Paraneoplastic neurologic syndrome and autoantibody accompaniments of germ cell tumors.

Paraneoplastic neurologic syndromes (PNSs) are a group of diseases affecting the central and/or peripheral nervous system caused by immune-mediated processes directed toward antigens with shared expression in tumor and neural tissue. Germ cell tumors (GCTs) are associated with PNSs with varied clinical phenotypes. Early diagnosis of PNS is vital to potentially uncover and treat underlying tumors, improving the chances of recovery, and preventing permanent neurologic complications. In this chapter, we outline the pathophysiology and epidemiology of PNS. We briefly provide a summary of GCTs in males and females. We review the neural-specific autoantibodies and PNSs associated with GCTs and their clinical and radiologic accompaniments. We also provide an overview of the treatment and prognosis of these disorders.

Tannic acid ameliorates the hazards effect of beryllium induced neuro-alterations and oxidative stress in adult male rats.

Background: Tannic acid (TA) is one of the most consumed and famous polyphenols with a widespread attention in the medical field according to its unique structural, pharmaceutical, physicochemical, antioxidant and other biological features. A rare study was conducted on the hazard effect of beryllium (Be) on the central nervous system. Aims: This study aims to show the ability of beryllium to cross the blood brain barrier. Demonstrate the effect of beryllium and tannic acid separately or with each other on brain ions (Na+, K+, Ca++) and on norepinephrine, dopamine, serotonin, finally on the glutathione and malondialdehyde. Animals grouping: Seventy-two rats were divided into four groups as control, Be, TA, and Be+TA where Be was injected intraperitoneally as 1 mg/Kg b. wt, TA was orally administrated as 5% in aquas solution. Results: The administration of beryllium showed its ability to cross the blood brain barrier and accumulated in cortex > cerebellum>hypothalamus also, a significant increase in Na+, Ca++ cooperated with a significant decrease in K+ ions content was observed. Norepinephrine, dopamine, and serotonin showed a general significant decrease in their content joined with a significant decrease in glutathione (GSH) and elevation in malondialdehydes (MDA) because of Be intoxication. On the other hands the daily oral administration of tannic acid showed a general significant decrease in Na+, Ca++ ions content parallel with a significant increase K+ also, a non-significant change in the three measured neurotransmitters was noticed. Conclusion: Tannic acid showed a mitigation effect against Be intoxication which may regarded to the tannic acid antioxidant, chelating effect.

Neurological study on the effect of CeNPs and/or La Cl3 on adult male albino rats.

Lanthanides are a group of 15 elements (8 heavy and 7 light) grouped for their proximity in the chemical and physical properties. Recently, this group of elements has received great attention because of their importance, and their entrance into many industrial technologies making the probability of the living organisms' exposure to it increase. The present study aims to study ability of cerium nanoparticles (CeNPs) or lanthanum (LaCl3) to cross the blood brain barrier also, investigate their neuro effect separately or together on some parameters in six brain areas (cortex, cerebellum, hippocampus, striatum, midbrain, and hypothalamus) of the adult male albino rats. The results showed the ability of both elements to distribute and accumulate in the different brain areas. Also, the results of CeNPs or LaCl3 treatment were in the same line where each element caused a significant decrease in norepinephrine (NE), dopamine (DA), serotonin (5-HT) and GABA accompanied with a significant increase in 5- hydroxyl indoleacetic acid (5-HIAA) glucose level. On the other hand, GSH and MDA showed a significant decrease after CeNPs treatment while, with LaCl3 treatment, MDA showed a significant increase in the different brain areas after 3 weeks of treatment. The coadministration of CeNPs and La Cl3 caused an ameliorating effect in all the tested parameters. In conclusion, from the previous studies the effects of lanthanides in the present study may be in part due to its effect on the release or turnover of neurotransmitters and insulin secretion. Finally, the ameliorative effect of CeNPs may be regarded as its high activity to scavenge the free radicals.

Osteogenic Effect of a Bioactive Calcium Alkali Phosphate Bone Substitute in Humans.

(1) Background: The desire to avoid autograft harvesting in implant dentistry has prompted an ever-increasing quest for bioceramic bone substitutes, which stimulate osteogenesis while resorbing in a timely fashion. Consequently, a highly bioactive silicon containing calcium alkali orthophosphate (Si-CAP) material was created, which previously was shown to induce greater bone cell maturation and bone neo-formation than ß-tricalcium phosphate (ß-TCP) in vivo as well as in vitro. Our study tested the hypothesis that the enhanced effect on bone cell function in vitro and in sheep in vivo would lead to more copious bone neoformation in patients following sinus floor augmentation (SFA) employing Si-CAP when compared to ß-TCP. (2) Methods: The effects of Si-CAP on osteogenesis and Si-CAP resorbability were evaluated in biopsies harvested from 38 patients six months after SFA in comparison to ß-TCP employing undecalcified histology, histomorphometry, and immunohistochemical analysis of osteogenic marker expression. (3) Results: Si-CAP as well as ß-TCP supported matrix mineralization and bone formation. Apically furthest away from the original bone tissue, Si-CAP induced significantly higher bone formation, bone-bonding (bone-bioceramic contact), and granule resorption than ß-TCP. This was in conjunction with a higher expression of osteogenic markers. (4) Conclusions: Si-CAP induced higher and more advanced bone formation and resorbability than ß-TCP, while ß-TCP's remarkable osteoconductivity has been widely demonstrated. Hence, Si-CAP constitutes a well-suited bioactive graft choice for SFA in the clinical arena.

Identification of SKOR2 IgG as a novel biomarker of paraneoplastic neurologic syndrome.

Introduction: The development of new autoantigen discovery techniques, like programmable phage immunoprecipitation sequencing (PhIP-Seq), has accelerated the discovery of neural-specific autoantibodies. Herein, we report the identification of a novel biomarker for paraneoplastic neurologic syndrome (PNS), Sloan-Kettering-Virus-Family-Transcriptional-Corepressor-2 (SKOR2)-IgG, utilizing PhIP-Seq. We have also performed a thorough clinical validation using normal, healthy, and disease/cancer control samples. Methods: Stored samples with unclassified staining at the junction of the Purkinje cell and the granule cell layers were analyzed by PhIP-Seq for putative autoantigen identification. The autoantigen was confirmed by recombinant antigen-expressing cell-based assay (CBA), Western blotting, and tissue immunofluorescence assay colocalization. Results: PhIP-Seq data revealed SKOR2 as the candidate autoantigen. The target antigen was confirmed by a recombinant SKOR-2-expressing, and cell lysate Western blot. Furthermore, IgG from both patient samples colocalized with a commercial SKOR2-specific IgG on cryosections of the mouse brain. Both SKOR2 IgG-positive patients had central nervous system involvement, one presenting with encephalitis and seizures (Patient 1) and the other with cognitive dysfunction, spastic ataxia, dysarthria, dysphagia, and pseudobulbar affect (Patient 2). They had a refractory progressive course and were diagnosed with adenocarcinoma (Patient 1: lung, Patient 2: gallbladder). Sera from adenocarcinoma patients without PNS (n=30) tested for SKOR2-IgG were negative. Discussion: SKOR2 IgG represents a novel biomarker for PNS associated with adenocarcinoma. Identification of additional SKOR2 IgG-positive cases will help categorize the associated neurological phenotype and the risk of underlying malignancy.

Biosynthesized silver nanoparticles (Ag NPs) from isolated actinomycetes strains and their impact on the black cutworm, Agrotis ipsilon.

Nanomaterials have been produced with the use of bio-nanotechnology, which is a low-cost approach. Currently, research is being conducted to determine whether actinomycetes isolated from Egyptian soil can biosynthesize Ag nanoparticles (Ag NPs) and characterized by using the following techniques: Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Fourier transforms infrared (FT-IR), Energy-dispersive X-ray spectroscopy (EDX), UV-Vis spectroscopy and X-ray diffraction (XRD). The most promising actinomycetes isolate were identified, morphologically, biochemically, and molecularly. Streptomyces avermitilis Azhar A.4 was found to be able to reduce silver metal nanoparticles from silver nitrate in nine isolates collected from Egyptian soil. Toxicity of biosynthesized against 2nd and 4th larval instar of Agrotis ipsilon (Hufn.) (Lepidoptera: Noctuidae) was estimated. In addition, activity of certain vital antioxidant and detoxifying enzymes as well as midgut histology of treated larvae were also investigated. The results showed appositive correlations between larval mortality percentage (y) and bio-AgNPs concentrations (x) with excellent (R2). The 4th larval instar was more susceptible than 2nd larval instar with LC50 (with 95% confirmed limits) =8.61 (2.76-13.89) and 26.44(13.25-35.58) ppml-1, respectively of 5 days from treatment. The initial stages of biosynthesized AgNps exposure showed significant increases in carboxylesterase (CarE) and peroxidases (PODs) activity followed by significant suppression after 5 days pos-exposure. While protease activity was significantly decreased by increasing time post-exposure. Midgut histology showed abnormality and progressive damage by increasing time post exposure leading to complete destruction of midgut cells after 5 days from exposure. These results make biosynthesized AgNPs an appropriate alternative to chemical insecticide in A. ipsilon management.

TS-HDS autoantibody: clinical characterization and utility from real-world tertiary care center experience.

OBJECTIVES: To evaluate clinical utility of trisulfated-heparin disaccharide (TS-HDS) IgM testing from real-world tertiary care center experience. METHODS: Medical records of patients with positive TS-HDS antibodies who were evaluated at Mayo Clinic from 2009 to 2022 were reviewed. RESULTS: Seventy-seven patients (50 females) had positive TS-HDS antibody. Median age was 48 (9-77) years. Median titer was 25,000 (range 11,000-350,000). Twenty-six patients (34%) did not have objective evidence of peripheral neuropathy. Nine patients (12%) had other known causes of neuropathy. Among the remaining 42 patients, half presented with subacute progressive course; the other half had chronic indolent course. Most common phenotypes were length-dependent peripheral neuropathy (n = 20, 48%), length-dependent small-fiber neuropathy (n = 11, 26%), and non-length-dependent small-fiber neuropathy (n = 7, 17%). Nerve biopsies showed epineurial inflammatory cell collections in 2 but no interstitial abnormalities in the remaining 7. The majority of intraepidermal nerve fiber densities (7/10), thermoregulatory sweat tests (12/21) and autonomic reflex screens (27/49) were normal. Post-immunotherapy improvement in mRS/INCAT disability score/pain was only seen in 13/42 (31%) TS-HDS IgM positive patients. Patients presenting with sensory ganglionopathy, non-length dependent small-fiber neuropathy, or subacute progressive neuropathy with and without TS-HDS antibody responded similarly to immunotherapy (40% vs 80%, p = 0.30). DISCUSSION: TS-HDS IgM has limited phenotypic or disease specificity; it was found to be positive among patients with various neuropathy phenotypes as well as patients without objective evidence of neuropathy. Clinical improvement with immunotherapy, although was observed in a small proportion of TS-HDS IgM seropositive patients, was not more frequent when compared to seronegative patients with similar presentations.

A systematic investigation of the relationship between properties of bulk foam and foam in porous media.

Bulk foam analysis (static test) is simple and fast, which makes it a cost-effective method for screening and ranking hundreds of surfactants being considered for foam applications. Coreflood tests (dynamic test) can also be used, but it is quite laborious and costly. However, previous reports show that ranking based on static tests sometimes differs from ranking based on dynamic tests. To date, the reason for such a discrepancy is not well understood. Some believe that it may be due to faulty experimental design while some others believe that there is no discrepancy if the right foam performance indices are used to describe and compare the results from both methods. For the first time, this study reports a systematic series of static tests conducted on different foaming solutions (with surfactant concentration ranging from 0.025 to 5 wt%) and duplicated in dynamic tests using the same core sample for all the surfactant solutions. The dynamic test was also repeated on three different rocks of a wide permeability range (26-5000 mD) for each of the surfactant solutions. Unlike previous studies, here multiple dynamic foam indices (limiting capillary pressure, apparent viscosity, trapped foam, and trapped to mobile foam ratio) were measured and compared with the performance indices measured from the static tests (foam texture and foam half-life). Dynamic tests were in total agreement with static tests for all the foam formulations. However, it was observed that the pore size of the base filter disk used in the static foam analyzer can be a potential source of conflicting results when comparing with dynamic test. This is because a threshold pore size exists above which some foam properties (apparent viscosity and trapped foam) significantly decreased compared to the properties before that threshold. Foam limiting capillary pressure is the only foam property that does not show such a trend. It also appears that such threshold occurs above a certain surfactant concentration (0.025 wt%). Apparently, it becomes imperative that the pore size of the filter disk used in the static test and the porous medium used in dynamic tests must be on the same side of the threshold point, otherwise there may be disparity in their results. The threshold surfactant concentration should also be determined. The role of these two factors (pore size and surfactant concentration) requires further investigation.

Expression of Enhancer of Zeste Homolog 2 (EZH2) Gene in Acute Myeloid Leukemia.

BACKGROUND: Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of the chromatin modifying enzyme polycomb repressive complex 2 (PRC2). As a complex, these proteins selectively silence target genes through trimethylation of histone 3 at lysine 27. EZH2 is strongly oncogenic. It has been observed in various malignancies which makes it an interesting therapeutic target. Whether it functions as a tumor suppressor or oncogene in acute leukemia is not settled. Aim of this work: This study aimed at determining the expression levels of EZH2 gene in a cohort of adult Egyptian patients newly diagnosed with acute myeloid leukemia (AML). MATERIALS AND METHODS: The present study included 45 de novo AML patients and 40 healthy subjects of matched age and sex as a control group. All study participants were subjected to complete blood count (CBC), bone marrow examination, immunophenotyping, conventional cytogenetic studies and Detection of EZH2 gene expression levels by real time quantitative polymerase chain reaction (RQ-PCR). RESULTS: EZH2 was significantly downregulated in AML patients compared to controls (p<0.001). There was no significant difference in EZH2 level when considering age, sex, bone marrow blasts count, cytogenetic studies, type or site of infection. Low EZH2 expression was associated with higher mortality (31 patients, 68.9%). CONCLUSIONS: Low EZH2 expression is prevalent in Egyptian AML patients subsequently; it is suggested to function as tumor suppressor gene rather than an oncogene. Moreover, EZH2 downregulation is associated with resistance to chemotherapy and high mortality rate.

Is it worth to insert uterine pack instead of Bakri balloon to control postpartum hemorrhage after vaginal delivery in hypertensive patients?

OBJECTIVE: To assess the safety and effectiveness of uterine packing with gauze compared to Bakri balloon to control postpartum hemorrhage (PPH) after vaginal delivery in patients with hypertensive disorders with pregnancy (HDP). METHODS: This was a prospective observational study conducted on 142 patients with HDP who suffered atonic PPH following vaginal delivery and were allocated either to insert uterine packing with gauze (n = 68) or insertion of Bakri balloon (n = 74). Success of the tamponade to arrest bleeding was the primary outcome measure. Data was collected and analyzed. RESULTS: Most of the included patients experienced spontaneous onset of labour (69%), had not receive I.V. antihypertensive drugs (83.1%) or magnesium sulphate (94.4%), or calcium channel blocker (95.7%), underwent spontaneous vaginal delivery (85.9%), received Pethidine by IMI for pain relief during labour (67.6%), did not need an episiotomy (59.2%), with spontaneous delivery of the placenta (95.77%). Bakri balloon was associated with a shorter duration to insert (p < 0.001), a higher failure rate with the need for laparotomy (p < 0.05) and more post-delivery hospital stay compared to uterine packing (p < 0.001). CONCLUSION: Although uterine packing with gauze to control PPH after vaginal delivery in patients with HDP requires a longer time to insert compared to Bakri balloon yet associated with a lesser need for laparotomy and shorter hospital stay. Larger trials are warranted to confirm or refute these findings.

Impact of blindness onset on the representation of sound categories in occipital and temporal cortices.

The ventral occipito-temporal cortex (VOTC) reliably encodes auditory categories in people born blind using a representational structure partially similar to the one found in vision (Mattioni et al.,2020). Here, using a combination of uni- and multivoxel analyses applied to fMRI data, we extend our previous findings, comprehensively investigating how early and late acquired blindness impact on the cortical regions coding for the deprived and the remaining senses. First, we show enhanced univariate response to sounds in part of the occipital cortex of both blind groups that is concomitant to reduced auditory responses in temporal regions. We then reveal that the representation of the sound categories in the occipital and temporal regions is more similar in blind subjects compared to sighted subjects. What could drive this enhanced similarity? The multivoxel encoding of the 'human voice' category that we observed in the temporal cortex of all sighted and blind groups is enhanced in occipital regions in blind groups , suggesting that the representation of vocal information is more similar between the occipital and temporal regions in blind compared to sighted individuals. We additionally show that blindness does not affect the encoding of the acoustic properties of our sounds (e.g. pitch, harmonicity) in occipital and in temporal regions but instead selectively alter the categorical coding of the voice category itself. These results suggest a functionally congruent interplay between the reorganization of occipital and temporal regions following visual deprivation, across the lifespan.

Structural and Functional Network-Level Reorganization in the Coding of Auditory Motion Directions and Sound Source Locations in the Absence of Vision.

hMT+/V5 is a region in the middle occipitotemporal cortex that responds preferentially to visual motion in sighted people. In cases of early visual deprivation, hMT+/V5 enhances its response to moving sounds. Whether hMT+/V5 contains information about motion directions and whether the functional enhancement observed in the blind is motion specific, or also involves sound source location, remains unsolved. Moreover, the impact of this cross-modal reorganization of hMT+/V5 on the regions typically supporting auditory motion processing, like the human planum temporale (hPT), remains equivocal. We used a combined functional and diffusion-weighted MRI approach and individual in-ear recordings to study the impact of early blindness on the brain networks supporting spatial hearing in male and female humans. Whole-brain univariate analysis revealed that the anterior portion of hMT+/V5 responded to moving sounds in sighted and blind people, while the posterior portion was selective to moving sounds only in blind participants. Multivariate decoding analysis revealed that the presence of motion direction and sound position information was higher in hMT+/V5 and lower in hPT in the blind group. While both groups showed axis-of-motion organization in hMT+/V5 and hPT, this organization was reduced in the hPT of blind people. Diffusion-weighted MRI revealed that the strength of hMT+/V5-hPT connectivity did not differ between groups, whereas the microstructure of the connections was altered by blindness. Our results suggest that the axis-of-motion organization of hMT+/V5 does not depend on visual experience, but that congenital blindness alters the response properties of occipitotemporal networks supporting spatial hearing in the sighted.SIGNIFICANCE STATEMENT Spatial hearing helps living organisms navigate their environment. This is certainly even more true in people born blind. How does blindness affect the brain network supporting auditory motion and sound source location? Our results show that the presence of motion direction and sound position information was higher in hMT+/V5 and lower in human planum temporale in blind relative to sighted people; and that this functional reorganization is accompanied by microstructural (but not macrostructural) alterations in their connections. These findings suggest that blindness alters cross-modal responses between connected areas that share the same computational goals.

Ligation of Intersphincteric Fistula Tract (LIFT) with or Without Injection of Bone Marrow Mononuclear Cells in the Treatment of Trans-sphincteric Anal Fistula: a Randomized Controlled Trial.

BACKGROUND: Ligation of intersphincteric fistula tract (LIFT) is a sphincter-saving procedure used for treatment of complex anal fistula. The current study aimed to assess the outcome of local injection of bone marrow mononuclear cells (BM-MNCs) in conjunction with LIFT as compared to LIFT alone in regards to healing rate, time to healing, and ultimate success rate. METHODS: This was a prospective randomized trial on patients with trans-sphincteric anal fistula. Patients were randomly allocated to one of two equal groups: LIFT and LIFT with BM-MNC injection. The main outcome measures were healing at 10 weeks of follow-up, recurrence after healing, and complications. RESULTS: Seventy patients (48 male and 22 female) of a mean age of 37.9 ± 10.4 years were included. The mean time to complete healing after LIFT + BM-MNCs was significantly shorter than after LIFT alone (20.5 ± 5.2 vs 28.04 ± 5.8 days; P < 0.0001). The ultimate success rates of both groups were similar (LIFT = 60% vs LIFT with BM-MNCs = 68.6%, P = 0.62). There was no significant difference in the mean operation time or complication rate between the two groups. Secondary extension and previous anal surgery were significant independent predictors of failure of healing. CONCLUSION: LIFT combined with BM-MNC injection was associated with a shorter time to complete healing than LIFT alone. However, BM-MNC injection did not have a significant impact on the overall healing and ultimate success rate.

Paraneoplastic neurological syndrome: growing spectrum and relevance.

Paraneoplastic neurological syndromes (PNSs) are group of disorders affecting one or multiple parts of the neuroaxis associated with underlying tumors. An antibody or autoantigen-specific cell-mediated immune response against neural antigen expressed in the tumor is the potential etiology for these rare but refractory disorders. In recent years, wide variety of neurological presentations and autoantibodies has been associated with paraneoplastic autoimmunity, leading to formulation of an updated expert consensus PNS diagnostic criteria. Recognition of these phenotypes and use of serological biomarkers may aid neurologists in early diagnosis of PNS cases encountered in the inpatient or outpatient practice. In this review article, we provide an overview of various clinical, radiological, and immunopathological characteristics of PNS. Furthermore, we discuss the updated PNS criteria and increasing recognition of neurological presentations resembling the PNS among patients receiving immune checkpoint inhibitors.

MicroRNA childhood cancer catalog (M3Cs): a resource for translational bioinformatics toward health informatics in pediatric cancer.

MicroRNA childhood Cancer Catalog (M3Cs) is a high-quality curated collection of published miRNA research studies on 16 pediatric cancer diseases. M3Cs scope was based on two approaches: data-driven clinical significance and data-driven human pediatric cell line models. Based on the translational bioinformatics spectrum, the main objective of this study is to bring miRNA research into clinical significance in both pediatric cancer patient care and drug discovery toward health informatics in childhood cancer. M3Cs development passed through three phases: 1. Literature Mining: It includes external database search and screening. 2. Data processing that includes three steps: (a) Data Extraction, (b) Data Curation and annotation, (c) Web Development. 3. Publishing: Shinyapps.io was used as a web interface for the deployment of M3Cs. M3Cs is now available online and can be accessed through https://m3cs.shinyapps.io/M3Cs/. For data-driven clinical significance approach, 538 miRNAs from 268 publications were reported in the clinical domain while 7 miRNAs from 5 publications were reported in the clinical & drug domain. For data-driven human pediatric cell line models approach, 538 miRNAs from 1268 publications were reported in the cell line domain while 211 miRNAs from 177 publications in the cell line & drug domain. M3Cs acted to fill the gap by applying translational bioinformatics general pathway to transfer data-driven research toward data-driven clinical care and/or hypothesis generation. Aggregated and well-curated data of M3Cs will enable stakeholders in health care to incorporate miRNA in the clinical policy. Database URL:https://m3cs.shinyapps.io/M3Cs/.