Delirium y delirium subsindrómico: prevalencia de un espectro de enfermedad

Introduction

Subsyndromal delirium (SSD) is a developing concept of disease with a spectrum beyond the diagnostic dichotomy of delirium with standard criteria.

Material and methods

To study the prevalence and significance of SSD we have conducted a cross-sectional prospective multicenter study of all patients admitted to three Geriatric Departments in tertiary hospitals. The SSD diagnostic criteria used were based on Marcantoniós criteria, and the DRS-R-98 scale was also used as a continuous variable of the degree of delirium.

Results

We studied 85 patients, 56% women, Barthel 62 (SD: 32), age 87 (SD: 6), CIRS-G 24 (SD: 6.85). Three quarters (75.3%) of patients had at least one CAM positive item, and half of them with at least 13 points in the DRS-R-98 scale. The prevalence of delirium was 53% and 22.3% for SSD. The degree of delirium-DSS was associated with different geriatric syndromes, levels of malnutrition, and degree of functional and cognitive impairment, with a significant linear trend between groups. Patients without delirium have higher levels than those with subsyndromal delirium, and these in turn are higher than those without diagnosed delirium. There is also a tendency in the degree of delirium measured by the DRS-R-98.

Conclusion

Beyond the dichotomous concept of the presence or absence of delirium, this study suggests the probable continuity of cognitive processes and the possibility of more effective and earlier diagnostic and therapeutic measures     

Sexual dimorphism of craniological characters in Eurasian badgers, Meles spp. (Carnivora, Mustelidae)

An analysis of 30 craniological characters of Eurasian badgers (Meles spp.) revealed different levels of sexual size dimorphism (SSD) and geographic variation in the three different species. SSD is displayed mostly in the general size of the skull (condylobasal length, zygomatic width, width of rostrum, and cranial height) and mandible (height of the vertical mandibular ramus, total length of the mandible, and length between the angular process and infradentale), and in some dental characters (length of the upper molar M¹). The most stable size dimorphism is manifested in the size of the canines, which is pronounced in all studied samples. SSD is not apparent in the length of the auditory bulla, the postorbital width, the minimum palatal width, the length of the lower molar M₂, and the talonid length of the lower carnassial tooth M₁.In both the European badgers, Meles meles, and the Asian badgers, Meles leucurus, two geographic forms that differ in the degree of SSD have been found. The most pronounced SSD of cranial characters is found in the Transcaucasian form of Meles meles and the Far-Eastern form of Meles leucurus. In the large European form of Meles meles, SSD is less pronounced in both absolute and relative criteria than in the smaller Transcaucasian form. An analogous situation is observed in the larger Siberian and smaller Far-Eastern forms of Meles leucurus. In the Japanese badgers, Meles anakuma, a downsizing of the skull is accompanied by a decrease in SSD (except in canine size) in comparison to the continental species. The significant differences in the manifestation of SSD in the Eurasian badgers support an earlier hypothesis (Abramov, 2001. Proc. Zool. Inst. Russ. Acad. Sci. 288, 221-233; Abramov, 2002. Russ. J. Theriol. 1 (1), 57-60; Abramov, 2003. Small Carnivore Conserv. 29, 5-7) that Meles meles, Meles leucurus, and Meles anakuma are separate species. The differences in the level of SSD among and within these three species of badgers may be attributed not to differences in the diet or social structure, but to the history of speciation events and formation of intraspecific distribution ranges.     

¿Qué pacientes se benefician más de la atención geriátrica hospitalaria en opinión de los especialistas en Geriatría?

Objective

To assess the most appropriate criteria considered by geriatricians to select patients who might benefit the most from geriatric hospital care.

Material and methods

We carried out a survey that consisted of various socio-demographic, clinical, functional and mental criteria included in the definition of the geriatric and frail elderly patient. The survey was sent to all specialists in geriatrics in the different hospitals of the Madrid Health Service. They were asked to answer to each criterion indicating whether they considered it as high priority, priority, low priority or no priority. The responses were clustered by type of hospital: acute hospitals with or without a post-graduate geriatric program for medical residents, and medium and long stay hospitals.

Results

A total of 83 questionnaires were completed (70% of the study population): 42 teaching hospitals a post-graduate geriatric program (74% of possible), 20 of those with an emergency department but without a post-graduate geriatric program (56% of possible), and 21 medium and long stay hospitals (84% of potential). All proposed criteria were considered individually as priority or high-priority by more than 50% of respondents. An age 85 years and over, admission for hip fracture, the presence of severe cognitive or functional impairment, frailty, and unexplained deterioration of health status, were considered individually as criteria for selecting high-priority target population by more than 85% of respondents.

Conclusions

Certain criteria, such as advanced age, or the presence of geriatrics-specific conditions, such as hip fracture or severe functional or cognitive impairment, are identified by geriatricians as useful to select patients to receive geriatric specialist hospital care.     

Phenotype guided characterization and molecular analysis of Indian patients with long QT syndromes

BackgroundLong QT syndromes (LQTS) are characterized by prolonged QTc interval on electrocardiogram (ECG) and manifest with syncope, seizures or sudden cardiac death. Long QT 1–3 constitute about 75% of all inherited LQTS. We classified a cohort of Indian patients for the common LQTS based on T wave morphology and triggering factors to prioritize the gene to be tested. We sought to identify the causative mutations and mutation spectrum, perform genotype-phenotype correlation and screen family members.MethodsThirty patients who fulfilled the criteria were enrolled. The most probable candidate gene among KCNQ1, KCNH2 and SCN5A were sequenced.ResultsOf the 30 patients, 22 were classified at LQT1, two as LQT2 and six as LQT3. Mutations in KCNQ1 were identified in 17 (77%) of 22 LQT1 patients, KCNH2 mutation in one of two LQT2 and SCN5A mutations in two of six LQT3 patients. We correlated the presence of the specific ECG morphology in all mutation positive cases. Eight mutations in KCNQ1 and one in SCN5A were novel and predicted to be pathogenic by in-silico analysis. Of all parents with heterozygous mutations, 24 (92%) of 26 were asymptomatic. Ten available siblings of nine probands were screened and three were homozygous and symptomatic, five heterozygous and asymptomatic.ConclusionsThis study in a cohort of Asian Indian patients highlights the mutation spectrum of common Long QT syndromes. The clinical utility for prevention of unexplained sudden cardiac deaths is an important sequel to identification of the mutation in at-risk family members.     

Leishmania (V.) braziliensis: detection by PCR in biopsies from patients with cutaneous leishmaniasis

Cutaneous leishmaniases present similar clinical appearances, but differing prognosis in the course of infection. Ulcers caused by parasites of the subgenus Viannia are more aggressive than ulcers caused by parasites of the subgenus Leishmania. Another problem is distinguishing between true Leishmania infection and other skin diseases in endemic areas, where cutaneous lesions and a single positive Montenegro intradermal test are enough to submit patients to specific treatment for cutaneous leishmaniasis. This study evaluated the efficacy of PCR in detecting in Leishmania in patients with cutaneous lesions. Leishmania (V.) braziliensis complex was determined by a primer pair from the multicopy spliced leader RNA. The results were compared to those of traditional methods. We analyzed biopsies of 109 patients with cutaneous lesions in the second most endemic region of Sao Paulo State, Brazil. Definitive diagnosis was established by clinical and “consensus laboratory criteria” (positive culture, stained tissue smears or PCR). Of 52 patients with cutaneous leishmaniasis, 96% had positive PCR, 69%, positive parasitological tests and 100%, positive Montenegro intradermal tests. Histopathological examination (only in 32 samples) were positive in 14 samples, suggestive in 14 and negative in 4 samples. All 57 patients with other etiologies had negative results in parasitological methods, PCR and histopathological examination (in 39 samples), but Montenegro intradermal tests were positive in 35%. PCR was highly sensitive and specific for L. (V.) braziliensis complex detection compared with other laboratory methods. Despite the specificity of the parasitological tests, the sensitivity was less than 70%. Montenegro intradermal reaction was highly sensitive, but with low specificity, only 65%. As suggestive results in histopathological examinations were shown in 14 samples, it was difficult to determine the true result. PCR applied to biopsies proved to be useful for differential diagnosis of cutaneous lesions of other etiologies in patients living in endemic areas. The advantages are most striking in clinical specimens with scarce amastigotes for which conventional methods have low sensitivity and should be considered for clinical and epidemiological patterns. On the other hand, both Montenegro intradermal test and parasitological methods are only modestly effective in cutaneous leishmaniasis diagnosis.     

Causes of secondary sexual differences in plants — Evidence from extreme leaf dimorphism in Leucadendron (Proteaceae)

In extreme cases leaves in male plants of the dioecious genus Leucadendron (Proteaceae) are up to an order of magnitude smaller than female leaves. This secondary sexual dimorphism (SSD) in leaf size has previously been suggested to be due to intra-male sexual selection, leading to an increase in male allocation to reproduction in dimorphic species. After critically evaluating previous data provided to support this hypothesis, I suggest on both theoretical grounds and on re-analysis that this argument is unlikely and unsupported. Leaf size dimorphism could theoretically evolve directly due to disruptive ecological selection between genders, leading to niche dimorphism either within or between habitats. I test this ecological causation hypothesis by providing data on specific leaf area (sla) and water use efficiency (δ ¹³C) of leaves from males and females of several Leucadendron species. Results confirm the expectation of minimal gender differences. I argue that leaf dimorphism is a consequence of selection on flower size and architecture.     

Repair efficiency of (5′S)-8,5′-cyclo-2′-deoxyguanosine and (5′S)-8,5′-cyclo-2′-deoxyadenosine depends on the complementary base

5′-R and 5′-S diastereoisomers of 8,5′-cyclo-2′-deoxyadenosine (cdA) and 8,5′-cyclo-2′-deoxyguanosine (cdG) containing a base-sugar covalent bond are formed by hydroxyl radicals. R-cdA and S-cdA are repaired by nucleotide excision repair (NER) in mammalian cellular extracts. Here, we have examined seven purified base excision repair enzymes for their ability to repair S-cdG or S-cdA. We could not detect either excision or binding of these enzymes on duplex oligonucleotide substrates containing these lesions. However, both lesions were repaired by HeLa cell extracts. Dual incisions by human NER on a 136-mer duplex generated 24–32 bp fragments. The time course of dual incisions were measured in comparison to cis-anti-B[a]P-N²-dG, an excellent substrate for human NER, which showed that cis-anti-B[a]P-N²-dG was repaired more efficiently than S-cdG, which, in turn, was repaired more efficiently than S-cdA. When NER efficiency of S-cdG with different complementary bases was investigated, the wobble pair S-cdG·dT was excised more efficiently than the S-cdG·dC pair that maintains nearly normal Watson-Crick base pairing. But S-cdG·dA mispair with no hydrogen bonds was excised less efficiently than the S-cdG·dC pair. Similar pattern was noted for S-cdA. The S-cdA·dC mispair was excised much more efficiently than the S-cdA·dT pair, whereas the S-cdA·dA pair was excised less efficiently. This result adds to complexity of human NER, which discriminates the damaged base pairs on the basis of multiple criteria.     

Responses of mink to auditory stimuli: Prerequisites for applying the ‘cognitive bias’ approach

The aim of the study was to determine and validate prerequisites for applying a cognitive (judgement) bias approach to assessing welfare in farmed mink (Neovison vison). We investigated discrimination ability and associative learning ability using auditory cues. The mink (n = 15 females) were divided into two groups (High, n = 8; Low, n = 7, representing the frequency of the tone they were habituated to, 18 and 2 kHz respectively) and were tested using a habituation–dishabituation procedure in experiment 1. In experiment 2 one auditory stimulus was followed by an inter-trial-interval (safe/neutral situation), whereas another auditory stimulus was followed by an aversive stimulus (air blow) before the inter-trial-interval (danger situation). We observed behaviour including latencies to show a response during both experiments. The High mink showed significant habituation in experiment 1 but the Low mink only showed habituation in experiment 2. Regardless of the frequency used (2 and 18 kHz), cues predicting the danger situation initially elicited slower responses compared to those predicting the safe situation but quickly became faster. Using auditory cues as discrimination stimuli for female farmed mink in a judgement bias approach would thus appear to be feasible. However several specific issues are to be considered in order to successfully adapt a cognitive bias approach to mink, and these are discussed.     

Disnea y psicopatología en el paciente anciano con enfermedad pulmonar obstructiva crónica

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease with dyspnoea perception as a main symptom. In severe stages, dyspnoea can constitute a risk factor for depression, anxiety and somatization disorders.

Objective

The objective was to evaluate the presence of these psychopathologies based on dyspnoea and severity stages in patients with COPD.

Materials and methods

Patients (n=51) were evaluated by means of the Hospital Anxiety and Depression Scale, the dyspnoea scale (MRC), the General Health Questionnaire (GHQ-28) and spirometric criteria.

Results

The increase in dyspnoea level and disease severity lead to a progressive worsening of anxiety, depressive and somatic symptoms with clinical relevance (P<0.05). There was a significant correlation between those parameters (P<0.05).

Conclusions

The early detection and treatment of these psychopathologies associated with dyspnoea and progression of the disease must be taken into account in this complex pathology.     

DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy

Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases.     

The antimicrobial susceptibility,biofilm formation and genotypic profiles of Staphylococcus haemolyticus from bloodstream infections

We analysed the antimicrobial susceptibility, biofilm formation and genotypic profiles of 27 isolates of Staphylococcus haemolyticus obtained from the blood of 19 patients admitted to a hospital in Rio de Janeiro, Brazil. Our analysis revealed a clinical significance of 36.8% and a multi-resistance rate of 92.6% among these isolates. All but one isolate carried the mecA gene. The staphylococcal cassette chromosome mec type I was the most prevalent mec element detected (67%). Nevertheless, the isolates showed clonal diversity based on pulsed-field gel electrophoresis analysis. The ability to form biofilms was detected in 66% of the isolates studied. Surprisingly, no icaAD genes were found among the biofilm-producing isolates.     

Biofunctionalization of cellulosic fibres with l-cysteine: Assessment of antibacterial properties and mechanism of action against Staphylococcus aureus and Klebsiella pneumoniae

The main purpose of this work is to obtain a cotton-based textile material functionalized with l-cysteine (l-cys) to achieve an antimicrobial effect with potential application in biomedical, geriatric or pediatric textiles. The binding capacity of l-cys to cotton fibres was assessed through different functionalization strategies—surface activation and exhaustion processes. A subsequent analysis of the possible antibacterial action against Staphylococcus aureus and Klebsiella pneumoniae was performed according with the Japanese International standard ( JISL, 2008). To determine the mechanism of action of l-cys on the selected strains, flow cytometry was used.     

Intestinal Helminthic Infections Diagnosed by Colonoscopy in a Regional Hospital during 2001-2008

The present study investigated characteristics of 24 parasite infection cases detected during colonoscopy in a regional hospital from January 2001 to December 2008. Sixteen patients were confirmed with Trichuris trichiura infection, 6 patients were with Ascaris lumbricoides infection, 1 patient with Enterobius vermicularis infection, and 1 patient with Anisakis infection. Among them, 7 patients (43.8%) were asymptomatic. Colonoscopy findings were normal in 18 patients (75.0%). Among the patients with T. trichiura infection, colonoscopy showed several erosions in 2 patients (8.3%) and non-specific inflammation of the affected segment of the colon in 3 patients (12.5%). In 1 patient with anisakiasis, colonoscopy revealed a markedly swollen colonic wall. Stool examinations were performed before treatment in 7 patients (29.2%) and were all negative for parasite eggs or worms. These results suggest that colonoscopy is a useful diagnostic approach for parasitic infections even for asymptomatic patients and for patients with negative stool examinations.     

Inhibition of autophagy attenuates pancreatic cancer growth independent of TP53/TRP53 status

Basal levels of autophagy are elevated in most pancreatic ductal adenocarcinomas (PDAC). Suppressing autophagy pharmacologically using chloroquine (CQ) or genetically with RNAi to essential autophagy genes inhibits human pancreatic cancer growth in vitro and in vivo, which presents possible treatment opportunities for PDAC patients using the CQ-derivative hydroxychloroquine (HCQ). Indeed, such clinical trials are ongoing. However, autophagy is a complex cellular mechanism to maintain cell homeostasis under stress. Based on its biological role, a dual role of autophagy in tumorigenesis has been proposed: at tumor initiation, autophagy helps maintain genomic stability and prevent tumor initiation; while in advanced disease, autophagy degrades and recycles cellular components to meet the metabolic needs for rapid growth. This model was proven to be the case in mouse lung tumor models. However, in contrast to prior work in various PDAC model systems, loss of autophagy in PDAC mouse models with embryonic homozygous Trp53 deletion does not inhibit tumor growth and paradoxically increases progression. This raised concerns whether there may be a genotype-dependent reliance of PDAC on autophagy. In a recent study, our group used a Trp53 heterozygous mouse PDAC model and human PDX xenografts to address the question. Our results demonstrate that autophagy inhibition was effective against PDAC tumors irrespective of TP53/TRP53 status.     

Expression and differential response to haloperidol treatment of Cyclon/CCDC86 mRNA in schizophrenia patients

A gene known as Cyclon (cytokine-induced protein with coiled-coil domain) or CCDC86 (coiled-coil domain-containing protein 86) is known for its expression in leukocytes in mice, where it regulates the immune response. We investigated whether Cyclon/CCDC68 is expressed in leukocytes of schizophrenia patients and whether it might be used as a biological marker for the disease endophenotype segregation. We examined the level of mRNA of Cyclon/CCDC68 in white blood cells obtained from schizophrenia patients in relapse and remission as well as in healthy controls. The mRNA of Cyclon/CCDC68 was expressed by white blood cells of both schizophrenia patients and healthy controls. There was a dichotomous change in the levels of Cyclon/CCDC68 of relapsed patients before and after treatment. High Cyclon/CCDC68 levels were associated with a recent disease and presence of psychotic symptoms, while low levels were associated with a long duration of the disease and an absence of psychotic symptoms. These data indicate that Cyclon/CCDC68 levels correlate with the clinical presentation of relapsed schizophrenia. Cyclon/CCDC68 might be involved in the immune system disturbances observed in schizophrenia.