Investigating the role of Epstein-Barr virus and human papillomavirus types 16 and 18 co-infections in cervical disease of Iranian women.

Introduction: High-risk human papillomaviruses (HR-HPVs) are known to contribute to cervical cancer (CC), but the role of Epstein-Barr virus (EBV) in this process remains unclear, despite EBV's widespread detection in premalignant and malignant cervical tissues. Methods: In this cross-sectional study of 258 cervical samples, including both formalin-fixed paraffin-embedded (FFPE) and fresh cervical tissues, the presence and viral load of HR-HPVs (HPV-16 and HPV-18) and EBV were evaluated in Iranian women with cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), and a cervicitis control group using real-time PCR. Results: The study revealed a significant correlation between disease severity and both increased HPV-16 positivity and HPV-16 and HPV-18 co-infection (p<0.001). Interestingly, the control group had a higher frequency of EBV-positive cases than SCC/CIN groups (p<0.001). HPV-16 DNA load increased with disease severity (P<0.001), while HPV-18 showed no significant difference (P=0.058). The control group had a higher EBV DNA load compared to SCC/CIN groups (P=0.033). HPV-16 increased the risk of CIN II, CIN III, and SCC, while HPV-18 increased the risk of CIN II and CIN III. Notably, EBV was associated with a lower risk of CIN groups and SCC. Conclusions: No significant difference in EBV co-infection with HPV-16/18 was found, failing to support the hypothesis that EBV is a cofactor in CC. However, high EBV viral load in the control group suggests a potential "hit and run hypothesis" role in CC progression. This hypothesis suggests that EBV may contribute briefly to the initiation of CC with an initial impact but then becomes less actively involved in its ongoing progression.

EBV and HPV Infections in Colorectal Cancer and Their Effect on P53 and P16 Protein Expression.

Viral infections contribute to 15-20% of newly diagnosed cancers worldwide. There is evidence of a possible etiological role of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HR-HPVs) in colorectal carcinoma (CRC). Loss of p53 and p16 function has been found in many cancers and this may occur in many different ways, including gene mutation or interaction with viral oncoproteins. This study aimed to evaluate the presence of EBV and HPV in CRC patients in northern Iran and to assess p53 and p16 protein expression related to these viral infections. Real-time PCR was used to amplify the DNA sequences of these viruses in 55 colorectal tumoral tissues, along with their corresponding non-tumoral adjacent tissues. Additionally, immunohistochemistry (IHC) was utilized to determine p53 and p16 protein expression. EBV DNA was detected in 49.1% of CRC tissues. Furthermore, HPV DNA was present in 7.3% of CRC tissues. Notably, the prevalence of EBV infection in tumoral tissues was significantly higher than in non-tumoral tissues (P=0.001). The EBV DNA polymerase catalytic subunit (BALF5) copy number in tumoral tissues was higher than in non-tumoral tissues and this difference was statistically significant (P=0.008). P53 was positive in 21/26 (80.8%) EBV-positive and in 11/25 (44%) EBV-negative samples and this difference was significant (P=0.007). P16 was positive in 13/26 (50%) EBV-positive and in 14/25 (58.3%) EBV-negative samples (P= 0.668). Our findings suggest that EBV infection can increase the risk of CRC. In addition, EBV seems to stabilize p53 in EBV-positive CRC which needs further research. No significant correlation was detected between EBV infection and p16 expression. Also, we could not find a causal relationship between HPV infection and CRC in the study population.

SARS-CoV-2 and Guillain-Barré Syndrome: Lessons from Viral Infections.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. COVID-19 has a broad clinical spectrum from asymptomatic patients to multiorgan dysfunction and septic shock. Most of the common symptoms of COVID-19 are classified as respiratory disorders, but some reports show neurological involvements. During the COVID-19 pandemic, a case series of neurological complications, such as Guillain-Barré syndrome (GBS), were reported. GBS is a neuroimmune disorder with acute inflammatory radicular polyneuropathy in different parts of the peripheral nerve. Some studies have reported GBS as an inflammatory neuropathy related to various viral infections, such as cytomegalovirus (CMV), Epstein-Barr Virus (EBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), influenza, and Zika virus. There are some immunomodulation approaches for the management of GBS. Studies have evaluated the effects of the various therapeutic approaches, including intravenous immunoglobulin (IVIG), plasma exchange (PE), complement inhibitors, and corticosteroids to regulate overactivation of immune responses during GBS in experimental and clinical studies. In this regard, the possible association between GBS and SARS-CoV-2 infection during the outbreak of the current pandemic and also the mentioned therapeutic approaches were reviewed.

Responsiveness of selected outcome measures of participation restriction and quality of life in patients with multiple sclerosis.

PURPOSE: To evaluate the responsiveness of two outcome measures of participation restriction [as measured by the Community Integration Questionnaire (CIQ)] and quality of life [as measured by the Multiple Sclerosis Quality of Life (MSQOL)] following a physiotherapy intervention in patients with multiple sclerosis (MS). METHOD: A sample of 265 patients completed both instruments first at the time of initial visit and then after 4-6 weeks physiotherapy. In addition, patients were asked to complete the 7-point global rating scale as an external criterion of change at the post-intervention time. The responsiveness was evaluated using the receiver operating characteristics (ROC) method and the correlation analysis. Two useful statistics were area under the ROC curve (AUC) and the minimally clinically important difference (MCID). The AUC and correlation coefficient greater than 0.70 were considered as acceptable responsiveness. RESULTS: The CIQ achieved the acceptable responsiveness with an AUC of 0.81. However, the AUCs of 0.61 and 0.66 were obtained for the MSQOL physical and mental, respectively. Moreover, good correlation coefficient was obtained for the CIQ (Gamma = 0.76) while fair correlations of 0.28 and 0.33 were obtained for the MSQOL physical and mental, respectively. The MCIDs were approximately 0.50, 1.5 and 2.5 points for the CIQ, MSQOL physical and mental, respectively. CONCLUSIONS: In contrast to the MSQOL, the CIQ was responsive outcome measure in detecting changes in participation restriction of patients with MS. Moreover, the MCID values obtained in this study will help the clinicians and researchers to determine if a patient with MS has experienced a true change following physiotherapy intervention. IMPLICATIONS FOR REHABILITATION: The results provide valuable information regarding to the ability of two outcome measures (i.e. the CIQ and MSQOL) to detect treatment effects in patients with MS. In contrast to the MSQOL, the CIQ is a responsive measure to changes in participation restriction due to physiotherapy. A patient with MS had to change at least 0.50 point on the CIQ, 1.5 points on the MSQOL physical and 2.5 points on the MSQOL mental to be judged as having clinically changed.