Associations of vitamin D receptor encoding gene variants with premenopausal breast cancer risk.

OBJECTIVE: This study evaluates whether vitamin D receptor (VDR) gene variations are associated with premenopausal breast cancer in Pakistani cohorts. METHODS: Genomic DNA was isolated from 228 breast cancer patients and 500 non-cancer controls. Six polymorphic variants (rs11568820, rs4516035, rs2228570, rs1544410, rs7975232, rs731236) of the VDR gene were genotyped using PCR-RFLP analysis. All statistical analysis was carried out on IBM-SPSS 23 at p-value <.05. Chi-square test and odds ratios (ORs) along with 95% confidence interval (CIs) were applied to evaluate the relationship between VDR gene polymorphisms and breast cancer. RESULTS: Results showed that the A/A genotype of EcoRV (OR = 2.125, 95% CI = 1.024 to 4.412) and the A/a genotype of Apa1 (OR = 6.094, 95%CI = 4.111 to 9.033) gene polymorphism had an increased risk of premenopausal breast cancer. No associations of the Bsm1 and Taq1 polymorphisms were observed in premenopausal women. Moreover, the Cdx2 GG (OR = 0.34, 95%CI = 0.192-0.602) genotype had a significant protective effect on breast cancer. However, strong LD was existed between Bsm1/Taq1 (D' = 0.757, CI = 0.67-0.82) and Apa1/Taq1 (D' = 0.695, CI = 0.6-0.77). Haplotype analysis showed no association between premenopausal breast cancer and VDR haplotypes. CONCLUSION: These analyses indicates that the VDR EcoRV A/A and Apa1 A/a genotypes may be risk factors for breast cancer development among premenopausal women.

Outcome of Impella 2.5 use in patients undergoing Percutaneous Coronary Intervention in Henan, China: a case series.

BACKGROUND: Acute myocardial infarction (AMI) complicated by cardiogenic shock (AMI-CS) or heart failure is associated with an unacceptably high in-hospital mortality of 33%-55% and a lost chance to accept PCI (Percutaneous Coronary Intervention). AIM: The aim of the study was to find out whether percutaneous hemodynamic support device Impella 2.5 improves prognosis of high-risk PCI patients or not. METHODS: This study was a case series involving six patients who underwent a Left Ventricular Assist Device (LVAD, Impella 2.5, Abiomed, Danvers, MA) implantation after suffering from AMI with a very low ejection fraction and acute heart failure. The clinical experience and outcomes of the patients are hereby discussed. RESULTS: All PCI procedures were safely completed under LVAD support. The hemodynamic parameters of all patients improved clinically over the next 30 days and following 12 months after Impella insertion except in two patients, of which one patient (Case number 6) died 4 days post-Impella protected PCI procedure due to acute left ventricle heart failure with cardiogenic shock and pulmonary oedema; and another one died at 12 months after Impella protected PCI procedure (Case number 4) due to decompensated heart failure and infected pneumonia. CONCLUSION: Percutaneous hemodynamic support is favorable and feasible during high risk Percutaneous Coronary Intervention (PCI). A bigger study is needed to substantiate the claims of the current study.

Estimates of past and future time trends in age-specific breast cancer incidence among women in Karachi, Pakistan: 2004-2025.

BACKGROUND: The current demographic trends indicate that breast cancer will pose an even greater public health concern in future for Pakistan. Details on the incidence, disease severity and mortality in respect of breast cancer are limited and without such data, therefore, future health policies or systems in respect of this disease cannot be strategically planned or implemented. The aim of this study was to examine past trends of age-specific breast cancer incidence rates (2004-2015), and to estimate the future volume of breast cancer cases in Karachi through the year 2025. METHODS: Two statistical methods, namely the functional time series models and the log-linear regression model were used; additionally, their real forecasting efficacy in epidemic time series was also evaluated. RESULTS: In the past, women aged 60-64 years had the highest overall breast cancer incidence rates, while from 2016 to 2025, large increases in breast cancer rates among women aged 50 to 64 years are expected. The total projected breast cancer incidence will increase by approximately 23.1% in 2020 to 60.7% in 2025. Cases of breast cancer diagnosed in younger women, aged 30-34 years, will increase from 70.7 to 130.6% in 2020 and 2025 relative to 2015. CONCLUSIONS: The breast cancer incidence appeared to have been rising more rapidly among post-menopausal women (aged 55 to 59), while a stable increase in incidence in the youngest age group (15-29 years) of women is expected. The results also infer an expected increase in incidence cases of breast cancer among middle aged women in Karachi, Pakistan. An increase in the number of incident cases of cancer has implications for understanding the health-care needs of growing population and the subsequent demands on health-care system.

A novel STM for quality atomic resolution with piezoelectric motor of high compactness and simplicity.

Scanning tunneling microscope (STM) is a renowned scientific tool for obtaining high-resolution atomic images of materials. Herein, we present an innovative design of the scanning unit with a compact yet powerful inertial piezoelectric motor inspired by the Spider Drive motor principle. The scanning unit mainly consists of a small 9 mm long piezoelectric tube scanner (PTS), one end of which is coaxially connected to the main sapphire body of the STM. Of particular emphasis in this design is the piezoelectric shaft (PS), constructed from piezoelectric material instead of conventional metallic or zirconium materials. The PS is a rectangular piezoelectric stack composed of two piezoelectric plates, which are elastically clamped on the inner wall of the PTS via a spring strip. The PTS and PS expand and contract independently with each other to improve the inertial force and reduce the threshold voltage. To ensure the stability of the PS and balance the stepping performance of the inertial motor, a counterweight, and a matching conical spring are fixed at the tail of the PS. This innovative design allows for the assessment of scanning unit performance by applying a driving signal, threshold voltage is 50 V at room temperature. Step sizes vary from 0.1 to 1 µm by changing the driving signal at room temperature. Furthermore, we successfully obtained atomic-resolution images of a highly oriented pyrolytic graphite (HOPG) sample and low drift rates of 23.4 pm/min and 34.6 pm/min in X-Y plane and Z direction, respectively, under ambient conditions. This small, compact STM unit has the potential for the development of a rotatable STM for use in cryogen-free magnets, and superconducting magnets.

A rigid and compact piezoelectric motor with high output efficiency.

We introduce a novel piezoelectric stepper motor featuring high compactness, rigidity, and any direction operability. Here, not only is the structure of high novelty but also the working principle very simple. The piezo stacks unit is sandwiched between two spring finger pieces, with almost equal clamping forces applied between the top of the piezo stacks' unit and the spring finger piece. Applying individual driving signals to each of the five piezo stack pairs, causing deformation one by one in the same direction, followed by simultaneous recovery in the reverse direction, enables movement of the frame part. The optimized clamping force of the piezoelectric stack units and spring fingers ensures maximum output force. The motor's operational capability at low threshold voltages, specifically 8 V for downward movement and 10 V for upward movement, confirmed its efficacy in both vertical and horizontal directions. The motor's operational capability at a low threshold voltage of 10 V confirmed its efficacy in both vertical and horizontal directions. At room temperature, step size ranges from 0.3 to 7.4 µm at 20 Hz frequency and varying driving voltage from 10 to 180 V. It has a maximum travel range of about 5 mm and can lift a maximum load of 220 g in an upward direction, so the maximum output force generated by this motor is 2.2 N. The compact and rigid design is capable of building an atomically resolved scanning probe microscope, and its working ability has the potential to use the cleavage of different types of samples in limited space environments, such as the small-bore superconducting magnet and low temperature.

Protein-C deficiency presenting as pulmonary embolism and myocardial infarction in the same patient.

Plasma protein-C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis occurring as a result of congenital protein-C deficiency is still controversial. We describe a young patient with heterozygous protein-C deficiency who experienced both pulmonary embolism as well as myocardial infarction due to thrombotic occlusion without underlying major risk factors. Acute myocardial infarction in young without underlying major risk factors may be evaluated for protein c deficiency.

Transcatheter aortic valve implantation with Core Valve: first Indian experience of three high surgical risk patients with severe aortic stenosis.

The prevalence of aortic stenosis is increasing with aging population. However with multiple co-morbidities and prior procedures in this aging population, more and more patients are being declared unfit for the 'Gold Standard' treatment i.e. surgical aortic valve replacement (AVR). Among the patients who are unfit or high risk for aortic valve replacement (AVR) by open heart surgery, transcatheter aortic valve implantation (TAVI) has been proven to be a valuable alternative improving survival and quality of life. We report first Indian experience of Core Valve (Medtronic Inc.) implantation in three high surgical risk patients performed on 22nd and 23rd February 2012.

The Effects of the SARS-CoV-2 Virus on the Cardiovascular System and Coagulation State Leading to Cardiovascular Diseases: A Narrative Review.

The novel coronavirus pandemic has led to morbidity and mortality throughout the world. Until now, it is a highly virulent contagion attacking the respiratory system in humans, especially people with chronic diseases and the elderly who are most vulnerable. A majority of afflicted are those suffering from cardiovascular and coronary diseases. In this review article, an attempt has been made to discuss and thoroughly review the mode of therapies that alleviate cardiac complications and complications due to hypercoagulation in patients infected with the SARS-CoV-2 virus. Presently a host of thrombolytic drugs are in use like Prourokinase, Retelapse, RhTNK-tPA and Urokinase. However, thrombolytic therapy, especially if given intravenously, is associated with a serious risk of intracranial haemorrhage, systemic haemorrhage, immunologic complications, hypotension and myocardial rupture. The effects of the SARS-CoV-2 virus upon the cardiovascular system and coagulation state of the body are being closely studied. In connection to the same, clinical prognosis and complications of thrombolytic therapy are being scrutinized. It is noteworthy to mention that myocardial oxygen supply/demand mismatch, direct myocardial cells injury and acute plaque rupture are the multiple mechanisms responsible for acute coronary syndrome and cardiac complications in Covid-19 infection. However, this review has limitations as data available in this context is limited, scattered and heterogenous that questions the reliability of the same. So, more multi-centric studies involving representative populations, carried out meticulously, could further assist in responding better to cardiac complications among Covid-19 patients.

Association of low penetrance vitamin D receptor Tru9I (rs757343) gene polymorphism with risk of premenopausal breast cancer.

Objective The aim of this study was to determine whether a novel polymorphism ( Tru9I) in the low penetrance vitamin D receptor (VDR) gene is associated with risk of premenopausal breast cancer (BC). Methods This case-control study included 228 patients with BC and 503 healthy women living in Pakistan who were analyzed for the VDR Tru9I (rs757343) single nucleotide polymorphism. BC cases were histopathologically confirmed, and all healthy controls were age-matched with patients (age range, 20-45 years). DNA was extracted, and the polymerase chain reaction and restriction fragment length polymorphism assays were performed. Results The VDR Tru9I polymorphism was not significantly associated with premenopausal BC. However, the risk of BC was associated with the 'uu' genotype (odds ratio [OR], 1.141; 95% confidence interval [95% CI], 0.206-6.317). Further, mutant Tru9I was significantly associated with Grade IV carcinoma (OR, 5.36; 95% CI, 1.181-24.338). Conclusion The VDR Tru9I 'uu' genotype may increase the risk of premenopausal BC.

Vitamin D receptor Cdx-2 polymorphism and premenopausal breast cancer risk in southern Pakistani patients.

BACKGROUND: Vitamin D3 is a secoster oid that exerts its effect by binding to its nuclear receptor called vitamin D receptor (VDR), inducing apoptosis and thereby inhibiting cell proliferation in cancer cells. The VDR receptor, located in the nucleus, is known to regulate the functions of over 200 genes. Various allelic forms of hVDR have been discovered that increase susceptibility to various cancers. The VDR-Cdx2 polymorphism, located in the promoter region of exon 1e in the VDR gene, influences the functional activity of the receptor, since the hVDR lacks consensus TATA and CAAT boxes. The current investigation examines the association between VDR-Cdx2 polymorphism and breast cancer in premenopausal females from Southern Pakistan. METHODS: We conducted a case control study on 264 subjects (103 cases and 161 controls) who were recruited from a tertiary hospital located in Karachi, Pakistan. Genomic DNA was extracted from peripheral blood using a commercial kit method, and the VDR-Cdx2 polymorphism was genotyped using tetraprimer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method. Pearson chi square test was used to assess the association between VDR-Cdx2 genotype and breast cancer while genotype distribution in controls was evaluated by Hardy-Weinberg equilibrium (HWE). Breast cancer risk was calculated using odds ratios and 95% confidence intervals. RESULTS: The genotype distribution in the control group was in HWE (p > 0.05) for the VDR-Cdx2 polymorphism. A non-significant association was observed between VDR cdx2 polymorphism and breast cancer, however the GG genotype was at risk (OR = 1.832, 95% CI = 0.695-4.828) of developing breast cancer. CONCLUSION: The GG genotype of Cdx2-VDR gene polymorphism may increase the risk of developing breast cancer in young female patients in South Pakistan. Further investigations examining additional single nucleotide polymorphisms (SNPs) in VDR are required to assess their relationships with breast cancer.

Transcatheter aortic valve implantation under conscious sedation - the first Indian experience.

Transcatheter aortic valve implantation (TAVI) is maturing strongly as an alternative to surgical aortic valve replacement (SAVR) in patients who are inoperable/high risk for open heart surgery. General anesthesia (GA) is the usual mode of anesthesia in these patients, but local anesthesia with conscious sedation (LACS) has recently been described as a safe alternative with some added advantages. We report 2 cases who were unfit for GA and were done successfully under LACS.

In vivo dosimetry with diodes in a radiotherapy department in Pakistan.

The International Commission of Radiological Units (ICRU) sets a tolerance of ±5 % on dose delivery, with more recent data limiting the overall tolerances to ±3 %. One of the best methods for accurate dose delivery and quality check is in vivo dosimetry, while radiotherapy is performed. The present study was carried out to test the applicability of diodes for performing in vivo entrance dose measurements in external photon beam radiotherapy for pelvic tumours and its implementation as quality assurance tool in radiotherapy. During November 2007 to December 2009, in 300 patients who received pelvic radiotherapy on a multileaf-collimator-assisted linear accelerator, the central axis dose was measured by in vivo dosimetry by p-Si diodes. Entrance dose measurements were taken by diodes and were compared with the prescribed dose. Totally 1000 calculations were performed. The mean and standard deviation between measured and prescribed dose was 1.26 ± 2.8 %. In 938 measurements (93.8 %), the deviation was <5 % (1.36 ± 2.9%); in 62 measurements (6.2 %) the mean deviation was >5 % (5.51 ± 2.3 %). Larger variations were seen in lateral and oblique fields more than anteroposterior fields. For larger deviations, patients and diode positional errors were found to be the common factors alone or in combination with other factors. After additional corrections, repeated measurements were achieved within tolerance levels. This study showed that diode-detector-based in vivo dosimetry was simple, cost-effective, provides quick results and can serve as a useful quality assurance tool in radiotherapy. The data acquired in the present study can be used for evaluating output calibration of therapy machine, precision of calculations, effectiveness of treatment plan and patient setup.