Temporary Immunity and Multiple Waves of COVID-19

ABSTRACTIn this work we use mathematical modeling to describe the potential phenomena which may occur if immunity to COVID-19 lasts for a finite time instead of being permanent, i.e. if a recovered COVID-19 patient may again become susceptible to the virus after a given time interval following his/her recovery. Whether this really happens or not is unknown at the current time. If it does happen, then we find that for certain combinations of parameter values (social mobility, contact tracing, immunity threshold duration etc), the disease can keep recurring in wave after wave of outbreaks, with a periodicity approximately equal to twice the immunity threshold. Such cyclical attacks can be prevented trivially if public health interventions are strong enough to contain the disease outright. Of greater interest is the finding that should such effective interventions not prove possible, then also the second and subsequent waves can be forestalled by a consciously relaxed intervention level which finishes off the first wave before the immunity threshold is breached. Such an approach leads to higher case counts in the immediate term but significantly lower counts in the long term as well as a drastically shortened overall course of the epidemic.As we write this, there are more than 1,00,00,000 cases (at least, detected cases) and more than 5,00,000 deaths due to COVID-19 all over the globe. The unknowns surrounding this disease outnumber the knowns by orders of magnitude. One of these unknowns is how long does immunity last i.e., once a person recovers from COVID-19 infection, how long does s/he remain insusceptible to a fresh infection. Most modeling studies assume lifetime immunity, or at least sufficiently prolonged immunity as to last until the outbreak is completely over. Among the exceptions are Giordano et. al. [1] and Bjornstad et. al. [2] who account for the possibility of re-infection – while the former find no special behaviour on account of this, the latter find an oscillatory approach towards the eventual equilibrium. In an article which appeared today, Kosinski [3] has found multiple waves of COVID-19 if the immunity threshold is finite. The question of whether COVID-19 re-infection can occur is completely open as of now. A study [4] has found that for benign coronaviruses (NOT the COVID-19 pathogen!), antibodies become significantly weaker six months after the original infection, and re-infection is common from one year onwards. Although it is currently unknown whether COVID-19 re-infections can occur, the mere possibility is sufficiently frightening as to warrant a discussion of what might happen if it is true. In this Article, we use mathematical modeling to present such a discussion. Before starting off, let us declare in the clearest possible terms that this entire Article is a what-if analysis, predicated on an assumption whose veracity is not known at the current time. The contents of this Article are therefore hypothetical – as of now they are neither factual nor counter-factual.

DURATION DEPENDENT ANTIAPOPTOTIC EFFICACY OF CAMELLIA SINENSIS (GREEN TEA) ON STREPTOZOTOCIN INDUCED DIABETES LINKED TESTICULAR HYPOFUNCTION IN ALBINO RAT: GENOMIC AND FLOW CYTOMETRIC ASSESSMENT

Objective: The study has been conducted to search out the threshold duration of treatment of ethyl acetate fraction of methanolic extract of leaves of Camellia sinensis (L.) Kuntze at the dose of 100 mg/kg body weight for the management of diabetes-induced testicular impairment in streptozotocin-induced diabetic rat in a duration dependent fashion. Methods: In this respect, the glycemic, androgenic, oxidative stress sensors, gene expression of testicular androgenic key enzymes along with apoptotic markers were evaluated in a duration dependent way (14, 28 and 56 d). Results: A significant correction was noted in the levels of glycated haemoglobin (HbA1C), testicular thiobarbituric acid reactive substances (TBARS), conjugated diene (CD), sperm viability, sperm mitochondrial status, serum testosterone, and genomic expression of testicular Δ5, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, Bax, Bcl-2 after treatment for different duration with the said fraction in diabetic groups in compare to respective vehicle-treated diabetic group without any toxicity induction in general. Thin layer chromatography (TLC) study of the fraction showed two spots with retention factors (Rf) of 0.78 and 0.51. Conclusion: The results showed that 28 d treatment was threshold duration of treatment for the correction of diabetes-induced testicular impairment.

First spikes in visual cortex enable perceptual discrimination

Visually guided perceptual decisions involve the sequential activation of a hierarchy of cortical areas. It has been hypothesized that a brief time window of activity in each area is sufficient to enable the decision but direct measurements of this time window are lacking. To address this question, we develop a visual discrimination task in mice that depends on visual cortex and in which we precisely control the time window of visual cortical activity as the animal performs the task at different levels of difficulty. We show that threshold duration of activity in visual cortex enabling perceptual discrimination is between 40 and 80 milliseconds. During this time window the vast majority of neurons discriminating the stimulus fire one or no spikes and less than 16% fire more than two. This result establishes that the firing of the first visually evoked spikes in visual cortex is sufficient to enable a perceptual decision.

First spikes in visual cortex enable perceptual discrimination

Visually guided perceptual decisions involve the sequential activation of a hierarchy of cortical areas. It has been hypothesized that a brief time window of activity in each area is sufficient to enable the decision but direct measurements of this time window are lacking. To address this question, we develop a visual discrimination task in mice that depends on visual cortex and in which we precisely control the time window of visual cortical activity as the animal performs the task at different levels of difficulty. We show that threshold duration of activity in visual cortex enabling perceptual discrimination is between 40 and 80 milliseconds. During this time window the vast majority of neurons discriminating the stimulus fire one or no spikes and less than 16% fire more than two. This result establishes that the firing of the first visually evoked spikes in visual cortex is sufficient to enable a perceptual decision.

Perbandingan efektivitas pemberian asam mefenamat dan natrium diklofenak sebelum pencabutan gigi terhadap durasi ambang nyeri setelah pencabutan gigi

Tooth extraction is one of a minor operative surgery in dentistry that could cause uncomfortable sense of pain at its surrounding area. In order to reduce that feeling, some pain management could be performed, such as local anesthetic administration or analgesic medication. This study aimed to compare the effectiveness of mefenamic acid and diclofenac sodium given before the extraction procedure against the pain threshold duration after tooth extraction. This was a clinical study with a case-control design and was carried out in July 11th – August 12th 2016 at Department of Oral Surgery RSGM FK Unsrat. There were 30 samples obtained by using the purposive sampling method, divided into three groups, each of 10 samples, as follows: the control group without any analgesic treatment; the treated group with mefenamic acid; and another treated group with diclofenac sodium before the extraction. The results showed that the control group had a lower average of pain threshold duration than the treated groups with a difference of 2 hours and 42 minutes. The group treated with mefenamic acid before the extraction had the highest average of pain threshold duration compared to the group of diclofenac sodium with 4 hours and 11 minutes vs. 3 hours and 49 minutes. Conclusion: Mefenamic acid given before the tooth extraction procedure had greater effect and higher pain threshold duration than diclofenac sodium.Keywords: tooth extraction, mefenamic acid, diclofenac sodium, pain threshold duration.Abstrak: Pencabutan gigi merupakan salah satu tindakan dalam bidang kedokteran gigi yang dapat menimbulkan rasa nyeri akibat adanya trauma pada soket gigi yang dicabut. Untuk mengurangi ketidaknyamanan pasien maka diberikan tindakan manajemen nyeri berupa anestesi lokal dan pemberian analgesik. Penelitian ini bertujuan untuk menganalisis perbandingan efektivitas pemberian asam mefenamat dan natrium diklofenak sebelum pencabutan gigi terhadap durasi ambang nyeri setelah pencabutan gigi. Penelitian ini menggunakan desain penelitian klinis dengan rancangan case-control study. Pengambilan sampel menggunakan teknik purposive sampling berdasarkan kriteria inklusi dan ekslusi dengan total sampel 30 pasien: 10 pasien dalam kelompok kontrol tanpa perlakuan; 10 pasien dalam kelompok uji dengan asam mefenamat; dan 10 pasien dalam kelompok uji dengan natrium diklofenak. Penelitian dilaksanakan pada bulan Juli-Agustus 2016 di Rumah Sakit Gigi dan Mulut Unsrat. Hasil penelitian menunjukkan dari 30 sampel, 10 sampel yang tidak mengonsumsi analgesik apapun sebelum pencabutan memiliki rata-rata durasi ambang nyeri lebih rendah dibandingkan dengan sampel-sampel lain yang mengonsumsi analgesik sebelum pencabutan dengan selisih 2 jam 42 menit. Pasien dengan rata-rata durasi ambang nyeri terbesar ialah yang diberikan asam mefenamat yaitu 4 jam 11 menit dan yang diberikan natrium diklofenak memiliki rata-rata durasi ambang nyeri sebesar 3 jam 49 menit dengan selisih 22 menit. Simpulan: Pemberian asam mefenamat sebelum pencabutan gigi memiliki efektivitas dan rata-rata durasi ambang nyeri yang lebih tinggi dibandingkan pemberian natrium diklofenak dengan selisih durasi ambang nyeri 2 jam 42 menit jika dibandingkan dengan kelompok tanpa pemberian analgesik.Kata kunci: pencabutan gigi, asam mefenamat, natrium diklofenak, durasi ambang nyeri

Is there a threshold duration of vascular occlusion for hindlimb reactive hyperemia?

Relatively brief changes in perfusion pressure and flow through arterioles occur in a number of conditions, such as in the flying environment and during such common everyday activities such as bending forward at the waist. Also, brief periods of negative vertical acceleration (Gz) stress, which reduces perfusion in the lower body, has been shown to impair the regulation of arterial pressure during subsequent positive Gz stress. To examine the contribution that reactive hyperemia makes in these settings, studies on the hindlimb circulation of anesthetized rats ( n = 8) were carried out by imposing graded duration vascular occlusion (1, 2, 4, 10, and 30 s) to test the hypothesis that there is a threshold duration of reduction in perfusion that must be exceeded for reactive hyperemia to be triggered. Vascular conductance responses to 1 s of terminal aortic occlusion were no different before and after myogenic responses were blocked with nifedipine, indicating that 1 s of occlusion failed to elicit reactive hyperemia. Two seconds of occlusion elicited a small but significant elevation in hindlimb vascular conductance. The magnitude of the reactive hyperemia was graded in direct relation to the duration of occlusion for the 2-, 4-, and 10-s periods of occlusion and appeared to be approaching a plateau for the 30-s occlusion. Thus there is a threshold duration of terminal aortic occlusion (∼2 s) required to elicit reactive hyperemia in the hindlimbs of anesthetized rats, and the reactive hyperemia that results possesses a threat to the regulation of arterial pressure.