Synthetic amyloid beta does not induce a robust transcriptional response in innate immune cell culture systems.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease that impacts nearly 400 million people worldwide. The accumulation of amyloid beta (Aß) in the brain has historically been associated with AD, and recent evidence suggests that neuroinflammation plays a central role in its origin and progression. These observations have given rise to the theory that Aß is the primary trigger of AD, and induces proinflammatory activation of immune brain cells (i.e., microglia), which culminates in neuronal damage and cognitive decline. To test this hypothesis, many in vitro systems have been established to study Aß-mediated activation of innate immune cells. Nevertheless, the transcriptional resemblance of these models to the microglia in the AD brain has never been comprehensively studied on a genome-wide scale. METHODS: We used bulk RNA-seq to assess the transcriptional differences between in vitro cell types used to model neuroinflammation in AD, including several established, primary and iPSC-derived immune cell lines (macrophages, microglia and astrocytes) and their similarities to primary cells in the AD brain. We then analyzed the transcriptional response of these innate immune cells to synthetic Aß or LPS and INFγ. RESULTS: We found that human induced pluripotent stem cell (hIPSC)-derived microglia (IMGL) are the in vitro cell model that best resembles primary microglia. Surprisingly, synthetic Aß does not trigger a robust transcriptional response in any of the cellular models analyzed, despite testing a wide variety of Aß formulations, concentrations, and treatment conditions. Finally, we found that bacterial LPS and INFγ activate microglia and induce transcriptional changes that resemble many, but not all, aspects of the transcriptomic profiles of disease associated microglia (DAM) present in the AD brain. CONCLUSIONS: These results suggest that synthetic Aß treatment of innate immune cell cultures does not recapitulate transcriptional profiles observed in microglia from AD brains. In contrast, treating IMGL with LPS and INFγ induces transcriptional changes similar to those observed in microglia detected in AD brains.

Routine chest CT for staging of gastric cancer.

BACKGROUND: International guidelines on clinical staging of gastric cancer recommend the use of chest CT for the detection of pulmonary metastases. This study assessed the clinical value of routine chest CT in the staging of gastric cancer. METHODS: This retrospective study included patients identified from the gastric cancer registry of Chang Gung Memorial Hospital, Linkou, Taiwan. All patients who underwent clinical staging between 2008 and 2014 were included. The pattern, site and number of metastases at initial presentation and after surgery with curative intent were evaluated. Pulmonary metastases were defined as multiple small round pulmonary nodules with a random distribution or of variable size. RESULTS: Some 1669 patients were included, of whom 478 (28·6 per cent) had metastatic disease at clinical presentation. The majority of metastases were to the peritoneum (75·7 per cent of patients) or liver (30·5 per cent), and only 27 patients (5·6 per cent) had pulmonary metastases at presentation, none of which were isolated to the lung. Of these 27 patients, 11 had primary lesions located at the cardia/fundus. In 19 patients the lung metastases were also detected on the staging chest X-ray. After surgery there were 196 cancer recurrences. Some 15 patients (7·6 per cent) had lung metastasis and this was not the only site of metastases in any patient. The prevalence of lung metastasis at presentation of the disease and after surgery was 1·6 and 1·5 per cent respectively. CONCLUSION: This study does not support the routine use of chest CT for staging of gastric cancer as isolated pulmonary metastasis in the absence of other metastatic sites could not be detected.

CT-guided percutaneous core-needle biopsy of pancreatic masses: comparison of the standard mesenteric/retroperitoneal versus the trans-organ approaches.

AIM: To compare the safety and efficacy of percutaneous computed tomography (CT)-guided core-needle biopsy (CNB) of pancreatic masses traversing the gastrointestinal tract or solid viscera versus trans-mesenteric and retroperitoneal approaches. MATERIALS AND METHODS: CT-guided CNB of pancreatic lesions performed between May 2004 and December 2014 were retrospectively analysed at a single centre. Biopsies were performed using 18- or 20-G needles with a coaxial system. CT images, histopathology reports, medical records, and procedural details for all patients were reviewed to evaluate the biopsy route, complications, and diagnostic accuracy. According to the routes, biopsies were divided into trans-mesenteric, retroperitoneal and trans-organ approaches for comparison. RESULTS: A total of 85 patients, who had undergone 89 CNBs for pancreatic masses were reviewed. The overall sensitivity, specificity, and accuracy of CNB for detecting malignancy via various routes were 88.8%, 100%, and 89.9%, respectively, with a complication rate of 20.2%. Trans-organ biopsies of pancreatic masses (n=22) were performed safely via a direct pathway traversing the stomach (n=14), colon (n=3), small bowel (n=2), liver (n=2), and spleen (n=1). The sensitivity, specificity, and accuracy were 90.5%, 100%, and 90.9%, respectively. In the trans-organ biopsy group, three biopsies (13.6%) resulted in minor haematomas, but no major complications occurred. There were no statistically significant differences in the diagnostic efficacy or complication rate among the different biopsy routes. CONCLUSION: Percutaneous CT-guided CNB using a trans-organ approach is a feasible technique for diagnosing pancreatic malignancy; however, as this series was small, more data is required.

Trans-organ versus trans-mesenteric computed tomography-guided percutaneous fine-needle aspiration biopsy of pancreatic masses: feasibility and safety.

AIM: To evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous fine-needle aspiration biopsy (FNAB) of pancreatic masses that traverses the gastrointestinal tract or solid viscera. MATERIALS AND METHODS: From January 2002 to December 2012, 144 patients underwent 165 CT-guided biopsies of pancreatic masses. Biopsies were performed using a 21 or 22 G needle. Cytology reports, medical records, and procedure details for all patients were retrospectively reviewed to evaluate the biopsy route, complications, and diagnostic accuracy. RESULTS: Trans-organ biopsies of pancreatic masses were safely performed via a direct pathway traversing the stomach (n = 45), colon (n = 14), jejunum (n = 4), or liver (n = 5). There were five self-limiting mesenteric haematomas along the biopsy route on immediate post-procedure CT and all patients remained asymptomatic. All haematomas occurred after a trans-mesenteric approach rather than passage through abdominal organs. Three patients had acute pancreatitis. There was no significant difference in complications and diagnostic yields between the groups. The sensitivity, specificity, positive predictive value, and negative predictive value of final FNAB cytology for malignancy were 98.3%, 100%, 100% and 71.4%, respectively. The overall accuracy was 98.4%. CONCLUSION: Percutaneous FNAB using the trans-organ approach is a safe and effective technique to diagnose pancreatic malignancy.

CT and MRI features of acinar cell carcinoma of the pancreas with pathological correlations.

AIM: To document the computed tomography (CT) and magnetic resonance imaging (MRI) features of acinar cell carcinoma of the pancreas and to correlate them with pathological findings to determine the unique imaging manifestations of this rare subtype tumour of the pancreas. MATERIALS AND METHODS: From January 1986 to August 2008, six patients (five men and one woman, mean age 61.3 years) with histologically proven acinar cell carcinoma of the pancreas underwent CT (n=6) and MRI (n=4) examinations. The imaging features of each tumour were documented and compared with pathological findings. RESULTS: The tumours were distributed in the head (n=4), body (n=1), and tail (n=1) of the pancreas. Four masses (67%) were uniformly or partially well-defined with thin, enhancing capsules. Central cystic components were found in five tumours (83%). Two tumours (33%) exhibited intratumoural haemorrhage, and one tumour (17%) had amorphous intratumoural calcification. In both CT and MRI, the tumours enhanced less than the adjacent normal pancreatic parenchyma. The signal intensity on MRI was predominantly T1 hypointense and T2 iso- to hyperintense. CONCLUSION: Acinar cell carcinoma of the pancreas has distinct imaging features, and both CT and MRI are useful and complementary imaging methods.

Combined hepatocellular cholangiocarcinoma: prognostic factors investigated by computed tomography/magnetic resonance imaging.

This study was designed to assess the clinical usefulness of imaging for predicting the prognosis of patients with combined hepatocellular cholangiocarcinoma (cHCC-CC). Between 1999 and 2004, 30 patients with histopathologically proven cHCC-CC underwent computed tomography (CT) or magnetic resonance imaging (MRI). The imaging data and survival were analysed. Univariate log-rank analysis of imaging findings revealed that tumour necrosis, bile duct invasion, major vascular branch invasion, multiplicity, bilobar distribution, regional lymph node involvement, regional organ invasion, distant metastasis and ascites had adverse influences on overall survival. Multivariate Cox proportional hazard analysis demonstrated that major vascular branch invasion, regional organ invasion, nodal and distant metastases were independent prognostic factors that adversely affected overall survival rates. Overall cumulative survival rates at 1, 3 and 5 years were 53%, 26% and 12%, respectively. Analysing the survival of our patients by using clinical stages of the newly updated American Joint Committee on Cancer (AJCC) classification for liver neoplasm based on the imaging findings, we found significant differences between stages I/II and III (p < 0.001) and between stages III and IV (p = 0.040). We conclude CT or MRI can be used to identify the prognostic factors and to estimate the outcomes of patients with cHCC-CC.

Surgical coverage of exposed hydroxyapatite implant with retroauricular myoperiosteal graft.

BACKGROUND: With the increasing use of hydroxyapatite orbital implants, the complication of exposure has become apparent to oculoplastic surgeons. Many kinds of patch grafts, such as sclera, dermis, and hard palate mucosa, have been used to cover exposed hydroxyapatite implants with inconsistent results. In this study, the authors use a newly developed technique, autogenous retroauricular myoperiosteal graft, and the results are reported. METHODS: A piece of retroauricular muscle together with its underlying periosteum was carefully harvested. This myoperiosteal graft was patched to the debrided hydroxyapatite exposure area with the periosteal surface facing outward. The margin of periosteal surface was secured with conjunctiva and left uncovered for the surrounding conjunctiva to epithelialise. RESULTS: Nine eyes with hydroxyapatite exposure more than 3 mm were managed with autogenous retroauricular myoperiosteal grafts. Seven cases were successfully treated with single graft surgery. The other two cases needed an additional graft surgery, and there was no re-exposure noted thereafter. Five patients received a successful insertion of the motility peg. All nine patients have been fitted with prosthesis with reasonable motility. There were no complication noted during more than 1 year of follow up. CONCLUSION: The thick composite nature of the myoperiosteal graft provides a durable and vascularised coverage for exposed hydroxyapatite implants. This technique offers an encouraging alternative for the management of exposed hydroxyapatite implants.

Manipulation of carbon assimilation with respect to expression of the pac gene for improving production of penicillin acylase in Escherichia coli.

A strategy of genetically manipulating carbon assimilation with respect to expression of the pac gene was employed for overproduction of recombinant penicillin acylase (PAC). Two expression plasmids of pCLL2902 and pCLL3201, which contain the pac coding region but differ in the pac regulatory region, were constructed for the production experiments. Expression of the pac gene was subjected to phenyl acetic acid (PAA-) induction and glucose catabolite repression for pCLL3201, whereas it was subjected to neither of the two transcriptional regulations for pCLL2902. The specific PAC activity for strains harboring pCLL2902 was significantly higher than that for strains harboring pCLL3201 due to an improved transcription efficiency. In addition, no inclusion bodies were observed upon production of PAC using the current expression systems. The results suggest that using the native pac promoter instead of a strong promoter such as tac for regulation is a feasible approach for production of PAC. The impact of the current expression systems is also significant from a process viewpoint since, using strains harboring pCLL2902, not only could glucose replace PAA as a carbon source of Escherichia coli cultures for production of PAC but also the volumetric PAC activity was highly improved.

Results of intraoperative mitomycin C application in dacryocystorhinostomy.

AIMS: To evaluate the long term results of intraoperative mitomycin C application in dacryocystorhinostomy (DCR) surgery compared with results of the conventional procedure. METHODS: In this prospective randomised controlled study, a total of 88 eyes diagnosed with acquired nasolacrimal duct obstruction were randomly divided into a conventional DCR group and a mitomycin C group in which mitomycin C was used during DCR surgery. The surgical procedures in both groups were exactly the same, except that in the patients in the mitomycin C group, a piece of neurosurgical cottonoid soaked with 0.2 mg/ml mitomycin C was applied to the osteotomy site for 30 minutes. The results of the DCR surgeries were evaluated by objective findings such as irrigation and the height of tear meniscus and subjective symptoms by asking patients the condition of tearing improvement. RESULTS: Among the 44 eyes in the mitomycin C group, 95.5% of patients remained totally symptom free after 10 months of follow up; while in the conventional group, 70.5% of patients were reported to be symptom free and 18% of patients to have an improvement in their symptoms. There was a significant difference between these two groups. As far as objective findings were concerned, there were 41 eyes in the mitomycin C group classified as having a normal and one eye with moderate tear meniscus level, compared with 32 eyes and seven eyes, respectively, in the conventional group. There was also a significant difference between these two groups. The non-patency rate in the mitomycin C group is 4.5% compared with 11.4% in the conventional group. There were no complications such as abnormal nasal bleeding, mucosal necrosis, or infection except one patient with delayed wound healing. CONCLUSIONS: Intraoperative mitomycin C application is effective in increasing the success rate of DCR surgery in standard nasolacrimal duct obstruction, and no significant complications resulted from its use.

Effect of SecB chaperone on production of periplasmic penicillin acylase in Escherichia coli.

The effect of SecB chaperone on production of periplasmic penicillin acylase (PAC) in Escherichia coli was investigated. It appears that formation of PAC required the function of SecB chaperone and the amount of SecB required was at a basal level. The secB mutant was defective in production of PAC, and the impairment could be complemented by extrachromosomally supplementing SecB in trans. The function of SecB might be primarily stabilizing the cytoplasmic PAC precursors. Overproduction of SecB chaperone usually resulted in an increase in the amount of PAC precursors without enhancing PAC activity. In addition, most of the PAC precursors were located in the periplasm, suggesting that formation of active PAC was likely limited by periplasmic processing steps.

Laparoscopic cholecystectomy for gallbladder lymphangiomas.

Intraabdominal lymphangiomas are rare benign tumors that can be difficult to diagnose preoperatively. The clinical presentation of these tumors is variable and potentially misleading. Therefore, complex imaging studies are required to evaluate this condition. Ultrasound and CT scan are important to make the correct preoperative diagnosis and also provide important information regarding location, size, and adjacent organ involvement. The treatment of choice is complete excision. This report describes two patients with cystic lymphangiomas originating in the gallbladder. The correct diagnosis was made preoperatively in one patient, and both patients were treated successfully by laparoscopy.

Recurrent intracerebral hemorrhages in cerebral amyloid angiopathy: a case report.

Cerebral amyloid angiopathy frequently causes recurrent intracerebral hemorrhages in elderly patients who do not have systemic hypertension. Surgery should be reserved for conditions which cannot be controlled by medical treatment. When surgery is needed, potential complications (such as bleeding near the operation site or remote area) should be kept in mind. A case study of a 66-year-old woman with cerebral amyloid angiopathy and recurrent intracerebral hemorrhages is presented.

Endoscopic extraperitoneal lumbar sympathectomy for plantar hyperhidrosis: case report.

A right sided endoscopic retroperitoneal lumbar sympathectomy was performed on a 23 year old female who had plantar hyperhidrosis. After the operation, the right foot temperature increased and the plantar hyperhidrosis was relieved. During the follow up period, both feet were warm and dry, although only the right side lumbar sympathectomy had been performed. The outcome appeared to be compatible with that of an open procedure but with minimal invasiveness.

Thoracoscopic sympathectomy for palmar hyperhidrosis: effects on pulmonary function.

Palmar hyperhidrosis, probably caused by an over-reactivity of sympathetic nerves passing through the second and the third thoracic sympathetic ganglia (T2 & T3 ganglia), can only be cured by sympathectomy. Such sympathetic denervation may also alter pulmonary function. Previous studies have shown that open sympathectomy can cause significant deterioration in pulmonary function, however, the surgical procedure itself may contribute to the change. Recently thoracoscopic sympathectomy has been developed as a minimally invasive but effective treatment for palmar hyperhidrosis. In order to investigate the effect of sympathectomy, pulmonary function was compared before and four weeks after operation in 20 patients. Forced vital capacity (FVC) (-2.3%), forced expiratory volume in one second (FEV1) (-6.1%), and FEV1/FVC (-4.6%) were all slightly but significantly decreased four weeks after thoracoscopic sympathectomy. Also the instantaneous forced expiratory flow at 75%, 50% and 25% of the FVC (Vmax25, Vmax50, Vmax75) in flow-volume curves were decreased (-1.6%, -8.4%, and -20% respectively). Therefore, thoracoscopic sympathectomy minimises pulmonary restrictive effects but allows subclinical small airway obstructive effects to become more evident.

[Changing seroepidemiology pattern of hepatitis B virus infection among elementary and junior high school children in Keelung, Taiwan, 1988].

A large-scale seroepidemiologic study of 20816 (35.6% of total) elementary and junior high school children (grades 1-9) in Keelung, Taiwan was conducted in April-May 1988. The study was to investigate the current status of hepatitis B virus (HBV) infection and to plan the extension of the present HBV prevention program to other age groups. Two HBV markers, hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs), were determined by enzyme immunoassay. The overall seropositivity rates of HBsAg and anti-HBs were 19.0% and 25.6%, respectively. Only 0.4% of the children studied were concurrently positive for both HBsAg and anti-HBs and 55.8% of them were negative for these two markers. It is noteworthy that the seropositivity rate of HBsAg increased with increasing age, from 15.4% in grade 1 (ages 6) to 23.7% in grade 9 (ages 15). This rate of HBsAg was not higher than the 1986 findings (14.0-25.5%) screened from children (4-13 years old) in Keelung, by comparing each age cohort strata, even though the age of study population was two years older. These data indicate that the current hepatitis control strategies have resulted in the reduction of the hepatitis B carrier rate among children from more than 20% to 15% at age 6 (grade 1) in Keelung, but the reduction is still higher than in Taipei children (10%). The seropositivity rate of anti-HBs was also increased with increasing age, from 13.5% (grade 1) to 44.1% (grade 9) and was similar to previous findings in Taiwan.(ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral cholangiocarcinoma with thoracic spine metastasis: a successful surgically treated case.

In this study we present a rare case of cholangiocarcinoma with metastasis to the thoracic spine. A 63-year-old female with peripheral cholangiocarcinoma associated with hepatolithiasis presented low back pain as a result of a thoracic spine (T12) compression fracture. Spine surgery and pathological examination revealed a metastatic mucinous adenocarcinoma of unknown origin. Two weeks after the spine surgery, a nontender palpable abdominal mass was found at the epigastric area. Abdominal sonography (US), abdominal computed tomography (CT), and magnetic resonance cholangiopancreaticogram (MRCP) revealed a hepatic tumor, hepatolithiasis, and gallbladder empyema. The patient underwent hepatic resection, cholecystectomy, and choledocholithotomy with T-tube stent. Pathological examination with immunohistochemical stain revealed hepatolithiasis concurrent with mucinous cholangiocarcinoma. Postoperative course was uneventful and no recurrence was noted during a 1-year follow-up period.

Clinicopathological analysis of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma: are they just apples and oranges?

BACKGROUNDS/AIMS: Intrahepatic cholangiocarcinoma and colorectal cancer liver metastasis are the most primary and secondary adenocarcinoma of the liver, respectively. A large-scale long-term comparative study of these two cohort patient is lacking. METHODS: A total of 166 colorectal cancer liver metastasis patients and 206 intrahepatic cholangiocarcinoma patients who had undergone curative liver resection were retrospectively analysed. Among 206 intrahepatic cholangiocarcinoma, there were 47 intraductal growth type-intrahepatic cholangiocarcinoma and 159 non-intraductal growth type-intrahepatic cholangiocarcinoma. The demographics, clinicopathological data, immunohistochemical study and survival were analysed. RESULTS: The intrahepatic cholangiocarcinoma patients were more female-predominated, associated with hepatolithiasis, symptomatic, jaundiced, and with larger tumour size compared with those of colorectal cancer liver metastasis. Prognostic factors of intrahepatic cholangiocarcinoma were pathologic staging, histologic pattern and section margin; whereas prognostic factors of colorectal cancer liver metastasis were rectal origin, differentiation, section margin and bilobar distribution. CK7 and CK20 differentiated majority of intrahepatic cholangiocarcinoma from colorectal cancer liver metastasis, while CDX2 and MUC5AC helped to differentiate inconclusive cases. The 1-, 3-, 5- and 10-year survival rates of colorectal cancer liver metastasis were 77%, 31%, 20% and 14%, compared to 53%, 21%, 13% and 7% of intrahepatic cholangiocarcinoma (p=.0001). Furthermore, the survival of colorectal cancer liver metastasis was comparable to staged II intrahepatic cholangiocarcinoma (p=.8866) and intraductal growth type-intrahepatic cholangiocarcinoma (p=.1915). CONCLUSIONS: Demographics, precipitating factor, clinical manifestations, and prognostic factors of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma differed remarkably. High incidence of CDX2 and MUC2 expression in colorectal cancer liver metastasis and intraductal growth type-intrahepatic cholangiocarcinoma might explain their similar cytoarchitecture and survival.

Organic Donor-Acceptor System Exhibiting Electrical Bistability for Use in Memory Devices.

An all-organic electrically bistable device and its application in non-volatile memory is reported. The switching mechanism is attributed to electric-field-induced charge transfer from an organic electron donor to an acceptor, so that the device switches from a low- to a high-conductivity state. This device provides a new direction for data-storage technology based on organic composites.