Comparative study on chromatin loop callers using Hi-C data reveals their effectiveness.

BACKGROUND: Chromosome is one of the most fundamental part of cell biology where DNA holds the hierarchical information. DNA compacts its size by forming loops, and these regions house various protein particles, including CTCF, SMC3, H3 histone. Numerous sequencing methods, such as Hi-C, ChIP-seq, and Micro-C, have been developed to investigate these properties. Utilizing these data, scientists have developed a variety of loop prediction techniques that have greatly improved their methods for characterizing loop prediction and related aspects. RESULTS: In this study, we categorized 22 loop calling methods and conducted a comprehensive study of 11 of them. Additionally, we have provided detailed insights into the methodologies underlying these algorithms for loop detection, categorizing them into five distinct groups based on their fundamental approaches. Furthermore, we have included critical information such as resolution, input and output formats, and parameters. For this analysis, we utilized the GM12878 Hi-C datasets at 5 KB, 10 KB, 100 KB and 250 KB resolutions. Our evaluation criteria encompassed various factors, including memory usages, running time, sequencing depth, and recovery of protein-specific sites such as CTCF, H3K27ac, and RNAPII. CONCLUSION: This analysis offers insights into the loop detection processes of each method, along with the strengths and weaknesses of each, enabling readers to effectively choose suitable methods for their datasets. We evaluate the capabilities of these tools and introduce a novel Biological, Consistency, and Computational robustness score ( B C C score ) to measure their overall robustness ensuring a comprehensive evaluation of their performance.

Mechanical circulatory support versus vasopressors alone in patients with acute myocardial infarction and cardiogenic shock undergoing percutaneous coronary intervention.

BACKGROUND: Previous studies have compared Impella use to intra-aortic balloon pump (IABP) use in patients with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI). Our objective was to compare clinical outcomes in patients with AMI-CS undergoing PCI who received Impella (percutaneous left ventricular assist device) without vasopressors, IABP without vasopressors, and vasopressors without mechanical circulatory support (MCS). METHODS: We queried the National Inpatient Sample (NIS) using ICD-10 codes (2015-2018) to identify patients with AMI-CS undergoing PCI. We created three propensity-matched cohorts to examine clinical outcomes in patients receiving Impella versus IABP, Impella versus vasopressors without MCS, and IABP versus vasopressors without MCS. RESULTS: Among 17,762 patients, Impella use was associated with significantly higher in-hospital major bleeding (31.4% vs. 13.6%; p < 0.001) and hospital charges (p < 0.001) compared to IABP use, with no benefit in mortality (34.1% vs. 26.9%; p = 0.06). Impella use was associated with significantly higher mortality (42.3% vs. 35.7%; p = 0.02), major bleeding (33.9% vs. 22.7%; p = 0.001), and hospital charges (p < 0.001), when compared to the use of vasopressors without MCS. There were no significant differences in clinical outcomes between IABP use and the use of vasopressor without MCS. CONCLUSIONS: In this analysis of retrospective data of patients with AMI-CS undergoing PCI, Impella use was associated with higher mortality, major bleeding, and in-hospital charges when compared to vasopressor therapy without MCS. When compared to IABP use, Impella was associated with no mortality benefit, along with higher major bleeding events and in-hospital charges. A vasopressor-only strategy suggested no difference in clinical outcomes when compared to IABP. This study uses the NIS for the first time to highlight outcomes in AMI-CS patients undergoing PCI when treated with vasopressor support without MCS, compared to Impella and IABP use.

CNNSplice: Robust models for splice site prediction using convolutional neural networks.

The identification of splice site, or segments of an RNA gene where noncoding and coding sequences are connected in the 5' and 3' directions, is an essential post-transcriptional step for the annotation of functional genes and is required for the study and analysis of biological function in eukaryotic organisms through protein production and gene expression. Splice site detection tools have been proposed for this purpose; however, the models of these tools have a specific use case and are inefficiently or typically untransferable between organisms. Here, we present CNNSplice, a set of deep convolutional neural network models for splice site prediction. Using the five-fold cross-validation model selection technique, we explore several models based on typical machine learning applications and propose five high-performing models to efficiently predict the true and false SS in balanced and imbalanced datasets. Our evaluation results indicate that CNNSplice's models achieve a better performance compared with existing methods across five organisms' datasets. In addition, our generality test shows CNNSplice's model ability to predict and annotate splice sites in new or poorly trained genome datasets indicating a broad application spectrum. CNNSplice demonstrates improved model prediction, interpretability, and generalizability on genomic datasets compared to existing splice site prediction tools. We have developed a web server for the CNNSplice algorithm which can be publicly accessed here: http://www.cnnsplice.online.

Diversity in U.S. Cardiovascular Trainees and Leadership Where we are and What the Future Holds.

Cardiovascular (CV) outcomes can be improved with commonality between provider and patient regarding gender and race/ethnicity. Slow growth in CV care provider diversity is an obstacle for women and underrepresented groups. The hope for more equitable outcomes is unlikely to be realized unless trends change in selection of CV fellows and program directors (PDs). We investigate longitudinal trends of gender and racial/ethnic composition of CV FITs. De-identified demographic data were compiled in a descriptive cross-sectional study from AAMC of internal medicine (IM) residents and CV FITs from 2011 through 2021 to evaluate gender and race/ethnicity trends among CV trainees. Trends of CV fellows who later became program directors were analyzed. In the US between 2011 and 2021, 53% of IM residents were male while 40% female (7% unreported). Among CV FITs, 78% were male and 21% female. Races/ethnicities among CV FITs consisted of 36% non-Hispanic white, 28% non-Hispanic Asian, 5% Hispanic, 4%Black, and 25% were classified within other race/ethnicity categories. The proportion who became CV program directors followed similarly: 79% of PDs were male and 21% female. Demographic profiles for CV FITs have not significantly changed over the past decade despite increased diversity among IM residents. Efforts to improve diversity of CV FITs and PDs need to be analyzed. Slow growth of diversity in CV FITs is outpaced by rising patient diversity, leading to disparities in care and poorer CV outcomes for women and underrepresented minorities. Recruiting, training, and retaining diverse CV FITs is necessary.

Outbreak of Ichthyophthirius multifiliis associated with Aeromonas hydrophila in Pangasianodon hypophthalmus: The role of turmeric oil in enhancing immunity and inducing resistance against co-infection.

Ichthyophthirius multifiliis, a ciliated parasite causing ichthyophthiriasis (white spot disease) in freshwater fishes, results in significant economic loss to the aquaculture sector. One of the important predisposing factors for ichthyophthiriasis is low water temperature (i.e., below 20°C), which affects the health and makes freshwater fishes more susceptible to parasitic infections. During ichthyophthiriasis, fishes are stressed and acute immune reactions are compromised, which enables the aquatic bacterial pathogens to simultaneously infect the host and increase the severity of disease. In the present work, we aimed to understand the parasite-bacteria co-infection mechanism in fish. Later, Curcuma longa (turmeric) essential oil was used as a promising management strategy to improve immunity and control co-infections in fish. A natural outbreak of I. multifiliis was reported (validated by 16S rRNA PCR and sequencing method) in Pangasianodon hypophthalmus from a culture facility of ICAR-CIFRI, India. The fish showed clinical signs including hemorrhage, ulcer, discoloration, and redness in the body surface. Further microbiological analysis revealed that Aeromonas hydrophila was associated (validated by 16S rRNA PCR and sequencing method) with the infection and mortality of P. hypophthalmus, confirmed by hemolysin and survival assay. This created a scenario of co-infections, where both infectious agents are active together, causing ichthyophthiriasis and motile Aeromonas septicemia (MAS) in P. hypophthalmus. Interestingly, turmeric oil supplementation induced protective immunity in P. hypophthalmus against the co-infection condition. The study showed that P. hypophthalmus fingerlings supplemented with turmeric oil, at an optimum concentration (10 ppm), exhibited significantly increased survival against co-infection. The optimum concentration induced anti-stress and antioxidative response in fingerlings, marked by a significant decrease in cortisol and elevated levels of superoxide dismutase (SOD) and catalase (CAT) in treated animals as compared with the controls. Furthermore, the study indicated that supplementation of turmeric oil increases both non-specific and specific immune response, and significantly higher values of immune genes (interleukin-1ß, transferrin, and C3), HSP70, HSP90, and IgM were observed in P. hypophthalmus treatment groups. Our findings suggest that C. longa (turmeric) oil modulates stress, antioxidant, and immunological responses, probably contributing to enhanced protection in P. hypophthalmus. Hence, the application of turmeric oil treatment in aquaculture might become a management strategy to control co-infections in fishes. However, this hypothesis needs further validation.

Clinical Characteristics and Implications of Bradycardia in COVID-19 Patients Treated with Remdesivir: A Single-Center Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Remdesivir is an antiviral drug used to treat coronavirus disease 2019 (COVID-19) with a relatively obscure cardiac effect profile. Previous studies have reported bradycardia associated with remdesivir, but few have examined its clinical characteristics. The objective of this study was to investigate remdesivir associated bradycardia and its associated clinical characteristics and outcomes. METHODS: This is a single-institution retrospective study that investigated bradycardia in 600 patients who received remdesivir for treatment of COVID-19. A total of 375 patients were included in the study after screening for other known causes of bradycardia (atrioventricular [AV] nodal blockers). All patients were analyzed for episodes of bradycardia from when remdesivir was initiated up to 5 days after completion, a time frame based on the drug's putative elimination half-life. Univariate and multivariate statistical tests were conducted to analyze the data. RESULTS: The mean age of the sample was 56.63 ± 13.23 years. Of patients who met inclusion criteria, 49% were found to have bradycardia within 5 days of remdesivir administration. Compared to the cohort without a documented bradycardic episode, patients with bradycardia were significantly more likely to experience inpatient mortality (22% vs 12%, p = 0.01). The patients with bradycardia were found to have marginally higher serum D-dimer levels (5.2 vs 3.4 µg/mL, p = 0.05) and were more likely to undergo endotracheal intubation (28% vs 14%, p = 0.008). Male sex, hyperlipidemia, and bradycardia within 5 days of completing remdesivir were significant predictors of inpatient mortality. No significant differences in length of stay were found. CONCLUSIONS: Bradycardia that occurs during or shortly after remdesivir treatment in COVID-19 patients may be associated with an increased rate of in-hospital mortality. However, COVID-19 and its cardiac complications cannot be excluded as potential contributors of bradycardia in the present study. Future studies are needed to further delineate the cardiac characteristics of COVID-19 and remdesivir.

A single-center retrospective study on the incidence and clinical significance of the electrocardiographic "Triangular QRS-ST-T Waveform" pattern*.

BACKGROUND: The triangular QRS-ST-T waveform is a rare presentation of ST-segment elevation acute myocardial infarction associated with a poor in-hospital prognosis. OBJECTIVE: To evaluate the incidence and clinical implications of the QRS-ST-T waveform pattern. METHODS: Clinical data from non-pregnant adult patients who presented as STEMI activations at a single institution between 2017 and 2021 were reviewed. Patients who met electrocardiographic criteria for triangular QRS-ST-T waveform - a giant wave from the fusion of the QRS complex, the ST-segment, and the T-wave - were included in the study. RESULTS: There were 417 STEMI activations, eight (1.9%) of which fulfilled the criteria for the triangular QRS-ST-T waveform pattern on electrocardiography. Coronary angiography was performed in five of these patients, four of whom demonstrated a significant lesion to the left anterior descending artery. Three patients did not undergo angiography secondary to hemodynamic instability. Seven of the patients in our study experienced cardiogenic shock requiring vasopressor, inotropic, and/or mechanical support. Only two patients survived to discharge; one was successfully bridged to coronary artery bypass grafting via intra-aortic balloon pump, while the other underwent a staged percutaneous coronary intervention. CONCLUSIONS: The triangular QRS-ST-T waveform pattern is a rare ECG finding that may indicate hyper-acute STEMI and is an ominous sign of impending hemodynamic instability. Patients who survived received prompt aggressive therapeutic management.

Are cause of death data for Shanghai fit for purpose? A retrospective study of medical records.

OBJECTIVES: To assess the quality of cause of death reporting in Shanghai for both hospital and home deaths. DESIGN AND SETTING: Medical records review (MRR) to independently establish a reference data set against which to compare original and adjusted diagnoses from a sample of three tertiary hospitals, one secondary level hospital and nine community health centres in Shanghai. PARTICIPANTS: 1757 medical records (61% males, 39% females) of deaths that occurred in these sample sites in 2017 were reviewed using established diagnostic standards. INTERVENTIONS: None. PRIMARY OUTCOME: Original underlying cause of death (UCOD) from medical facilities. SECONDARY OUTCOME: Routine UCOD assigned from the Shanghai Civil Registration and Vital Statistics (CRVS) system and MRR UCODs from MRR. RESULTS: The original UCODs as assigned by doctors in the study facilities were of relatively low quality, reduced to 31% of deaths assigned to garbage codes, reduced to 2.3% following data quality and follow back procedures routinely applied by the Shanghai CRVS system. The original UCOD had lower chance-corrected concordance and cause-specific mortality fraction accuracy of 0.57 (0.44, 0.70) and 0.66, respectively, compared with 0.75 (0.66, 0.85) and 0.96, respectively, after routine data checking procedures had been applied. CONCLUSIONS: Training in correct death certification for clinical doctors, especially tertiary hospital doctors, is essential to improve UCOD quality in Shanghai. A routine quality control system should be established to actively track diagnostic performance and provide feedback to individual doctors or facilities as needed.

Improving cause of death certification in the Philippines: implementation of an electronic verbal autopsy decision support tool (SmartVA auto-analyse) to aid physician diagnoses of out-of-facility deaths.

BACKGROUND: The majority of deaths in the Philippines occur out-of-facility and require a medical certificate of cause of death by Municipal Health Officers (MHOs) for burial. MHOs lack a standardised certification process for out-of-facility deaths and when no medical records are available, certify a high proportion of ill-defined causes of death. We aimed to develop and introduce SmartVA Auto-Analyse, a verbal autopsy (VA) based electronic decision support tool in order to assist the MHOs in certifying out-of-facility deaths. METHOD: We conducted a stakeholder consultation, process mapping and a pre-test to assess feasibility and acceptability of SmartVA Auto-Analyse. MHOs were first asked to conduct an open-ended interview from the family members of the deceased, and if they were not able to arrive at a diagnosis, continue the interview using the standardised SmartVA questionnaire. Auto-Analyse then presented the MHO with the three most likely causes of death. For the pilot, the intervention was scaled-up to 91 municipalities. We performed a mixed-methods evaluation using the cause of death data and group discussions with the MHOs. RESULTS: Of the 5649 deaths registered, Auto-Analyse was used to certify 4586 (81%). For the remaining 19%, doctors believed they could assign a cause of death based on the availability of medical records and the VA open narrative. When used, physicians used the Auto-Analyse diagnosis in 85% of cases to certify the cause of death. Only 13% of the deaths under the intervention had an undetermined cause of death. Group discussions identified two themes: Auto-Analyse standardized the certification of home deaths and assisted the MHOs to improve the quality of death certification. CONCLUSION: Standardized VA combined with physician diagnosis using the SmartVA Auto-Analyse support tool was readily used by MHOs in the Philippines and can improve the quality of death certification of home deaths.

Panhypopituitarism in an Adult Male and Hypogonadism as a First Clue.

Hypopituitarism is a rare entity with reported incidence, 4 per 100,000 and about 50% of such patients present with three to five pituitary hormone deficits. A slow onset of symptoms is typical. But, diversified presentations from absence of symptoms to vague clinical features to lethal effects leading to mortality are not uncommon in such disorder. In adults, in such cases symptoms of hypogonadism may be the first noticeable illness for reporting to physicians, but it is often under evaluated or even ignored. Here, we present a case of 40-year-old adult male with panhypopituitarism, who presented with loss of generalized body hair and loss of libido for about last five years but the problem was not evaluated adequately. Later, he developed lethargy, generalized weakness, weight loss and then the underneath cause detected was panhypopituitarism due to pituitary macro adenoma. So, suspicion and hormonal evaluation for hypogonadism would help in early detection and management of progressive hypopituitarism in symptomatic adult patients. Cases of panhypopituitarism need lifelong hormone replacement and follow-up and if pituitary adenoma is present, surgical removal by trans-sphenoidal approach is preferable.

Association of Serum Vitamin D (25OHD) Level with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Acute exacerbations of COPD is characterized by a change in the patients baseline dyspnoea, cough and/or sputum that is beyond normal day to day differences and guides to a change in standard medications in a patient with COPD. Vitamin D influences the innate & adaptive immune system, and exerts pleiotropic antimicrobial and anti-inflammatory responses. Vitamin D deficiency is frequent among COPD patients but its contributory role in disease exacerbations is widely debated. This study was aimed to assess relationship between reduced serum vitamin D (25-OHD) level with COPD severity and acute exacerbation. This observational cross-sectional study was carried out in the department of Respiratory Medicine, NIDCH, Mohakhali, Dhaka, Bangladesh from October 2016 to September 2017. Consecutive 80 hospital admitted patients with acute exacerbation of chronic obstructive pulmonary disease diagnosed on the basis of clinical history & pulmonary function tests and 78 age & sex matched controls were investigated for serum vitamin D (25-OHD) level. Among the COPD patients, 37% had Vitamin D deficiency (<20ng/ml) and 28.75% had Vitamin D insufficiency (20-29ng/ml). Mean vitamin D (25-OHD) level of COPD patients (25.82±10.62ngm/ml) was found to be significantly lower than healthy controls (32.57±11.32ngm/ml). Vitamin D deficiency was found, by Pearson correlation test, to be significantly associated with severity of COPD. Multivariate analysis showed that age (in years), FEV1 (percent predicted), frequent exacerbators (≥2 in the last year), and smoking (>40 pack year) were significantly associated with Vitamin D deficiency. Acute exacerbation of chronic obstructive pulmonary disease patients was found to have vitamin D deficiency and vitamin D deficiency was significantly associated with severity of COPD. Vitamin D deficiency was also associated with frequent disease exacerbation.

BMPRII deficiency impairs apoptosis via the BMPRII-ALK1-BclX-mediated pathway in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disorder characterized by the remodelling of pre-capillary pulmonary arteries. The vascular remodelling observed in PAH patients results from excessive proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs) and pulmonary arterial endothelial cells (PAECs). We have previously demonstrated that mutations in the type II receptor for bone morphogenetic protein (BMPRII) underlie the majority of the familial and inherited forms of the disease. We have further demonstrated that BMPRII deficiency promotes excessive proliferation and attenuates apoptosis in PASMCs, but the underlying mechanisms remain unclear. The major objective of this study is to investigate how BMPRII deficiency impairs apoptosis in PAH. Using multidisciplinary approaches, we demonstrate that deficiency in the expression of BMPRII impairs apoptosis by modulating the alternative splicing of the apoptotic regulator, B-cell lymphoma X (Bcl-x) transcripts: a finding observed in circulating leukocytes and lungs of PAH subjects, hypoxia-induced PAH rat lungs as well as in PASMCs and PAECs. BMPRII deficiency elicits cell specific effects: promoting the expression of Bcl-xL transcripts in PASMCs while inhibiting it in ECs, thus exerting differential apoptotic effects in these cells. The pro-survival effect of BMPRII receptor is mediated through the activin receptor-like kinase 1 (ALK1) but not the ALK3 receptor. Finally, we show that BMPRII interacts with the ALK1 receptor and pathogenic mutations in the BMPR2 gene abolish this interaction. Taken together, dysfunctional BMPRII responsiveness impairs apoptosis via the BMPRII-ALK1-Bcl-xL pathway in PAH. We suggest Bcl-xL as a potential biomarker and druggable target.

Subvalvular aortic stenosis: a review of current literature.

Subvalvular aortic stenosis (SAS) is one of the common adult congenital heart diseases, with a prevalence of 6.5%. It is usually diagnosed in the first decade of life. Echocardiography is the test of choice to diagnose SAS. Surgical correction is the best treatment modality, and the prognosis is usually excellent. In this review, we describe the pathophysiology, diagnosis, prognosis, and management of SAS with a focus on different pathophysiologic mechanisms, diagnostic approach, and prognosis of the disease by reviewing the current literature.

Aminoglycoside-mediated promotion of translation readthrough occurs through a non-stochastic mechanism that competes with translation termination.

Attempts have been made to treat nonsense-associated genetic disorders by chemical agents and hence an improved mechanistic insight into the decoding of readthrough signals is essential for the identification and characterisation of factors for the treatment of these disorders. To identify either novel compounds or genes that modulate translation readthrough, we have employed dual reporter-based high-throughput screens that use enzymatic and fluorescence activities and screened bioactive National Institute of Neurological Disease Syndrome (NINDS) compounds (n = 1000) and siRNA (n = 288) libraries. Whilst siRNAs targeting kinases such as CSNK1G3 and NME3 negatively regulate readthrough, neither the bioactive NINDS compounds nor PTC124 promote readthrough. Of note, PTC124 has previously been shown to promote readthrough. Furthermore, the impacts of G418 on the components of eukaryotic selenocysteine incorporation machinery have also been investigated. The selenocysteine machinery decodes the stop codon UGA specifying selenocysteine in natural selenoprotein genes. We have found that the eukaryotic SelC gene promotes the selenocysteine insertion sequence (SECIS)-mediated readthrough but inhibits the readthrough activity induced by G418. We have previously reported that SECIS-mediated readthrough at UGA codons follows a non-processive mechanism. Here, we show that G418-mediated promotion of readthrough also occurs through a non-processive mechanism which competes with translation termination. Based on our observations, we suggest that proteins generated through a non-processive mechanism may be therapeutically beneficial for the resolution of nonsense-associated genetic disorders.

Significance of inferior wall ischemia in non-dominant right coronary artery anatomy.

AIM: To investigate the relationship of inferior wall ischemia on myocardial perfusion imaging in patients with non-dominant right coronary artery anatomy. METHODS: This was a retrospective observational analysis of consecutive patients who presented to the emergency department with primary complaint of chest pain. Only patients who underwent single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) were included. Patients who showed a reversible defect on SPECT MPI and had coronary angiography during the same hospitalization was analyzed. Patients with prior history of coronary artery disease (CAD) including history of percutaneous coronary intervention and coronary artery bypass graft surgerys were excluded. True positive and false positive results were identified on the basis of hemodynamically significant CAD on coronary angiography, in the same territory as identified on SPECT MPI. Coronary artery dominance was determined on coronary angiography. Patients were divided into group 1 and group 2. Group 1 included patients with non-dominant right coronary artery (RCA) (left dominant and codominant). Group 2 included patients with dominant RCA anatomy. Demographics, baseline characteristics and positive predictive value (PPV) were analyzed for the two groups. RESULTS: The mean age of the study cohort was 57.6 years. Sixty-one point seven percent of the patients were males. The prevalence of self-reported diabetes mellitus, hypertension and dyslipidemia was 36%, 71.9% and 53.9% respectively. A comparison of baseline characteristics between the two groups showed that patients with a non-dominant RCA were more likely to be men. For inferior wall ischemia on SPECT MPI, patients in study group 2 had a significantly higher PPV, 32/42 (76.1%), compared to patients in group 1, in which only 3 out of the 29 patients (10.3%) had true positive results (P value < 0.001 Z test). The difference remained statistically significant even when only patients with left dominant coronary system (without co-dominant) were compared to patients with right dominant system (32/40, 76.1% in right dominant group, 3/19, 15.8% in left dominant group, P value < 0.001 Z test). There was no significant difference in mean hospital stay, re-hospitalization, and in-hospital mortality between the two groups. CONCLUSION: The positive predictive value of SPECT MPI for inferior wall ischemia is affected by coronary artery dominance. More studies are needed to explain this phenomenon.

Mini-Laparoscopic Cholecystectomy: Review of 7200 Cases. Could it be the New Gold Standard?

Mini-Laparoscopy by reducing the instrument size and hence incision can lead to better surgical outcome. The safety and feasibility of mini-laparoscopic cholecystectomy (mini-Lch) has not been documented with a large patient sample. This observational descriptive study reports the results of 7200 cases of mini-Lch performed at Ibrahim General Hospital and Eden Multi-care hospital, Dhaka, Bangladesh by a single surgeon. From May 1998 till July 2013in total 8700 patients were offered Mini-lch and 7200 procedures were completed successfully. The operative indication, total operative time, conversion rate, hospital stay, patient satisfaction, post operative pain, complications, morbidity and mortality were reviewed. In this series conversion to open surgery was 0.39%. Average operating time was 30.22 minutes. Early acute cases (9%) did not require conversion to open. Average post operative hospital stay was 21 hours. There was no mortality in the series. Six patients developed incisional hernia at the umbilical port site and 16 patients had umbilical wound infection. Patient acceptance was excellent, postoperative analgesic requirement was less. With Mini Lch better cosmetic result was achieved, recovery was early. Minilaparoscopic cholecystectomy is an economically feasible, and more acceptable considering the cosmetic outcome and patient acceptance. Our results indicate that this procedure could be performed successfully and safely by experienced surgeons.

Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism.

Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis--often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.