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Chronic asthma accounts for a significant amount of unscheduled office and emergency department (ED) visits. According to the latest World Health Organization statistics, asthma worldwide affects 300 million individuals and creates a substantial health burden by restricting the patient’s lifetime activities. Data estimate that asthma causes a loss of disability-adjusted life years over 150,000/year [1]. While most individuals with asthma can be controlled with current therapies, 5-10% of patients have difficult-to-control/refractory asthma. Severe or refractory asthma places a significant burden on the patient and often requires treatment with systemic glucocorticoids, which have significant side effects. The American Thoracic Society and the European Respiratory Society define refractory asthma as asthma that requires treatment with high-dose inhaled corticosteroids (ICS) plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or asthma that remains ‘‘uncontrolled’’ despite this aggressive therapy. To fully meet this definition the diagnosis of asthma needs to be confirmed and comorbidities addressed as well. The above are considered major criteria for severe asthma and only one needs to be present for considering the diagnosis of refractory asthma [2]. For these reasons, clinicians must learn to identify and formulate additional diagnoses of “asthma imitators” [3]. One of the more common disorders associated with difficult-to-control asthma is vocal cord dysfunction (VCD) [4]. This disorder is known by many names, but current nomenclature endorsed by European and American societies correctly refers it as “Inducible Laryngeal Obstruction” (ILO) [5]. The following case demonstrates the importance of recognizing the clinical and spirometric features of ILO when asthma remains “refractory” to multiple therapies.

Seizure is clinical manifestation of sudden disruption of the normal electrical activity of cortical neurons. The brain electrical activity is periodically disturbed, alteration in neural cell integrity, increase in firing impulses and spread to adjacent normal neurons result in temporary brain dysfunction with alterations in consciousness, behavior or motor function. It may be triggered by illness, infection, stress, stroke, brain tumor, or the underlying cause may not completely understand. Status epilepticus (SE) is a medical emergency and requires prompt diagnosis and treatment. Treatment includes general support measures, drugs to suppress epileptic activity and relieving the underlying condition. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. For SE treatment, benzodiazepines are the first line antiepileptic agents, and if benzodiazepines fail to control seizures, Phenytoin is usually indicated; Phenobarbital or Valproate may also be considered. For refractory SE, Propofol and Thiopental represent first line agents after careful assessment of potential risks. In refractory SE, general anesthesia may be required. There is currently no unique consensus for definite treatment option of RSE. In this review, the management protocol of seizure, assessment, monitoring, and different alternative therapy would be discussed.

Background: Multiple sclerosis (MS) is an autoimmune disorder of the central nerve system (CNS), which affects the brain and spinal cord. Experimental autoimmune encephalomyelitis (EAE) is the most commonly applied experimental model for studying the MS. The aim of this study was to determine the effects of Sesamum indicum seeds oil on Experimental Autoimmune Encephalomyelitis (EAE) in mice. Methods: Sesame oil was administrated intraperitoneally three days before immunization. IFN-γ, IL-10, IL-17 and TGF-β levels and mRNA expression in supernatant of and within cultured mononuclear cells were assessed. Results: According to our results, sesame oil treated mice demonstrated significant disease severity reduction (P=0.01 and 0.001, respectively). Treated EAE mice also represented statistically significant delay in the onset of symptoms in comparison with control group. The average IFN-γ levels and mRNA of sesame oil treated EAE mice were less than untreated EAE group. IL-10 and TGF-β levels and mRNA did not differ significantly in sesame oil treated EAE mice in comparison to untreated EAE group. IL-17 levels and mRNA were also found to be decreased significantly in treated mice in comparison to untreated mice. Conclusions: Even thoughTH1 and TH17 cells through secretion of IFN-γ and IL-17, respectively, are involved in the pathogenesis of multiple sclerosis and EAE, but IL-10 has been shown to exhibit suppressive effects on these disorders. It can be concluded that sesame oil is able to induce TH2 and TH17-related immune responses and suppress TH1 type in EAE

Biliary cystadenoma is a rare cystic tumor of the liver. It has a high recurrence rate and malignant transformation risk in middle-aged women. Pre-operative diagnosis is difficult because of the lack of clinical, biological and radiological specificity. The confirmation of the diagnosis is made by the histopathological examination. Complete surgical resection is preferred because of the high risk of malignant transformation and recurrence.

Background: Asthma is the most common chronic respiratory disorder in childhood. Asthmatic attacks are described and classified according to the type of wheezing to Non –atopic and Atopic asthma (IgE mediated wheezing). The aim of this review is to determine the onset of clinical diagnosis in relation to clinical presentation of asthma in children and obstacles related to delay of Asthma diagnosis. Methods: This review highlights the results of studies done regarding clinical diagnosis in relation to clinical presentation and of asthma in children. An extensive search has been conducted for researches about asthma in children. This search based on the publications posted on the National Center for Biotechnology Information PubMed or by Google Scholar. Key words used for the research: Asthma, clinical diagnosis, children. Results and Conclusion: Diagnosing asthma in young children is difficult because children often cough and wheeze with colds and chest infections, but this is not necessarily asthma. Miss diagnosis of asthma in children occurs when physicians diagnose patients with asthma from the clinical diagnosis in the first attack without excluding other asthma mimickers which can be any other respiratory problem. There is over-diagnosis of asthma due to the symptoms which mimic other respiratory infections. First episodes of cough, runny nose and fever that happen in cold/flu season- fall/winter/early spring is likely not asthma. If the child has several more episodes of wheeze and cough, it is likely to be asthma. Since there is no diagnostic test available for children younger than 6 years of age, making a diagnosis in this age group is more difficult than in older children. Over the age of about 6 years it is possible for a child to have a spirometer test

It is estimated that there are 36.9 million individuals living with HIV-1 from who 21.7 million patients receiving antiretroviral therapy (ART) [1,2]. ART has had a significant effect on the patients’ quality of life recently, however, its global coverage declines to 16-35% in low or middle income parts of Africa [3]. ART is unable to eliminate the virus from the infected individuals despite the fact of great impact on virus life cycle. There is no doubt that vaccination is considered as the most important medical strategy to prevent and suppress the infectious diseases. Nevertheless, there are many difficulties toward the cure or prevention of HIV-1 including the virus characteristics, lack of ideal animal model and funding [4-7].

Observing relevant biomedical literature we have see that clinical pharmacist play a crucial role in ICU settings with reducing in mortality rate and improving some clinical outcomes.

Treatment of various inflammatory processes, including acute pneumonia(АP), over the past decades is identical and does not reflect the specifics of a particular disease. The basis of such treatment is «antibiotics alone». The need for additional therapeutic efforts is realized by the use of General therapeutic techniques, regardless of the diagnosis. This does not take into account the important fact that the localization of inflammation not only determines its clinical picture,but,above all,the mechanisms of influence on other organs and systems of the body.

Cystic fibrosis (CF) is a hereditary syndrome composed of exocrine gland dysfunction involving multiple systems which if untreated may result in chronic respiratory infections, pancreatic enzyme deficiency and failure to thrive. The association between CF and other inherited diseases or congenital anomalies is rare. We describe a rare case of CF with concomitant congenital adrenal hyperplasia (CAH). 21- Hydroxylase deficiency accounts for most CAH cases. Varity in clinical phenotypes depends on the amount of enzymatic activity which in turn depends on different combination of gene mutations. The genes of CAH and CF are located in different locations. The chance of these diseases coexisting in our patient would be a rare combination. However, such a case will be more frequent in our population than others because of consanguineous marriage and common ancestors. There are diagnostic difficulties, similarities and contradictions between two diseases and they are pointed out.

By researching the factors related to exposure to indoor and outdoor allergens, such seasons, climate changes and particulate matter, allergists can screen the sensitization profile of individuals according to their exposures and conduct preventive treatment and individualized immunotherapy. Molecular allergology has improved aerobiological screening of allergenic components toward more specific results on allergic exposure, sensitization, and symptoms [1,2]. The Enzyme-Linked Immunosorbent Assay (ELISA) is a colorimetric enzyme immunoassay technique used to quantify soluble substances such as proteins, peptides, antibodies, and hormones. Due to its high sensitivity and specificity, ELISA can quantify substances at low concentrations, such as allergens [3].

Depression is a psychiatric disease resulting mainly by dysfunction of serotoninergic and monoaminergic neurotransmission in central nervous system (CNS). Due to the multifaceted nature of depression and our limited understanding on its etiology, depression is difficult to be treated with currently available pharmaceuticals. Then, new therapeutic strategies for depression have been proposed. Since 1975, several clinical studies have reported that L-type Ca2+ channel blockers (CCBs), used in anti-hypertensive therapy, produce increase of plasma catecholamine levels and tachycardia, typical symptoms of sympathetic hyperactivity. Despite these adverse effects of CCBs have been initially attributed to adjust reflex of arterial pressure, during almost four decades these enigmatic phenomena remained unclear. In 2013, we discovered that this paradoxical sympathetic hyperactivity produced by CCBs results from the increase of catecholamines release from sympathetic nerves, and adrenal chromaffin cells, due to its modulatory action on the interaction between intracellular signaling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signalling interaction). Then, the pharmacological modulation of this interaction by combined use of L-type CCBs, and cAMP-enhancer compounds, could be a more efficient (and safer) therapeutic strategy to produce increase of serotoninergic and monoaminergic neurotransmission in the CNS due to enhance of serotonin and monoamines release, thus attenuating clinical symptoms of depression in humans. 

The Ontario government has been battling with the issue of extensive wait times in hospitals for several years. Although there are many complex reasons that stem off of the issues of wait times, such as available in patient beds and bed blockers (patients who stay in the hospitals for long periods of time after sustaining a massive injury), the primary cause is concentrated as a system wide problem in access to care [1]. Through numerous reforming and restructuring plans, the Ontario government devised a Wait Time Strategy plan to monitor, manage and improve access to health care services including surgeries and time spent in the ER. The strategy was also devised to enhance the efficiency and effectiveness of healthcare provision. The information derived from the results of the Ontario Wait Time Strategy (OWTS) was to be made public to citizens and providers to ensure that everyone is well aware of the results. Yet, it is quite difficult to implement such a strategy if the leadership challenges within the hospital are not addressed [2].

Alcohol abuse is a global health problem. Alcohol withdrawal syndrome (AWS) ranges from mild to severe symptoms that can lead to fatal delirium tremens requiring ICU admission and incurring high health care cost as high as $20,000 a month. The latest published reports suggest that phenobarbital is a promising therapeutic option for management of AWS as evidenced by less ICU admissions, length of stay in hospital, use of adjunctive agents, health care costs and attention from the nursing staff than that of patients treated with commonly used benzodiazepines such as lorazepam, diazepam, and chlordiazepoxide. Phenobarbital is beneficial for the treatment of AWS, both in the emergency and inpatient settings and both as monotherapy or in conjunction with benzodiazepines. It is safe for patients without severe hepatic impairment, has a better mechanism of action and longer half-life than benzodiazepines, and leads to less delirium and agitation. Powered randomized controlled trials with large populations are required, yet phenobarbital can be used to safely to treat AWS.

The emergence of COVID-19 worldwide in an unprecedented pandemic. COVID-19 has a significant mortality, mostly from acute lung injury. We reviewed the available literature from China and Europe in regard to the behavior of SARS-Cov2 and ability to adhere to the cell wall [1,2]. The evidence based literature describes three component for the virus to grant entry to the target cells including Cathepsin B/L (the viral cap protein needed for initial connectivity to the cell wall), the angiotensin converting enzyme 2 and a low PH environment to allow the first connectivity of the virus to the cell wall [3]. The goal of our Case study was to prevent SARS- SARS-Cov2 from entering target cells by raising the airways PH using sodium bicarbonate inhalation. The sodium Bicarbonate inhalation (4.2% concentration) has been used safely in Cystic fibrosis (CF) patients with inspissated mucoid impaction [3,4] and in chloride inhalation toxicity by opposing the effect of the low PH induced by the insulting agent [4,5]. It has not been administered for COVID -19 patients particularly prior to this study. 

In this article different numerical techniques for solving optimal control problems is introduced, the aim of this paper is to achieve the best accuracy for the Optimal Control Problem (OCP) which has the objective of minimizing the size of tumor cells by the end of the treatment. An important aspect is considered, which is, the optimal concentrations of drugs that not affect the patient’s health significantly. To study the behavior of tumor growth, a mathematical model is used to simulate the dynamic behavior of tumors since it is difficult to prototype dynamic behavior of the tumor. A tumor-immune model with four components, namely, tumor cells, active cytotoxic T-cells (CTLs), helper T-cells, and a chemotherapeutic drug is used. Two general categories of optimal control methods which are indirect methods and direct ones based on nonlinear programming solvers and interior point algorithms are compared. Within the direct optimal control techniques, we review three different solutions techniques namely (i) multiple shooting methods, (ii) trapezoidal direct collocation method, (iii) Hermit- Simpson’s collocation method and within the indirect methods we review the Pontryagin’s Maximum principle with both collocation method and the backward forward sweep method. Results show that the direct methods achieved better control than indirect methods.

For the millions of patients experiencing chronic pain despite pharmacotherapy, deep brain stimulation (DBS) provides a beacon of hope. Over the past decade the field has shifted away from DBS towards other forms of neuromodulation, particularly spinal cord stimulation (SCS). DBS for pain is still performed, albeit off-label in US and UK, and experiences variable success rates. SCS is an extremely useful tool for the modulation of pain but is limited in its application to specific pain aetiologies. We advocate use of DBS for pain, for patients for whom pharmacology has failed and for whom spinal cord stimulation is inadequate. DBS for chronic pain is at risk of premature neglect. Here we outline how this has come to pass, and in the process argue for the untapped potential for this procedure.

Background: the level of alcohol consumption per capita is an important indicator of the alcohol-related problems. However, it is difficult to estimate the real level of alcohol consumption, since part of the consumption comes from illegal sources. Aim: an overview of studies estimating the overall level of alcohol consumption in Russia. Methods: in this review, 9 articles were analyzed estimating the overall level of alcohol consumption in Russia. Results: in the period from 1956 to 2015 the overall level of alcohol consumption was subject to significant fluctuations: it grew almost linearly in the period from 1965 to 1979; decreased markedly in 1981; declined sharply between 1984 and 1987; rose sharply between 1991 and 1994; decreased significantly between 1995 and 1998; then increased significantly in the period from 1999 to 2003, after which it began to decline. The lowest estimate of the level of alcohol consumption for the entire period under consideration was obtained using the method proposed by Razvodovsky (7.25 litres - 1987), and the highest - using the method proposed by Norstrom (19.64 litres - 1994). Conclusion: despite a significant decrease in the level of alcohol consumption in Russia over the past decade, this level remains high.

Rectourethral fistula (RUF) is a divesting complication after prostate cancer treatment. The RUF incidence after radical prostatectomy is about 0.5% to 2%, [1,2]. Radiotherapy, criotherapy and high intensity focused ultrasound are other more severe causes [3,4]. Repair of RUF is a challenging surgical procedure. There are some possible approaches but transperineal is the most utilized. In cases of complex fistulas interposition of muscle flaps between the rectum and urethra is highly recommended. Gracilis muscle transposition (GMT) is the preferred, due to excellent mobility and vascularization for perineal reconstruction [5,6]. Dissection of the gracilis muscle is done using one, 2 or 3 large incisions in the medial border of the thigh. The aim of this report is present a new minimally invasive access to obtain a pediculate flap of gracilis muscle to interposition between bladder and rectum to treat RUF.

Inferior vena cava (IVC) involvement by intraluminal extension of tumor is infrequent, occuring in 4% to 10% of patients with renal cell carcinoma (RCC) [1-5]. Based on the cephalic extension of the thrombus, Mayo [6] described a classification of inferior vena cava thrombi in 4 categories, which has implications on surgical complexity, estimated blood loss (EBL) and peri-operative complications, but not cancer-specific survival [2,7]. Level III IVC thrombus is classified as being located in the retro-hepatic IVC below the diaphragm. Total resection of this tumor is the best chance of cure when no distant metastases are present [4,8]. Actually, open radical nephrectomy with concomitant thrombectomy is still the standard treatment. This procedure is technically challenging and involves a large incision and prolonged convalescence [9]. Recently, the feasibility of robotic IVC thrombectomy has been demonstrated, with potential lower EBL and shorter hospitalization and convalescence [7,10-14]. This surgery requires thorough knowledge of surgical anatomy, detailed pre-operative preparation and meticulous robotic technique [7]. The key point in the surgical management is the correct assessment of the extension of the endocaval thrombus, what is mainly based on radiological examinations [8]. Although Ultrasonography (US) and computerized tomography (CT) are useful in demonstrating the extent of the thrombus, CT is not always accurate in delineating the superior margin of the tumor in the IVC. More precisely, magnetic resonance imaging (MRI) can demonstrate a tumor thrombus and its extension, besides signs of wall invasion, being extremely useful to surgical procedure planning [8,15]. Vena cavography is not additive to US, CT, and MRI, and it increases the risk of contrast-associated renal injury [4,8]. However, new modern image technologies has emerged to help surgical planning, as three-dimensional visualization technique (3DVT) based on routine CT or MRI processed image data [16-20]. Recently, a comparative study showed advantage of 3DVT in management of complex renal tumor during laparoscopic partial nephrectomy [20]. This modality is able to demonstrate anatomy relations, allowing the surgeon to observe the relationship between targeted tumor and peripheral structure before surgery and perform virtual manipulation. This kind of preoperative accurate assessment can enhance surgeons confidence of surgical procedure and decrease surgical risk and incidence of complications [20]. There is no report in the literature of the use of this type of technology in cases of IVC tumor thrombus. We present the use of 3D holographic interactive reconstruction in a single case of robotic radical nephrectomy with level III IVC thrombectomy.

Introduction: Carotid space is a deep neck space within the carotid sheath. .Mosher called carotid sheath as the Lincoln Highway of the neck. Abscess in this space is rare to be seen by young Ear, Nose and Throat (ENT) surgeons in this era of early diagnosis and good antibiotics. We are reporting a case of isolated carotid space abscess in a 20 year old male to familiarize young surgeons with this abscess. Case report: A 20 year old young boy came to our Outpatient Department (OPD) with complaints of fever, painful neck swelling, progressive difficulty in swallowing from the last 7 days. Contrast Enhanced Computed Tomography (CECT) was done which revealed abscess located adjacent to carotid artery in the carotid sheath. Incision and drainage was done and carotid sheath was opened and pus drained .Patient was discharged after few days on oral antibiotics. Conclusion: Carotid space abscesses are rarely seen in developed countries. Tender and fluctuating swelling over the carotid artery area points towards it. CECT is the investigation of choice. Needle aspiration should be avoided especially by less trained persons. Small abscesses may respond to intravenous antibiotics but when frank and large abscess is formed, incision and drainage is the treatment of choice.