Correlation Between Estrogen Receptor α Gene Polymorphism (c454-397T>C) with Serum Estradiol Levels and Known Risk Factors in Patients with Myocardial Infarction.

Myocardial infarction (MI) remains the most common cause of cardiac failure and continuous increasing rate of morbidity and mortality. We aimed to investigate the association of estrogen receptor-α (ESR1) gene polymorphism c454-397T>C with serum estradiol levels and dyslipidemia in 220 patients with MI in the age range of 35-70 years of both the genders. Genotyping study was performed through PCR-RFLP method using PvuII restriction enzyme. Serum estradiol level was estimated using the Access Sensitive Estradiol assay kit. Men patients had 43.2% increased risk for TC heterozygote in co-dominant (OR 10.66) and over-dominant models (OR 8.30), while women patients had 50% increased risk in co-dominant (OR 16.57) and over-dominant (OR 14.04) models. Variant C allele showed 25% increased risk of MI for in men (OR 2.24; CI 1.49-3.36; p = 0.0001), and 24% increased risk in women (OR 3.35; CI 1.95-5.76; p = 0.0001). Men patients had significantly increased serum estradiol levels compared to controls (25.28 ± 5.80 vs 17.04 ± 2.01; p < 0.0001). Significant difference was observed in estradiol levels between men and women patients (25.28 ± 5.80 vs 17.56 ± 3.32; p < 0.0001). Furthermore, significantly increased estradiol level was found in men patients compared to women for TT (25.46 ± 5.91 vs 16.71 ± 4.46; p < 0.0001), and TC genotypes (25.47 ± 5.91 vs 17.70 ± 2.86; p < 0.0001). Significantly increased HDL levels were observed in men patients with TC (43.10 ± 8.18 vs 38.91 ± 7.84; p < 0.01) and CC (47.16 ± 8.09 vs 38.91 ± 7.84; p < 0.001) genotypes compared to TT genotype. These findings suggest that TC heterozygote plays an important role as a genetic risk factor during MI pathogenesis in the South Indian population. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01104-1.

Alcanivorax borkumensis biofilms enhance oil degradation by interfacial tubulation.

During the consumption of alkanes, Alcanivorax borkumensis will form a biofilm around an oil droplet, but the role this plays during degradation remains unclear. We identified a shift in biofilm morphology that depends on adaptation to oil consumption: Longer exposure leads to the appearance of dendritic biofilms optimized for oil consumption effected through tubulation of the interface. In situ microfluidic tracking enabled us to correlate tubulation to localized defects in the interfacial cell ordering. We demonstrate control over droplet deformation by using confinement to position defects, inducing dimpling in the droplets. We developed a model that elucidates biofilm morphology, linking tubulation to decreased interfacial tension and increased cell hydrophobicity.

Evaluation of effects of temperature and humidity on the secondary structure of Ganirelix in an injectable formulation and comparison with Orgalutran® using circular dichroism spectroscopy.

Ganirelix, a drug used in in vitro fertilization (IVF), prevents ovulation in women who are not ready to have children by inhibiting a gene that produces gonadotropin. Peptides are macromolecules that are able to preserve a predetermined shape while carrying out the structural and regulatory roles for which they were originally intended. Peptide structures can be altered in the production and storage processes. Therapeutic peptides' biological activity can be drastically altered by even small modifications in their primary and secondary structures. The molecules' secondary structures can be monitored by subjecting them to different processing or storage conditions. In our investigation, we used circular dichroism (CD) spectroscopy with two different software programs for secondary structure evaluation to look at how environmental factors like temperature and humidity affected the secondary structure of Ganirelix in an injectable formulation. The CD results revealed that the alpha-helical (regular and distorted), beta-sheet, beta-strands (regular and distorted), beta-turn, and random coil structures of temperature and humidity stressed generic drug products are comparable to reference-listed drug.

Evolution of pathogenicity-associated genes in Rhizoctonia solani AG1-IA by genome duplication and transposon-mediated gene function alterations.

BACKGROUND: Rhizoctonia solani is a polyphagous fungal pathogen that causes diseases in crops. The fungal strains are classified into anastomosis groups (AGs); however, genomic complexity, diversification into the AGs and the evolution of pathogenicity-associated genes remain poorly understood. RESULTS: We report a recent whole-genome duplication and sequential segmental duplications in AG1-IA strains of R. solani. Transposable element (TE) clusters have caused loss of synteny in the duplicated blocks and introduced differential structural alterations in the functional domains of several pathogenicity-associated paralogous gene pairs. We demonstrate that the TE-mediated structural variations in a glycosyl hydrolase domain and a GMC oxidoreductase domain in two paralogous pairs affect the pathogenicity of R. solani. Furthermore, to investigate the association of TEs with the natural selection and evolution of pathogenicity, we sequenced the genomes of forty-two rice field isolates of R. solani AG1-IA. The genomic regions with high population mutation rates and with the lowest nucleotide diversity are enriched with TEs. Genetic diversity analysis predicted the genes that are most likely under diversifying and purifying selections. We present evidence that a smaller variant of a glucosamine phosphate N-acetyltransferase (GNAT) protein, predicted to be under purifying selection, and an LPMP_AA9 domain-containing protein, predicted to be under diversifying selection, are important for the successful pathogenesis of R. solani in rice as well as tomato. CONCLUSIONS: Our study has unravelled whole-genome duplication, TE-mediated neofunctionalization of genes and evolution of pathogenicity traits in R. solani AG1-IA. The pathogenicity-associated genes identified during the study can serve as novel targets for disease control.

Patient-reported outcomes of laparoscopic versus robotic primary ventral and incisional hernia repair: a systematic review and meta-analysis.

BACKGROUND: Patient-Reported Outcome Measures (PROM's) are increasingly used to assess surgical outcomes in low-risk surgeries such as minimally invasive primary ventral and incisional hernia repair. The purpose of this meta-analysis was to systematically summarize the available evidence for the effect of laparoscopic versus robotic primary ventral and incisional hernia repair on PROM's. METHODS: A systematic review and meta-analysis were performed in accordance with PRISMA guidelines. Randomised control trials, retrospective and prospective studies were included. Medline, Embase, SCOPUS, Web of Science, and Cochrane CENTRAL, and two trial registers were searched. Pooled effect sizes and 95% confidence intervals were calculated using the Mantel-Haenszel method. The overall quality of evidence was assessed using GRADE. RESULTS: Of the 2728 titles screened, eight studies involving 41,205 participants were included. Return to activities of daily living, return to work day and recurrence rate were statistically better in the robotic group. Length of stay, readmission, postoperative pain, quality of life, body image, and patient satisfaction were similar in both groups. The GRADE rating of the quality of evidence was moderate for postoperative pain and low to very low for the quality of life, length of stay, recurrence and readmission. CONCLUSION: The available data of PROM's of laparoscopic and robotic primary ventral and incisional hernia repair is scarce and highly heterogeneous, thus making it difficult to assess the superiority of the laparoscopic technique over the robotic technique. Further studies with uniform reporting of PROM's in laparoscopic and robotic primary ventral and incisional hernia repair are needed.

Effect of dietary supplementation of organic and inorganic Se on performance and antioxidant response in commercial broiler chickens.

1. The study was carried out to determine the effects of supplementing organic (OG) or inorganic (IOG) Se to record the performance, immune and anti-oxidant response in broiler chickens.2. One-day-old Vencobb-400 (50.1 ± 0.84 g; n = 280) male broiler chicks were allocated randomly into seven treatments to give eight replicates containing five chicks each and housed in deep littered floor pens (76 cm × 91 cm) for a period of 42 d.3. The control diet (CD) was formulated without any Se supplementation (diet I), CD plus 0.15, 0.30 or 0.45 mg/kg OG Se (diets II, III and IV, respectively) and CD plus 0.15, 0.30 or 0.45 mg/kg IOG Se (diets V, VI and VII, respectively).4. Feed intake (FI), body weight gain (BWG), immune variables and mRNA expression profile of hepatic selenoproteins (SepW, GSHPx1, TrxR and GSHPx3) genes were determined. The BWG, FI and feed conversion ratio did not differ among various dietary treatments.5. The lipid peroxidation and activity of RBC catalase were lower (P < 0.05) in groups fed diets supplemented OG Se compared to those fed IOG Se and CD. The activity of GSH Px was higher among the groups fed diet supplemented OG Se compared to those groups fed OG Se and CD. However, supplementing diets with OG or IOG Se did not affect humoral or cell mediated immune responses.6. The expression levels of SepW were higher (P < 0.01) among the groups supplemented with OG Se. Expression levels of GSH-Px1, TrxR and GSHPx3 were higher (P < 0.01) among the groups supplemented with OG Se compared to those groups fed IOG Se or CD.7. Supplementing OG Se improved the activities of anti-oxidant enzymes and hepatic expression of selenoproteins genes in the present study. However, supplementing OG or IOG Se did not affect growth performance and immune variables in broiler chickens.

Neurofibromatosis from Head to Toe: What the Radiologist Needs to Know.

Neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) are autosomal dominant inherited neurocutaneous disorders or phakomatoses secondary to mutations in the NF1 and NF2 tumor suppressor genes, respectively. Although they share a common name, NF1 and NF2 are distinct disorders with a wide range of multisystem manifestations that include benign and malignant tumors. Imaging plays an essential role in diagnosis, surveillance, and management of individuals with NF1 and NF2. Therefore, it is crucial for radiologists to be familiar with the imaging features of NF1 and NF2 to allow prompt diagnosis and appropriate management. Key manifestations of NF1 include café-au-lait macules, axillary or inguinal freckling, neurofibromas or plexiform neurofibromas, optic pathway gliomas, Lisch nodules, and osseous lesions such as sphenoid dysplasia, all of which are considered diagnostic features of NF1. Other manifestations include focal areas of signal intensity in the brain, low-grade gliomas, interstitial lung disease, various abdominopelvic neoplasms, scoliosis, and vascular dysplasia. The various NF1-associated abdominopelvic neoplasms can be categorized by their cellular origin: neurogenic neoplasms, interstitial cells of Cajal neoplasms, neuroendocrine neoplasms, and embryonal neoplasms. Malignant peripheral nerve sheath tumors and intracranial tumors are the leading contributors to mortality in NF1. Classic manifestations of NF2 include schwannomas, meningiomas, and ependymomas. However, NF2 may have shared cutaneous manifestations with NF1. Lifelong multidisciplinary management is critical for patients with either disease. The authors highlight the genetics and molecular pathogenesis, clinical and pathologic features, imaging manifestations, and multidisciplinary management and surveillance of NF1 and NF2. Online supplemental material is available for this article. ©RSNA, 2022.

Anatomical Challenges during Pancreaticoduodenectomy for Adenocarcinoma Head of Pancreas in Presence of Intestinal Rotation Abnormalities: A Report of Two Cases.

Purpose Pancreaticoduodenenctomy is a complex surgery and the sequence of steps is affected by anatomical variations involving small intestine and major vascular structures. This article depicts our approach to two such cases and highlights the importance of identifying these variations preoperatively on imaging, so as to modify the surgery plan accordingly. Cases We report following two cases of pancreatic head adenocarcinoma (1) one with incomplete intestinal rotation with a replaced right hepatic artery and (2) one with intestinal nonrotation. In both cases, the small bowel was aggregated on the right side of the abdomen, making duodenal mobilization challenging. The surgical approach was modified to prevent injury to these vessels. A superior mesenteric artery (SMA)-first approach helped in early isolation of vascular structures especially when vascular anomaly was also present. Interbowel adhesiolysis, limited kocherisation, tracing all vessels to its origin before division, paracolic anastomotic limb after a longer jejunal limb resection in nonrotation cases, and modification in retropancreatic tunnel creation are few of the key surgical adaptations. Conclusion Asymptomatic Intestinal malrotation is rare in adults and must be identified on preoperative imaging. Resultant intestinal and vascular anatomical variations need meticulous surgical planning and modification of conventional surgical approach for safe performance of PD.

The efficacy, challenges, and facilitators of telemedicine in post-treatment cancer survivorship care: an overview of systematic reviews.

BACKGROUND: Telemedicine services have been increasingly used to facilitate post-treatment cancer survivorship care, including improving access; monitoring health status, health behaviors, and symptom management; enhancing information exchange; and mitigating the costs of care delivery, especially since the COVID-19 pandemic. To inform guidance for the use of telemedicine in the post-COVID era, the aim of this overview of systematic reviews (SRs) was to evaluate the efficacy of, and survivor engagement in, telemedicine interventions in the post-treatment survivorship phase, and to consider implementation barriers and facilitators. METHODS: PubMed, Cochrane CENTRAL, CINAHL, Embase, and Web of Science databases were searched. SRs that examined the use of telemedicine in the post-treatment phase of cancer survivorship, published between January 2010 and April 2021, were included. Efficacy data were synthesized narratively. Implementation barriers and facilitators were synthesized using the Consolidated Framework for Implementation Research. RESULTS: Twenty-nine SRs were included. A substantive body of evidence found telemedicine to benefit the management of psychosocial and physical effects, particularly for improving fatigue and cognitive function. There was a lack of evidence on the use of telemedicine in the prevention and surveillance for recurrences and new cancers as well as management of chronic medical conditions. This overview highlights a range of diverse barriers and facilitators at the patient, health service, and system levels. CONCLUSIONS: This review highlights the benefits of telemedicine in addressing psychosocial and physical effects, but not in other areas of post-treatment cancer survivorship care. This large review provides practical guidance for use of telemedicine in post-treatment survivorship care.

COVID-19 restrictions and their influences on ambient air, surface water and plastic waste in a coastal megacity, Chennai, India.

Anthropogenic activities experienced a pause due to the nationwide lockdown, imposed to contain the rapid spread of COVID-19 in the third week of March 2020. The impacts of suspension of industrial activities, vehicular transport and other businesses for three months (25 March-30 June) on the environmental settings of Chennai, a coastal megacity was assessed. A significant reduction in the key urban air pollutants [PM2.5 (66.5%), PM10 (39.5%), NO2 (94.1%), CO (29%), O3 (45.3%)] was recorded as an immediate consequence of the reduced anthropogenic activities. Comparison of water quality of an urban river Adyar, between pre-lockdown and lockdown, showed a substantial drop in the dissolved inorganic N (47%) and suspended particulate matter (41%) during the latter period. During the pandemic, biomedical wastes in India showed an overall surge of 17%, which were predominantly plastic. FTIR-ATR analysis confirmed the polymers such as polypropylene (25.4%) and polyester (15.4%) in the personal protective equipment.

Enhancing phytoremediation of hazardous metal(loid)s using genome engineering CRISPR-Cas9 technology.

Rapid and drastic changes in the global climate today have given a strong impetus to developing newer climate-resilient phytoremediation approaches. These methods are of great public and scientific importance given the urgency of this environmental crisis. Climate change has adverse effects on the growth, outputs, phenology, and overall productivity of plants. Contamination of soil with metal(loid)s is a major worldwide problem. Some metal(loids) are carcinogenic pollutants that have a long half-life and are non-degradable in the environment. There are many instances of the potential link between chronic heavy metal exposure and human disease. The adaptation of plants in the changing environment is, however, a major concern in phytoremediation practice. The creation of climate-resistant metal hyperaccumulation plants using molecular techniques could provide new opportunities to mitigate these problems. Consequently, advancements in molecular science would accelerate our knowledge of adaptive plant remediation/resistance and plant production in the context of global warming. Genome modification using artificial nucleases has the potential to enhance phytoremediation by modifying genomes for a sustainable future. This review focuses on biotechnology to boost climate change tolerant metallicolous plants and the future prospects of such technology, particularly the CRISPR-Cas9 genome editing system, for enhancing phytoremediation of hazardous pollutants.

Hybrid Spectral-IRDx: Near-IR and Ultrasound Attenuation System for Differentiating Breast Cancer From Adjacent Normal Tissue.

OBJECTIVE: While performing surgical excision for breast cancer (lumpectomy), it is important to ensure a clear margin of normal tissue around the cancer to achieve complete resection. The current standard is histopathology; however, it is time-consuming and labour-intensive requiring skilled personnel. METHOD: We describe a Hybrid Spectral-IRDx - a combination of the previously reported Spectral-IRDx tool with multimodal ultrasound and NIR spectroscopy techniques. We show how this portable, cost-effective, minimal-contact tool could provide rapid diagnosis of cancer using formalin-fixed (FF) and deparaffinized (DP) breast biopsy tissues. RESULTS: Using this new tool, measurements were performed on cancerous/fibroadenoma and its adjacent normal tissues from the same patients (N = 14). The acoustic attenuation coefficient (α) and reduced scattering coefficient (µ's) (at 850, 940, and 1060 nm) for the cancerous/fibroadenoma tissues were reported to be higher compared to adjacent normal tissues, a basis of delineation. Comparing FF cancerous and adjacent normal tissue, the difference in µ's at 850 nm and 940 nm were statistically significant (p = 3.17e-2 and 7.94e-3 respectively). The difference in α between the cancerous and adjacent normal tissues for DP and FF tissues were also statistically significant (p = 2.85e-2 and 7.94e-3 respectively). Combining multimodal parameters α and µ's (at 940 nm) show highest statistical significance (p = 6.72e-4) between FF cancerous/fibroadenoma and adjacent normal tissues. CONCLUSION: We show that Hybrid Spectral-IRDx can accurately delineate between cancerous and adjacent normal breast biopsy tissue. SIGNIFICANCE: The results obtained establish the proof-of-principle and large-scale testing of this multimodal breast cancer diagnostic platform for core biopsy diagnosis.

Discussions of Fluorescence in Selenium Chemistry: Recently Reported Probes, Particles, and a Clearer Biological Knowledge.

In this review from literature appearing over about the past 5 years, we focus on selected selenide reports and related chemistry; we aimed for a digestible, relevant, review intended to be usefully interconnected within the realm of fluorescence and selenium chemistry. Tellurium is mentioned where relevant. Topics include selenium in physics and surfaces, nanoscience, sensing and fluorescence, quantum dots and nanoparticles, Au and oxide nanoparticles quantum dot based, coatings and catalyst poisons, thin film, and aspects of solar energy conversion. Chemosensing is covered, whether small molecule or nanoparticle based, relating to metal ion analytes, H2S, as well as analyte sulfane (biothiols-including glutathione). We cover recent reports of probing and fluorescence when they deal with redox biology aspects. Selenium in therapeutics, medicinal chemistry and skeleton cores is covered. Selenium serves as a constituent for some small molecule sensors and probes. Typically, the selenium is part of the reactive, or active site of the probe; in other cases, it is featured as the analyte, either as a reduced or oxidized form of selenium. Free radicals and ROS are also mentioned; aggregation strategies are treated in some places. Also, the relationship between reduced selenium and oxidized selenium is developed.

Direct versus indirect transfer for traumatic brain injury to James Cook University Hospital: a retrospective study.

INTRODUCTION: Patients with traumatic brain injury are referred to the neurosurgical unit at James Cook University Hospital, Middlesbrough, either from local accident and emergency departments (direct transfer from the scene) or from other hospitals (indirect transfer). This study looked at the outcome in both groups. MATERIAL AND METHODS: This was a retrospective observational study using trauma audit research network data for patients treated for traumatic brain injury at the neurosurgery department at the neurosurgical unit at James Cook University Hospital. RESULTS: A total of 356 patients with traumatic brain injury were admitted under the care of neurosurgeons; 143 (40%) of these patients had a neurosurgical procedure. Of the patients undergoing a neurological procedure, 111 patients were transferred directly while 32 were indirect transfers; 213 patients were managed conservatively. Of those managed conservatively, 165 were transferred directly while 48 were indirect transfers. We compared the length of hospital stay and Glasgow Outcome Scale score for the patients based on whether they were conservatively managed or required surgery in the direct and indirect transfer groups. The difference in the length of stay in the surgical and conservative groups following direct and indirect transfer was insignificant (p = 0.07). The time to the operation in direct and indirect transfer was also not statistically significant (p = 0.06). CONCLUSION: Patients are as safe, if not safer, by reaching the nearest trauma unit with facilities for resuscitation and imaging.

Pneumorenum-A Technique to Ease Laparoscopic Nephrectomy in Giant Hydronephrotic Nonfunctioning Kidney.

Laparoscopic nephrectomy in a giant hydronephrotic nonfunctioning kidney occupying the most of the abdomen is challenging task. To overcome the difficulty in laparoscopic dissection of such kidneys we described a technique "Pneumorenum," wherein the kidney is decompressed by suction through a 5 mm trocar inserted directly into kidney under vision. Following suction decompression, the kidney is inflated later during dissection with carbon dioxide gas to moderate size to do the dissection in an easy manner.

Tandem Olefin Isomerization/Cyclization Catalyzed by Complex Nickel Hydride and Brønsted Acid.

We disclose a nickel/Brønsted acid-catalyzed tandem process consisting of double bond isomerization of allyl ethers and amines and subsequent intramolecular reaction with nucleophiles. The process is accomplished by [(Me3P)4NiH]N(SO2CF3)2 in the presence of triflic acid. The methodology provides rapid access to tetrahydropyran-fused indoles and other oxacyclic scaffolds under very low catalyst loadings.

Radiologic and Pathologic Correlation in EVALI.

OBJECTIVE. The purpose of this article is to characterize the appearance on CT of e-cigarette or vaping product use-associated lung injury (EVALI) in a cohort with histopathologic evidence of this disorder. MATERIALS AND METHODS. Twenty-four patients with EVALI were identified. Chest CT examinations were reviewed by two radiologists for various chest CT findings. For comparison with pathologic findings, CT assessments were distilled into previously described patterns of EVALI seen on CT: acute lung injury (ALI), chronic eosinophilic pneumonia (CEP) or organizing pneumonia (OP), acute eosinophilic pneumonia (AEP), alveolar hemorrhage, hypersensitivity pneumonitis (HP), lipoid pneumonia, and mixed or unclassifiable patterns. RESULTS. Sixteen of 24 (67%) patients were men; the mean age was 34.5 years (range, 17-67 years). The most common CT finding was ground-glass opacities, which was present in 23 of 24 (96%) patients and the dominant finding in 18 of 24 (75%) patients. Consolidation was the next most common finding in 42% of patients. Interlobular septal thickening was present in 29%. Lobular low attenuation was conspicuous in six patients. Distribution was multifocal in 54% of patients, peripheral in 17%, and centrally predominant in 8%. Subpleural sparing was seen in 45%. The predominant CT pattern was ALI (42%), concordant with histopathologic findings in 75%; the next most predominant pattern was ground-glass opacity centrilobular nodules resembling HP (33%). A CT pattern of CEP or OP was seen in 13% of patients, all showing ALI on lung biopsy. No patient showed macroscopic lung parenchymal fat. Two patients with CT ALI patterns showed OP on histopathologic examination. Of the eight patients with ground-glass opacity centrilobular nodules resembling HP at CT, none showed HP at histopathologic examination. CONCLUSION. EVALI manifests at CT as ALI with multifocal ground-glass opacity, often with organizing consolidation, and a small centrilobular nodular pattern resembling HP.

Synthesis and characterization of novel tamarind gum and rice bran oil-based emulgels for the ocular delivery of antibiotics.

In this study, we developed tamarind gum (TG) and rice bran oil (RBO)-based emulgels. The control formulation (TR0), did not contain RBO. The emulgels were named as TR1, TR2, TR3, and TR4, which contained 5% (w/w), 10% (w/w), 15% (w/w), and 20% (w/w/) of RBO, respectively. The microscopic studies showed that the emulgels were biphasic in nature. FTIR spectroscopy revealed the reduction in the hydrogen bonding with an increase in the RBO content. Impedance profiles suggested that the resistive component of the emulgels was increased as the RBO content was increased. The thermal analysis suggested that the addition of RBO reduced the water holding capacity of the emulgels. Stress relaxation studies revealed that the fluidic component was considerably higher in TG/RBO-based emulgels as compared to TR0. In vitro release study of the model drug (ciprofloxacin HCl; a hydrochloride salt of ciprofloxacin) suggested a significantly lower release from the emulgel matrices (TR1-TR4) in comparison to TR0. However, ex vivo corneal permeation of the drug increased with an increase in the RBO content. Since the emulgels were able to improve the corneal permeation of the model drug, the emulgels can be explored to deliver drugs to the internal structures of the eye.

BCL11B-related disorder in two canadian children: Expanding the clinical phenotype.

The product of the BCL11B (B-Cell Leukemia 11) gene is a bi-functional transcriptional regulator that can act as either a repressor or an activator. It plays an important role in the development of the nervous, immune, and cutaneous systems, and is also involved in dental and craniofacial development. BCL11B-Related Disorder (BCL11BRD) is a novel rare neurodevelopmental disorder associated with mutations in BCL11B. A total of 17 patients have been described in the literature thus far. The main symptoms of BCL11BRD include global developmental delay, speech impairment, dental anomalies, feeding difficulties, refractive errors, dysmorphic features, and immunological abnormalities. In this report, we describe two Canadian girls, with pathogenic de novo BCL11B variants, both diagnosed via exome sequencing. One of the patients had global developmental delay, dental anomalies, dysmorphic features, dyskinesia and hypotonia; the latter two symptoms have not been previously reported in patients with BCL11BRD. She also had dysgenesis of corpus callosum and dilatation of the frontal horns of lateral ventricles, a brain anomaly that has been previously reported in only one other patient. The second patient had developmental delay, dysmorphic features, spasticity in lower limbs and dental anomalies. Our report contributes to the knowledge of the BCL11BRD, expands the clinical phenotype, and can also aid with genetic counseling of newly identified patients.

Multimodality Management of Ruptured Large Hepatocellular Carcinoma and Its Recurrence: Rupture at Presentation Should Not Rupture Hope of Long-Term Survival.

A 59-year-old gentleman with a history of aortic valve replacement presented with spontaneously ruptured hepatocellular carcinoma in right lobe of a hepatitis C virus (HCV)-related chronic liver disease with hemoperitoneum. This acute emergency was managed by transarterial embolization. Right trisectionectomy with preservation of segment IVB after augmentation of future liver remnant by transarterial chemoembolization followed by portal vein embolization was subsequently performed. Sustained virological response to HCV was attained after surgery using sofosbuvir-based regimen. He had a delayed operative bed recurrence 1.5 years later with pulmonary metastatic disease which was managed by operative bed metastasectomy with mesh reconstruction of diaphragm and sorafenib. He is on sorafenib since past 3 years and doing well at 4.5-years follow-up since the first presentation, with significant regression of pulmonary disease and no other disease elsewhere, which highlights that where there is hope, there is a way.