Expression of biomarkers vimentin and Metastasis Associated 1(MTA1) protein in different stages of laryngeal cancer and their impacts on survival

Laryngeal cancer is the second most common cancer after the lip and oral cavity cancer ofhead and neck region1. Laryngeal malignancy is the seventh most common malignancy in males in India. Total number of new laryngeal cancer and death from laryngeal cancer have been estimated 12410 and 3760 respectively in 20192. As per last survey available the number of new cases diagnosed and total number of deaths from laryngeal malignancy were 25,460 and 17,560 respectively in 2012 in India3 . The incidence of cancer larynx is 1.26-8.18 per 100,000 populations in different regions of India. Carcinoma larynx constitutes40% of all Head and Neck cancers. Squamous cell carcinoma constitutes 95% of all malignancies of larynx. Glottis being the most common subsite followed by supraglottis and the least common site is the subglottis. There is an increasing incidence rate of this malignancy among middle aged and elderly men and women throughout the world. Expression of Biomarkers at different stages of laryngeal cancers and their impact on survival can play a crucial role in future management of laryngeal malignancies. In spite of having different modalities of treatments like surgery, radiotherapy, chemoradiation, the prognosis of laryngeal malignancies is still poor. The most common adverse factor for laryngeal cancer has been found lymph node metastasis. The process of progression of LSCC is complex and difficult to know it completely. Despite multi-modality therapeutic advances in recent decades, improvements in overall survival and disease free survival is very less. In this study we emphasized the role of expression of biomarkers vimentin and metastasis associated 1(MTA1) protein in different stages of laryngeal cancer and their impacts on survival.

Double-edged effects caused by magnesium ions and alkaline environment regulate bioactivities of magnesium-incorporated silicocarnotite in vitro

Magnesium (Mg) is an important element for its enhanced osteogenic and angiogenic properties in vitro and in vivo, however, the inherent alkalinity is the adverse factor that needs further attention. In order to study the role of alkalinity in regulating osteogenesis and angiogenesis in vitro, magnesium-silicocarnotite [Mg-Ca5(PO4)2SiO4, Mg-CPS] was designed and fabricated. In this study, Mg-CPS showed better osteogenic and angiogenic properties than CPS within 10 wt.% magnesium oxide (MgO), since the adversity of alkaline condition was covered by the benefits of improved Mg ion concentrations through activating Smad2/3-Runx2 signaling pathway in MC3T3-E1 cells and PI3K-AKT signaling pathway in human umbilical vein endothelial cells in vitro. Besides, provided that MgO was incorporated with 15 wt.% in CPS, the bioactivities had declined due to the environment consisting of higher-concentrated Mg ions, stronger alkalinity and lower Ca/P/Si ions caused. According to the results, it indicated that bioactivities of Mg-CPS in vitro were regulated by the double-edged effects, which were the consequence of Mg ions and alkaline environment combined. Therefore, if MgO is properly incorporated in CPS, the improved bioactivities could cover alkaline adversity, making Mg-CPS bioceramics promising in orthopedic clinical application for its enhancement of osteogenesis and angiogenesis in vitro.

Pretransplant Determinants of Outcome in Patients with Myeloma Undergoing Autologous Transplantation in Lower Resource Settings

The treatment landscape in multiple myeloma has significantly changed since the introduction of high-dose melphalan with autologous stem cell rescue in the 1980s. Many randomised controlled trials have clearly demonstrated the superiority of autologous stem cell transplantation in improving survival compared to conventional chemotherapy. However, outcomes in myeloma are highly variable with median survival as short as 2 years and as long as 10 years or more. The main adverse factor predicting shorter survival is presence of high-risk cytogenetics. However, there are many other potential factors that can contribute to the treatment outcomes. This review looks at the various pretransplant variables that are associated with post-transplant outcomes in myeloma.

Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.

INTERFERENCE AND MASKING ACTION OF HIGH-INTENSITY NOISE AND METHODS OF MITIGATION

Noise is the leading adverse factor in the day-to-day activities of the Russian force units. External nose, high-intensity in particular, degrades operator's efficiency increasing the probability of erroneous actions. The paper dwells on noise interference and masking effects on sound transmission and speech communication. Personal mufflers are unable to reduce noise interference fully, high-intensity noise specifically. Bone conduction is regarded to be an optional pathway of sound transmission. The use of bone conduction gadgets will afford clear communication in high-intensity noise environments.

Daratumumab for systemic AL amyloidosis: prognostic factors and adverse outcome with nephrotic-range albuminuria

Daratumumab has shown promising first results in systemic amyloid light-chain (AL) amyloidosis. We analyzed a consecutive series of 168 patients with advanced AL receiving either daratumumab/dexamethasone (DD, n = 106) or daratumumab/bortezomib/dexamethasone (DVD, n = 62). DD achieved a remission rate (RR) of 64% and a very good hematologic remission (VGHR) rate of 48% after 3 months. Median hematologic event-free survival (hemEFS) was 11.8 months and median overall survival (OS) was 25.6 months. DVD achieved a 66% RR and a 55% VGHR rate. Median hemEFS was 19.1 months and median OS had not been reached. Cardiac organ responses were noted in 22% with DD and 26% with DVD after 6 months. Infectious complications were common (Common Terminology Criteria [CTC] grade 3/4: DD 16%, DVD 18%) and likely related to a high rate of lymphocytopenia (CTC grade 3/4: DD 20%, DVD 17%). On univariable analysis, hyperdiploidy and gain 1q21 conferred an adverse factor for OS and hemEFS with DD, whereas translocation t(11;14) was associated with a better hemEFS. N-terminal prohormone of brain natriuretic peptide >8500 ng/L could not be overcome for survival with each regimen. Multivariable Cox regression analysis revealed plasma cell dyscrasia (difference between serum free light chains [dFLC]) >180 mg/L as an overall strong negative prognostic factor. Additionally, nephrotic-range albuminuria with an albumin-to-creatinine-ratio (ACR) >220 mg/mmol was a significantly adverse factor for hemEFS (hazard ratio, 2.1 and 3.1) with DD and DVD. Daratumumab salvage therapy produced good results and remission rates challenging any therapy in advanced AL. Outcome is adversely influenced by the activity of the underlying plasma cell dyscrasia (dFLC) and nephrotic-range albuminuria (ACR).

Lymphopenia acted as an adverse factor for severity in patients with COVID-19: a single-centered, retrospective study

Purpose: The outbreak of SARS-CoV-2 began in December and rapidly caused a pandemic. To investigate the significance of lymphopenia for the severity of the disease, this study was performed.Methods: 115 patients confirmed COVID-19 from a tertiary hospital in Changsha, China were enrolled. The clinical, laboratory, treatment and outcome data were collected and compared between patients with lymphopenia or not.Results: The median age was 42 years (1-75). 54 patients (47.0%) of the patients had lymphopenia on admission. In the group of lymphopenia, more patients had hypertension (30.8% vs 10.0%, P=0.006) and coronary heart disease (3.6% vs 0%, P=0.029) and more patients with leucopenia (48.1% vs 14.8%, P<0.001) and eosinophilia (92.6% vs 54.1%, P<0.001) were observed. Lymphopenia was also correlated with severity grades of pneumonia (P<0.001) and C-reactive protein (CRP) level (P=0.0014). Lymphopenia was associated with a prolonged duration of hospitalization (17.0 days vs 14.0 days, P=0.002). Moreover, the recovery of lymphocyte appeared the earliest before CRP and chest radiographs in severe cases, suggesting its predictive value for disease improvement. Conclusion: Our results showed the clinical significance of lymphopenia for predicting the severity of COVID-19 and the recovery of the disease, emphasizing the need to monitor the lymphocyte count dynamically.

The Impacts of Different Air Pollutants on Domestic and Inbound Tourism in China

Previous studies have reported that air pollution negatively affects the tourism industry. This paper attempted to answer the following question: among different air pollutants, which one acts as the most adverse factor? The study was based on a sample of panel data covering 337 Chinese cities for the period between 2007 and 2016. Four pollutant indicators were inspected: PM 2 . 5 (particulate matter 2.5 micrometers or less in size), PM 10 (particulate matter 10 micrometers or less in size), SO 2 (sulfur dioxide), and NO 2 (nitrogen dioxide). It was found that PM 2 . 5 had a significantly negative impact on both domestic and inbound tourist arrivals. Regarding the other three pollutant indicators, except for the negative influence of NO 2 on inbound tourist arrivals, no statistically significant impact was found. This study suggests that tourism policy makers should primarily focus on PM 2 . 5 , when considering the nexus between air quality and tourism development. According to our estimates, the negative impact of PM 2 . 5 on tourism is substantial. If the PM 2 . 5 concentration in the ambient air increases by 1 μ g/m 3 (= 0.001 mg/m 3 ), domestic and inbound tourist arrivals will decline by 0.482% and 1.227%, respectively. These numbers imply an average reduction of 81,855 person-times in annual domestic tourist arrivals and 12,269 in inbound tourist arrivals in each city.

MORTALITY ANALYSIS OF THE PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS

Background. Alcohol is considered to be the main risk factor for adverse event deaths around the world. In Ukraine, mortality due to alcoholic liver disease (ALD) has taken the second place in the structure of death causes from diseases of the digestive system. Objective. The aim of the research was to study the peculiarities of the causes of death in the patients with alcoholic liver disease at the stage of liver cirrhosis (LC) based on the analysis of protocols of pathoanatomical research. Methods. The analysis of 149 protocols of the pathoanatomical study of the patients, who died from alcoholic LC, has been carried out at the premises of the Pathoanatomical Department of the Ivano-Frankivsk Regional Clinical Hospital in 2006-2018. Results. Most people were young and middle aged. Fatal cases were caused by decompensation of the LC with the development of hepatic, hepatic-renal, cardio-pulmonary insufficiency, pancreatic necrosis, gastrointestinal bleeding (GIB), sepsis, hepatocellular carcinoma (HCC). In 37.6 % of the patients the concomitant illness was coronary heart disease (CHD), 10.7 % of the people had hypertension. In 6 % of the patients, ischemic stroke of the brain was diagnosed. In most people atherosclerotic vascular changes were revealed. Conclusions. Excessive consumption of alcohol and, consequently, the development of LC, can be considered as an adverse factor in the reducing social standard of living. In the majority of people, who died from the decompensation of alcoholic LC, atherosclerotic vascular lesions have been detected. This indicates a significant prevalence of lipid metabolism disturbance in the people with alcoholic LC.