Age-stratified transmission model of COVID-19 in Ontario with human mobility during pandemic's first wave.

In this work, we employ a data-fitted compartmental model to visualize the progression and behavioral response to COVID-19 that match provincial case data in Ontario, Canada from February to June of 2020. This is a "rear-view mirror" glance at how this region has responded to the 1st wave of the pandemic, when testing was sparse and NPI measures were the only remedy to stave off the pandemic. We use an SEIR-type model with age-stratified subpopulations and their corresponding contact rates and asymptomatic rates in order to incorporate heterogeneity in our population and to calibrate the time-dependent reduction of Ontario-specific contact rates to reflect intervention measures in the province throughout lockdown and various stages of social-distancing measures. Cellphone mobility data taken from Google, combining several mobility categories, allows us to investigate the effects of mobility reduction and other NPI measures on the evolution of the pandemic. Of interest here is our quantification of the effectiveness of Ontario's response to COVID-19 before and after provincial measures and our conclusion that the sharp decrease in mobility has had a pronounced effect in the first few weeks of the lockdown, while its effect is harder to infer once other NPI measures took hold.

Controlling infection in predator-prey systems with transmission dynamics.

We propose in this paper a prophylactic treatment strategy for a predator-prey system. The objective is to fight against the propagation of an infectious disease within two populations, one of which preys on the other. This propagation is modeled by means of an SIS (susceptible-infectious-susceptible) epidemic model with vital dynamics and infection propagation in both species through contact and predation, including mortality rates in both populations due directly to the disease. Treatment strategies are represented by new parameters modeling the uptake rates in the populations. We analyze the effect of various treatment strategy scenarios (prey only, predator only, or both) via their uptake rates and possible cost structures, on the size of the infected populations. We illustrate if and when applying such preventive treatments lead to a disease prevalence drop in both populations. We conduct our study using an optimal control model seeking to minimize the treatment cost(s), subject to the transmission dynamics and predator-prey dynamics.

Lack of association between ACE ID polymorphism and colorectal cancer in Romanian patients.

BACKGROUND: The insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene has recently been linked to the pathogenesis of human cancers. The goal of this study was to analyze the possible association between ACE gene I/D polymorphism and colorectal cancer in Romanian patients. METHODS: Blood samples were obtained, after informed consent, from individuals with colorectal cancer (n=108, M:W = 64:44), and healthy persons (n=150, M:W = 84:66). Genomic DNA was extracted from peripheral blood leucocytes using commercial kits and the insertion (I) / deletion (D) polymorphism was assessed by PCR. Statistical analysis was done using the chi2 test. We determined the odds ratio using the genotype II as risk factor. A p value < 0.05 was considered statistically significant. RESULTS: The distribution of ACE II: ID: DD genotypes was 23.1%: 46.3%: 30.6% in patients and respectively 20%: 48.7%: 31.3% in controls. The distribution of genotype (chi2 0.37, p = 0.54) and alleles (chi2 0.19, p = 0.65) did not differ significantly between cancer patients and control. CONCLUSIONS: Study results do not demonstrate an association between ACE ID polymorphism and colorectal cancer in our patients.

Root Resorption Diagnostic: Role of Digital Panoramic Radiography.

INTRODUCTION: Root resorption is a pathological process characterized by loss of dental root substance, caused by bacterial infections, traumatic injuries or chemical irritation. Root resorption might be accidentally observed on digital panoramic radiography. OBJECTIVE: The objective of the study was to identify characteristic radiological aspects for the different types of root resorption that could be observed on digital panoramic radiography, to make an easier diagnostic of root resorption. MATERIAL AND METHOD: The retrospective study used the X-ray base from the Oral Rehabilitation and Dental Prosthetics Clinic of UMF Craiova to identify the most representative images for different types of root resorption. Digital panoramic radiographies were analysed by two investigators, of which the most suggestive images were selected and described. RESULTS: Digital panoramic radiographies and dental charts of 240 patients were analyzed. 113 cases of root resorption were identified. External inflammatory root resorption (EIRR) was present in 27.07% of studied cases, external cervical root resorption (ECRR) was identified in 10.83% of all studied cases, external replacement root resorption (ERRR) was diagnosed in 7.08% of studied cases and internal root resorption (IRR) was the most rare type of root resorption, with only 2.08% from all studied cases. 16 cases were selected to describe the radiologic features of different types of root resorption, featuring the most interesting images of root resorption evident on digital panoramic radiographies. DISCUSSION: Comparative analyses have been made between our results and the results of other specific studies, with both similar and different values. The radiological features which lead to the diagnostic of each type of RR were highlighted, assessing the causes that caused the lesions, as well as the treatment recommendations. CONCLUSIONS: Digital panoramic radiography is a useful tool to identify root resorption, since it has become the most common radiological investigation for diagnostic in dentistry. Description of radiological aspects of different types of root resorption on panoramic digital radiography allows faster diagnosis. Still, the CBCT may be recommended in some cases to confirm the diagnosis.

Adoption costs of new vaccines - A Stackelberg dynamic game with risk-perception transition states.

Vaccination has become an integral part of public health, since an increase in overall vaccination in a given population contributes to a decline in infectious diseases and mortality. Vaccination also contributes to a lower rate of infection even for nonvaccinators due to herd immunity ((Brisson and Edmunds, 2002)). In this work we model human decision-making (with respect to a vaccination program in a single-payer health care provider country) using a leader-follower game framework. We then extend our model to a discrete dynamic game, where time passing is modelled by risk perception changes among population groups considering whether or not to vaccinate. The risk perception changes are encapsulated by probability transition matrices. We assume that the single-payer provider has a given fixed budget which would not be sufficient to cover 100% of a new vaccine for the entire population. To increase the potential coverage, we propose the introduction of a partial vaccine adoption policy, whereby an individual would pay a portion of the vaccine price and the single payer would support the rest for the entire population. We show how this policy, together with changes in risk perceptions regarding vaccination, impact the strategic decisions of individuals in each group, the policy cost under budgetary constraints and, ultimately, how it impacts the overall uptake of the vaccine in the entire population.

New insight into the rheumatoid vasculitis.

Vasculitis in rheumatoid arthritis (rheumatoid vasculitis, RV) has a heterogeneous clinical presentation that includes skin disorders, neuropathy, eye symptoms and systemic inflammation. Rheumatoid vasculitis is an unusual complication of longstanding, severe rheumatoid arthritis (RA). While RA affects the body's joints, vasculitis is a condition in which blood vessels become inflamed. Rheumatoid vasculitis occurs in approximately 2 to 5% of patients who have RA. The blood vessels most often involved are arteries that bring blood to the skin, nerves, and internal organs. Veins can also be involved. Rheumatoid vasculitis is skin condition that is a typical feature of RA, presenting as peripheral vascular lesions that are localized (purpura, cutaneous ulceration, and gangrene of the distal parts of the extremities). The cause of RV is unknown, but given the prominence of immune components and the pathologic changes in involved blood vessels, an autoimmune process is suggested. Compared to other forms of vasculitis, there has been relativejy little research in recent years on the specific entity of RV. There is some evidence that the incidence of RV has decreased over the past several decades, perhaps because of a better treatment of the underlying RA. In the present review, we discuss the clinical features, laboratory tests, the pathogenesis of RV.

Multiple Intracerebral Hemorrhages in an Old Patient with Rheumatoid Arthritis.

A 78-year-old Caucasian man was admitted in the Department of Neurology for visual disturbances, started two days before. The next day the patient experienced headache, fever and gait disturbances. He had hypertension, diabetes mellitus, an ischemic stroke 13 years ago, longstanding seronegative rheumatoid arthritis (17 years), polynodular goiter, right ischio-pubian fracture and right femoral vein thrombosis a year ago due to a car accident, since he is treated with oral anticoagulants associated to antiaggregant, hypotensors, statin and oral antidiabetics. The neurologic examination had evidenced nuchal rigidity, left homonymous hemianopsia, left central facial palsy, ataxia of the inferior limbs with wide-based gait, achilean reflexes abolished bilaterally, bilaterally abolished plantar reflexes, ideomotor apraxia, dysarthria, hypoprosexia, and preserved consciousness patient. A non-contrast cerebral CT scan had shown right temporal and parieto-occipital intraparenchymatous hemorrhages, a right frontal sequelar lesion, multiple old lacunar infarets, cortical atrophy. Laboratory findings included an inflammatory syndrome, absence of rheumatoid arthritis positive serology, normal coagulogram, an elevated proteinuria. The cerebral IRM performed on the seventh day of hospitalisation was suggestive for subacute right parietal hemorrhage, old cerebral infarction in the right anterior cerebral artery area, old lacunar infarcts and cerebral atrophy. The anticoagulant and antiaggregant treatment was stopped after a generalized tonic-clonic seizure occurred. Antiedematous, hypotensor, anticonvulsivant, beta-blocker, and symptomatic treatment was started, while the antidiabetic treatment was continued. All symptoms remitted. Arguments for amyloid angiopathy in our patient are previous non-cardioembolic ischemic stroke and a chronic inflammatory disease- rheumatoid arthritis in his personal medical history.

Trigger points--ultrasound and thermal findings.

RATIONALE: Muscle pain can be elicited by any irritation of the nociceptors in the muscle or central sensitization in the central nervous system. The most frequently described muscle pain syndromes are myofascial pain syndrome and fibromyalgia syndrome. Myofascial pain syndrome has a more localized manifestation, the trigger points. OBJECTIVE: If there is a correlation between the clinical findings, the ultrasound examination and the thermal pattern of trigger points exist. MATERIAL AND METHOD: The presence of trigger points can be identified by using clinical criteria. An ultrasound examination was performed to evaluate the trigger point dimensions. The ultrasound showed an ellipsoidal hypoechogenic area in the muscle. A thermography of the low back region was performed in order to observe the thermal pattern of the area. RESULTS: Trigger points are represented by a higher temperature area surrounded by a cooler area, probably caused by a deficit in the blood flow around those points. DISCUSSION: Infrared thermography could be a great asset for the monitoring of neuromusculoskeletal disorders and their dynamics, as well as an important aid for the initial diagnosis of conditions associated with tissue temperature alterations.

Thermal patterns in zoster.

RATIONALE: Varicella zoster virus is a neurotropic virus that causes an infectious disease characterized by skin changes and neuropathic pain. After the resolution of the first infection, the virus lies dormant within the sensory ganglia. The reactivation of the virus causes zoster. An alteration in skin infrared emission might be expected in the areas of the skin affected by inflammatory changes and demyelination of the affected peripheral nerve. OBJECTIVE: To establish the importance of thermal imaging in the follow up of Zoster Zone with different localization. An infrared thermal camera was used in order to assess if the evolution of the disease determines a thermal pattern. METHODS AND RESULTS: Infrared thermography can be used for the assessment of the affected area also by using a thermography camera that is sensitive to the infrared spectrum. An intense and diffuse infrared emission is highly suggestive for the inflammation and implies that a more aggressive treatment should be initiated. After the clinical resolution of the affected area, the symmetry of the thermal pattern should be restored. If the asymmetry persists, a neuropathic complication of the virus reactivation could be involved. DISCUSSIONS: The integration of infrared thermography with the clinical findings is very useful in order to create a complete picture of the zoster lesions and this method could determine the beginning of a correct treatment and, by doing so, minimizing the risk of complications.

The intrinsic synthesis of juvenile hormone-III diol by locust corpora allata in vitro.

Juvenile hormone (JH)-III 10-11-diol is intrinsically synthesized and released from the corpora allata (CA) of adult locust females in vitro, together with JH-III. JH-III synthesis is preferentially stimulated and diol production only slightly enhanced, by cerebral locust allatotropin. The identification of JH-III diol is based on: similar ratio of incorporation of 14C/3H from radiolabelled [2-14C]acetate and [methyl-3H]methionine, to that of JH-III; similar chromatographic properties to those of synthetic diol on an RP-18 column eluted with acetonitrile, and similar chromatographic properties of acetylated derivatives; mass spectrometric analysis of derivatives and fragmentation products. Exogenous radiolabelled JH-III is not degraded during incubation with locust CA in vitro, corroborating the endogenous production of JH-III diol. Allatal diol formation may be an additional mechanism for the control of JH-III levels in locusts, preceding release into the hemolymph.

Synthesis of 19-nor-aldosterone, 18-hydroxy-19-nor-corticosterone and 18,19-dihydroxycorticosterone in the human aldosterone-producing adenoma.

The recently synthesized 18-C-steroid derivative, 19-nor-aldosterone(19-nor- aldo) and 18-hydroxy-19-nor-corticosterone(18-OH-19-nor-corticosterone) possess mineralocoroticoid and hypertensinogenic activity. They and an additional newly synthesized steriod, 18,19-dihydroxycorticosterone[18,19(OH)2-corticosterone], may play a role in the etiology and pathogenesis of disorders thought to be caused by steroids with mineralocorticoid and hypertensionogenic properties. In this study we provide evidence that 19-nor-aldo, 18-OH-19-nor-corticosterone and 18,19(OH)2-corticosterone are produced in vitro by aldosterone-producing adrenal adenomas and adenomas and adenoma of Cushing's syndrome. "silent" adrenal adenomas and the adjacent adrenal tissue. Measurable amounts of these steroids were found in the incubation fluids of adrenal tissues using specific RIAs performed after a sequence of HPLC systems. The rates of production of the three steroids were high in the aldosterone-producing adrenal adenomas and in adrenal hyperplasia compared with in either Cushing's adenoma or "silent" adenoma.

Synthesis of 4,19-disubstituted derivatives of DOC. Radioreceptor assay of some corticosteroid derivatives in human mononuclear leukocytes.

Several new 4,19-substituted steroids and previously synthesized corticosteroids were assayed for affinity to type 1 receptors in human mononuclear leukocytes. 11 beta,19-epoxy-4,21-dihydroxypregn-4-ene-3,20-dione (2) was hydrogenated with Pd-C to yield a mixture of all four dihydro derivatives 5, accompanied by 4,21-diacetoxy-11 beta,19-epoxy-3-hydroxypregnan-20-one (6) and 21-acetoxy-11 beta,19-epoxy-4-hydroxypregnane-3,20-dione (7). With hot acetic + p-toluenesulfonic acid 5 underwent rearrangement to 21-acetoxy-11 beta,19-epoxypregn-5-ene-4,20-dione (8) Pd-C hydrogenation of 3,21-diacetoxy-5 beta,19-cyclopregna-2,9(11)-diene-4,20-dione (10) gave 3,21-diacetoxy-5 beta,19-cyclopregn-5-ene-4,20-dione (11) and the 9,11-dihydro derivative of the latter. Treatment of 10 with warm HCl furnished 19-chloro-4,21-dihydroxypregna-4,9(11)-diene-3,20-dione (13). Pd-C hydrogenation of its diacetate 14 afforded the 4,5-dihydro derivative 18, 19-chloro-21-acetoxypregn-9(11)-en-20-one (15), its 4-acetoxy derivative 16 and the 3,4-diacetoxy derivative 17. When tested in a radioreceptor assay in human mononuclear leukocytes the synthesized compounds showed only low relative binding affinities (RBA) to type 1 receptor, the highest being 0.72% for 13 (aldosterone = 100%). For comparison, other RBA in this system were: 19-noraldosterone, 20%; 18-deoxyaldosterone, 5.8%; 18-deoxy-19-noraldosterone, 4.7%; 18,21-anhydroaldosterone, 0.37%; 17-isoaldosterone, 7.6% and apoaldosterone, 4.3%

Bound amino acids in uremic sera: search for peptidic middle molecules by preparative polyacrylamide gel electrophoresis and high performance liquid chromatography.

The samples of normal and uremic sera were ultrafiltered, separated on SEP-PAK C18 cartridges and subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The serum material extracted from the slab gel was purified from SDS and further fractionated by reverse-phase high performance liquid chromatography (HPLC). The obtained fractions were examined by amino acid analysis and mass spectrometry. An increased number of moderately polar fractions containing bound amino acids was found in sera of uremic patients on hemodialysis. Two most prominent uremic fractions corresponded to N-benzoylglycine (hippuric acid) (fraction I, k' = 9,4) and phenylacetylglutamine (fraction II, k' = 9,7). Increased amounts of bound glutamine, glycine, serine, leucine, asparagine, alanine, valine, phenylalanine were found in other moderately polar uremic fractions. These fractions (k' range from 12.1 to 13.2) contained no free amino acids, nor any other known small uremic serum compounds; they were considered as peptide 'middle molecules' (MM) of a molecular mass smaller than 1700.

Synthesis of 18,19-dihydroxycorticosterone.

A four-step synthesis of 18,19-dihydroxycorticosterone 5c, starting with 19,21-dihydroxy-3,20-dioxopregn-5-ene-18,11 beta-lactone-di-(ethylene ketal) 2, is presented. Reduction of 2 with sodium aluminum bis-(methoxyethoxy)hydride gave 11 beta,18,19,21-tetrahydroxy-pregn-5-ene-3,20-dione-di-(ethylene ketal) 3a. Acetylation furnished the corresponding 18,19,21-triacetate 3b, which on treatment with a mixture of perchloric and acetic acids gave 18,19-dihydroxycorticosterone 18,19,21-triacetate 4b. Mild saponification yielded the title compound which, on the basis of ir and nmr spectra, exists as one C-20 isomer of the hemiacetal structure 5c. Periodate oxidation of 5c gave the expected 11 beta, 19-dihydroxy-3-oxoandrost-4-ene-17 beta, 18-carbolactone 6b.

18,21-Anhydroaldosterone and derivatives.

18,21-Anhydroaldosterone 8, 18,21-anhydro-19-noraldosterone 9, and 3 alpha, 5 beta-tetrahydro-18,21-anhydro-19-noraldosterone 13, which may be present in acid-processed urine, were prepared by cleaving their 20-ketal derivatives 2, 3, and 12 with hot mineral acid. Compounds 8 and 9 were also made by direct dehydration of aldosterone 5 and 19-noraldosterone 10 in good yield. The reverse ring opening of 8 to 5 could be carried out in moderate yield with an acetic acid-acetic anhydride-perchloric acid mixture, while an analogous ring opening of 9 gave only a poor yield of 10.

Synthesis of 18-hydroxy-19-norcorticosterone and 18-deoxy-19-noraldosterone. Structure determination of related 19-nor steroids by means of 2-D 1H nmr.

The compounds named in the title have been synthesized from the di-(ethylene ketal) of 21-hydroxy-3,20-dioxo-19-norpregn-5-ene-18, 11 beta-lactone and its 5(10)-ene isomer. Reduction of this mixture 1 with sodium aluminum bis-(methoxyethoxy)hydride furnished the 11 beta, 18, 21-triol 2a. Conversion to the 18,21-diacetate 2b, followed by deketalization to the free dione 3 and hydrolysis, afforded 18-hydroxy-19-norcorticosterone 4a which, in the solid state and probably in solution, has the 18,20-hemiacetal structure. Periodate oxidation of 4a gave 11 beta-hydroxy-3-oxo-19-norandrost-4-ene-17 beta, 18-carbolactone 5a, and acid treatment of 4a or its precursor 2a yielded 18-deoxy-19-noraldosterone 6a. The structure of 5a was confirmed by mass spectrometry and 1H nmr, and compared with that of its C-19 methyl homolog 5b and 19-noraldosterone-gamma-etiolactone 8. In particular, 2-D nmr COSY 45 experiments, affording full 1H line assignments, have rigorously established the "natural" beta (axial) configuration of the C-10 hydrogen in the 19-nor lactones 5a and 8, and therefore also in the related 4a, 6a and 19-noraldosterone 7.

Cardiac conduction abnormalities during carbamazepine therapy for neuralgia following Guillain-Barré syndrome.

A 61-year-old man without previous medical history was admitted for Guillain-Barré syndrome (GBS). Carbamazepine was prescribed on day 72 for dysesthesia occurring at the time of recovery. Subsequently, severe cardiac conduction disturbances (asystole, atrioventricular block) were observed and a permanent pacemaker had to be inserted. The possible relationship between carbamazepine therapy and cardiac side effects is discussed in this condition, as GBS itself is often complicated by cardiac arrhythmias.

The human microbiome in autoimmune diseases.

The human microbiome is the collection of all of the genes in all of the microbes in and on our bodies. Recently, the more appropriate term is "microbiota". There are numerous and complex relationships between the microbiome and our immune system. It is also becoming clear that if there is a disruption or disorganization in the microbiome community an inflammatory disease can occur.

The role of heavy metals in autoimmunity.

Our understanding of autoimmune diseases has progressed tremendously in the past 20 years. Estimates of the prevalence of autoimmune diseases in the population may be 4% or higher. It is evident that heavy metals present serious risk to human health. Heavy metals are capable of altering the immune response; they have been implicated in influencing autoimmunity. In fact, they are usually inhibitory to immune cell proliferation and activation. This paper reviews the possible mechanisms which may play a role in metal-induced autoimmunity. A better understanding of these interactions remains a priority for the future.

Cerebrovascular complications in patients with inflammatory bowel disease.

UNLABELLED: Cerebrovascular complications in 9 patients with inflammatory bowel disease (IBD) are presented, 6 with Crohn's disease (CD) and 3 with ulcerative colitis (UC), 7 men and 2 women, mean age 36.5 +/- 3.5 years, 4 of them during acute disease. Cerebrovascular complications were: cerebral venous thrombosis (CVT)--7 cases (5 CD and 2 UC) and ischemic stroke--2 cases (1 CD and 1 UC). Out of 7 cases with CVT 5 were superior sagittal sinus thrombosis (SSS), 2 SSS and transverse and sigmoid sinus thrombosis. Both ischemic strokes were infarctions in the middle cerebral artery area. No correlation between high doses of corticosteroids or their lowering, IBD activity, duration of the disease, and the appearance of cerebrovascular complications was observed. Tendency to hypercoagulation even in the inactive stage of the IBD was revealed. Investigations for thrombophilia were negative. Significantly high levels of homocysteine were observed in all patients. CONCLUSION: Neurovascular complications may be observed in IBD, both of venous and arterial type. Pathogenic mechanisms of these vascular complications are complex, low serum folate levels, of vitamin B6 and B12 being associated with elevation of homocysteine levels, high activation of platelets and microvascular endothelial dysfunction. A guide for the orientation of prophylaxis of cerebrovascular complications in IBD patients is necessary.