Parapharyngeal metastasis in hepatocellular carcinoma-a rare entity.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It most commonly metastasizes haematogenously to the lungs and bones, less commonly via lymphatics to lymph nodes. However, metastasis to the parapharyngeal space has yet to be reported. This is the first clinical report of the treatment of parapharyngeal metastasis from HCC. The case of a 46-year-old man who was found to have a parapharyngeal soft tissue mass during routine follow-up 12 years post deceased-donor liver transplantation for hepatitis B-related HCC is reported here. This was investigated and diagnosed to be metastatic HCC. He underwent excision of the parapharyngeal metastasis, followed by adjuvant radiotherapy. Parapharyngeal metastasis is a rare occurrence in HCC. It is important to be cognizant of the possibility of disease spread to this location in order to ensure early detection and treatment. Surgical excision with adjuvant radiotherapy should be considered to achieve disease control.

The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy.

Sudden cardiac death (SCD) is often associated with structural abnormalities of the heart during autopsy. This study sought to compare the diagnostic yield of postmortem genetic testing in (1) cases with structural findings of uncertain significance at autopsy to (2) cases with autopsy findings diagnostic of cardiomyopathy. We evaluated 57 SCD cases with structural findings at cardiac autopsy. Next-generation sequencing using a panel of 77 primary electrical disorder and cardiomyopathy genes was performed. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. In 29 cases (51%) autopsy findings of uncertain significance were identified whereas in 28 cases (49%) a diagnosis of cardiomyopathy was established. We identified a pathogenic or likely pathogenic variant in 10 cases (18%); in 1 (3%) case with non-specific autopsy findings compared with 9 (32%) cases with autopsy findings diagnostic of cardiomyopathy (p = 0.0054). The yield of genetic testing in SCD cases with autopsy findings consistent with cardiomyopathy is comparable with the yield in cardiomyopathy patients that are alive. Genetic testing in cases with findings of uncertain significance offers lower clinical utility than in cardiomyopathy, with lower yields than detected previously. This highlights the need for stringent evaluation of variant pathogenicity.

Neo-antigen specific T cell responses indicate the presence of metastases before imaging.

Non-small cell lung cancer (NSCLC) causes 19% of all Australian cancer deaths, with a 5-year survival post-resection of around 60%. Post-operative recurrence is due to metastases that were undetectable pre-operatively, or growth of microscopic locoregional residual disease. However, post-operative imaging modalities typically only detect more advanced tumours; where PET-CT has a detection limit of 6-7 mm. Detection of small deposits of lung metastatic disease is of importance in order to facilitate early and potentially more effective treatment. In this study, in a murine model of lung metastatic disease, we explore whether neo-antigen specific T cells are a sensitive marker for the detection of lung cancer after primary tumour resection. We determine lung metastatic disease by histology, and then compare detection by PET-CT and neo-antigen specific T cell frequency. Detection of lung metastatic disease within the histology positive group by PET-CT and neo-antigen specific T cell frequency were 22.9% and 92.2%, respectively. Notably, neo-antigen specific T cells in the lung draining lymph node were indicative of metastatic disease (82.8 ± 12.9 spots/105 cells; mean ± SE), compared to healthy lung control (28.5 ± 8.6 spots/105 cells; mean ± SE). Potentially, monitoring tumour neo-antigen specific T cell profiles is a highly sensitive method for determining disease recurrence.

Study of Superconducting, Structural, and Thermal Properties of SnO2 Added MgB2 Bulks.

A series of SnO2 added MgB2 bulk superconductors were prepared by in situ route to study the effect of oxygen doping on superconducting and structural properties of MgB2. Several (MgB2)1-x (SnO2) x samples were fabricated with x ranging from 0, 3 wt%, 4 wt%, and 6 wt%. Upper critical field (B C2) and irreversible field (B irr) were measured by physical property measurement system. Thermal analysis was performed on the as-received SnO2 powder. Critical current densities (J cm ) were obtained at 4.2 K using magnetic measurement. X-ray diffraction results showed evidence of full SnO2 decomposition in all the doped bulk samples and a shift of a-axis in MgB2 lattice was seen. Oxygen was successfully released during heat treatment, yet no enhancement of B C2 or B irr was seen, indicating that oxygen atoms did not end up in the host lattice. Further exploration of different processing procedures is still needed in order to get oxygen substitution on the host lattice sites.

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. METHODS: We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. RESULTS: A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10-5). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. CONCLUSIONS: Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation.

Titin-truncating variants affect heart function in disease cohorts and the general population.

Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ∼1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease.

Bladder repair following iatrogenic cystotomy in irradiated small capacity bladders.

During laparotomy in a previously irradiated and operated pelvis, incidental cystotomies can occur and a tension-free, watertight, two- or three-layer closure of the bladder may be impossible. We herein report two cases of iatrogenic defects of the bladders in post-irradiated pelvises and compare the two different methods of bladder repair employed - an ileal augmentation segment used in the first case and bovine pericardial graft used in the second. Successful closures of the bladder defects were achieved in both cases. Native irradiated bowel and bovine pericardium can be useful substitutes in situations involving bladder defects in a previously irradiated pelvis. The advantages and disadvantages of the two approaches are also herein discussed.

High-volume hydrodissection: increasing the safety and efficiency of perforator dissection.

BACKGROUND: Although perforator flaps have advanced the field of reconstructive microsurgery, these flaps increase operative time and difficulty of dissection. A prospective experimental animal study was performed to study the use of high-volume hydrodissection to simultaneously decrease the operative time while increasing the safety of perforator dissection. METHODS: Sixteen Sprague-Dawley rats underwent bilateral "deep inferior epigastric perforator" flap dissections with hydrodissection used on the study side and a traditional dissection performed on the control side. Primary outcome measurements included dissection time and dissection difficulty score (1-5 in order of increasing difficulty). RESULTS: The mean (SD) dissection time for the hydrodissected perforators was 9.29 (2.50) minutes versus 13.22 (2.44) minutes for the control perforators (P < 0.001). The mean (SD) dissection difficulty score was 4.44 (0.73) for the dissection of the control side compared with 1.69 (0.87) for the hydrodissected side (P < 0.001). CONCLUSION: The mechanical benefits of hydrodissection of perforators were evident in reduction of perforator dissection time and difficulty.

Blood monocyte chemotactic protein-1 (MCP-1) and adapted disease activity Score28-MCP-1: favorable indicators for rheumatoid arthritis activity.

OBJECTIVE: We assessed blood pentraxin 3 (PTX3) and macrophage chemotactic factor-1 (MCP-1) levels as indicators of disease activity in rheumatoid arthritis (RA) patients, because data on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP) are still imperfect. METHODS: In 111 patients with RA, we examined longitudinal and cross-sectional correlations of blood PTX3, MCP-1, CRP, and ESR levels with measures of clinical arthritic activity, namely, swollen joint count (SJC), tender joint count (TJC), visual analog scale for general health (GH), DAS28, and adapted DAS28-MCP-1. RESULTS: Blood MCP-1, but not PTX3, was significantly correlated with SJC, TJC, DAS28, and DAS28-CRP. DAS28-MCP-1 was strongly correlated with DAS28 (r  = 0.984, P<0.001) and DAS28-CRP (r  = 0.971, P<0.001), and modestly correlated with CRP (r  = 0.350, P<0.001), and ESR (r  = 0.386, P<0.001). Similarly, the duration of arthritic symptoms, but not sex, was significantly correlated with variables of arthritic activity. In particular, DAS28-MCP-1 significantly correlated with DAS28 during a 6-month period (r  = 0.944, P<0.001; r  = 0.951, P<0.001; r  = 0.862, P<0.001; and r  = 0.865, P<0.001 for month 0, 1, 3, and 6, respectively). CONCLUSION: Blood MCP-1 and adapted DAS28-MCP-1, but not blood PTX3, may be useful in monitoring RA activity.

Expression of Aeromonas caviae polyhydroxyalkanoate synthase gene in Burkholderia sp. USM (JCM15050) enables the biosynthesis of SCL-MCL PHA from palm oil products.

AIMS: Burkholderia sp. USM (JCM15050) isolated from oil-polluted wastewater is capable of utilizing palm oil products and glycerol to synthesize poly(3-hydroxybutyrate) [P(3HB)]. To confer the ability to produce polymer containing 3-hydroxyhexanoate (3HHx), plasmid (pBBREE32d13) harbouring the polyhydroxyalkanoate (PHA) synthase gene of Aeromonas caviae (phaC(Ac)) was transformed into this strain. METHODS AND RESULTS: The resulting transformant incorporated approximately 1 ± 0·3 mol% of 3HHx in the polymer when crude palm kernel oil (CPKO) or palm kernel acid oil was used as the sole carbon source. In addition, when the transformed strain was cultivated in the mixtures of CPKO and sodium valerate, PHA containing 69 mol% 3HB, 30 mol% 3-hydroxyvalerate and 1 mol% 3HHx monomers was produced. Batch feeding of carbon sources with 0·5% (v/v) CPKO at 0 h and 0·25% (w/v) sodium valerate at 36 h yielded 6 mol% of 3HHx monomer by controlled-feeding strategies. CONCLUSIONS: Burkholderia sp. USM (JCM15050) has the metabolic pathways to supply both the short-chain length (SCL) and medium-chain length (MCL) PHA monomers. By transforming the strain with the Aer. caviae PHA synthase with broader substrate specificity, SCL-MCL PHA was produced. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study demonstrating the ability of transformant Burkholderia to produce P(3HB-co-3HHx) from a single carbon source.

Influenza A/H1N1 (2009) infection in pregnancy--an Asian perspective.

OBJECTIVE: To describe the characteristics of an obstetric population with influenza A/H1N1 (2009) infection, with a focus on the need for hospitalisation and complications. DESIGN: Cohort study. SETTING: Tertiary referral centre. POPULATION: Two hundred and eleven pregnant women with influenza A/H1N1 (2009) infection diagnosed by nasopharyngeal swab polymerase chain reaction (PCR). METHODS: Obstetric patients presenting to our centre were recruited and followed up. Data collected included demographic and clinical information. MAIN OUTCOME MEASURES: H1N1 and pregnancy complications, and hospitalisation needs. RESULTS: The median age of the cohort was 29.0 years (range 16-42 years), the median gestation at referral was 23.0 weeks (range 4-38 weeks), the median time interval between illness onset and presentation was 2.0 days (range 1-7 days), and the median time interval between illness onset and commencement of oseltamivir was 2.0 days (range 1-11 days). Hospital admission was significantly associated with the presence of co-morbidity (OR 4.14, 95% CI 1.82-9.37, P = 0.0001), breathlessness (OR 5.2, 95% CI 2.19-12.41, P = 0.0003) and sore throat (OR 0.35, 95% CI 0.16-0.73, P = 0.005). There were two cases of pneumonia complicating H1N1 infection, but no mortality. Nine cases developed pregnancy complications. All women recovered. CONCLUSIONS: The need for hospitalisation was significantly associated with breathlessness and co-morbidity. There was minimal morbidity and no mortality observed. We attribute this to early presentation, diagnosis and treatment.

Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons.

Many have hypothesized that cell death in Parkinson's disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP+ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP+ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, -8, -6 and -7. A time-course study indicated that activation of caspase-2 and -8 occurred upstream of caspase-6 and caspase-7. Upon MPP+ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.

Endometrioid adenocarcinoma of the uterus: surgico-pathological correlations and role of pelvic lymphadenectomy.

INTRODUCTION: In 1988, FIGO added lymph node surgery to the staging system for endometrial cancer. This change remains controversial to date. From our study we aim to determine the significance of surgico-pathological parameters of endometrioid carcinoma for pelvic nodal metastases and survival, as well as to study the role of pelvic lymphadenectomy in the surgical treatment of this disease. MATERIALS AND METHODS: A retrospective study was conducted in 198 women with endometrioid carcinoma who underwent full surgical staging including pelvic lymphadenectomy. The multiple variant regression analysis and the multi-variant logistic regression analysis were applied in the analysis of relationship. RESULTS: A positive correlation between nodal metastases and grade, myometrial invasion, peritoneal cytology, adnexal involvement, lympho-vascular space involvement and tumour size was found. For survival, significant prognosticators were grade, myometrial invasion, peritoneal cytology, lympho-vascular space involvement, adnexal involvement, associated atypia and pelvic nodal metastases. Thirty-five per cent of the patients had high risk of recurrence based on uterine pathological factors but were node negative. They were spared external beam radiation and its associated morbidities, and were treated with adjuvant vault brachytherapy instead. Six per cent of the patients would have been understaged based on uterine factors alone if pelvic lymphadenectomy had not been done. CONCLUSION: We infer that routine pelvic lymphadenectomy should be considered for all surgically fit patients with endometrioid carcinoma. The accurate staging will allow individualized adjuvant therapy and prevent understaging and overtreatment.

Passive mode locking with a nonlinear external coupled cavity at high pulse repetition rates.

A general consideration is presented for obtaining high repetition rates in passively mode-locked lasers with a nonlinear external coupled cavity. Without modification of the main cavity, as much as a sixfold increase over the original repetition rate of 76 MHz has been obtained in a coupled-cavity passively mode-locked Nd:YLF laser. At a constant average output power, the pulse width increases linearly, while the detuning range decreases with increasing repetition rates.

Noncritical matching of cavity lengths for uninterrupted additive-pulse mode locking of a cw Nd:YLF laser.

Stable interferometrically insensitive operation of an additive-pulse mode-locked Nd:YLF laser is observed over 4.8 microm of continuous detuning of the cavity lengths. This phenomenon continuously persists over 250 microm of coarse cavity-length detuning. Outside this range interferometric mode locking typically associated with additive-pulse mode locking is observed for detuning lengths of over 1 mm. The external cavity of the system consists of a multimode fiber whose four possible second-order proper modes are all excited. The underlying mechanism is a slow process with response times in the subhertz and hertz regions.

Passive mode locking of a cw Nd:YLF laser with a nonlinear external coupled cavity.

Using an optical fiber as the nonlinear medium in an external cavity, we demonstrated passive mode locking of a cw Nd:YLF laser at a 1.053-microm wavelength. Nearly transform-limited pulses as short as 3.7 psec were obtained at a repetition rate of 76 MHz directly from the laser output without further compression. The average output power ranged from 1 to 7 W.

Raman-assisted parametric frequency and polarization conversion in a birefringent fiber.

Highly efficient energy conversion of the pump into the downshifted parametric Stokes radiation resulting from the phase-matched parametric four-photon mixing and subsequent perpendicular Raman amplification in a birefringent fiber is presented. We also observed significant polarization conversion from the fast y axis to the slow x axis of the birefringent fiber as a consequence of group-velocity-matched perpendicular Raman amplification of the x-polarized parametric Stokes radiation by the y-polarized pump.

Compression of Stokes pulses generated through a parametric four-photon mixing process in a birefringent optical fiber.

We demonstrate the compressibility of Stokes pulses at a 1.075-microm wavelength that are generated through the parametric four-photon mixing process in a highly birefringent single-mode fiber pumped by 35-psec pulses at 1.053 microm from a cw mode-locked Nd:YLF laser. With a 300-m fiber and a grating pair the pump pulses at 1.053 microm are compressed to 350 fsec, with an average output power of 370 mW after compression. With a different input pump polarization angle and a different grating separation the Stokes pulses are compressed to 470 fsec, with the same average output power after compression.