Intraarticular Tramadol-Bupivacaine Combination Prolongs the Duration of Postoperative Analgesia After Outpatient Arthroscopic Knee Surgery

BACKGROUND: Intraarticular (IA) local anesthetics are often used for the management and prevention of pain after arthroscopic knee surgery. Recently, IA tramadol was also used for the management of these patients. However, the IA combination of local anesthetic and tramadol has not been evaluated in arthroscopic outpatients. Our primary aim in this study was to evaluate the analgesic effect of an IA combination of bupivacaine and tramadol when compared with each drug alone using visual analog scale (VAS) pain scores in patients undergoing day-care arthroscopic knee surgery. Additionally, we assessed analgesic demand. METHODS: Ninety ASA I/II patients undergoing arthroscopic partial meniscectomy, performed by a single surgeon under general anesthesia, were assigned in a randomized, double-blind manner into three groups: group B (n = 30) received 0.25% bupivacaine, group T (n = 30) received 100 mg tramadol, and group BT (n = 30) received 0.25% bupivacaine and 100 mg tramadol to a total volume of 20 mL by the IA route after surgery. Postoperative pain scores were measured on a VAS, at rest and on mobilization at 0.5, 1, 2, 4, 6, 8, 12, and 24 h. Duration of analgesia, the subsequent 24 h consumption of rescue analgesia, time to ambulation, and time to discharge were evaluated. In addition, the systemic side effects of the IA injected drugs were also assessed. RESULTS: The results showed significantly lower VAS pain scores in group BT (P << 0.1) when compared with groups T and B. Group BT had a later onset of postsurgical pain and longer time to first rescue analgesic than groups B and T. The 24 h consumption of analgesic was significantly less in group BT when compared with the other two groups (26.7% of the patients required rescue analgesia in group BT, whereas this number was 90% in group B and 86.7% in group T). In addition, time in hours to discharge and time to unassisted ambulation were significantly shorter in group BT when compared with groups T and B, and this was not associated with any detectable systemic effects. CONCLUSION: The IA admixture of tramadol 100 mg with bupivacaine 0.25% provides a pronounced prolongation of analgesia compared with either drug alone in patients undergoing day care arthroscopic knee surgery

HDM2 antagonist MI-219 (spiro-oxindole), but not Nutlin-3 (cis-imidazoline), regulates p53 through enhanced HDM2 autoubiquitination and degradation in human malignant B-cell lymphomas

Abstract Background Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, thereby compromising p53 activity. Therefore, lymphoma is a suitable model for studying the therapeutic value of disrupting the HDM2-p53 interaction by small-molecule inhibitors (SMIs). HDM2 have been developed and are under various stages of preclinical and clinical investigation. Previously, we examined the anti-lymphoma activity of MI-319, the laboratory grade of a new class of HDM2 SMI, the spiro-oxindole, in follicular lymphoma. Since then, MI-219, the clinical grade has become readily available. This study further examines the preclinical effects and mechanisms of MI-219 in a panel of human lymphoma cell lines as well as a cohort of patient-derived B-lymphcytes for its potential clinical use. Results Preclinical assessment of MI-219 was evaluated by means of an in vitro and ex vivo approach and compared to Nutlin-3, the gold standard. Characterization of p53 activity and stability were assessed by quantitative PCR, Western blot, and immunoprecipitation. Biological outcome was measured using Trypan blue exclusion assay, Annexin V/PI, PARP and caspase-3 cleavage. Surprisingly, the overall biological effects of Nutlin-3 were more delayed (48 h) while MI-219 triggered an earlier response (12-24 h), predominantly in the form of apoptotic cell death. Using a cell free autoubiquitination assay, neither agent interfered with HDM2 E3 ligase function. MI-219 was more effective in upregulating wt-p53 stabilization compared to Nutlin-3. MI-219, but not Nutlin-3, enhanced the autoubiquitination and degradation of HDM2. Conclusions Our data reveals unexpected differences between MI-219 and the well-studied Nutlin-3 in lymphoma cell lines and patient samples. We suggest a novel mechanism for MI-219 that alters the functional activity of HDM2 through enhanced autoubiquitination and degradation. Additionally, this mechanism appears to correspond to biological outcome. Our results provide evidence that different classes of HDM2 SMIs elicit molecular events that extend beyond HDM2-p53 dissociation which may be of biological and potentially therapeutic importance

Exhaustive Search for Optimal Offline Spectrum Assignment in Elastic Optical Networks

Heuristic-based approaches are widely deployed in solving Spectrum Assignment problem. This causes the results to be unreliable in some test cases when the results are very far from the lowerbound. This paper presents an exhaustive search approach that starts with an initial seed of a solution achieved by a heuristic-based algorithm called “Longest First Fit” (LFF) and tries all possible permutations starting from this initial seed. The algorithm skips some branches and all its descendant permutations if it meets certain criteria that guarantees that those permutations will not lead to a better result. The experimental results show that the new algorithm has succeeded in achieving the lower-bound in 93% of the randomly generated test cases while the heuristic solver LFF can achieve 65%. The algorithm achieves these results in a reasonable running time of less than 10 seconds

Evaluation of harmonic generating properties of schottky barrier diodes

Low noise figure communication receivers require more efficient frequency converters. Frequency conversion and multiplication processes cannot take place without the existence of harmonic sources in the system and the inherent property of a nonlinear element is to generate harmonics. Such nonlinearity, in general, may be provided by semiconductor diodes. This research project deals with the theoretical analysis as well as the experimental verifications of the harmonic generating properties of a nonlinear resistive device, i.e. Schottky-barrier diode. Laboratory measurements associated with the equivalent circuit representation of hot-carrier diodes show that their i-v characteristics can be accurately described by the modified exponential law, i = I(_s) [exp α (V–iR(_T)-1, over a wide range of the applied voltage V. Using this equation, a procedure is developed for the harmonic analysis of the resistive diode and calculation of any of a finite number of harmonic currents having a single frequency sinusoidal voltage V(_p) cos w(_p)t as the drive. The amplitudes of the harmonic currents are expressed as a power series in αR(_T)I(_S)) exp (αR(_T)I(_S)) where the coefficients of the power series are represented through the modified Bessel function of the k(^th) of order n. The integers k and n represent the power of the series and the harmonic number respectively, e.g. i(_n) α I(_n) (k α v(_p)) [αR(_T)I(_S) exp (αR(_T)I(_S))](^k). The power series solutions for the exponential diodes do not normally converge quickly enough to be of practical value for numerical evaluations. A different approach is proposed which is suitable for numerical evaluations of harmonic amplitudes. The results are compared with experimental data on twelve diodes, four in each of the three groups of different types. A good agreement, within the measuring instruments tolerances, was found between the calculated and the experimental results. Finally, it is believed that such studies were justified as the new method of approach presented here evaluates fully the capabilities of these diodes in practice. Many analyses published over the years have tended to introduce severe approximations which were only valid in practice over limited ranges of operation. In this project, attempts were made over almost two years to obtain mathematical solutions for the exponential diode law which are useful in practice and which give accurate prediction of harmonic amplitudes and spectrum. Various methods were employed to achieve the necessary convergence of the infinite series solutions. This involved a good understanding of the mathematical methods employed and computer programming. During the same period at every stage experimental verifications were being attempted, many times unsuccessfully, which finally led to a good agreement between the theory and experimental results as shown in this thesis

Research ethics challenges during the COVID-19 pandemic: what should and what should not be done

This article is directed primarily at how clinical trials can be ethically conducted in the midst of the current global COVID-19 pandemic. We explain why ethical issues are more complicated than they once were. Furthermore, we discuss the relevant parties` roles in protecting participants` rights and in keeping basic research ethics of justice, respect, equity, and beneficence strongly implemented on the ground. &nbsp; References Moorthy V, Restrepo H, Preziosi MP, Swaminathan S. Data sharing for novel coronavirus (COVID-19). Bull World Health Organ. 2020; 98: 150. http://dx.doi.org/10.2471/BLT.20.251561 Angus DC. Optimizing the trade-off between learning and doing in a pandemic. Epub ahead of print, 2020. https://doi.org/10.1001/jama.2020.4984)JAMA Park YR, Koo H, Yoon YK, Park S, Lim Y-S, Baek S, et al. Expedited Safety Reporting to Sponsors Through the Implementation of an Alert System for Clinical Trial Management at an Academic Medical Center: Retrospective Design Study. JMIR Med Inform. 2020;8(2): e14379. https://doi.org/2196/14379. Bae J, Lee J, Jang Y, Lee Y. Development of simulation education debriefing protocol with faculty guide for enhancement clinical reasoning. BMC Med Educ. 2019;19(1):197. https://doi.org/10.1186/s12909-019-1633-8. Cox EM, Edmund AV, Kratz E, Lockwood SH, Shankar A. Regulatory Affairs 101: Introduction to Expedited Regulatory Pathways. Clin Transl Sci. 2020;13(3):451‐ https://doi.org/10.1111/cts.12745. Epub 2020 Feb 6. Rivenbark JG, Ichou M. Discrimination in healthcare as a barrier to care: experiences of socially disadvantaged populations in France from a nationally representative survey. BMC Public Health. 2020;20(1):31. https://doi.org/1186/s12889-019-8124-z Arsenijevic J, Tummers L, Bosma N. Adherence to Electronic Health Tools Among Vulnerable Groups: Systematic Literature Review and Meta-Analysis. J Med Internet Res. 2020;22(2): e11613. https://doi.org/2196/11613 Plotkin S, Robinson JM, Cunningham G, Iqbal R, Larsen S. The complexity and cost of vaccine manufacturing: An overview. Vaccine. 2017;35(33):4064–71. https://doi.org/1016/j.vaccine.2017.06.003. Deming D. Do extraordinary claims require extraordinary evidence? Philosophia (Ramat Gan). 2016;44(4):1319‐ https://doi.org/10.3389/fpsyg.2011.0011

Siraj al-Tavarikh

Covers the history of Afghanistan from, 17th-20th century. It includes historical events and biographical descriptions of Afghan kings and rulers. The book is in Persian language, in two volumes. Published in Kabul: Matbaah-i Hurufi-i Dal al-Saltanah, 1331 (1952)https://digitalcommons.unomaha.edu/daripashtobooks/1001/thumbnail.jp

I-kappa-kinase-2 (IKK-2) inhibition potentiates vincristine cytotoxicity in non-Hodgkin\u27s lymphoma

Abstract Background IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin\u27s lymphoma. Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small molecule inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), doxorubicin (H) or vincristine (V) was evaluated in vitro using short-term culture assay. We also determined efficacy of the combination in vivo using the SCID mouse xenografts. Results ML120B down-regulated p-IκBα protein expression in a concentration dependent manner, caused growth inhibition, increased G0/G1 cells, but did not induce apoptosis. There was no significant enhancement of cell kill in the M/C or M/H combination. However, there was strong synergy in the M/V combination where the vincristine concentration can be lowered by a hundred fold in the combination for comparable G2/M arrest and apoptosis. ML120B prevented vincristine-induced nuclear translocation of p65 subunit of NF-κB. In vivo, ML120B was effective by itself and enhanced CHOP anti-tumor activity significantly (P = 0.001) in the WSU-DLCL2-SCID model but did not prevent CNS lymphoma in the WSU-FSCCL-SCID model. Conclusions For the first time, this study demonstrates that perturbation of IKK-2 by ML120B leads to synergistic enhancement of vincristine cytotoxicity in lymphoma. These results suggest that disruption of the NF-κB pathway is a useful adjunct to cytotoxic chemotherapy in lymphoma

Emphysematous epididymo-orchitis with involvement of the prostate, seminal vesicles, and the scrotum: a case report

Emphysematous epididymo-orchitis is a rare clinical entity. Up until July 2020, only 9 cases have been reported in PubMed and Scopus platforms, one of which also had scrotal involvement. Therefore, we are reporting the second case with prostate, seminal vesicle, and scrotal involvement. The condition represents an aggressive form of infection caused by gas-forming microbes. The radiological detection of air within the organs involved in the characteristic diagnostic sign. The case we are reporting is a 47 years old diabetic, chronic renal failure patient on regular hemodialysis who had a fulminant emphysematous infection in the left testis, epididymis, spermatic cord, the prostate, seminal vesicles, and the scrotum. Emergency orchiectomy has been carried out. The most significant part of the case is the pictures showing ballooning scrotum and gas bubbles in abnormal anatomical locations

Assessing the Impact of Policies in Developing Countries Using Social Accounting Matrices (SAM): The Case of Somalia 2025

This study explored Somalia’s economic structure and public policy landscape through the lens of the Social Accounting Matrix (SAM) framework, with the objective of positioning SAM as a viable tool for future evidence-based policy analysis. Drawing exclusively on secondary data, the study examined available information on government revenue and expenditure, macroeconomic performance, household welfare, labor market dynamics, and vulnerability indicators. Data sources included national reports such as the Somalia Integrated Household Budget Survey, Labour Force Survey, GDP Statistical Release, and the Financial Governance Report, among others. The analysis revealed critical trends including heavy reliance on external grants, limited capital investment, persistently high unemployment, and widespread household vulnerability. While existing indicators provided useful benchmarks, the study found that Somalia’s data systems remain fragmented and inadequate for constructing a complete SAM. The study concludes by recommending the establishment of a national think tank or coordination platform to spearhead SAM development, emphasizing the need for long-term investment in harmonized data systems and national accounts capacity. This paper serves as an early academic contribution to the institutionalization of SAM-based policy modeling in Somalia. Keywords: Developing Countries, Social Accounting Matrices (SAM) &amp; Somali