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.

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.

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.

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.

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.

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.

Low-noise parametric frequency comb for continuous C-plus-L-band 16-QAM channels generation.

A low phase noise frequency comb generated from a continuous-wave seed is experimentally demonstrated across continuous C- and L-bands. Parametrically generated carriers with optical signal-to-noise ratio in excess of 45 dB were used to generate 16-ary quadrature amplitude modulated signals. We characterize 20 GBaud channels' performance that was varied by only 1.7 dB across the combined C/L band.

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.

Genomic, genetic and functional dissection of bitter taste responses to artificial sweeteners.

Bitter taste perception is initiated by TAS2R receptors, which respond to agonists by triggering depolarization of taste bud cells. Mutations in TAS2Rs are known to affect taste phenotypes by altering receptor function. Evidence that TAS2Rs overlap in ligand specificity suggests that they may also contribute joint effects. To explore this aspect of gustation, we examined bitter perception of saccharin and acesulfame K, widely used artificial sweeteners with aversive aftertastes. Both substances are agonists of TAS2R31 and -43, which belong to a five-member subfamily (TAS2R30-46) responsive to a diverse constellation of compounds. We analyzed sequence variation and linkage structure in the ∼140 kb genomic region encoding TAS2R30-46, taste responses to the two sweeteners in subjects, and functional characteristics of receptor alleles. Whole-gene sequences from TAS2R30-46 in 60 Caucasian subjects revealed extensive diversity including 34 missense mutations, two nonsense mutations and high-frequency copy-number variants. Thirty markers, including non-synonymous variants in all five genes, were associated (P< 0.001) with responses to saccharin and acesulfame K. However, linkage disequilibrium (LD) in the region was high (D', r(2) > 0.95). Haplotype analyses revealed that most associations were spurious, arising from LD with variants in TAS2R31. In vitro assays confirmed the functional importance of four TAS2R31 mutations, which had independent effects on receptor response. The existence of high LD spanning functionally distinct TAS2R loci predicts that bitter taste responses to many compounds will be strongly correlated even when they are mediated by different genes. Integrative approaches combining phenotypic, genetic and functional analysis will be essential in dissecting these complex relationships.

Phase-preserving parametric wavelength conversion to SWIR band in highly nonlinear dispersion stabilized fiber.

The first successful translation of a phase modulated optical signal over 80 THz, from the near infrared to the short-wave infrared (SWIR) band is demonstrated. A signal, phase-modulated at 10 Gbps, was received in an error-free manner in the SWIR(1.7-2.2 µm) band. A new class of highly nonlinear fiber with reduced dispersion fluctuation was utilized as the platform for this phase-preserving distant parametric conversion.

Noise performance of phase-insensitive frequency multicasting in parametric mixer with finite dispersion.

Noise performance of dual-pump, multi-sideband parametric mixer operated in phase-insensitive mode is investigated theoretically and experimentally. It is shown that, in case when a large number of multicasting idlers are generated, the noise performance is strictly dictated by the dispersion characteristics of the mixer. We find that the sideband noise performance is significantly degraded in anomalous dispersion region permitting nonlinear noise amplification. In contrast, in normal dispersion region, the noise performance converges to the level of four-sideband parametric process, rather than deteriorates with increased sideband creation. Low noise generation mandates precise dispersion-induced phase mismatch among pump and sideband waves in order to control the noise coupling. We measure the noise performance improvement for a many-sideband, multi-stage mixer by incorporating new design technique.

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 up most 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 up most 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 care for these patients.Key words: communication, sickle cell disease (SCD), sickle cell anemia (SCA), blood inherited disorder, sickle cell trait, crisis, African Americans, deoxygenation, hemoglobin,supporting dentist, prophylactic antibiotics, and infection.

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.

Continuous-wave, short-wavelength infrared mixer using dispersion-stabilized highly-nonlinear fiber.

A new type of highly nonlinear fiber (HNLF) was designed and fabricated. The new HNLF was engineered to reduce dispersion shift due to transverse fluctuations while maintaining the modal confinement superior to that of the conventional fibers. The new design strategy was validated by the measurements of the global and local dispersive characteristics under considerable core and index profile deformation induced by tensile stress, which indicated that the dispersive and phase matching characteristics of the fiber did not change even under the highest tensile stress. The characteristics effectively decoupled tension-based Brillouin suppression from phase-matching impairments in parametric mixers for the first time. The new HNLF was used to demonstrate the first coherence-preserving mixer operating in the short-wavelength infrared (SWIR) band. The SWIR mixer was driven by continuous-wave near-infrared (NIR) pump and did not require pump phase dithering to suppress Brillouin scattering.

Highly nonlinear fiber with dispersive characteristic invariant to fabrication fluctuations.

New class of highly nonlinear fibers possessing dispersive characteristics invariant to transverse geometry fluctuations is described. The sensitivity to stochastic core fluctuations is reduced by order of magnitude while maintaining the fiber nonlinear coefficient. The effectiveness of the new highly nonlinear fiber type is demonstrated on stochastically perturbed distant-band mixer that could not be previously constructed with high-confinement fiber. The new fiber design offers a unique platform for ideally phase matched parametric exchange with significantly increased Brillouin threshold.

Generation of wideband frequency combs by continuous-wave seeding of multistage mixers with synthesized dispersion.

We numerically and experimentally demonstrate efficient generation of an equalized optical comb with 150-nm bandwidth. The comb was generated by low-power, continuous-wave seeds, eliminating the need for pulsed laser sources. The new architecture relies on efficient creation of higher-order mixing tones in phase-matched nonlinear fiber stages separated by a linear compressor. Wideband generation was enabled by precise dispersion engineering of multiple-stage parametric mixers.

Spectral linewidth preservation in parametric frequency combs seeded by dual pumps.

We demonstrate new technique for generation of programmable-pitch, wideband frequency combs with low phase noise. The comb generation was achieved using cavity-less, multistage mixer driven by two tunable continuous-wave pump seeds. The approach relies on phase-correlated continuous-wave pumps in order to cancel spectral linewidth broadening inherent to parametric comb generation. Parametric combs with over 200-nm bandwidth were obtained and characterized with respect to phase noise scaling to demonstrate linewidth preservation over 100 generated tones.