Carriage of multidrug-resistant Gram-negative bacilli: duration and risk factors.

Identification of risk factors influencing the duration of carriage of multidrug-resistant Gram-negative bacilli (MDR-GNB) may be useful for infection control. The aim of this study is to estimate the impact of several factors collected for routine hospital surveillance on the duration of carriage of selected MDR-GNB. From January 2015 to July 2021, patients with at least two clinical/surveillance samples positive for MDR-GNB different from ESBL-producing E. coli or AmpC - exclusively producing Enterobacterales were assessed. Microorganisms, age, number of admissions, clinical or rectal sample, sex, and admission service were evaluated as risk factors. Multivariate analysis was performed by a Cox proportional hazard model. A total of 1981 episodes of colonization were included. Involved microorganisms were ESBL-Klebsiella pneumoniae (KP) in 1057 cases (53.4%), other ESBL-non-E. coli Enterobacterales in 91 (4.6%), OXA-48-KP in 263 (13.3%), KPC-KP in 90 (4.5%), VIM-KP in 29 (1.5%), carbapenemase-producing non-KP Enterobacterales (CP-non-KP) in 124 (6.3%), and MDR Pseudomonas aeruginosa (MDR-PAER) in 327 (16.5%). No differences in duration of colonization were observed among ESBL-KP (median colonization time 320 days), ESBL-non-E. coli Enterobacterales (226 days), OXA48-KP (305 days), and MDR-PAER (321 days). For each group, duration of colonization was significantly longer than that of KPC-KP (median colonization time 60 days), VIM-KP (138 days), and CP-non-KP (71 days). Male sex (HR = 0.88; 95% CI 0.78-0.99), detection in Hepatology-Gastroenterology (HR = 0.71; 95% CI 0.54-0.93), clinical sample (HR = 0.61; 95% CI 0.53-0.69), and > 2 admissions after first detection (HR = 0.47; 95% CI 0.42-0.52) were independent predictors of longer carriage, whereas VIM-KP (HR = 1.61; 95% CI 1.04-2.48), KPC-KP (HR = 1.85; 95% CI 1.49-2.3), and CP-non-KP (HR = 1.92; 95% CI 1.49-2.47) were associated with shorter colonization time. Duration of colonization was significantly longer for ESBL-KP, other ESBL-non-E. coli Enterobacterales, OXA-48-KP, and MDR-PAER. For these microorganisms, prolonging surveillance up to 2.5-3 years should be considered. Male sex, clinical sample, multiple readmissions, admission service, and type of microorganism are independent predictors of the duration of carriage.

Stem cell paracrine effect and delivery strategies for spinal cord injury regeneration.

Spinal cord injury (SCI) is a complicated neuropathological condition that results in functional dysfunction and paralysis. Various treatments have been proposed including drugs, biological factors and cells administered in several ways. Stem cell therapy offers a potentially revolutionary mode to repair the damaged spinal cord after injury. Initially, stem cells were considered promising for replacing cells and tissue lost after SCI. Many studies looked at their differentiation to replace neuronal and glial cells for a better functional outcome. However, it is becoming clear that different functional improvements recognized to stem cells are due to biomolecular activities by the transplanted stem cells rather than cell replacement. This review aimed to discuss the paracrine mechanisms for tissue repair and regeneration after stem cell transplantation in SCI. It focuses on stem cell factor production, effect in tissue restoration, and novel delivery strategies to use them for SCI therapy.

Courtship anomalies caused by doublesex mutations in Drosophila melanogaster.

The role played by the sex-determining gene doublesex (dsx) and its influence on Drosophila courtship were examined. Against a background of subnormal male-like behavior that is reported to be an attribute of haplo-X flies homozygous for the original dsx mutation, and given that a sex-specific muscle is unaffected by genetic variation at this locus, analyses of several reproductive behaviors and control for genetic background effects indicated that XY dsx mutants are impaired in their willingness to court females. When they did court, certain behavioral actions were normal, including components of courtship song. However, these mutants never produced courtship humming sounds. Mature XY dsx flies elicited anomalously high levels of courtship; that this occurs merely because of a delay in imaginal development was experimentally discounted. The current analysis reconciled two ostensibly conflicting reports involving the courtship-stimulating qualities of this mutant type. Such experiments also uncovered a new behavioral anomaly: dsx mutations caused chromosomal males to court other males at abnormally high levels. These results are discussed from the perspective of doublesex's influence on internal tissues of adult Drosophila involved in the triggering and neural control of male- and female-like elements of courtship, reproductive pheromone production, or a combination of such factors.

Extended reproductive roles of the fruitless gene in Drosophila melanogaster revealed by behavioral analysis of new fru mutants.

The fruitless mutants fru3 and fru4 were assessed for sex-specific reproductive-behavioral phenotypes and compared to the previously reported fru mutants. Among the several behavioral anomalies exhibited by males expressing these relatively new mutations, some are unique. fru3 and fru4 males are less stimulated to court females than fru1 and fru2. No courtship pulse song is generated by either fru3 or fru4 males, even though they perform brief wing extensions. fru3 and fru4 males display significantly less chaining behavior than do fru1 males. The hierarchy of courtship responses by fru males directed toward females vs. males, when presented with both sexes simultaneously, is that fru1 males perform vigorous and indiscriminant courtship directed at either sex; fru4 males are similarly indiscriminant, but courtship levels were lower than fru1; fru2 males prefer females; fru3 males show a courtship bias toward males. fru3 and fru4 males essentially lack the Muscle of Lawrence (MOL). On several reproductive criteria, there was no difference between fru-variant females and fru+. The increases in phenotypic severity measured for the new mutants are discussed in the context of the emerging molecular genetics of fru and with regard to the gene's position within the sex-determination pathway.

Courtship and visual defects of cacophony mutants reveal functional complexity of a calcium-channel alpha1 subunit in Drosophila.

We show by molecular analysis of behavioral and physiological mutants that the Drosophila Dmca1A calcium-channel alpha1 subunit is encoded by the cacophony (cac) gene and that nightblind-A and lethal(1)L13 mutations are allelic to cac with respect to an expanded array of behavioral and physiological phenotypes associated with this gene. The cacS mutant, which exhibits defects in the patterning of courtship lovesong and a newly revealed but subtle abnormality in visual physiology, is mutated such that a highly conserved phenylalanine (in one of the quasi-homologous intrapolypeptide regions called IIIS6) is replaced by isoleucine. The cacH18 mutant exhibits defects in visual physiology (including complete unresponsiveness to light in certain genetic combinations) and visually mediated behaviors; this mutant (originally nbAH18) has a stop codon in an alternative exon (within the cac ORF), which is differentially expressed in the eye. Analysis of the various courtship and visual phenotypes associated with this array of cac mutants demonstrates that Dmca1A calcium channels mediate multiple, separable biological functions; these correlate in part with transcript diversity generated via alternative splicing.

Aberrant splicing and altered spatial expression patterns in fruitless mutants of Drosophila melanogaster.

The fruitless (fru) gene functions in Drosophila males to establish the potential for male sexual behaviors. fru encodes a complex set of sex-specific and sex-nonspecific mRNAs through the use of multiple promoters and alternative pre-mRNA processing. The male-specific transcripts produced from the distal (P1) fru promoter are believed to be responsible for its role in specifying sexual behavior and are only expressed in a small fraction of central nervous system (CNS) cells. To understand the molecular etiology of fruitless mutant phenotypes, we compared wild-type and mutant transcription patterns. These experiments revealed that the fru(2), fru(3), fru(4), and fru(sat) mutations, which are due to P-element inserts, alter the pattern of sex-specific and sex-nonspecific fru RNAs. These changes arise in part from the P-element insertions containing splice acceptor sites that create alternative processing pathways. In situ hybridization revealed no alterations in the locations of cells expressing the P1-fru-promoter-derived transcripts in fru(2), fru(3), fru(4), and fru(sat) pharate adults. For the fru(1) mutant (which is due to an inversion breakpoint near the P1 promoter), Northern analyses revealed no significant changes in fru transcript patterns. However, in situ hybridization revealed anomalies in the level and distribution of P1-derived transcripts: in fru(1) males, fewer P1-expressing neurons are found in regions of the dorsal lateral protocerebrum and abdominal ganglion compared to wild-type males. In other regions of the CNS, expression of these transcripts appears normal in fru(1) males. The loss of fruitless expression in these regions likely accounts for the striking courtship abnormalities exhibited by fru(1) males. Thus, we suggest that the mutant phenotypes in fru(2), fru(3), fru(4), and fru(sat) animals are due to a failure to appropriately splice P1 transcripts, whereas the mutant phenotype of fru(1) animals is due to the reduction or absence of P1 transcripts within specific regions of the CNS.

Molecular genetic dissection of the sex-specific and vital functions of the Drosophila melanogaster sex determination gene fruitless.

A multibranched hierarchy of regulatory genes controls all aspects of somatic sexual development in Drosophila melanogaster. One branch of this hierarchy is headed by the fruitless (fru) gene and functions in the central nervous system, where it is necessary for male courtship behavior as well as the differentiation of a male-specific abdominal structure, the muscle of Lawrence (MOL). A preliminary investigation of several of the mutations described here showed that the fru gene also has a sex-nonspecific vital function. The fru gene produces a complex set of transcripts through the use of four promoters and alternative splicing. Only the primary transcripts produced from the most distal (P1) promoter are sex-specifically spliced under direction of the sex-determination hierarchy. We have analyzed eight new fru mutations, created by X-ray mutagenesis and P-element excision, to try to gain insight into the relationship of specific transcript classes to specific fru functions. Males that lack the P1-derived fru transcripts show a complete absence of sexual behavior, but no other defects besides the loss of the MOL. Both males and females that have reduced levels of transcripts from the P3 promoter develop into adults but frequently die after failing to eclose. Analysis of the morphology and behavior of adult escapers showed that P3-encoded functions are required for the proper differentiation and eversion of imaginal discs. Furthermore, the reduction in the size of the neuromuscular junctions on abdominal muscles in these animals suggests that one of fru's sex-nonspecific functions involves general aspects of neuronal differentiation. In mutants that lack all fru transcripts as well as a small number of adjacent genes, animals die at an early pupal stage, indicating that fru's function is required only during late development. Thus, fru functions both in the sex-determination regulatory hierarchy to control male sexual behavior through sex-specific transcripts and sex-nonspecifically to control the development of imaginal discs and motorneuronal synapses during adult development through sex-nonspecific transcript classes.

Screening for silent myocardial ischaemia in type 2 diabetic patients with additional atherogenic risk factors: applicability and accuracy of the exercise stress test.

OBJECTIVE: Coronary artery disease (CAD), a major cause of mortality in patients with type 2 diabetes (T2D), is often diagnosed late because of silent myocardial ischaemia (SMI). Exercise electrocardiogram testing (ECG) stress is the most utilized screening test for SMI. Its applicability and accuracy, which have never been reported in asymptomatic high-risk T2D patients, have been investigated in this study. DESIGN: A cross-sectional study with coronary angiography as the gold standard for detecting CAD was used. METHODS: Two hundred and six consecutive T2D patients, without symptoms and resting ECG signs of ischaemia but with peripheral vascular disease (PVD) and/or > or = two atherogenic factors, were studied. Ischaemia at ECG stress was indicated by horizontal or downsloping ST segment depression > or =1 mm at 0.08 s after the J point. CAD was defined by stenosis > or =70%. RESULTS: Only 141/206 (68%) patients had a diagnostic test: 27 (19%) tested positive and 114 (81%) tested negative. Coronary angiography in 71 patients (the 27 who tested positive and 44 randomly selected patients who tested negative) indicated a CAD prevalence of 29% and the ECG stress accuracy was 79%. 'False negative' patients (18%) had a higher prevalence (P<0.01) of long duration of diabetes and PVD. CONCLUSIONS: This is the first study which provides insights into the applicability and accuracy of ECG stress in screening SMI in high-risk patients with T2D. Due to the high prevalence of CAD, alternative screening tests in patients unable to perform the test and in those with a high chance of being 'false negative' should be looked for and validated.

Systolic ejection murmurs in the elderly: aortic valve and carotid arteries echo-Doppler findings.

UNLABELLED: Two-dimensional echographic and color Doppler studies of the heart and carotid arteries (CA) were performed in 45 patients greater than sixty-five years old without aortic stenosis, 23 with (Group 1) and 22 without (group 2) precordial ejection systolic murmur (SM). Aortic cusps thickening was found in 11 Group 1 (48%) and 2 Group 2 (9%) patients (p less than 0.001). Aortic root and aortic arch size were similar in the two groups. Maximum aortic flow velocity was significantly greater in Group 1 (200 60 cm/sec) than in Group 2 (120 20 cm/sec) (p less than 0.001). Left ventricular outflow systolic maximum velocity was similar in the two groups. A bilateral neck murmur was heard in 10/23 Group 1 patients (43%); in this group, patients with cervical SM had a greater maximum aortic flow velocity than those without cervical SM (230 + 60 cm/sec vs 172 + 32 cm/sec, p less than 0.001). In Group 1, 3 patients had a cervical SM louder on one neck side; only in these 3 patients were ipsilateral obstructive CA plaques found. A unilateral neck SM was heard in 4/22 Group 2 patients (18%); in these 4, ipsilateral obstructive CA were found. CONCLUSIONS: (1) in the elderly, precordial ejection SM is related to mild increase in maximum aortic flow velocity and thickening of aortic cusps; (2) in patients with precordial SM radiated to both neck sides, maximum aortic flow velocity tends to be more markedly increased; (3) in patients with precordial SM, a cervical SM louder on one neck side should suggest coexistent ipsilateral CA stenosis.

[Unusual cause of acute abdomen in childhood. Cystic fibrolymphangioma of the mesentery]. / Cause rare di addome acuto nell'infanzia. Il fibrolinfangioma cistico del mesentere.

Cystic fibrolymphangioma of the mesentery as an unusual cause of acute abdomen in infancy is described. This form is one of the many mesenteric cysts whose pathogenesis has not yet been established. Preoperative diagnosis of such cysts is very difficult, and there are very few cases in which a close study has been possible in the light of clinical suspicion. Intraoperative diagnosis is the most likely, therefore, though there are cases - such as that reported here - in which surgery is indicated to remedy the occlusion caused by the cyst, and not because a swelling has been noted on clinical examination.

[Sinoatrial node disease in cardiac amyloidosis. Description of 2 cases]. / Malattia del nodo senoatriale in corso di amiloidosi cardiaca. Descrizione di due casi.

We describe two patients with probable amyloid infiltrative cardiomyopathy and episodes of syncope. A sick sinus syndrome was suspected by Holter monitoring in both patients. The diagnosis was supported by the finding of a marked prolongation of sinus node recovery time in one case. In both patients a permanent pacemaker was implanted which prevented recurrence of syncopal episodes.

Reassessment of the effect of biological rhythm mutations on learning in Drosophila melanogaster.

A link between learning deficits and circadian period-lengthening mutations in Drosophila melanogaster previously has been reported. Mutant long-period males performed poorly in two learning assays involving experience-dependent courtship inhibition. In one, normal males that have courted fertilized females subsequently show courtship inhibition with virgin females. In the other, normal males that have courted sexually immature males subsequently fail to court other immature males. Those results have been reassessed in an extended study of genetic variants involving the period gene. 1. Long-period perL1 males demonstrated poor conditioned courtship inhibition when exposed to fertilized females; they showed normal courtship conditioning when exposed to immature males. This could be due to a perL1-associated olfactory deficit with fertilized females, since perL1 males were unable to discriminate behaviorally between fertilized and virgin females. 2. Other long-period males, including perL2 males and transgenic perL1 males bearing a truncated form of the per+ gene, were conditioned normally by fertilized females. Thus, the courtship inhibition defect is specific to the perL1 mutant strain. 3. perL1 (and other per mutant) flies showed normal acquisition and retention of a classically conditioned olfactory avoidance response. 4. Results from a new conditioned courtship inhibition experiment are presented; males exposed to fertilized females during training showed further courtship inhibition during subsequent exposure to fertilized females. From the perspective of learning theory, this can be viewed as a savings experiment.

Wing-beat frequency mutants and courtship behavior in Drosophila melanogaster males.

Flightless mutations that affect wing-beat frequency (WBF) of Drosophila melanogaster were examined for their effect on male courtship. WBFs were measured using a fixed-wire tether that completely supports the fly in an attitude similar to hovering flight. The two spontaneous mutations, one of which reduces WBF to one-half normal and the other to zero, were placed on an isogenic background and were compared to an isogenic wildtype strain and to a genetically heterogeneous wildtype strain. Time to mating under noncompetitive conditions (single pair matings) was not significantly different among the four male types in one experiment. In a second experiment, although the time to mating varied significantly among the four male types, there was no association between the WBF that was characteristic of a male type and the length of time to mating. Time to mating was not significantly correlated with WBF, wing size, or body mass in either experiment. Genetically heterogeneous wild-type females were significantly more receptive (had shorter times to mating) than inbred wild-type females toward all four male types. During the time-to-mating tests, all four male types appeared to show typical courtship behaviors. Therefore, the male types were compared for possible differences in four components of the male courtship song: sine song frequency, interpulse interval, intrapulse frequency (= carrier frequency), and wing cycles per pulse. One or another of these components showed significant differences among the four male types (e.g., genetically heterogeneous, wild-type males showed a significantly higher sine song frequency and intrapulse frequency than males of the three isogenic types). However, the average values for all four male types were within reported wild-type ranges for each courtship song component. Although the two mutations drastically reduce WBF during tethered flight, they do not have any similar major effect on courtship. Apparently they affect muscles or neuronal control mechanisms that are not common elements shared by the wing movement of flight and male courtship song.

Promoting activity in the elderly through interdisciplinary linkages.

Interdisciplinary collaboration helped a group of health care providers plan, implement, and evaluate an exercise program for sedentary older adults in a long-term care facility. The program, designed as a research study, can be implemented by paraprofessional care givers with minimal supervision. The synergy resulting from collaboration between the investigator and colleagues in the practice arena was the cornerstone of the program's success. This paper describes the results of a Sit and Get Fit exercise program, a project funded by The University of Akron.