Diseases, Volume 6, Issue 1 (March 2018) – 22 articles

The role of low-density lipoproteins (LDLs) as a major risk factor for cardiovascular disease has been demonstrated by several epidemiological studies. The molecular basis for LDLs in atherosclerotic plaque formation and progression is not completely unraveled yet. Pharmacological modulation of plasma LDL-C concentrations and randomized clinical trials addressing the impact of lipid-lowering interventions on cardiovascular outcome have clearly shown that reducing plasma LDL-C concentrations results in a significant decrease in major cardiovascular events. For many years, statins have represented the most powerful pharmacological agents available to lower plasma LDL-C concentrations. In clinical trials, it has been shown that the greater the reduction in plasma LDL-C concentrations, the lower the rate of major cardiovascular events, especially in high-risk patients, because of multiple risk factors and recurrent events. However, in a substantial number of patients, the recommended LDL target is difficult to achieve because of different factors: genetic background (familial hypercholesterolemia), side effects (statin intolerance), or high baseline plasma LDL-C concentrations. In the last decade, our understanding of the molecular mechanisms involved in LDL metabolism has progressed significantly and the key role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged. This protein is an enzyme able to bind the LDL receptors (LDL-R) on hepatocytes, favoring their degradation. Blocking PCSK9 represents an intriguing new therapeutic approach to decrease plasma LDL-C concentrations, which in recent studies has been demonstrated to also result in a significant reduction in major cardiovascular events. Full article

Inflammatory-mediated reactions have been implicated as contributors in a number of dermatological disorders, including psoriasis. However, the potential of interleukin (IL)-32 and its isoforms to contribute to the pathogenesis of psoriasis remains unexplored. This study was undertaken to investigate the role of IL-32 and its isoforms IL-32α, IL-32β, IL-32γ, and IL-32δ in the peripheral blood of psoriatic patients. The majority of chronic plaque psoriatic patients showed elevated IL-32 mRNA levels in the peripheral blood mononuclear cells (PBMCs) as compared with the levels of IL-32 mRNA in PBMCs of healthy controls (p = 0.001). To further investigate the role of elevated levels of IL-32 in psoriatic patients, IL-32 isoforms mRNAs were determined. All tested isoforms IL-32α, IL-32β, IL-32γ, and IL-32δ were overexpressed in psoriatic patients PBMCs as compared with healthy controls’ PBMCs (p < 0.05). IL-32α mRNA expression was also significantly higher as compared with all other isoforms of IL-32 in PBMCs of psoriatic patients (p < 0.001). In short, this is the first study that shows the role of IL-32 and its isoforms in the peripheral blood of psoriatic patients. Our novel findings support an association between elevated levels of IL-32 and psoriasis. The data also suggest that a major proinflammatory response of IL-32 may derive from IL-32α isoform in psoriasis. Full article

Photoplethysmogram (PPG) signals collected using a pulse oximeter are increasingly being used for screening and diagnosis purposes. Because of the non-invasive, cost-effective, and easy-to-use nature of the pulse oximeter, clinicians and biomedical engineers are investigating how PPG signals can help in the management of many medical conditions, especially for global health application. The study of PPG signal analysis is relatively new compared to research in electrocardiogram signals, for instance; however, we anticipate that in the near future blood pressure, cardiac output, and other clinical parameters will be measured from wearable devices that collect PPG signals, based on the signal’s vast potential. This article attempts to organize and standardize the names of PPG waveforms to ensure consistent terminologies, thereby helping the rapid developments in this research area, decreasing the disconnect within and among different disciplines, and increasing the number of features generated from PPG waveforms. Full article

Gout is caused by a chronic hyperuricemia whose complications are not currently well evaluated in Africa. The aim of this study was to determine the prevalence and risk factors of hyperuricemia and gout in 85 patients recruited. A total of 26 cases of hyperuricemia, i.e., 30.6% of the study population, with 12 cases of gout and seven cases of gouty access. In this population, hyperuricemia was proportional to age (p-value < 10^−4, OR = 2.6), but it was more prevalent in men, 23.5% versus 7.1% for women (p-value = 0.0047). In addition, none of these women showed signs of a gouty affection. Consumption of alcohol (OR = 13) and nucleoprotein-rich foods, obesity (BMI 30 kg/m²; OR = 6), family history of gout (OR = 6.8), as well as diseases such as high blood pressure (associated with taking diuretics; OR = 1.7), renal insufficiency (OR = 4.4) and diabetes (p < 0.049) were the main factors of the diseases associated with gout and hyperuricemia in this population. The biochemical role of these factors may increase and/or decrease the processes of synthesis and/or elimination of uric acid by acting on metabolites involved in the regulation of urate production. Full article

In the digital medicine field, biosignals, such as those of an electrocardiogram (ECG), are collected regularly for screening and diagnosis, and there continues to be an increasingly substantial shift towards collecting long-term ECG signals for remote monitoring, e.g., in smart homes. ECG signal collection is quite simple and only requires the use of inexpensive sensors, an active Internet connection, and a mobile device that acts as the medium between the sensors and the Internet (e.g., a mobile phone or laptop). Despite the ease and convenience of remote ECG data collection and transmission, the amount of time and energy required for the related remote computational processes remains a major limitation. This short note discusses a biosignal approach that uses fewer biomedical data for screening and diagnosis that is, compared to current data collection methods, equally, if not more, efficient. Full article

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with both atherosclerotic cardiovascular disease (CVD) and Fetuin-A. However, the association of Fetuin-A with atherosclerosis is more controversial. We hypothesized that the pathogenic interplay of NAFLD, Fetuin-A and atherosclerosis varies based on arterial site. Accordingly, we aimed to assess NAFLD prevalence, Fetuin-A values and their relationship with symptomatic atherosclerosis occurring in different localizations: coronary artery disease (CAD) vs. peripheral arterial disease (PAD). Methods: One hundred and forty-nine consecutive patients with symptomatic atherosclerotic CVD were recruited: 45 with CAD diagnosed by coronary angiography and 104 with PAD detected by doppler-ultrasound and/or computed tomography angiography and/or angiography. NAFLD was diagnosed based on both ultrasonography and exclusion of competing etiologies. Serum Fetuin-A was measured with ELISA. Results: NAFLD was detected in 54% of the overall group, with higher rates in PAD (59%) than CAD (42%) patients. Median Fetuin-A values were 256 (111–662) μg/mL, higher in patients with CAD (378 (124−662) μg/mL) than those with PAD (236 (111−461) μg/mL). The main findings were: (1) CAD patients had higher Fetuin-A values and less frequently NAFLD than PAD patients; (2) NAFLD was positively associated with Fetuin-A values; however, this association was limited to CAD patients only; (3) Fetuin-A values were positively associated with both CAD and NAFLD. Conclusion: The pathogenic interplay of NAFLD, Fetuin-A and atherosclerosis probably varies according to the arterial site. Full article

The diaphragm is the primary muscle of respiration, and its weakness can lead to respiratory failure. Diaphragmatic palsy can be caused by various causes. Injury to the phrenic nerve during thoracic surgeries is the most common cause for diaphragmatic palsy. Depending on the cause, the symptoms of diaphragmatic palsies vary from completely asymptomatic to disabling dyspnea requiring mechanical ventilation. On pulmonary function tests, there will be a decrease in the maximum respiratory muscle power. Spirometry shows reduced lung functions and a significant drop of lung function in supine position is typical of diaphragmatic palsy. Diaphragmatic movements with respiration can be directly visualized by fluoroscopic examination. Currently, this test is being replaced by bedside thoracic ultrasound examination, looking at the diaphragmic excursion with deep breathing or sniffing. This test is found to be equally efficient, and without risks of ionizing radiation of fluoroscope. Treatment of diaphragmatic palsy depends on the cause. Surgical approach of repair of diaphragm or nonsurgical approach of noninvasive ventilation has been tried with good success. Overall prognosis of diaphragmatic palsy is good, except when it is related to neuromuscular degeneration conditions. Full article

Objective: The aim of this study was to estimate the incidence of carotid artery calcification (CAC) in a sample of Lebanese population using digital panoramic radiographs. Materials and Methods: Panoramic radiographs of 500 patients (281 females and 219 males), aged between 18 and 88 years (mean: 47.9 years), were assessed for CAC. Data collected were analyzed statistically using IBM^® SPSS^® for Windows version 20.0 (SPSS, Chicago, IL, USA). Results: CAC were found in 34 cases (6.8%), among them, 23 females (8.18%) and 11 males (5.02%). Six of all the calcifications were on the right side, against six on the left side, and 22 on both sides. The mean age of patients affected with CAC was 60.9 years (ranging from 18 to 88 years). Chi-square test showed no statistical significance between gender and CAC, while Spearman correlation analysis showed positive low correlation with age (r = 0.179). Conclusion: CAC can be found on routine panoramic radiographs taken in dental clinics; dentists should automatically refer the patients in question for specialized medical evaluation. Full article

Very little is known about laboratory-confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design and implement antibiotic stewardship policy and introduce interventions to reduce LCBIs in resource-limited settings. Full article

The p53 gene is also known as tumor suppressor p53. The main functions of the p53 gene are an anticancer effect and cellular genomic stability via various pathways including activation of DNA repair, induction of apoptosis, and arresting of cell growth at the G1/S phase. Normally, the p53 gene is inactivated by mouse double minute 2 proteins (mdm2), but it is activated in chronic myeloid leukemia (CML). Tyrosine kinase inhibitors are effective chemotherapeutic agents in the management of CML. The purpose of the present study was to evaluate the differential effect of imatinib and nilotinib on p53 gene serum levels in patients with CML. A total number of 60 patients with chronic myeloid leukemia with ages ranging from 47 to 59 years were recruited from the Iraqi Hematology Center. They started with tyrosine kinase inhibitors as first-line chemotherapy. They were divided into two groups—Group A, 29 patients treated with imatinib and Group B, 31 patients treated with nilotinib—and compared with 28 healthy subjects for evaluation p53 serum levels regarding the selective effect of either imatinib or nilotinib. There were significantly (p < 0.01) high p53 gene serum levels in patients with CML (2.135 ± 1.44 ng/mL) compared to the control (0.142 ± 0.11 ng/mL). Patients with CML that were treated with either imatinib or nilotinib showed insignificant differences in most of the hematological profile (p > 0.05) whereas, p53 serum levels were high (3.22 ± 1.99 ng/mL) in nilotinib-treated patients and relatively low (1.18 ± 0.19 ng/mL) in imatinib-treated patients (p = 0.0001). Conclusions: Nilotinib is more effective than imatinib in raising p53 serum levels in patients with chronic myeloid leukemia. Full article

Background: The influence of metabolic syndrome (MetS) on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR) and/or the presence of microalbuminuria/macroalbuminuria. Methods: 149 patients (77 males/72 females) were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components) including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x² = 50.3, p = 0.001 and x² = 26.9, p = 0.003 respectively) was found to be significant. The MetS presence showed an odds 5.3-fold (1.6–17.8) higher for low eGFR and 3.2-fold (1.2–8.8) higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1–11.3). Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x² = 11.8, p = 0.003, x² = 11.4, p = 0.003 and x² = 9.1, p = 0.01 respectively), and it was mildly associated with a low HDL-C (x² = 5.7, p = 0.06). A significant association between classified eGFR and both high triglycerides and hypertension (x² = 9.7, p = 0.04 and x² = 16.1, p = 0.003 respectively) was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus. Full article

Background: Home telemonitoring is a modern and effective disease management model that is able to improve medical care, quality of life, and prognosis of chronically ill patients, and to reduce expenditure. The objective of this study was to evaluate the efficacy, costs, and patients’ and caregivers’ acceptance of our model of telemedicine in a high-risk chronic heart failure (CHF) older population. Methods: Patients with high risk/refractory CHF were included. In the case of alarm parameters’ modifications, a cardiologist decided to inform the emergency department (ED), the patient’s General Practioner, or to programme a clinical ambulatory control. Results: Forty-eight CHF patients (28 males; 58.3%), with a mean age of 80.4 ± 7.7 years, entered this clinical experience. During the 20-months follow-up, four patients dropped out from counselling (8.3%), ambulatory clinical control within-24 h was planned in 18% of patients, 11% of patients were admitted to an ED, and 18% were hospitalized. Thirteen patients (29.5%) died a cardiac death; hospital admissions for heart failure decreased during the year after the enrolment when compared to the year before (from 35 to 12 acute HF hospitalizations/year; p = 0.0001). Moreover, in these HF patients followed, accesses to an ED for an acute episode of HF decompensation reduced from 21/year to five/year (p = 0.0001). The economic expenditure, calculated for the year before and after the enrolment, reduced from 116.856 Euros to 40.065 Euros/year. Conclusions: A telemedicine surveillance in high-risk older CHF patients determines a continuous and active contact between patients/caregivers, the Heart Failure Clinic, and family physicians, permitting an early evaluation of signs and symptoms of acute decompensation. Full article

Adipose tissue-derived serine protease inhibitor (vaspin), which has endocrine and local roles in atherosclerosis growth, is also synthesized by adipose tissue; it was found that vaspin was negatively correlated with blood pressure in obese patients, while vaspin levels were decreased in endothelial dysfunction. The aim of the present study was to determine rosuvastatin modulation effects on serum vaspin levels in acute coronary syndrome (ACS) with class I obesity. A total number of seventy patients with acute coronary syndrome previously and currently treated with rosuvastatin was compared to 40 patients with IHD not treated by rosuvastatin as a control. Vaspin serum levels were higher in rosuvastatin-treated patients with acute coronary syndrome compared to the patients with acute coronary syndrome not treated by rosuvastatin, p < 0.01. Additionally, in the rosuvastatin-treated group, patients with STEMI showed higher vaspin serum levels compared to NSTEMI p < 0.01. Conclusion: Rosuvastatin significantly increases vaspin serum levels in acute coronary syndrome. Full article

Generally, pancreatic polypeptide-secreting tumor of the distal pancreas (PPoma) is classified as a rare tumor, and may occur sporadically or be associated in families or with multiple endocrine neoplasia type 1 (NEM 1). It grows slowly, reaching large dimensions at the time of diagnosis and the symptomatology is fundamentally due to the mass effect, causing either non-specific abdominal pain or symptoms suggestive of obstruction of the pancreatic or biliary duct. Therefore, when detected, they are usually malignant, with metastases mainly in the liver. The combination of serum analysis of increased levels of chromogranin A and pancreatic polypeptide and pancreastatin is very useful with a sensitivity of up to 95%. However, in addition, scintigraphicexams with somatostatin analogues should be performed to better clarify the diagnosis. Surgical resection is the treatment of choice, despite surgical difficulty and because they are generally palliative due to the metastases. Surgeries for tumor volume reduction are also performed to relieve symptoms. Chemotherapy commonly uses streptozotocin and somatostatin analogues to treat residual disease. Unfortunately, the survival rates are still very low, less than 10%, and if metastases already exist, this percentage drops to 3%. Full article

West Nile virus infection in humans is mostly asymptomatic. Less than 1% of neuro-invasive cases show a fatality rate of around 10%. Acute flaccid paralysis of respiratory muscles leading to respiratory failure is the most common cause of death. Although the peripheral nervous system can be involved, isolated phrenic nerve palsy leading to respiratory failure is rare and described in only two cases in the English literature. We present another case of neurological respiratory failure due to West Nile virus-induced phrenic nerve palsy. Our case reiterates the rare, but lethal, consequences of West Nile virus infection, and the increase of its awareness among physicians. Full article

Algorithm development in digital medicine necessitates ongoing knowledge and skills updating to match the current demands and constant progression in the field. In today’s chaotic world there is an increasing trend to seek out simple solutions for complex problems that can increase efficiency, reduce resource consumption, and improve scalability. This desire has spilled over into the world of science and research where many disciplines have taken to investigating and applying more simplistic approaches. Interestingly, through a review of current literature and research efforts, it seems that the learning and teaching principles in digital medicine continue to push towards the development of sophisticated algorithms with a limited scope and has not fully embraced or encouraged a shift towards more simple solutions that yield equal or better results. This short note aims to demonstrate that within the world of digital medicine and engineering, simpler algorithms can offer effective and efficient solutions, where traditionally more complex algorithms have been used. Moreover, the note demonstrates that bridging different research disciplines is very beneficial and yields valuable insights and results. Full article

Luminal breast cancers express estrogen (ER) and progesterone (PR) receptors, and respond to endocrine therapies. However, some ER+PR+ tumors display intrinsic or acquired resistance, possibly related to PR. Two PR isoforms, PR-A and PR-B, regulate distinct gene subsets that may differentially influence tumor fate. A high PR-A:PR-B ratio is associated with poor prognosis and tamoxifen resistance. We speculate that excessive PR-A marks tumors that will relapse early. Here we address mechanisms by which PR-A regulate transcription, focusing on SUMOylation. We use receptor mutants and synthetic promoter/reporters to show that SUMOylation deficiency or the deSUMOylase SENP1 enhance transcription by PR-A, independent of the receptors’ dimerization interface or DNA binding domain. De-SUMOylation exposes the agonist properties of the antiprogestin RU486. Thus, on synthetic promoters, SUMOylation functions as an independent brake on transcription by PR-A. What about PR-A SUMOylation of endogenous human breast cancer genes? To study these, we used gene expression profiling. Surprisingly, PR-A SUMOylation influences progestin target genes differentially, with some upregulated, others down-regulated, and others unaffected. Hormone-independent gene regulation is also PR-A SUMOylation dependent. Several SUMOylated genes were analyzed in clinical breast cancer database. In sum, we show that SUMOylation does not simply repress PR-A. Rather it regulates PR-A activity in a target selective manner including genes associated with poor prognosis, shortened survival, and metastasis. Full article

In older adults, chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure with reduced ejection fraction (HFrEF), and the high prevalence of this combination suggests that customized treatment is highly necessary in patients with COPD and HFrEF. To investigate whether the treatment of COPD with tiotropium, an anticholinergic bronchodilator, reduces the severity of heart failure in patients with HFrEF complicated by mild to moderate COPD, forty consecutive participants were randomly divided into two groups and enrolled in a crossover design study. Group A inhaled 18 μg tiotropium daily for 28 days and underwent observation for another 28 days. Group B completed the 28-day observation period first and then received tiotropium inhalation therapy for 28 days. Pulmonary and cardiac functions were measured on days 1, 29, and 56. In both groups, 28 days of tiotropium inhalation therapy substantially improved the left ventricular ejection fraction (from 36.3 ± 2.4% to 41.8 ± 5.9%, p < 0.01, in group A; from 35.7 ± 3.8% to 41.6 ± 3.8%, p < 0.01, in group B) and plasma brain natriuretic peptide levels (from 374 ± 94 to 263 ± 92 pg/mL, p < 0.01, in group A; from 358 ± 110 to 246 ± 101 pg/mL, p < 0.01, in group B). Tiotropium inhalation therapy improves pulmonary function as well as cardiac function, and reduces the severity of heart failure in patients with compensated HFrEF with concomitant mild to moderate COPD. Full article

Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis B virus (HBV) infections is 6.5% and accounts for 60% of hepatocellular carcinoma. HBV has nine genotypes that have been identified by molecular genetic analysis. HBV genotypes are associated with several clinical features. We reviewed the prevalence of HBV genotypes in Myanmar and neighboring countries. We also reviewed HBV genotypes in refugees from Myanmar. HBV subgenotype C1 is predominant in Myanmar. As HBV genotype C is associated with hepatocellular carcinoma (HCC), it is important to screen for cirrhosis and HCC and to prevent their development in HBV-infected individuals of Myanmar. Full article

Over the past two decades, the biopharmaceutical industry has seen unprecedented expansion and innovation in concert with significant technological advancements. While the industry has experienced marked growth, the regulatory system in the United States still operates at a capacity much lower than the influx of new drug and biologic candidates. As a result, it has become standard for months or even years of waiting for commercial approval by the U.S. Food and Drug Administration. These regulatory delays have generated a system that stifles growth and innovation due to the exorbitant costs associated with awaiting approval from the nation’s sole regulatory agency. The recent re-emergence of diseases that impact pediatric demographics represents one particularly acute reason for developing a regulatory system that facilitates a more efficient commercial review process. Herein, we present a range of initiatives that could represent early steps toward alleviating the delays in approving life-saving therapeutics. Full article

Background and aims: Maximum phonation time (MPT), which is related to respiratory function, is widely used to evaluate maximum vocal capabilities, because its use is non-invasive, quick, and inexpensive. We aimed to examine differences in MPT by age, following recovery phase II cardiac rehabilitation (CR). Methods: This longitudinal observational study assessed 50 consecutive cardiac patients who were divided into the middle-aged group (<65 years, n = 29) and older-aged group (≥65 years, n = 21). MPTs were measured at 1 and 3 months after cardiac surgery, and were compared. Results: The duration of MPT increased more significantly from month 1 to month 3 in the middle-aged group (19.2 ± 7.8 to 27.1 ± 11.6 s, p < 0.001) than in the older-aged group (12.6 ± 3.5 to 17.9 ± 6.0 s, p < 0.001). However, no statistically significant difference occurred in the % change of MPT from 1 month to 3 months after cardiac surgery between the middle-aged group and older-aged group, respectively (41.1% vs. 42.1%). In addition, there were no significant interactions of MPT in the two groups for 1 versus 3 months (F = 1.65, p = 0.20). Conclusion: Following phase II, CR improved MPT for all cardiac surgery patients. Full article