An investigation into the reliability and methodology of the Linburg-Comstock anomaly clinical test.

STUDY DESIGN: This is a cross-sectional study. INTRODUCTION: An intertendinous connection between the flexor pollicis longus (FPL) and index flexor digitorum profundus (IFDP) tendons causes involuntary index flexion during active thumb flexion and has been named the Linburg-Comstock anomaly (LCA). It may become symptomatic or cause functional limitations. Literature has documented the prevalence to range from 13% to 70%. Cadaver studies have reported an anatomical connection in 5% to 25%. PURPOSE: This study aimed to examine the methodology and reliability of the LCA clinical diagnostic test and to explore the wide range of reported incidence and the discrepancy between cadaver and subject prevalence. METHODS: Two examiners observed for the presence of involuntary index flexion during 3 separate variations of thumb flexion in 67 subjects (134 limbs); results were considered positive if involuntary flexion occurred at either index interphalangeal joint. Intertester reliability was assessed using Cohen's kappa coefficient. The volar forearm and wrist of 53 cadavers (106 limbs) were dissected and assessed for an observable and mechanical tendinous connection between the FPL and IFDP tendons. RESULTS: Prevalence for subjects (5%-32%) was at the lower end of the range of previously reported values; results differed with altering thumb flexion motion. Observation for the presence of an intertendinous connection between the FPL and IFDP tendons in cadaver specimens (23%) fell within previously reported ranges. Intertester reliability coefficients ranged from no to weak agreement and varied according to specific thumb flexion motion performed during the test. CONCLUSIONS: The identification of index finger flexion during thumb flexion varied both with thumb flexion motions and with whether flexion was assessed at the index proximal interphalangeal or distal interphalangeal joint. Intertester reliability was low for all variations of the LCA clinical test performed. The wide range in previously reported LCA incidence may be due to variability in testing procedure, and there is a need to establish a reliable and valid clinical test for this potentially symptomatic anatomic anomaly.

Encoding Temporal Regularities and Information Copying in Hippocampal Circuits.

Discriminating, extracting and encoding temporal regularities is a critical requirement in the brain, relevant to sensory-motor processing and learning. However, the cellular mechanisms responsible remain enigmatic; for example, whether such abilities require specific, elaborately organized neural networks or arise from more fundamental, inherent properties of neurons. Here, using multi-electrode array technology, and focusing on interval learning, we demonstrate that sparse reconstituted rat hippocampal neural circuits are intrinsically capable of encoding and storing sub-second-order time intervals for over an hour timescale, represented in changes in the spatial-temporal architecture of firing relationships among populations of neurons. This learning is accompanied by increases in mutual information and transfer entropy, formal measures related to information storage and flow. Moreover, temporal relationships derived from previously trained circuits can act as templates for copying intervals into untrained networks, suggesting the possibility of circuit-to-circuit information transfer. Our findings illustrate that dynamic encoding and stable copying of temporal relationships are fundamental properties of simple in vitro networks, with general significance for understanding elemental principles of information processing, storage and replication.

Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation.

In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. In the absence of incoming sound, a fraction of the MET channels on top of the sensory hair cells are open, resulting in a sustained depolarizing current. By genetically manipulating the in vivo expression of molecular components of the MET apparatus, we show that during pre-hearing stages the MET current is essential for establishing the electrophysiological properties of mature inner hair cells (IHCs). If the MET current is abolished in adult IHCs, they revert into cells showing electrical and morphological features characteristic of pre-hearing IHCs, including the re-establishment of cholinergic efferent innervation. The MET current is thus critical for the maintenance of the functional properties of adult IHCs, implying a degree of plasticity in the mature auditory system in response to the absence of normal transduction of acoustic signals.

Outbreak of KPC-3 Producing Carbapenem-Resistant Klebsiella pneumoniae in a US Pediatric Hospital.

BACKGROUND: The increase in carbapenem-resistant Enterobacteriaceae (CRE) infections is a critical public health issue. We recently experienced the largest single-center pediatric outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) at our hospital. The objective of this study was to describe the molecular epidemiology of this outbreak before and after infection-prevention interventions. METHODS: All positive cultures and associated clinical conditions were reviewed to determine whether health care-associated infections (HAIs) exist. HAIs were defined using Centers for Disease Control and Prevention guidelines. CRKP isolates were collected and screened for the presence of ß-lactamase genes. Strain relatedness of CRKP isolates was determined by field-inversion gel electrophoresis (FIGE) and multilocus sequence typing (MLST). Polymerase chain reaction (PCR) amplification and sequencing of blaTEM, blaSHV, and blaKPC genes were performed on representative isolates. RESULTS: During March-July 2010, 18 CRKP isolates were recovered from 15 unique patients. Six isolates were considered HAIs; all were central-line-associated bloodstream infections. All isolates testing positive by PCR for blaKPC were found to carry KPC-3 in transposon Tn4401 isotype "b." FIGE revealed 2 prevalent patterns (accounting for 10 and 3 CRKP isolates, respectively) that MLST demonstrated to consist entirely of strains from ST730; the remaining FIGE types corresponded to ST14, ST15, and ST1559 (a single-locus variant of ST730), with these alternate backgrounds appearing later in the outbreak. New CRKP cases decreased after the implementation of infection-control interventions. All isolates were ciprofloxacin sensitive. CONCLUSIONS: Molecular analyses document the introduction of a KPC-3-producing CRKP clone into our hospital setting, though some isolates appear to have other mechanisms of carbapenem resistance. The transition to a polyclonal epidemiology suggests that the initial outbreak was due to nosocomial spread of a single ST730 clone, while latter isolates may have been secondary to the introduction of a blaKPC-3/Tn4401 isotype "b"-containing plasmid into other K pneumoniae strain backgrounds versus new carbapenemase-producing bacteria.

Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.

Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (V(m)), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the V(m) of apical and basal IHCs by triggering small-conductance Ca(2+)-activated K(+) (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.

Control of an outbreak of infection with the hypervirulent Clostridium difficile BI strain in a university hospital using a comprehensive "bundle" approach.

BACKGROUND: In June 2000, the hospital-acquired Clostridium difficile (CD) infection rate in our hospital (University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, PA) increased to 10.4 infections per 1000 hospital discharges (HDs); the annual rate increased from 2.7 infections per 1000 HDs to 7.2 infections per 1000 HDs and was accompanied by an increase in the frequency of severe outcomes. Forty-seven (51%) of 92 HA CD isolates in 2001 were identified as the "epidemic BI strain." A comprehensive CD infection control "bundle" was implemented to control the outbreak of CD infection. METHODS: The CD infection control bundle consisted of education, increased and early case finding, expanded infection-control measures, development of a CD infection management team, and antimicrobial management. Process measures, antimicrobial usage, and hospital-acquired CD infection rates were analyzed, and CD isolates were typed. RESULTS: The rates of compliance with hand hygiene and isolation were 75% and 68%, respectively. The CD management team evaluated a mean of 31 patients per month (11% were evaluated for moderate or severe disease). Use of antimicrobial therapy associated with increased CD infection risk decreased by 41% during the period 2003-2005 (P<.001). The aggregate rate of CD infection during the period 2001-2006 decreased to 4.8 infections per 1000 HDs (odds ratio, 2.2; 95% confidence interval, 1.4-3.1; P<.001) and by 2006, was 3.0 infections per 1000 HDs, a rate reduction of 71% (odds ratio, 3.5; 95% confidence interval, 2.3-5.4; P<.001). During the period 2000-2001, the proportion of severe CD cases peaked at 9.4% (37 of 393 CD infections were severe); the rate decreased to 3.1% in 2002 and further decreased to 1.0% in 2006--a 78% overall reduction (odds ratio, 20.3; 95% confidence interval, 2.8-148.2; P<.001). In 2005, 13% of CD isolates were type BI (20% were hospital acquired), which represented a significant reduction from 2001 (P<.001). CONCLUSIONS: The outbreak of CD infection with the BI strain in our hospital was controlled after implementing a CD infection control "bundle." Early identification, coupled with appropriate control measures, reduces the rate of CD infection and the frequency of adverse events.

A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use.

BACKGROUND AND OBJECTIVE: Fluoroquinolones have not been frequently implicated as a cause of Clostridium difficile outbreaks. Nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1000 discharges (P < .001). During the first 2 years of the outbreak, there were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a large C. difficile outbreak in our hospital to identify risk factors and characterize the outbreak. METHODS: A retrospective case-control study of case-patients with C. difficile infection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed. RESULTS: On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P < .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes. CONCLUSIONS: Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak