Routine Antenatal Echocardiography in High-Prevalence Areas of Rheumatic Heart Disease: A WHO-Guideline Systematic Review.

Background: Rheumatic Heart Disease (RHD) is the most common cause of valvular heart disease worldwide. Undiagnosed or untreated RHD can complicate pregnancy and lead to poor maternal and fetal outcomes and is a significant factor in non-obstetric morbidity. Echocardiography has an emerging role in screening for RHD. We aimed to critically analyse the evidence on the use of echocardiography for screening pregnant women for RHD in high-prevalence areas. Methods: We searched MEDLINE and Embase to identify the relevant reports. Two independent reviewers assessed the reports against the eligibility criteria in a double-blind process. Results: The searches (date: 4 April 2023) identified 432 records for screening. Ten non-controlled observational studies were identified, five using portable or handheld echocardiography, comprising data from 23,166 women. Prevalence of RHD varied across the studies, ranging from 0.4 to 6.6% (I2, heterogeneity >90%). Other cardiac abnormalities (e.g., congenital heart disease and left ventricular systolic dysfunction) were also detected <1% to 2% of cases. Certainty of evidence was very low. Conclusion: Echocardiography as part of antenatal care in high-prevalence areas may detect RHD or other cardiac abnormalities in asymptomatic pregnant women, potentially reducing the rates of disease progression and adverse labor-associated outcomes. However, this evidence is affected by the low certainty of evidence, and lack of studies comparing echocardiography versus standard antenatal care. Prospective Registration: PROSPERO 2022 July 4; CRD42022344081 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=344081. Research question: 'In areas with a high prevalence of rheumatic heart disease, should handheld echocardiography be added to routine antenatal care?'

p21 Protein Outperforms Clinico-pathological Criteria in Predicting Liver Metastases in Pancreatic Endocrine Tumors.

BACKGROUND/AIM: P21 is a cyclin-dependent kinase inhibitor regulating the cell cycle as a tumor suppressor. Using a p21 immunohistochemistry (IHC) assay, we compared tumor p21 levels with conventional clinico-pathological criteria in primary pancreatic endocrine tumor subsets with and without liver metastases. MATERIALS AND METHODS: Sections from tissue microarray (TMA) including 13 archival metastatic primary and 18 non-metastatic primary pancreatic endocrine carcinomas/tumors (MP-PECAs/NMP-PETs) were stained with a monoclonal anti-p21WAFI,CIP primary antibody. Tumor p21 IHCs were scored as the sum of intensity (0-3) and proportion scores (0-5) (Total Allred score: 0-8), and as p21% labelling index in the tumor. ROC curve analysis was used for most optimal p21 score cut-off (4 or >) and Fisher's exact test was used to compare the association among tumor p21 scores, conventional prognostic criteria, and liver metastases. RESULTS: For PET/PECA patients, mean ages were 55.6 years (27-73) and 49.3 years (28-71), M/F ratios were 7/11 and 7/6. Mean p21 labelling index (%) for MP- PECAs was 24% (range=3-63%) vs. 9% for NMP-PETs (range=1-25%) (p=0.022). The mean p21 index in MP-PECAs was significantly higher (24%) as compared to PIs (7%) (p=0.0047). Using a p21 Allred score of ≥4, high p21 IHC score had strong association with the presence of liver metastases (p-value <0.001). High tumor p21 IHC score had a 93% sensitivity, 68% specificity, 78% predictive accuracy, 66% positive, and 94% negative predictive values. CONCLUSION: In patients with primary PETs, p21 IHC is superior to conventional criteria in predicting presence or absence of liver metastases.

Expression deregulation of matrix metalloproteinases and vasoconstriction related genes in Pakistani females with abnormal uterine bleeding.

BACKGROUND: Abnormal uterine bleeding (AUB) is irregular menstrual bleeding which has great impact on female health and life style. Various genetic factors are involved in etiology and pathology of AUB. Present study was designed to explore the association of PTGFR, MMP9, MMP2, TGFB3 and VEGFB with AUB. METHODS: Blood samples of 212 females with AUB were collected along with age-matched healthy control. Expression variation of targeted genes was evaluated using qPCR. Present study cohort was divided into different groups based on demographic parameters and all targeted genes were correlated with study demographics. RESULTS: Expression of targeted genes was significantly (P < 0.001) downregulated in females with AUB compared to control. Reduced (P < 0.01) expression of targeted genes was observed in all age groups (21-30, 31-40, 41-50 year) of AUB patients compared to respective control. Expression of VEGFB increased (P < 0.05) in AUB females with > 9 days bleeding compared to AUB patient had < 9 days bleeding. AUB women with miscarriage history showed upregulation in MMP2, TGFB3 (P < 0.05), and downregulation in MMP9 and VEGFB (P < 0.05) expression compared to AUB group with no miscarriage history. Expression of MMP2 increased (P < 0.05) in AUB females with > 60 kg body weigh compared to AUB patient with < 60 kg weight. CONCLUSION: Present study open a new window for diagnosis of AUB at early stages and suggested a possible involvement of PTGFR, MMP9, MMP2, TGFB3 and VEGFB as candidate biomarkers in AUB.

Morphological and Molecular Characterization of Tylenchorhynchus Clarus Allen, 1955 and T. Zeae Sethi & Swarup, 1968 (Rhabditida: Telotylenchidae) from Iraq.

During a survey on the biodiversity of plant-parasitic nematodes in Misan province (southeast Iraq), Tylenchorhynchus clarus and T. zeae were discovered around the rhizosphere of sugarcane and pumpkin, respectively. The morphological and morphometric data were provided for the recovered species. The morphological characters of both populations are in agreement with the type populations and other populations of them. To the best of our knowledge, this is the first report of these two species from Iraq, and a first report of the association of T. zeae with pumpkin. Molecular phylogenetic analyses of the Iraqi populations of T. clarus and T. zeae using the D2-D3 expansion segments of 28S rDNA and internal transcribed spacer (ITS) rDNA sequences using Bayesian inference (BI), showed they form maximally supported clades with other sequences of both species.

A facile synthesis of CeO2 from the GO@Ce-MOF precursor and its efficient performance in the oxygen evolution reaction.

Electrochemical water splitting has enticed fascinating consideration as a key conduit for the advancement of renewable energy systems. Fabricating adequate electrocatalysts for water splitting is fervently preferred to curtail their overpotentials and hasten practical utilizations. In this work, a series of Ce-MOF, GO@Ce-MOF, calcinated Ce-MOF, and calcinated GO@Ce-MOF were synthesized and used as high-proficient electrocatalysts for the oxygen evolution reaction. The physicochemical characteristics of the prepared samples were measured by diverse analytical techniques including SEM, HRTEM, FTIR, BET, XPS, XRD, and EDX. All materials underwent cyclic voltammetry tests and were evaluated by electrochemical impedance spectroscopy and oxygen evolution reaction. Ce-MOF, GO@Ce-MOF, calcinated Ce-MOF, and calcinated GO@Ce-MOF have remarkable properties such as enhanced specific surface area, improved catalytic performance, and outstanding permanency in the alkaline solution (KOH). These factors upsurge ECSA and intensify the OER performance of the prepared materials. More exposed surface active-sites present in calcinated GO@Ce-MOF could be the logic for superior electrocatalytic activity. Chronoamperometry of the catalyst for 15°h divulges long-term stability of Ce-MOF during OER. Impedance measurements indicate higher conductivity of synthesized catalysts, facilitating the charge transfer reaction during electrochemical water splitting. This study will open up a new itinerary for conspiring highly ordered MOF-based surface active resources for distinct electrochemical energy applications.

Fyn and Lyn gene polymorphisms impact the risk of thyroid cancer.

Thyroid cancer is the most common malignancy of the endocrine glands, and during last couple of decades, its incidence has risen alarmingly, across the globe. Etiology of thyroid cancer is still debatable. There are a few worth mentioning risk factors which contribute to initiation of abnormalities in thyroid gland leading to cancer. Genetic instability is major risk factors in thyroid carcinogenesis. Among the genetic factors, the Src family of genes (Src, Yes1, Fyn and Lyn) have been implicated in many cancers but there is little data regarding the association of these (Src, Yes1, Fyn and Lyn) genes with thyroid carcinogenesis. Fyn and Lyn genes of Src family found engaged in proliferation, migration, invasion, angiogenesis, and metastasis in different cancers. This study was planned to examine the effect of Fyn and Lyn SNPs on thyroid cancer risk in Pakistani population in 500 patients and 500 controls. Three polymorphisms of Fyn gene (rs6916861, rs2182644 and rs12910) and three polymorphisms of Lyn gene (rs2668011, rs45587541 and rs45489500) were analyzed using Tetra-primer ARMS-PCR followed by DNA sequencing. SNP rs6916861 of Fyn gene mutant genotype (CC) showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs2182644 of Fyn gene, mutant genotype (AA) indicated statistically significant 17-fold increased risk of thyroid cancer (P < 0.0001). Statistically significant threefold increased risk of thyroid cancer was observed in genotype AC (P < 0.0001) of Fyn gene polymorphism rs12910. In SNP rs2668011 of Lyn gene, TT genotype showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs45587541 of Lyn gene, GA genotypes showed statistically significant 11-fold increased risk in thyroid cancer (P < 0.0001). Haplotype analysis revealed that AAATAG*, AGACAG*, AGCCAA*, AGCCAG*, CAATAG*, CGCCAG* and CGCCGA* haplotypes of Fyn and Lyn polymorphisms are associated with increased thyroid cancer risk. These results showed that genotypes and allele distribution of Fyn and Lyn are significantly linked with increased thyroid cancer risk and could be genetic adjuster for said disease.

Non-neoplastic pathologies mimicking sarcoma - Experience from a tertiary referral centre multidisciplinary team.

OBJECTIVE: Distinguishing non-neoplastic tumour-mimicking pathologies from bone and soft tissue tumours is one of the fundamental aims of a tertiary centre sarcoma multidisciplinary team (MDT) service. In this study, we aim to analyse the incidence of non-neoplastic lesions referred to a tertiary referral service as suspected sarcoma, and to analyse the spectrum of conditions comprising these tumour-mimicking pathologies. MATERIALS AND METHODS: We conducted a retrospective observational study compiling the biopsy-proven non-neoplastic outcomes of suspected sarcoma cases referred to our MDT in the last year. We identified all referrals made to our service between 1st January 2020 and 31st December 2020 and compiled their histological diagnoses. RESULTS: A total of 976 new cases were referred to our MDT as suspected sarcoma in one year. Of these referrals, 8.6% (84/976) received a biopsy-proven outcome of non-neoplastic pathology. These non-neoplastic outcomes were categorised into the following types of pathology: 32.1% vascular, 31.0% inflammatory, 14.3% traumatic, 6.0% degenerative, 6.0% idiopathic, 4.8% infective, 3.6% metabolic, 1.2% autoimmune, and 1.2% genetic. CONCLUSION: A significant proportion of pathologies referred to a tertiary centre sarcoma MDT are non-neoplastic in nature. These lesions are made up of a range of pathologies, with vascular and inflammatory conditions being the most common. Our study, the first of its kind, offers clinicians an insight into tumour-mimicking pathologies encountered by a tertiary centre.

Role of Chk1 gene in molecular classification and prognosis of gastric cancer using immunohistochemistry and LORD-Q assay.

Purpose: The aim of the current study was to assess the prognostic value of the Chk1 gene in the DNA damage response pathway in gastric cancer (GC). Methods: Expression levels of the Chk1 were measured in 220 GC tumor tissues and adjacent healthy/noncancerous tissues using real-time PCR and immunohistochemical staining. Genomic instability in GC patients was measured using the long-run real-time PCR technique for DNA-damage quantification assay and comet assay. Results: Significantly downregulated expression of Chk1 was observed at the mRNA level (p < 0.0001) and protein level (p < 0.0001). Significantly increased frequency of lesions/10 kb and comets was observed in tumor tissues compared with control tissues. Conclusion: The data suggest that downregulated expression of Chk1 and positive Heliobacter pylori infection status may have prognostic significance in GC.

A Comparison of Outcomes of 'Extensor Carpi Ulnaris Tenodesis' versus 'No Tenodesis' after Resection of the Distal Ulna in Patients with Giant Cell Tumor.

Background: One of the methods of stabilizing the stump of the ulna following resection of the distal ulna is tenodesis of the extensor carpi ulnaris (ECU). Some studies have recommended stabilization, whereas others have not found it useful. Most of these studies have a mix of different pathologies and often do not have a control group. The aim of this study is to compare the outcomes of ECU tenodesis versus no tenodesis after resection of the distal ulna in patients with grade III giant cell tumor (GCT) of the distal ulna. Methods: The retrospective study included 10 patients with Campanacci grade III GCT of the distal ulna treated by resection of the distal ulna between 2014 and 2019. Patients were stratified into two groups based on whether they underwent ECU tenodesis (n = 5) or no tenodesis (n = 5). The patients were assessed at 6 weeks, 6 months, and 12 months for complications and outcomes using the Mayo wrist score (MWS) and the revised musculoskeletal tumor society score (MSTS). Results: The MWS and the MSTS were significantly better in the ECU tenodesis group at 6 weeks. At 6 months, MWS was similar in both groups, but MSTS continued to be significantly better in ECU tenodesis group. At 12 months, both groups reported similar MWS and MSTS. There were no recurrences in either groups. One patient in the ECU tenodesis group developed ECU tendonitis that resolved with conservative treatment. Conclusions: The outcomes of ECU tenodesis were better in the short term (6 months), although both groups reported similar outcomes at 12 months. Level of Evidence: Level III (Therapeutic).

Genetic interactions of mitochondrial sirtuins in brain tumorigenesis.

Purpose: The present study was designed to understand the role of expression variations of mitochondrial imported sirtuins in brain tumorigenesis. The expression levels of mitochondrial imported sirtuins were further analyzed for biomarker potential. Methods: Samples from 200 brain tumors and 200 healthy control tissues were used for expression analysis using quantitative PCR and for DNA damage using LORD-Q analysis. Results: Significant deregulation of SIRT3 (p = 0.002), SIRT4 (p = 0.03) and SIRT5 (p = 0.006) was observed in brain tumors versus controls. Co-expression analysis showed a significant correlation between the mitochondrial imported sirtuins versus apoptotic genes. LORD-Q analysis showed a significantly increased frequency of lesions/10 kb of mitochondrial imported sirtuins (p < 0.0001) in brain tumor tissue versus controls. Conclusion: The present study showed a correlation between variations of mitochondrial imported sirtuins and increased brain tumor risk.

Mitochondrial sirtuins genetic variations and gastric cancer risk: Evidence from retrospective observational study.

AIMS: The purpose of the present study was to analyze the role of selected polymorphisms of SIRT3 and SIRT5 in gastric carcinogenesis. METHODS: For this study, 500 blood samples of GC patients and 500 blood samples of healthy individuals were collected. Six selected polymorphisms of mitochondrial sirtuins were analyzed for analysis using Tetra-Arms PCR followed by DNA sequencing. RESULTS: Mutant allele frequencies of selected polymorphisms [rs3782116 (p < 0.0001), rs6598072 (p < 0.0001) and rs11246020 (p < 0.0001), rs938222 (p = 0.0136), rs3757261 (p = 0.0005) and rs2841511 (p = 0.0015)] were observed significant higher in GC patients vs controls. Haplotype analysis was performed, and 51 haplotypes were generated using haploview software. Among these haplotypes, eleven haplotypes were found associated with a significantly increased risk of GC. Furthermore, SNP-SNP interaction showed a significant correlation between studied SNPs and GC risk. Kaplan Meier analysis showed that mutant allele frequencies of selected polymorphisms are linked with a significant decrease in survival of GC patients CONCLUSIONS: It can be concluded that selected SNPs may be associated with enhanced risk of GC and hence can be potential prognostic markers for prognosis and predisposition of GC.

Deregulation of mitochondrial sirtuins and OGG1-2a acts as a prognostic and diagnostic biomarker in leukemia.

Purpose: The present study was planned to explore the expression variations of mitochondrial sirtuins and the mitochondrial DNA repair enzyme OGG1-2a in leukemia patients. Oxidative stress and deacetylation levels of leukemia patients were measured in the present study. Methods: A total of 200 leukemia patients along with 200 healthy controls were evaluated using quantitative PCR, 8OXOG assay and deacetylation assay. Results: Significant deregulation of SIRT3 (p < 0.0001), SIRT4 (p < 0.0001), SIRT5 (p < 0.0001), Ki-67 (p < 0.0001) and OGG1-2a (p < 0.0001) was detected in patients versus controls. Survival analysis showed that deregulation of said genes was associated with decreased survival of leukemia patients (SIRT3: p < 0.004; SIRT4: p < 0.0009; SIRT5: p < 0.0001; OGG1-2a: p < 0.03). Receiver operating characteristic curve analysis confirmed the diagnostic values of selected genes in leukemia patients. Levels of 8OXOG adducts were measured, and significantly increased 8OXOG adduct levels were observed in patients versus controls. Conclusion: These data suggest that deregulation of SIRT3, SIRT4, SIRT5 and OGG1-2a acts as a diagnostic and prognostic marker in leukemia.

Lay abstract Leukemia is a type of blood cancer that has shown an increased rate of occurrence worldwide. Studies have shown that environmental and genetic factors are involved in the increased rate of this disease. Of the genetic factors, sirtuins (SIRT3, SIRT4 and SIRT5) and OGG1-2a have not been studied in leukemia. In the present study, the authors aimed to study the genetic/epigenetic changes in these genes in leukemia patients. Results of the present study showed involvement of selected gene variations in the increased rate of leukemia, at least in the Pakistani population.

Polymorphism in miRNA target sites of CEP-63 and CEP-152 ring complex influences expression of CEP genes and favors tumorigenesis in glioma.

Purpose: The present study was designed to screen the genetic polymorphisms and expression profiling of CEP-152 and CEP-63 genes in brain tumor patients. Methods: The amplification refractory mutation system PCR technique (ARMS-PCR) was used for mutation analysis using 300 blood samples of brain tumor patients and 300 overtly healthy controls. For expression analysis, 150 brain tumor tissue samples along with adjacent uninvolved/normal tissues (controls) were collected. Results: A significantly higher frequency of the mutant genotype of the CEP-152 single nucleotide polymorphism (rs2169757) and CEP-63 single nucleotide polymorphisms (rs9809619 and rs13060247) was observed in patients versus overtly healthy controls. The authors' results showed highly significant deregulation of CEP-152 (p < 0.0001) and CEP-63 (p < 0.0001) in glioma/meningioma tumor tissues versus adjacent normal tissue. Conclusion: The present study showed that variations in CEP-152 and CEP-63 genes were associated with an increased risk of brain tumor.

Lay abstract The purpose of this research was to explore the role of CEP-63 and CEP-152 in brain tumors in the Pakistani population. Loss of function or genetic deletion of these genes results in a mismatch of cell cycle, culminating in a cell phenotype conducive to transformation and tumorigenesis in different regions, including the brain region. Brain tumor is the most common cancer and the second most common cause of cancer death in Asia. The highest incidence rates are observed in Eastern Asia, including Pakistan. The aim of this research was initially to detect genetic variations of CEP-63 and CEP-152 in brain tumor patients. Secondly, expression variation of CEP-63 and CEP-152 was also examined in brain tumor cohort. Results from present study showed the significant involvement of CEP-63 and CEP-152 variations in brain carcinogenesis. Further analysis showed that CEP genes variations may act as predictive or prognostic markers for brain cancer.

Chromosome 5 harbors two independent deletion hotspots at 5q13 and 5q21 that characterize biologically different subsets of aggressive prostate cancer.

Deletion of chromosome 5q is common in prostate cancer and is linked to aggressive disease. Most previous studies focused on 5q21 where CHD1 is located, but deletion of mapping studies has identified a second deletion hotspot at 5q13. To clarify the prevalence and clinical relevance of 5q13 deletions and to determine the relative importance of 5q13 and 5q21 abnormalities, a tissue microarray containing samples from 12 427 prostate cancers was analyzed by fluorescence in situ hybridization. Deletion of 5q13 and 5q21 was found in 13.5% and 10%, respectively, of 7932 successfully analyzed cancers. Deletion was restricted to 5q13 in 49.4% and to 5q21 in 32.0% of cancers with a 5q deletion. Only 18.6% of 5q-deleted cancers had deletions of both loci. Both 5q13 and 5q21 deletions were significantly linked to advanced tumor stage, high Gleason grade, nodal metastasis and early biochemical recurrence (P < .005 each). Cancers with co-deletion of 5q13 and 5q21 had a worse prognosis than cancers with isolated 5q13 or 5q21 deletion (P = .0080). Comparison with TMPRSS2:ERG fusion status revealed that 5q21 deletions were tightly linked to ERG negativity (P < .0001) while 5q13 deletions were unrelated to the ERG status. In summary, 5q13 deletion and 5q21 deletion are common, but independent genomic alterations with different functional effects lead to aggressive prostate cancer.

Neuropeptide S receptor gene Asn107 polymorphism in obese male individuals in Pakistan.

Neuropeptide S (NPS) is a naturally occurring appetite stimulant, associated with anxiety, stress, and excitement regulation. Neuropeptide S serves as a hypothalamic energy regulator that enhances food intake with a reduced level of satiety. NPS activates fat angiogenesis and the proliferation of new adipocytes in obesity. NPS has an established role in energy regulation by many pre-clinical investigations; however we have limited data available to support this notion in humans. We found significant association of Neuropeptide S receptor (NPSR1) Asn107Ile (rs324981, A>T) polymorphism with obese male participants. The current investigation carried out genotype screening of NPSR1 allele to assess the spectrum of the Asn107Ile polymorphism in obese and healthy Pakistani individuals. We revealed a significant (p = 0.04) difference between AA vs TT + AT genotype distribution of NPSR1 (SNP rs324981,) between obese and healthy individuals (p = 0.04). In this genotype analysis of (SNP rs324981) of the NPSR1 gene, T allele was marked as risk allele with higher frequency in the obese (38%) compared to its frequency in the controls (25%). Single Nucleotide Polymorphism (SNP, rs324981) Asn107Ile of NPSR1gene, that switches an amino acid from Asn to Ile, has been found associated with increased susceptibility to obesity in Pakistani individuals. Furthermore, molecular simulation studies predicted a lower binding affinity of NPSR1 Asn107Ile variant to NPS than the wild-type consistent with the genotype studies. These molecular simulation studies predict a possible molecular mechanism of this interaction by defining the key amino acid residues. However, a significantly (p<0.0001) lower concentration of NPS was recorded independent of genotype frequencies in obese subjects compared to healthy controls. We believe that large scale polymorphism data of population for important gene players including NPSR1 will be more useful to understand obesity and its associated risk factors.

Trends of utilization of Complete Blood Count parameters for patient management among doctors in Azad Kashmir.

OBJECTIVE: To determine the trends of utilization of CBC parameters in patient management among doctors in different hospitals in Kashmir, Pakistan. METHODD: A self-administered questionnaire-based survey was carried out amongst doctors working in four hospitals of Kashmir i.e. Combined Military Hospital, Muzaffarabad, Combined Military Hospital, Rawalakot, Abbas Institute of Medical Sciences, Muzaffarabad, and District Hospital, Kotli during August to December 2017. RESULTS: Out of 500 physicians, 217 physicians answered the questionnaire, representing a response rate of 43.4%. Only three of the 11 parameters in the CBC report i.e. hemoglobin, white blood cell count and platelets were selected as frequently or always useful by more than 80% of physicians. Rest of the eight parameters of the CBC were found useful by less than 80% of the physicians. Most agreed that the current format of a CBC report gives adequate information. CONCLUSION: The present study concludes that majority of the physicians utilize only three of the basic parameters on the complete blood count. An educational intervention can be planned for the physicians to increase their knowledge about the utility of other parameters.

Efficacy of Dexmedetomidine vs Morphine as an Adjunct in a Paravertebral Block with Bupivacaine in Postoperative Analgesia Following Modified Radical Mastectomy.

Objective To observe the efficacy of dexmedetomidine vs morphine as an adjunct in a paravertebral block (PVB) with bupivacaine in postoperative analgesia following modified radical mastectomy. Study design This was a randomized controlled trial performed from June 2018 to August 2019 in the Department of Anesthesia, Bakhtawar Amin Medical and Dental College, Ch. Pervaiz Ellahi Institute of Cardiology, Multan, Gurki Hospital, Services Institute of Medical Sciences, and Sheikh Zayed Hospital, Lahore. Methodology Seventy-eight patients were equally divided into group M, which received morphine (3 mg) and group D, which received dexmedetomidine (1 µg/kg), along with 20 cc 0.25% bupivacaine, for PVB. The primary outcome included morphine requirements in the post-anesthesia care unit (PACU). Secondary outcomes included the quality and duration of analgesia, intraoperative doses of fentanyl and propofol, postoperative doses of diclofenac required, postoperative nausea and vomiting (PONV), and the Ramsey sedation score. Data were entered into SPSS version 23 (IBM Corp., Armonk, NY) and analyzed by applying the independent t-test, Mann Whitney U-test, and the chi-square test or Fischer's exact test, as appropriate. P≤0.05 was considered statistically significant. Results The mean time for the first analgesic administration was much shorter in group D as compared to group M (p<0.001). The average doses of ephedrine and morphine used were higher in group D (p-value 0.033 and 0.013, respectively). In the PACU, 33.3% of group D patients as compared to 12.8% of group M patients needed morphine (p=0.032). Postoperatively, diclofenac consumption was higher in group D (p<0.001). Postoperative pain was lower and sedation was higher in group M (p<0.05). Conclusion As an adjunct to bupivacaine in PVB for MRM, morphine is superior to dexmedetomidine.

Association between single nucleotide polymorphisms of DNA damage response pathway genes and increased risk in breast cancer.

Aim: We aimed to evaluate the role of selected single nucleotide polymorphisms of DNA damage response pathway genes in breast cancer (BC). Materials & methods: In present study, 500 BC patients and 500 controls was used to estimate the frequency of single nucleotide polymorphisms of DNA damage response pathway genes. Tetra-amplification refractory mutation system-PCR technique was used for screening of the six selected polymorphisms. Results: Logistic regression analysis showed that heterozygous mutant genotype of rs1800057 (p < 0.0001) and homozygous mutant genotype of rs1801516 (p < 0.0001) was associated with significant increased risk of BC. In the ATR gene, heterozygous mutant genotype of rs2227931 (p < 0.0001) was associated with significant increased risk of BC. However, significant decreased risk of BC was found associated with heterozygous mutant genotype of rs2227928 (p < 0.0002) and homozygous mutant genotype of rs2229032 (p < 0.0001) in patients compared with controls. Conclusion: The present results showed that alteration in DNA damage response pathway gene (ATM & ATR) results in increased BC risk.

Aortic Valve Calcification as a Predictor of Post-Transcatheter Aortic Valve Replacement Pacemaker Dependence.

BACKGROUND: Atrioventricular block requiring permanent pacemaker (PPM) implantation is a common complication of transcatheter aortic valve replacement (TAVR). The mechanism of atrioventricular (AV) block during TAVR is not fully understood, but it may be due to the mechanical stress of TAVR deployment, resulting in possible injury to the nearby compact AV node. Aortic valve calcification (AVC) may worsen this condition and has been associated with an increased risk for post-TAVR PPM implantation. We performed a retrospective analysis to determine if AVC is predictive for long-term right ventricular (RV) pacing in post-TAVR pacemaker patients at 30 days. METHODS: A total of 262 consecutive patients who underwent TAVR with a balloon-expandable valve were analyzed. AVC data were derived from contrast-enhanced computed tomography and characterized by leaflet sector and region. RESULTS: A total of 25 patients (11.1%) required post-TAVR PPM implantation. Seventeen patients did not require RV pacing at 30 days. Nine of these 17 patients had no RV pacing requirement within 10 days. The presence of intra-procedural heart block (P = 0.004) was the only significant difference between patients who did not require PPM and those who required PPM but they were not RV pacing-dependent at 30 days. Non-coronary cusp (NCC) calcium volume was significantly higher in patients who were pacemaker-dependent at 30 days (P = 0.01) and a calcium volume of > 239.2 mm3 in the NCC was strongly predictive of pacemaker dependence at 30 days (area under the curve (AUC) = 0.813). Pre-existing right bundle branch block (RBBB) (odds ratio (OR) 105.4, P = 0.004), bifascicular block (OR 12.5, P = 0.02), QRS duration (OR 70.43, P = 0.007) and intra-procedural complete heart block (OR 12.83, P = 0.03) were also predictive of pacemaker dependence at 30 days. CONCLUSIONS: In patients who required PPM after TAVR, quantification of AVC by non-coronary leaflet calcium volume was found to be a novel predictor for RV pacing dependence at 30 days. The association of NCC calcification and PPM dependence may be related to the proximity of the conduction bundle to the non-coronary leaflet. Further studies are necessary to improve risk prediction for long-term RV pacing requirements following TAVR.

Genetic and expression variations of cell cycle pathway genes in brain tumor patients.

The present study was designed to determine the association between the genetic polymorphisms/expression variations of RB1 and CCND1 genes and brain tumor risk. For this purpose, 250 blood samples of brain tumor patients along with 250 controls (cohort I) and 96 brain tumor tissues (cohort II) with adjacent control section were collected. Mutation analysis of RB1 (rs137853294, rs121913300) and CCND1 (rs614367, rs498136) genes was performed using ARMS-PCR followed by sequencing, and expression analysis was performed using real-time PCR and immunohistochemistry. The results showed homozygous mutant genotype of RB1 gene polymorphism, rs121913300 (P=0.003) and CCND1 gene polymorphism rs614367 (P=0.01) were associated significantly with brain tumor risk. Moreover, significant down-regulation of RB1 (P=0.005) and up-regulation of CCND1 (P=0.0001) gene was observed in brain tumor sections vs controls. Spearman correlation showed significant negative correlation between RB1 vs proliferation marker, Ki-67 (r = -0.291*, P<0.05) in brain tumors. Expression levels of selected genes were also assessed at protein level using immunohistochemical analysis (IHC) and signification down-regulation of RB1 (P=0.0001) and up-regulation of CCND1 (P=0.0001) was observed in brain tumor compared with control sections. In conclusion, it is suggested that polymorphisms/expression variations of RB1 and CCND1 genes may be associated with increased risk of brain tumor.