BNT162b2 COVID-19 Vaccine Induced Immune Thrombocytopenic Purpura.

Immune thrombocytopenic purpura (ITP) has been reported following vaccinations such as MMR as well as after viral infections such as hepatitis C and HIV. Few case reports have been reported of ITP after COVID-19 infections and COVID-19 vaccines. Herein, we present a patient who presented with severe ITP with a platelet count of 0 after receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine (also known as the Pfizer BioNTech). She subsequently recovered with a prolonged treatment course.

Pattern-Reversal Visual Evoked Potentials Tests in Persons with Type 2 Diabetes Mellitus with and without Diabetic Retinopathy.

BACKGROUND: Currently, diabetic retinopathy (DR) has a wide recognition as a neurovascular rather than a microvascular diabetic complication with an increasing need for enhanced detection approaches. Pattern-reversal visual evoked potentials (PRVEPs) test, as an objective electrophysiological measure of the optic nerve and retinal function, can be of great value in the detection of diabetic retinal changes. OBJECTIVES: The use of two sizes of checkerboard PRVEPs testing to detect any neurological changes in persons with type 2 diabetes mellitus (T2DM) with and without a clinically detected DR. Also, to compare the results according to the candidate age, duration, and glycemic status of T2DM. METHODS: This study included 50 candidates as group A with T2DM and did not have a clinically detected DR and 50 candidates as group B with T2DM and had a clinically detected early DR and 50 candidates as controls who were neither diabetic nor had any other medical or ophthalmic condition that might affect PRVEPs test results. The PRVEPs were recorded in the consultant unit of ophthalmology in Almawani Teaching Hospital. Monocular PRVEPs testing of both eyes was done by using large (60 min) and small (15 min) checks to measure N75 latency and P100 latency and amplitude. RESULTS: There was a statistically significant P100 latency delay and P100 amplitude reduction in both groups A and B in comparison with the controls. The difference between groups A and B was also significant. In both test results of groups A and B, the proportions of abnormal P100 latency were higher than those of P100 amplitude with a higher abnormal proportions in 15 min test. CONCLUSIONS: The PRVEP test detected neurological changes, mainly as conductive alterations affecting mostly the foveal region prior to any overt DR clinical changes, and these alterations were heightened by the presence of DR clinical changes.

Tumor suppressor WWOX binds to ΔNp63α and sensitizes cancer cells to chemotherapy.

The WWOX tumor suppressor is a WW domain-containing protein. Its function in the cell has been shown to be mediated, in part, by interacting with its partners through its first WW (WW1) domain. Here, we demonstrated that WWOX via WW1 domain interacts with p53 homolog, ΔNp63α. This protein-protein interaction stabilizes ΔNp63α, through antagonizing function of the E3 ubiquitin ligase ITCH, inhibits nuclear translocation of ΔNp63α into the nucleus and suppresses ΔNp63α transactivation function. Additionally, we found that this functional crosstalk reverses cancer cells resistance to cisplatin, mediated by ΔNp63α, and consequently renders these cells more sensitive to undergo apoptosis. These findings suggest a functional crosstalk between WWOX and ΔNp63α in tumorigenesis.

Isolated greater tuberosity fracture: Short-term functional outcome following a specific rehabilitation program.

BACKGROUND: Evaluate the functional outcome of a specific program of rehabilitation during conservative treatment of fracture of the greater tuberosity. METHODS: We retrospectively studied the records of 22 patients, with minimally displaced greater tuberosity fracture, according to inclusion criteria. All patients have received an early (one week after the injury) rehabilitation program based on physical analgesic therapy means, techniques for recovering range of motion, strengthening exercises, proprioceptive stabilization exercises and usability advices. The evaluation was done at baseline, one, two and three months of the end of physical treatment. RESULTS: Pain, perceived disability and range of motion were improved significantly since the end of rehabilitation. The improvement of function (Constant score) was significant at different evaluation times. The functional result seems to be poor when patients are aged and pain is severe at baseline. CONCLUSION: During conservative treatment of fracture of the greater tuberosity, earlier rehabilitation allows rapid range of motion and functional recovery limiting care duration. After fracture healing, the rehabilitation program becomes similar to that advocated in rotator cuff disease. Whatever the initial treatment choice, rehabilitation must be considered at the waning of the first week.

Unusual clinical presentation of a partial tibialis anterior rupture.

Subcutaneous rupture of the tibialis anterior tendon is rare. Diagnosis is usually clear. The essential clinical symptoms are progressively: footdrop gait, loss of ankle flexion strength, ankle foot pain and claw toes. But the occurrence of an asymptomatic time period between the injury and the onset of clinical signs can make the diagnosis more difficult. MRI is the gold standard examination for tendons injuries and associated bone and joints damages. Surgical exploration confirms MRI findings. It constitutes the treatment of choice for tibialis anterior tendon rupture. Surgical or functional techniques used have an impact on the design of the rehabilitation program, essential step in the care management of these injuries. It avoids postoperative tendon adhesions and their functional consequences. We report here a case of a man presenting with footdrop gait as the only clinical symptom.

WW domain interactions regulate the Hippo tumor suppressor pathway.

The Hippo kinase pathway is emerging as a conserved signaling pathway that is essential for organ growth and tumorigenesis in Drosophila and mammalians. Although the signaling of the core kinases is relatively well understood, less is known about the upstream inputs, downstream outputs and regulation of the whole cascade. Enrichment of the Hippo pathway components with WW domains and their cognate proline-rich interacting motifs provides a versatile platform for further understanding the mechanisms that regulate organ growth and tumorigenesis. Here, we review recently discovered mechanisms of WW domain-mediated interactions that contribute to the regulation of the Hippo signaling pathway in tumorigenesis. We further discuss new insights and future directions on the emerging role of such regulation.

Wwox inactivation enhances mammary tumorigenesis.

Breast cancer is the leading cause of cancer-related death in women worldwide. Expression of the WWOX tumor suppressor is absent or reduced in a large proportion of breast tumors suggesting that loss of WWOX may contribute to breast tumorigenesis. Wwox-deficient mice die by 3-4 weeks of age precluding adult tumor analysis. To evaluate the effect of WWOX-altered expression on mammary tumor formation, the Wwox-heterozygous allele was back crossed onto the C3H mammary tumor-susceptible genetic background (Wwox(C3H)+/-) and incidence of mammary tumor formation was evaluated. Although 50% of the female Wwox(C3H)+/- mice developed mammary carcinomas, only 7% of Wwox(C3H)+/+ mice did. Intriguingly, mammary tumors in Wwox(C3H)+/- mice frequently lost WWOX protein expression suggesting a genetic predisposition toward mammary tumorigenesis. Immunohistochemical staining of hormone receptors revealed loss of estrogen receptor-α (ER) and progesterone receptor in the majority of these tumors. In vitro, depletion of WWOX in MCF7 ER-positive cells led to reduced ER expression and reduced sensitivity to tamoxifen and estrogen treatment and was associated with enhanced survival and anchorage-independent growth. Finally, cDNA array analyses of murine normal mammary epithelial cells and mammary tumors identified 163 significantly downreguated and 129 upregulated genes in the tumors. The majority of differentially expressed genes were part of pathways involved in cellular movement, cell-to-cell signaling and interaction, cellular development, cellular growth and proliferation and cell death. These changes in gene expression of mouse mammary tumors in Wwox(C3H)+/- mice resemble, at least in part, human breast cancer development. Our findings demonstrate the critical role that the WWOX tumor suppressor gene has in preventing tumorigenesis in breast cancer.

The value of intermittent cervical traction in recent cervical radiculopathy.

OBJECTIVE: Our objective is to assess the effect of mechanical and manual intermittent cervical traction on pain, use of analgesics and disability during the recent cervical radiculopathy (CR). METHODS: We made a prospective randomized study including patients sent for rehabilitation between April 2005 and October 2006. Thirty-nine patients were divided into three groups of 13 patients each. A group (A) treated by conventional rehabilitation with manual traction, a group (B) treated with conventional rehabilitation with intermittent mechanical traction and a third group (C) treated with conventional rehabilitation alone. We evaluated cervical pain, radicular pain, disability and the use of analgesics at baseline, at the end and at 1, 3 and 6 months after treatment. RESULTS: At the end of treatment improving of cervical pain, radicular pain and disability is significantly better in groups A and B compared to group C. The decrease in consumption of analgesics is comparable in the three groups. At 6 months improving of cervical and radicular pain and disability is still significant compared to baseline in both groups A and B. The gain in consumption of analgesics is significant in the three groups: A, B and C. CONCLUSION: Manual or mechanical cervical traction appears to be a major contribution in the rehabilitation of CR particularly if it is included in a multimodal approach of rehabilitation.

Osteoarthritis of the sacroiliac joint complicating resection of the pubic symphysis. Interest of a rehabilitation programme.

Sacroiliac joint (SIJ) is an uncommon localisation of osteoarthritis. Instability of this joint is one of rare aetiologies. It can occur after resection of the pubic symphysis for whatever the reason. The biomechanical consequences on the SIJ are increasing shear forces and vertical restrain. This leads to secondary progressive SIJ osteoarthritis. There is no specific rehabilitation programme for this pathology. Here, we report the case of a patient who presents SIJ osteoarthritis 20 years after surgical resection of the pubic symphysis for osteochondroma. We proposed a rehabilitation programme based on the pelvic biomechanical characteristics. It included specific exercises of muscular strengthening (the transversely oriented abdominal muscles and pelvic floor muscles) and muscular stretching (the psoas major muscle). We obtained an improvement of pain and functional capacity in our patient.

p53 controls hPar1 function and expression.

Human protease-activated receptor 1 (hPar1) is a bona fide receptor of the hemostatic protease thrombin, and has a central function in tumor progression. Inactivation of the tumor suppressor gene p53 is one of the most common genomic alterations occurring in cancer. Here, we address the interrelations between p53 and hPar1 in cancer. We demonstrate an inverse correlation between hPar1 gene expression and wild-type (wt) p53 levels, and a direct correlation with levels of the mutant (mt) p53. Bioinformatic search revealed the presence of at least two p53 motifs in the hPar1 promoter. Indeed, temperature-sensitive (ts) p53 forms reduced hPar1 promoter activity on wt p53 expression. Ectopic introduction of the p53R175H mutant into cells lacking p53 caused a moderate two-fold induction of hPar1 promoter activity. Chromatin immunoprecipitation (ChIP) analyses confirmed a physical association between the p53 protein and hPar1 chromatin fragments. In parallel, PAR1 function is attenuated by p53, as shown by inhibition of pFAK levels and a Matrigel invasion assay. Ectopic reinforcement of hPar1 rescued the inhibition conferred by p53, confirming that p53 directly affects hPar1 expression and function. Altogether, we provide evidence for a direct binding between p53 and hPar1 chromatin, and assign hPar1 as a target of p53.

N-Acetyltransferase and sulfotransferase activity in human prostate: potential for carcinogen activation.

BACKGROUND: N-Acetyltransferases (NATs) and sulfotransferases (SULTs) are key phase II metabolizing enzymes that can be involved both in the detoxification and in the activation of many human promutagens and procarcinogens. METHODS AND RESULTS: We investigated the expression of NATs and SULTs in human prostate and tested their role in the activation the N-hydroxy (N-OH) metabolite of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a dietary carcinogen, to form DNA adducts. Western blotting showed detectable levels of NAT1, SULT1A1 and SULT1A3 with marked inter-individual variation. NAT2 and other SULT enzymes were not detectable. NAT1 was localized by immunohistochemistry to the cytoplasm of epithelial cells. The presence of acetyl Co-enzyme A (acetyl CoA) and 3'-phosphoadenosine-5'-phosphosulfate (PAPS), NAT and SULT cofactors, respectively, significantly increased the level of DNA adducts, detected by P-postlabelling analysis, in calf thymus DNA incubated with N-OH-IQ and prostate cytosolic fractions. The enhancement in the level of DNA adducts in the presence of PAPS correlated with the level of SULT1A1 protein. A single prostate cytosol with the SULT1A1*2/*2 genotype produced less DNA adducts than cytosols with the *1/*2 and *1/*1 genotypes. No significant correlation was observed between NAT1 protein level and the formation of DNA adducts, even in the presence of acetyl CoA. CONCLUSIONS: In conclusion, we demonstrated that NAT1, SULT1A1 and SULT1A3 are present in human prostate and that both enzyme classes significantly contribute to the activation of N-hydroxylated heterocyclic amines to DNA-damaging species in this tissue. Variation in expression levels, in combination with dietary and/or environmental exposure to carcinogens, could be influential in determining individual susceptibility to prostate cancer.

The structural determination of a new steroidal metabolite from the brown alga Sargassum asperifolium.

An investigation of the natural products chemistry of the brown alga Sargassum asperifolium from the red sea yielded a new steroidal metabolite, 24-vinyl cholest-4-ene-24-ol-3-one, saringosterone (3), a known steroidal metabolite, 24-vinyl cholest-5-ene-3b,24-diol, saringosterol (4), and known diterpene with a hydroazulene skeleton, dictyone (1). The identification of the isolated metabolites was established mainly by spectral methods and chemical transformation of the dictyone (1) to its acetate (2).

Influence of gender and behavioural lateralisation on two exploratory models of anxiety in C3H mice.

Behavioural lateralisation, which has been postulated to be an individual personality trait, is related to the activity of various physiological systems including the immune system. As lateralisation has been related to anxiety, which is known to influence immune reactivity, it can be hypothesized that the relation between lateralisation and immune reactivity involves individual behavioural patterns as they appear in exploratory-based anxiety models. In order to answer this question, a behavioural investigation focussing on exploratory activity was undertaken in male and female C3H mice previously selected for their paw preference. The observations were performed using two generic paradigms: elevated plus-maze and open field. Exploratory behaviour in the open field, but not in the plus-maze, was influenced by the interactive effect of gender and behavioural lateralisation. A significant difference between male and female mice was found in left-pawed but not in right-pawed nor ambidextrous animals, left-pawed female mice displaying the less exploratory behaviours. These results provide a first evidence of inter-individual variations in exploratory behaviours involving interaction between gender and lateralisation.