Frequency‐specific disruptions of neuronal oscillations reveal aberrant auditory processing in schizophrenia

Individuals with schizophrenia exhibit abnormalities in evoked brain responses in oddball paradigms. These could result from (a) insufficient salience‐related cortical signaling (P300), (b) insufficient suppression of irrelevant aspects of the auditory environment, or (c) excessive neural noise. We tested whether disruption of ongoing auditory steady‐state responses at predetermined frequencies informed which of these issues contribute to auditory stimulus relevance processing abnormalities in schizophrenia. Magnetoencephalography data were collected for 15 schizophrenia and 15 healthy subjects during an auditory oddball paradigm (25% targets; 1‐s interstimulus interval). Auditory stimuli (pure tones: 1 kHz standards, 2 kHz targets) were administered during four continuous background (auditory steady‐state) stimulation conditions: (1) no stimulation, (2) 24 Hz, (3) 40 Hz, and (4) 88 Hz. The modulation of the auditory steady‐state response (aSSR) and the evoked responses to the transient stimuli were quantified and compared across groups. In comparison to healthy participants, the schizophrenia group showed greater disruption of the ongoing aSSR by targets regardless of steady‐state frequency, and reduced amplitude of both M100 and M300 event‐related field components. During the no‐stimulation condition, schizophrenia patients showed accentuation of left hemisphere 40 Hz response to both standard and target stimuli, indicating an effort to enhance local stimulus processing. Together, these findings suggest abnormalities in auditory stimulus relevance processing in schizophrenia patients stem from insufficient amplification of salient stimuli.     

Genetic and Biochemical Characterization of an Acquired Subgroup B3 Metallo-β-Lactamase Gene,blaAIM-1, and Its Unique Genetic Context in Pseudomonas aeruginosa from Australia

Three clinical Pseudomonas aeruginosa isolates (WCH2677, WCH2813, and WCH2837) isolated from the Women''s and Children''s Hospital, Adelaide, Australia, produced a metallo-β-lactamase (MBL)-positive Etest result. All isolates were PCR negative for known MBL genes. A gene bank was created, and an MBL gene, designated bla_AIM-1, was cloned and fully characterized. The encoded enzyme, AIM-1, is a group B3 MBL that has the highest level of identity to THIN-B and L1. It is chromosomal and flanked by two copies (one intact and one truncated) of an ISCR element, ISCR15. Southern hybridization studies indicated the movement of both ISCR15 and bla_AIM-1 within the three different clinical isolates. AIM-1 hydrolyzes most β-lactams, with the exception of aztreonam and, to a lesser extent, ceftazidime; however, it possesses significantly higher k_cat values for cefepime and carbapenems than most other MBLs. AIM-1 was the first mobile group B3 enzyme detected and signals further problems for already beleaguered antimicrobial regimes to treat serious P. aeruginosa and other Gram-negative infections.     

Allyl isothiocyanate sensitizes TRPV1 to heat stimulation

The powerful plant-derived irritant allyl isothiocyanate (AITC, aka mustard oil) induces hyperalgesia to heat in rodents and humans through mechanisms that are not yet fully understood. It is generally believed that AITC activates the broadly tuned chemosensory cation channel transient receptor potential cation channel subfamily A member 1 (TRPA1), triggering an inflammatory response that sensitizes the heat sensor transient receptor potential cation channel subfamily V member 1 (TRPV1). In the view of recent data demonstrating that AITC can directly activate TRPV1, we here explored the possibility that this compound sensitizes TRPV1 to heat stimulation in a TRPA1-independent manner. Patch-clamp recordings and intracellular Ca²⁺ imaging experiments in HEK293T cells over-expressing mouse TRPV1 revealed that the increase in channel activation induced by heating is larger in the presence of AITC than in control conditions. The analysis of the effects of AITC and heat on the current–voltage relationship of TRPV1 indicates that the mechanism of sensitization is based on additive shifts of the voltage dependence of activation towards negative voltages. Finally, intracellular Ca²⁺ imaging experiments in mouse sensory neurons isolated from Trpa1 KO mice yielded that AITC enhances the response to heat, specifically in the subpopulation expressing TRPV1. Furthermore, this effect was strongly reduced by the TRPV1 inhibitor capsazepine and virtually absent in neurons isolated from double Trpa1/Trpv1 KO mice. Taken together, these findings demonstrate that TRPV1 is a locus for cross sensitization between AITC and heat in sensory neurons and may help explaining, at least in part, the role of this channel in AITC-induced hyperalgesia to heat.     

The Short-Term Effect of Lumbar Positional Distraction

Abstract

The purpose of this study was to test the hypothesis that positional distraction provides immediate relief of unilateral leg pain suspected to be caused by lumbar-nerve root irritation. Thirty subjects with true neurological signs were randomly assigned to a treatment group or control group. The treatment group received positional distraction for five minutes and the control group lay in side-lying for the same amount of time. Pain intensity, pain location, and SLR test height data was taken pre- and post-test. Statistical analysis was completed with the Wilcoxin-signed rank test for the data of pain intensity and with the paired sample t-test for the SLR height. The treatment group was found to have significantly less pain, more centralization of pain, and an increase in SLR test height (p-values of 0.001, 0.006, and 0.005 respectively). The control group showed no significant change (p-values of 0.506, 0.480, 0.884).     

Cardiac myosin binding protein-C restricts intrafilament torsional dynamics of actin in a phosphorylation-dependent manner

We have determined the effects of myosin binding protein-C (MyBP-C) and its domains on the microsecond rotational dynamics of actin, detected by time-resolved phosphorescence anisotropy (TPA). MyBP-C is a multidomain modulator of striated muscle contraction, interacting with myosin, titin, and possibly actin. Cardiac and slow skeletal MyBP-C are known substrates for protein kinase-A (PKA), and phosphorylation of the cardiac isoform alters contractile properties and myofilament structure. To determine the effects of MyBP-C on actin structural dynamics, we labeled actin at C374 with a phosphorescent dye and performed TPA experiments. The interaction of all three MyBP-C isoforms with actin increased the final anisotropy of the TPA decay, indicating restriction of the amplitude of actin torsional flexibility by 15–20° at saturation of the TPA effect. PKA phosphorylation of slow skeletal and cardiac MyBP-C relieved the restriction of torsional amplitude but also decreased the rate of torsional motion. In the case of fast skeletal MyBP-C, its effect on actin dynamics was unchanged by phosphorylation. The isolated C-terminal half of cardiac MyBP-C (C5–C10) had effects similar to those of the full-length protein, and it bound actin more tightly than the N-terminal half (C0–C4), which had smaller effects on actin dynamics that were independent of PKA phosphorylation. We propose that these MyBP-C-induced changes in actin dynamics play a role in the functional effects of MyBP-C on the actin–myosin interaction.     

Glucose Sensing in the Peritoneal Space Offers Faster Kinetics Than Sensing in the Subcutaneous Space

The paramount goal in the treatment of type 1 diabetes is the maintenance of normoglycemia. Continuous glucose monitoring (CGM) technologies enable frequent sensing of glucose to inform exogenous insulin delivery timing and dosages. The most commonly available CGMs are limited by the physiology of the subcutaneous space in which they reside. The very same advantages of this minimally invasive approach are disadvantages with respect to speed. Because subcutaneous blood flow is sensitive to local fluctuations (e.g., temperature, mechanical pressure), subcutaneous sensing can be slow and variable. We propose the use of a more central, physiologically stable body space for CGM: the intraperitoneal space. We compared the temporal response characteristics of simultaneously placed subcutaneous and intraperitoneal sensors during intravenous glucose tolerance tests in eight swine. Using compartmental modeling based on simultaneous intravenous sensing, blood draws, and intraarterial sensing, we found that intraperitoneal kinetics were more than twice as fast as subcutaneous kinetics (mean time constant of 5.6 min for intraperitoneal vs. 12.4 min for subcutaneous). Combined with the known faster kinetics of intraperitoneal insulin delivery over subcutaneous delivery, our findings suggest that artificial pancreas technologies may be optimized by sensing glucose and delivering insulin in the intraperitoneal space.     

A review of the physiological and histological effects of laser osteotomy

Osteotomy is the surgical cutting of bone. Some obstacles to laser osteotomy have been melting, carbonisation and subsequent delayed healing. New cooled scanning techniques have resulted in effective bone cuts without the strong thermal side effects, which were observed by inappropriate irradiation techniques with continuous wave and long pulsed lasers. With these new techniques, osteotomy gaps histologically healed with new bone formation without any noticeable or minimum thermal damage. No significant cellular differences in bone healing between laser and mechanical osteotomies were noticed. Some studies even suggest that the healing rate may be enhanced following laser osteotomy compared to conventional mechanical osteotomy. Additional research is necessary to evaluate different laser types with appropriate laser setting variables to increase ablation rates, with control of depth, change in bone type and damage to adjacent soft tissue. Laser osteotomy has the potential to become incorporated into the armamentarium of bone surgery.     

Percutaneous renal tumour biopsy

The use of percutaneous renal tumour biopsy (RTB) as a diagnostic tool for the histological characterization of renal masses has increased dramatically within the last 30 years. This increased utilization has paralleled advances in imaging techniques and an evolving knowledge of the clinical value of nephron sparing surgery. Improved biopsy techniques using image guidance, coupled with the use of smaller gauge needles has led to a decrease in complication rates. Reports from series containing a large number of cases have shown the non‐diagnostic rate of RTB to range from 4% to 21%. Re‐biopsy has been shown to reduce this rate, while the use of molecular markers further improves diagnostic sensitivity. In parallel with refinements of the biopsy procedure, there has been a rapid expansion in our understanding of the complexity of renal cell neoplasia. The 2013 Vancouver Classification is the current classification for renal tumours, and contains five additional entities recognized as novel forms of renal malignancy. The diagnosis of tumour morphotype on RTB is usually achievable on routine histology; however, immunohistochemical studies may be of assistance in difficult cases. The morphology of the main tumour subtypes, based upon the Vancouver Classification, is described and differentiating features are discussed.     

Clitoral Avulsion Successfully Repaired with 2-Octylcyanoacrylate

IntroductionClitoral piercing is becoming more popular in the general populace, playing an aesthetic as well as likely sexual role. However, potential for injury also impacts future clitoral sexual function, thus highlighting the importance of proper repair.AimTo report a 29-year-old woman presented to the emergency department after a clitoral piercing injury. Examination revealed avulsion of most of the clitoral body. After the patient refused expectant and surgical management, reapproximation was performed using 2-octylcyanoacrylate.Methods2-Octylcyanoacrylate, commonly known as Dermabond® (Ethicon Inc., Somerville, NJ, USA), was used to reapproximate the clitoral laceration for this patient. It is a cyanoacrylate tissue adhesive, forming a strong bond between wound edges to allow for normal healing to occur below. Benefits of use are decreased time of repair, water-resistant flexible coating, and no need for suture removal.ResultsThe laceration was successfully reapproximated with 2-octylcyanoacrylate. The tissue held together satisfactorily and the patient was discharged to home. She was seen as an outpatient 3 days later, with a moderately tender and swollen clitoris, but with an intact repair and improved pain. A visit 8 weeks later showed a well-healed clitoris, and the patient reported resolution of pain and return of sexual function, with successful orgasms.ConclusionsThe delicacy of clitoral anatomy and the potential impact of its injury on future sexual function make it an intimidating area of repair for the general physician. The method of repair must be tailored to the injury, patient, and physician; however, 2-octylcyanoacrylate is a viable alternative to traditional surgical or expectant management, offering strength and flexibility while avoiding further trauma with suture. Berger A and Worly B. Clitoral avulsion successfully repaired with 2-octylcyanoacrylate.