Atypical Spindle Cell/Pleomorphic Lipomatous Tumor With Sarcomatous Transformation: Clinicopathologic and Molecular Analysis of 4 Cases.

Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a recently described adipocytic tumor predominantly affecting the subcutaneous soft tissues of adults. Previous studies have shown that ASPLT follows a benign clinical course with a 4% to 12% local recurrence rate and no risk of dedifferentiation. Herein, we describe the clinicopathologic and molecular findings of 4 cases of ASPLT showing unequivocal sarcomatous transformation. Three patients were male and one was female, aged 65, 70, 74, and 78 years. Two cases presented as mass-forming lesions, while 1 case was incidentally discovered. The tumors measured 30, 55, 80, and 110 mm and occurred in the chest wall (n = 2) or arm (n = 2); all were subcutaneous. Microscopically, they showed a biphasic appearance comprising a low-grade ASPLT component and a high-grade sarcomatous component. The low-grade components showed features in the spectrum of either atypical pleomorphic lipomatous tumor (n = 2) or atypical spindle cell lipomatous tumor (n = 2). The high-grade components displayed leiomyosarcoma-like (n = 2), pleomorphic liposarcoma-like (n = 1) or undifferentiated sarcoma-like (n = 1) morphology. On immunohistochemistry, tumors were negative for MDM2 and showed loss of RB1 expression. In addition, the leiomyosarcoma-like areas seen in 2 cases were positive for smooth muscle actin and H-caldesmon. Single-nucleotide polymorphism array, performed in 3 cases, showed deletions of TP53, RB1, and flanking genes in both components. In contrast, the sarcomatous components showed more complex genomic profiles with rare segmental gains and recurrent loss of PTEN (n = 3), ATM (n = 2), and CDKN2A/B (n = 2) among other genes. Whole exome sequencing identified a TP53 variant in one case and an ATRX variant in another, each occurring in both tumor components. Limited clinical follow-up showed no recurrence or metastasis after 1 to 13 months (median, 7.5 months) postsurgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offer insights into the molecular mechanisms underlying this event.

Subungual melanoma with cartilaginous differentiation: Molecular insights.

Melanoma's rare capacity to undergo heterologous differentiation can create significant diagnostic challenges. The molecular mechanisms underlying this phenomenon are not well understood. We present an unusual case of subungual melanoma exhibiting extensive cartilaginous differentiation and provide insights into its molecular and cytogenomic features. Histopathologically, the tumor was predominantly composed of nodules of malignant cartilage in association with a smaller population of nested epithelioid to rhabdoid cells. Immunohistochemically, the tumor cells in both components were positive for S100, SOX10, and PRAME, and were negative for Melan-A and HMB-45. Molecular analysis by whole exome DNA sequence did not detect any pathogenic variants in genes commonly implicated in melanoma. Additional analysis by SNP chromosomal microarray revealed a complex genome characterized by numerous chromosomal losses and gains, including a homozygous deletion of the CDKN2A locus and a heterozygous deletion of the locus containing EXT2, a tumor suppressor implicated in hereditary multiple osteochondromas and secondary chondrosarcomas. This case underscores the importance of recognizing cartilaginous differentiation as a rare manifestation of melanoma, particularly at subungual sites, and suggests that at least some of these melanomas may be driven by non-canonical molecular pathways.

The immunosuppressive, growth-hindering, hepatotoxic, and oxidative stress and immune related-gene expressions-altering effects of gibberellic acid in Oreochromis niloticus: A mitigation trial using alpha-lipoic acid.

This study aimed to examine the effects of gibberellic acid (GBA) on growth, hemato-biochemical parameters related to liver functions, digestive enzymes, and immunological response in Oreochromis niloticus. Besides, the probable underlying mechanisms were explored by assessing antioxidant, apoptotic, and immune-related gene expression. Furthermore, the likelihood of restoration following alpha-lipoic acid (LIP) dietary supplementation was explored. The fish (average initial weight 30.75 ± 0.46) were equally classified into four groups: the control group, the LIP group (fed on a basal diet plus 600 mg/kg of LIP), the GBA group (exposed to 150 mg GBA/L), and the GBA + LIP group (exposed to 150 mg GBA/L and fed a diet containing LIP and GBA) for 60 days. The study findings showed that LIP supplementation significantly reduced GBA's harmful effects on survival rate, growth, feed intake, digestive enzymes, and antioxidant balance. Moreover, the GBA exposure significantly increased liver enzymes, stress markers, cholesterol, and triglyceride levels, all of which were effectively mitigated by the supplementation of LIP. Additionally, LIP addition to fish diets significantly minimized the histopathological alterations in the livers of GBA-treated fish, including fatty change, sharply clear cytoplasm with nuclear displacement to the cell periphery, single-cell necrosis, vascular congestion, and intralobular hemorrhages. The GBA-induced reduction in lysozyme activity, complement C3, and nitric oxide levels, together with the downregulation of antioxidant genes (cat and sod), was significantly restored by dietary LIP. Meanwhile, adding LIP to the GBA-exposed fish diets significantly corrected the aberrant expression of hsp70, caspase- 3, P53, pcna, tnf-a, and il-1ß in O. niloticus liver. Conclusively, dietary LIP supplementation could mitigate the harmful effects of GBA exposure on fish growth and performance, physiological conditions, innate immunity, antioxidant capability, inflammatory response, and cell apoptosis.

Metabolic syndrome and the phenotype of multiple sclerosis.

BACKGROUND: Comorbidities, particularly vascular comorbidities, have been shown to exacerbate the progression of disability in multiple sclerosis (MS). Metabolic syndrome (MetS) is a cluster of conditions including abdominal obesity, insulin resistance, atherogenic dyslipidemia, and vascular dysfunction, which contribute to vascular morbidity and chronic inflammation. OBJECTIVE: To describe the characteristics of MetS in a cohort of MS patients and evaluate its relationship with the MS phenotype. METHODS: A monocentric cohort study was conducted on MS patients, collecting demographic, clinical, radiological, and therapeutic data, as well as metabolic data including waist circumference, blood pressure, serum triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. RESULTS: Among the 84 patients included in the study, 27% were diagnosed with MetS. MetS was found to be associated with secondary progressive MS (SPMS). Patients with SPMS had a higher prevalence of MetS compared to those with relapsing-remitting MS (RRMS), even after adjusting for disease duration. While MetS was associated with Expanded Disability Status Scale (EDSS) progression in the 3-year period according to univariate analysis, it did not show a significant association with disease activity. CONCLUSION: This study provides evidence supporting the connection between MetS and the progression of disability in MS, independent of disease relapse activity.

Herbal inclusions ameliorate effect of heat stress on haematology, proinflammatory cytokines, adipokines and oxidative stress of weaned rabbit does in humid tropics.

A study was designed to evaluate the effect of Moringa oleifera, Phyllanthus amarus and Viscum album leaf meal as herbal inclusions to alleviate the detrimental outcomes of heat stress in weaned female rabbits. Forty (40) weaned rabbit does (527.99 ± 10.35 g; 28 days old) were randomly allotted to four dietary groups consisting of Diet 1(control diet; without leaf meal), Diets 2 (supplemented with 10% V. album); 3 (supplemented with 10% M. oleifera) and 4 (supplemented with 10% P. amarus) in an 84 days trial at the peak of heat stress in Southwest Nigeria. At the end of the trial, blood samples were collected to assess physiological responses and oxidative status of the rabbit does. The results obtained revealed that rabbit does were exposed to heat stress; rabbit does fed control diet had higher leucocyte and neutrophil/lymphocyte ratio compared to rabbit does fed on herbal inclusions. The herbal inclusions enhanced oxidative stability of rabbit does by lowering lipid peroxidation and enhancing antioxidant activities during heat stress conditions. Rabbit does fed control-based diet had significantly higher heat shock protein 70, leptin and adiponectin compared to rabbit does on M. oleifera, P. amarus and V. album supplemented diets. The herbal inclusions tend to suppress proinflammatory cytokines in rabbit does during heat stress condition. In conclusion, the herbal inclusions suppress inflammation, adipokines and promotes oxidative stability of rabbit does exposed to heat stress conditions.

Effects of dietary supplementation with benthic diatom Amphora coffeaeformis on blood biochemistry, steroid hormone levels and seed production efficiency of Nile tilapia Oreochromis niloticus broodstock.

Aquafeed additive quality and quantity remain pivotal factors that constrain the sustainability and progress of aquaculture feed development. This study investigates the impact of incorporating the benthic diatom Amphora coffeaeformis into the diet of Nile tilapia (Oreochromis niloticus) broodstock, on the blood biochemistry, steroid hormone (SH) levels and seed production efficiency. Broodstock females displaying mature ovary indications were initially combined with males at a ratio of three females to one male. A total of 384 adult Nile tilapia (288 females and 96 males) were used, with 32 fish (24 females and eight males) assigned to each of 12 concrete tanks (8 m³; 2 m × 4 m × 1 m), with three replicate tanks for each dietary treatment, throughout a 14-day spawning cycle until egg harvest. Fish were fed one of four different dietary treatments: AM0% (control diet), and AM2%, AM4% and AM6% enriched with the diatom A. coffeaeformis at levels of 20, 40 and 60 g/kg of diet respectively. At the trial's conclusion, total protein, albumin, triglyceride and creatinine), SHs (follicle-stimulating hormone, luteinizing hormone, free testosterone, total testosterone, progesterone and prolactin) and seeds production efficiency of Nile tilapia improved significantly (p < 0.05) in alignment with the increment of A. coffeaeformis supplementation. The findings propose that including A. coffeaeformis at levels ranging from 4% to 6% could be effectively employed as a feed additive during the Nile tilapia broodstock's spawning season.

Antinuclear antibody titration and pattern are helpful in the diagnosis of systemic autoimmune rheumatic diseases.

INTRODUCTION: Anti-nuclear antibody (ANA) testing is among the most common immunological test requested in the diagnostic immunology laboratory. The main purpose of this test is to screen for the underlying systemic autoimmune rheumatic diseases (SARDs). The gold standard laboratory method for ANA detection is by the indirect immunofluorescence (IIF) assay. In most laboratories, positive ANA-IIF is reported in terms of titration and pattern. OBJECTIVE: This study was conducted with the aim of determining the correlation between ANA-IIF titration and pattern for the diagnosis of SARDs. MATERIALS AND METHODS: A retrospective study was conducted whereby the positive ANA-IIF samples from 1st July 2018 until 31st December 2019 and 1st January 2021 until 31st March 2021 were included in this study. The duplicate samples were excluded. ANA-IIF titration and pattern were recorded for all patients. The demographic, clinical, and final diagnosis data were retrieved from each patient's clinical note. RESULTS: A total of 179 patients were included for analysis. The majority of the patients were female (79.9%) and from Malay ethnicity (66.5%). Sixty-five patients (36.3%) had ANA-IIF positive at 1:80 titration followed by 45 patients (25.1%) positive at titration of equal or more than 1:160. Speckled was the predominant pattern visualised in 90 patients (50.3%) followed by homogeneous in 76 patients (42.5%). Forty-five patients (25.1%) were finally diagnosed with SARDs with 41 of them diagnosed as SLE. ANA titration was significantly associated with the final diagnosis of SARDs at all titres (p<0.001) but the best cut-off was noted at a titre of equal or more than 1:320 with the sensitivity and specificity of 86.7% and 77.6% respectively. The homogeneous pattern was also significantly associated with SARDs (p=0.04). The final diagnosis of SARDs were significantly higher in female (p=0.03) and their age was significantly younger (p<0.001). CONCLUSION: ANA-IIF titration of equal or more than 1:320 can be used as the best titration for differentiating between SARDs and non-SARDs in a positive ANA sample. Patients with homogeneous pattern were more likely to be diagnosed with SARDs than other ANA-IIF patterns.

Immunostimulatory effect of mannan-oligosaccharides supplementation diet in milkfish (Chanos chanos).

The current study was designed to examine the impacts of dietary mannan-oligosaccharides (MOS) on growth, hemato-biochemical changes, digestive-antioxidant enzyme activity, immune response, and disease resistance of milkfish (Chanos chanos) fed diets contained MOS i.e. 1g, 2g, and 3g MOS. The growth parameters were significantly influence in milkfish fed all MOS diets, whereas the feed conversion ratio (FCR) and protein efficiency ratio (PER) were significantly influence with 2g or 3g MOS diets. The total protein (TP), globulin (GB), and glucose (GLU) levels, amylase, protease, liver enzymes were found significantly high in fish fed 2g or 3g MOS diets; but, lipase, trypsin, and alkaline phosphatase (ALP) enzymes were increased significantly at 3g MOS diet. All MOS inclusion levels were significantly increased total and Lactobacillus intestinal microflora population. The oxidative enzymes activity as superoxide desmutase (SOD) and catalyze (CAT) were progressively increased with all MOS supplementation diet, but the glutathione peroxidase (GPx) and lactate dehydrogenase (LDH) content were found significantly high in fish fed 2g or 3g MOS diets. Similarly, the reduced glutathione (GSH) and glutathione reductase (GR) contents were observed significantly high level in fish fed 3g MOS diet. The phagocytic (PC) and lysozyme (LYZ) activities were found gradually increase in fish fed increasing level of MOS diets, while the respiratory burst (RB) and malondialdehyde (MDA) activities were seen significant in fish fed 2g and 3g MOS diets. The current research work confirmed that C. chanos fed diets contained 3g kg-1 MOS recorded better growth performance, digestive-antioxidant, immune response, and disease resistance.

Effect of dietary supplementation of Spirulina platensis powder on performance, some serum biochemistry, digestive enzymes, microbial content, antioxidant parameters and immune responses of growing Japanese quail.

This study was performed to examine the influences of Spirulina platensis powder (SPP) on growth performance, physiological status, blood biochemistry, and intestinal microbial population in quail. 240-10-days old Japanese quail chicks were distributed into five groups. Each group had four replicate pens with 12 birds each. The first group received a basal diet (control group). Groups from two to five received the basal diet with SPP at levels of 1.5, 3.0, 4.5, and 6.0% as dietary ingredients, respectively. Results clarified significantly higher live body weight and body weight gain (p < 0.001) with significant enhancements (p < 0.001) in feed conversion values for groups that received SPP levels, especially 4.5% compared with the control and other groups. Birds fed on a diet containing SPP had significantly higher amylase, trypsin and lipase levels (p < 0.001) than the control. Intestinal Lactobacillus sp. was significantly increased, and Escherichia coli and Salamonella populations were significantly decreased by dietary SPP levels (p < 0.001). Liver function, total lipid profile, antioxidant parameters and immune response were significantly affected by SPP levels compared with the control (p < 0.001). In conclusion, the inclusion of SPP until 4.5% in quail diets could improve the growth performance, intestinal microbial population and serum biochemical constituents of growing quail.

Alpha-lipoic acid suppresses gibberellic acid nephrotoxicity in Nile tilapia (Oreochromis niloticus) via modulating oxidative stress, inflammation, cytokine production, and apoptosis.

Globally, gibberellic acid (GA) is one of the extensively used plant growth regulators in agriculture. Yet, there is limited information about their toxicity to fish. Recently, alpha lipoic acid (ALA) has drawn much interest due to its antioxidant properties. This study was planned to determine whether ALA might protect Nile tilapia's kidneys from the toxic effects of GA and the probable underlying mechanisms. Thus, 240 Oreochromis niloticus fish (average initial weight 30.67 ± 0.57) were allocated into four groups received a basal diet or a basal diet supplemented with 600 mg/kg ALA or a basal diet but exposed to a GA (150 mg/L), or ALA-fortified diet and concurrently exposed to GA as previously described. After 60 days, hematological, oxidative stress, lipid peroxidation, stress indices, selected kidney toxic byproducts, histological investigations, and associated gene expression were assessed. Anemia, leukopenia, hypoproteinemia, and elevated kidney function indicators were noticed in the GA-treated group. Additionally, there were detectable cortisol, glucose, 8-OHdG, and MDA increases. However, there was a considerable drop in Cat, Sod, Gpx, GSH, and AChE levels. Structural damage to the kidneys was also identified. In the kidney of fish treated with GA, pro-inflammatory cytokines (tnfα, il-1ß), stress, and apoptotic genes (hsp70, pcna, caspase-3, and p53) genes were markedly up-regulated, while anti-oxidative (cat, sod) gene expression was downregulated. Conversely, adding ALA to the diet abolished the GA-induced changes in most of the markers mentioned above. Conclusively, ALA protects against GA-induced hematotoxicity, oxidative damage, and nephrotoxic effects in Nile tilapia fish.

Effect of dietary supplementation of Jerusalem Artichoke extract on performance, blood biochemistry, antioxidant parameters, and immune response of growing Japanese quail.

This study aimed to examine the impact of the Jerusalem Artichoke extract (JAEx) as a feed additive on the performance, blood biochemistry, antioxidant indices, immunity, and intestinal microbiota in growing Japanese quails. In total, 270 birds were randomly divided into three groups, with six replicates of 15 birds each. The first group was fed a control diet without JAEx. The second and third groups received the control diet plus 200 and 400 ppm JAEx, respectively. The groups fed the diet containing 200 and 400 ppm JAEx had the best body weight, body weight gain and feed conversion ratio, and faster growth rate with the best performance index, compared with the control group (p < 0.05). The control quails had a lower feed intake than the JAEx-treated quails. The groups fed JAEx 200 and 400 ppm had the lowest lipid profile, blood glucose, liver enzymes, Salmonella and Escherichia coli population and the highest antioxidant indices, immune responses and Lactobacilli population number compared to the control group (p < 0.05). In conclusion, the addition of JAEx at 400 ppm followed by 200 ppm improved the productive performance, antioxidant capacity, blood biochemical and immunological indices, and intestinal microbiota in growing Japanese quails.

The recognition of anti-nuclear antibody's dense fine speckled pattern and the detection of anti-DFS70 antibodies in the laboratory practice: Its prevalence and clinical significance.

Anti-nuclear antibody test (ANA) is the test commonly requested for the working diagnosis of systemic autoimmune rheumatic diseases (SARDs) particularly in ANA-associated rheumatic diseases (AARDs) such as SLE, systemic sclerosis, Sjogren syndrome, mixed connective tissue diseases, and dermatomyositis. Dense fine speckled (DFS) pattern is an ANA fluorescence pattern that is commonly encountered in laboratories. This pattern is largely detected among the healthy population and in non-SARDs patients. Although this pattern is still can be observed among SARDs patients, the low prevalence of monospecific or isolated anti-DFS70 antibodies makes it useful for ruling out AARDs diagnosis. Thus, the inclusion of anti-DFS70 antibodies is perhaps logical for the exclusion of SARDs/AARDs. This review provides evidence of the prevalence of anti-DFS70 antibodies in different populations including healthy individuals, patients with SARDs and non- SARDs. The algorithm that includes the detection of anti-DFS70 antibodies during ANA screening is also suggested.

Antifungal susceptibility profile and biofilm-producing capability of Candida tropicalis isolates in a tertiary medical centre.

BACKGROUND: Candida tropicalis is a globally distributed yeast that has been popping up in the medical literature lately, albeit for unenviable reasons. C. tropicalis is associated with substantial morbidity, mortality as well as drug resistance. The aims of this study were to ascertain the antifungal susceptibility profile and the biofilm-producing capability of this notorious yeast in our centre. METHODS: C. tropicalis isolates from sterile specimens were collected over a 12-month period. Conclusive identification was achieved biochemically with the ID 32 C kit. Susceptibility to nine antifungal agents was carried out using the colourimetric broth microdilution kit Sensititre YeastOne YO10. Biofilm-producing capability was evaluated by quantifying biomass formation spectrophotometrically following staining with crystal violet. RESULTS: Twenty-four non-repetitive isolates of C. tropicalis were collected. The resistance rates to the triazole agents were 29.2% for fluconazole, 16.7% for itraconazole, 20.8% for voriconazole and 8.3% for posaconazole-the pan-azole resistance rate was identical to that of posaconazole. No resistance was recorded for amphotericin B, flucysosine or any of the echinocandins tested. A total of 16/24 (66.7%) isolates were categorized as high biomass producers and 8/24 (33.3%) were moderate biomass producers. None of our isolates were low biomass producers. CONCLUSION: The C. tropicalis isolates from our centre were resistant only to triazole agents, with the highest resistance rate being recorded for fluconazole and the lowest for posaconazole. While this is not by itself alarming, the fact that our isolates were prolific biofilm producers means that even azole-susceptible isolates can be paradoxically refractory to antifungal therapy.

Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case-control diagnostic accuracy study (DIPSOC study).

BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Impact of maternal desvenlafaxine exposure on brain development in pregnant albino rats and their fetuses.

Depression during pregnancy adversely affects fetal development. Desvenlafaxine drug is used for the treatment of gestational depression. In light of the well-established role of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in regulating neurogenesis and neural survival, the role of S100b in nerve cell energetic metabolism, differentiation of neurons and glial cells, an aberrant increase in NGF, BDNF and S100b expression in the fetal brain may contribute to desvenlafaxine cognitive disorders by altering brain development. This study is trying to determine the effect of desvenlafaxine on brain development. Thirty timed pregnant rats (from the 5th to the 20th day) were divided into three groups: control, low dose (5.14 mg/kg/day) and high dose (10.28 mg/kg/day) of desvenlafaxine where all animals received the corresponding doses by gavage. Maternal and fetal brain samples were fixed for histological, immunohistochemical (IHC) study of NGF and evaluated for BDNF and S100b genes expression. Desvenlafaxine induced some of the histopathological alterations in maternal and fetal rat brains. Moreover, IHC analysis of maternal and fetal rat brains showed that groups treated with desvenlafaxine demonstrated a significant increase of NGF protein immunoreactivity compared with that in the controls. Gene expression results revealed upregulation of messenger RNA BDNF and S100B expression. According to developmental changes in the brain, desvenlafaxine affects neonatal growth during pregnancy, which may lead to delay of brain development. So, it is essential to survey the roles of antidepressant drugs on neonatal development during pregnancy.

Clinical and laboratory observation on immunoglobulin replacement therapy switching from an intravenous to a subcutaneous route in a Malaysian X-linked agammaglobulinemia patient.

We report a clinical and laboratory observation in a boy with X-linked agammaglobulinemia (XLA) who underwent an immunoglobulin replacement therapy (IRT) via the subcutaneous route (IGSC) seven years after his IRT via intravenous route (IGIV). He was free of invasive infections when on IGIV but not the troublesome coughs a week before the next infusion. A switch to a subcutaneous route resulted in significant improvement of symptoms with good weight gain. When on 2-weekly IGSC cycle, adjusting dose for weight resulted in an IgG trough level of > 600 mg/dl.

High-Throughput CRISPR-Cas13 SARS-CoV-2 Test.

BACKGROUND: The ability to control the spread of COVID-19 continues to be hampered by a lack of rapid, scalable, and easily deployable diagnostic solutions. METHODS: We developed a diagnostic method based on CRISPR (clustered regularly interspaced short palindromic repeats) that can deliver sensitive, specific, and high-throughput detection of Sudden Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The assay utilizes SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the qualitative detection of SARS-CoV-2 RNA and may be performed directly on a swab or saliva sample without nucleic acid extraction. The assay uses a 384-well format and provides results in <1 hour. RESULTS: Assay performance was evaluated with 105 (55 negative, 50 positive) remnant SARS-CoV-2 specimens previously tested using Food and Drug Administration emergency use authorized assays and retested with a modified version of the Centers for Disease Control and Prevention (CDC) quantitative PCR with reverse transcription (RT-qPCR) assay. When combined with magnetic bead-based extraction, the high-throughput SHERLOCK SARS-CoV-2 assay was 100% concordant (n = 60) with the CDC RT-qPCR. When used with direct sample addition the high-throughput assay was also 100% concordant with the CDC RT-qPCR direct method (n = 45). With direct saliva sample addition, the negative and positive percentage agreements were 100% (15/15, 95% CI: 81.8-100%) and 88% (15/17, 95% CI: 63.6-98.5%), respectively, compared with results from a collaborating clinical laboratory. CONCLUSIONS: This high-throughput assay identifies SARS-CoV-2 from patient samples with or without nucleic acid extraction with high concordance to RT-qPCR methods. This test enables high complexity laboratories to rapidly increase their testing capacities with simple equipment.

Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Yeast as growth promoter in two breeds of growing rabbits with special reference to its economic implications.

The present study investigated the effects of dietary supplementation of Saccharomyces cerevisiae (SC) on growth performance, carcass traits, blood biochemical parameters, histological changes in intestinal wall and economic indices in two breeds of weanling rabbits (V-Line and Rex). One-hundred and twenty weaned male rabbits were allotted randomly into four groups in factorial arrangement. The results could be summarized as follows: dietary supplementation of SC significantly accelerated body weight gain (BWG), reduced feed conversion ratio (FCR) and increased profit. The highest BWG and the lowest FCR were noticed in each breed when interacted with SC. There were non-significant differences in carcass traits due to the studied factors, except in loin and dressing percentages. The highest percentages of loin and dressing were obtained from V-line when fed diet supplemented with SC. The treated rabbits with yeast were characterized by an increase in Brunner`s gland and villi. Dietary Supplementation of SC decreased blood total glycerides and cholesterol and increased blood total protein, albumin and A/G ratio. The treated group showed higher profitability than the control. Conclusively, dietary supplementation of SC provided beneficial effects in growth performance and profitability of rabbits. Finally, dietary supplementation of SC is highly recommended in growing rabbits.