Med. Sci., Volume 9, Issue 2 (June 2021) – 27 articles

Background: Mounting data suggest that exposure to chronic stress is associated with worse breast cancer outcomes. This study aimed to explore the impact of social environmental adversity (SEA, e.g., child abuse, crime, sexual, and physical violence), depressive symptomatology, and anxiety on immune cell infiltration into the breast tumor microenvironment. Methods: Participants (n = 33) completed a series of surveys assessing depression and anxiety symptoms, adverse childhood events (ACE), and trauma history. Tumor-associated macrophages (CD68+), B cells (CD19+), and T cells (CD3+) were identified by immunohistochemical analyses of formalin-fixed paraffin-embedded tumor samples and quantified. Spearman rank tests were used to explore the relationships between the variables studied. Results: Exposure to SEA was high (ACE = 72%, exposure to crime = 47%, and exposure to physical/sexual assault = 73%) among participants. Moreover, 30% reported a comorbid history of depression and ACE; 39% reported one or more traumatic events, and clinically significant depression symptomatology, while 21% reported trauma history and significant anxiety symptomatology. Increased tumor-infiltrating B cells were significantly correlated with exposure to crime, anxiety symptoms, and exposure to an ACE. The ACE plus anxiety group presented the highest infiltration of B cells, T cells, and macrophages. Conclusion: These findings support a role for SEA, anxiety symptoms, and depression as potential modulators of the immune tumor microenvironment in breast cancer. Full article

Usually, cutaneous wound healing does not get impeded and processes uneventfully, reaching wound closure easily. The goal of this repair process is to restore the integrity of the body surface by creating a resilient and stable scar. Surgical practice and strategies have an impact on the course of wound healing and the later appearance of the scar. By considering elementary surgical principles, such as the appropriate suture material, suture technique, and timing, optimal conditions for wound healing can be created. Wounds can be differentiated into clean wounds, clean–contaminated wounds, contaminated, and infected/dirty wounds, based on the degree of colonization or infection. Furthermore, a distinction is made between acute and chronic wounds. The latter are wounds that persist for longer than 4–6 weeks. Care should be taken to avoid surgical site infections in the management of wounds by maintaining sterile working conditions, using antimicrobial working techniques, and implementing the principles of preoperative antibiotics. Successful wound closure is influenced by wound debridement. Wound debridement removes necrotic tissue, senescent and non-migratory cells, bacteria, and foreign bodies that impede wound healing. Additionally, the reconstructive ladder is a viable and partially overlapping treatment algorithm in plastic surgery to achieve successful wound closure. Full article

Putrescine, spermine, and spermidine are the important polyamines (PAs), found in all living organisms. PAs are formed by the decarboxylation of amino acids, and they facilitate cell growth and development via different cellular responses. PAs are the integrated part of the cellular and genetic metabolism and help in transcription, translation, signaling, and post-translational modifications. At the cellular level, PA concentration may influence the condition of various diseases in the body. For instance, a high PA level is detrimental to patients suffering from aging, cognitive impairment, and cancer. The levels of PAs decline with age in humans, which is associated with different health disorders. On the other hand, PAs reduce the risk of many cardiovascular diseases and increase longevity, when taken in an optimum quantity. Therefore, a controlled diet is an easy way to maintain the level of PAs in the body. Based on the nutritional intake of PAs, healthy cell functioning can be maintained. Moreover, several diseases can also be controlled to a higher extend via maintaining the metabolism of PAs. The present review discusses the types, important functions, and metabolism of PAs in humans. It also highlights the nutritional role of PAs in the prevention of various diseases. Full article

Background and Objectives: Hemoglobin A1c (HbA1c) is widely used for the monitoring and management of diabetes mellitus. The aim of this study is to investigate the influence of hemoglobin (Hb) variants on the measurement of HbA1c. Materials and Methods: HbA1c levels of 845 blood samples obtained from diabetic patients with various hemoglobin types were measured using a turbidimetric inhibition immunoassay and capillary electrophoresis. Results: Of 845 patients with diabetes, 65.7% (555/845) have the normal hemoglobin type (A₂A) and 34.3% (290/845) have various abnormal hemoglobin types, including heterozygous HbE 30.2% (255/845), homozygous HbE 1.9 % (16/845), Hb Constant Spring (CS) trait 1.4% (12/845), CSEA Bart’s 0.2% (2/845), and beta-thalassemia trait 0.6% (5/845). In most of the patients with diabetes, HbA1c levels determined by two different methods, inhibition immunoassay and capillary electrophoresis, gave strong positive correlation (R = 0.901, P < 0.001), except for those with homozygous HbE (N = 16) and CSEA Bart’s (N = 2). In all 18 patients with homozygous HbE and CSEA Bart’s, the HbA1c was undetectable by capillary electrophoresis, meaning that their estimated average glucose was undeterminable, although their HbA1c levels could be measured using an inhibition immunoassay. The discrepancy of HbA1c results obtained from two different methods is noted in patients without HbA. Conclusions: We have demonstrated the erroneous nature of HbA1c measurement in patients with hemoglobin variants, especially in those without HbA expression. Therefore, in the population with a high prevalence of hemoglobinopathies, hemoglobin typing should be considered as basic information prior to HbA1c measurement. Full article

Background: Aromatase inhibitors (AIs) are associated with musculoskeletal pain in one third (20–47%) of breast cancer patients. Recently, CDK4/6 inhibitors have emerged as a new therapeutic approach in hormone receptor (HR)-positive breast cancer. While hematological and gastrointestinal toxicities are frequently reported during treatment with CDK4/6 inhibitors, musculoskeletal symptoms are less commonly encountered. Methods: Herein, we present a retrospective study of 47 breast cancer patients who received CDK4/6 inhibitors along with endocrine therapy in our department between 01/01/2018 and 01/09/2020. Results: Median age at diagnosis was 58 years (29–81). Median duration of treatment was 8.76 months (SD: 7.68; 0.47–30.13 months). Median PFS was 24.33 months (95% CI; 1.71–46.96). Overall, toxicity was reported in 61.7% of the cases (29/47). Arthralgia was reported in 6.4% (3/47) of the patients. Hematological toxicity was reported in 51.1% (24/47) of the patients. Neutropenia was the main hematological toxicity observed (86.8%; 22/47) along with anemia (4.3%; 2/47), thrombocytopenia (2.1%; 1/47), and leukopenia (4.2%; 1/24). Conclusions: Though our data reflect a small sample size, we report a reduced arthralgia rate (6.4%) during treatment with CDK4/6 inhibitors compared with that reported in studies of AIs (20–47%). Full article

The direct-acting oral anticoagulant (DOAC) has become an alternative to low-molecular-weight heparin (LMWH) for treatment and prophylaxis of venous thromboembolism (VTE) in cancer patients. The clinicians are, however, faced with difficult decisions regarding DOAC treatment: Which patients cannot use DOACs? Should incidental VTE be treated similar to symptomatic VTE? Is it safe to give DOACs to patients with gastrointestinal or urogenital cancers? How about drug–drug interactions? Should all cancer patients receive thromboprophylaxis? Is arterial thrombosis a problem? The current article reviews the available literature regarding these questions and aims to provide practical solutions based on data from the clinical trials and new guidelines. Full article

Background: An outbreak of an unknown respiratory illness caused by a novel coronavirus, SARS-CoV-2, emerged in the city of Wuhan in Hubei Province, China, in December 2019 and was referred to as coronavirus disease-2019 (COVID-19). Soon after, it was declared as a global pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 mainly infects the respiratory tract with different outcomes ranging from asymptomatic infection to severe critical illness leading to death. Different SARS-CoV-2 variants are emerging of which three have raised concerns worldwide due to their high transmissibility among populations. Objective: To study the prevalence of COVID-19 in the region of Nabatieh-South Lebanon during the past year and assess the presence of SARS-CoV-2 variants and their effect on the spread of infection during times of lockdown. Methods: In our study, 37,474 nasopharyngeal swab samples were collected and analyzed for the detection of SARS-CoV-2 virus in suspected patients attending a tertiary health care center in South Lebanon during the period between 16 March 2020 and 21 February 2021. Results: The results demonstrated a variation in the prevalence rates ranging from less than 1% during full lockdown of the country to 8.4% upon easing lockdown restrictions and reaching 27.5% after the holidays and 2021 New Year celebrations. Interestingly, a new variant(s) appeared starting January 2021 with a significant positive association between the prevalence of positive tests and the percentage of the variant(s). Conclusions: Our results indicate that the lockdown implemented by the Lebanese officials was an effective intervention to contain COVID-19 spread. Our study also showed that lifting lockdown measures during the holidays, which allowed indoor crowded gatherings to occur, caused a surge in COVID-19 cases and rise in the mortality rates nationwide. More importantly, we confirmed the presence of a highly transmissible SARS-CoV-2 variant(s) circulating in the Lebanese community from at least January 2021 onwards. Full article

Hepatocrinology is defined as a bidirectional, complex relationship between hepatic physiology and endocrine function, hepatic disease and endocrine dysfunction, hepatotropic drugs and endocrine function, and endocrine drugs and hepatic health. The scope of hepatocrinology includes conditions of varied etiology (metabolic, infectious, autoimmune, and invasive) that we term as hepato-endocrine syndromes. This perspective shares the definition, concept, and scope of hepatocrinology and shares insight related to this aspect of medicine. It is hoped that this communication will encourage further attention and research in this critical field. Full article

Evidence suggests a major contribution of postprandial glucose (PPG) excursions to the increased risk of micro- and macro-vascular complications in individuals with type 2 diabetes mellitus (T2DM). Administration of bolus insulin remains a very effective therapeutic option for PPG control. The aim of this expert group recommendation document was to provide practical and easy-to-execute guidelines for physicians on the appropriate use of bolus insulin in the management of T2DM. A panel of key opinion leaders from India reviewed and discussed the available clinical evidence and guideline recommendations on the following topics: (1) optimum control of PPG; (2) choice of bolus insulin; and (3) special situations and practical considerations. The expert panel critically analyzed the current literature and clinical practice guidelines and factored their rich clinical experience to develop a set of nine expert group recommendations for the effective use of bolus insulin. These recommendations will not only result in a more evidence-based application of bolus insulin in the clinical setting but also trigger further research and provide a valuable base for the development of future guidelines on the use of bolus insulin in the management of individuals with T2DM. Full article

Breast cancer is the most common malignancy in women, with alarming mortalities. Neoadjuvant treatments employ chemotherapy to shrink tumours to a well-defined size for a better surgical outcome. The current means of assessing effectiveness of chemotherapy management are imprecise. We previously showed that breast cancer patients have higher serum circulating cell-free DNA concentrations. cfDNA is degraded cellular DNA fragments released into the bloodstream. We further report on the utility of cfDNA in assessing the response to chemotherapy and its potential as a monitoring biomarker. A total of 32 newly diagnosed and treatment-naive female breast cancer patients and 32 healthy females as controls were included. Anthropometric, demographic and clinicopathological information of participants were recorded. Each participant donated 5 mL of venous blood from which sera were separated. Blood sampling was carried out before the commencement of chemotherapy (timepoint 1) and after the third cycle of chemotherapy (timepoint 2). qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) was determined. ALU 115 and 247 levels were elevated in cancer patients but were significantly decreased after the third cycle of chemotherapy (T2) compared to T1. DNA integrity increased after the third cycle. Serum cfDNA may provide a relatively inexpensive and minimally invasive procedure to evaluate the response to chemotherapy in breast cancer. Full article

SARS-CoV-2 infection has generated the biggest pandemic since the influenza outbreak of 1918–1919. One clear difference between these pandemics has been the ability to test for the presence of the virus or for evidence of infection. This review examined the performance characteristics of sample types via PCR detection of the virus, of antibody testing, of rapid viral antigen detection kits and computerised tomography (CT) scanning. It was found that combined detection approaches, such as the incorporation of CT scans, may reduce the levels of false negatives obtained by PCR detection in both symptomatic and asymptomatic patients, while sputum and oral throat washing sample types should take precedence over swabbing when available. Rt-PCR assays for detection of the virus remain the gold-standard method for SARS-CoV-2 diagnosis and can be used effectively on pooled samples for widespread screening. The novel Oxford antibody assay was found to have the highest sensitivity and specificity of four currently available commercial antibody kits but should only be used during a specific timeframe post-symptom onset. Further research into transmission modes between symptomatic and asymptomatic patients is needed. Analysis of the performance characteristics of different sampling and detection methods for SARS-CoV-2 showed that timing of sampling and testing methods used can greatly influence the rate of false-positive and false-negative test results, thereby influencing viral spread. Full article

Low serum high-density lipoproteins-cholesterol (HDL-C) levels and high blood pressure are linked to each other and are recognized as independent risk factors of cardiovascular disease and dementia. HDL can cross the blood–brain barrier to remove amyloid plaque and the blood–testis barrier to supply cholesterol for spermatogenesis, but LDL cannot. During the teenage period, between 10 and 19 years of age, the systolic blood pressure (BP) increased gradually to 7.9% in boys (p < 0.001), but not in girls (p = 0.141). The boys’ group showed a remarkable decrease in the total cholesterol (TC) and HDL-C from 10 to 15 years of age (p < 0.001). After then, the TC level increased again at 19 years of age to the previous level (p < 0.001). On the other hand, the HDL-C level at 19 years of age in the boys’ group was not restored to the previous level at 10 years of age. The girls’ group maintained similar TC (p < 0.001) and HDL-C (p < 0.001) levels from 10 to 19 years of age. These results suggest there was a remarkable difference in cholesterol consumption, particularly in the HDL-C level between boys and girls during the pubertal period. Correlation analysis showed an inverse association between the HDL-C level and SBP in boys (r = −0.133, p < 0.001) and girls (r = −0.065, p = 0.009) from 10 to 19 years of age. Interestingly, only the boys’ group showed an inverse association with the diastolic BP (r = −0.122, p < 0.001); the girls’ group did not have such an association (r = −0.016, p = 0.516). In conclusion, the boys’ group showed a sharp decrease in the HDL-C level from 10 to 15 years of age, whereas the girls’ group showed an increase in the HDL-C level during the same period. These results explain why men have a lower serum HDL-C level than women in adulthood. Full article

Community-acquired pneumonia is still a major cause of morbidity and mortality worldwide. Since the inflammatory response induced by the immune system is often a major contributor to the lung injury, it becomes reasonable to assess the potential benefit of anti-inflammatory agents in treating community-acquired pneumonia. The role of corticosteroids as adjunct anti-inflammatory agents in treating community-acquired pneumonia is still controversial. Several studies have assessed the benefit of their use in patients with community-acquired pneumonia. In most of those studies, the route of corticosteroids administration was systemic. The aim of this article is to provide a concise review of the role of corticosteroids in treating community-acquired pneumonia when administered via inhalational route, with the potential benefit of avoiding systemic side effects of corticosteroids while exerting the same anti-inflammatory effects on the lungs. Conclusion: the use of inhaled corticosteroids may be of benefit in certain patient subsets with community-acquired pneumonia. Further randomized controlled trials are needed for better determination of such patient subsets. Full article

Background: Mindfulness Meditation (MM) is known to improve glycemic control and enhance the quality of life (QoL) in type 2 diabetes (T2D) patients. Unfortunately, the role of meditation in type 1 diabetes (T1D) has not been studied extensively. Therefore, we conducted this study to determine the effect of MM on the glycemic control and QoL in people living with T1D. Methodology: Thirty-two adults living with T1D were equally randomized into intervention (meditation) and control groups. The glycemic control and QoL were assessed at the baseline and after six months of intervention. Results: A total of thirty-two adults (15 males, 46.9%; mean age 23.8 ± 6.6 years) with type 1 diabetes (mean diabetes duration 12.7 ± 6.2 years) participated in the study. At the end of six months, a statistically significant improvement was seen in the mean blood glucose level in the control group (222.4 ± 77.8 versus 182.6 ± 52.0; p = 0.007) and the intervention group (215.3 ± 50.1 versus 193.2 ± 31.8; p = 0.008). Additionally, there was a significant reduction in the total diabetes distress score in the intervention group (1.6 ± 0.3 versus 1.3 ± 0.3; p = 0.003), while no change was observed in the control group (1.6 ± 0.7 versus 1.7 ± 0.4; p = 0.762). A statistically significant improvement was noticed in the health and functioning domain in the intervention group (p = 0.023). Conclusions: An improvement in the glycemic control and quality of life of the patients was observed in our study. MM certainly plays an important role in attaining peace of mind and helps patients to channel their energy in a positive direction. Full article

Background: Achalasia and other esophageal dysmotility disorders mimicking achalasia can be associated with cancer. This study aimed to review the main mechanisms for which cancer may develop in esophageal dysmotility disorder patients. Methods: A narrative review was performed. Results: The mechanism for developing squamous cell carcinoma and adenocarcinoma are discussed. Besides, achalasia-like syndromes related to familial KIT-gene mutation and pseudoachalasia are discussed. Conclusions: Knowing the main mechanism for which achalasia can be related to cancer is essential for clinicians to conduct the proper investigation, surveillance, and treatment. Full article

Sleep complaints can be both common and complex in the older patient. Their consideration is an important aspect of holistic care, and may have an impact on quality of life, mortality, falls and disease risk. Sleep assessment should form part of the comprehensive geriatric assessment. If sleep disturbance is brought to light, consideration of sleep disorders, co-morbidity and medication management should form part of a multifaceted approach. Appreciation of the bi-directional relationship and complex interplay between co-morbidity and sleep in older patients is an important element of patient care. This article provides a brief overview of sleep disturbance and sleep disorders in older patients, in addition to their association with specific co-morbidities including depression, heart failure, respiratory disorders, gastro-oesophageal reflux disease, nocturia, pain, Parkinson’s disease, dementia, polypharmacy and falls. A potential systematic multidomain approach to assessment and management is outlined, with an emphasis on non-pharmacological treatment where possible. Full article

A novel coronavirus related to a condition known as a severe acute respiratory syndrome (SARS) was termed as SARS Coronavirus-19 (SARS-CoV-2 or COVID-19), which has caused an unprecedented global pandemic. Extensive efforts have been dedicated worldwide towards determining the mechanisms of COVID-19 associated pathogenesis with the goals of devising potential therapeutic approaches to mitigate or overcome comorbidities and mortalities. While the mode of SARS-CoV-2 infection, its structural configuration, and mechanisms of action, including the critical roles of the Spike protein have been substantially explored, elucidation of signaling pathways regulating its cellular responses is yet to be fully determined. Notably, phosphoinositide 3-kinases (PI3K) and its downstream pathway have been exploited among potential therapeutic targets for SARS-CoV-2, and its activation modulates the release of cytokines such as IL-8. To that end, the current studies were sought to determine the response of the SARS-CoV-2 Spike S1 protein on PI3K-mediated IL-8 release using relevant and widely used cellular models. Overall, these studies indicate that PI3K signaling does not directly mediate Spike S1 protein-induced IL-8 release in these cellular models. Full article

The optimal timing of aortic valve replacement (AVR) remains controversial. Several biomarkers reflect the underlying pathophysiological processes in aortic stenosis (AS) and may be of use as mortality predictors. The aim of this systematic review and meta-analysis is to evaluate the blood biomarkers utilised in AS and assess whether they associate with mortality. PubMed and Embase were searched for studies reporting baseline biomarker level and mortality outcomes in patients with AS. A total of 83 studies met the inclusion criteria and were systematically reviewed. Of these, 21 reporting brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin and Galectin-3 were meta-analysed. Pooled analysis demonstrated that all-cause mortality was significantly associated with elevated baseline levels of BNP (HR 2.59; 95% CI 1.95–3.44; p < 0.00001), NT-proBNP (HR 1.73; 95% CI 1.45–2.06; p = 0.00001), Troponin (HR 1.65; 95% CI 1.31–2.07; p < 0.0001) and Galectin-3 (HR 1.82; 95% CI 1.27–2.61; p < 0.001) compared to lower baseline biomarker levels. Elevated levels of baseline BNP, NT-proBNP, Troponin and Galectin-3 were associated with increased all-cause mortality in a population of patients with AS. Therefore, a change in biomarker level could be considered to refine optimal timing of intervention. The results of this meta-analysis highlight the importance of biomarkers in risk stratification of AS, regardless of symptom status. Full article

Polycationic polyamines are present in nearly all living organisms and are essential for mammalian cell growth and survival, and for development. These positively charged molecules are involved in a variety of essential biological processes, yet their underlying mechanisms of action are not fully understood. Several studies have shown both beneficial and detrimental effects of polyamines on human health. In cancer, polyamine metabolism is frequently dysregulated, and elevated polyamines have been shown to promote tumor growth and progression, suggesting that targeting polyamines is an attractive strategy for therapeutic intervention. In contrast, polyamines have also been shown to play critical roles in lifespan, cardiac health and in the development and function of the brain. Accordingly, a detailed understanding of mechanisms that control polyamine homeostasis in human health and disease is needed to develop safe and effective strategies for polyamine-targeted therapy. Full article

Polyamines are small organic cations that are important for several biological processes such as cell proliferation, cell cycle progression, and apoptosis. The dysregulation of intracellular polyamines is often associated with diseases such as cancer, diabetes, and developmental disorders. Although polyamine metabolism has been well studied, the effects of key enzymes in the polyamine pathway on lipid metabolism are not well understood. Here, we determined metabolic effects resulting from the absence of spermidine synthase (SpdS) and spermine synthase (Sms) in Drosophila. While SpdS mutants developed normally and accumulated triglycerides, Sms mutants had reduced viability and stored less triglyceride than the controls. Interestingly, when decreasing SpdS and Sms, specifically in the fat body, triglyceride storage increased. While there was no difference in triglycerides stored in heads, thoraxes and abdomen fat bodies, abdomen fat body DNA content increased, and protein/DNA decreased in both SpdS- and Sms-RNAi flies, suggesting that fat body-specific knockdown of SpdS and Sms causes the production of smaller fat body cells and triglycerides to accumulate in non-fat body tissues of the abdomen. Together, these data provide support for the role that polyamines play in the regulation of metabolism and can help enhance our understanding of polyamine function in metabolic diseases. Full article

Background: Antidepressants are one of the most prescribed medications, particularly for patients with mental disorders. Nevertheless, there are still limited data regarding the risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) associated with these medications. Thus, we performed systemic review and meta-analysis to characterize the risks of VA and SCD among patients who used common antidepressants. Methods: A literature search for studies that reported risk of ventricular arrhythmias and sudden cardiac death in antidepressant use from MEDLINE, EMBASE, and Cochrane Database from inception through September 2020. A random-effects model network meta-analysis model was used to analyze the relation between antidepressants and VA/SCD. Surface Under Cumulative Ranking Curve (SUCRA) was used to rank the treatment for each outcome. Results: The mean study sample size was 355,158 subjects. Tricyclic antidepressant (TCA) patients were the least likely to develop ventricular arrhythmia events/sudden cardiac deaths at OR 0.24, 0.028–1.2, OR 0.32 (95% CI 0.038–1.6) for serotonin and norepinephrine reuptake inhibitors (SNRI), and OR 0.36 (95% CI 0.043, 1.8) for selective serotonin reuptake inhibitors (SSRI), respectively. According to SUCRA analysis, TCA was on a higher rank compared to SNRI and SSRI considering the risk of VA/SCD. Conclusion: Our network meta-analysis demonstrated the low risk of VA/SCD among patients using antidepressants for SNRI, SSRI and especially, TCA. Despite the relatively lowest VA/SCD in TCA, drug efficacy and other adverse effects should be taken into account in patients with mental disorders. Full article

The nasal cavity lined by nasal mucosa, is a significant part of respiratory system of human. However, there are no studies aimed to detect a molecular phenotype of healthy and normal functioning nasal mucosa, obtained after rhinoseptoplasty procedure, to understand its physiology and growth and inflammation processes. Thus, our aim is to identify human healthy nasal mucosa cytokines, neuropeptide-containing innervation and cell proliferation markers to form a control group for further tissue investigation of human nasal polyposis as the next step of our research. The study included surgery materials from 17 healthy humans. Biotin-streptavidin immunohistochemistry was performed for detection of tissue PGP9.5, Ki-67, β-Defensin 2, IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12. Results were evaluated semi-quantitatively and by Friedman ANOVA and Spearman rang correlation tests. All factors were more widely expressed by superficial epithelium than by glandular one. Abundance of ILs-8, -10 and -12 positive cells was detected in comparison with moderate to numerous distributions of IL-1, IL-6 and β-Defensin 2. Moderate number of PGP 9.5-containing nerve fibers and only few to moderate Ki-67 positive cells were found in healthy nasal mucosa. We revealed statistically significant difference between Ki-67 and ILs-4, -6, -7, -8, -10, -12 both in healthy nasal mucosa superficial and glandular epithelium. From nasal epithelia, commonly the surface one displays more cytokines and β-Defensin 2 in comparison to the glandular one. Numerous to abundant expression of ILs-4, -6, -7, -8, -10, -12 and β-Defensin 2 in nasal superficial and glandular epithelia proves probably these factors’ role into the common immune response of tissue and stimulation of immune cell differentiation. Full article

Background: Radical prostatectomy (RP) is the standard treatment in patients with high-risk prostate cancer (PCa). However, there is a high rate of recurrence, and new approaches are required to improve surgical efficacy. Here, we evaluated the feasibility and safety of neoadjuvant chemohormonal therapy (NCHT) before RP for Japanese patients with high-risk localized prostate cancer (PCa). Methods: From February 2009 to April 2016, 21 high-risk patients were enrolled in this prospective study. Patients were treated with docetaxel (70 mg/m²) every four weeks for three cycles and luteinizing hormone-releasing hormone agonist. Patients with grade 3–4 toxicities had 25% dose reductions for the following course. Results: Median follow-up was 88.6 months. The dose of docetaxel was reduced in 13 patients. The estimated five-year biochemical progression-free survival (bPFS) rate was 57.1%. National Comprehensive Cancer Network criteria (high-risk, but not very high-risk (nVHR) versus VHR) was associated with bPFS (p = 0.03). Five-year bPFS rates in the nVHR and VHR groups were 76.9% and 25.0%, respectively. There was a significant difference in bPFS between the nVHR and VHR groups (p = 0.023) by Kaplan–Meier analysis. Conclusions: Although our study included a small number of cases, at least in our exploration, NCHT was safe and feasible. However, more extensive treatment modalities are needed to improve outcomes, especially in VHR patients. Full article

Background: Globally, the application of medicinal plants in the management of acute and chronic wounds can be considered a common occurrence in most traditional medicine practices. In view of this, many plants in the tropical and subtropical regions have been screened for their wound-healing activities. Consequently, plants having antimicrobial activity against multidrug-resistant (MD-R) pathogens can be considered great assets. Therefore, this study evaluated ethanolic and aqueous extracts of five medicinal plants (Psidium guajava, Myrianthus arboreus, Alchornea cordifolia, Momordica charantia, and Justicia flava) for their antimicrobial activities against MD-R bacterial pathogens isolated from post-operative wounds; Methods: This involved the aqueous and ethanolic extraction of the selected medicinal plants. Preliminary phytochemical constituents of the plants were examined. The agar well diffusion method was then used to determine the antibacterial activity of the leaves against reference strains (Escherichia coli ATCC 25922, Salmonella typhi ATCC 19430, Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 25923, and a Methicillin-Resistant Staphylococcus aureus strain) as well as the MDR clinical isolates (E. coli, P. aeruginosa, S. aureus and CoNS) from the wounds; Results: The preliminary phytochemical analysis of the leaves showed the presence of saponins, phenolics, and reducing sugars in almost all the plants tested. All plant extracts were observed to have some antimicrobial activity against at least one reference strain. For the clinical MDR isolates, A. cordifolia from this study showed highest inhibition to growth of all bacteria used. Activity of J. flava against S. aureus was highest as compared to that of E.coli and P. aeruginosa. Similar observation was made for M. arboreus, P. guajava and M. charantia where the highest activity was observed against S. aureus; Conclusion: This study has mainly shown that P. guajava, M. arboreus, A. cordifolia, M. charantia, and J. flava exhibits antimicrobial activities against MD-R bacterial pathogens isolated from post-operative wounds. Also, these plants has bioactive phytochemical compounds with potential medicinal values for the treatment of numerous infections. Therefore, these plants may be helpful in the management of acute and chronic wounds, especially in traditional medicine practices. Full article

The Japanese diet and the Mediterranean diet are rich in polyamines (spermidine and spermine). Increased polyamine intake elevated blood spermine levels, inhibited aging-associated pro-inflammatory status (increases in lymphocyte function-associated antigen-1 (LFA-1) on immune cells), suppressed aberrant gene methylation and extended the lifespan of mice. To test the effects of increased polyamine intake by humans, 30 healthy male volunteers were asked to eat polyamine-rich and ready-to-eat traditional Japanese food (natto) for 12 months. Natto with high polyamine content was used. Another 27 male volunteers were asked not to change their dietary pattern as a control group. The volunteers’ age of intervention and control groups ranged from 40 to 69 years (median 48.9 ± 7.9). Two subjects in the control group subsequently dropped out of the study. The estimated increases in spermidine and spermine intakes were 96.63 ± 47.70 and 22.00 ± 9.56 µmol per day in the intervention group, while no changes were observed in the control group. The mean blood spermine level in the intervention group gradually rose to 1.12 ± 0.29 times the pre-intervention level after 12 months, and were significantly higher (p = 0.019) than those in the control group. Blood spermidine did not increase in either group. LFA-1 on monocytes decreased gradually in the intervention group, and there was an inverse association between changes in spermine concentrations relative to spermidine and changes in LFA-1 levels. Contingency table analysis revealed that the odds ratio to decrease LFA-1 by increased polyamine intake was 3.927 (95% CI 1.116–13.715) (p = 0.032) when the effect of acute inflammation was excluded. The results in the study were similar to those of our animal experiments. Since methylation changes of the entire genome are associated with aging-associated pathologies and our previous studies showed that spermine-induced LFA-1 suppression was associated with the inhibition of aberrant gene methylation, the results suggest that dietary polyamine contributes to human health and longevity. Full article

Introduction: This study was designed to compare the Datex neuromuscular transmission (NMT) kinemyography (NMTK) device with the TOFscan (TS) accelerometer during the onset and recovery of neuromuscular blockade. Patients and methods: This prospective study included adult patients who were scheduled to undergo elective surgery with general anesthesia and orotracheal intubation. The TS accelerometer was randomly placed at the adductor pollicis on one hand, and the NMTK was placed on the opposite arm. Anesthesia was initiated with remifentanil target-controlled infusion (TCI) and 2.0–3.0 mg/kg of propofol. Thereafter, 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium was injected. If needed, additional neuromuscular blocking agents were administered to facilitate surgery. First, we recorded the train of four (TOF) response at the onset of neuromuscular blockade to reach a TOF count of 0. Second, we recorded the TOF response at the recovery of neuromuscular blockade to obtain a T4/T1 90% by both TS and NMTK. Results: There were 32 patients, aged 38–83 years, with the American Society of Anesthesiologists (ASA) Physical Status Classification I–III included and analyzed. Surgery was abdominal, gynecologic, or head and neck. The Bland and Altman analysis for obtaining zero responses during the onset showed a bias (mean) of 2.7 s (delay) of TS in comparison to NMTK, with an upper/lower limit of agreement of [104; −109 s] and a bias of 36 s of TS in comparison to NMTK, with an upper/lower limit of agreement of [−21.8, −23.1 min] during recovery (T4/T1 > 90%). Conclusions: Under the conditions of the present study, the two devices are not interchangeable. Clinical decisions for deep neuromuscular blockade should be made cautiously, as both devices appear less accurate with significant variability. Full article

Neuroelectric measures derived from human magnetoencephalographic (MEG) recordings hold promise as aides to diagnosis and treatment monitoring and targeting for chronic sequelae of traumatic brain injury (TBI). This study tests novel MEG-derived regional brain measures of tonic neuroelectric activation for long-term test-retest reliability and sensitivity to symptoms. Resting state MEG recordings were obtained from a normative cohort, Cambridge Centre for Ageing and Neuroscience (CamCAN), baseline: n = 619; mean 16-month follow-up: n = 253) and a chronic symptomatic TBI cohort, Targeted Evaluation, Action and Monitoring of Traumatic Brain Injury (TEAM-TBI), baseline: n = 64; mean 6-month follow-up: n = 39). For the CamCAN cohort, MEG-derived neuroelectric measures showed good long-term test-retest reliability for most of the 103 automatically identified stereotypic regions. The TEAM-TBI cohort was screened for depression, somatization, and anxiety with the Brief Symptom Inventory and for insomnia with the Insomnia Severity Index. Linear classifiers constructed from the 103 regional measures from each TEAM-TBI cohort member distinguished those with and without each symptom, with p < 0.01 for each—i.e., the tonic regional neuroelectric measures of activation are sensitive to the presence/absence of these symptoms. The novel regional MEG-derived neuroelectric measures obtained and tested in this study demonstrate the necessary and sufficient properties to be clinically useful—i.e., good test-retest reliability, sensitivity to symptoms in each individual, and obtainable using automatic processing without human judgement or intervention. Full article