slow the cost increase temporarily but if the same trend of consumption persists, costs will rise.

"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

A lifestyle adjustments program in long COVID-19 improves symptomatic severity and quality of life. A randomized control trial.

OBJECTIVE: To evaluate the efficacy of a therapeutic intervention based on self-adjustment strategies for improving of symptomatic severity and quality of life. METHODS: The study was a randomised single-blind clinical trial. Quality of life, disability, and functional impairment were collected. The control group received a leaflet with information on the main symptoms of Long-COVID-19 syndrome, in addition to standard medical treatment. The intervention group received treatment following a dual approach; on the one hand, monitoring and recognition of symptomatology and on the other hand, adaptation and functional improvement. RESULTS: A total of 54 participants were included, 27 were included in the intervention group and 27 in the control group. At the beginning of the study, no significant differences were found between groups. After intervention, the quality of life variable showed significant differences between groups in the self-care and anxiety/depression dimensions. Significant between-groups differences were also found for the self-care subscale of the disability variable. The intervention group showed significant differences from baseline on some subscales of the quality of life, disability, and functional impairment variables. CONCLUSION: Strategies based on lifestyle adjustments are adequate for the improvement of quality of life and symptom severity in the long COVID-19 population. PRACTICE IMPLICATION: The findings suggest that applying an intervention focused in self-adjustment for long COVID patients can have positive effects.

Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma.

The aim of this study was to assess patterns of CCND3 gene amplification in bladder cancer and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 102 primary bladder tumor samples in which there was enough tissue material to assess CCND3 gene status by fluorescent in situ hybridization (FISH) was the study group. CCND3 gene FISH amplification present in 31.4 percent of bladder carcinomas, was related to tumor progression (p=0.021) and lower time to progression (mean+-SD; 25.75+-15.25 months) as compared to 33.29+-11.0 months in the CCND3 not amplified group (p=0.05). By immunohistochemistry, Cyclin D3 labeling index was higher in the CCND3 amplified group (mean+-SD, 76.69+-27.51) than in not amplified (mean+-SD, 21.57+-7.02) (p less than 0.0001). The univariate survival analysis showed CCND3 gene amplification to be associated to a shorter progression-free survival (p=0.020) together with WHO histological grade (p=0.001) and pT stage category (p less than 0.0001). Cox’s regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p= 0.030, RR3.561, 95 percent CI 1.128-11.236) together with pT category (p less than 0.0001, RR5.834, 95 percent CI 2.364-14.395). Our FISH analysis suggests that CCND3 gene amplification is a marker of aggressiveness and might be a predictor of tumor progression in bladder urothelial carcinoma.

Spatial distribution and source identification of phthalates and organochlorine compounds in Galician mussels (NW Spain).

The spatial distribution of five phthalate esters (PAEs) and 17 organochlorine compounds (OCs) in wild and raft mussels from Galician littoral collected in 2020, and its relationship with anthropogenic activities was studied in this work. The Rías de Foz and Muros-Noia were the most polluted by PAEs, while the Rías de Ferrol and Barqueiro by PCBs. The highest levels of all contaminants were present in wild mussel, except DEHP that were predominant in raft mussel. The levels of most PAEs were negatively correlated with levels of the lower chlorinated PCBs and OCPs. The spatial distribution of pollutants confirmed by PCA was affected by the proximity to anthropogenic sources, phthalates by urban wastewater and PCBs by industrial inputs, mainly. The study of human exposure assessment suggests that Risk Quotient values were < 1, so the consumption of Galician raft mussels did not pose a risk to human health.

Lactogens protect rodent and human beta cells against glucolipotoxicity-induced cell death through Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5) signalling.

AIMS/HYPOTHESIS: A leading cause of type 2 diabetes is a reduction in functional beta cell mass partly due to increased beta cell death, triggered by stressors such as glucolipotoxicity (GLT). This study evaluates the hypothesis that lactogens can protect beta cells against GLT and examines the mechanism behind the pro-survival effect. METHODS: The effect of exogenous treatment or endogenous expression of lactogens on GLT-induced beta cell death was examined in INS-1 cells, and in rodent and human islets. The mechanism behind the pro-survival effect of lactogens was determined using an inhibitor, siRNAs, a dominant negative (DN) mutant, and Cre-lox-mediated gene deletion analysis. RESULTS: Lactogens significantly protect INS-1 and primary rodent beta cells against GLT-induced cell death. The pro-survival effect of lactogens in rodent beta cells is mediated through activation of the Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5) signalling pathway. Lactogen-induced increase in the anti-apoptotic B cell lymphoma-extra large (BCLXL) protein is required to mediate its pro-survival effects in both INS-1 cells and primary rodent beta cells. Most importantly, lactogens significantly protect human beta cells against GLT-induced cell death, and their pro-survival effect is also mediated through the JAK2/STAT5 pathway. CONCLUSIONS/INTERPRETATION: These studies, together with previous work, clearly demonstrate the pro-survival nature of lactogens and identify the JAK2/STAT5 pathway as an important mediator of this effect in both rodent and human beta cells. Future studies will determine the effectiveness of this peptide in vivo in the pathophysiology of type 2 diabetes.

Characterization of coagulase-positive staphylococci isolated from tank and silo ewe milk.

The prevalence of coagulase-positive staphylococci (CPS) was studied among 390 samples of ewe milk. Fifty-seven (14.85%) samples of tank milk and all samples (6) of silo milk gave a positive result on Baird-Parker agar base supplemented with rabbit plasma fibrinogen, whereas amplification of the coagulase (coa) gene was successful in 6 (1.56%) samples of tank milk and in all silo samples. Phenotypic and genetic analysis of 153 isolates identified 151 (98.69%) as Staphylococcus aureus. Amplification of the coa gene was positive for 149 isolates (97.39%). The staphylococcal enterotoxin (SE) C gene was detected in 116 strains (75.82%), whereas more than one SE gene was carried in 5 strains (3.26%). None of the isolates harbored the genes for SEE or for methicillin resistance. A high prevalence of CPS carrying enterotoxin genes should be of concern because ewe milk is mainly processed into raw milk cheeses. The detection of the coa gene from milk samples could help to assess the microbiological safety of raw milk intended for direct use in the dairy industry.

Walking-and Running and Jumping-with Dinosaurs and Their Cousins, Viewed Through the Lens of Evolutionary Biomechanics.

Archosauria diversified throughout the Triassic Period before experiencing two mass extinctions near its end ∼201 Mya, leaving only the crocodile-lineage (Crocodylomorpha) and bird-lineage (Dinosauria) as survivors; along with the pterosaurian flying reptiles. About 50 years ago, the "locomotor superiority hypothesis" (LSH) proposed that dinosaurs ultimately dominated by the Early Jurassic Period because their locomotion was superior to other archosaurs'. This idea has been debated continuously since, with taxonomic and morphological analyses suggesting dinosaurs were "lucky" rather than surviving due to being biologically superior. However, the LSH has never been tested biomechanically. Here we present integration of experimental data from locomotion in extant archosaurs with inverse and predictive simulations of the same behaviours using musculoskeletal models, showing that we can reliably predict how extant archosaurs walk, run and jump. These simulations have been guiding predictive simulations of extinct archosaurs to estimate how they moved, and we show our progress in that endeavour. The musculoskeletal models used in these simulations can also be used for simpler analyses of form and function such as muscle moment arms, which inform us about more basic biomechanical similarities and differences between archosaurs. Placing all these data into an evolutionary and biomechanical context, we take a fresh look at the LSH as part of a critical review of competing hypotheses for why dinosaurs (and a few other archosaur clades) survived the Late Triassic extinctions. Early dinosaurs had some quantifiable differences in locomotor function and performance vs. some other archosaurs, but other derived dinosaurian features (e.g., metabolic or growth rates, ventilatory abilities) are not necessarily mutually exclusive from the LSH; or maybe even an opportunistic replacement hypothesis; in explaining dinosaurs' success.

A new cynodont from the Upper Triassic Los Colorados Formation (Argentina, South America) reveals a novel paleobiogeographic context for mammalian ancestors.

Probainognathia is a derived lineage of cynodonts which encompass Mammalia as their crown-group. The rich record of probainognathians from the Carnian of Argentina contrasts with their Norian representation, with only one named species. Here we describe a new probainognathian, Tessellatia bonapartei gen. et sp. nov., from the Norian Los Colorados Formation of the Ischigualasto-Villa Unión Basin of Argentina. The new taxon, represented by a partial cranium with associated lower jaws, was analyzed through neutron and X-rays micro-tomography (µCT). The high-resolution neutron µCT data allowed the identification of a unique character combination, including features inaccessible through traditional techniques. We constructed the largest phylogenetic data matrix of non-mammalian cynodonts. The new species and its sister taxon, the Brazilian Therioherpeton cargnini, are recovered as probainognathians, closely related to Mammaliamorpha. We conducted the first quantitative paleobiogeographic analysis of non-mammalian cynodonts, focusing in probainognathians. The results indicate that Probainognathia and Mammaliamorpha originated in southwestern Gondwana (in the Brazilian Paraná Basin), which was an important center of diversification during the Triassic. Finally, the Chinese Lufeng Basin is identified as the ancestral area of Mammaliaformes. These new findings, besides adding to the knowledge of the poorly represented Norian cynodonts from the Los Colorados Formation, are significant to improve our understanding of probainognathian diversity, evolution, and paleobiogeographic history.

Systemic and acute administration of parathyroid hormone-related peptide(1-36) stimulates endogenous beta cell proliferation while preserving function in adult mice.

AIMS/HYPOTHESIS: A major focus in the treatment of diabetes is to identify factors that stimulate endogenous beta cell growth while preserving function. The first 36 amino acids of parathyroid hormone-related protein (PTHrP) are sufficient to enhance proliferation and function in rodent and human beta cells in vitro. This study examined whether acute and systemic administration of the amino-terminal PTHrP(1-36) peptide can achieve similar effects in rodent beta cells in vivo. METHODS: Adult male mice were injected with 40, 80 or 160 µg of PTHrP(1-36) per kg body weight or with vehicle for 25 days. Glucose and beta cell homeostasis, as well as expression of differentiation markers and cell cycle genes were analysed. RESULTS: All three doses of PTHrP(1-36) significantly enhanced beta cell proliferation in vivo at day 25, with 160 µg/kg PTHrP(1-36) increasing proliferation as early as day 5. Importantly, the two higher doses of PTHrP(1-36) caused a significant 30% expansion of beta cell mass, with a short-term improvement in glucose tolerance. PTHrP(1-36) did not cause hypercalcaemia, or change islet number, beta cell size, beta cell death or expression of differentiation markers. Analysis of islet G1/S cell cycle proteins revealed that chronic overabundance of PTHrP(1-139) in the beta cell significantly increased the cell cycle activator cyclin D2 and decreased levels of cyclin-dependent kinase 4 inhibitor (p16( Ink4a ) [Ink4a also known as Cdkn2a]), but acute treatment with PTHrP(1-36) did not. CONCLUSIONS/INTERPRETATION: Acute and systemic administration of PTHrP(1-36) increases rodent beta cell proliferation and mass without negatively affecting function or survival. These findings highlight the future potential therapeutic effectiveness of this peptide under diabetes-related pathophysiological conditions.

Activities of daily living after hip fracture: profile and rate of recovery during 2 years of follow-up.

SUMMARY: In this study 509 hip fracture patients were followed-up during 24 months measuring their recuperation in activities of daily living. The different activities measured had both different profile and probability of recovery. INTRODUCTION: Recovery of pre-fracture functional level is a goal of hip fracture treatment. The objective of this study was to measure recovery of previous functional level for ambulation and for the activities of daily living during the 24 months after osteoporotic hip fracture. METHODS: This is a longitudinal prospective study of the patients admitted to the orthopaedics department of a university hospital for hip fracture and followed up by a geriatrician during three years (2003-2005). Demographic, clinical, functional and treatment data were collected during hospitalisation. Telephone follow-up was made at 3, 6, 12 and 24 months. Data were analysed by survival analysis applying the Kaplan-Meier estimator. RESULTS: Five hundred and nine patients were included. The mean age was 84.5 (SD 6.3) years. The activities with lower probability of recovery to the previous level at 24 months were climbing stairs, chair/bed transfers, ambulation, dressing, bathing and use of toilet (between 67.5% and 76% recovery). The activities with higher probability of recovery were grooming, feeding and bladder and bowel control (between 86.3% and 95.4%). Recovery of previous performance level for ambulation, chair/bed transfers, use of toilet, feeding, grooming and bladder control occurred primarily during the first 6 months, whereas recovery of bathing, dressing and climbing stairs occurred mainly in the first 12 months after the fracture. CONCLUSIONS: The activities with lower likelihood of recovery were ambulation, chair/bed transfers, climbing stairs, use of toilet, bathing and dressing. Time of recovery varied by activity; bathing, dressing and climbing stairs were the activities with the longest recovery time.

Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury.

OBJECTIVE: To assess the effects of growth hormone (GH) treatment combined with cognitive rehabilitation in patients with adult growth hormone deficiency (GHD) and cognitive disorders occurring after traumatic brain injury (TBI). PARTICIPANTS: Nineteen adult patients with TBI: GHD was found in 11 of them. INTERVENTION: Patients were treated with GH (GHD; sc; 1 mg/day) or vehicle (controls; sc; 1 mg/day); daily cognitive rehabilitation therapy was performed in both groups for 3 months. MAIN OUTCOME MEASURES: The GHRH-arginine test established GHD. The neuropsychological test WAIS was performed before commencing the treatment and 3 months after commencing it. RESULTS: Controls achieved significant improvements in digits and in manipulative intelligence quotient (IQ) (p < 0.05 vs. baseline). GHD achieved significant improvements in more cognitive parameters: understanding, digits, numbers and incomplete figures (p < 0.05 vs. baseline) and similarities, vocabulary, verbal IQ, manipulative IQ and total IQ (p < 0.01). GHD reached significantly greater improvements than controls in similarities (p < 0.01) and in vocabulary, verbal IQ and total IQ (p < 0.05). CONCLUSION: GH administration significantly improved cognitive rehabilitation in GHD patients. Since at the end of treatment period plasma IGF-I levels were similar in both groups it is likely that exogenous GH administration is responsible for the significant differences found.