Sound: Production, perception, hearing loss and treatment options.

Sound is an important communication tool for humans that contain information about the surrounding environment. It may signify a danger or a reward for an organism. In humans, the mechanism of sound production and perception is complex and sophisticated. Sound is produced by vibrating body in a medium that contains molecules in the surrounding space. The sound perception starts in the human foetus at around the third trimester where it plays a vital role in organising the foetal brain. This process continues after birth and can be exploited by various endogenous and exogenous factors. Many mechanisms that can modulate hearing process at different levels lead to subclinical or clinical presentation of hearing-related problems. It is important to contemplate the mechanisms underlying sound production, perception and pathogenesis of hearing loss. This will facilitate prescribing a relevant treatment option according to the cause and its underlying mechanism. The current narrative review was planned to focus on sound production, its perception, types of hearing loss and available treatment options vited in relevant literature searched by using Google Scholar and PubMed.

Recent advances in diagnostic and prognostic aspects of acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a group of haematological malignant disorders. Although not a new disease, many studies have been conducted to explore AML etiology, pathogenesis and prognosis at molecular level over the past two decades. A meticulous and continuous review of the available literature is still required to contemplate currently discovered information. We searched Google Scholar and PubMed by using different key word such as: updates in diagnostic criteria of AML, WHO classification of AML, new prognostic factors and risk stratification of AML. Mostly articles are referred from international sources published during last five years. Some older articles were only used when pivotal information required could not be surpassed by newer articles. Initially 50 relevant articles were included which were subsequently reduced to 36 by excluding articles with similar information. In this review an attempt is made to approach the subject in the light of currently available literature.

Clinical presentation of acute myeloid leukaemia - A decade-long institutional follow-up.

OBJECTIVE: To analyse a decade-long pattern of clinical presentation of acute myeloid leukaemia patients and compare it with contemporary data. METHODS: The retrospective cohort study was conducted at the National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, and comprised of medical record of acute myeloid leukaemia patients from March 2006 to October 2016. Data noted age at presentation, gender, medical history, physical examination, blood and bone marrow investigations such as, haemoglobin levels, blood cell count myeloperoxidase activity, periodic acid-Schiff and reticulin staining as well as final diagnosis. Comparison, where possible, was done with contemporary literature. SPSS 19 was used for data analysis. RESULTS: Of the 626 subjects, 248(39.6%) were females and 378(60.4%) males. The overall mean age was 35.3±17.1 years. The most common age group was 15-40 years with 354(56.5%) patients. The most common subtype was acute myeloid leukaemia with maturation 183(33.6%). Myeloperoxidase activity was positive for the majority of the acute myeloid leukaemia patients. Periodic acid-Schiff test, done on only selected patients, was mostly negative. Reticulin staining was positive for 113(65.3%) patients. The most common presenting complaints were fever 266(71.9%) and weakness 168(45.4%). Mean haemoglobin and red blood cell count were 8.3 ± 2.4 g/dL and 2.9 ± 1.2 1012/L, respectively. CONCLUSIONS: Acute myeloid leukaemia was found to be a highly variable disease that presented with non-specific signs and symptoms.

Impact of Intermittent Fasting on Lipid Profile-A Quasi-Randomized Clinical Trial.

Background: Sub-optimal HDL is a prognostic marker of cardiovascular disease. South Asia has a high prevalence of sub-optimal HDL compared to other parts of the world. Intermittent fasting (IF) is a type of energy restriction which may improve serum HDL and other lipids thereby reducing the risk of cardiovascular diseases. Objective: The aim of the study was to evaluate the effect of IF on lipid profile and HDL-cholesterol in a sample of South Asian adults. Methods: A 6-week quasi-experimental (non-randomized) clinical trial was conducted on participants with low HDL (< 40 mg/dl for men and < 50 mg/dl for women). Participants of the control group were recommended not to change their diet. The intervention group was recommended to fast for ~12 h during day time, three times per week for 6 weeks. Pulse rate, blood pressure, body weight, waist circumference, serum lipid profile, and blood glucose levels were measured at baseline and after 6 weeks. Result: A total of 40 participants were enrolled in the study (N = 20 in each group), while 35 (20 control and 15 intervention) completed the trial and were included in data analysis of the study. Body measurements, including body weight, BMI and waist circumference, showed significant interaction effects (p's < 0.001), indicating that there were larger reductions in the IF group than in the control group. Significant interaction effects were also observed for total (p = 0.033), HDL (p = 0.0001), and LDL cholesterol (p = 0.010) with larger improvements in the IF group. Conclusion: This study suggests that intermittent fasting may protect cardiovascular health by improving the lipid profile and raising the sub-optimal HDL. Intermittent fasting may be adopted as a lifestyle intervention for the prevention, management and treatment of cardiovascular disorders. Clinical Trial Registration: NCT03805776, registered on January 16, 2019, https://clinicaltrials.gov/ct2/show/NCT03805776.

Cocoa Flavonoids Reduce Inflammation and Oxidative Stress in a Myocardial Ischemia-Reperfusion Experimental Model.

: Consumption of flavonoid-rich nutraceuticals has been associated with a reduction in coronary events. The present study analyzed the effects of cocoa flavonols on myocardial injury following acute coronary ischemia-reperfusion (I/R). A commercially available cocoa extract was identified by chromatographic mass spectrometry. Nineteen different phenolic compounds were identified and 250 mg of flavan-3-ols (procyanidin) were isolated in 1 g of extract. Oral administration of cocoa extract in incremental doses from 5 mg/kg up to 25 mg/kg daily for 15 days in Sprague Dawley rats (n = 30) produced a corresponding increase of blood serum polyphenols and become constant after 15 mg/kg. Consequently, the selected dose (15 mg/kg) of cocoa extract was administered orally daily for 15 days in a treated group (n = 10) and an untreated group served as control (n = 10). Both groups underwent surgical occlusion of the left anterior descending coronary artery and reperfusion. Cocoa extract treatment significantly reversed membrane peroxidation, nitro-oxidative stress, and decreased inflammatory markers (IL-6 and NF-kB) caused by myocardial I/R injury and enhanced activation of both p-Akt and p-Erk1/2. Daily administration of cocoa extract in rats is protective against myocardial I/R injury and attenuate nitro-oxidative stress, inflammation, and mitigates myocardial apoptosis.

Lung resistance-related protein (LRP) predicts favorable therapeutic outcome in Acute Myeloid Leukemia.

There is conflicting evidence that MDR1, MRP2 and LRP expression is responsible for chemotherapy resistance. We conducted this study to explore their role in AML therapy outcomes. Bone marrow and peripheral blood samples of 90 AML patients, receiving chemotherapy, were analyzed by real time PCR. Gene expression was calculated by the 2-ΔΔCt method. The patients who had a persistent remission were labelled 'Good Responder' (GRes) whereas, those with relapse or drug resistance were labelled 'Poor Responders' (PRes). Higher LRP expression in bone marrow, but not in peripheral blood, was positively associated with persistent remission (p = 0.001), GRes (p = 0.002), 1-year overall as well as disease-free survival (p = 0.02 and p = 0.007, respectively). Marrow and blood MDR1 and MRP2 expression did not differ significantly between the above groups. Logistic regression analysis showed that only a diagnosis of acute promyelocytic leukemia (APL; M3) or high marrow LRP expression significantly predicted a favorable therapeutic outcome. This is the first report showing that high bone marrow LRP expression predicts significant favorable therapeutic outcome. Peripheral blood LRP expression as well as marrow and blood MDR1 and MRP2 expression have no predictive value in AML patients treated with standard dose cytarabine and daunorubicin 3+7 regimen.

Gene expression of hENT1, dCK, CDA, dCMPD and topoisomerase IIα as an indicator of chemotherapy response in AML treated with cytarabine and daunorubicin.

PURPOSE: Acute myeloid leukemia patients are commonly treated with cytarabine (Ara-C) and anthracyclines but the sustained remission rate is not very promising. We explored the role of drug-metabolizing enzymes and transporters in the therapeutic response. PATIENTS AND METHODS: Bone marrow and peripheral blood samples of 90 newly diagnosed acute myeloid leukemia patients treated with standard 3+7 regimen were analyzed through real-time PCR for expression of human equilibrative nucleoside transporter 1, deoxycytidine kinase, cytidine deaminase (CDA), deoxycytidine monophosphate deaminase (dCMPD) and topoisomerase IIα (Topo-IIa). The expression of these markers was studied in relationship with good (persistent remission) and poor therapeutic response (relapse/resistance). RESULTS: High Topo-IIa expression in peripheral blood was associated with good response (P=0.006). Relapse was higher among low expressors of Topo-IIa in peripheral blood (OR: 26.25). Bone marrow Topo-IIa expression followed a similar trend but did not reach statistical significance. In contrast, patients with high bone marrow dCMPD expression had poor response (OR: 3; P=0.043). One-year disease-free survival (DFS) was better among those with high bone marrow Topo-IIa (P=0.04) or CDA (P=0.03) expression. High bone marrow Topo-IIa expression also had better DFS at 6 months (P=0.04) and at 12 months (P=0.04). CONCLUSION: High expression of Topo-IIa in peripheral blood is a favorable indicator of persistent remission, good therapeutic response and DFS. High dCMPD and low CDA expression in bone marrow is associated with poor therapeutic outcome.

Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?

PURPOSE: Many anticancer drugs induce apoptosis in malignant cells, and resistance to apoptosis could lead to suboptimal or no therapeutic benefit. Two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, act as a promoter and an inhibitor of apoptosis, respectively. Both Bax and Bcl-2 as well as their ratio have been regarded as prognostic markers in various cancers. However, conflicting results have been reported. A clear understanding of apoptosis has also become crucial due to reports about anti-Bcl-2 chemotherapy. We explored the relationship of Bax and Bcl-2 gene expression and their ratio with the therapeutic response in acute myeloid leukemia (AML) patients. PATIENTS AND METHODS: Bone marrow and/or blood samples from 90 AML patients treated with cytarabine and daunorubicin were included. Expression of Bax and Bcl-2 was determined through real-time polymerase chain reaction by using ΔΔCt method of relative expression. RESULTS: Bax and Bcl-2 expression among marrow and blood samples correlated with each other (rs=0.5, p<0.01). Although bone marrow expression of Bax and Bcl-2 tended to remain higher among responders (median 1.01 and 0.29, respectively) as compared to non-responders (median 0.66 and 0.24, respectively), the difference failed to reach statistical significance (U=784.5 and 733; p=0.68 and 0.28, respectively). Conversely, Bax/Bcl-2 ratio was higher among poor responders (median 3.07 vs 1.78), though again failed to reach statistical significance (U=698.5, p=0.07). CONCLUSION: Expression of Bax and Bcl-2 does not differ significantly among AML patients treated with cytarabine and daunorubicin in terms of remission, relapse, resistance, overall survival, and disease-free survival, thus questioning the utility of emerging anti-Bcl-2 therapy.

Association of serum C-reactive protein and LDL:HDL with myocardial infarction.

OBJECTIVE: To identify frequency of the following markers of atherosclerosis risk: high C-Reactive Protein (CRP) and ratio between serum levels of low density lipoprotein (LDL) and high density lipoprotein (HDL) and to determine the association of high serum CRP levels and LDL:HDL in the patients presenting at NICVD with first myocardial infarction. METHODS: This case control study was conducted at National Institute for Cardiovascular Disease (NICVD), in Karachi, comprising of 50 male patients of acute myocardial infarction (without any other co-morbidity) and 50 matching controls. RESULTS: In this study, CRP levels were significantly high (p = 0.003) and serum HDL levels significantly low (p = 0.006) in patients as compared to controls. Serum LDL levels and the ratio of LDL and HDL were not significantly different among the two groups. CONCLUSION: High serum CRP levels rather than high LDL:HDL are associated with myocardial infarction in the patients presenting at NICVD with first myocardial infarction.

Stress, anxiety, and depression among medical students in a multiethnic setting.

BACKGROUND: Contemporary literature suggests that medical education might adversely affect students' mental health. Alfaisal University in Riyadh, Saudi Arabia is a developing institution; hence, there has been a concern regarding the mental well-being of the students. OBJECTIVES: This study was designed to assess the traits of depression, anxiety, and stress among students in relation to potential underlying reasons. METHODS: All 575 medical students across the 5 years of study participated by filling out the Depression, Anxiety, and Stress Scale-21 (DASS-21) questionnaire anonymously twice. Firstly, 2-3 weeks before a major examination (pre-examination), and secondly, during regular classes (post-examination). Correlation was sought regarding sex, year of scholarship, attendance of a premedical university preparatory program (UPP), housing, and smoking. Subjective comments from students were also obtained. RESULTS: A total of 76.8% and 74.9% of students participated in pre-and post-examination groups, respectively. The majority were the children of expatriate workers in Saudi Arabia, and included Arabs, South Asians, and North Americans. Prevalence of depression, anxiety, and stress was high (43%, 63%, and 41%, respectively) which reduced (to 30%, 47%, and 30%, respectively) to some extent after examinations. Saudis and those who had attended UPP had higher DASS-21 scores. Smoking and female sex predicted higher levels of "baseline" depression, anxiety, or stress. The students perceived the curriculum and schedule to be the primary causes of their high DASS-21 scores. CONCLUSION: The students had high "baseline" traits of depression, anxiety, and stress, and these were higher if an examination was near, especially among Saudis and those who had attended UPP. Smoking and female sex predicted higher levels of "baseline" depression, anxiety, or stress. Students suggested that study burden and a busy schedule were the major reasons for their high DASS-21 scores.

Breast cancer pattern and chemotherapy response--an institutional study in Pakistan.

BACKGROUND: This study was planned to audit female breast cancers and their chemotherapy in a busy public sector institution. As a case-study, Pakistan provides an opportunity to explore the issue in a low-GDP, low-literacy, populous developing country. METHOD: Retrospective analysis of the records at Karachi Institute of Radiotherapy and Nuclear Medicine. RESULTS: A total of 3,431 female breast cancer patients presented during 2001-2008, half being <45 years, mostly suffering from infiltrating ductal carcinoma of breast. Further analyzing a subgroup of 183 consecutive patients over six months revealed that only 1.6% were at stage-I, whereas 75% had node-positive disease, including 19.1% with distant metastases. Some 41.6% were either high grade or poorly differentiated. The low grade tumors showed a two-fold likelihood of ER and PR positivity as compared to high grade lesions. 5-Flourouracil, doxorubicin and cyclophosphamide (FAC) constituted the most common chemotherapy. Earlier diagnosis was associated with complete remission. Overall, 33% developed myelotoxicity, more often if age ≥ 45 years (p=0.012), out of which 60% needed active correction. All those patients who did not experience a drop in total leukocyte count (TLC) below 4 x 109/L did not show complete remission. CONCLUSIONS: Infiltrating ductal carcinoma of the breast is the most common type. FAC is the most common chemotherapy. Tendency for late diagnosis, metastatic disease, treatment failure as well as leukopenia especially in ≥ 45 years is present. Failure to show leukopenia is suggestive of poor therapeutic outcome.