Nodal-paranodal antibodies in HIV-immune mediated radiculo-neuropathies: Clinical phenotypes and relevance.

BACKGROUND: The frequency of nodal-paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described. METHODS: HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for immunoglobulin G (IgG) antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein(Caspr1)) cell adhesion molecules, using a live, cell-based assay. To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury. RESULTS: Twenty-four HIV-infected patients with IMRN were included in the study, 15 with chronic inflammatory demyelinating polyneuropathy (CIDP), 4 with ventral root radiculopathies (VRR), and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination (CCPD). Three patients (12.7%) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive, and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis, respectively. CONCLUSION: The frequency of nodal-paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.

Community-Acquired Pseudomonas aeruginosa Meningitis in a Pediatric Patient.

This case report presents a rare and significant case of community-acquired Pseudomonas aeruginosa meningitis in a healthy 13-month-old male patient in rural Liberia. Pseudomonas aeruginosa meningitis, particularly in the absence of predisposing factors, is a rare occurrence with a high mortality rate. The challenges in diagnosing this condition, especially in resource-limited settings, are highlighted. The patient initially presented with fever, seizures, and altered consciousness, and lumbar puncture revealed turbid cerebrospinal fluid (CSF) with elevated white blood cell count. Subsequent CSF culture confirmed Pseudomonas aeruginosa infection. Prompt initiation of appropriate antibiotic therapy, including a push dose of meropenem, resulted in clinical improvement. However, the patient exhibited post-meningitis sequelae, including hearing and visual impairments. Comprehensive follow-up care and rehabilitation services are crucial for managing these long-term complications. By sharing this case, we aim to increase awareness and facilitate early recognition of Pseudomonas aeruginosa meningitis, leading to improved patient care and outcomes in similar clinical scenarios.

Post-trauma behavioral phenotype predicts the degree of vulnerability to fear relapse after extinction in male rats.

Current treatments for trauma-related disorders remain ineffective for many patients.1,2 Fear extinction deficiency is a prominent feature of these diseases,3 and many behavioral treatments rely on extinction training.4,5 However, in many patients, therapy is followed by a relapse of symptoms, and the underpinnings of such interindividual variations in vulnerability to relapse remain unknown.6-8 Here, we modeled interindividual differences in post-therapy fear relapse with an ethologically relevant trauma recovery paradigm. After fear conditioning, male rats underwent fear extinction while foraging in a large enriched arena, permitting the expression of a wide spectrum of behaviors. An automated multidimensional behavioral assessment revealed that post-conditioning fear response profiles clustered into two groups: some animals expressed fear by freezing more, whereas others darted more, as if fleeing from danger. Remarkably, the tendency of an animal to dart or to freeze after CS presentation during the first extinction session was, respectively, associated with stronger or weaker fear renewal. Moreover, genome-wide transcriptional profiling revealed that these groups differentially regulated specific sets of genes, some of which were previously implicated in anxiety and trauma-related disorders. Our results suggest that post-trauma behavioral phenotypes and the associated gene expression landscapes can serve as markers of fear relapse susceptibility and thus may be instrumental for future development of more effective treatments for psychiatric patients.

Systematic notes on Sinacroneuria Yang amp; Yang, 1995 (Plecoptera: Perlidae), with descriptions of two new species from China.

Two previously unrecognized species of Sinacroneuria Yang Yang, 1995 are formally described from Chinese specimens collected in Fujian Province. In addition, S. orientalis Yang Yang, 1995 type of the genus, is a synonym of Kamimuria flavata Navás, 1933, however K. flavata is a secondary homonym of Perla (Kamimuria) flavata Navás, 1924 and is invalid. A checklist of valid Sinacroneuria species is provided.

The Plecoptera of Panama. II. Two new species, one new country record, and additional locality records of Anacroneuria (Perlidae) from western Panama.

Two new species of Anacroneuria (A. chiriqui sp. n. and A. ngabe sp. n.) are described from Chiriqui Province, Panama, and compared with related species. One new country record, A. divisa (Navás), is herein recorded and new locality records are presented for several species previously reported from Panama. Three unassociated females, including one species from Bocas del Toro province are described under informal designations. There are now 25 described species of Plecoptera known from Panama.

Ultra-broadband multimode 3dB optical power splitter using an adiabatic coupler and a Y-branch.

As an essential component of mode division multiplexing (MDM) system, a multimode 3dB power splitter with low loss, high power balance, and low mode crosstalk is highly desired. In this paper, we propose an ultra-broadband on-chip multimode 3dB optical power splitter using an adiabatic coupler and an S-bend based Y-branch. As an example, a splitter for the four-lowest modes of a rib waveguide on silicon on insulator (SOI) platform is designed. Simulation results show that the device exhibits < 0.12dB insertion losses, within ± 0.38dB power imbalances, and < -18.5dB mode crosstalks for the four-lowest modes within a large operating wavelength range of 165 nm (from 1400 nm to 1565 nm). The fabrication tolerance of gap size at the output end of the adiabatic coupler is also analyzed.

Channel cloning by multi-mode phase-sensitive parametric mixer.

We investigate high fidelity channel replication approaching the idealized notion of channel cloning with negligible excess noise and distortion. Previously proposed cloning architectures require that the channel carriers to be externally seeded, limiting their ultimate usefulness, whereas the self-seeded approach limits the channel number and signal-to-noise ratio. Specifically, when a single channel is replicated, the noise figure (NF) remains above the well-known 3-dB limit, and multi-channel replication by a dual-pump driven parametric mixer faces a theoretical NF limit of 6-dB. On the other hand, large-channel-count cloning is of particular importance as it allows for rate scaling in generalized signal processing. Recognizing the limits of conventional architectures that rest on homogeneous parametric mixers, we here propose multi-stage, dispersion-managed parametric mixers in multi-mode phase-sensitive architecture to clone the input signal to a substantial number of channels. In particular, when the new mixer is operated in four-mode phase-sensitive architecture, a 17-copy-count channel cloning with maximum NF less than 6-dB and a record-low NF of 2-dB was experimentally implemented and demonstrated in this paper.

Octave-spanning coherent supercontinuum generation in silicon on insulator from 1.06 µm to beyond 2.4 µm.

Efficient complementary metal-oxide semiconductor-based nonlinear optical devices in the near-infrared are in strong demand. Due to two-photon absorption in silicon, however, much nonlinear research is shifting towards unconventional photonics platforms. In this work, we demonstrate the generation of an octave-spanning coherent supercontinuum in a silicon waveguide covering the spectral region from the near- to shortwave-infrared. With input pulses of 18 pJ in energy, the generated signal spans the wavelength range from the edge of the silicon transmission window, approximately 1.06 to beyond 2.4 µm, with a -20 dB bandwidth covering 1.124-2.4 µm. An octave-spanning supercontinuum was also observed at the energy levels as low as 4 pJ (-35 dB bandwidth). We also measured the coherence over an octave, obtaining , in good agreement with the simulations. In addition, we demonstrate optimization of the third-order dispersion of the waveguide to strengthen the dispersive wave and discuss the advantage of having a soliton at the long wavelength edge of an octave-spanning signal for nonlinear applications. This research paves the way for applications, such as chip-scale precision spectroscopy, optical coherence tomography, optical frequency metrology, frequency synthesis and wide-band wavelength division multiplexing in the telecom window.

Clozapine counteracts a ketamine-induced depression of hippocampal-prefrontal neuroplasticity and alters signaling pathway phosphorylation.

Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be modeled with alterations in neuroplasticity, we examined the impact of acutely-administered ketamine and clozapine on in vivo long-term potentiation (LTP) in the rat's hippocampus-to-prefrontal cortex (H-PFC) pathway. We found that a low dose of ketamine depressed H-PFC LTP, whereas animals that were co-administrated the two drugs displayed LTP that was similar to a saline-treated control. To address which signaling molecules might mediate such effects, we also examined phosphorylation and total protein levels of GSK3ß, GluA1, TrkB, ERK, and mTOR in prefrontal and hippocampal sub-regions. Among the statistically significant effects that were detected (a) both ketamine and clozapine increased the phosphorylation of Ser9-GSK3ß throughout the prefrontal cortex and of Ser2481-mTOR in the dorsal hippocampus (DH), (b) clozapine increased the phosphorylation of Ser831-GluA1 throughout the prefrontal cortex and of Ser845-GluA1 in the ventral hippocampus, (c) ketamine treatment increased the phosphorylation of Thr202/Tyr204-ERK in the medial PFC (mPFC), and (d) clozapine treatment was associated with decreases in the phosphorylation of Tyr705-TrkB in the DH and of Try816-TrkB in the mPFC. Further analyses involving phosphorylation effect sizes also suggested Ser831-GluA1 in the PFC displayed the highest degree of clozapine-responsivity relative to ketamine. These results provide evidence for how ketamine and clozapine treatments affect neuroplasticity and signaling pathways in the stress-sensitive H-PFC network. They also demonstrate the potential relevance of H-PFC pathway neuroplasticity for modeling ketamine-clozapine interactions in regards to psychosis.

In Vivo Sarcomere Length Measurement in Whole Muscles during Passive Stretch and Twitch Contractions.

Muscle force is dictated by micrometer-scale contractile machines called sarcomeres. Whole-muscle force drops from peak force production to zero with just a few micrometers of sarcomere length change. No current technology is able to capture adequate dynamic sarcomere data in vivo, and thus we lack fundamental data needed to understand human movement and movement disorders. Methods such as diffraction, endoscopy, and optical coherence tomography have been applied to muscle but are prohibitively invasive, sensitive to motion artifact, and/or imprecise. Here, we report dynamic sarcomere length measurement in vivo using a combination of our recently validated resonant reflection spectroscopy method combined with optical frequency domain interferometry. Using a 250-µm-wide fiber optic probe, we captured nanometer sarcomere length changes from thousands of sarcomeres on the sub-millisecond timescale during whole-muscle stretch and twitch contraction. We believe that this demonstrates the first large-scale sensing of sarcomere dynamics in vivo, which is a necessary first step to understand movement disorders and to create patient-specific surgical interventions and rehabilitation.

Defining the brain circuits involved in psychiatric disorders: IMI-NEWMEDS.

Despite the vast amount of research on schizophrenia and depression in the past two decades, there have been few innovative drugs to treat these disorders. Precompetitive research collaborations between companies and academic groups can help tackle this innovation deficit, as illustrated by the achievements of the IMI-NEWMEDS consortium.

Rats can acquire conditional fear of faint light leaking through the acrylic resin used to mount fiber optic cannulas.

Rodents are exquisitely sensitive to light and optogenetic behavioral experiments routinely introduce light-delivery materials into experimental situations, which raises the possibility that light could leak and influence behavioral performance. We examined whether rats respond to a faint diffusion of light, termed caplight, which emanated through the translucent dental acrylic resin used to affix deep-brain optical cannulas in place. Although rats did not display significant changes in locomotion or rearing to caplight in a darkened open field, they did acquire conditional fear via caplight-footshock pairings. These findings highlight the potential confounding influence of extraneous light emanating from light-delivery materials during optogenetic analyses.

Wireless inertial measurement of head kinematics in freely-moving rats.

While miniature inertial sensors offer a promising means for precisely detecting, quantifying and classifying animal behaviors, versatile inertial sensing devices adapted for small, freely-moving laboratory animals are still lacking. We developed a standalone and cost-effective platform for performing high-rate wireless inertial measurements of head movements in rats. Our system is designed to enable real-time bidirectional communication between the headborne inertial sensing device and third party systems, which can be used for precise data timestamping and low-latency motion-triggered applications. We illustrate the usefulness of our system in diverse experimental situations. We show that our system can be used for precisely quantifying motor responses evoked by external stimuli, for characterizing head kinematics during normal behavior and for monitoring head posture under normal and pathological conditions obtained using unilateral vestibular lesions. We also introduce and validate a novel method for automatically quantifying behavioral freezing during Pavlovian fear conditioning experiments, which offers superior performance in terms of precision, temporal resolution and efficiency. Thus, this system precisely acquires movement information in freely-moving animals, and can enable objective and quantitative behavioral scoring methods in a wide variety of experimental situations.

Dynamic Regulation of AMPAR Phosphorylation In Vivo Following Acute Behavioral Stress.

The tuning of glutamatergic transmission is an essential mechanism for neuronal communication. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are ionotropic glutamate receptors that mediate fast synaptic transmission. The phosphorylation states of specific serine residues on the GluA1 and GluA2 AMPAR subunits are considered critical post-translational modifications that regulate AMPAR activity and subcellular trafficking. While behavioral stress, via stress hormones, exerts specific alterations on such glutamatergic processes, there have been conflicting data concerning the influence of stress on AMPAR phosphorylation in different brain regions, and the post-stress signaling mechanisms mediating these processes are not well delineated. Here, we examined the dynamics of phosphorylation at three AMPAR serine residues (ser831-GluA1, ser845-GluA1, and ser880-GluA2) in four brain regions [amygdala, medial prefrontal cortex (mPFC), dorsal hippocampus, and ventral hippocampus] of the rat during the hour following behavioral stress. We also tested the impact of post-stress corticosteroid receptor blockade on AMPAR phosphorylation. Both GluA1 subunit residues exhibited elevated phosphorylation after stress, yet post-stress administration of corticosteroid receptor antagonists curtailed these effects only at ser831-GluA1. In contrast, ser880-GluA2 displayed a time-dependent tendency for early decreased phosphorylation (that was selectively augmented by mifepristone treatment in the amygdala and mPFC of stressed animals) followed by increased phosphorylation later on. These findings show that the in vivo regulation of AMPAR phosphorylation after stress is a dynamic and subunit-specific process, and they provide support for the hypothesis that corticosteroid receptors have an ongoing role in the regulation of ser831-GluA1 phosphorylation during the post-stress interval.

Salivary cortisol in early psychosis: New findings and meta-analysis.

BACKGROUND: Schizophrenia is a multifactorial disorder and environmental risk factors for it might contribute to hypothalamo-pituitary-adrenal axis (HPA) dysregulation. While increased cortisol levels have been reported in schizophrenia, as well as in early psychosis (compared to healthy controls), a crucial unresolved issue is whether elevated cortisol levels could be related to the distress of an emerging illness, rather than being specific to psychosis. Here, we report new findings from the first French cohort of young help-seekers (ICAAR) including ultra-high risk subjects (UHR), first-episode of psychosis (FEP) and non at-risk help seekers controls (HSC), followed by a meta-analysis of all available reports on salivary basal cortisol levels in early psychosis (UHR and FEP). METHODS: In the ICAAR study, 169 individuals (15-30 years old) had their basal cortisol levels sampled and they were categorized (at baseline) as either UHR, FEP, or HSC using the criteria of the Comprehensive Assessment of At-Risk Mental States (CAARMS). The three groups were compared at baseline, and the UHR and HSC individuals were also included in a one-year longitudinal follow-up. UHRs who converted to psychosis at the follow up (UHR-P) were compared to non-converters (UHR-NP). We also performed a meta-analysis from case-control studies with basal salivary measures of cortisol, drawing from a systematic bibliographic search using the keywords 'cortisol', 'glucocorticoid', 'HPA' with 'UHR', 'CHR', 'at-risk mental state', 'schizotypal ', 'prodromal schizophrenia', 'first-episode psychosis', 'first episode schizophrenia', 'newly diagnosed schizophrenia', 'recent onset schizophrenia' [in Medline, Web of Knowledge (WOS), EBSCO], followed by a systematic screening of the resulting articles. RESULTS: Basal cortisol levels were not significantly different between UHR, FEP, and HSC controls in the ICAAR cohort. Interestingly, initial cortisol levels were correlated with positive symptoms at the one year follow-up in the ICAAR cohort. The meta-analysis revealed a significant elevation of the salivary basal cortisol levels in UHR individuals compared to controls (8 studies--1060 individuals), but not between FEP and controls (6 studies--441 individuals). Indirect comparison of salivary basal cortisol levels between UHR and FEP did not yield significant differences. Finally, no differences were detected between the baseline cortisol of UHR-P and UHR-NP (4 studies--301 individuals). CONCLUSION: The meta-analysis (including new data) indicates that basal cortisol levels were increased in UHR compared to controls, but FEP levels were not different from UHR or controls. Many confounding factors could decrease the effect size in FEP especially medication intake. Taken together with our new results (which made use of help-seeker controls, and not merely healthy controls), the findings indicate that basal cortisol levels may not be a reliable biomarker for early psychosis. Further studies are needed to clarify the precise role of the HPA axis in psychotic conversion.

All optical wavelength multicaster and regenerator based on four-mode phase-sensitive parametric mixer.

Four-mode phase-sensitive (4MPS) process has been employed in a parametric mixer based wavelength multicaster, enhancing the multicasting conversion efficiency and signal-to-noise ratio. In addition, the 4MPS parametric multicaster is an outstanding candidate for all-optical regeneration, owing to its inherent capabilities to clamp amplitude fluctuations by the saturated parametric effect and to squeeze phase distortions by the phase sensitive process. The investigation in this paper focuses on the 4MPS multicaster operated in the saturation gain regime, including theoretical simulations and experimental demonstrations on amplitude and phase noise regeneration over 20 multicasting signal copies.

The impact of visiting student electives on surgical Match outcomes.

BACKGROUND: Residency applicants commonly complete visiting student electives (VSEs) hoping to increase their odds of matching at host institutions. Existing evidence on Match outcomes for applicants who complete VSEs is limited. As VSEs involve monetary and opportunity costs to students and administrators, data on their utility are vital for student well-being, preparedness for residency, and, ultimately, success in the Match. We investigated the utilization and impact of VSEs for all applicants. We hypothesized that completion of VSEs would increase the likelihood of matching at a host institution. MATERIALS AND METHODS: A retrospective review was conducted of academic records and National Resident Matching Program outcomes for the graduates of one institution and visiting students to that institution over the course of 7 y. RESULTS: Utilization of VSEs varied significantly among specialties. Across all specialties and in general surgery, applicants were more likely to match into host programs than others. The size of the effect of VSEs on outcomes varied by specialty. Host programs were applicants' top choice for residency in 48% of cases. CONCLUSIONS: Completion of VSEs may give surgical applicants increased control over Match outcomes. Our findings may assist future students in strategic decision making when determining whether and where to use VSEs.

The Banded-wing Moselia infuscata (Claassen) Phenotype from California and Oregon, U.S.A. (Plecoptera: Leuctridae).

Moselia specimens from California and Oregon with a banded-wing phenotype were found to be indistinguishable morphologically from those of M. infuscata (Claassen) with typical wing pigment pattern. Preliminary DNA barcode data (Cytochrome c Oxidase subunit I [COI]), however, show significant genetic variation among four populations including three from northern California sites and one from southern Oregon. Although this genetic variation exceeded standard divergence thresholds often used to recognize distinct stream insect species, no new taxa are proposed at this time due to the preliminary nature of the data. 

Digital multi-channel stabilization of four-mode phase-sensitive parametric multicasting.

Stable four-mode phase-sensitive (4MPS) process was investigated as a means to enhance two-pump driven parametric multicasting conversion efficiency (CE) and signal to noise ratio (SNR). Instability of multi-beam, phase sensitive (PS) device that inherently behaves as an interferometer, with output subject to ambient induced fluctuations, was addressed theoretically and experimentally. A new stabilization technique that controls phases of three input waves of the 4MPS multicaster and maximizes CE was developed and described. Stabilization relies on digital phase-locked loop (DPLL) specifically was developed to control pump phases to guarantee stable 4MPS operation that is independent of environmental fluctuations. The technique also controls a single (signal) input phase to optimize the PS-induced improvement of the CE and SNR. The new, continuous-operation DPLL has allowed for fully stabilized PS parametric broadband multicasting, demonstrating CE improvement over 20 signal copies in excess of 10 dB.

What dentists should know about sickle cell disease.

The medical history should be a communication between the patient and the dentist. A good history will reveal a patient's medical problems, concerns, ideas, and expectations. Understanding medical conditions on a patient's medical history is of upmost importance in providing the patient with the best possible standard of care. Sickle cell disease is an inherited blood disorder that affects red blood cells. Normal red blood cells contain hemoglobin A. People with sickle cell disease have red blood cells containing mostly hemoglobin S, an abnormal type of hemoglobin. These mutated sickle cells do not have the smooth motion needed for oxygenation and deoxygenation. One of the main concerns in sickle cell disease is the reversible extreme pain episodes called "sickle cell crisis." Pain episodes occur when sickle cells clog small vessels, depriving the body of adequate blood and oxygen. Treatment of the sickle cell patient should be a team approach between dentist, patient, and physician, Dental treatments should be conservative and stress free for the patient. Prevention of dental disease and infections are of the upmost importance to the sickle cell patient. If your patient has sickle cell disease, know about it and talk to your patient about the disease. Maintaining excellent oral health to decrease the possibility of oral infections will ensure the best core for these patients.