Sudden sensorineural hearing loss in COVID-19: A case series from the Wrightington, Wigan and Leigh Teaching Hospitals, United Kingdom.

Sudden sensory neural hearing Loss (SSNHL) needs to be identified and managed correctly in a secondary or tertiary centre. Whilst 45% of presentations are said to be idiopathic in nature, several viruses have been linked to its aetiology. It was noted, anecdotally, that more patients were presenting with SSNHL during the COVID-19 pandemic to our ENT service at Wrightington Wigan and Leigh teaching hospitals, UK (WWL). We identified 4 COVID-19 positive patients who presented to our ENT service with SSNHL. Despite normal findings on external ear examination, three of the patients showed bilateral hearing loss, whilst one had a predominantly unilateral loss. Given our findings we would like to present these four cases, as well as providing hypotheses on possible aetiology of this association. This may aid in research, diagnosis and treatment of future COVID positive patients with SSNHL.

X-ray illumination of the ejecta of supernova 1987A.

When a massive star explodes as a supernova, substantial amounts of radioactive elements--primarily (56)Ni, (57)Ni and (44)Ti--are produced. After the initial flash of light from shock heating, the fading light emitted by the supernova is due to the decay of these elements. However, after decades, the energy powering a supernova remnant comes from the shock interaction between the ejecta and the surrounding medium. The transition to this phase has hitherto not been observed: supernovae occur too infrequently in the Milky Way to provide a young example, and extragalactic supernovae are generally too faint and too small. Here we report observations that show this transition in the supernova SN 1987A in the Large Magellanic Cloud. From 1994 to 2001, the ejecta faded owing to radioactive decay of (44)Ti as predicted. Then the flux started to increase, more than doubling by the end of 2009. We show that this increase is the result of heat deposited by X-rays produced as the ejecta interacts with the surrounding material. In time, the X-rays will penetrate farther into the ejecta, enabling us to analyse the structure and chemistry of the vanished star.

Lack of detection of human papillomavirus DNA in prostate carcinomas in patients from northeastern Brazil.

Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied.

Exercise HIMALAYAN SERPENT: feedback article.

Exercise HIMALAYAN SERPENT was open to junior doctors from the United Kingdom (UK) Armed Forces and aimed to educate potential expedition doctors on aspects of high altitude and wilderness medicine as well as conducting adventurous training (AT) and medical research. This was the first time such an exercise had been undertaken and this article explores the views of those junior doctors taking part to assess whether the exercise met the aims and objectives it set out.

Prognostic value of the TP53 Arg72Pro single-nucleotide polymorphism and susceptibility to medulloblastoma in a cohort of Brazilian patients.

Medulloblastoma is a highly cellular malignant embryonal neoplasm, being the most common malignant pediatric brain tumor, accounting for 20-25 % of pediatric central nervous system tumors. To investigate the effect of the TP53 Arg72Pro single-nucleotide polymorphism (SNP) on clinicopathological and phenotypic parameters, we performed a case-controlled study of 122 patients and 122 healthy controls from Brazil. No significant associations were found between the TP53 Arg72Pro genotypes and the clinicopathological parameters studied. Compared with Arg/Arg, which is the most common genotype in the study population, both the Arg/Pro and Pro/Pro genotypes did not influence the medulloblastoma development risk [odds ratio (OR) = 1.36 and P = 0.339 for the Arg/Pro genotype; OR = 1.50 and P = 0.389 for the Pro/Pro genotype]. With regard to prognosis, disease-free survival was not significantly different among the TP53 Arg72Pro SNP genotypes (P > 0.05), but the less frequent genotype (Pro/Pro) was associated with shorter overall survival of medulloblastoma patients (P = 0.021). These data suggest that, although there is no association between the TP53 Arg72Pro SNP and medulloblastoma risk, the Pro/Pro genotype is associated with shorter overall survival of patients submitted to adjuvant therapy. Nevertheless, due to the interethnic composition of the Brazilian population, future studies on larger populations from other parts of the world are essential for a definitive conclusion on the function of the TP53 Arg72Pro SNP.

Telomere length and telomerase activity of leukocytes as biomarkers of selective serotonin reuptake inhibitor responses in patients with major depressive disorder.

We analyze the leukocyte telomere length (LTL) and telomerase activity in patients with major depressive disorder (MDD) before and after treatment with selective serotonin reuptake inhibitors (SSRIs). Before treatment, there was a reduction in the LTLs and expression levels of the human telomerase reverse transcriptase (hTERT) in the patients with MDD compared with controls. However, after 24 weeks of treatment with SSRIs, there was a significant increase in the LTLs and the expression levels of hTERT, with values approaching those observed in the controls. We conclude that SSRI antidepressant therapy can directly influence the increased expression levels of hTERT in patients.

Inhibitory effect of pisosterol on human glioblastoma cell lines with C-MYC amplification.

Despite the remarkable progress in the characterization of the molecular pathogenesis of glioblastoma multiforme (GBM), these tumors remain incurable and, in most cases, refractory to aggressive cytotoxic treatments. We conducted a morphological and cytogenetic study in two GBM cell lines (U343 and AHOL1), before and after treatment with pisosterol (at 0.5, 1.0 and 1.8 µg ml⁻¹), a triterpene isolated from the fungus Pisolithus tinctorius. No significant alteration was observed in the morphology and frequency of chromosomal abnormalities in the cell lines analyzed after treatment with pisosterol. Using fluorescence in situ hybridization analysis with a locus-specific probe for C-MYC showed that 72% of U343 and 65% of AHOL1 cells contained more than two alleles of C-MYC before treatment. After treatment, no effects were detected at lower concentrations of pisosterol (0.5 and 1.0 µg ml⁻¹). However, at 1.8 µg ml⁻¹ of pisosterol, only 33% of U343 cells and 15% of AHOL1 cells presented more than two fluorescent signals, suggesting that pisosterol blocks the cells with gene amplification. Cells that do not show a high degree of C-MYC gene amplification have a less aggressive and invasive behavior and are easy targets for chemotherapy. Therefore, further studies are needed to examine the use of pisosterol in combination with conventional anti-cancer therapy.

Classification and retrieval of thoracic diseases using patch-based visual words: a study on chest x-rays.

This research work explores the Content-Based Medical Image Retrieval system (CBMIR) to categorization and retrieval of different types of common thoracic diseases such as Atelectasis, cardiomegaly, Effusion, Infiltration etc, based on local patch representation of 'Bag of Visual Words' approach, when performing patch-based image representation, the selected patch size has significant impact on image categorization and retrieval process. It is a challenging task in selecting the appropriate patch size to the current experimental dataset. Chest Xray8 medical image database is used, to analyze the impact of different patch size to categorize and retrieval of eight common thorax diseases. 1000 frontal view x-ray images is obtained (100 images from each category and 200 images combination of more than one disease) from the database. Different sizes of image patches (16 × 16 and 32 × 32) and different codebook sizes (500, 1000, 1500, 2000) created to identify best precision and recall values. From the excremental result, 32 × 32 patch size and 1500 codebook size gives the good precision and recall value using Radial Basis Function SVM kernel.

Association study of an epidermal growth factor gene functional polymorphism with the risk and prognosis of gliomas in Brazil.

Epidermal growth factor (EGF) plays an important role in cancer. A functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of the EGF gene (+61 A>G) may influence its expression and contribute to cancer predisposition and aggressiveness. Aiming to investigate the role of EGF +61 A>G in the susceptibility to glioma and its prognosis, we performed a case-control study with 165 patients and 200 healthy controls from Brazil. Comparisons of genotype distributions and allele frequencies did not reveal any significant differences between the groups. The mean overall survival was 9.2 months for A/A, 8.2 months for A/G, and 7.7 months for G/G. When survival curves were plotted we found that the +61G allele is associated with poor overall survival (p=0.023) but not with disease-free survival (p=0.527). Our data suggest that, although there is no association between the EGF +61 A>G genotype and glioma susceptibility, this SNP is associated with shorter overall survival of glioma patients in the Brazilian population. Nevertheless, future studies utilizing a larger series are essential for a definitive conclusion.

New prognostic markers revealed by RNA-Seq transcriptome analysis after MYC silencing in a metastatic gastric cancer cell line.

MYC overexpression is considered a driver event in gastric cancer (GC), and is frequently correlated with poor prognosis and metastasis. In this study, we evaluated the prognostic value of genes upregulated by MYC in patients with GC. Metastatic GC cells (AGP01) characterized by MYC amplification, were transfected with siRNAs targeting MYC. RNA-seq was performed in silenced and non-silenced AGP01 cells. Among the differentially expressed genes, CIAPIN1, MTA2, and UXT were validated using qRT-PCR, western blot, and immunohistochemistry in gastric tissues of 213 patients with GC; and their expressions were correlated with clinicopathological and survival data. High mRNA and protein levels of CIAPIN1, MTA2, and UXT were strongly associated with advanced GC stages (P < 0.0001). However, only CIAPIN1 and UXT gene expressions were able to predict distant metastases in patients with early-stage GC (P < 0.0001), with high sensitivity (> 92%) and specificity (> 90%). Overall survival rate of patients with overexpressed CIAPIN1 or UXT was significantly lower (P < 0.0001). In conclusion, CIAPIN1 and UXT may serve as potential molecular markers for GC prognosis.

Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa.

BACKGROUND: Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. METHODS: We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. RESULTS: From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3-15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5-13.5). The median change in CD4% from baseline (p < 0.001) was 10.2 (IQR 5.0-13.8) at 6 months (n = 90), and 16.2 (IQR 9.6-20.3) at 12 months (n = 59). Viral loads (VLs) were available for 100 children at 6 months of which 84% had HIV-1 RNA levels < or = 50 copies/mL. At 12 months, 80.3% (n = 61) had undetectable VLs. Sixty-five out of 88 children (73.8%) reported a significant increase (p < 0.001) in weight after the first month. Eighty-nine percent of the cohort (n = 132) reported < or = 2 missed doses during any given treatment month (> 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8-94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95% CI, 1.27-119.71) and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95% CI, 0.02-0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. CONCLUSION: This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting.

Teratologic evaluation of ethylene glycol monobutyl ether in Fischer 344 rats and New Zealand white rabbits following inhalation exposure.

Timed-pregnant Fischer 344 rats and New Zealand White rabbits were exposed to ethylene glycol monobutyl ether vapors by inhalation on gestational days 6 through 15 (rats) or 6 through 18 (rabbits) at concentrations of 0, 25, 50, 100 or 200 ppm. The animals were sacrificed on gestational day 21 (rats) or 29 (rabbits). In rats, exposure to 200 or 100 ppm resulted in maternal toxicity (clinical signs, decreased body weight and weight gain, decreased absolute and relative organ weights, decreased food and water consumption and evidence of anemia), embryotoxicity (increased number of totally resorbed litters and decreased number of viable implantations per litter) and fetotoxicity (reductions in skeletal ossification). No increase in fetal malformations was observed in any exposure group relative to controls. At 50 or 25 ppm, there was no maternal, embryo or fetal toxicity (including malformations) in rats. In rabbits, exposure to 200 ppm resulted in maternal toxicity (apparent exposure-related increases in deaths and abortions, clinical signs, decreased weight during exposure and reduced gravid uterine weight at sacrifice) and embryotoxicity (reduced number of total and viable implantations per litter). No treatment-related fetotoxicity was seen. No treatment-related increased in fetal malformations or variations were seen at any exposure concentration tested. There was no evidence of maternal, embryo, or fetal toxicity (including malformations) at 100, 50 or 25 ppm in rabbits.

In vitro susceptibility of recent gram-positive isolates to ciprofloxacin, levofloxacin, and trovafloxacin.

Gram-positive isolates (n = 290) were tested for their susceptibility to three fluoroquinolone antibiotics by standard disk-diffusion technology. Overall, 59%, 72%, and 85% were susceptible and 29%, 25%, and 11% were resistant to ciprofloxacin, levofloxacin, and trovafloxacin, respectively. Of Staphylococcus aureus isolates (n = 84), 55%, 57%, and 88% were susceptible to the three antibiotics, respectively. Staphylococcus epidermidis (n = 45), too, was more susceptible to trovafloxacin, although the differences were smaller (60%, 62%, and 78%). Of 35 Enterococcus faecalis isolates, 66% and 74% were susceptible to levofloxacin and trovafloxacin, respectively, but only 9% were susceptible to ciprofloxacin.

In vitro activity of ciprofloxacin, levofloxacin, and trovafloxacin, alone and in combination with beta-lactams, against clinical isolates of Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia.

We tested three fluoroquinolones (ciprofloxacin, levofloxacin, and trovafloxacin), each combined with each of four beta-lactams (cefoperazone, ceftriaxone, imipenem, and meropenem) for synergy against clinical isolates of nosocomial strains of Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia. The ciprofloxacin-beta-lactam combinations showed synergy against none or only a small fraction (7 to 10%) of the P. aeruginosa and B. cepacia isolates. Ciprofloxacin-cefoperazone, -ceftriaxone, and -meropenem were synergic against 50%, 25%, and 30% of the S. maltophilia isolates, respectively. Among the levofloxacin combinations, only those with cefoperazone and imipenem showed significant synergy, and this only against B. cepacia (50% and 30%, respectively). Trovafloxacin-cefoperazone and -imipenem showed modest synergy against P. aeruginosa (23% and 27%, respectively), as did trovafloxacin-cefoperazone and -ceftriaxone against B. cepacia (30%). The trovafloxacin-imipenem combination was synergic against all isolates of B. cepacia. Because of their synergy, the following combinations may be useful in the nosocomial setting: trovafloxacin-cefoperazone or -imipenem against P. aeruginosa; ciprofloxacin-cefoperazone, -ceftriaxone, or -meropenem against S. maltophilia; levofloxacin-cefoperazone and trovafloxacin-imipenem against B. cepacia.

Evaluation of three disinfectants after in-use stress.

Solutions of 2.0% and 3.4% glutaraldehyde, and of 0.5% phenate with 0.18% glutaraldehyde were stressed with a microbial and organic soil load for the periods advocated by the respective manufacturers. The disinfecting efficacy of the stressed solutions was challenged with Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Mycobacterium bovis (BCG), a water Mycobacterium sp. and Candida albicans. The three disinfectants were active against the fast-growing bacteria in appropriate dilutions; lesser dilutions of the glutaraldehyde solutions killed the mycobacteria and the yeast, while stressed phenate with glutaraldehyde did not. One hour exposure of the stressed disinfectants failed to kill the spore preparations while reducing the number of survivors.

Microbial adherence to and disinfection of laryngoscopes used in office practice.

This study reports the appropriate disinfection methods for flexible and rigid laryngoscopes when used in an outpatient setting. This investigation presents evidence that an appreciable number of laryngoscopes are contaminated during use. A brief tap water rinse serves to eliminate gross soil of host origin known to interfere with disinfectant efficacy. Disinfection with 3.2% glutaraldehyde (Cidexplus) for 10 minutes effectively eliminated microbial contaminants. Since potentially harmful microorganisms were included among the more than 100 isolates during our baseline experiments, the need to eliminate bacteria, viruses, fungi, and protozoa from laryngoscopes is obvious and can be attained readily.

A multiple-baseline, double-blind evaluation of the effects of trimeprazine tartrate on infant sleep disturbance.

Infant sleep disturbance involving chronic night waking and resistance to settling to sleep or returning to sleep is a common problem for families with children 6-27 months old. Prescription and nonprescription sedatives are frequently administered without clear evidence that they are effective as either long-term or short-term palliatives. Trimeprazine tartrate, administered either 15 mg/5 mL or 30 mg/5 mL, was compared with both baseline and placebo in a multiple-baseline-across participants, double-blind study. No clinically significant effects of the low dose were detected, whereas the effects of the high dose were not consistently replicated across nor within participants. During active drug treatment, only 2 of 12 children achieved Sleep Behaviour Scale scores indicative of nonproblem sleep. Trimeprazine tartrate is not recommended as a pharmacological treatment for infant sleep disturbance unless as an adjunct to a behavioral therapy program.

Treatment of infant sleep disturbance by trimeprazine in combination with extinction.

Chronic sleep disturbance is a common problem in preschool children. Prescription and non-prescription sedatives provide short-term palliative relief. Behavioral extinction by withdrawal of parental attention is enduringly effective but may be distressing short-term because of postextinction bursts of intense activity by the child. This study evaluated the effects of combining extinction and sedative medication (trimeprazine tartrate), prescribed in a reducing dose over the first 10 days of extinction. Control groups received either extinction alone or a placebo administered double-blind. After baseline, all subjects reduced their sleep disturbance to low levels, the extinction and placebo groups declining slowly, the medication group abruptly. These gains were maintained at follow-up. Measures of infant security and maternal anxiety showed improvements with treatment.

A behavioral model of infant sleep disturbance.

Chronic sleep disturbance, such as bed refusal, sleep-onset delay, and night waking with crying, affects 15% to 35% of preschool children. Biological factors, particularly arousals associated with recurrent episodes of rapid-eye-movement sleep, render infants vulnerable to repeated awakenings. Parental failure to establish appropriate stimulus control of sleep-related behaviors and parent-mediated contingencies of reinforcement for sleep-incompatible behaviors may shape and maintain infant sleep disturbance. Treatment and prevention strategies are discussed, and research needs are identified.

Behavior management of infant sleep disturbance.

Using a nonconcurrent multiple baseline design, we evaluated the effects of extinction and stimulus control on nighttime sleep disturbances exhibited by 7 infants. Results showed that frequency and duration of night wakings decreased for all subjects, with corresponding improvements reflected through changes in responses to the sleep behavior scale. Observed improvements maintained at 3 and 24 months posttreatment.