Predictors of Hospitalization Among Newly Admitted Skilled Nursing Facility Residents: Rethinking the Role of Functional Decline

Purpose: Hospital transfer from a skilled nursing facility (SNF) is costly, and many are potentially preventable. This study examines: 1) whether functional decline is a predictor of hospital transfer, and 2) the magnitude of relationships between predictors (functional impairment and chronic medical illness) and hospital transfer from SNFs. Methods: We used Minimum Data Set (MDS) Version 2.0 in the state of Michigan between 2007 and 2009. In total, 196,662 new SNF admissions were observed. Multilevel generalized estimating equations and regression models were performed for each functional and clinical domain while adjusting for demographic variables and change in activities of daily living (ADL). Results: 65% of recently admitted SNF residents experienced functional decline after SNF admission, and 58% were readmitted to a hospital. Residents who needed extensive assistance or were completely dependent in their functional domains had pressure ulcers, deteriorated mood or lower cognitive performance scale scores. These residents experienced higher chances of hospital transfer. However, a deteriorated ADL played a significant role in all multivariate models, indicating that a decline in ADL is a stronger predictor of hospital transfer than other functional or clinical predictors. Conclusion: Although all functional impairments and chronic medical illness can be associated with hospital transfer, functional decline may be the most important predictor of hospital transfer in patients newly admitted to an SNF

WRN Exonuclease activity is blocked by specific oxidatively induced base lesions positioned in either DNA strand

Werner syndrome (WS) is a premature aging disorder caused by mutations in the WS gene (WRN). Although WRN has been suggested to play an important role in DNA metabolic pathways, such as recombination, replication and repair, its precise role still remains to be determined. WRN possesses ATPase, helicase and exonuclease activities. Previous studies have shown that the WRN exonuclease is inhibited in vitro by certain lesions induced by oxidative stress and positioned in the digested strand of the substrate. The presence of the 70/86 Ku heterodimer (Ku), participating in the repair of double-strand breaks (DSBs), alleviates WRN exonuclease blockage imposed by the oxidatively induced DNA lesions. The current study demonstrates that WRN exonuclease is inhibited by several additional oxidized bases, and that Ku stimulates the WRN exonuclease to bypass these lesions. Specific lesions present in the non-digested strand were shown also to inhibit the progression of the WRN exonuclease; however, Ku was not able to stimulate WRN exonuclease to bypass these lesions. Thus, this study considerably broadens the spectrum of lesions which block WRN exonuclease progression, shows a blocking effect of lesions in the non-digested strand, and supports a function for WRN and Ku in a DNA damage processing pathway

ADAM r-WBC system used for leukocyte measurement in leukoreduced blood components

Jedyną skuteczną metodą otrzymania ubogoleukocytarnych składników krwi jest poddanie ich filtracji przy użyciu filtrów antyleukocytarnych. W pracach na temat usuwania leukocytów ze składników krwi stwierdzono, że leukoredukcja nie tylko zapobiega przeniesieniu czynników zakaźnych, niehemolitycznym reakcjom gorączkowym oraz zmniejsza ryzyko alloimmunizacji HLA, ale także zapobiega wystąpieniu oporności na przetaczanie krwinek płytkowych. W centrach krwiodawstwa i krwiolecznictwa (CKiK) na terenie Polski od wielu lat stosuje się procedury usuwania leukocytów ze składników krwi przeznaczonych dla pacjentów wymagających stosowania tylko składników ubogoleukocytarnych. Kryteria akceptacji dla zawartości leukocytów pozwalające zakwalifikować składnik krwi jako ubogoleukocytarny (tzw. zakresy normy) są różne w Europie i w Ameryce Północnej. Według standardów Rady Europy oraz zaleceń Dyrektywy 2002/98/EC składniki krwi przeznaczone do przetoczenia uznaje się za ubogoleukocytarne, jeżeli zawierają poniżej 1 × 106 leukocytów/jednostkę. Norma ta obowiązuje również w Polsce. Wdrażanie europejskich wytycznych w zakresie zmniejszania zawartości leukocytów w krwi i jej składnikach wymaga stosowania szybkich i wiarygodnych metod kontroli jakości. Ostatnio coraz większym zainteresowaniem cieszy się urządzenie ADAM r-WBC (Advanced Detection Accurate Measurement, Nano Entek, Seul, Korea Płd.), stosowane do oznaczania liczby leukocytów w ubogoleukocytarnych koncentratach krwinek czerwonych (UKKCz) i ubogoleukocytarnych koncentratach krwinek płytkowych (UKKP). Urządzenie to jest alternatywą dla dotychczasowych metod liczenia leukocytów w ubogoleukocytarnych składnikach krwi. Celem niniejszej pracy było porównanie wyników oznaczania liczby leukocytów w ubogoleukocytarnych składnikach krwi przy zastosowaniu 3 metod: mikroskopowej, cytometrii przepływowej i automatycznej z wykorzystaniem systemu ADAM r-WBC. Badania prowadzono w dwóch ośrodkach — w Instytucie Hematologii i Transfuzjologii (IHiT) w Warszawie (etap I) oraz w Regionalnym Centrum Krwiodawstwa i Krwiolecznictwa (RCKiK) w Katowicach (etap II, po weryfikacji producenta i ponownej walidacji). W etapie I wykorzystano 94 próbki pobrane z UKKP i 34 próbki z UKKCz, zaś w etapie II użyto 29 próbek UKKP i 26 UKKCz. Wyniki etapu I wykazały, że liczba leukocytów oznaczona za pomocą systemu ADAM r-WBC była znacznie wyższa („fałszywie” zawyżona) niż uzyskana przy użyciu metody mikroskopowej. Pomimo zawyżonych wyników uzyskanych w I etapie badań, w RCKiK w Katowicach urządzenie ADAM r-WBC jest rutynowo stosowane do oznaczania liczby leukocytów w preparatach ubogoleukocytarnych, ponieważ zostało poddane weryfikacji zgodnie z uwagami IHiT i RCKiK, jak również ponownej walidacji.  The only effective method of obtaining leukoreduced blood components is filtration. Literature on leukoreduction reports that implementation of leukocyte reduction in blood components minimizes the risk of transmission of bacterial or viral infections, non-hemolytic febrile reactions, alloimmunization with HLA antigens as well as platelet transfusion refractoriness. In the Polish Blood Transfusion Centers leukoreduction has been used for many years now for the preparation of blood components dedicated to patients who can be administered only leukoreduced blood components. Standards set for residual leukocyte count ( a component to be marked as leukoreduced) are different for Europe and the United States. European standards set the residual leukocyte count below 1 × 106 leukocytes per unit of blood component. The criterium is also obligatory in Poland. European recommendations for leukoreduction require the implementation of effective and reliable methods of quality control. Much attention has lately been paid to the ADAM r-WBC system (Advanced Detection Accurate Measurement, Nano Entek, Seul, South Korea) based on counting WBCs in leukoreduced red blood cell concentrates (RBCCs) and leukoreduced platelet concentrates (PCs). The method was developed as an alternative to the hitherto used methods of residual leukocyte measurements in leukodepleted blood components. The aim of the study was to compare the leukocyte count measurements in leukoreduced RBCCs and leukoreduced PCs performed with 3 methods: microscopic, flow cytometry and automatic with ADAM r-WBC system. The study was conducted in two centers; the Institute of Hematology and Transfusion Medicine (IHTM — stage I) and in the Regional Blood Transfusion Center in Katowice (RBTC — stage II, following manufacturer’s verification and repeated validation). In stage I we used 94 samples of leukoreduced PCs and 34 samples of RBCC while in stage II — 29 samples of PCs and 26 samples of RBCC. The results of study stage I revealed that the residual leukocyte count measured with ADAM r-WBC system was much higher than the measurement with the microscopic method. Despite the higher values obtained in study stage I, the ADAM r-WBC system is in routine use for the measurement of residual leukocyte count in leukoreduced blood components at RBTC in Katowice as the system/ /equipment was verified and re-validated by the manufacturer according to the recommendations of IHTM and RBTC in Katowice

Lung-protective ventilation for the surgical patient: international expert panel-based consensus recommendations

Postoperative pulmonary complications (PPCs) occur frequently and are associated with substantial morbidity and mortality. Evidence suggests that reduction of PPCs can be accomplished by using lung-protective ventilation strategies intraoperatively, but a consensus on perioperative management has not been established. We sought to determine recommendations for lung protection for the surgical patient at an international consensus development conference. Seven experts produced 24 questions concerning preoperative assessment and intraoperative mechanical ventilation for patients at risk of developing PPCs. Six researchers assessed the literature using questions as a framework for their review. The modified Delphi method was utilised by a team of experts to produce recommendations and statements from study questions. An expert consensus was reached for 22 recommendations and four statements. The following are the highlights: (i) a dedicated score should be used for preoperative pulmonary risk evaluation; and (ii) an individualised mechanical ventilation may improve the mechanics of breathing and respiratory function, and prevent PPCs. The ventilator should initially be set to a tidal volume of 6-8 ml kg-1 predicted body weight and positive end-expiratory pressure (PEEP) 5 cm H2O. PEEP should be individualised thereafter. When recruitment manoeuvres are performed, the lowest effective pressure and shortest effective time or fewest number of breaths should be used. ispartof: BJA: British Journal of Anaesthesia vol:123 issue:6 pages:898-913 ispartof: location:England status: Published onlin

Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPPIRI3L/iASPP

Background: Previous results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls. Methods and Results: Studying one marker at a time, we found a region spanning the gene RAI ( alias PPP1R13L or iASPP) and the 5' portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age. In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3' d1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41 - 4.23, p = 0.0008, all cases; RR = 6.29 (1.49 - 26.6), p = 0.01, cases up to 55 years of age). Conclusion: We expect the marker RAI-3' d1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer

International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria)

Primary Ciliary Dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM. A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres. The final guideline a) Provides agreed terminology and a definition of class 1 defects which are diagnostic for PCD; b) Identifies class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) Describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD d) Defines adequacy of a diagnostic sample. This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally.</p

Staphylococcus aureus DinG, a helicase that has evolved into a nuclease

DinG (damage inducible gene G) is a bacterial superfamily 2 helicase with 5′→3′ polarity. DinG is related to the XPD (xeroderma pigmentosum complementation group D) helicase family, and they have in common an FeS (iron–sulfur)-binding domain that is essential for the helicase activity. In the bacilli and clostridia, the DinG helicase has become fused with an N-terminal domain that is predicted to be an exonuclease. In the present paper we show that the DinG protein from Staphylococcus aureus lacks an FeS domain and is not a DNA helicase, although it retains DNA-dependent ATP hydrolysis activity. Instead, the enzyme is an active 3′→5′ exonuclease acting on single-stranded DNA and RNA substrates. The nuclease activity can be modulated by mutation of the ATP-binding cleft of the helicase domain, and is inhibited by ATP or ADP, suggesting a modified role for the inactive helicase domain in the control of the nuclease activity. By degrading rather than displacing RNA or DNA strands, the S. aureus DinG nuclease may accomplish the same function as the canonical DinG helicase

Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. 'Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The second BEAT-PCD conference, and third PCD training school were held jointly in April 2017 in Valencia, Spain. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting

Proceedings of the 3rd BEAT-PCD Conference and 4th PCD Training School

Abstract Primary ciliary dyskinesia (PCD) is a chronic suppurative airways disease that is usually recessively inherited and has marked clinical phenotypic heterogeneity. Classic symptoms include neonatal respiratory distress, chronic rhinitis since early childhood, chronic otitis media, recurrent airway infections leading to bronchiectasis, chronic sinusitis, laterality defects with and without congenital heart disease including abnormal situs in approximately 50% of the cases, and male infertility. Lung function deteriorates progressively from childhood throughout life. ‘Better Experimental Approaches to Treat Primary Ciliary Dyskinesia’ (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The third BEAT-PCD conference and fourth PCD training school were held jointly in February 2018 in Lisbon, Portugal. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting

Measurement of inclusive D*+- and associated dijet cross sections in photoproduction at HERA

Inclusive photoproduction of D*+- mesons has been measured for photon-proton centre-of-mass energies in the range 130 < W < 280 GeV and a photon virtuality Q^2 < 1 GeV^2. The data sample used corresponds to an integrated luminosity of 37 pb^-1. Total and differential cross sections as functions of the D* transverse momentum and pseudorapidity are presented in restricted kinematical regions and the data are compared with next-to-leading order (NLO) perturbative QCD calculations using the "massive charm" and "massless charm" schemes. The measured cross sections are generally above the NLO calculations, in particular in the forward (proton) direction. The large data sample also allows the study of dijet production associated with charm. A significant resolved as well as a direct photon component contribute to the cross section. Leading order QCD Monte Carlo calculations indicate that the resolved contribution arises from a significant charm component in the photon. A massive charm NLO parton level calculation yields lower cross sections compared to the measured results in a kinematic region where the resolved photon contribution is significant.Comment: 32 pages including 6 figure