Circannual variation in lymphocyte subsets, revisited

BACKGROUND: Circadian and circannual variations in lymphocyte subsets, especially CD8+ T-lymphocytes, have been reported. This study focuses on CD4+ T-lymphocyte seasonal variation over a 6-year 8-month period. STUDY DESIGN AND METHODS: Lymphocyte subsets were quantitated monthly for four healthy individuals from 1986 through 1992 as part of a flow cytometry quality-control program. RESULTS: In general, there were no significant seasonal changes in the total number of white cells or in total lymphocyte counts. The absolute numbers of CD4+ T-lymphocytes were lowest in summer when the CD8+ T-lymphocytes were highest. Mean CD4+ T-lymphocyte counts were 846, 967, 618, and 695 per microL for Subjects 1 through 4, respectively, in winter and 432, 670, 355, and 766 per microL, respectively, in summer. Two healthy subjects had CD4+ T-lymphocyte counts lower than 300 per microL on one or more occasions during the study period. In three of the four subjects, the percentage of B-lymphocytes in winter was almost double that in summer. In one of the four subjects, no circannual rhythm was observed in these lymphocyte subpopulations. CONCLUSION: The seasonal variation in CD4+ T- lymphocyte counts demonstrated in three healthy individuals over almost 7 years is again of interest in light of renewed consideration of using surrogate tests, such as CD4+ T-lymphocyte counts, to screen for AIDS- like diseases that may be in the blood supply.     

The family history in family practice: a questionnaire study

OBJECTIVES: Our aims were to investigate family medical history taking in general practice, and to evaluate the value attached to the family medical history as an aid to decision making in general practice. METHOD: A postal questionnaire survey was conducted among all 291 GPs working within the Calderdale and Kirklees Health Authority area. Each questionnaire was followed by a reminder. The main outcome measures were answers to questions on routine and opportunistic family history taking and a question about transmitting knowledge about genetic risk to other members of the family. Questions were also posed about the value attached to the family medical history as an aid to decision making. RESULTS: A total of 193 GPs returned the questionnaire (response rate 66.3%). On registration, 94.3% of GPs indicated that enquiries were made about a family history of coronary heart disease. Breast and colorectal cancer were specifically asked about by 48.4% and 30.7% of GPs, respectively. One-fifth of respondents indicated that they asked a general question about family medical history. A little over one-quarter of respondents indicated that they made opportunistic enquiries about the family history or suggested that the patient should inform other members of the family about possible risks. In the scenarios highlighted in this study, the majority of respondents felt that the family medical history had value as an aid to decision making. This was particularly the case for checking a patient's cholesterol (92.1%) and for initiating referrals in younger patients with possible cancer-related symptoms (three-quarters of respondents). CONCLUSION: GPs value the family medical history as an aid to decision making. Unfortunately, apart from enquiries about coronary heart disease, routine or opportunistic family history taking is not occurring in practice. Mechanisms need to be sought to extract information from the family medical history so that it can be more effectively used by GPs.      

Dexamethasone increases 1,25-dihydroxyvitamin D3 receptor levels and augments bioresponses in rat osteoblast-like cells

Glucocorticoids increase the level of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors in primary cultures of rat calvarial osteoblast-like (OB) cells. The present study investigated how this dexamethasone (DEX) up-regulation of 1,25-(OH)2D3 receptors modulates three 1,25-(OH)2D3 bioresponses: inhibition of collagen synthesis, stimulation of osteocalcin synthesis, and induction of 25-hydroxyvitamin D3-24-hydroxylase activity. Pretreatment of OB cells with 13 nM DEX for 24 h doubled the 1,25-(OH)2D3 receptor level without changing receptor affinity for 1,25-(OH)2D3 to study bioresponses. After DEX treatment to increase the 1,25-(OH)2D3 receptor level, the magnitude and sensitivity of all three 1,25-(OH)2D3 bioresponses were enhanced. The maximal 1,25-(OH)2D3 inhibition of collagen synthesis was increased by DEX pretreatment compound to control values: 30 to 50% (1 day treatment) and 50 to 70% (2 day treatment). The sensitivity to 1,25-(OH)2D3, as measured by reduction of the half-maximal inhibitory dose (ED50), was increased 50%. This potentiation of 1,25-(OH)2D3 inhibitory action on collagen synthesis was still evident after correction for the inhibitory effect on collagen synthesis by DEX alone. The maximal stimulation of osteocalcin by 1,25-(OH)2D3 was also enhanced from 2- to 3-fold in controls to over 4- to 5-fold by DEX pretreatment. Similarly, the ED50 of the response was reduced 50%. For the induction of 25-hydroxyvitamin D3-24-hydroxylase activity, DEX doubled the enzyme activity over that seen with 1,25-(OH)2D3 alone, but only slightly affected the sensitivity of the enzyme induction. In conclusion, after DEX up-regulation of 1,25-(OH)2D3 receptor levels, there was a general potentiation of 1,25-(OH)2D3 bioresponses in rat OB cells. However, the detailed patterns of the augmented responses were different for each of the three biological functions we studied.     

Increased glycogen accumulation in transgenic mice overexpressing glycogen synthase in skeletal muscle.

To investigate the role of glycogen synthase in controlling glycogen accumulation, we generated three lines of transgenic mice in which the enzyme was overexpressed in skeletal muscle by using promoter-enhancer elements derived from the mouse muscle creatine kinase gene. In all three lines, expression was highest in muscles composed primarily of fast-twitch fibers, such as the gastrocnemius and anterior tibialis. In these muscles, glycogen synthase activity was increased by as much as 10-fold, with concomitant increases (up to 5-fold) in the glycogen content. The uridine diphosphoglucose concentrations were markedly decreased, consistent with the increase in glycogen synthase activity. Levels of glycogen phosphorylase in these muscles increased (up to 3-fold), whereas the amount of the insulin-sensitive glucose transporter 4 either remained unchanged or decreased. The observation that increasing glycogen synthase enhances glycogen accumulation supports the conclusion that the activation of glycogen synthase, as well as glucose transport, contributes to the accumulation of glycogen in response to insulin in skeletal muscle.     

Has Omicron Changed the Evolution of the Pandemic?

BackgroundVariants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy.ObjectiveThe aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak.MethodsWe analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections.ResultsThe observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread.ConclusionsThe transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning.     

Strategies for the endodontic management of concurrent endodontic and periodontal diseases

Endodontic and periodontal diseases can provide many diagnostic and management challenges to clinicians, particularly when they occur concurrently. As with all diseases, a thorough history combined with comprehensive clinical and radiographic examinations are all required so an accurate diagnosis can be made. This is essential since the diagnosis will determine the type and sequence of treatment required. This paper reviews the relevant literature and proposes a new classification for concurrent endodontic and periodontal diseases. This classification is a simple one that will help clinicians to formulate management plans for when these diseases occur concurrently. The key aspects are to determine whether both types of diseases are present, rather than just having manifestations of one disease in the alternate tissue. Once it is established that both diseases are present and that they are as a result of infections of each tissue, then the clinician must determine whether the two diseases communicate via the periodontal pocket so that appropriate management can be provided using the guidelines outlined. In general, if the root canal system is infected, endodontic treatment should be commenced prior to any periodontal therapy in order to remove the intracanal infection before any cementum is removed. This avoids several complications and provides a more favourable environment for periodontal repair. The endodontic treatment can be completed before periodontal treatment is provided when there is no communication between the disease processes. However, when there is communication between the two disease processes, then the root canals should be medicated until the periodontal treatment has been completed and the overall prognosis of the tooth has been reassessed as being favourable. The use of non-toxic intracanal therapeutic medicaments is essential to destroy bacteria and to help encourage tissue repair.