Estimation of the size of the COVID-19 pandemic using the epidemiological wavelength model: results from OECD countries.

OBJECTIVES: This study aimed to simplify the previously developed epidemiological wavelength model and to expand the scope of the model with additional variables to estimate the magnitude of the COVID-19 pandemic. The applicability of the extended wavelength model was tested in Organisation for Economic Cooperation and Development (OECD) member countries. STUDY DESIGN: The epidemiological wavelengths of OECD member countries for the years 2020, 2021 and 2022 were estimated comparatively, considering the cumulative number of COVID-19 cases. METHODS: The size of the COVID-19 pandemic was estimated using the wavelength model. The scope of the wavelength model was expanded to include additional variables. The extended estimation model was improved by adding population density and human development index variables, in addition to the number of COVID-19 cases and number of days since the first case reported from the previous estimation model. RESULTS: According to the findings obtained from the wavelength model, the country with the highest epidemiological wavelength for the years 2020, 2021 and 2022 was the United States (We = 29.96, We = 28.63 and We = 28.86, respectively), and the country with the lowest wavelength was Australia (We = 10.50, We = 13.14 and We = 18.44, respectively). The average wavelength score of OECD member countries was highest in 2022 (We = 24.32) and lowest in 2020 (We = 22.84). The differences in the periodic wavelengths of OECD countries were analysed with the dependent t-test for paired samples in two periods, 2020-2021 and 2021-2022. There was a statistically significant difference between wavelengths in the 2020-2021 and 2021-2022 groups (t(36) = -3.670; P < 0.001). CONCLUSIONS: Decision-makers can use the extended wavelength model to easily follow the progress of the epidemic and to make quicker and more reliable decisions.

The impact of ageing, fasting and high-fat diet on central and peripheral glucose tolerance and glucose-sensing neural networks in the arcuate nucleus.

Obesity and ageing are risk factors for diabetes. In the present study, we investigated the effects of ageing, obesity and fasting on central and peripheral glucose tolerance and on glucose-sensing neuronal function in the arcuate nucleus of rats, with a view to providing insight into the central mechanisms regulating glucose homeostasis and how they change or are subject to dysfunction with ageing and obesity. We show that, following a glucose load, central glucose tolerance at the level of the cerebrospinal fluid (CSF) and plasma is significantly reduced in rats maintained on a high-fat diet (HFD). With ageing, up to 2 years, central glucose tolerance was impaired in an age-dependent manner, whereas peripheral glucose tolerance remained unaffected. Ageing-induced peripheral glucose intolerance was improved by a 24-hour fast, whereas central glucose tolerance was not corrected. Pre-wean, immature animals have elevated basal plasma glucose levels and a delayed increase in central glucose levels following peripheral glucose injection compared to mature animals. Electrophysiological recording techniques revealed an energy-status-dependent role for glucose-excited, inhibited and adapting neurones, along with glucose-induced changes in synaptic transmission. We conclude that ageing affects central glucose tolerance, whereas HFD profoundly affects central and peripheral glucose tolerance and, in addition, glucose-sensing neurones adapt function in an energy-status-dependent manner.

[Ulipristal acetate (Esmya): a selective modulator of progesterone receptors, new treatment of uterine fibromatosis]. / Le médicament du mois. L'acétate d'ulipristal (Esmya): un modulateur sélectif des récepteurs à la progesterone, nouveau traitement de la fibromatose utérine.

Uterine fibromatosis is a frequent benign gynaecological disease causing heavy menstrual bleeding and in some cases anaemia. Until now, medical treatment aimed to obtain amenorrhea by administration of progestins or Gn-RH agonists. By inducing hypo-oestrogenism, a reduction of myoma size is observed with Gn-RH agonists but after cessation of the treatment, initial myoma size is noted. The impact of progesterone in myoma growth is nowadays demonstrated and use of selective modulators of progesterone receptors represents a new medical approach of this disease.

Short photoperiod-induced decrease of histamine H3 receptors facilitates activation of hypothalamic neurons in the Siberian hamster.

Nonhibernating seasonal mammals have adapted to temporal changes in food availability through behavioral and physiological mechanisms to store food and energy during times of predictable plenty and conserve energy during predicted shortage. Little is known, however, of the hypothalamic neuronal events that lead to a change in behavior or physiology. Here we show for the first time that a shift from long summer-like to short winter-like photoperiod, which induces physiological adaptation to winter in the Siberian hamster, including a body weight decrease of up to 30%, increases neuronal activity in the dorsomedial region of the arcuate nucleus (dmpARC) assessed by electrophysiological patch-clamping recording. Increased neuronal activity in short days is dependent on a photoperiod-driven down-regulation of H3 receptor expression and can be mimicked in long-day dmpARC neurons by the application of the H3 receptor antagonist, clobenproprit. Short-day activation of dmpARC neurons results in increased c-Fos expression. Tract tracing with the trans-synaptic retrograde tracer, pseudorabies virus, delivered into adipose tissue reveals a multisynaptic neuronal sympathetic outflow from dmpARC to white adipose tissue. These data strongly suggest that increased activity of dmpARC neurons, as a consequence of down-regulation of the histamine H3 receptor, contributes to the physiological adaptation of body weight regulation in seasonal photoperiod.

[Treatment of severe preeclampsia: until when and for what risks/benefits?]. / Traitement de la prééclampsie sévère: jusqu' où, et pour quels risques/bénéfices?

The four major hypertensive disorders related to pregnancy are preeclampsia, chronic hypertension, preeclampsia superimposed upon chronic hypertension, and gestational hypertension. The development of hypertension and proteinuria in pregnancy is usually due to preeclampsia, particularly in a primigravida. These findings typically become apparent in the latter part of the third trimester and progress until delivery, but some women develop symptoms in the latter half of the second trimester, or intrapartum, or the early postpartum period. Preeclampsia is characterized as mild or severe. Severe hypertension, coagulopathy, thrombocytopenia, liver function abnormalities, and fetal growth restriction are features of severe disease. Laboratory evaluation should assess haemoglobin/hematocrit and platelet count, renal and hepatic function, as well as assessment of fetal well-being and growth. Timing of delivery is based upon gestational age, maternal and fetal condition, and the severity of preeclampsia. Maternal end organ dysfunction and nonreassuring tests of fetal well-being are indications for delivery at any gestational age. Antihypertensive treatment aims at protecting the mother from severe hypertensive encephalopathy, but may jeopardize the fetus. We recommend antenatal corticosteroids (betamethasone) be given to women with preeclampsia at 26 to 34 weeks of gestation. Magnesium sulfate is more effective than phenytoin for prevention of eclamptic seizures.

Pharmacological and molecular characterization of ATP-sensitive K(+) conductances in CART and NPY/AgRP expressing neurons of the hypothalamic arcuate nucleus.

The role of hypothalamic ATP-sensitive potassium channels in the maintenance of energy homeostasis has been extensively explored. However, how these channels are incorporated into the neuronal networks of the arcuate nucleus remains unclear. Whole-cell patch-clamp recordings from rat arcuate nucleus neurons in hypothalamic slice preparations revealed widespread expression of functional ATP-sensitive potassium channels within the nucleus. ATP-sensitive potassium channels were expressed in orexigenic neuropeptide Y/agouti-related protein (NPY/AgRP) and ghrelin-sensitive neurons and in anorexigenic cocaine-and-amphetamine regulated transcript (CART) neurons. In 70% of the arcuate nucleus neurons recorded, exposure to glucose-free bathing medium induced inhibition of electrical excitability, the response being characterized by membrane hyperpolarization, a reduction in neuronal input resistance and a reversal potential consistent with opening of potassium channels. These effects were reversible upon re-introduction of glucose to the bathing medium or upon exposure to the ATP-sensitive potassium channel blockers tolbutamide or glibenclamide. The potassium channel opener diazoxide, but not pinacidil, also induced a tolbutamide and glibenclamide-sensitive inhibition of electrical excitability. Single-cell reverse transcription-polymerase chain reaction revealed expression of mRNA for sulfonylurea receptor 1 but not sulfonylurea receptor 2 subunits of ATP-sensitive potassium channels. Thus, rat arcuate nucleus neurons, including those involved in functionally antagonistic orexigenic and anorexigenic pathways express functional ATP-sensitive potassium channels which include sulfonylurea receptor 1 subunits. These data indicate a crucial role for these ion channels in central sensing of metabolic and energy status. However, further studies are needed to clarify the differential roles of these channels, the organization of signaling pathways that regulate them and how they operate in functionally opposing cell types.

Integration of metabolic stimuli in the hypothalamic arcuate nucleus.

Integration of peripheral and central anabolic and catabolic inputs within the hypothalamic arcuate nucleus (ARC) is believed to be central to the maintenance of energy balance. In order to perform this complex task, neurons in the ARC express receptors for all major humoral and central transmitters involved in the maintenance of energy homeostasis. The integration of these inputs occurs at the cellular and circuit level and the resulting electrical output forms the origins for the activation of feeding and energy balance-related networks. Here, we discuss the role that active intrinsic membrane conductances, K(ATP) channels and intracellular second messenger systems play in the integration of metabolic stimuli at the cellular level in the ARC. We conclude that the research into the integration of hunger and satiety signals in the ARC has made substantial progress in the last decade, but we are far from unraveling the complex neuronal networks involved in the maintenance of energy homeostasis. The diverse range of inputs, neuronal integrative properties, targets, output signals and how these signals relate to the physiological output provides us with a colossal challenge for years to come. However, to battle the current obesity epidemic, target-specific drugs need to be developed for which the knowledge of neuronal pathways involved in the maintenance of energy homeostasis will be crucial.

Melatonin generates an outward potassium current in rat suprachiasmatic nucleus neurones in vitro independent of their circadian rhythm.

The present study investigated the membrane mechanisms underlying the inhibitory influence of melatonin on suprachiasmatic nucleus (SCN) neurones in a hypothalamic slice preparation. Perforated-patch recordings were performed to prevent the rapid rundown of spontaneous firing rate as observed during whole cell recordings and to preserve circadian rhythmicity in SCN neurones. In current-clamp mode melatonin (1 microM or 1 nM) application, in the presence of agents that block action potential generation and fast synaptic transmission, resulted in a membrane hyperpolarisation accompanied with a decrease in input resistance in the majority of SCN neurones (71-86%). The amplitude of the hyperpolarisation was not found to be significantly different between circadian time 5-12 and 14-21. In voltage-clamp mode melatonin (1 microM or 1 nM) induced an outward current accompanied with an increase in membrane conductance. The current was found to be mainly potassium driven with voltage kinetics resembling those of an open rectifying potassium conductance. Investigations into the signal transduction mechanism revealed melatonin-induced inhibition of SCN neurones to be sensitive to pertussis toxin but independent of intracellular cAMP levels and phospholipase C activity. The present study shows that melatonin, at night-time physiological concentrations, reduces the neuronal excitability of the majority of SCN neurones independent of the time of application in the circadian cycle. Thus in vivo melatonin may be important for circadian time-keeping by amplifying the circadian rhythm in SCN neurones, by lowering their sensitivity to phase-shifting stimuli occurring at night.

Development of a human lung surfactant, derived from extracted amniotic fluid.

Using a surfactant preparation of human origin for the treatment of the respiratory distress syndrome (RDS) instead of an animal-derived surfactant will minimize immunological problems. Therefore we isolated surfactant material from human amniotic fluid. Protein and phospholipid fractions of extracted human amniotic fluid (HAFS) were separated by Lipidex 5000 or acidulated LH20 liquid chromatography systems. Fractions of HAFS, the phospholipid or the recombined phospholipid-protein fractions, were tested in the 27-day fetal rabbit model. The results were compared with the results of the corresponding fractions of extracted ovine lung lavage (EOS) and of the already clinically tested surfactant Curosurf. The in situ surface activity of HAFS, EOS, and of their combined phospholipid + protein fractions (200 mg/kg body wt.) resulted in a lung compliance which was significantly higher than the control (saline) values. The compliances of HAFS, EOS, their combined fractions, and Curosurf were similar, but the lung stability values (V5) differed significantly among these surfactant extracts. The best V5 values (greater than or equal to 0.020 ml/g body wt.) were found after installing EOS or its LH20 phospholipid + protein fractions. HAFS had a poor stabilizing capacity which increased significantly after Lipidex chromatography and even more after enrichment of the Lipidex material with 10% palmitic acid. The Lipidex HAFS + 10% palmitic acid surfactant is at present the best obtainable human surfactant extract. Further development is in progress for the clinical application of this surfactant in preterm neonates.

[An evaluation of the first two years of activity at the in vitro fertilization center in the +Notre Dame Clinic in Charleroi+(Belgium)]. / Bilan des deux premières années d'activité du Centre de Fécondation in vitro de la Clinique Notre-Dame à Charleroi (Belgique).

An in vitro fertilisation unit has been working since the 1 st May 1988 in the Notre-Dame Clinic in Charleroi in the Beligium province of Hainaut. This work analyses the practice and results of the first two years activity in which 185 oocytes retrievals were carried out. The account not only deals with the results (according to 8 criteria for evaluation) but also on the factors that modify these results (9 parameters). It is scientific tools that makes it possible to analyse objectively and precisely, the factors leading to success or failure in our technique. The results are compared with those in the literature and in the French national enquiries (these do not exist in Belgium) show that even in modest conditions (2 gynaecologists and a biologist who have other duties) it is possible to carry out in the first year 62 and in the second year 123 oocyte recoveries. The scrupulous attention to technical details in this university centre of reference made it possible from the beginning to achieve worthwhile results (21% pregnancies for all recoveries and 32% pregnancies for all embryo transfers).