Floquet Engineering Correlated Materials with Unpolarized Light.

Floquet engineering is a powerful tool that drives materials with periodic light. Traditionally, the light is monochromatic, with amplitude, frequency, and polarization varied. We introduce Floquet engineering via unpolarized light built from quasimonochromatic light and show how it can modify strongly correlated systems, while preserving the original symmetries. Different types of unpolarized light can realize different strongly correlated phases As an example, we treat insulating magnetic materials on a triangular lattice and show how unpolarized light can induce a Dirac spin liquid.

Rationale and design for fractional microablative CO2 laser versus photothermal non-ablative erbium:YAG laser for the management of genitourinary syndrome of menopause: a non-inferiority, single-blind randomized controlled trial.

Genitourinary syndrome of menopause (GSM) is a common condition affecting up to 50% of postmenopausal women and up to 70% of postmenopausal breast cancer survivors. GSM is a chronic condition with a significant impact on sexual health and quality of life. The mainstay of treatment has been with symptomatic relief using topical emollients or lubricants. Second-line treatment is with topical vaginal estrogens to restore the physiology of the vaginal epithelium. For some, the latter is not suitable or acceptable. Newer treatments with ospemifene and vaginal lasers have now been introduced. The two main types of laser currently used for the treatment of GSM are the fractional microablative CO2 laser and the non-ablative photothermal erbium:YAG laser. We present a study protocol for a multicenter, prospective, non-inferiority, single-blinded, randomized controlled trial comparing the fractional microablative CO2 laser versus the photothermal non-ablative erbium:YAG laser for the management of GSM. We will recruit 88 postmenopausal women across two sites who will be randomized to one of the two laser groups. Participants will all have GSM symptoms and a Vaginal Health Index Score < 15. All participants will receive an active treatment. Each participant will receive three applications of vaginal laser 1 month apart and will be followed up at 1 month, 6 months, and 12 months. Our primary outcomes will look at all changes of GSM symptoms (dryness, dyspareunia, itching, burning, dysuria, frequency, urgency), urinary incontinence (if present), and overall sexual satisfaction. Both subjective and objective means will be used to assess participants. The findings of this trial have the potential to allow clinicians and women suffering from GSM to make an informed decision when opting for a specific laser type. The trial will add to the current growing body of evidence for the safe use of vaginal lasers in GSM as an alternative treatment. We hope this trial will provide robust and long-term data for the safe use of both lasers.

Therapeutic Drug Monitoring in Neonates: What Makes them Unique?

INTRODUCTION: Therapeutic drug monitoring (TDM) refers to the interpretation of quantified drug concentrations in strategically timed samples of bodily fluids, with the aim to maximize therapeutic benefit, while minimizing toxicity. In essence, TDM criteria for neonates are similar to those for adults, but specific issues should be considered. This review focusses on the relevance of these specific issues: larger variability in pharmacokinetics (PK), and non-PK related factors, sampling opportunities, analytical techniques, therapeutic range. Specific issues: Larger variability in PK, and non-PK related factors in neonates compared to adults result in a less clear relation between the administered dose and the concentration measured. Sophisticated dosing regimens derived from population PK-models can partly overcome this variability, thereby reducing the need for TDM. Dosing can be further individualized using Bayesian forecasting as a tool for TDM. Besides PK related factors, concentrations of endogenous substances (e.g. immunoglobulin A, plasma protein) in neonates differ from those in adults, which may complicate interpretation of measured drug concentrations. Blood sampling opportunities in neonates are limited by the small blood volume and the need to minimize painful procedures. Dried blood spot sampling may be less invasive. This method has been facilitated by more sensitive analytical techniques, such as chromatography followed by mass spectrometry. For the same reason, saliva is gaining attention as an alternative non-invasive bodily fluid. Lastly, reference values for therapeutic ranges of drugs in neonates are mostly adapted from adult studies, although pharmacodynamics may be quite different in neonates. This review concludes with recommendations for future research on these specific issues.

Remarkably Robust and Correlated Coherence and Antiferromagnetism in (Ce(1-x)La(x))Cu2Ge2.

We present magnetic susceptibility, resistivity, specific heat, and thermoelectric power measurements on (Ce(1-x)La(x))Cu2Ge2 single crystals (0≤x≤1). With La substitution, the antiferromagnetic temperature TN is suppressed in an almost linear fashion and moves below 0.36 K, the base temperature of our measurements for x>0.8. Surprisingly, in addition to robust antiferromagnetism, the system also shows low temperature coherent scattering below Tcoh up to ∼0.9 of La, indicating a small percolation limit ∼9% of Ce. Tcoh as a function of magnetic field was found to have different behavior for x<0.9 and x>0.9. Remarkably, (Tcoh)(2) at H=0 was found to be linearly proportional to TN. The jump in the magnetic specific heat δCm at TN as a function of TK/TN for (Ce(1-x)La(x))Cu2Ge2 follows the theoretical prediction based on the molecular field calculation for the S=1/2 resonant level model.

Nodal to nodeless superconducting energy-gap structure change concomitant with fermi-surface reconstruction in the heavy-fermion compound CeCoIn(5).

The London penetration depth λ(T) was measured in single crystals of Ce_{1-x}R_{x}CoIn_{5}, R=La, Nd, and Yb down to T_{min}≈50 mK (T_{c}/T_{min}∼50) using a tunnel-diode resonator. In the cleanest samples Δλ(T) is best described by the power law Δλ(T)∝T^{n}, with n∼1, consistent with the existence of line nodes in the superconducting gap. Substitutions of Ce with La, Nd, and Yb lead to similar monotonic suppressions of T_{c}; however, the effects on Δλ(T) differ. While La and Nd substitution leads to an increase in the exponent n and saturation at n∼2, as expected for a dirty nodal superconductor, Yb substitution leads to n>3, suggesting a change from nodal to nodeless superconductivity. This superconducting gap structure change happens in the same doping range where changes of the Fermi-surface topology were reported, implying that the nodal structure and Fermi-surface topology are closely linked.

C1 inhibitor concentrate treatment of multiple laryngeal attacks in a 53-year-old woman with hereditary angioedema.

This report describes a woman who experienced a high number of laryngeal hereditary angioedema (HAE) attacks during her participation in the IMPACT2 clinical trial of C1-INH concentrate. A 53-year-old caucasian female with a 31-year history of type 1 HAE experienced 16 laryngeal HAE attacks between 3 August 2006 and 23 February 2010, 15 of which were severe. All laryngeal attacks were successfully treated with C1-INH 20 U/kg, with a median onset of relief of 14 min and median time to complete resolution of symptoms of 20 h, and no need for redosing. The reliable success of C1-INH for these potentially fatal events is reassuring for both patients and prescribers.

Reconsolidation of a long-term spatial memory is impaired by cycloheximide when reactivated with a contextual latent learning trial in male and female rats.

Reconsolidation of long-term memory has become a topic of great interest in recent years, and has the potential to provide important information regarding memory processes and the treatment of memory-related disorders. The present study examined the role of systemic protein synthesis inhibition in reconsolidation of a long-term spatial memory reactivated by a contextual latent learning trial in male and female rats. Using the Morris water maze, we demonstrate that: 1) a contextual latent reactivation treatment enhances memory, 2) systemic protein synthesis inhibition selectively impairs test performance when administered in conjunction with a memory reactivation treatment, and 3) that these effects are more pronounced in female rats. These findings indicate a role for protein synthesis in the reconsolidation of a contextually reactivated long-term spatial memory using the water maze, and a potential differential effect of sex in this apparatus. The role of the strength of the memory trace is discussed and the relevance of these findings to theories of reconsolidation and therapeutic treatment of post-traumatic stress disorder is discussed.

The role of the intestine in the pathophysiology and management of severe acute pancreatitis.

BACKGROUND: The outcome of severe acute pancreatitis has scarcely improved in 10 years. Further impact will require new paradigms in pathophysiology and treatment. There is accumulating evidence to support the concept that the intestine has a key role in the pathophysiology of severe acute pancreatitis which goes beyond the notion of secondary pancreatic infection. Intestinal ischaemia and reperfusion and barrier failure are implicated in the development of multiple organ failure. DISCUSSION: Conventional management of severe acute pancreatitis has tended to ignore the intestine. More recent attempts to rectify this problem have included 1) resuscitation aimed at restoring intestinal blood flow through the use of appropriate fluids and splanchnic-sparing vasoconstrictors or inotropes; 2) enteral nutrition to help maintain the integrity of the intestinal barrier; 3) selective gut decontamination and prophylactic antibiotics to reduce bacterial translocation and secondary infection. Novel therapies are being developed to limit intestinal injury, and these include antioxidants and anti-cytokine agents. This paper focuses on the role of the intestine in the pathogenesis of severe acute pancreatitis and reviews the implications for management.

Alcohol/drug abuse, driving convictions, and risk-taking dispositions among trauma center patients.

The objective of this study was to evaluate the relationship between alcohol/drug abuse diagnoses, driving convictions (speeding, reckless driving, impaired driving, license violations), and risk-taking dispositions among a series of injured drivers admitted to a trauma center. The driving records of 778 patients were linked to diagnoses of psychoactive substance use disorders (PSUDs), admission blood alcohol concentration (BAC), mode of injury, and results of a risk-taking disposition survey. Twenty-nine percent of patients had one or more convictions in the 3 years before injury. Types of violation were not related to mode of injury. Although there was a positive association between prior impaired-driving convictions, current alcohol dependence, and a BAC + status, a consistent pattern relative to other violations, PSUDs, and BAC status was not apparent. Risk-taking disposition scale scores indicated that patients without PSUDs and without convictions tended toward less risk-taking behavior than patients with PSUDs and with convictions. The complex inter-relationships between PSUDs, risk-taking dispositions, and being convicted of driving dangerously require additional study so that intervention programs and injury prevention initiatives can be targeted effectively.

MK-801 induced retrieval, but not acquisition, deficits for passive avoidance conditioning.

Two experiments using a state-dependent retention (SDR) design determined whether MK-801 blocked the acquisition and retention of an avoidance response. In Experiments 1 and 2, rats were trained and tested 30 min after injections of either saline or MK-801 (0.05 and 0.10 mg/kg, respectively). Two minutes after training, subjects were immediately tested, and in both experiments, the avoidance response was acquired. The 24-h retention tests for Experiment 1 revealed that the data marginally supported a SDR interpretation. In Experiment 2, the dose of MK-801 was increased to 0.10 mg/kg, and the results showed that MK-801 rendered passive avoidance (PA) state-dependent. These experiments indicate that neither the 0.05 nor 0.10 mg/kg doses of MK-801 prevented acquisition of the avoidance response and that the latter dose rendered memory for PA training state-dependent. It is suggested that doses of MK-801 that did not impair PA learning can function as a cue state and influence expression of memory for PA.

Differential effects of glucose on modulation of emotional and nonemotional spatial memory tasks.

Research examining the memory-enhancing effects of glucose in humans has been limited to mnemonic tasks lacking affective components, even though glucose may be a mechanism for emotion-induced memory enhancement. This limitation does not permit analysis of interactions between the enhancing properties of emotional stimuli and glucose. Participants were administered either glucose or saccharin 15 min prior to completing a neutral or emotional spatial memory task. Performance under three glycemic conditions (100 mg/kg or 50 g glucose, or placebo) for the two sets of emotional stimuli revealed a significant interaction. Both 100-mg/kg and 50-g doses of glucose resulted in impaired performance for emotional stimuli. For neutral stimuli, a 100-mg/kg dose enhanced memory, whereas a 50-g dose showed no effect. Results indicate that the enhancing effects of emotional stimuli may be attenuated by the consumption of glucose and suggest that recent food consumption should be considered in paradigms examining memory.

Post-training glucose administration attenuates forgetting of passive-avoidance conditioning in 18-day-old rats.

The study of memory modulation in infant rats has typically focused on reminder/retrieval treatments involving reexposure to components of the internal or external training context. Rarely have studies employed pharmacological treatments to investigate the neurochemical substrates of memory storage in preweanling rats. The present study investigated the effect of 100 mg/kg of glucose, a common memory modulator in adult mammals, on memory for passive-avoidance conditioning in 18-day-old Sprague-Dawley rats. Subjects that were administered an immediate post-training injection of glucose performed significantly better, on a retention test 24 h following training, than those animals that received saline. The glucose group also performed comparably to a control group that was tested 10 min following training. These results are consistent with those of the memory modulation literature in adults and suggest that the rapid rate of forgetting in immature organisms may be the result of a deficiency in a general memory modulatory system.

Pretest administration of glucose attenuates infantile amnesia for passive avoidance conditioning in rats.

Infantile amnesia in rats may be attenuated by a wide variety of retrieval cues which reactivate memory for the training episode. The present study investigated the effects of glucose on memory retrieval in infant rats. In Experiment 1, 17-day-old preweanling rats were trained to criterion on passive avoidance conditioning. Twenty-four hours later, each subject received a subcutaneous injection of either saline, 100 mg/kg, or 250 mg/kg of glucose just prior to testing. Saline animals displayed poor retention scores, suggesting infantile amnesia; however, glucose significantly attenuated the 24-hr retention loss. Experiment 2 attempted to replicate the previous experiment, control for age and general drug effects, and extend the dose of glucose to 400 mg/kg. The results of Experiment 2 were consistent with Experiment 1 and also indicated that infant subjects performed significantly worse than adults. Both 100 and 250 mg/kg of glucose significantly attenuated infantile amnesia; however, 400 mg/kg had no effect. These results support a retrieval failure view of infantile amnesia and extend the memory-influencing properties of glucose to infants. Context and neuroendocrine views of memory retrieval are discussed.

Myositis ossificans traumatica of the masseter muscle: review of the literature and report of two additional cases.

Myositis ossificans traumatica of the masseter muscle is uncommon. The condition is benign and results in reactive heterotopic bone formation, usually producing limitation of opening of the jaws. Radiographic and microscopic examination can confirm the diagnosis. Treatment of myositis ossificans traumatica of the masseter muscle is surgical, with other modalities used when occurring in other muscles of the body.

Anterior rhinal cortex and amygdala: dissociation of their contributions to memory and food preference in rhesus monkeys.

Rhesus monkeys were trained on 2 versions of delayed nonmatching-to-sample, one with multiple pairs of objects and the other with a single pair, to evaluate their ability to remember objects. They then received either bilateral aspiration lesions of the anterior rhinal cortex or bilateral excitotoxic lesions of the amygdala, or were retained as unoperated controls. On re-presentation of the multiple-pair task, monkeys with anterior rhinal cortex lesions failed to show the improvement observed in both other groups in remembering the objects over delay intervals ranging from 10 to 60 s. Also, monkeys with anterior rhinal cortex lesions were impaired relative to the controls in relearning the single-pair version of the task. Conversely, on a formal test of food preference, monkeys with amygdala lesions showed abnormal patterns of food choice, whereas monkeys with anterior rhinal cortex lesions did not. Visual memory impairments formerly attributed to amygdala damage are probably due to the rhinal cortex damage associated with aspiration lesions of the amygdala.

Supplementary motor area seizures: propagation pathways as studied with invasive recordings.

We studied propagation of epileptic discharges in five patients with supplementary motor area (SMA) seizures with subdural grid electrodes implanted over the dorsolateral frontal neocortex and in the interhemispheric fissure. We found that both interictal and ictal epileptic discharges occurred synchronously in the SMA and the primary cortex. The actively involved electrodes were separated by silent electrodes. The time lag between the SMA and the primary motor cortex averaged 25 msec for interictal and 100 msec for ictal discharges. Cortical stimulations of the affected electrodes showed motor effects in corresponding body parts. All patients underwent resections of the EEG onset zone within the SMA while sparing the primary motor cortex and experienced a significant (>90%) reduction of seizure frequency. We conclude that epileptic activity is propagated between the SMA and the primary motor cortex by a somatotopically organized monosynaptic pathway.