COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.

Key Clinical Message: Vincristine therapy can be effective in refractory Immune thrombocytopenia (ITP) following COVID-19 vaccination. Our case report highlights the need for further research to establish standard management guidelines for COVID-19-vaccine-associated ITP. Abstract: Adult immune thrombocytopenia (ITP) can occur as a rare complication following several viral infections or a rare adverse event or complication of vaccination. In this paper, we report a case of a 39-year-old male patient with severe refractory ITP that began 4-weeks after receiving his third (booster) dose of the COVID-19 vaccine (BNT162b2, Pfizer-BioNTech). He was given oral dexamethasone 40 mg daily for 4 days followed by prednisone at 1 mg/kg (85 mg daily) for 10 days. In the following weeks, we attempted several other lines of therapy to treat his ITP, including anti-RhD immunoglobulin, which, unfortunately, caused moderate hemolysis requiring packed red blood cell transfusion, intravenous immunoglobulin (given at a subtherapeutic dose of 0.4 g/kg for only 1 day since it was not available), rituximab, and eltrombopag. The patient, unfortunately, showed no response to any of these treatments. This was an indicator to initiate salvage therapy with vincristine 2 mg weekly for 3 weeks. The patient's platelet count started to increase remarkably during the third week of vincristine and normalized after 4 weeks. We review the findings, clinical characteristics, and management approaches that were reported in the literature regarding COVID-19-vaccine-induced ITP. More in-depth research is needed to delineate standard guidelines for the management of such cases. This report underscores the importance of resorting to vincristine and eltrombopag as great options for severe and refractory ITP related to the COVID-19 vaccine.

Effects of Myofascial Release Technique along with Cognitive Behavior Therapy in University Students with Chronic Neck Pain and Forward Head Posture: A Randomized Clinical Trial.

The purpose of this randomized controlled trial was to evaluate the effectiveness of the Myofascial Release Technique (MRT) along with Cognitive Behavioral Therapy (CBT) on pain, craniovertebral angle (CVA), and neck disability in university students with chronic neck pain and forward head posture. A total of sixty-six eligible participants with chronic neck pain and forward head posture were randomized into the Myofascial Release Therapy (MRT) group (n = 33) and MRT and Cognitive Behavior Therapy (CBT) group (n = 33). Clinical outcomes included neck pain measured using the numerical pain rating scale, neck disability measured through the neck disability index, and forward head posture measured through the cranial vertebral angle. The outcomes were assessed at baseline and the four and eight weeks after the intervention. Both groups showed significant improvement in pain intensity, CVA, and neck disability after the intervention. However, the CBT group demonstrated greater improvements than the MRT group. The difference in outcomes between the groups was statistically significant. Myofascial Release Therapy combined with CBT is an effective treatment method for patients with chronic neck pain and forward head posture.

Canonical Wnt signaling is not required for Tgfb3 expression in the basal medial edge epithelium during palatogenesis.

The secondary palate forms from two lateral primordia called the palatal shelves which form a contact in the midline, become adherent at the fusing interface (medial edge epithelia, MEE) and subsequently fuse. The gene encoding transforming growth factor-ß3 (Tgfb3) is strongly and specifically expressed in MEE cells. Our previous study suggested that Tgfb3 expression is controlled via upstream cis-regulatory elements in and around the neighboring Ift43 gene. Another study suggested that the canonical Wnt signaling via ß-Catenin is responsible for the MEE-specific Tgfb3 gene expression, since deletion of the Ctnnb1 gene by a commonly used Keratin 14-Cre (K14Cre) mouse line almost completely abolished Tgfb3 expression in the MEE resulting in cleft palate. Here, we wanted to analyze whether Tcf/Lef consensus binding sites located in the previously identified regions of the Ift43 gene are responsible for the spatiotemporal control of Tgfb3 expression during palatogenesis. We show that contrary to the previous report, deletion of the Ctnnb1 gene in basal MEE cells by the K14Cre driver (the same K14Cre mouse line was used as in the previous study referenced above) does not affect the MEE-specific Tgfb3 expression or TGFß3-dependent palatal epithelial fusion. All mutant embryos showed a lack of palatal rugae accompanied by other craniofacial defects, e.g., a narrow snout and a small upper lip, while only a small subset (<5%) of Ctnnb1 mutants displayed a cleft palate. Moreover, the K14Cre:Ctnnb1 embryos showed reduced levels and altered patterns of Shh expression. Our present data imply that epithelial ß-catenin may not be required for MEE-specific Tgfb3 expression or palatal epithelial fusion.

A new murine Rpl5 (uL18) mutation provides a unique model of variably penetrant Diamond-Blackfan anemia.

Ribosome dysfunction is implicated in multiple abnormal developmental and disease states in humans. Heterozygous germline mutations in genes encoding ribosomal proteins are found in most individuals with Diamond-Blackfan anemia (DBA), whereas somatic mutations have been implicated in a variety of cancers and other disorders. Ribosomal protein-deficient animal models show variable phenotypes and penetrance, similar to human patients with DBA. In this study, we characterized a novel ENU mouse mutant (Skax23m1Jus) with growth and skeletal defects, cardiac malformations, and increased mortality. After genetic mapping and whole-exome sequencing, we identified an intronic Rpl5 mutation, which segregated with all affected mice. This mutation was associated with decreased ribosome generation, consistent with Rpl5 haploinsufficiency. Rpl5Skax23-Jus/+ animals had a profound delay in erythroid maturation and increased mortality at embryonic day (E) 12.5, which improved by E14.5. Surviving mutant animals had macrocytic anemia at birth, as well as evidence of ventricular septal defect (VSD). Surviving adult and aged mice exhibited no hematopoietic defect or VSD. We propose that this novel Rpl5Skax23-Jus/+ mutant mouse will be useful in studying the factors influencing the variable penetrance that is observed in DBA.

Case reported for iatrogenic cystectomy during cesarean delivery.

Although bladder injury is a rare complication during cesarean delivery (CD), its incidence is increasing due to the growing trend in elective CD. Herein, we report a case of a 28-year-old woman, who presented during labor. An emergency CD and hysterectomy were done to control bleeding. The case was complicated by and inadvertent cystectomy. Urine was diverted immediately by ureterostomy. After five months, augmentation ileocytoplasty, bilateral ureteral re-implantation, and abdominal catheterizable stoma formation were carried out. This case highlights the surgical management of inadvertent cystectomy during CD.

The role of the neurometer CPT/C in sacral neuromodulation.

OBJECTIVE: The aim of the current research project was to study the role of the Neurometer® as a tool to predict responders to sacral neuromodulation therapy (SNM). MATERIAL AND METHODS: This was a prospective, open study in male and female patients, aged 18 and over with voiding dysfunction [non-obstructive retention and/or frequency/ urgency syndrome]. The first group underwent a screening test to evaluate percutaneous nerve functions (PNE) and to determine whether they are candidates for SNM with the InterStim®. Prior to PNE testing, all patients were evaluated with the pain tolerance test (PTT) using the electro-diagnostic Neurometer® CPT/C device. An InterStim® implant was placed in patients who were responders to PNE testing underwent. On the other hand, non-responders underwent a staged implant placement. The second group consisted of patients who already had InterStim® implanted for voiding dysfunction. During the routine office follow-up, the patients implanted with Interstim® underwent a PTT using the Neurometer® CPT/C device. All the testing using the Neurometer CPT/C was performed on the day of the PNE for the first group, and the day of the routine follow-up visit for the second group. All of the results for the Neurometer® testing were kept blinded from the PNE results, and those of the outcome of the follow-up visit. The study received approval by the Research Ethics Board of the University Health Network (No. 14-8196). RESULTS: We recruited a total of 123 patients. The results presented here include 110 patients who completed the study, 48 of whom were in the first group, and 62 in the second group. The statistical analysis used was as follows: Group 1: Simple linear regression analysis and the linear discriminate analysis were preformed. It was found that for patients without the InterStim® implant with a combined CPT/CPD of 800 and above, the Neurometer® could predict the test screening results with an accuracy of 71%. Group 2: Same analysis and tests were conducted for patients with the InterStim® implant, and the results showed that if the patient had a combined CPT/CPD of 600 and above, the Neurometer® could predict the patients satisfaction or dissatisfaction with an accuracy of 72%. CONCLUSION: Neurometer® may play a role in predicting test trial positive responders and patient satisfaction after the placement of InterStim® implant.

Nanomaterial Induced Immune Responses and Cytotoxicity.

Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electronics, clothes and cosmetic products. Due to its size (< 100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This potential role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce allergic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre-cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines.

Association between nocturia and anxiety in Parkinson's disease.

OBJECTIVE: The objective of the study was to determine whether there exists any relationship between nocturia and anxiety in patients with Parkinson's disease (PD). Although the exact cause of anxiety and nocturia in PD is unknown, we hypothesized that there is a relationship between these two PD symptoms. Anxiety may exacerbate nocturia or an opposite relationship may be present in which nocturia may result in heightened levels of anxiety. METHODS: Our study consisted of 314 PD patients, selected at random, and divided into groups based on the presence or absence of anxiety and nocturia. The occurrence of anxiety and nocturia was studied individually and collectively within these groups. RESULTS: The study found a significant association between anxiety and nocturia primarily driven by all PD patients (P < 0.0001), with greater significance found for the male patients (P < 0.0001) than female patients (P = 0.021). DISCUSSION: Based on these findings, we can conclude that anxiety and nocturia are not entirely independent symptoms in all PD patients. Thus, addressing anxiety may improve nocturia in PD or vice versa.

Epigallocatechin-3-gallate inhibits tax-dependent activation of nuclear factor kappa B and of matrix metalloproteinase 9 in human T-cell lymphotropic virus-1 positive leukemia cells.

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol molecule from green tea and is known to exhibit antioxidative as well as tumor suppressing activity. In order to examine EGCG tumor invasion and suppressing activity against adult T-cell leukemia (ATL), two HTLV-1 positive leukemia cells (HuT-102 and C91- PL) were treated with non-cytotoxic concentrations of EGCG for 2 and 4 days. Proliferation was significantly inhibited by 100 µM at 4 days, with low cell lysis or cytotoxicity. HTLV-1 oncoprotein (Tax) expression in HuT- 102 and C91-PL cells was inhibited by 25 µM and 125 µM respectively. The same concentrations of EGCG inhibited NF-kB nuclearization and stimulation of matrix metalloproteinase-9 (MMP-9) expression in both cell lines. These results indicate that EGCG can inhibit proliferation and reduce the invasive potential of HTLV-1- positive leukemia cells. It apparently exerted its effects by suppressing Tax expression, manifested by inhibiting the activation of NF-kB pathway and induction of MMP-9 transcription in HTLV-1 positive cells.

Cancer chemoprevention by polyphenols and their potential application as nanomedicine.

Today cancer is a leading cause of death among the developed countries. Its highly complex nature makes it difficult to understand as it entails multiple cellular physiological systems such as cell signaling and apoptosis. The biggest challenges faced by cancer chemoprevention/chemotherapy is maintaining drug circulation and avoiding multidrug resistance. Overall there is modest evidence regarding the protective effects of nutrients from supplements against a number of cancers. Numerous scientific literatures available advocate the use of polyphenols for chemoprevention. Some groups have also suggested use of combination of nutrients in cancer prevention. However, we have yet to obtain the desired results in the line of cancer chemotherapy research. Nanotechnology can play a pivotal role in cancer treatment and prevention. Moreover, nanoparticles can be modified in various ways to prolong circulation, enhance drug localization, increase drug efficacy, and potentially decrease the chances of multidrug resistance. In this communication, we will cover the use of various polyphenols and nutrients in cancer chemoprevention. The application of nanotechnology in this regard will also be included. In view of available reports on the potential of nanoparticles, we suggest their usage along with different combination of nutrients as cancer chemotherapeutic agents.

New anticancer agents: recent developments in tumor therapy.

Increasing recurrence of mammalian tumors and severe side-effects of chemotherapeutic agents reduce the clinical efficacy of a large variety of anticancer agents that are currently being used. Thus, there is always a constant need to develop alternative or synergistic anticancer drugs with minimal side-effects. One important strategy to develop effective anticancer agents is to study into anticancer agents derived from natural sources. Anticancer agents derived from plants and their derivatives have been proven to be effective for cancer prevention and therapeutics. Vinca alkaloid and their derivatives, alone and in combination with therapeutic agents, have been used for a long time for the treatment of various types of cancers. Polyphenols form one of the most important and extensively used classes of plant-derived therapeutics for cancer prevention or chemotherapy. The present review highlights a plethora of studies focused on the antineoplastic properties of plant-derived chemicals, such as Vinca alkaloid, saponins, and flavonoids.

Papillary thyroid carcinoma-like tumor of the kidney: a case report.

Thyroid carcinoma-like tumor of the kidney is an extremely rare variant of renal cell carcinoma. Most previously reported cases were incidental finding; and none of them showed papillary thyroid carcinoma (PTC) nuclear features. This study reports the first case of PTC (follicular variant)-like tumor of the kidney in which a female patient presented with hematuria, weight loss, and flank pain. Imaging studies revealed a left renal mass with enlarged hilar lymph nodes. Histologically, the renal tumor had a striking resemblance to follicular variant of PTC. However, no radiological abnormalities were found in the thyroid, mediastinum, or pelvis. Tumor cells were negative for thyroid markers (thyroglobulin and TTF1). According to the authors, this is the first case of PTC (follicular variant)-like tumor of the kidney.

Genotoxicity testing and biomarker studies on surface waters: an overview of the techniques and their efficacies.

Rapid industrialization, use of modern agriculture practices, and fast urbanization vis-a-vis indiscriminate use of xenobiotics have led to the serious problems of water pollution in India and abroad. The complexicity of the pollutants in environmental samples demands a multitude of genotoxicity testing with increasing simplicity, sensitivity, and affordability. Moreover, various pollutants mutually affect their own toxic behavior, which complicates the problem of risk assessment. An overview, highlighting the genotoxicity testing system, such as Ames plate incorporation test, Ames fluctuation test, E. coli survival assay, Allium cepa toxicity/genotoxicity test, comet assay, and plasmid nicking assay, is presented in this article, and a comparison has been made to estimate the efficacy of these genotoxicity bioassays performed on some surface waters. Some work on toxicity biomarkers vis-a-vis studies on surface waters has also been included in the present review.