Estimation of the Basic Reproduction Number for the COVID-19 Pandemic in Minnesota.

This paper focuses on the dynamics of the COVID-19 pandemic and estimation of associated real-time variables characterizing disease spread. A nonlinear dynamic model is developed which enhances the traditional SEIR epidemic model to include additional variables of hospitalizations, ICU admissions, and deaths. A 6-month data set containing Minnesota data on infections, hospital-ICU admissions and deaths is used to find least-squares solutions to the parameters of the model. The model is found to fit the measured data accurately. Subsequently, a cascaded observer is developed to find real-time values of the infected population, the infection rate, and the basic reproduction number. The observer is found to yield good real-time estimates that match the least-squares parameters obtained from the complete data set. The importance of the work is that it enables real-time estimation of the basic reproduction number which is a key variable for controlling disease spread.

Effects of regular exercise in management of chronic idiopathic constipation.

Regular physical exercise has long been considered in the management of chronic constipation. This recommendation is probably based on the assumption that exercise shortens the transit time through the gastrointestinal tract. However, on the basis of previous studies, the effect of exercise on the transit remains controversial at best. Therefore, it was the goal of the present study to assess the influence of regular physical exercise, what average people may consider routine exercise, in the management of chronic idiopathic constipation. The study population consisted of eight patients, seven women and a man, with chronic idiopathic constipation. They were studied for six weeks, including two weeks of rest and four weeks of regular exercise. Patients had a submaximal exercise test, before and after the exercise period, to determine their rate of perceived exertion (RPE), the target heart rate, and the intensity of exercise they can perform. In addition to their routine daily activities, they exercised 1 hr a day, five days a week according to their performance at the initial exercise tolerance test. They kept a daily activity log and maintained their normal dietary intake during this period. The patients overall physical activity was assessed by a pedometer. They also maintained a diary of the number and consistency of their bowel movements and the amount of straining required for defecation. The impact of exercise on constipation was assessed by utilizing an index that took into consideration all three parameters of bowel function. Results of the study revealed that patients covered 1.8+/-0.33 and 3.24+/-0.28 miles/day in the rest period and during the exercise period, respectively (P = 0.007). The intensity of exercise may have improved the level of training as reflected on the mean maximum time before and after exercise period (P = 0.039). This level of exercise did not improve their constipation indices, which were 9.11+/-0.65 and 8.57+/-1.08 in the rest and exercise periods, respectively (P = 0.68). In conclusion, physical activity, to the extent that people consider "regular exercise," does not play a role in the management of chronic idiopathic constipation.

Pharmacological characterization of the "silent" 5-hydroxytryptamine1B-like receptors of rabbit ear artery.

Serotonin acts on 5-hydroxytryptamine (5-HT)1B-like receptors in isolated rabbit ear artery precontracted with phenylephrine (PHE). These receptors are inactive, or "silent," in untreated vessels. Ear artery rings were mounted in tissue baths for the measurement of isometric contraction to further characterize these 5-HT1B-like receptors. The 5-HT1-selective receptor agonist sumatriptan failed to contract the untreated ear artery rings but caused a powerful, concentration-dependent contraction in PHE-precontracted vessels. The 5-HT1A/rat 1B receptor antagonist propranolol (1 microM) had no effect, whereas the 5-HT1B receptor antagonists rauwolscine (0.1 microM) and GR127935 (1-100 nM) markedly inhibited the contraction to sumatriptan. In vessels precontracted with phenylephrine, nifedipine reduced and calcium-free medium abolished the contractile response to serotonin. Relaxation to the adenylate cyclase activator forskolin was studied in contracted ear artery rings. Low concentrations (0.1-0.3 microM) of forskolin rapidly and completely relaxed ear artery rings contracted with PHE. In contrast, when PHE-precontracted vessels were contracted with either serotonin or sumatriptan, forskolin caused little or no relaxation at low concentrations and only partial relaxation at 10- to 30-fold higher concentrations. The resistance of these vessels to relaxation by forskolin was markedly reduced in the presence of GR127935 or in ear artery rings from pertussis toxin-treated rabbits. However, pertussis toxin treatment had no effect on the contractile response of PHE-precontracted ear artery rings to serotonin. It is concluded that the silent 5-HT1-like receptor of rabbit ear artery closely resembles the 5-HT1B receptor subtype. This receptor is inversely coupled to adenylate cyclase through a pertussis toxin-sensitive G protein; however, this coupling is unlikely to contribute to the serotonin-induced contraction of PHE-precontracted ear artery rings. Instead, this contraction is mediated at the second-messenger level by pertussis toxin-insensitive influx of calcium.

Clinical value of anorectal manometry index in neurogenic fecal incontinence.

PURPOSE: The present communication is an endeavor to assess the value of a simple motility index to separate patients with neurogenic or idiopathic fecal incontinence from those patients with the secondary form of the disease. METHODS: Study population consisted of 23 patients with idiopathic fecal incontinence and 13 patients with fecal incontinence secondary to surgical or obstetric trauma. They all had a standard anorectal manometric study after a 12-hour fast. A motility index was then prepared taking into consideration the peak sphincter pressure values, contractility endurance, and rectal sensory threshold. RESULTS: Despite differences in the mean peak squeeze pressure and sensory threshold between the two groups, there were significant overlaps for all parameters of standard anorectal manometry in both groups. However, patients with idiopathic incontinence had an index of smaller than 28, and the group with the secondary form of incontinence had indexes higher than 30. CONCLUSIONS: 1) None of the four parameters of a conventional anorectal manometry can accurately separate patients with neurogenic incontinence from those with secondary forms of the disorder. 2) The anorectal motility index presented here can accurately separate the two groups. 3) This index is superior to the standard anorectal manometry in evaluating patients with fecal incontinence.

Effect of alpha adrenergic agonist on the rabbit ear artery contraction to serotonin: enhanced response mediated by serotonergic1-like receptors.

The effect of methoxamine or phenylephrine (PHE) on the contractile response of the rabbit ear artery to serotonin was assessed by using isolated arterial rings mounted in tissue baths for the measurement of isometric force development. A contractile threshold concentration of methoxamine or PHE (10-30 nM) shifted the serotonin concentration-response curve to the left by approximately 200-fold. Neither mechanical removal of the vascular endothelium nor chemical denervation had any effect on the alpha agonist-amplified response of ear artery to serotonin. Although the response to serotonin in the absence of the alpha agonist was mediated primarily by alpha-1 adrenergic receptors, prazosin did not block the amplified response to serotonin. Ketanserin (10 nM), ritanserin (50 nM) and MDL 72222 (1 microM) also had no effect on the amplified response, ruling out the involvement of serotonergic (5-HT)2 and 5-HT3 receptors. However, methiothepin (3 nM) and 1-(1-naphthyl)piperazine (10 and 100 nM) blocked the PHE-amplified contraction of ear artery to serotonin. When the contractile response of ear artery to 5-carboxamidotryptamine was measured in the presence of a threshold concentration of alpha agonist, the concentration-response curve was shifted 8300-fold to the left. The amplified response to 5-carboxyamidotryptamine was insensitive to 10 nM ketanserin, but was blocked by 3 nM methiothepin. Sumatriptan, a selective 5-HT1 agonist, failed to induce vasoconstriction in the absence of a threshold concentration of alpha agonist. However, in the presence of PHE, sumatriptan induced a concentration-dependent contraction.(ABSTRACT TRUNCATED AT 250 WORDS)