bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of Weight and Fat‐Free Mass with Oral Nutritional Supplementation in Patients with Alzheimer's Disease at Risk of Malnutrition: A Prospective Randomized Study
Authors: Lauque Sylvie , Arnaud‐Battandier Franck , Gillette Sophie , Plaze Jean‐Marie , Andrieu Sandrine , Cantet Christelle , Vellas Bruno 
Published: September 2004

Objectives: To study the effects of oral nutritional supplements (OS) on body weight, body composition, nutritional status, and cognition in elderly patients with Alzheimer's disease (AD).Design: Prospective, randomized, controlled study.Setting: Geriatric wards and day care centers in the Toulouse area, France.Participants: Ninety‐one subjects with AD aged 65 and older at risk of undernutrition as evaluated using the Mini Nutritional Assessment.Intervention: After randomization, 46 patients (intervention group) received 3‐month OS. The other 45 patients (control group) received usual care.Measurements: Weight, body composition (evaluated using dual‐energy x‐ray absorptiometry), cognitive function, activities of daily living, eating behavior, and dietary intakes were evaluated at the beginning of the study and at 3 months and 6 months. Supplement compliance was recorded each day.Results: Between baseline and 3 months, energy and protein intakes significantly improved in the intervention group, resulting in a significant increase in weight and fat‐free mass, but no significant changes were found for dependence, cognitive function, or biological markers. The nutritional benefit was maintained in the intervention group after discontinuation of OS at 3 months.Conclusion: Three‐month daily OS significantly improves body weight. It is practicable and effective, and the patients accepted it well. The improvement that was observed even in the control group showed that caregiver education is an important factor in maintaining the nutritional status of patients with AD. Moreover, regular courses of OS may help to maintain the increase in fat‐free mass and improve the nutritional status of these patients.
Nursing Home Characteristics and Potentially Preventable Hospitalizations of Long‐Stay Residents
Authors: Intrator Orna , Zinn Jacqueline , Mor Vincent 
Published: September 2004

Objectives: To examine the association between having a nurse practitioner/physician assistant (NP/PA) on staff, other nursing home (NH) characteristics, and the rate of potentially preventable/avoidable hospitalizations of long‐stay residents, as defined using a list of ambulatory care–sensitive (ACS) diagnoses.Design: Cross‐sectional prospective study using Minimum Data Set (MDS) assessments, Centers for Medicare and Medicaid Services inpatient claims and eligibility records, On‐line Survey Certification Automated Records, (OSCAR) and Area Resource File (ARP).Setting: Freestanding urban NHs in Maine, Kansas, New York, and South Dakota.Participants: Residents of 663 facilities with a quarterly or annual MDS assessment in the 2nd quarter of 1997, who had a prior MDS assessment at least 160 days before, and who were not health maintenance organization members throughout 1997 (N=54,631).Measurements: A 180‐day multinomial outcome was defined as having any hospitalization with primary ACS diagnosis, otherwise having been hospitalized, otherwise died, and otherwise remained in the facility.Results: Multilevel models show that facilities with NP/PAs were associated with lower hospitalization rates for ACS conditions (adjusted odds ratio (AOR)=0.83), but not with other hospitalizations. Facilities with more physicians were associated with higher ACS hospitalizations (ACS, AOR=1.14, and non‐ACS, AOR=1.10). Facilities providing intravenous therapy, and those that operate a nurses' aide training program were associated with fewer hospitalizations of both types.Conclusion: Employment of NP/PAs in NHs, the provision of intravenous therapy, and the operation of certified nurse assistant training programs appear to reduce ACS hospitalizations, and may be feasible cost‐saving policy interventions.
Effect of Antipsychotic Withdrawal on Behavior and Sleep/Wake Activity in Nursing Home Residents with Dementia: A Randomized, Placebo‐Controlled, Double‐Blinded Study The Bergen District Nursing Home Study
Authors: Ruths Sabine , Straand Jørund , Nygaard Harald A. , Bjorvatn Bjørn , Pallesen Ståle 
Published: September 2004

Objectives: To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia.Design: Randomized, placebo‐controlled, double‐blind trial.Setting: NHs in Bergen, Norway.Participants: Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms.Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks.Measurements: Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI‐Q) and actigraphy.Results: After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24‐hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI‐Q. One patient was restarted on antipsychotics.Conclusion: Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long‐term effect of these changes is not known. The NPI‐Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies.
Health Care for Older Persons in Argentina: A Country Profile
Authors: Montero‐Odasso Manuel , Przygoda Pablo , Redondo Nélida , Adamson Juan , Kaplan Roberto 
Published: September 2004

Argentina is a large country situated at the southern end of the Americas. It is highly urbanized, and almost one‐third of the population lives in the capital city and its surrounding area (Buenos Aires). The population is composed of heterogeneous groups, formed primarily by descendants of European immigration who constitute 85% of the inhabitants. In the last 30 years, Argentina has witnessed a growth in the elderly population from less than 7% to nearly 10% of the total population. Additionally, in Buenos Aires City, more than 17% are aged 65 or older.The healthcare systems for the elderly lack nationwide coverage. The Programa de Atención Médica Integral (PAMI) is the largest program for elderly care. It is a state‐run program for disabled and senior citizens. PAMI serves 65% of the approximately 3.6 million older people in Argentina. The quality of PAMI healthcare delivery has decreased in the last 2 decades and has largely declined since the Argentinean economic crisis of late 2001. The rehabilitation and long‐term care services are relatively underdeveloped, and fewer than 2% of senior citizens live in residential or nursing homes. Recently, the government has proposed a system of care built up from the primary care resources of the community.
A Series of Diaryltriazines and Diarylpyrimidines Are Highly Potent Nonnucleoside Reverse Transcriptase Inhibitors with Possible Applications as Microbicides
Authors: Van Herrewege Yven , Vanham Guido , Michiels Jo , Fransen Katrien , Kestens Luc , Andries Koen , Janssen Paul , Lewi Paul 
Published: September 2004

ABSTRACT

An in vitro model of monocyte-derived dendritic cells (MO-DC) and CD4
+
T cells, representing the primary targets of sexual human immunodeficiency virus (HIV) transmission, was used to evaluate the antiviral and immune suppressive activity of new classes of nonnucleoside reverse transcriptase inhibitors, diaryltriazines (DATAs) and diarylpyrimidines (DAPYs), compared to the reference compounds UC-781 and PMPA. Antiviral activity (as reflected by the 50% effective concentration [EC
50
]) was determined by treating HIV-infected MO-DC/CD4
+
-T-cell cocultures with a dose range of a compound during 14 days, followed by analysis of supernatants in HIV p24 antigen enzyme-linked immunosorbent assay. A limited, 24-h treatment evaluated the compounds as microbicides. Viral rescue was evaluated in a PCR by monitoring proviral DNA in secondary cultures with phytohemagglutinin-interleukin-2 blasts. We determined 50% immunosuppressive concentrations in mixed leukocyte cultures of MO-DC and allogeneic T cells, with compound either continuously present or present only during the first 24 h. The EC
50
values of DATA and DAPY compounds ranged from 0.05 to 3 nM compared to 50 nM for UC-781 and 89 nM for PMPA. When evaluated in the “microbicide” setting, the most potent compounds completely blocked HIV infection at 10 to 100 nM. The immunosuppressive concentrations were well above the EC
50
, resulting in favorable therapeutic indices for all compounds tested. The DATA and DAPY compounds described here are more potent than earlier reverse transcriptase inhibitors and show favorable pharmacological profiles in vitro. They could strengthen the antiretroviral armamentarium and might be useful as microbicides.
Posaconazole Is a Potent Inhibitor of Sterol 14α-Demethylation in Yeasts and Molds
Authors: Munayyer Hanan K. , Mann Paul A. , Chau Andrew S. , Yarosh-Tomaine Taisa , Greene Jonathan R. , Hare Roberta S. , Heimark Larry , Palermo Robert E. , Loebenberg David , McNicholas Paul M. 
Published: September 2004

ABSTRACT

Posaconazole (POS; SCH 56592) is a novel triazole that is active against a wide variety of fungi, including fluconazole-resistant
Candida albicans
isolates and fungi that are inherently less susceptible to approved azoles, such as
Candida glabrata
. In this study, we compared the effects of POS, itraconazole (ITZ), fluconazole (FLZ), and voriconazole (VOR) on sterol biosynthesis in strains of
C. albicans
(both azole-sensitive and azole-resistant strains),
C. glabrata
,
Aspergillus fumigatus
, and
Aspergillus flavus
. Following exposure to azoles, nonsaponifiable sterols were extracted and resolved by liquid chromatography and sterol identity was confirmed by mass spectroscopy. Ergosterol was the major sterol in all but one of the strains;
C. glabrata
strain C110 synthesized an unusual sterol in place of ergosterol. Exposure to POS led to a decrease in the total sterol content of all the strains tested. The decrease was accompanied by the accumulation of 14α-methylated sterols, supporting the contention that POS inhibits the cytochrome P450 14α-demethylase enzyme. The degree of sterol inhibition was dependent on both dose and the susceptibility of the strain tested. POS retained activity against
C. albicans
isolates with mutated forms of the 14α-demethylase that rendered these strains resistant to FLZ, ITZ, and VOR. In addition, POS was a more potent inhibitor of sterol synthesis in
A. fumigatus
and
A. flavus
than either ITZ or VOR.
Emergence and Spread of Three Clonally Related Virulent Isolates of CTX-M-15-Producing
Escherichia coli
with Variable Resistance to Aminoglycosides and Tetracycline in a French Geriatric Hospital
Authors: Leflon-Guibout Véronique , Jurand Cécile , Bonacorsi Stéphane , Espinasse Florence , Guelfi Marie Claude , Duportail Françoise , Heym Beate , Bingen Edouard , Nicolas-Chanoine Marie-Hélène 
Published: September 2004

ABSTRACT

Three types of multidrug-resistant
Escherichia coli
isolates, called GEN S, GEN R, and AMG S, according to their three different aminoglycoside resistance patterns, were responsible for urinary tract colonization or infection in 87, 12, and 13 new patients, respectively, in a French 650-bed geriatric hospital over a 13-month period. The three
E. coli
types belonged to the same clone and phylogenetic group (group B2) and had identical transferable plasmid contents (a 120-kb plasmid), β-lactam and fluoroquinolone resistance genotypes (
bla
TEM-1B
,
bla
CTX-M-15
, and double mutations in both the
gyrA
and the
parC
genes), and virulence factor genotypes (
aer
,
fyuA
, and
irp2
). They disseminated in the geriatric hospital, where the antibiotics prescribed most often were fluoroquinolones and ceftriaxone, but not in the affiliated acute-care hospital, where isolation precautions were applied to the transferred patients. Thus,
E. coli
isolates, both CTX-M-type β-lactamase producers and fluoroquinolone-resistant isolates, might present a new challenge for French health care settings.
Inhibition of Human Cytomegalovirus Replication by Benzimidazole Nucleosides Involves Three Distinct Mechanisms
Authors: Evers David L. , Komazin Gloria , Ptak Roger G. , Shin Dongjin , Emmer Brian T. , Townsend Leroy B. , Drach John C. 
Published: September 2004

ABSTRACT

The benzimidazole nucleosides 2-bromo-5,6-dichloro-1-(β-
d
-ribofuranosyl)benzimidazole (BDCRB) and 2-isopropylamino-5,6-dichloro-1-(β-
l
-ribofuranosyl)benzimidazole (1263W94, or maribavir) are potent and selective inhibitors of human cytomegalovirus (HCMV) replication. These inhibitors act by two different mechanisms: BDCRB blocks the processing and maturation of viral DNA, whereas maribavir prevents viral DNA synthesis and capsid nuclear egress. In order to determine by which of these two mechanisms other benzimidazole nucleosides acted, we performed time-of-addition studies and other experiments with selected new analogs. We found that the erythrofuranosyl analog and the α-lyxofuranosyl analog acted late in the viral replication cycle, similar to BDCRB. In marked contrast, the α-5′-deoxylyxofuranosyl analog of 2,5,6-trichloro-1-(β-
d
-ribofuranosyl)benzimidazole (compound UMJD1311) acted early in the replication cycle, too early to be consistent with either mechanism. Similar to other reports on early acting inhibitors of herpesviruses, compound 1311 was multiplicity of infection dependent, an observation that could not be reproduced with UV-inactivated virus. HCMV isolates resistant to BDCRB and maribavir were sensitive to compound 1311, as were viruses resistant to ganciclovir, cidofovir, and foscarnet. The preincubation of host cells with compound 1311 and removal prior to the addition of HCMV did not produce an antiviral cellular response. We conclude that this newly discovered early mode of action occurs at a stage of viral replication after entry to cells but prior to viral DNA synthesis, thereby strongly suggesting that the trisubstituted benzimidazole nucleoside series possesses three distinct biochemical modes of action for inhibition of HCMV replication.
Combination Therapy Counteracts the Enhanced Transmission of Drug-Resistant Malaria Parasites to Mosquitoes
Authors: Hallett Rachel L. , Sutherland Colin J. , Alexander Neal , Ord Rosalynn , Jawara Musa , Drakeley Chris J. , Pinder Margaret , Walraven Gijs , Targett Geoffrey A. T. , Alloueche Ali 
Published: September 2004

ABSTRACT

Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resistant parasites from treated patients to mosquito vectors has not been measured directly. In a trial comparing CQ monotherapy to the combination CQ plus artesunate (AS) in Gambian children with uncomplicated falciparum malaria, we measured transmissibility by feeding
Anopheles gambiae
mosquitoes with blood from 43 gametocyte-positive patients through a membrane. In the CQ-treated group, gametocytes from patients carrying parasites with the CQ resistance-associated allele
pfcrt
-76T prior to treatment produced infected mosquitoes with 38 times higher
Plasmodium falciparum
oocyst burdens than mosquitoes fed on gametocytes from patients infected with sensitive parasites (
P
< 0.001). Gametocytes from parasites carrying the resistance-associated allele
pfmdr1
-86Y produced 14-fold higher oocyst burdens than gametocytes from patients infected with sensitive parasites (
P
= 0.011). However, parasites carrying either of these resistance-associated alleles pretreatment were not associated with higher mosquito oocyst burdens in the CQ-AS-treated group. Thus, combination therapy overcomes the transmission advantage enjoyed by drug-resistant parasites.
Antibody Mapping of the Linear Epitopes of CMY-2 and SHV-1 β-Lactamases
Authors: Hujer Andrea M. , Bethel Christopher R. , Bonomo Robert A. 
Published: September 2004

ABSTRACT
Knowledge of the amino acids that define recognition of anti-β-lactamase antibodies is critical to the interpretation of sensitivity and specificity of these antibodies when they are used in a clinical or research setting. To this end, we mapped the epitopes of the CMY-2 and SHV-1 β-lactamases by using the SPOT synthesis method. Eight linear epitopes in SHV-1 and seven linear epitopes in CMY-2 were identified by using anti-SHV-1 and anti-CMY-2 polyclonal antibodies, respectively. The epitopes of SHV-1 were mapped to amino acids at the Ambler positions ABL 28 to 38, 42 to 54, 88 to 100, 102 to 114, 170 to 182, 186 to 194, 202 to 210, and 276 to 288. In the epitope spanning amino acids 102 to 114, alanine and X-Scan analysis demonstrated that D104, Y105, P107, and S109 are essential residues for antibody recognition. In the epitope containing amino acids 170 to 182, N170, L173, P174, G175, and D176 were immunodominant. In CMY-2 β-lactamase, amino acids 4 to 16, 70 to 79, 211 to 223, 274 to 286, 289 to 298, 322 to 334, and 343 to 358 of the mature enzyme defined the major linear epitopes. A detailed analysis of the recognition sites that are located in an area analogous to the omega loop of class A β-lactamases (V211 to V223) showed that the amino acids Q215 to E219 are important in antibody binding. Incubation of CMY-2 β-lactamase with a 10-fold molar excess of anti-CMY-2 antibody for 60 min resulted in greater than 80% inhibition of nitrocefin hydrolysis. A 10-fold molar excess of anti-SHV-1 antibody reduced the activity of SHV-1 by 69%. Analysis of the CMY-2 and SHV-1 structures suggest that this reduction of hydrolytic activity may be due in part to the direct binding of antibodies to the omega loop, thereby hindering access of substrate to the active site.
Dual-Action Mechanism of Viramidine Functioning as a Prodrug and as a Catabolic Inhibitor for Ribavirin
Authors: Wu Jim Zhen , Larson Gary , Hong Zhi 
Published: September 2004

ABSTRACT

An investigational nucleoside analogue drug, viramidine, has recently emerged as a potentially safer alternative to ribavirin for the treatment of hepatitis C viral infection. We have reported that viramidine mainly functions as a prodrug of ribavirin that is enriched in the liver. This in vitro study further explores viramidine's activity against nucleoside phosphorylase, a host enzyme that is responsible for phosphorolysis of ribavirin in vivo. Our experiments show that viramidine inhibits ribavirin phosphorolysis with a

K
i

of 2.5 μM. This result suggests that viramidine may act through a dual-action mechanism by serving as a prodrug of ribavirin and concomitantly as an inhibitor for nucleoside phosphorylase catabolism of ribavirin.
On issues of confidence in determining the time constant for oxygen uptake kinetics
Authors: Markovitz G H , Sayre J W , Storer T W , Cooper C B 
Published: September 2004

Background:τV˙o2at the onset of constant work rate (CWR) exercise is a variable of aerobic fitness that shortens with physical training and lengthens with cardiopulmonary disease. Determination of τV˙o2with sufficiently high confidence has typically required multiple exercise transitions limiting its clinical application.Objectives:To design a protocol to determine τV˙o2reliably but simply.Methods:On each of three days, five healthy men performed two CWR tests on a cycle ergometer below the metabolic threshold (V˙o2θ) for blood lactate accumulation as determined by gas exchange measurements followed by an incremental work rate (IWR) test. τV˙o2was determined (a) from the on-transit (on-τV˙o2) and off-transit (off-τV˙o2) of six CWR tests both individually and superimposed, using non-linear regression with a monoexponential model, and (b) by geometric analysis of the IWR tests (ramp-τV˙o2).Results:Group means (SD) were: V˙o2max3.84 (0.44) litres/min, V˙o2θ 1.88 (0.23) litres/min, steady state exercise V˙o21.67 (0.07) litres/min, on-τV˙o238.0 (5.3) seconds, off-τV˙o239.0 (4.3) seconds, and ramp-τV˙o260.8 (15.4) seconds. On-τV˙o2correlated with off-τV˙o2(r =  0.87), V˙o2max(r =  −0.73), and V˙o2θ (r =  0.89). The pooled mean τV˙o2from six superimposed tests agreed with the arithmetic grand mean of the six tests.Conclusions:The average of on-τV˙o2and off-τV˙o2fell within the 95% confidence interval of the pooled mean by the second test. Ramp-τV˙o2was longer and less reproducible. These findings support the use of both on- and off-transit data for the determination of τV˙o2, an approach that reduces the number of transitions necessary for accurate determination of τV˙o2, potentially enhancing its clinical application.