Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial.

OBJECTIVE: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. METHODS: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.

Near-Infrared Spectroscopy Monitoring in Pediatric Anesthesiology: A Pro-Con Discussion.

Near-infrared spectroscopy (NIRS) has been increasingly used as a non-invasive measurement of cerebral tissue oxygen saturation. The aim of this short review is to discuss the benefits and drawbacks of its use in the pediatric anesthesia population. In the context of cardiac surgery, lower intraoperative NIRS values have shown a modest association with neurodevelopmental outcomes while lower neonatal intensive care unit NIRS values have been correlated with reduced neurodevelopment in children. However, it is still unclear if management aimed at increasing cerebral tissue oxygenation would have any benefit on these outcomes. Without prospective research looking into the effects of intervention given proper thresholds, the true benefit of NIRS use is still up for debate. Even with current research gaps, its use in the clinical setting continues.

Using a Student-Generated Mock Magazine Issue To Improve Students' Awareness of Diverse Scientists.

This study explores whether integrating multicultural content within a genetics laboratory course affected students' awareness of diversity and their perceptions of scientists' identities. Genetics laboratory curricula typically focus on content and experimental procedures, with cursory references to the scientists who made these discoveries. The resulting poor racial and gender representation in the curricula propagate biases about the abilities and contributions of scientists from underrepresented groups, which may adversely affect the retention and success of students in these groups. Initially, students completed a pre-test in which they were asked to recall the names of geneticists and their scientific contributions. Later students created a mock magazine issue featuring a diverse set of experts in genetics, specifically members of traditionally underrepresented gender/sexuality and/or racial/ethnic groups. To facilitate this assignment, students were randomly assigned a geneticist from a pool of active research scientists, spanning a wide range of scientific and cultural backgrounds and identities. Each student wrote a 500-word biography of their assigned geneticist and read biographies composed by peers. Then, in groups, the students categorized biographies based on student-selected unifying themes into a table of contents. On the final exam, the pre-test was repeated as a post-test. In the pre-test, scientists listed by students were 94% male and 6% female, with no members of other underrepresented groups included. In the post-test, scientists listed by students shifted to 84% male and 16% female with 18% from underrepresented groups. These data suggest that this intervention increases awareness of the multicultural nature of scientists.

Robust Selections of Various Hematopoietic Cell Fractions on the CliniMACS Plus Instrument.

Cell separation technologies play a vital role in the graft engineering of hematopoietic cellular fractions, particularly with the rapid expansion of the field of cellular therapeutics. The CliniMACS Plus Instrument (Miltenyi Biotec) utilizes immunomagnetic techniques to isolate hematopoietic progenitor cells (HPCs), T cells, NK cells, and monocytes. These products are ultimately used for HPC transplantation and for the manufacture of adoptive immunotherapies. We evaluated the viable cell recovery and cell purity of selections and depletions performed on the CliniMACS Plus over a 10-year period at our facility, specifically assessing for the isolation of CD34+, CD4+, CD3+/CD56+, CD4+/CD8+, and CD25+ cells. Additionally, patient- and instrument-related factors affecting these parameters were examined. Viable cell recovery ranged from 32.3 ± 10.2% to 65.4 ± 15.4%, and was the highest for CD34+ selections. Cell purity ranged from 86.3 ± 7.2% to 99.0 ± 1.1%, and was the highest for CD4+ selections. Undesired cell fractions demonstrated a range of 1.2 ± 0.45 to 5.1 ± 0.4 log reductions. Red cell depletions averaged 2.12 ± 0.68 logs, while platelets were reduced by an average of 4.01 ± 1.57 logs. Donor characteristics did not impact viable cell recovery or cell purity for CD34+ or CD4+ cell enrichments; however, these were affected by manufacturing variables, including tubing size, bead quantity, and whether preselection platelet washes were performed. Our data demonstrate the efficient recovery of hematopoietic cellular fractions on the CliniMACS Plus that may be optimized by adjusting manufacturing variables.

Primary tuberculous osteomyelitis of the mandible: A rare case report.

Tuberculosis (TB) has become a rare disease in the developed countries but it is still a serious problem in developing countries. Incidence of tuberculous osteomyelitis of the jaw bones is very low. This rare incidence is the primary reason that this lesion gets mis-diagnosed many times. Here we report the diagnosis, treatment and follow-up of a case, which is a classical presentation of tuberculous osteomyelitis of mandible. Primary tuberculous osteomyelitis is a very rare entity but in the recent times, increased incidence of TB as a coinfection of HIV, has posed a big challenge in developing countries. If not diagnosed, at the right time, this can lead to serious complications like internal organ damage, tuberculous meningitis etc., Early diagnosis of tuberculous osteomyelitis will certainly reduce the morbidity of this disease condition.

Validating an objective video-based dyskinesia severity score in Parkinson's disease patients.

Dyskinesia is a common side effect of prolonged dopaminergic therapy in Parkinson's disease patients. Assessing the severity of dyskinesia could help develop better pharmacological and surgical interventions. We have developed a semi-automatic video-based objective dyskinesia quantifying measure called the severity score (SVS) that was evaluated on 35 patient videos. We present a study to evaluate the utility of our severity score and compare its performance to clinical ratings of neurologists. In addition to the Unified Dyskinesia Rating Scale (UDysRS) score for each video, four neurologists provided three sets of time lapsed ratings and rankings of the 35 videos using a specifically developed protocol. The statistical analysis of our data using Kendall's tau-b and intra-class correlations shows that (a) ranking patient videos based on severity is suitable for studying the utility of the SVS, and (b) SVS exhibits moderate utility to quantify dyskinesia severity when compared to manual assessment of dyskinesia by neurologists using the UDysRS. These results support the effective use of SVS as an objective measure to quantify dyskinesia and the rationale for a ranking system that complements traditional rating scales.

Quantifying drug induced dyskinesia in Parkinson's disease patients using standardized videos.

This paper presents a video based method to quantify drug induced dyskinesias in Parkinson's disease (PD) patients. Dyskinetic movement in standard clinical videos of patients is analyzed by tracking landmark points on the video frames using non-rigid image registration. The novel application of Point Distribution Models (PDM) allows geometric variations and covariations of the landmark points to be captured from each video sequence. The PDM parameters represent quantifiable information that can be used to rate dyskinesia effectively, analogously to a neurologist's strategy of assessing the movement of multiple body parts simultaneously to effectively rate dyskinesia. A heuristic decision function is then developed using the PDM parameters to quantify the severity of the dyskinesia. The severity score using our decision function showed a high correlation to the dyskinesia rating of a neurologist on the corresponding patient videos.