Background: Melatonin (Mel) has lower levels and can be used as monotherapy in schizophrenia. Mel alleviated liver steatosis induced by atypical antipsychotics. Goals: To investigate Mel effect as monotherapy and addon treatment on ketamine-induced behavioral changes in rat schizophrenia model and olanzapine (Ola)-induced metabolic derangement. Methods: 24 male rats divided into four groups; C: control; O: Ola; OM: Ola plus Mel and M: Mel. All groups treated orally daily for 25 days. We measured activities of daily life (ADL) and rat performance in radial arm water maze (RAWM) before and after ketamine (Ket) injection, serum level of liver enzymes, lipoproteins, sugar, inflammatory markers and liver histopathology. Results: Ket significantly reduced burrowing and hoarding behavior, increased working memory errors (WME) and time to reach target (TRT). Ola antagonized the deleterious effects of Ket on ADL, WME and TRT. Mel monotherapy significantly reduced burrowing and doesn’t affect hoarding, WME or TRT in RAWM. Significant rise in ALT, AST, IL-1 beta, IL-6, IL-10, TNF-alpha, LDL, TGs and hepatic steatosis score (HSS) in O compared to C group. Co administration of Mel significantly decreased ALT, AST, IL-1 beta, IL-6 and TNF alpha. Insignificant difference in IL-10, TGs or LDL and significant improvement in HSS in OM compared to O group. Insignificant change in HDL or blood sugar in both O and OM groups compared to C group detected. Conclusion: Although ineffective as monotherapy, Mel co administration provides promising natural way to improve Ola-induced hepatic derangement in psychotic disorders.

Background: Melatonin (Mel) has lower levels and can be used as monotherapy in schizophrenia. Mel alleviated liver steatosis induced by atypical antipsychotics. Goals: To investigate Mel effect as monotherapy and addon treatment on ketamine-induced behavioral changes in rat schizophrenia model and olanzapine (Ola)-induced metabolic derangement. Methods: 24 male rats divided into four groups; C: control; O: Ola; OM: Ola plus Mel and M: Mel. All groups treated orally daily for 25 days. We measured activities of daily life (ADL) and rat performance in radial arm water maze (RAWM) before and after ketamine (Ket) injection, serum level of liver enzymes, lipoproteins, sugar, inflammatory markers and liver histopathology. Results: Ket significantly reduced burrowing and hoarding behavior, increased working memory errors (WME) and time to reach target (TRT). Ola antagonized the deleterious effects of Ket on ADL, WME and TRT. Mel monotherapy significantly reduced burrowing and doesn’t affect hoarding, WME or TRT in RAWM. Significant rise in ALT, AST, IL-1 beta, IL-6, IL-10, TNF-alpha, LDL, TGs and hepatic steatosis score (HSS) in O compared to C group. Co administration of Mel significantly decreased ALT, AST, IL-1 beta, IL-6 and TNF alpha. Insignificant difference in IL-10, TGs or LDL and significant improvement in HSS in OM compared to O group. Insignificant change in HDL or blood sugar in both O and OM groups compared to C group detected. Conclusion: Although ineffective as monotherapy, Mel co administration provides promising natural way to improve Ola-induced hepatic derangement in psychotic disorders.

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy

Urinary bladder cancer (UBC) is the most common malignancy involving the urinary system .In Egypt; it represents an important health problem constituting, 40.6% of cancers in men and 14.3% of cancers in women. The presence of tumor infiltrating lymphoytes (TILs), either CD4 or CD8, within the tumor microenvironment is considered to be an indication of the host immune response against tumor antigens and is thought to reflect the dynamic process of cancer immunoediting. The aim of this study is to evaluate immunohistochemical expression of CD4, CD8 and CD/CD8 ratio in 30 formalin-fixed paraffin-embedded blocks of muscle invasive urothelial carcinoma and to correlate their expression with different clinicopathological parameters. Both CD4 and CD8 positive cells showed brown membranous staining mainly present in tumor stroma with the mean staining was 35.9 and 31.5 for CD4 and CD8 respectively. CD4/CD8 ratio ranged from 0.18 to 12.6 with the mean staining was 2.57. The mean of both CD4 & CD8 expression was significantly higher in urothelial carcinoma with squamous differentiation (P= 0.001) for each, PT3 stage (P=0.001) for each and negative lymphvascular invasion (P=0.041& P= 0.001) respectively. While the mean of only CD4 expression was significantly higher in cases with absent lymph node metastasis (P=0.01). On the other hand, the mean of CD4/CD8 ratio was significantly higher in pure urothelial carcinoma (P=0.036), PT2a stage (P=0.013) and absence of lymph node metastasis (P=0.024). There was a statistically significant positive correlation (P= 0.014) between expression of CD4 and CD8. In conclusion, our findings suggest that, in the setting of muscle invasive UC, the existence of both CD4 and CD8 TILs within the tumor microenvironment points to ongoing immune response that might be able to suppress further progression and metastasis. Higher CD4/CD8 ratio was observed in pure UC than other variants. Lower CD4/CD8 ratio may be associated with advanced stage and lymph node metastasis.

Urinary bladder cancer (UBC) is the most common malignancy involving the urinary system .In Egypt; it represents an important health problem constituting, 40.6% of cancers in men and 14.3% of cancers in women. The presence of tumor infiltrating lymphoytes (TILs), either CD4 or CD8, within the tumor microenvironment is considered to be an indication of the host immune response against tumor antigens and is thought to reflect the dynamic process of cancer immunoediting. The aim of this study is to evaluate immunohistochemical expression of CD4, CD8 and CD/CD8 ratio in 30 formalin-fixed paraffin-embedded blocks of muscle invasive urothelial carcinoma and to correlate their expression with different clinicopathological parameters. Both CD4 and CD8 positive cells showed brown membranous staining mainly present in tumor stroma with the mean staining was 35.9 and 31.5 for CD4 and CD8 respectively. CD4/CD8 ratio ranged from 0.18 to 12.6 with the mean staining was 2.57. The mean of both CD4 & CD8 expression was significantly higher in urothelial carcinoma with squamous differentiation (P= 0.001) for each, PT3 stage (P=0.001) for each and negative lymphvascular invasion (P=0.041& P= 0.001) respectively. While the mean of only CD4 expression was significantly higher in cases with absent lymph node metastasis (P=0.01). On the other hand, the mean of CD4/CD8 ratio was significantly higher in pure urothelial carcinoma (P=0.036), PT2a stage (P=0.013) and absence of lymph node metastasis (P=0.024). There was a statistically significant positive correlation (P= 0.014) between expression of CD4 and CD8. In conclusion, our findings suggest that, in the setting of muscle invasive UC, the existence of both CD4 and CD8 TILs within the tumor microenvironment points to ongoing immune response that might be able to suppress further progression and metastasis. Higher CD4/CD8 ratio was observed in pure UC than other variants. Lower CD4/CD8 ratio may be associated with advanced stage and lymph node metastasis.

Urinary bladder cancer (UBC) is the most common malignancy involving the urinary system .In Egypt; it represents an important health problem constituting, 40.6% of cancers in men and 14.3% of cancers in women. The presence of tumor infiltrating lymphoytes (TILs), either CD4 or CD8, within the tumor microenvironment is considered to be an indication of the host immune response against tumor antigens and is thought to reflect the dynamic process of cancer immunoediting. The aim of this study is to evaluate immunohistochemical expression of CD4, CD8 and CD/CD8 ratio in 30 formalin-fixed paraffin-embedded blocks of muscle invasive urothelial carcinoma and to correlate their expression with different clinicopathological parameters. Both CD4 and CD8 positive cells showed brown membranous staining mainly present in tumor stroma with the mean staining was 35.9 and 31.5 for CD4 and CD8 respectively. CD4/CD8 ratio ranged from 0.18 to 12.6 with the mean staining was 2.57. The mean of both CD4 & CD8 expression was significantly higher in urothelial carcinoma with squamous differentiation (P= 0.001) for each, PT3 stage (P=0.001) for each and negative lymphvascular invasion (P=0.041& P= 0.001) respectively. While the mean of only CD4 expression was significantly higher in cases with absent lymph node metastasis (P=0.01). On the other hand, the mean of CD4/CD8 ratio was significantly higher in pure urothelial carcinoma (P=0.036), PT2a stage (P=0.013) and absence of lymph node metastasis (P=0.024). There was a statistically significant positive correlation (P= 0.014) between expression of CD4 and CD8. In conclusion, our findings suggest that, in the setting of muscle invasive UC, the existence of both CD4 and CD8 TILs within the tumor microenvironment points to ongoing immune response that might be able to suppress further progression and metastasis. Higher CD4/CD8 ratio was observed in pure UC than other variants. Lower CD4/CD8 ratio may be associated with advanced stage and lymph node metastasis.

Urinary bladder cancer (UBC) is the most common malignancy involving the urinary system .In Egypt; it represents an important health problem constituting, 40.6% of cancers in men and 14.3% of cancers in women. The presence of tumor infiltrating lymphoytes (TILs), either CD4 or CD8, within the tumor microenvironment is considered to be an indication of the host immune response against tumor antigens and is thought to reflect the dynamic process of cancer immunoediting. The aim of this study is to evaluate immunohistochemical expression of CD4, CD8 and CD/CD8 ratio in 30 formalin-fixed paraffin-embedded blocks of muscle invasive urothelial carcinoma and to correlate their expression with different clinicopathological parameters. Both CD4 and CD8 positive cells showed brown membranous staining mainly present in tumor stroma with the mean staining was 35.9 and 31.5 for CD4 and CD8 respectively. CD4/CD8 ratio ranged from 0.18 to 12.6 with the mean staining was 2.57. The mean of both CD4 & CD8 expression was significantly higher in urothelial carcinoma with squamous differentiation (P= 0.001) for each, PT3 stage (P=0.001) for each and negative lymphvascular invasion (P=0.041& P= 0.001) respectively. While the mean of only CD4 expression was significantly higher in cases with absent lymph node metastasis (P=0.01). On the other hand, the mean of CD4/CD8 ratio was significantly higher in pure urothelial carcinoma (P=0.036), PT2a stage (P=0.013) and absence of lymph node metastasis (P=0.024). There was a statistically significant positive correlation (P= 0.014) between expression of CD4 and CD8. In conclusion, our findings suggest that, in the setting of muscle invasive UC, the existence of both CD4 and CD8 TILs within the tumor microenvironment points to ongoing immune response that might be able to suppress further progression and metastasis. Higher CD4/CD8 ratio was observed in pure UC than other variants. Lower CD4/CD8 ratio may be associated with advanced stage and lymph node metastasis.

Background The lateral femoral condyle (LFC) flap is a vascularized bone flap based on the superior lateral genicular artery (SLGA). Harvest technique for this flap has not yet been demonstrated. The purpose of this study was to better delineate the blood supply to the bone and skin of this flap to allow for a safe and effective harvest. Materials and methods Twenty-three lower extremities were injected with latex or a mixture of latex and barium sulfate. The SLGA was identified and dissected, documenting the course, diameter, anatomical relations, length, and branches. In the mixture group, high-resolution CT scanning was performed prior to dissection. Two additional specimens were dissected to illustrate the harvest technique. Results The SLGA originated from the popliteal artery at an average of 44.3 mm proximal to the knee joint line. The SLGA had an average diameter of 1.9 mm at origin and length of 56 mm. It coursed posterior to the femur, reaching the lateral intermuscular septum (IMS), dividing into superficial (patellar) and deep (condylar) branches, which coursed toward and gave branches to the patella and the LFC, respectively. At least one (average 1.4) septocutaneous skin perforator >5 mm emerged and ran posterior to the IMS. 3D reconstructions of the CT scans were used to confirm anatomic findings and describe a standard harvest technique. Conclusions The SLGA has consistent anatomy, adequate length, suitable diameter at origin for microvascular anastomosis, and constant perforators to bone and skin. The LFC flap provides a useful alternative to flaps from the medial knee or iliac crest.