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Myelin is a natural and dynamic multilamellar membrane structure that continues to be of significant biological and neurological interest, especially with respect to its biosynthesis and assembly during its normal formation, maintenance, and pathological breakdown. To explore the usefulness of neutron diffraction in the structural analysis of myelin, we investigated the use of in vivo labeling by metabolically incorporating non-toxic levels of deuterium (2H; D) via drinking water into a pregnant dam (D-dam) and her developing embryos. All of the mice were sacrificed when the pups (D-pups) were 55 days old. Myelinated sciatic nerves were dissected, fixed in glutaraldehyde and examined by neutron diffraction. Parallel samples that were unfixed (trigeminal nerves) were frozen for mass spectrometry (MS). The diffraction patterns of the nerves from deuterium-fed mice (D-mice) vs. the controls (H-mice) had major differences in the intensities of the Bragg peaks but no appreciable differences in myelin periodicity. Neutron scattering density profiles showed an appreciable increase in density at the center of the lipid-rich membrane bilayer. This increase was greater in D-pups than in D-dam, and its localization was consistent with deuteration of lipid hydrocarbon, which predominates over transmembrane protein in myelin. MS analysis of the lipids isolated from the trigeminal nerves demonstrated that in the pups the percentage of lipids that had one or more deuterium atoms was uniformly high across lipid species (97.6% ​± ​2.0%), whereas in the mother the lipids were substantially less deuterated (60.6% ​± ​26.4%) with levels varying among lipid species and subspecies. The mass distribution pattern of deuterium-containing isotopologues indicated the fraction (in %) of each lipid (sub-)species having one or more deuteriums incorporated: in the D-pups, the pattern was always bell-shaped, and the average number of D atoms ranged from a low of ∼4 in fatty acid to a high of ∼9 in cerebroside. By contrast, in D-dam most lipids had more complex, overlapping distributions that were weighted toward a lower average number of deuteriums, which ranged from a low of ∼3–4 in fatty acid and in one species of sulfatide to a high of 6–7 in cerebroside and sphingomyelin. The consistently high level of deuteration in D-pups can be attributed to their de novo lipogenesis during gestation and rapid, postnatal myelination. The widely varying levels of deuteration in D-dam, by contrast, likely depends on the relative metabolic stability of the particular lipid species during myelin maintenance. Our current findings demonstrate that stably-incorporated D label can be detected and localized using neutron diffraction in a complex tissue such as myelin; and moreover, that MS can be used to screen a broad range of deuterated lipid species to monitor differential rates of lipid turnover. In addition to helping to develop a comprehensive understanding of the de novo synthesis and turnover of specific lipids in normal and abnormal myelin, our results also suggest application to studies on myelin proteins (which constitute only 20–30% by dry mass of the myelin, vs. 70–80% for lipid), as well as more broadly to the molecular constituents of other biological tissues.

Transdifferentiation of Schwann cells is essential for functional peripheral nerve regeneration after injury. By activating a repair program, Schwann cells promote functional axonal regeneration and remyelination. However, chronic denervation, aging, metabolic diseases, or chronic inflammatory processes reduce the transdifferentiation capacity and thus diminish peripheral nerve repair. It was recently described that the sphingosine-1-phosphate receptor (S1PR) agonist Fingolimod enhances the Schwann cell repair phenotype by activation of dedifferentiation markers and concomitant release of trophic factors resulting in enhanced neurite growth. Since Fingolimod targets four out of five S1PRs (S1P1, S1P3-5) possibly leading to non-specific adverse effects, identification of the main receptor(s) responsible for the observed phenotypic changes is mandatory for future specific treatment approaches. Our experiments revealed that S1P3 dominates and that along with S1P1 acts as the responsible receptor for Schwann cell transdifferentiation as revealed by the combinatory application of specific agonists and antagonists. Targeting both receptors reduced the expression of myelin-associated genes, increased PDGF-BB representing enhanced trophic factor expression likely to result from c-Jun induction. Furthermore, we demonstrated that S1P4 and S1P5 play only a minor role in the adaptation of the repair phenotype. In conclusion, modulation of S1P1 and S1P3 could be effective to enhance the Schwann cell repair phenotype and thus stimulate proper nerve repair. [ABSTRACT FROM AUTHOR]

In December 2019, the novel coronavirus disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection broke. With the gradual deepening understanding of SARS-CoV-2 and COVID-19, researchers and clinicians noticed that this disease is closely related to the nervous system and has complex effects on the central nervous system (CNS) and peripheral nervous system (PNS). In this review, we summarize the effects and mechanisms of SARS-CoV-2 on the nervous system, including the pathways of invasion, direct and indirect effects, and associated neuropsychiatric diseases, to deepen our knowledge and understanding of the relationship between COVID-19 and the nervous system. • About 1/3 of people with COVID-19 will show some kind of neurological symptoms. • These symptoms will be produced through direct infection and indirect effects. • These effects will relate to almost all common types of nervous system disease. [ABSTRACT FROM AUTHOR]

Secure quantum key distribution (QKD) promises a revolutionizing in optical applications such as encryption, and imaging. However, their implementation in real-world scenarios continues to be challenged. The goal of this work is to verify the presence of photon number splitting (PNS) attack in quantum cryptography system based on BB84 protocol and to obtain a maximum secure key length as possible. This was realized through randomly interleaving decoy states with mean photon numbers of 5.38, 1.588, and 0.48 between the signal states with mean photon numbers of 2.69, 0.794, and 0.24. Experiment results show that a maximum secure key length obtained from our system, which ignores eavesdropping cases, is 125 with 20% decoy states and 82 with 50% decoy states for mean photon number of 0.794 for signal states and 1.588 for decoy states. [ABSTRACT FROM AUTHOR]

Computed tomography is one of the medical imaging tests in diagnosis. Multiple images of the inside of the body get captured in CT, like in traditional x-ray, but in various planes, can reformat the generated images. In CT, more excellent images are captured than in x-rays, especially for soft tissue and blood vessels. Four pairs of sinuses are there in the body, and small openings connect each to the nasal cavity. Out of the four sinuses, the paranasal sinus, a hollow and air-filled space, is located within the bones of the face. A vital role is played by Computed Tomography (CT) in the study of Paranasal Sinuses to diagnose and determine the various diseases related to paranasal sinuses. For example, multiple conditions like inflammatory, malignant neoplastic, and benign affect the paranasal sinus; all these conditions are diagnosed by CT Scans which directly help reduce the mortality and morbidity in patients suffering from diseases that affect the paranasal sinus. Besides this, CT Scans of paranasal sinus before functional endoscopic sinus surgery also help evaluate paranasal sinus disease and many more. The article aims to study the pathologies for which paranasal sinuses are affected and CT features of paranasal sinus diseases. Paranasal sinus computed tomography scans are performed for the measurements of - the volume of the nasal cavity. CT scan is also essential in evaluating anatomical variations to prove the correlation between the extent of disease and disease process in Sinonasal polyposis patients. Also, because of CT, paranasal sinus anatomy is delineated. This is the overview of the role of CT in paranasal sinus study (diagnostic, anatomical). [ABSTRACT FROM AUTHOR]

In this study, novel Panax notoginseng saponins (PNS)-loaded nanoparticles coated with the Trimethyl chitosan (TMC) derivatives TMC-VB 12 and TMC-Cys (PPTT-NPs) were developed to improve the oral absorption of the constituents. PPTT-NPs were prepared by the double emulsion method and showed different encapsulation effects on the major components, including Rg1, Rb1, and R1, in PNS. In vivo, the absorption rate constant and apparent absorption coefficient of PPTT-NPs were higher than PNS solution. These findings preliminarily proved that PPTT-NPs can promote intestinal absorption to a certain extent. The pharmacokinetic results indicated that the blood concentration and the area under the curve of Rg1 and Rb1 in the PPTT-NPs were higher than Xueshuantong capsules. The cell viability of PPTT-NPs was above 90% within 25-150 μg/mL. PPTT-NPs promoted the cellular uptake of PNS by receptor-mediated endocytosis. In summary, NPs coated with TMC-VB 12 and TMC-Cys can be used as promising drug delivery systems. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses the innate immune response in the host, reducing and delaying neutralizing antibody production against PRRSV infection and promoting viral infection. Here, we aimed to assess the potential of Panax notoginseng saponins (PNS) for improving the immune response exerted upon PRRSV-2-modified live virus (MLV) vaccine administration. Thirty piglets were randomly divided into six groups. Group 1 piglets were injected with medium 0 days post vaccination (dpv). Group 2 piglets were fed PNS 0–28 dpv. Group 3 and group 4 piglets were administered the JXA1-R vaccine 0 dpv. Group 4 piglets were also fed PNS 0–28 dpv. Group 1–4 piglets were challenged intranasally with the PRRSV JXA1 strain 28 dpv. Group 5 piglets were fed with PNS without challenge. Group 6 piglets served as controls. During the experiment, the samples were collected regularly for 49 days. Compared with group 1 piglets, group 3 piglets showed significantly reduced viremia and clinical scores, and significantly increased average daily gain (ADWG). Compared with group 3 piglets, group 4 piglets showed significantly improved neutralizing antibody titers, IFN-α and IFN-β mRNA expression, and significantly decreased viremia and viral load in the lungs and lymph nodes, but did not demonstrate any further improvement in PRRSV-specific antibody titer, rectal temperature, ADWG, or clinical scores. PNS upregulates neutralizing antibodies against PRRSV-2 and enhances the expression of IFN-α and IFN-β, which may reduce PRRSV viremia upon PRRSV-2 MLV vaccine administration. PNS may serve as an effective immunomodulator for boosting the immune defense against PRRSV.

Abstract Background Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder with unclear causes. Paraneoplastic etiology may be a cause. We report a case of CLIPPERS with parotid carcinoma. Case presentation A 54-year-old man with a history of lymphoma was hospitalized with a pontocerebellar syndrome. Brain MRI revealed that the pons and cerebellum were “peppered” with punctate and curvilinear enhancement lesions that supported the diagnosis of CLIPPERS. The relapse of lymphoma was excluded by a further cerebellum biopsy revealing predominantly CD3+ T cells in white matter. The patient was relieved after pulse therapy with intravenous methylprednisolone and a large dose of corticosteroids, but he complained of a worsening gait problem when corticosteroids were tapered to a lower dose. Although the clinical symptoms gradually improved again by increasing the dosage of corticosteroids with Azathioprine, the patient still had a slight unsteady gait during follow-up. At the 7-month follow-up, a parotid mass was detected by MRI and was verified as carcinoma by biopsy. After resection of parotid carcinoma, the residual symptoms and previous MRI lesions disappeared, and no relapse occurred. Conclusions CLIPPERS may not be a distinct nosologic entity but an overlapping diagnosis with other diseases. Some cases of CLIPPERS might be a subtype of paraneoplastic neurological syndromes (PNS) due to the similar mechanism of antibody-mediated encephalitis. Tumor screening and serum paraneoplastic autoantibody tests are recommended for patients with CLIPPERS, especially for those who relapse when corticosteroids treatment is stopped or tapered.

Abstract Axon regeneration in the central nervous system is inefficient. However, the neurons in the peripheral nervous system display robust regeneration after injury, indicating that axonal regeneration is differentially controlled under various conditions. To identify those molecules regulating axon regeneration, comparative analysis from dorsal root ganglion neurons at embryonic or adult stages is utilized, which reveals that PDK1 is functions as a negative regulator of axon regeneration. PDK1 is downregulated in embryonic neurons after axotomy. In contrast, sciatic nerve axotomy upregulated PDK1 at protein levels from adult mice. The knockdown of PDK1 or the chemical inhibition of PDK1 promotes axon regeneration in vitro and in vivo. Here we present PDK1 as a new player to negatively regulate axon regeneration and as a potential target in the development of therapeutic applications.

Relatively little is known about how peripheral nervous systems (PNSs) contribute to the patterning of behavior in which their role transcends the simple execution of central motor commands or mediation of reflexes. We sought to draw inferences to this end in the aeolid nudibranch Berghia stephanieae , which generates a rapid, dramatic defense behavior, "bristling." This behavior involves the coordinated movement of cerata, dozens of venomous appendages emerging from the animal's mantle. Our investigations revealed that bristling constitutes a stereotyped but non-reflexive two-stage behavior: an initial adduction of proximate cerata to sting the offending stimulus (stage 1) followed by a coordinated radial extension of remaining cerata to create a pincushion-like defensive screen around the animal (stage 2). In decerebrated specimens, stage 1 bristling was preserved, while stage 2 bristling was replaced by slower, uncoordinated ceratal movements. We conclude from these observations that, first, the animal's PNS and central nervous system (CNS) mediate stages 1 and 2 of bristling, respectively; second, the behavior propagates through the body utilizing both peripheral- and central-origin nerve networks that support different signaling kinetics; and third, the former network inhibits the latter in the body region being stimulated. These findings extend our understanding of the PNS' computational capacity and provide insight into a neuroethological scheme in which the CNS and PNS both independently and interactively pattern different aspects of non-reflexive behavior. • The gastropod Berghia rapidly moves its cerata (venomous appendages) when provoked • "Bristling" involves both retaliatory and preemptive actions • Berghia 's peripheral and central nervous systems, respectively, drive these movements • Peripheral-to-central inhibition underlies an anatomical division of labor Little is known about the capacity of the peripheral nervous system to contribute autonomously to non-reflexive behavior. Brown et al. demonstrate that the peripheral and central nervous systems of a gastropod mollusk both independently and interactively pattern different aspects of "bristling," a rapid, targeted defense behavior. [ABSTRACT FROM AUTHOR]

Background: Paraneoplastic neurological syndromes (PNS) affecting the CNS (central nervous system) are rare, presenting in less than 1% of all those with cancer. The pathogenesis of paraneoplastic neurological syndromes is not fully understood, but it is presumed to result from an immune attack on the underlying malignancy. The presence of different types of onconeural antibodies may occur in different tumors and can lead to different clinical manifestations, making the early detection of cancers challenging. Aim: An evaluation of [18F]FDG PET/CT in neoplastic tumor detection in patients with paraneoplastic neurological syndromes having negative or unremarkable results of conventional radiological imaging. Methods: Among all patients diagnosed with paraneoplastic neurological syndromes in the Neurology Department in 2016–2020, 15 patients with unremarkable conventional radiological findings who underwent [18F]FDG PET/CT were included in the study. Results: [18F]FDG PET/CT enabled localization of suspected malignancy in 53% (8 of 15) of PNS cases with previous unremarkable conventional radiological findings. Conclusion: [18F]FDG PET/CT may be considered as a useful tool for neoplastic tumor detection in patients with paraneoplastic neurological syndromes, accelerating the diagnostic process and enabling faster initiation of appropriate treatment. [ABSTRACT FROM AUTHOR]

Exosomes, nano-sized extracellular vesicles, are produced via the endosomal pathway and released in the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Recent evidence shows that these extracellular vesicles play a key role in cell-to-cell communication. Exosomes transport bioactive proteins, mRNAs, and microRNA (miRNAs) in an active form to adjacent cells or to distant organs. In this review, we focus on the role of exosomes in peripheral nerve maintenance and repair, as well as peripheral nerve/organ crosstalk, and discuss the potential benefits of exploiting exosomes for treating PNS injuries. In addition, we will highlight the emerging role of exosomes as new important vehicles for physiological systemic crosstalk failures, which could lead to organ dysfunction during neuroinflammation or aging. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the effect of purinergic ligand‐gated ion channel 7 receptor (P2X7R) antagonist A438079 in kidneys of children with primary nephrotic syndrome (PNS). In vitro, human podocytes were respectively stimulated with oxLDL (80 µg/ml), A438079 (10 µmol/L), or the compound oxLDL and A438079 together. CXC chemokine ligand 16 (CXCL16) and P2X7R expression levels were detected by Western blot and immunofluorescence assay, respectively. Immunofluorescence assay was used to detect Dil‐oxLDL, and a Colorimetric Cholesterol Detection Kit was used for quantitative determination. Our results demonstrated that CXCL16 and P2X7R expression levels were remarkably increased in the renal tissue from children with PNS, particularly in the same location. Furthermore, in contrast to children with minimal change disease, the expressions of P2X7R and CXCL16 in renal tissue of children with focal segmental glomerulosclerosis were more obvious. In vitro, CXCL16 and P2X7R expression levels in human podocytes stimulated with oxLDL were markedly elevated accompanying higher intracellular lipid accumulation compared with the normal control group. In addition, pretreatment of human podocytes with A438079 before the start of oxLDL stimulation causes a significant reduction in CXCL16 expression and a decrease in lipid accumulation. Overall, CXCL16 and P2X7R may participate in the progression of PNS. The lipid accumulation reduction caused by A438079 may be through deregulating the CXCL16 pathway, suggesting that there is a potential role for P2X7R antagonists to remedy PNS. [ABSTRACT FROM AUTHOR]

After nerve injury, both Schwann cells and neurons switch to pro-regenerative states. For Schwann cells, this involves reprogramming of myelin and Remak cells to repair Schwann cells that provide the signals and mechanisms needed for the survival of injured neurons, myelin clearance, axonal regeneration and target reinnervation. Because functional repair cells are essential for regeneration, it is unfortunate that their phenotype is not robust. Repair cell activation falters as animals get older and the repair phenotype fades during chronic denervation. These malfunctions are important reasons for the poor outcomes after nerve damage in humans. This review will discuss injury-induced Schwann cell reprogramming and the concept of the repair Schwann cell, and consider the molecular control of these cells with emphasis on c-Jun. This transcription factor is required for the generation of functional repair cells, and failure of c-Jun expression is implicated in repair cell failures in older animals and during chronic denervation. Elevating c-Jun expression in repair cells promotes regeneration, showing in principle that targeting repair cells is an effective way of improving nerve repair. In this context, we will outline the emerging evidence that repair cells are sustained by autocrine signaling loops, attractive targets for interventions aimed at promoting regeneration. [ABSTRACT FROM AUTHOR]

Allopregnanolone (ALLO), a potent neuroactive steroid, is synthesized and active in the peripheral nervous system. Previous studies have shown that ALLO participates in the central regulation of reproduction with effects on ovarian physiology, although there is little evidence for its ability to modulate peripheral tissues. The present study aimed to determine whether ALLO, administered to an ex vivo system that comprises the superior mesenteric ganglion (SMG), the ovarian nervous plexus (ONP) and the ovary (O), or to the denervated ovary (DO), was able to modify ovarian apoptosis, proliferation and angiogenesis. For this purpose, the SMG‐ONP‐O system and DO were incubated during 120 min at 37°C, in the presence of two ALLO doses (0.06 µm and 6 µm). The intrinsic and extrinsic pathways of apoptosis were analyzed. Incubation of the SMG‐ONP‐O system with ALLO 0.06 µm led to an increase in the BAX/BCL‐2 ratio and a reduction of FAS‐L mRNA levels. ALLO 6 µm induced a decrease of FAS‐L levels. Incubation of DO with ALLO 0.06 µm reduced FAS‐L, whereas ALLO 6 µm significantly increased it. Cyclin D1 mRNA was measured to evaluate proliferation. Treatment with ALLO 6 µm increased proliferation in both SMG‐ONP‐O and DO. ALLO 0.06 µm produced an increase of Cyclin D1 in DO only. Administration of either ALLO dose led to a higher ovarian expression of vascular endothelial growth factor in the SMG‐ONP‐O system, but a lower one in the DO system. ALLO 6 µm induced ovarian sensitization to GABA by increasing GABAA receptor expression. In conclusion, ALLO participates in the peripheral neural modulation of ovarian physiology. It can also interact directly with the ovarian tissue, modulating key mechanisms involved in normal and pathological processes in a dose‐dependent manner. [ABSTRACT FROM AUTHOR]

Sensorineural hearing loss is caused by the loss of sensory hair cells and/or their innervating neurons within the inner ear and affects millions of people worldwide. In mammals, including humans, the underlying cell types are only produced during fetal stages making loss of these cells and the resulting consequences irreversible. In contrast, zebrafish produce sensory hair cells throughout life and additionally possess the remarkable capacity to regenerate them upon lesion. Recently, we showed that also inner ear neurogenesis continues to take place in the zebrafish statoacoustic ganglion (SAG) well into adulthood. The neurogenic niche displays presumptive stem cells, proliferating Neurod-positive progenitors and a high level of neurogenesis at juvenile stages. It turns dormant at adult stages with only a few proliferating presumptive stem cells, no proliferating Neurod-positive progenitors, and very low levels of newborn neurons. Whether the neurogenic niche can be reactivated and whether SAG neurons can regenerate upon damage is unknown. To study the regenerative capacity of the SAG, we established a lesion paradigm using injections into the otic capsule of the right ear. Upon lesion, the number of apoptotic cells increased, and immune cells infiltrated the SAG of the lesioned side. Importantly, the Neurod-positive progenitor cells re-entered the cell cycle displaying a peak in proliferation at 8 days post lesion before they returned to homeostatic levels at 57 days post lesion. In parallel to reactive proliferation, we observed increased neurogenesis from the Neurod-positive progenitor pool. Reactive neurogenesis started at around 4 days post lesion peaking at 8 days post lesion before the neurogenesis rate decreased again to low homeostatic levels at 57 days post lesion. Additionally, administration of the thymidine analog BrdU and, thereby, labeling proliferating cells and their progeny revealed the generation of new sensory neurons within 19 days post lesion. Taken together, we show that the neurogenic niche of the adult zebrafish SAG can indeed be reactivated to re-enter the cell cycle and to increase neurogenesis upon lesion. Studying the underlying genes and pathways in zebrafish will allow comparative studies with mammalian species and might provide valuable insights into developing cures for auditory and vestibular neuropathies.

After nerve injury, both Schwann cells and neurons switch to pro-regenerative states. For Schwann cells, this involves reprogramming of myelin and Remak cells to repair Schwann cells that provide the signals and mechanisms needed for the survival of injured neurons, myelin clearance, axonal regeneration and target reinnervation. Because functional repair cells are essential for regeneration, it is unfortunate that their phenotype is not robust. Repair cell activation falters as animals get older and the repair phenotype fades during chronic denervation. These malfunctions are important reasons for the poor outcomes after nerve damage in humans. This review will discuss injury-induced Schwann cell reprogramming and the concept of the repair Schwann cell, and consider the molecular control of these cells with emphasis on c-Jun. This transcription factor is required for the generation of functional repair cells, and failure of c-Jun expression is implicated in repair cell failures in older animals and during chronic denervation. Elevating c-Jun expression in repair cells promotes regeneration, showing in principle that targeting repair cells is an effective way of improving nerve repair. In this context, we will outline the emerging evidence that repair cells are sustained by autocrine signaling loops, attractive targets for interventions aimed at promoting regeneration.

Background People with diabetes are more likely to develop cardiovascular diseases. Lipotoxicity plays a key role in the development of diabetic cardiomyopathy. Panax notoginseng saponin (PNS) has been used to treat diabetes and obesity. However, the role of PNS in diabetic cardiomyopathy remains unclear. Methods and Results Diabetic db/db mice received high‐dose (200 mg/kg per day) or medium‐dose (100 mg/kg per day) PNS by gavage for 12 weeks until week 36. Lipid accumulation and cardiac function in diabetic mice were detected and possible mechanisms involved were explored. PNS significantly improved body weight, body fat content, serum lipids, adipocytokines, and antioxidative function in db/db mice. Lipid accumulation in adipose tissue, liver, and heart were also alleviated by PNS treatment. Cardiac function and mitochondrial structure were also improved by PNS. H9c2 cells were treated with palmitate acid, and PNS pretreatment reduced lipid accumulation, mitochondrial reactive oxygen species, as well as improved mitochondrial membrane potential and mitochondrial oxygen consumption rate. Levels of proteins and expression of genes related to glucose and lipid metabolism, antioxidative function, and mitochondrial dynamics were also improved by PNS administration. Conclusions PNS attenuated heart dysfunction in diabetic mice by reducing lipotoxicity as well as modulating oxidative stress and improving mitochondrial function.

Chronic pain is a common source of morbidity in many patient populations worldwide. There are growing concerns about the potential side effects of currently prescribed medications and a continued need for effective treatment. Related to these concerns, peripheral nerve stimulation has been regaining popularity as a potential treatment modality. Peripheral nerve stimulation components include helically coiled electrical leads, which direct an applied current to afferent neurons providing sensory innervation to the painful area. In theory, the applied current to the peripheral nerve will alter the large-diameter myelinated afferent nerve fibers, which interfere with the central processing of pain signals through small-diameter afferent fibers at the level of the spinal cord. Multiple studies have shown success in the use of peripheral nerve stimulation for acute post-surgical pain for orthopedic surgery, including post total knee arthroplasty and anterior cruciate ligament surgery, and chronic knee pain. Many studies have investigated the utility of peripheral nerve stimulation for the management of chronic shoulder pain. Peripheral nerve stimulation also serves as one of the potential non-pharmacologic therapies to treat back pain along with physical therapy, application of transcutaneous electrical neurostimulation unit, radiofrequency ablation, epidural steroid injections, permanently implanted neurostimulators, and surgery. Studies regarding back pain treatment have shown that peripheral nerve stimulation led to significant improvement in all pain and quality-of-life measures and a reduction in the use of opioids. Further studies are needed as the long-term risks and benefits of peripheral nerve stimulation have not been well studied as most information available on the effectiveness of peripheral nerve stimulation is based on shorter-term improvements in chronic pain. [ABSTRACT FROM AUTHOR]

The abuse ofnarcoticsinPariamancityisnotonlydoneby publicbutalsoby civil servant.The narcoticscrime are done by civilservantinPariamancityisabuse of narcotics Part Ifor theirselves asmentionedin theLaw Number 35Year 2009 about Narcotics.Forthis action,thePariamanCourtgivespunishmentnamelyasprisoner forone yeartotheaccuses.The problemsinthisstudyare:First,howaboutthe implementationofcriminalsanctionto civilservantwhodoesthenarcoticcriminal law in the cases 109/Pid.Sus/2016/PN.Pmn and the cases number:104/Pid.Sus/2018/PN.Pmn?Second,howthejudge’sconsiderationinapplyingthecriminalsanctiontothecivilservantwhodoesthenarcoticcriminallawinthecases109/Pid.Sus/2016/PN.Pmn the cases number: 104/Pid.Sus/2018/PN.Pmn?This research is legal research with analytical descriptive specifications. The approachusedisanormativejuridicalapproachandsupportedbyanempirical juridicalapproach.Thedatasourcesusedaresecondarydatawithdatacollection techniquesintheformof documentstudiesandfieldstudiesthrough interviews.Then the data is analyzed qualitatively and described indescriptiveanalytical form. Keyword : Criminal, Civil Servant, Narcotics

Abstract Glutamate (Glu) is the predominant excitatory neurotransmitter in the central nervous system (CNS). Glutamatergic transmission is critical for controlling neuronal activity. In presynaptic neurons, Glu is stored in synaptic vesicles and released by stimulation. The homeostasis of glutamatergic system is maintained by a set of transporters in the membrane of synaptic vesicles. The family of vesicular Glu transporters in mammals is comprised of three highly homologous proteins: VGLUT1-3. Among them, VGLUT1 accounts for the largest proportion. However, most of the Glu is transported into the synaptic vesicles via the type 1 vesicle Glu transporter (VGLUT1). So, the expression of particular VGLUT1 is largely complementary with limited overlap and so far it is most specific markers for neurons that use Glu as neurotransmitter. Controlling the activity of VGLUT1 could potentially modulate the efficiency of excitatory neuro-transmission and change the filling level of synaptic vesicles. This review summarizes the recent knowledge concerning molecular and functional characteristic of VGLUT1, their development, contribution to a series of central nervous system and peripheral nervous system diseases such as learning and memory disorders, Alzheimer’s disease, Parkinson’s disease and sensitized nociception or pain pathology et al.

In the peripheral nervous system, the vast majority of axons are accommodated within the fibre bundles that constitute the peripheral nerves. Axons within the nerves are in close contact with myelinating glia, the Schwann cells that are ideally placed to respond to, and possibly shape, axonal activity. The mechanisms of intercellular communication in the peripheral nerves may involve direct contact between the cells, as well as signalling via diffusible substances. Neurotransmitter glutamate has been proposed as a candidate extracellular molecule mediating the cross-talk between cells in the peripheral nerves. Two types of experimental findings support this idea: first, glutamate has been detected in the nerves and can be released upon electrical or chemical stimulation of the nerves; second, axons and Schwann cells in the peripheral nerves express glutamate receptors. Yet, the studies providing direct experimental evidence that intercellular glutamatergic signalling takes place in the peripheral nerves during physiological or pathological conditions are largely missing. Remarkably, in the central nervous system, axons and myelinating glia are involved in glutamatergic signalling. This signalling occurs via different mechanisms, the most intriguing of which is fast synaptic communication between axons and oligodendrocyte precursor cells. Glutamate receptors and/or synaptic axon-glia signalling are involved in regulation of proliferation, migration, and differentiation of oligodendrocyte precursor cells, survival of oligodendrocytes, and re-myelination of axons after damage. Does synaptic signalling exist between axons and Schwann cells in the peripheral nerves? What is the functional role of glutamate receptors in the peripheral nerves? Is activation of glutamate receptors in the nerves beneficial or harmful during diseases? In this review, we summarise the limited information regarding glutamate release and glutamate receptors in the peripheral nerves and speculate about possible mechanisms of glutamatergic signalling in the nerves. We highlight the necessity of further research on this topic because it should help to understand the mechanisms of peripheral nervous system development and nerve regeneration during diseases.

The homotrimeric P2X7 receptor (P2X7R) is expressed by virtually all cells of the innate and adaptive immune system and plays a crucial role in various pathophysiological processes such as autoimmune and neurodegenerative diseases, inflammation, neuropathic pain and cancer. Consequently, the P2X7R is considered a promising target for therapy and diagnosis. As the development of tracers comes hand-in-hand with the development of potent and selective receptor ligands, there is a rising number of PET tracers available in preclinical and clinical studies. This review analyzes the development of P2X7R positron emission tomography (PET) tracers and their potential in various PET imaging applications.

This research aims to analyze and design a zakat accounting information system at the Bengkalis District National Amil Zakat Board which is not well systemized. At the same time to design the management of income zakat for Civil Servants of Bengkalis Regency in accordance with the Bengkalis Regency Regional Government's plans regarding Regional Regulations on Zakat. Data collection techniques used were observation, interviews, documentation and literature study. In carrying out system design activities database design techniques, system design and user interface design are used. With this system design is able to answer the needs of the general public, especially for Civil Servants in Bengkalis Regency and provide transparency in the management of zakat, infaq and alms funds through financial reports that can be accessed by the public.

Objective. Rapid switching of magnetic resonance imaging (MRI) gradient fields induces electric fields that can cause peripheral nerve stimulation (PNS) and so accurate characterization of PNS is required to maintain patient safety and comfort while maximizing MRI performance. The minimum magnetic gradient amplitude that causes stimulation, the PNS threshold, depends on intrinsic axon properties and the spatial and temporal properties of the induced electric field. The PNS strength-duration curve is widely used to characterize simulation thresholds for periodic waveforms and is parameterized by the chronaxie and rheobase. Safety limits to avoid unwanted PNS in MRI rely on a single chronaxie value to characterize the response of all nerves. However, experimental magnetostimulation peripheral nerve chronaxie values vary by an order of magnitude. Given the diverse range of chronaxies observed and the importance of this number in MRI safety models, we seek a deeper understanding of the mechanisms contributing to chronaxie variability. Approach. We use a coupled electromagnetic-neurodynamic PNS model to assess geometric sources of chronaxie variability. We study the impact of the position of the stimulating magnetic field coil relative to the body, along with the effect of local anatomical features and nerve trajectories on the driving function and the resulting chronaxie. Main results. We find realistic variation of local axon and tissue geometry can modulate a given axon's chronaxie by up to two-fold. Our results identify the temporal rate of charge redistribution as the underlying determinant of the chronaxie. Significance. This charge distribution is a function of both intrinsic axon properties and the spatial stimulus along the nerve; thus, examination of the local tissue topology, which shapes the electric fields, as well as the nerve trajectory, are critical for better understanding chronaxie variations and defining more biologically informed MRI safety guidelines., (© 2024 IOP Publishing Ltd.)

COVID 19 often presents with flu-like symptoms. Elderly patients with systemic comorbidities are more likely to have severe COVID 19 infections and deaths. Severe neurological complications are frequently reported in severely and critically ill patients. In COVID-19, both central and peripheral nervous systems can be affected. The study aims to overview the spectrum, characteristics, and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: A total of 1000 confirmed CoVID-19 patients were enrolled for the study. Demographic features and initial clinical manifestations were noted, and patients were followed during the hospital stay to develop any new neurological signs and symptoms. For analytical purposes, neurological presentations were grouped into the central nervous system, peripheral nervous system, and musculoskeletal system manifestations. Appropriate laboratory testing was employed as required on a case-to-case basis. Results: The mean age was 44.6 ± 14.3 years. 625 (62.5%) patients were male, while 375 (37.5%) were female. The neurological illness was a primary manifestation in 119 (11.9%) cases. These included encephalopathy (n=78), ischemic stroke (n=28), Guillain- Barre syndrome, (n=3), facial nerve palsy (n=4), and encephalitis (n=6). The most common neurological symptoms were headache 313 (31.3%) and hyposmia 52 (5.2%), followed by encephalopathy 78 (7.8%). More serious complications like seizures 18 (1.8%) and stroke 28 (2.8%) were also seen. Conclusion: CoVID-19 can present with a neurological illness, and we should remain vigilant to the possibility of neurological presentation of COVID-19 that can be thrombo-embolic, inflammatory, or immune-mediated [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate and validate electric field (E‐field) calculation and peripheral nerve stimulation (PNS) prediction methods that are accurate, computationally efficient, and that could be used to inform regulatory standards. Methods: We describe a simplified method for calculating the spatial distribution of induced E‐field over the volume of a body model given a gradient coil vector potential field. The method is easily programmed without finite element or finite difference software, allowing for straightforward and computationally efficient E‐field evaluation. Using these E‐field calculations and a range of body models, population‐weighted PNS thresholds are determined using established methods and compared against published experimental PNS data for two head gradient coils and one body gradient coil. Results: A head‐gradient‐appropriate chronaxie value of 669 µs was determined by meta‐analysis. Prediction errors between our calculated PNS parameters and the corresponding experimentally measured values were ~5% for the body gradient and ~20% for the symmetric head gradient. Our calculated PNS parameters matched experimental measurements to within experimental uncertainty for 73% of ∆Gmin estimates and 80% of SRmin estimates. Computation time is seconds for initial E‐field maps and milliseconds for E‐field updates for different gradient designs, allowing for highly efficient iterative optimization of gradient designs and enabling new dimensions in PNS‐optimal gradient design. Conclusions: We have developed accurate and computationally efficient methods for prospectively determining PNS limits, with specific application to head gradient coils. [ABSTRACT FROM AUTHOR]

Secure exchange of cryptographic keys is extremely important for any communication system where security and privacy of data is desirable. Although classical cryptographic algorithms provide computationally secure methods for secret key exchange, quantum key distribution (QKD) provides an extraordinary means to this end by guaranteeing unconditional security. Any malicious interception of communication by a man-in-the-middle on a QKD link immediately alerts sender and receiver by introducing an unavoidable error-rate. Higher-dimensional QKD protocols such as KMB09 exhibit higher eavesdropping error-rates with improved intrusion detection but their practical implementation is still awaited. In this paper, we present the design and implementation of KMB09 protocol using Laguerre–Gaussian orbital angular momentum to demonstrate and highlight the advantages of using dynamic spatial modes in QKD system. A complete error-rate analysis of KMB09 protocol implementation is presented with two different types of eavesdropping error-rates. Furthermore, we also demonstrate the decoy state method to show the robustness of the protocol against photon-number-splitting attack. [ABSTRACT FROM AUTHOR]

The unremitting coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked a year-long phase of public health adversaries and has severely compromised healthcare globally. Early evidence of COVID-19 noted its impact on the pulmonary and cardiovascular functions, while multiple studies in recent time shed light on its substantial neurological complications, though a comprehensive understanding of the cause(s), the mechanism(s), and their neuropathological outcomes is scarce. In the present review, we conferred evidence of neurological complications in COVID-19 patients and shed light on the SARS-CoV-2 infection routes including the hematogenous, direct/neuronal, lymphatic tissue or cerebrospinal fluid, or infiltration through infected immune cells, while the underlying mechanism of SARS-CoV-2 invasion to the central nervous system (CNS) was also discussed. In an up-to-date manner, we further reviewed the impact of COVID-19 in developing diverse neurologic manifestations associated with CNS, peripheral nervous system (PNS), skeletal muscle, and also pre-existing neurological diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and myasthenia gravis. Furthermore, we discussed the involvement of key factors including age, sex, comorbidity, and disease severity in exacerbating the neurologic manifestations in COVID-19 patients. An outlook of present therapeutic strategies and state of existing challenges in COVID-19 management was also accessed. Conclusively, the present report provides a comprehensive review of COVID-19-related neurological complications and emphasizes the need for their early clinical management in the ongoing COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

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Fibroblast growth factors (FGFs) act as key signalling molecules in brain development, maintenance, and repair. They influence the intricate relationship between myelinating cells and axons as well as the association of astrocytic and microglial processes with neuronal perikarya and synapses. Advances in molecular genetics and imaging techniques have allowed novel insights into FGF signalling in recent years. Conditional mouse mutants have revealed the functional significance of neuronal and glial FGF receptors, not only in tissue protection, axon regeneration, and glial proliferation but also in instant behavioural changes. This review provides a summary of recent findings regarding the role of FGFs and their receptors in the nervous system and in the pathogenesis of major neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Transdifferentiation of Schwann cells is essential for functional peripheral nerve regeneration after injury. By activating a repair program, Schwann cells promote functional axonal regeneration and remyelination. However, chronic denervation, aging, metabolic diseases, or chronic inflammatory processes reduce the transdifferentiation capacity and thus diminish peripheral nerve repair. It was recently described that the sphingosine-1-phosphate receptor (S1PR) agonist Fingolimod enhances the Schwann cell repair phenotype by activation of dedifferentiation markers and concomitant release of trophic factors resulting in enhanced neurite growth. Since Fingolimod targets four out of five S1PRs (S1P1, S1P3-5) possibly leading to non-specific adverse effects, identification of the main receptor(s) responsible for the observed phenotypic changes is mandatory for future specific treatment approaches. Our experiments revealed that S1P3 dominates and that along with S1P1 acts as the responsible receptor for Schwann cell transdifferentiation as revealed by the combinatory application of specific agonists and antagonists. Targeting both receptors reduced the expression of myelin-associated genes, increased PDGF-BB representing enhanced trophic factor expression likely to result from c-Jun induction. Furthermore, we demonstrated that S1P4 and S1P5 play only a minor role in the adaptation of the repair phenotype. In conclusion, modulation of S1P1 and S1P3 could be effective to enhance the Schwann cell repair phenotype and thus stimulate proper nerve repair.

Electrical nerve fiber stimulation is a technique widely used in prosthetics and rehabilitation, and its study from a computational point of view can be a useful instrument to support experimental tests. In the last years, there was an increasing interest in computational modeling of neural cells and numerical simulations on nerve fibers stimulation because of its usefulness in forecasting the effect of electrical current stimuli delivered to tissues through implanted electrodes, in the design of optimal stimulus waveforms based on the specific application (i.e., inducing limb movements, sensory feedback or physiological function restoring), and in the evaluation of the current stimuli properties according to the characteristics of the nerves surrounding tissue. Therefore, a review study on the main modeling and computational frameworks adopted to investigate peripheral nerve stimulation is an important instrument to support and drive future research works. To this aim, this paper deals with mathematical models of neural cells with a detailed description of ion channels and numerical simulations using finite element methods to describe the dynamics of electrical stimulation by implanted electrodes in peripheral nerve fibers. In particular, we evaluate different nerve cell models considering different ion channels present in neurons and provide a guideline on multiscale numerical simulations of electrical nerve fibers stimulation. [ABSTRACT FROM AUTHOR]

Purpose: To develop new concepts for minimum electric-field (E-field) gradient design, and to define the extents to which E-field can be reduced in gradient design while maintaining a desired imaging performance. Methods: Efficient calculation of induced electric field in simplified patient models was integrated into gradient design software, allowing constraints to be placed on the peak E-field. Gradient coils confined to various build envelopes were designed with minimum E-fields subject to standard magnetic field constraints. We examined the characteristics of E-field-constrained gradients designed for imaging the head and body and the importance of asymmetry and concomitant fields in achieving these solutions. Results: For transverse gradients, symmetric solutions create high levels of E-fields in the shoulder region, while fully asymmetric solutions create high E-fields on the top of the head. Partially asymmetric solutions result in the lowest E-fields, balanced between shoulders and head and resulting in factors of 1.8 to 2.8 reduction in E-field for x-gradient and y-gradient coils, respectively, when compared with the symmetric designs of identical gradient distortion. Conclusions: We introduce a generalized method for minimum E-field gradient design and define the theoretical limits of magnetic energy and peak E-field for gradient coils of arbitrary cylindrical geometry. [ABSTRACT FROM AUTHOR]

Objective To observe the therapeutic of PNS on wound healing and the expression of PDGF-BB, PDGFR-β in rats superficial second-degree burn model, and to explore the underlying mechanism of PNS on second-degree burn wound healing. Methods Rats with superficial second-degree burn were treated with PNS, applying HE staining to detect burn severity, and then biopsied biological tissue on days 0, 7, 14, 21 after administration, respectively. Moreover, Immunohistochemistry (IHC), Western blot and RT-PCR methods were used to detect protein and mRNA expression levels of PDGF-BB/PDGFR-β in skin tissues after treatment with PNS, respectively. Furthermore, the skin wound healing at different time points was monitored by macroscopic observation. Results HE staining suggested that the replication of rats second-degree burn model was successful. Macro monitoring data demonstrates that compared with model group, the removal time of scab and fur-growthing were shortened, and the wound healing rate was increased in the PNS high-dose group (P < 0.05). Combination of IHC, WB and RT-PCR showed that the expression levels of PDGF-BB/PDGFR-β increased sharply on day 7, maintaining a high level until day 14, approaching normal levels on day 21 after PNS treatment. However, the protein and mRNA expressions of PDGF-BB/PDGFR-β showed high values on day 21 in the model group, which was a slow process. Our results suggest that compared with model group, the peak expression of PDGF-BB/PDGFR-β are earlier, shortening of fur-growthing and decrustation time, and improvement of wound healing rate in rats superficial second-degree burn model. Conclusion PNS can significantly promote skin wound healing in rats superficial second-degree burn model, and its mechanism is closely related to the up-regulation of the expression levels of PDGF-BB/PDGFR-β in skin tissue. [ABSTRACT FROM AUTHOR]

There exists a dichotomy in regenerative capacity between the PNS and CNS, which poses the question – where do cranial nerves fall? Through the discussion of the various cells and processes involved in axonal regeneration, we will evaluate whether the assumption that cranial nerve regeneration is analogous to peripheral nerve regeneration is valid. It is evident from this review that much remains to be clarified regarding both PNS and CNS regeneration. Furthermore, it is not clear if cranial nerves follow the PNS model, CNS model or possess an alternative novel regenerative process altogether. Future research should continue to focus on elucidating how cranial nerves regenerate; and the various cellular interactions, molecules and pathways involved. [ABSTRACT FROM AUTHOR]

Key points: We compare the effects on corticospinal excitability of repeatedly delivering peripheral nerve stimulation at three time points (−30 ms, 0 ms, +50 ms) relative to muscle onset in a cue‐guided task.Plastic changes in excitability are only observed when stimuli are delivered immediately before the time when muscles activate, while stimuli delivered at muscle onset or shortly later (0, +50 ms) have no effect.Plastic effects are abolished if there is ongoing volitional electromyogram activity in the muscles prior to the onset of the phasic contraction.The plastic effects induced by timing peripheral stimulation relative to electromyographic markers of muscle activation are as effective as those that occur if stimulation is timed relative to electroencephalographic markers of motor cortical activation. We provide a simple alternative protocol to induce plasticity in people in whom electroencephalogram recording is difficult. Plastic changes in corticospinal excitability (CSE) and motor function can be induced in a targeted and long‐term manner if afferent volleys evoked by peripheral nerve stimulation are repeatedly associated with the peak of premovement brain activity assessed with an electroencephalogram (EEG). The present study investigated whether other factors might also characterize this optimal brain state for plasticity induction. In healthy human volunteers (n = 24), we found that the same reliable changes in CSE can be induced by timing peripheral afferent stimulation relative to the onset of electromyogram (EMG) activity rather than using the EEG peak. Specifically, we observed an increase in CSE when peripheral stimulation activated the cortex just before movement initiation. By contrast, there was no effect on CSE if the afferent input reached the cortex at the same time or after EMG onset, consistent with the idea that the temporal order of synaptic activation from afferent input and voluntary movement is important for production of plasticity. Finally, in 14 volunteers, we found that background voluntary muscle activity prior to movement also abolished the effect on CSE. One possible explanation is that the intervention strengthens synapses that are inactive at rest but change their activity in anticipation of movement, and that the intervention fails when the synapses are tonically active during background EMG activity. Overall, we demonstrate that, in individuals with voluntary control of muscles targeted by our intervention, EMG signals are a suitable alternative to an EEG for inducing plasticity by coupling movement‐related brain states with peripheral afferent input. Key points: We compare the effects on corticospinal excitability of repeatedly delivering peripheral nerve stimulation at three time points (−30 ms, 0 ms, +50 ms) relative to muscle onset in a cue‐guided task.Plastic changes in excitability are only observed when stimuli are delivered immediately before the time when muscles activate, while stimuli delivered at muscle onset or shortly later (0, +50 ms) have no effect.Plastic effects are abolished if there is ongoing volitional electromyogram activity in the muscles prior to the onset of the phasic contraction.The plastic effects induced by timing peripheral stimulation relative to electromyographic markers of muscle activation are as effective as those that occur if stimulation is timed relative to electroencephalographic markers of motor cortical activation. We provide a simple alternative protocol to induce plasticity in people in whom electroencephalogram recording is difficult. [ABSTRACT FROM AUTHOR]

Paraneoplastic neurological syndromes (PNS) are rare neurological disorders arising from malignancy-triggered autoimmunity, yet their association with urothelial carcinoma remains unclear. This systematic review intends to explore any connection, alongside patient/clinical features and management. A literature search identified 25 cases of bladder and upper tract carcinoma linked to PNS. Overall, while infrequent, a meaningful association between PNS and urothelial carcinoma was found in that 84% of cases met a 'possible'-or-'higher-likelihood' PNS diagnosis. Most cases presented with high-risk PNS phenotypes, predominantly cerebellar syndromes and encephalomyelitis/sensory neuronopathy, ∼17 months within cancer diagnosis/recurrence. Review findings suggest a female preponderance in suspected PNS despite higher male incidence of urothelial cancer. Main treatments consisted of surgery alongside chemotherapy or immunotherapeutics (IVIG and/or corticosteroids), which improved symptoms for a slight majority (60%). Ultimately, while common PNS-associated neoplasms should always first be excluded in suspected PNS, in the absence of alternative causes, urothelial carcinomas do merit clinical consideration. [Display omitted] • The association between PNS and urothelial carcinoma to date remains unclear. • Findings suggest that PNS can occur in the context of urothelial carcinoma but rare. • Most PNS-suspected cases met 'possible' or higher PNS scores, notably elderly women. • Key PNS signs include syndrome type, high-risk Abs and tumour antigen expression. • Immunomodulation plus tumour resection may help to lead to PNS symptom improvement. [ABSTRACT FROM AUTHOR]

Calcium sulfate hemihydrate is widely used for gypsum product fabrication; however, it requires superplasticizers to improve its fluidity and workability. In this study, we aimed to develop a novel superplasticizer based on partially sulfonated polystyrene (PStSS- f SS) for calcium sulfate hemihydrate. We synthesized PStSS -f SS by polymerization of styrene and sodium 4-styrenesulfonate and compared its performance with polynapthalene sulfonate (PNS) in terms of fluidity, zeta potential, hydration rate, and water resistance. PStSS -f SS exhibited higher fluidity than PNS without hydration delay of hemihydrate. The higher fluidity was attributed to the enhanced polymer adsorption on the hemihydrate surface because of the hydrophobic units. PStSS -f SS also imparted better water-resist properties to the gypsum products. PStSS -f SS is confirmed as a better superplasticizer than PNS for calcium sulfate hemihydrate, providing higher fluidity and improved water resistance. [Display omitted] • PStSS is a novel superplasticizer for CaSO 4 hemihydrates. • PStSS improves hemihydrate slurry fluidity over PNS. • Lower sulfonate content in PStSS increases fluidity. • PStSS enhances the water resistance of gypsum products. [ABSTRACT FROM AUTHOR]

Abstract Neurons and glial cells coordinate with each other in many different aspects of nervous system development. Both types of cells are receiving multiple guidance cues to guide the neurons and glial cells to their proper final position. The lateral chordotonal organs (lch5) of the Drosophila peripheral nervous system (PNS) are composed of five sensory neurons surrounded by four different glial cells, scolopale cells, cap cells, attachment cells and ligament cells. During embryogenesis, the lch5 neurons go through a rotation and ventral migration to reach their final position in the lateral region of the abdomen. We show here that the extracellular ligand sli is required for the proper ventral migration and morphology of the lch5 neurons. We further show that mutations in the Sli receptors Robo and Robo2 also display similar defects as loss of sli, suggesting a role for Slit-Robo signaling in lch5 migration and positioning. Additionally, we demonstrate that the scolopale, cap and attachment cells follow the mis-migrated lch5 neurons in sli mutants, while the ventral stretching of the ligament cells seems to be independent of the lch5 neurons. This study sheds light on the role of Slit-Robo signaling in sensory neuron development.

Renee Siu Yu Ma,1 Kayani Kayani,1 Danniella Whyte-Oshodi,1 Aiyesha Whyte-Oshodi,2 Nitish Nachiappan,3 Shaene Gnanarajah,1 Raihan Mohammed1 1Department of Medicine, University of Cambridge, Cambridge, UK; 2Faculty of Medicine, University College London, London, UK; 3Faculty of Medicine, Imperial College London, London, UKCorrespondence: Raihan MohammedSchool of Clinical Medicine, University of Cambridge, Hills Road, Cambridge CB2 0SP, UKTel +44 787 173 6004Email rm758@cam.ac.ukAbstract: Being maladaptive and frequently unresponsive to pharmacotherapy, chronic pain presents a major unmet clinical need. While an intact central nervous system is required for conscious pain perception, nociceptor hyperexcitability induced by nerve injury in the peripheral nervous system (PNS) is sufficient and necessary to initiate and maintain neuropathic pain. The genesis and propagation of action potentials is dependent on voltage-gated sodium channels, in particular, Nav1.7, Nav1.8 and Nav1.9. However, nerve injury triggers changes in their distribution, expression and/or biophysical properties, leading to aberrant excitability. Most existing treatment for pain relief acts through non-selective, state-dependent sodium channel blockage and have narrow therapeutic windows. Natural toxins and developing subtype-specific and molecular-specific sodium channel blockers show promise for treatment of neuropathic pain with minimal side effects. New approaches to analgesia include combination therapy and gene therapy. Here, we review how individual sodium channel subtypes contribute to pain, and the attempts made to develop more effective analgesics for the treatment of chronic pain.Keywords: nociceptors, TTX, neuropathic, electrogenesis, CNS, PNS

Three hundred and sixty-four out of 547 children with primary nephrotic syndrome (PNS) treated at the Department of Child Health, Medical School, University of Indonesia between January 1970 and December 1979, were biopsied. The clinical, laboratory, and pathological characteristics of these patients were evaluated and compared with those reported by the International Study of Kidney Disease in Children (ISKOC, 1978) comprising children of Western countries with PNS. Results of this study showed that the spectrum of the histopathological changes in the 2 study populations was slightly different. Clinical and laboratory characteristics of certain types of PNS also showed some differences compared with those of ISKDC report. Patients with non-minimal changes nephrotic syndrome (NMCNS) were more frequently found in this study, and they were older than those of ISKDC report, i.e., more children < 6 years of age were affected with this disease in Jakarta. Similarly, this study showed that patients with minimal changes nephrotic syndrome (MCNS) were older than those of ISKDC report; the peak age of Western patients was less than 6 years. Patients with focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN) reported by ISKDC were more severe than those of this study as far as clinical and laboratory characteristics were concerned. The causes of these clinical and histopathological discrepancies between the two studies need to be further elucidated.