Effects of nucleoside analogs and sodium butyrate on recovery from potentially lethal X ray damage in human colon tumor cells

The effects of 5-azacytidine (5-aza-CR) and 5-aza-2'-deoxycytidine (5-aza-CdR) both alone and in combination with sodium butyrate (NaB) on intrinsic radiation sensitivity and ability to recover from potentially lethal damage (PLDR) were studied in two subpopulations of cells (clones A and D) from a heterogeneous human colon adenocarcinoma (DLD-1). Growth for three passages in medium containing 1 mM NaB alone enhanced radiation cell killing in the low dose ("shoulder") region of the survival curve for both cell lines. Neither 1.0 microM 5-aza-CR nor 0.25 microM 5-aza-CdR alone enhanced cell killing. However, treatment of these cells with a combination of either 5-aza-CR or 5-aza-CdR and NaB enhanced radiation cell killing at a clinically relevant dose level of 2.0 Gy by approximately 25% for both clone A and clone D cells. Also, while exposure to these differentiation-inducing agents separately enhanced the expression of PLDR in both tumor subpopulations, treatment with either of the combinations reversed this increase in PLDR. These results indicate that the gene-activating agents 5-aza-CR, 5-aza-CdR, and NaB may interact to modify the radiation sensitivity of two human tumor cell lines. Such combinations may prove useful clinically, if enhanced X ray cell killing of tumor cells can be achieved without a concomitant enhancement of recovery from potentially lethal X ray damage.     

Thiamin Deficiency in People with Obesity

Although obesity has been viewed traditionally as a disease of excess nutrition, evidence suggests that it may also be a disease of malnutrition. Specifically, thiamin deficiency was found in 15.5–29% of obese patients seeking bariatric surgery. It can present with vague signs and symptoms and is often overlooked in patients without alcohol use disorders. This review explores the relatively new discovery of high rates of thiamin deficiency in certain populations of people with obesity, including the effects of thiamin deficiency and potential underlying mechanisms of deficiency in people with obesity. The 2 observational studies that examined the prevalence in preoperative bariatric surgery patients and gaps in our current knowledge (including the prevalence of thiamin deficiency in the general obese population and whether the current RDA for thiamin meets the metabolic needs of overweight or obese adults) are reviewed. Suggestions for future areas of research are included.     

Internal Medicine Residents’ Perceptions of Virtual Morning Report: a Multicenter Survey

ImportanceThe COVID-19 pandemic disrupted graduate medical education, compelling training programs to abruptly transition to virtual educational formats despite minimal experience or proficiency. We surveyed residents from a national sample of internal medicine (IM) residency programs to describe their experiences with the transition to virtual morning report (MR), a highly valued core educational conference.ObjectiveAssess resident views about virtual MR content and teaching strategies during the COVID-19 pandemic.DesignAnonymous, web-based survey.ParticipantsResidents from 14 academically affiliated IM residency programs.Main MeasuresThe 25-item survey on virtual MR included questions on demographics; frequency and reason for attending; opinions on who should attend and teach; how the virtual format affects the learning environment; how virtual MR compares to in-person MR with regard to participation, engagement, and overall education; and whether virtual MR should continue after in-person conferences can safely resume. The survey included a combination of Likert-style, multiple option, and open-ended questions.ResultsSix hundred fifteen residents (35%) completed the survey, with a balanced sample of interns (39%), second-year (31%), and third-year (30%) residents. When comparing their overall assessment of in-person and virtual MR formats, 42% of residents preferred in-person, 18% preferred virtual, and 40% felt they were equivalent. Most respondents endorsed better peer-engagement, camaraderie, and group participation with in-person MR. Chat boxes, video participation, audience response systems, and smart boards/tablets enhanced respondents’ educational experience during virtual MR. Most respondents (72%) felt that the option of virtual MR should continue when it is safe to resume in-person conferences.ConclusionsVirtual MR was a valued alternative to traditional in-person MR during the COVID-19 pandemic. Residents feel that the virtual platform offers unique educational benefits independent of and in conjunction with in-person conferences. Residents support the integration of a virtual platform into the delivery of MR in the future.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06963-7.KEY WORDS: graduate medical education, internal medicine residency, morning report, virtual     

Application of a low-pressure differential filtration technique to suspensions of red blood cells

The paper describes a low-pressure 2 cm H₂O, 5μm nuclepore filtration system for assessing red blood cell flexibility in suspensions of native plasma. Details are given of the white cell removal technique and filter handling methods for improved repeatability. Calibration of the system and filters using physiological saline controls is detailed and the advantages of a constant-pressure system are discussed. Data on filtration rates from normal controls and diabetics are given. Comparison of thisin votro system with literature data onin vivo systems is made.     

Quantitative Structure-Pharmacokinetics Relationships: I. Development of a Whole-Body Physiologically Based Model to Characterize Changes in Pharmacokinetics Across a Homologous Series of Barbiturates in the Rat

As pan of an overall program to develop a framework for evaluating the contribution of structural and physicochemical properties to pharmacokinetics, the distribution kinetics of nine 5-n-alkyl-5-ethyl barbituric acids in arterial blood and 14 tissues (lung, liver, kidney, stomach, pancreas, spleen, gut, muscle, adipose, skin, bone, heart, brain, testes) was examined after iv bolus administration in rats. The barbituric acids studied form a true homologous series; therefore any differences in pharmacokinetics, noted between congeners, can be directly linked to the increase in lipophilicity, resulting from the addition of a methylene group. A whole-body physiologically based pharmacokinetic model has been developed, assuming most of the tissues to be well-stirred compartments. Brain and testes, in which distribution for the lower homologues was permeability rate-limited, were represented by two compartments. For each homologue, the model parameters have been optimized, using the tissue concentration–time data. The initial distribution processes in the system were very rapid, making it quite stiff, and essentially over before the first samples were taken. A progressively increasing redistribution from lean tissues into adipose on ascending the homologous series was observed, characterized by a tendency for a progressive decrease in the magnitude of the concentration–time profiles for some of the lean and well-perfused tissues, an increase in the adipose concentration–time profile, and an increase in the time to reach the maximum adipose concentration. A shift from permeability rate limitation to perfusion rate limitation of the distribution processes for brain and testes, as well as an increase in the intrinsic hepatic clearance and decrease in the renal clearance with the increase of lipophilicity of the homologues, were quantified. An increase in the total unbound volume of distribution on ascending the homologous series was also observed. Muscle was found to be the major drug depot at steady state, accounting for approximately 50% of the total unbound volume of distribution, regardless of the lipophilicity of the homologue; the unbound volume of distribution of adipose increases more than 10-fold with the increase of lipophilicity.     

Hypodontus macropi, M?nnig, 1929 from a Bennetts' wallaby Macropus rufogrisea.

Hypodontus macropi was found in Macropus rufogrisea. Males measured 12.73--13.93 mm in length; one female was 19.07 mm in length. The buccal capsule was funnel-shaped. The mouth opening was directed antero-ventrally. There was a pair of large cutting plates on the dorsal margin of the buccal capsule. The brusal rays were well-developed. Spicules were equal and each bore a cuticular wing. A gubernaculum and a telamon were present. The vulva was situated near the anus. The female tail, 0.163 mm in length, was suddenly tapering.     

Hydatid disease in the Turkana District of Kenya, IV. The prevalence of Echinococcus granulosus infections in dogs, and observations on the role of the dog in the lifestyle of the Turkana

The prevalence of Echinococcus granulosus in dogs in the Turkana District of Kenya was 39.4% of 695 examined. Of these, 98 (35.8%) had heavy Echinococcus worm burdens (10(3)-5 X 10(4) ), while 54 (19.7%) and 122 (44.5%) had medium (201-1000) and light (1-200) burdens. The possible sources of these infections are discussed. The prevalence rate differed in various parts of the district, ranging from 63.5% in the northwest, where the highest incidence of human hydatidosis also occurs, to nil along the shores of Lake Turkana. Infection rates of 32.0% and 16.7% were recorded at Lokitaung (north-east) and Lodwar (central), while in the south 48.9% of dogs harboured Echinococcus. This latter figure is surprising as the area has a low incidence of human hydatidosis. The Turkana keep a large number of dogs, and the reasons for this and the social role of the dog in the district is discussed. No difference in susceptibility was found between Turkana-type dogs and those of mixed breeds from Nairobi when they were experimentally infected with hydatid protoscolices from man, camels, cattle, sheep and goats. However, it proved difficult to infect the Turkana-type of dogs with viable protoscolices of cattle origin. The reasons for this and its epidemiological implications remain unclear. It is suggested that droughts, which affect Turkana every six to ten years, may play an important role in the perpetuation of hydatid disease in the area.     

Amalgamated Reference Data for Size‐Adjusted Bone Densitometry Measurements in 3598 Children and Young Adults—the ALPHABET Study

The increasing use of dual‐energy X‐ray absorptiometry (DXA) in children has led to the need for robust reference data for interpretation of scans in daily clinical practice. Such data need to be representative of the population being studied and be “future‐proofed” to software and hardware upgrades. The aim was to combine all available pediatric DXA reference data from seven UK centers to create reference curves adjusted for age, sex, ethnicity, and body size to enable clinical application, using in vivo cross‐calibration and making data back and forward compatible. Seven UK sites collected data on GE Lunar or Hologic Scanners between 1996 and 2012. Males and females aged 4 to 20 years were recruited (n = 3598). The split by ethnic group was white 2887; South Asian 385; black Afro‐Caribbean 286; and mixed heritage 40. Scans of the total body and lumbar spine (L₁ to L₄) were obtained. The European Spine Phantom was used to cross‐calibrate the 7 centers and 11 scanners. Reference curves were produced for L₁ to L₄ bone mineral apparent density (BMAD) and total body less head (TBLH) and L₁ to L₄ areal bone mineral density (aBMD) for GE Lunar Prodigy and iDXA (sex‐ and ethnic‐specific) and for Hologic (sex‐specific). Regression equations for TBLH BMC were produced using stepwise linear regression. Scans of 100 children were randomly selected to test backward and forward compatibility of software versions, up to version 15.0 for GE Lunar and Apex 4.1 for Hologic. For the first time, sex‐ and ethnic‐specific reference curves for lumbar spine BMAD, aBMD, and TBLH aBMD are provided for both GE Lunar and Hologic scanners. These curves will facilitate interpretation of DXA data in children using methods recommended in ISCD guidelines. The databases have been created to allow future updates and analysis when more definitive evidence for the best method of fracture prediction in children is agreed. © 2016 American Society for Bone and Mineral Research.