Transformation and Sustainable Development of Shopping Centers: Case of Czech and Slovak Cities

The aim of the paper is to critically evaluate the similarities and differences in the development of the temporal and spatial structure of shopping centers in the Czech and Slovak republics. We focused on the retail transformation and sustainable manifestations of the location and construction of shopping centers. We classified shopping centers according to their genesis, location in the city, and size of the gross leasable area. To analyze migration trends and geographic distribution characteristics of shopping centers in the capital cities of both countries (local level of analysis), we used spatial gravity and standard deviational ellipse. Generally, there is an analogous trend in the development of shopping centers in the Czech Republic and Slovakia, with a particular two- to four-year lag in Slovakia (west–east gradient). Despite this, we still perceive the demand for shopping centers in both countries as above average, and it is not declining. The construction of shopping centers, mainly in small towns, also indicates this trend. In Prague and Bratislava, the pattern of spatial expansion of shopping centers differs. Prague probably represents a more advanced phase of shopping center agglomeration. However, neither country has reached the state of clustering.

Herbal Preparation (Bromelain, Papain, Curcuma, Black Pepper) Enhances Mineralization and Reduces Glucocorticoid-Induced Osteoporosis in Zebrafish

Natural foods with antioxidant properties, such as curcuma, papain, bromelain and black pepper, have been indicated as a potential natural therapeutic approach against osteoporosis. Zebrafish are an excellent animal model to study the effects of herbal preparations on osteogenesis and bone metabolism, both in physiological and in pathological conditions. Our study was aimed at evaluating whether curcuma-bromelain-papain-pepper herbal preparation (CHP) administered in embryos and adult fish is capable of promoting bone wellness in physiological and osteoporotic conditions. The effect of CHP has been studied in embryonic osteogenesis and glucocorticoid-induced osteoporosis (GIOP) in an adult fish model in which drug treatment induces a bone-loss phenotype in adult scales very similar to that which characterizes the bones of human patients. CHP prevented the onset of the osteoporotic phenotype in the scales of GIOP in adult zebrafish, with the osteoblastic and osteoclastic metabolic activity maintaining unaltered. CHP is also able to attenuate an already established GIOP phenotype, even if the alteration is in an advanced phase, partially restoring the normal balance of the bone markers alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) and stimulating anabolic reparative processes. The results obtained indicated CHP as a potential integrative antioxidant therapy in human bone-loss diseases.

Blast and accelerated phase CML: room for improvement

Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). With TKI therapy, the percentage of patients who progress to accelerated phase (AP) or blast phase (BP) CML has decreased from more than 20% to 1% to 1.5% per year. Although AP- and BP-CML occur in a minority of patients, outcomes in these patients are significantly worse compared with chronic phase CML, with decreased response rates and duration of response to TKI. Despite this, TKIs have improved outcomes in advanced phase CML, particularly in de novo AP patients, but are often inadequate for lasting remissions. The goal of initial therapy in advanced CML is a return to a chronic phase followed by consideration for bone marrow transplantation. The addition of induction chemotherapy with TKI is often necessary for achievement of a second chronic phase. Given the small population of patients with advanced CML, development of novel treatment strategies and investigational agents is challenging, although clinical trial participation is encouraged in AP and BP patients, whenever possible. We review the overall management approach to advanced CML, including TKI selection, combination therapy, consideration of transplant, and novel agents.

Exploring the Shift From HIV Pre-exposure Prophylaxis Awareness to Uptake Among Young Gay and Bisexual Men

Introduction: HIV pre-exposure prophylaxis (PrEP) in the form of a daily oral medication is highly effective at preventing HIV. In the United States, awareness about PrEP has steadily increased over time among individuals vulnerable to HIV, however awareness has not translated into widescale uptake. Estimates are that fewer than 20% of 1.2 million Americans for whom PrEP is indicated are utilizing it. We sought to understand how individuals moved from PrEP awareness to PrEP utilization.Methods: We conducted a series (n = 31) of in-depth interviews with young people, predominantly gay and bisexual men, ages 18–29 years old between February 2015 and January 2016, as part of the evaluation of a multi-year demonstration project funded to test innovative approaches to improve sexual health outcomes and curb the HIV epidemic in California. Interviews were audio-recorded and transcribed verbatim. We conducted a thematic analysis.Results: We present a continuum of PrEP awareness that spans three phases—basic, moderate and advanced. Participants rarely reported becoming well-informed about PrEP over the course of an initial exposure to PrEP information. Learning occurred after multiple exposures to PrEP information through numerous intersecting forms, messengers and formal and informal communication channels. Positively framed messages delivered by formal messengers emphasizing PrEP as a sensible HIV prevention strategy and explicitly communicating a regard for sexual wellness were overwhelmingly persuasive and facilitated movement to the advanced awareness phase. Once participants reached the advanced phase of PrEP awareness, uptake was possible.Conclusions: Our analysis provides insights into how PrEP awareness led to PrEP uptake among young gay and bi-sexual men. Building demand among those in the basic awareness phase took longer than those in the moderate phase. Individuals involved in formal and informal PrEP education can set reasonable expectations about whether, when and how eventual uptake may occur when keeping the continuum of PrEP awareness framework in mind. Many young, gay and bi-sexual male prospective PrEP users will benefit from positively framed messages that emphasize personal well-being, including social, sexual and emotional benefits of PrEP use.

HIV Y TOXOPLASMOSIS CEREBRAL A PROPÓSITO DE UN CASO

Introducción: En Ecuador al igual que en el resto del mundo la infección por virus de inmunodeficiencia humana (VIH) constituye un problema de salud pública, con diagnósticos tardíos en fase avanzada del síndrome de inmunodeficiencia adquirida (SIDA), con toxoplasmosis cerebral una de las infecciones oportunistas más frecuentes que ocurre en pacientes con linfocitos CD4<200/µL. Objetivo: realizar diagnóstico precoz de toxoplasmosis cerebral en pacientes con SIDA y considerar como una verdadera emergencia a fin de disminuir la mortalidad de los pacientes inmunosuprimidos. Caso clínico: paciente de género masculino de 31 años, con antecedente de infección por HIV diagnosticado hace 19 días, con convulsiones tónico-clónicas generalizadas de tres meses de evolución, cefalea holocraneana de moderada intensidad, parestesias en hemicara derecha, asimetría comisura labial, tres días antes de su ingreso las crisis convulsivas se hacen diarias, repetitivas y se acompañan de fiebre, al examen físico disartria leve y monoparesia del miembro superior derecho, con biometría hemática con leucocitos 5270 mm3, IgG positiva anti-Toxoplasma gondii, linfocitosis discreta, pruebas de cuarta y tercera generación para HIV positivas, CD4 de 74/mm3, carga viral de 61500 copias/ml, resonancia magnética nuclear cerebral contrastada con lesiones intra-axilares corticales, con área hipointensa central, a nivel del lóbulo parietal izquierdo y occipital bilateral, se establece el diagnóstico de encefalitis toxoplásmica, indicándose tratamiento con trimetropin/cotrimoxazol, dexametosona y fármacos antirretrovirales con abacavir-lamivudina y lopinavir-ritonavir teniendo una buena evolución clínica. Conclusiones: El diagnóstico precoz de encefalitis toxoplásmica basado en criterios epidemiológicos, clínicos, de laboratorio y a la resonancia magnética, permitió buena respuesta al tratamiento empírico antitoxoplásmico. Palabras claves: Toxoplasmosis, infecciones oportunistas, encefalitis ABSTRACT Introduction: In Ecuador, as in the rest of the world, human immunodeficiency virus (HIV) infection constitutes a public health problem, with late diagnoses in an advanced phase of acquired immunodeficiency syndrome (AIDS), with cerebral toxoplasmosis one of the more frequent opportunistic infections that occur in patients with CD4 lymphocytes <100 / µL. Objective: to make an early diagnosis of cerebral toxoplasmosis in patients with AIDS and to consider it as a true emergency in order to reduce the mortality of immunosuppressed patients. Clinical case: a 31-year-old male patient, with generalized tonic-clonic seizures of three months of evolution, moderate intensity holocranial headache, paresthesia in the right side of the face, asymmetry of the labial commissure, three days before admission the seizures become daily, frequent and accompanied by fever, on physical examination mild dysarthria and monoparesis of the right upper limb, with hematic biometry with leukocytes 5270 mm3, discrete lymphocytosis, fourth and third generation tests for HIV positive, CD4 of 74 / mm3, viral load of 61,500 copies / ml, brain nuclear magnetic resonance with cortical intra-axillary lesions, with a central hypointense area, at the level of the left parietal lobe and bilateral occipital, the diagnosis of toxoplasmic encephalitis is established, indicating treatment with trimethropin / cotrimoxazole, dexamethasone and antiretroviral drugs with abacavir-lamivudine and lopinavir-ritonavir having a good clinical evolution. Conclusions: The early diagnosis of toxoplasmic encephalitis based on epidemiological, clinical, laboratory and magnetic resonance criteria, allowed a good response to empirical antitoxoplasmic treatment. Keywords: Toxoplasmosis, opportunistic infections, encephalitis

Results of a Single Center Survey on Vaccination Against COVID-19 in Patients with Chronic Myeloid Leukemia

Introduction Despite the availability of vaccination against COVID 19 for all population categories since January 2021, it is moving slowly in Russia. Patients (pts) with chronic myeloid leukemia (CML) usually lead a normal life with social interactions. In the context of the COVID 19 pandemic, we find it important to identify the factors of adherence to vaccination and clarify the concerns. Objective: To determine the proportion of CML pts willing to consider vaccination against COVID 19, adherence factors and reasons for not vaccinating. Materials and methods. A survey on the attitude to vaccination against COVID 19 was prospectively carried out among all pts with CML consulted at the outpatient department of National Research Center for Hematology (Moscow, Russia) who agreed to participate. The key questions included considerations for and against vaccination, socio-demographic and clinical characteristics, lifestyle, comorbidities and history of COVID 19. Results. Within 4 months (from March 15 to July 19, 2021), 172 CML pts completed the questionnaire. CML chronic phase, advanced phase and blast crisis were in 167 (97%), 4 (2%) and 1(1%) respectively. In total, 141 (82%) pts were on therapy with 1 st, 2 nd and &gt;3 rd therapy line in 77 (55%), 33 (23%) and 31 (22%) pts, respectively. Thirty one (18%) had no therapy: 6 (3.5%) newly diagnozed, 25 (14.5%) in a treatment-free remission. A deep and major molecular response was in 77 (45%) and 30 (17%) pts, respectively. Presence and absence of molecular response MR2 was in 20 (12%) and 45 (26%) pts respectively. The median age of pts was 46 years (range 19-82), 75(44%) were males. Married 108 (63%), 70 (41%) lived with elderly relatives, 35 (20%) with children. A higher education was in 123 (72%) pts, 123 (72%) could not work remotely and 46 (27%) had interactions to people by work. Any comorbidity was in 89 (52%) pts, 42(24%) had &gt;1 concomitant disease, 48 (28%) had cardiovascular diseases, 44 (26%) had an obesity. A history of COVID 19 was in 41 (24%) pts and in the close circle of 74 (43%) pts. Vaccination was supported by 94(55%) pts (with 29 (17%) already vaccinated) and not supported by 76 (44%) pts, 2 (1%) pts did not answer. Among those supporting vaccination vs not supporting there was significantly more males (52% vs 33%, p=0,012), married pts (73% vs 49%, p&lt;0,001) and pts with higher education (88% vs 51%, p=0,006). Other factors (age, comorbidities, obesity, profession-related features, COVID 19 in pts or their environment, living with elderly relatives or children, therapy and treatment response) were not significant. Less pts were against vaccination in June-July 2021 before the 3 rd outbreak of COVID 19 compared to spring period (33% vs 50%, p=0,045). The two most common reasons to avoid vaccination were the fear of complications in 37(49%) pts and waiting for additional data in 19(25%) (Fig.1). Notably, 7 (9%) pts considered CML as a contraindication to vaccination. Among those supporting vaccination, 55(59%) preferred to choose the GamCovidVac (Sputnik V) vaccine, 20(21%) had no preference (Fig.2). Out of 32 pts who gave the rationale for the Sputnik V choice 19(59%) noted its best availability, study or popularity (Fig.3). Among 23 pts with additional questions 12 (52%) wondered about the possibility of vaccination with CML diagnosis and 6 (26%) asked help with a vaccine choice. Conclusion: Despite access to vaccines against COVID 19 with proven efficacy and safety, almost half of CML pts (44%) do not support vaccination. Socio-demographic factors such as gender, education, marriage status appeared to be significant for this decision. Considering the frequent concerns of the possibility of vaccination with CML diagnosis as well as the fear of complications, hematologists should provide a relevant clarifying information on these issues. Figure 1 Figure 1. Disclosures Chelysheva: Pfizer: Speakers Bureau; Novartis Pharma: Speakers Bureau; Pharmstandart: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Petrova: Pfizer: Speakers Bureau; Novartis Pharma: Speakers Bureau. Gurianova: Pfizer: Speakers Bureau. Kokhno: Novartis Pharma: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Turkina: Novartis Pharma: Speakers Bureau; Pfizer: Speakers Bureau; Pharmstandart: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau.

Challenges in Treating Charcot-Marie-Tooth Disease and Related Neuropathies: Current Management and Future Perspectives

There is still no effective drug treatment available for Charcot-Marie-Tooth neuropathies (CMT). Current management relies on rehabilitation therapy, surgery for skeletal deformities, and symptomatic treatment of pain; fatigue and cramps are frequent complaints that are difficult to treat. The challenge is to find disease-modifying therapies. Several approaches, including gene silencing, to counteract the PMP22 gene overexpression in the most frequent CMT1A type are under investigation. PXT3003 is the compound in the most advanced phase for CMT1A, as a second-phase III trial is ongoing. Gene therapy to substitute defective genes or insert novel ones and compounds acting on pathways important for different CMT types are being developed and tested in animal models. Modulation of the Neuregulin pathway determining myelin thickness is promising for both hypo-demyelinating and hypermyelinating neuropathies; intervention on Unfolded Protein Response seems effective for rescuing misfolded myelin proteins such as P0 in CMT1B. HDAC6 inhibitors improved axonal transport and ameliorated phenotypes in different CMT models. Other potential therapeutic strategies include targeting macrophages, lipid metabolism, and Nav1.8 sodium channel in demyelinating CMT and the P2X7 receptor, which regulates calcium influx into Schwann cells, in CMT1A. Further approaches are aimed at correcting metabolic abnormalities, including the accumulation of sorbitol caused by biallelic mutations in the sorbitol dehydrogenase (SORD) gene and of neurotoxic glycosphingolipids in HSN1.

Design and Application of Innovative 3DVC in AI Server System

With the accelerated application of cloud computing and artificial intelligence, the computing power and power consumption of chips are greatly enhanced, which brings severe challenges to heat dissipation. Based on this, Baidu has adopted advanced phase change cooling technology and successfully developed an innovative 3dvc air cooling scheme for AI server system. This paper introduces the design, test and verification of the innovative scheme in detail. The results show that the scheme can reduce the GPU temperature by more than 5 °C compared with the traditional heat pipe cooling scheme, save 30%+ of the fan power consumption, and achieve good cooling and energy saving effect.

Diagnostic Yield of Chilaiditi’s Sign in Advanced-Phase Late-Onset Pompe Disease

Purpose: Chilaiditi’s sign (CS), hepatodiaphragmatic interposition of the intestine, was caused by morphological abnormalities such as diaphragmatic atrophy, intestinal dilation, and liver atrophy. The sign is potentially important due to associations with clinically recurrent abdominal pain or even colonic volvulus. In general, neuromuscular disease (NMD) could have the high prevalence of CS because of widened hepatodiaphragmatic space, following diaphragmatic atrophy. Particularly, in late-onset Pompe disease (LOPD), glycogen accumulation in smooth muscle of intestine could lead to the abnormal dilation of intestine. Though the prevalence of CS in LOPD could be high because of developing two main factors of CS, no studies have evaluated the prevalence of CS in LOPD. Our aim was to investigate the prevalence of CS in LOPD, and to identify the risk factors of CS in LOPD patients. Methods: Medical records of genetically confirmed patients of Pompe disease at the National Center Hospital, National Center of Neurology and Psychiatry were retrospectively reviewed. We evaluated CS using chest X-ray (CXR) and abdominal CT and assessed the prevalence of CS in LOPD patients. We also divided the patients into two groups, CS and non-CS group, and evaluated the factor associated with CS compared to clinical variables between groups. Results: Three of seven (43%) were detected in CS. CS group (P5-7) and non-CS group (P1-4) were obtained. In comparison of clinical variables, the severity of atrophy in right diaphragms was significantly higher in CS than non-CS groups (p =0.029). Also, the frequency of abnormal position of right diaphragm and liver, and abnormally dilated bowel was seen in all of CS patients, but none of non-CS patient (p = 0.029, each). Conclusion: In LOPD patients, the prevalence of CS was much higher of 43%, compared to healthy groups, or even in similarly respiratory muscle impaired neuromuscular diseases such as Duchenne muscular dystrophy (DMD) or Myotonic dystrophy type 1 (DM1). The anatomically abnormal position of diaphragm and liver, atrophy and fat infiltration of diaphragms, and abnormally dilated bowel were significantly associated with CS in LOPD. Since CS can cause intestinal symptoms or even contribute to sudden-death of intestinal volvulus, we should pay more attention to CXR or abdominal CT as follow up in LOPD patients.

All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort

Purpose Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary. Methods 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account. Results Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05). Conclusion In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients.