Anthony J. Guarascio, PharmD, BCPS
https://www.duq.edu/assets/Documents/pharmacy/Faculty%20CVs/2017-18/Guarascio.pdf The double-membrane structure most likely evolved to assist in the preservation of essential organelle functions antibiotics for sinus infection and bronchitis order keflex no prescription. Thus antibiotics for dogs uti order keflex 500 mg on-line, it is essential that the organelle selectively control the permeability of the mitochondrial membrane to chemicals bacteria 5 letters generic keflex 750 mg on-line. Therapeutic drugs must overcome this barrier to effectively deliver drugs to mitochondria oral antibiotics for acne while pregnant order discount keflex on line. To date, numerous investigators have attempted to construct mitochondria-targeted delivery systems; however, it is difficult to efficiently deliver therapeutic drugs to mitochondria [8-10]. In this review, we will describe unique features of mitochondria, such as electron 8 Yamada, Y. In addition, we will review various lines of investigation concerning mitochondrial drug delivery. In particular, strategies for mitochondrial delivery of macromolecules, such as proteins and nucleic acids will be discussed. The discussion of protein delivery focuses primarily mitochondrial protein import machinery. This review will also summarize our current efforts regarding liposomal delivery system. Mitochondria-based treatments for cancer that use intracellular trafficking regulation systems also will be discussed [13, 14]. Structural features of the mitochondrion and various functions Mitochondria are composed of a double membrane. The inner-most mitochondrial space is the matrix, while the intermembrane space is located between the membranes. Like all membranes, mitochondrial membranes are composed of a phospholipid bilayer with embedded proteins. The outer membrane does not offer a barrier to small molecules (< 5 kDa), which can simply diffuse through pores in the membrane formed by a membrane-spanning protein called porin. Large molecules, such as proteins, cross the outer membrane via a unique protein-import apparatus. This hydrogen/electron current forms three cascades in which the redox energy is adequate for the extrusion of protons from the mitochondrial matrix to the intermembrane space. This gradient is composed of the electric 2 component (fifi) and the proton concentration gradient. Thus, mitochondria are unique cellular organelles that build up a transmembrane electric potential of up to 200 mV, have a negative integral charge, and an internal pH of approximately 8. As described above, electron transfer system requires various small molecules such as coenzyme Q10, in addition to proteins [20]. Therefore, mitochondrial delivery of these small molecules and proteins has the probability of mitochondrial diseases therapy. A particularly relevant protein that loses function upon oxidation is superoxide dismutase. Loss of superoxide dismutase activity further compromises antioxidant capacity, leading to additional oxidative stress. Antioxidant supplements and drugs have been used to scavenge free radicals that are produced in mitochondria. Drugs inhibit mitochondria, thereby killing cancer cells; they protect cells from oxidative damage; and, they repair defects. Because of the complex nature of the mitochondrion, different strategies may be required for mitochondrial uptake of different pharmacotherapeutic agents. Mitochondria and apoptosis Mitochondria are involved in apoptotic programmed cell death. One of them is initiated by ligand binding to the so-called death receptors at the cell surface [41], whereas the route involves mitochondria [5]. In the latter case, an early trigger of the apoptotic pathway is an increase in the permeability of the outer membrane, causing release of apotogenic factors, such as cytochrome c (cyt c) [42]. Along with another mitochondrial protein, a cascade of events in the cytosol that activates intracellular proteases of the caspase family [43] and, eventually, results in partial self-digestion of the cell. These proteins belong to the Bcl-2 family, which also contains pro-apoptosis proteins, such as Bax and Bid. Under normal conditions, cyt c is bound to the inner membrane by association with cardiolipin [55]. Peroxidation of cardiolipin leads to dissociation and release of cyt c through the outer membrane into the cytosol [56]. In the cytosol, cyt c causes activation of caspase 9, which in turn, activates the caspase cascade. We will describe mitochondria-based therapies for cancer that involve apoptosis in section 6. Mitochondrial small-molecule drug delivery systems as therapeutic strategies A variety of small-molecule drugs have been investigated as potential therapeutic agents for mitochondrial diseases [9]. In this section, we discuss the potential role of small compounds targeted to the mitochondria as therapeutic drugs. Although these strategies have limited positive therapeutic effects, they do not allow for complete recovery of lost function [57-60]. Without a drug carrier, the tissue distribution, cellular uptake and intracellular trafficking of therapeutic agents into mitochondria cannot be actively controlled and, therefore, are insufficient for therapeutic activity. In contrast, Koga et al reported that oral administration of L-arginine without a carrier was an effective mitochondrial disease therapy. Oral administration remarkably decreased the frequency and severity of stroke-like episodes. Flow-mediated dilation decreased to a greater degree in patients than in controls. Moreover, two years of oral supplementation with L-arginine improved endothelial function to the level of controls and normalized plasma L-arginine concentrations in patients. Antioxidant delivery using lipophilic triphenylphosphonium cations Selective targeting of antioxidants to mitochondria in intact cells was recently reported by Murphy and coworkers [62-66]. First, selective delivery of an effective antioxidant, vitamin E, to mitochondria was attempted in an in vitro cell culture system 16 Yamada, Y. Such positively charged compounds, can accumulate in mitochondria up to a thousand-fold, driven by a transmembrane electric potential of approximately 200 mV (negative inside) in fully energized mitochondria. The accumulation of positively charged compounds can be further increased by the electric potential of 30 to 60 mV at the plasma membrane. Thus, the calculated ratio of intrato extra-mitochondrial concentrations may reach 10000:1. In mitochondria, MitoQ is reduced by the respiratory chain to its active ubiquinol form. The ubiquinol derivative thus formed is an effective antioxidant that prevents lipid peroxidation and protects mitochondria from oxidative damage. MitoQ protects mitochondria against oxidative damage both in vitro and in vivo, following oral administration. The antioxidant action of these compounds can be attributed to the tyrosine and dimethyltyrosine residues. These peptide antioxidants are cell-permeable and are concentrated up to 1000-fold in the mitochondrial inner membrane. The authors also speculated that these mitochondrial inner membrane-targeted antioxidants might be very effective treatments for aging and diseases associated with oxidative stress. Based on the results of these studies, it was concluded that mitochondrially targeted electron acceptors and superoxide dismutase mimics are potentially valuable therapeutics for the treatment of serious acute conditions, such as lethal hemorrhagic shock, which are associated with marked tissue ischemia. Thus, replacement of defective proteins via mitochondrial protein delivery can be a useful treatment of disease. Mitochondrial protein delivery via the protein import machinery Mitochondria contain ~1000 different proteins. Greater than 99% of all known mitochondrial proteins are synthesized on cytosolic ribosomes as precursor proteins that must be imported into the organelle.
After that impressive and tense procedure antibiotics for uti late period safe keflex 750mg, which grabbed the attention of everybody in the injection room virus 10 states order keflex 500 mg without a prescription, he stood up looking relieved antibiotic levaquin purchase 750mg keflex otc. In the days to come antibiotics for sinus infection webmd cheap 750mg keflex amex, I would see him visiting the physiotherapy room every day until his treatment could resume. Although Milena believes that physical therapy is absolutely necessary for soldiers to be able to endure Glucantime injections, she also thinks that leishmaniasis patients should receive physical therapy sessions after the treatment. In her opinion, this would help people who have gone through such a strong treatment to regain some weight and muscle mass without forcing the heart, an organ that is greatly affected by Glucantime. In the case of soldiers, she says, this would help them to be in better physical and emotional conditions before returning to their military work. In her view, her discipline was well-positioned to do this because Physiotherapy is a way of approaching a patient, a human being, not in the traditional way, as a physician does, using medicines only. I like physiotherapy because you really interact with the person, so you handle not just bodies, but souls, everything. So you may not have done much to him, but you told him a joke and made him feel good. If such a service was needed, soldiers would have to go to the dispensary of the Silva Plazas battalion and request an appointment to receive physiotherapy sessions. Such work keeps the standard from failing to produce the outcomes it promises and prevents this document from losing both its usefulness and its legitimacy. In front of the central building, there were about fifteen young men who, while roaming around, rubbed their buttocks with both hands and made gestures of discomfort and pain. Some of them had gauze bandages on visible parts of their bodies that covered their leishmaniasis ulcers on the face, the scalp, the neck, or the hands. He was born in the south of Bolivar, in a town historically devastated by violence (Verdad Abierta 2016). At the age of 11, Velandia began to work on illegal coca plantations as a raspachin [coca harvester]. He used to move constantly from one place to another across the Colombian rurality, looking for coca crops ready for their leaves to be stripped off. He used to spend that money mostly in cockfight betting, alcohol, and sex workers. He went to the nearest battalion but was denied admission because of health Figure 6. Without taking no for an answer and with less than 50,000 pesos in his pockets, he gathered a group of sixteen young men who also wanted to be recruited by the Army and introduced them to a sub-officer. Once he regained his civilian status, he eventually found himself missing the Army. Thus, he decided to go back to the military with the intention of becoming a professional soldier. To be admitted despite his teeth and spine problems, this time he had to bribe those Army members behind the formalization of his enrollment. Since Velandia completed his training as a professional soldier, he has spent most of his time patrolling rural areas in Caqueta, in the south of Colombia. It was there that in 2007, Velandia became infected with Leishmania parasites for the first time. When he was evacuated from the operations area, the ulcer was very large, which was the reason why the therapy with Glucantime did not work for him. However, ten days after returning to his military unit he had to go back into the selva and leishmaniasis reappeared in other areas of his body. When I asked him how he perceived the effects of these medications on his body, he said this: I liked to jog a lot. He also wanted to understand why he had not been able to have children yet, something he sensed had to do with leishmaniasis therapy. As Velandia said, this talk was primarily about telling soldiers that feeling sick because of Glucantime was entirely normal and letting them know about all the things they were not allowed to do: drinking black beverages (Coke or tinto [black coffee]),115 drinking alcohol, doing cardiovascular activities,116 having sex, taking vitamins, or getting someone pregnant in the three-month period after the treatment. The talk never included information about leishmaniasis, the toxicity of the drug, the long-term known and unknown effects of Glucantime, or the compensations to which these military members are entitled because of both the scars and the after-effects of the treatment. Otherwise, like many other soldiers, he would never have known that he could initiate a relatively straightforward medical-administrative procedure to receive financial compensation. However, these health-training sessions are never about leishmaniasis and do not constitute safe spaces for soldiers to resolve the doubts they have about the disease or the treatment. The etiology of leishmaniasis, for example, is a topic that constantly puzzles soldiers. They often compare and contrast their experiences with what they have heard about the disease and the scarce biomedical knowledge they have informally learned. For instance, given their lived experience with tick bites, contusions, or wounds that ended up developing into a sore, later diagnosed as leishmaniasis, many doubt that the disease is actually transmitted by sandflies. Soldiers are willing to know more, have their experiences checked against biomedical knowledge, see if what they have experienced reflects or not what scientists and doctors say, fill (their) knowledge gaps, and find out the answers to the many questions they have. I asked Velandia to tell me about the strategies they used in the operations area to prevent leishmaniasis. Nonetheless, he told me that many of his fellow soldiers prefer not to use it because it does not seem to work for many of them. While they were patrolling in the selvas of Caqueta, they came across a clearing in the forest. Neither he nor his companions had been told that this repellent burns the skin when exposed to the sun, so they all ended up suffering several skin burns. Soldiers also buy and take tablets of Thiamine (vitamin B1) and so-called garlic pearls so that their bodies expel certain odors that function as insect repellents. They also eat raw garlic cloves and make preparations with tobacco leaves to rub on their skin. He told me he did not want to transport more weight than he already had to carry on his back. For him, the risk of leishmaniasis is less significant than the body fatigue produced from carrying things that are not absolutely indispensable. So, deciding whether or not to carry a bottle of repellent is far from being a minor issue. If a guerrilla ambush or attack takes him by surprise, it is not very clever to be inside of a net, having fewer possibilities to move and flee rapidly, he told me. In other words, soldiers often have to choose to leave the selva with leishmaniasis or leave it dead. For him, that is the way servicemen with leishmaniasis are usually regarded by commanders, officers, and military doctors. These are six-month courses where professional soldiers learn to perform complex air, land, and water operations with the highest level of military training (Ejercito Nacional 2016). Another reason the sacroiliac joint is more stable in Sacrum extension virus us keflex 250mg online, or counternutation antibiotic 2013 order keflex 500 mg amex, occurs as the males is related to positioning differences in the center of base moves posteriorly with trunk extension or bilateral gravity antibiotic resistance markers in plasmids buy cheap keflex 750 mg line. The sacrum also rotates along an axis rundown antibiotics for uti how long to take safe keflex 250 mg, tightening the posterior ligaments and forcing the ning diagonally across the bone. This provides stability to the nated if the anterior surface of the sacrum faces to the right joint and is the close-packed position for the sacroiliac and left rotation if the anterior surface faces to the left. In females, the center of gravity is in the same this sacral torsion is produced by the piriformis muscle in plane as the sacrum, but in males, the center of gravity a side-bending exercise of the trunk (129). Thus, in males, a greater load is placed in the case of asymmetrical movement such as standing on on the sacroiliac joint, which in turn creates a tighter and one leg, there can be asymmetrical movement at the sacromore stable joint (164). The sacrum also rotates to the right or left with lateral flexion of the trunk (not shown). Both anterior tilt and posterior tilt in an open-chain movement Right Right can substitute for hip extension and hip flexion, respectively. Left (C) and right (D) lateral tilt accompany weight the pelvis can also tilt laterally and naturally tries to bearing on the right and left limbs, respectively, or lateral movements move through a right lateral tilt when weight is supported of the thigh or trunk. In the closed-chain weight-bearing posiright rotation of the trunk, respectively, or unilateral leg movement. This movement is controlled by muscles, parand the ilium, there is movement of the pelvic girdle as a ticularly the gluteus medius, so that it is not pronounced whole. These movements, shown in Figure 6-5, accomunless the controlling muscles are weak. Thus, right and pany trunk and thigh movements to facilitate positionleft lateral tilts occur with weight bearing and any lateral ing of the hip joint and the lumbar vertebrae. One Giant Step for Humankind Movements of the pelvis are described by monitoring the ilium, specifically, the anterior superior, and anterior have a partner start with their left foot forward and inferior iliac spines on the front of the ilium. Does the chain weight-bearing movement, the pelvis moves about pelvis have any lateral tiltfi Why a fixed femur, and anterior tilt of the pelvis occurs when does it tilt in this directionfi As shown on the left, the hip abduction movement in the open chain occurs as the thigh moves up toward the pelvis. In the closed-chain movement shown on the right, abduction occurs as the pelvis lowers on the weight-bearing side. Finally, the pelvic girdle rotates to the left and right the acetabulum is the concave surface of the ball as unilateral leg movements take place. As the right limb and socket, facing anteriorly, laterally, and inferiorly swings forward in a walk, run, and kick, the pelvis rotates (118,132). The hip, which has 3 degrees of freedom (df), is a ballthe spherical head of the femur fits snugly into the and-socket joint consisting of the articulation between acetabular cavity, giving the joint both congruency and a the acetabulum on the pelvis and the head of the femur. Both the femoral head and the the structure of the hip joint and femur is illustrated in acetabulum have large amounts of spongy trabecular bone Figure 6-8. It is formed by the concave surface of the acetabulum on the pelvis and the Patellar surface Medial Medial large head of the femur. The head is also lined with articular the cortical layer is reinforced on the lower surface of cartilage that is thicker in the middle central portions the neck, where greater strength is required in response of the head, where most of the load is supported. Also, the medial femoral neck is cartilage on the head thins out at the edges, where the the portion responsible for withstanding ground reaction acetabular cartilage is thick (118). The lateral portion of the neck resists compression of the head of the femur articulates with the acetabulum forces created by the muscles (118). The shaft is very Surrounding the whole hip joint is a loose but strong narrow in the middle, where it is reinforced with the thickcapsule that is reinforced by ligaments and the tendon of est layer of cortical bone. Also, the shaft bows anteriorly to the psoas muscle and encapsulates the entire femoral head offer the optimal structure for sustaining and supporting and a good portion of the femoral neck. The iliofemoof the femoral neck with respect to the shaft of the femur ral ligament, or Y-ligament, is strong and supports the in the frontal plane. This angle is larger at birth by almost sion, external rotation, and some adduction (151). The angle of inclination is important the second ligament on the front of the hip joint, the because it determines the effectiveness of the hip abducpubofemoral ligament, primarily resists abduction, with tors, the length of the limb, and the forces imposed on the some resistance to external rotation and extension. This increase in the angle of moral ligament, on the posterior capsule, where it resists inclination lengthens the limb, reduces the effectiveness of extension, adduction, and internal rotation (151). None the hip abductors, increases the load on the femoral head, of the ligaments surrounding the hip joint resist during and decreases the stress on the femoral neck (151). The neck is formed by cancellous gives the hip abductors a mechanical advantage needed trabecular bone with a thin cortical layer for strength. When the angle is reduced in coxa vara, the limb is shortened and the abductors are more effective because of a longer moment arm resulting in less load on the femoral head but more load on the femoral neck. The coxa valgus position lengthens the limb, reduces the effectiveness of the abductors because of a shorter moment arm, increases the load on the femoral head, and decreases the load on the neck. Anteversion in the hip increases the toeing-in accompanying excessive femoral anteversion mechanical advantage of the gluteus maximus, making it is illustrated in Figure 6-12. If the angle of anteversion is reversed so the femoral neck moves posteriorly, it is termed retroversion. A position of instability for the hip joint is in flexion and adduction, as when the legs are crossed (74). Movement Characteristics the hip joint allows the thigh to move through a wide range of motion in three directions. These measurements are made with respect to a fixed axis and vary considerably if measured with respect to the pelvis (7). Also, if thigh extension is limited or impaired, compensatory joint actions at the knee or in the lumbar vertebrae accommodate the lack of hip extension. There is also usually an adaptation in the tibia that develops external tibial torsion to reorient the foot straight ahead. Excessive anteversion has also been associated with increased hip joint contact forces and higher bending moments (62) as well as higher patellofemoral joint contact pressures (121). If the angle of anteversion is reversed so that it moves posteriorly, it is termed retroversion. Retroversion creates an externally rotated gait, a supinated foot, and a decrease in the Q-angle (142). The hip is one of the most stable joints in the body because of powerful muscles, the shape of the bones, the labrum, and the strong capsule and ligaments (122). The hip is a stable joint even though the acetabulum is not deep enough to cover all of the femoral head. The acetabular labrum deepens the socket to increase stability, and the joint is in a close-packed position in full extension when the lower body is stabilized on the pelvis. In hip flexion movements in an freely with the knees flexed but is severely limited by the open chain (leg raise), the pelvis rotates posteriorly in hamstrings if the flexion occurs with knee extension (74). In a leg raise with the knees Extension is limited by the anterior capsule, the strong flexed or extended, 26% to 39% of the hip flexion motion hip flexors, and the iliofemoral ligament. Purchase keflex 250mg fast delivery. Natural eyewash remedies| Fennel seeds cure| Infections eyesight eye pressure glaucoma cataracts.
Little wonder antibiotic green capsule buy discount keflex 250mg line, then infection 6 months after c section buy keflex on line amex, that on weekends many sought the fresh air and open spaces of Shek O Country Park or the paved paths and trails that encircle Victoria Peak antibiotic honey generic 500mg keflex free shipping. But even here antibiotics long term effects discount keflex 750mg with amex, above the mosquito line, comfort was not guaranteed and the island could still spring a surprise. Indeed, long-time residents know that for all that Hong Kong boasts its own subway system, at heart it is still a jungle. Those inviting hillsides, for instance, teem with wild boar and venomous snakes, and hikers are advised to keep a wary eye on the undergrowth for hungry pythons. Nor is it mosquitoes: malaria and dengue are no longer endemic to Hong Kong, though on occasion doctors see imported cases. From Kowloon, on the opposite side of Victoria Bay, it is just ninety minutes by train to Shenzhen and the gateway to Guangdong, the most populous province in China, which is home to some 80 million people. Animal traders responded to this increased demand by sourcing exotic game from countries such as Laos and Vietnam, or breeding game animals on small, unregulated farms, from where they were transferred to animal markets in Guangzhou and Shenzhen when they were ready to be eaten. The result was a mixing of multiple species in animal markets that would rarely, if ever, encounter one another in nature, and certainly not in such crowded conditions. Fortunately, Hong Kong, unlike Guangzhou and other provincial towns and cities in Guangdong, benefts from world-class medical facilities and teaching hospitals equipped with the latest diagnostic technologies. Rather, Hong Kong health ofcials, many of whom were trained overseas in American and European universities, seek to apply the same clinical and public health standards as they would anywhere else in the world. In short, when a new epidemic or pandemic virus emerges somewhere in China, it is in Hong Kong that the alarm is likely to sound frst. For the soft-spoken microbiologist with a passion for epidemiology and viruses that cross the species barrier, it is the perfect situation. In the winter, geese, teal and other wild migratory birds swoop past his window en route to the Mai Po Nature Reserve, a protected wetland on the edge of the Inner Deep Bay that is an important waystation for birds migrating south from Siberia to New Zealand during the northern winter. A viral disease spread by mosquitoes that breed in rice paddies, Japanese encephalitis had broken out in Anuradhapura, an historic city in northern Sri Lanka famous for its architectural ruins. This was puzzling; although the virus can be transmitted to humans, it usually cycles between birds, mosquitoes and pigs. Moreover, although outbreaks of Japanese encephalitis in humans had previously been documented in Japan and other parts of Asia, large human outbreaks had not occurred in Sri Lanka before. At frst, Peiris and his colleagues thought that the outbreak might be due to a sudden change in the virulence of the virus, but when they looked at the virus in the lab they could see it had not mutated. In so doing, Peiris discovered, the pigs not only provided mosquitoes with a ready blood meal, but greatly increased the chances of transmission of Japanese encephalitis to humans. With the best intentions, somebody puts this in and, boom, you have this huge explosion. His appointment coincided with the frst documented transmission of avian infuenza from birds to humans. An infuenza virus, known as H5N1, had been isolated from the throat washings of a three-year-old boy. He had been admitted to Queen Elizabeth Hospital in Kowloon in early May with what appeared to be a run-of-the-mill upper respiratory tract infection. Not only that but several weeks before he had fallen ill, teachers at his nursery school had brought in three baby chicks and two ducklings for the children to play with. By the time Fukuda arrived at the school in August both ducklings had died, as had two of the chicks. One moment they are clucking contentedly, the next they are staggering from side to side as their brains, stomachs, lungs and eyes leak bloody haemorrhagic fuids. Indeed, scientists hypothesize that it is when these avian and human strains exchange genes, reconfguring their surface proteins and generating a new, hybrid virus, that you get pandemics. In addition, scientists suspect that pandemics may also be triggered by spontaneous mutations of avian viruses. Viruses are continuously making copying errors, and avian viruses are no exception. The theory is that some of these mutations could result in subtle changes to the molecules on the surface of the virus, enabling it to bind deeper into the human respiratory tract. As people are not ordinarily infected with bird fus, once such a virus found a way of transmitting efciently to humans, runs the theory, there would be little to stop it because our immune systems would be powerless to mount an antibody response. Instead, the infection might trigger a catastrophic cascade similar to the syndrome that killed the three-year-old Hong Kong boy. Indeed, when scientists looked more closely at the genome of H5N1 they discovered that its surface proteins had the ability to bind to both avian receptor sites and human cells deep in the lungs. That discovery sparked renewed interest in the natural history of infuenza and the ecological conditions driving adaptations of wild viruses circulating in aquatic bird populations. Then in November there were two further human cases, followed in December by several more. Although the virus continued to turn up every now and again in samples collected from wild birds, no more cases were reported in domestic chickens. Nevertheless, by the time the outbreak ended in 1998, eighteen people had been infected and six had died, fve of them adults. This was followed by an advertisement by the Chinese subsidiary of the Swiss drug company Roche that its antiviral medication Tamifu was efective against bird fu. Although she was buried before the cause of death could be ascertained, nine days later her father was stricken with what appeared to be the same disease, dying in mid-February in Hong Kong.
Ultrasound in Obstetrics & Gynecology: the oficial journal of the International Society of Ultrasound in Obstetrics and Gynecology antibiotic resistance doxycycline cheapest keflex, 2006 bacteria uti purchase 250mg keflex with amex,27:107-113 antimicrobial yoga towel buy generic keflex on-line. Ultrasound in Obstetrics & Gynecology: the oficial journal of the International Society of Ultrasound in Obstetrics and Gynecology antibiotic coverage buy 500 mg keflex with mastercard, 2007,29:109-116. Estimation of birth weight by use of ultrasonographic formulas targeted to large-, appropriate-, and small-for-gestational-age fetuses. Practice guidelines for performance of the routine mid-trimester fetal ultrasound. Ultrasound in Obstetrics & Gynecology: the oficial journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2011,37:116-126. Fetal weight estimation formulas with head, abdominal, femur, and thigh circumference measurements. Mullerian duct anomalies and mimics in children and adolescents: correlative intraoperative assessment with clinical imaging. Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: a multicenter study by the International Ovarian Tumor Analysis Group. Tubo-ovarian abscesses: spectrum of sonographic fndings with surgical and pathological correlations. Analysis of sonographic features for the diferentiation of benign and malignant breast tumors of diferent sizes. Characterization of solid breast masses: use of the sonographic breast imaging reporting and data system lexicon. Diagnostic breast imaging mammography, sonography, magnetic resonance imaging, and interventional procedures,2nd edition. Ultrasound is a useful adjunct to mammography in the assessment of breast tumours in all patients. Solid breast nodules: use of sonography to distinguish between benign and malignant lesions. Sonography of the neonatal spine: part 1, Normal anatomy, imaging pitfalls, and variations that may simulate disorders. Sonography of the normal ankle: a target approach using skeletal reference points. The first known coronavirus, the avian infectious bronchitis virus, was isolated in 1937 and was the cause of devastating infections in chicken. However, coronaviruses have been present in humans for at least 500-800 years, and all originated in bats (Chan, P. Given the high prevalence and wide distribution of coronaviruses, their large genetic diversity as well as the frequent recombination of their genomes, and increasing activity at the humananimal interface, these viruses represent an ongoing threat to human health (Hui, D. This appearance is produced by the peplomers of the spike [S] glycoprotein radiating from the virus lipid envelope (Chan, J. The viral genome is associated with the basic phosphoprotein [N] within the capsid. One coronavirus can gain a genomic fragment of hundreds or thousands base-pair long from another CoV strain when the two co-infect the same host, enabling the virus to increase its ecological niche or to make the leap to a new species (Chan, P. The researchers looked at 1,137 samples obtained from asymptomatic individuals, general community, patients with comorbidities and hospitalized patients. Fifty-two percent of patients with CoV infections required hospitalization, and two patients required intensive care. In late 2019, another new coronavirus began causing febrile respiratory illness in China. Also as of January 26, at least 80 deaths from 2019-nCoV had been confirmed in China. It originated in the Chinese province of Guandong in November 2002, and was first reported at the beginning of 2003 in Asia, followed by reports of a similar disease in North America and Europe (Anderson, L. The rapid spread of the virus to different continents after the initial outbreak underscored the ease with which infectious diseases can be spread internationally among members of our highly mobile global population (Hui, D. These lessons were again put to test in 2020 with the emergence and explosive spread of 2019-nCoV in China and globally. The new coronavirus was only distantly related to previously known and characterized coronaviruses (Falsey, A. These changes include formation of double-membrane vesicles, presence of nucleocapsid inclusions and granulations in the cytoplasm (Goldsmith, C. The viral particles assemble in the Golgi, accumulate in dilated vesicles that are then transported and secreted to the cell surface, where they are released by exocytosis. The genome contains a total of 11 predicted open reading frames that potentially encode as many as 23 mature proteins (Ruan, Y. The lack of sequence homology with any of the known human coronavirus strains makes a recombination event among human pathogens a remote possibility. Yuen KwokYung, a microbiologist at Hong Kong University, reported that the coronavirus had been found in the feces of masked palm civets, a nocturnal species found from Pakistan to Indonesia. Sequence analysis showed a phylogenetic distinction between animal and human viruses, making passage from humans to the analyzed animals unlikely. This finding points to the possibility of 8 interspecies transmission route within animals held in the market, making the identification of the natural reservoir even more difficult. The first phase was characterized by cases of independent transmissions in which the viral genomes were found to be identical to those of the animal hosts. In the second phase, clusters of transmission among humans were observed that were characterized by a rapid adaptation of the virus to the human host. The third phase was characterized by the selection and stabilization of the genome, with one common genotype predominating throughout the epidemic (Unknown Author (2004)). The virus can reach a concentration of about 100 million particles per ml in sputum (Drosten, C. Thus patients are most infectious at the time of seeking health care (McDonald, L. A superspreading event was believed to be involved in the rapid propagation of the virus in the Amoy Gardens apartment building outbreak, where more than 300 residents were infected, presumably by a single patient (Cleri, D. Superspreading seems to be 9 associated with high virus titer, aerosol generation, contamination of the environment, and close contact with others in a healthcare setting (Cleri, D. Unfortunately, the initial symptoms and clinical appearance are not easily distinguishable from other common respiratory infections, and fever may be absent in older adults. The infection progresses through an inflammatory or exudative phase (characterized by hyaline-membrane formation, pneumocyte proliferation and edema), a proliferative phase and a fibrotic phase (Gralinski, L. Seroconversion was detected during the second week and was followed by a reduction of viral load. Nearly 100% of adults and children presented with fever, and approximately half with cough and/or myalgia. Others presented with symptoms unexpected in a respiratory infection, such as acute abdominal pain (Poutanen, S. Older patients had greater morbidity and mortality, the result of an 10 aging-related attenuation in the adaptive immune response (Frieman, M. Independent correlates of adverse clinical outcome included known history of diabetes/hyperglycemia (Yang, J. A positive association was reported between air pollution and higher case-fatality rates (Cleri, D. Health care utilization, especially with respect to psychiatric care, was significantly higher than normal during the period of evaluation, and patients reported important decrements in mental health.
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