Retraction Note: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The potential application of a transcriptionally regulated oncolytic herpes simplex virus for human cancer therapy.

BACKGROUND: Emerging studies have shown the potential benefit of arming oncolytic viruses with therapeutic genes. However, most of these therapeutic genes are placed under the regulation of ubiquitous viral promoters. Our goal is to generate a safer yet potent oncolytic herpes simplex virus type-1 (HSV-1) for cancer therapy. METHODS: Using bacterial artificial chromosome (BAC) recombineering, a cell cycle-regulatable luciferase transgene cassette was replaced with the infected cell protein 6 (ICP6) coding region (encoded for UL39 or large subunit of ribonucleotide reductase) of the HSV-1 genome. These recombinant viruses, YE-PC8, were further tested for its proliferation-dependent luciferase gene expression. RESULTS: The ability of YE-PC8 to confer proliferation-dependent transgene expression was demonstrated by injecting similar amount of viruses into the tumour-bearing region of the brain and the contralateral normal brain parenchyma of the same mouse. The results showed enhanced levels of luciferase activities in the tumour region but not in the normal brain parenchyma. Similar findings were observed in YE-PC8-infected short-term human brain patient-derived glioma cells compared with normal human astrocytes. intratumoural injection of YE-PC8 viruses resulted in 77% and 80% of tumour regression in human glioma and human hepatocellular carcinoma xenografts, respectively. CONCLUSION: YE-PC8 viruses confer tumour selectivity in proliferating cells and may be developed further as a feasible approach to treat human cancers.

Chronic chikungunya disease (CCD): clinical insights, immunopathogenesis and therapeutic perspectives.

Chikungunya virus, an arthropod-borne pathogen is recognized by the World Health Organization as a top priority Emerging Infectious Disease and is ranked fourth in public health needs according to the Coalition for Epidemic Preparedness Innovations. Despite its substantial impact, as evidenced by an annual estimate of 120 274 disability-adjusted life years, our understanding of the chronic aspects of chikungunya disease remains limited. This review focuses on chronic chikungunya disease, emphasizing its clinical manifestations, immunopathogenesis, therapeutic options and disease burden.

Perspectives on Academic Training in Clinical Oncology in the United Kingdom: A National Cross-Sectional Analysis.

AIMS: There are longstanding concerns relating to clinical academic training pipelines, with evidence for multiple barriers and enablers to clinical academic career progression. We sought to assess the extent to which these and other factors apply to academic training in clinical oncology in the United Kingdom. MATERIALS AND METHODS: A cross-sectional survey was undertaken using a bespoke, pre-piloted online electronic questionnaire that was distributed to clinical oncology specialty trainees and consultants who had at any point between January 2013-January 2024 commenced an academic post whilst in training. Collated information included demographic data, location and stage of training, research experience and ambitions, research skill confidence and academic career progression. RESULTS: Seventy eligible responses were included, representing 84% (n = 16/19) of UK training deaneries. Thirty-seven (53%) of the respondents had obtained their certificate of completion of training (CCT) whilst 11% (n = 8/70) and 40% (n = 28/70) were at specialty trainee level and respectively pre- or within-/post-doctoral studies. Of 34 post-CCT respondents, 58% (n = 20) had ongoing research commitments but this reached 30% of their overall activity for just 30% (n = 10). Barriers to academic progression included clinical training requirements, post availability and limited mentorship. Most (60%; n = 35/58) undertook doctoral studies in their final two training years. A majority of respondents lacked confidence in radiation oncology (RO) skills relevant to their career ambitions, with 60%, 40% and 30%, respectively, confident in RO clinical research outcome evaluation, in vitro radiation analyses and using RO animal models. CONCLUSION: These data provide a granular, long-term analysis of academic clinical oncology training at a national level; identifying poor progression to research independence underlined by limited confidence in RO research skills and multiple barriers to academic career progression. These data provide areas in which policy makers, research funders and training programmes can focus to improve academic training in clinical oncology.

Modified maxillomandibular advancement surgery for the treatment of obstructive sleep apnoea: a scoping review.

Modified maxillomandibular advancement (MMMA) has been proposed as an alternative to the classic maxillomandibular advancement (MMA) in East and Southeast Asian populations in which bimaxillary protrusion is a prevalent trait. The key difference between MMMA and MMA is the inclusion of anterior segmental osteotomies to reduce the protrusion of the perioral region. The aim of this scoping review was to identify the variations in MMMA and treatment outcomes. A search was conducted in the PubMed, Embase, and Cochrane electronic databases for articles published up to January 2023. Ten articles were included in this review. Three variations of MMMA have been reported in the literature. Treatment outcomes have mostly been favourable for all of these variations. Mandibular advancement of >10 mm and a greater than 50% reduction in the apnoea-hypopnoea index (AHI) have been well reported. Improvements in other outcome measures, such as enlargement of the airway dimension on computed tomography and the Epworth Sleepiness Scale score, have also been shown. Despite additional surgical procedures, complications have been uncommon and mostly minor in nature. It is necessary to be cognizant of MMMA and its variations when providing sleep surgery for East and Southeast Asian patients, tailoring this to the patient's profile and needs.

Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors.

Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirus-mediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

Committee machines-a universal method to deal with non-idealities in memristor-based neural networks.

Artificial neural networks are notoriously power- and time-consuming when implemented on conventional von Neumann computing systems. Consequently, recent years have seen an emergence of research in machine learning hardware that strives to bring memory and computing closer together. A popular approach is to realise artificial neural networks in hardware by implementing their synaptic weights using memristive devices. However, various device- and system-level non-idealities usually prevent these physical implementations from achieving high inference accuracy. We suggest applying a well-known concept in computer science-committee machines-in the context of memristor-based neural networks. Using simulations and experimental data from three different types of memristive devices, we show that committee machines employing ensemble averaging can successfully increase inference accuracy in physically implemented neural networks that suffer from faulty devices, device-to-device variability, random telegraph noise and line resistance. Importantly, we demonstrate that the accuracy can be improved even without increasing the total number of memristors.

A simple and cost-effective method of fixation of deep brain stimulation (DBS) electrode.

Unplanned migration of a deep brain stimulation (DBS) electrode after accurate placement at the intended target can result in a poor surgical outcome and added cost to the procedure. There are various fixation methods described in the literature. The authors describe the use of a modified burr-hole cover which serves as a simple and cost-effective method of fixation of the DBS lead with excellent results.

Psychogenic coma after dental surgery under general anaesthesia.

Delayed awakening after general anaesthesia due to psychogenic coma is a phenomenon that rarely presents to the oral and maxillofacial surgeon. A case of psychogenic coma following general anaesthesia for dental extractions is presented here. It is recommended that patients at risk of conversion disorder should be counselled about the risks of psychogenic coma. Early diagnosis of this condition could lead to better patient management.

Intrinsic Resistance Switching in Amorphous Silicon Suboxides: The Role of Columnar Microstructure.

We studied intrinsic resistance switching behaviour in sputter-deposited amorphous silicon suboxide (a-SiO x ) films with varying degrees of roughness at the oxide-electrode interface. By combining electrical probing measurements, atomic force microscopy (AFM), and scanning transmission electron microscopy (STEM), we observe that devices with rougher oxide-electrode interfaces exhibit lower electroforming voltages and more reliable switching behaviour. We show that rougher interfaces are consistent with enhanced columnar microstructure in the oxide layer. Our results suggest that columnar microstructure in the oxide will be a key factor to consider for the optimization of future SiOx-based resistance random access memory.

An active surveillance study of vancomycin-resistant Enterococcus in Queen Elizabeth Hospital, Hong Kong.

OBJECTIVE: To assess the rate of faecal vancomycin-resistant Enterococcus colonisation in high-risk patients in a regional hospital. DESIGN: Prospective observational surveillance study. SETTING: Queen Elizabeth Hospital, Hong Kong. PATIENTS: From September 2001 to December 2002, stool samples from patients in the intensive care unit and patients in whom Clostridium difficile testing was requested were used for study using a broth enrichment method. MAIN OUTCOME MEASURES: Number of faecal vancomycin-resistant Enterococcus colonisation. RESULTS: A total of 2414 cultures from 1792 patients were tested for vancomycin-resistant Enterococcus using a broth enrichment method. Only one (0.06%) patient was found to harbour a vancomycin-resistant Enterococcus faecalis in the gastro-intestinal tract. Surveillance cultures from contacts of the case revealed another six with vancomycin-resistant Enterococcus faecalis. Vancomycin-resistant Enterococcus faecalis was also later reported from a clinical specimen (catheterized urine) of another patient. They were all epidemiologically linked to the index case. Mean inhibitory concentrations of vancomycin and teicoplanin were determined to be higher than 256 and 0.5 microgram/mL, respectively by E-test for all the vancomycin-resistant Enterococcus isolates. Polymerase chain reaction analysis confirmed the presence of vanB genes and the result was in line with the phenotype. Pulsed-field gel electrophoresis confirmed a monoclonal vancomycin-resistant Enterococcus outbreak. Strict infection control measures recommended by the Centers for Disease Control and Prevention were followed and the outbreak was successfully controlled. CONCLUSION: Vancomycin-resistant Enterococcus colonisation is rare, but present among high-risk patients in our hospital. A routine surveillance programme should be implemented that will enable early case detection and prompt initiation of infection control measures to prevent the emergence of an endemic situation.

Desmoid tumor (fibromatosis) of the breast. A clinician's dilemma--a case report and review.

Desmoid tumor of the breast is a clinician's dilemma as it is difficult to differentiate it from carcinoma clinically, mammographically, and cytologically. Histologically, it must be distinguished from fibrosarcoma. Current management favors wide excision with clear margins. Recurrence is relatively common and usually occurs within 3 years of excision. Adjuvant hormonal therapy does not reduce local recurrence rates; evidence indicates that postoperative radiotherapy can improve the 10-year recurrence-free survival rate.

Nitric oxide and subarachnoid hemorrhage: elevated level in cerebrospinal fluid and their implications.

OBJECTIVE: Nitric oxide (NO) plays an important role in the pathogenesis of neuronal injury after brain ischemia, and decreased levels of NO have been implicated in the pathogenesis of vasospasm after subarachnoid hemorrhage (SAH). In this study, we measured the ventricular cerebrospinal fluid (CSF) NO levels in patients with SAH and correlated the levels with clinical grade and middle cerebral artery velocities measured with transcranial Doppler ultrasound. METHODS: All patients with spontaneous SAH documented on computed tomography and with an external ventricular drain inserted within 24 hours of hemorrhage were included in the study. A total of 16 patients were studied between August 1999 and August 2000. CSF was collected serially at the time of surgery and subsequently at daily intervals. It was collected during the time that the external ventricular drain remained patent and in situ. NO levels were measured by photometric analysis by using a nitrite/nitrate assay kit (Cayman Chemical, Ann Arbor, MI). RESULTS: The peak NO level in patients with SAH ranged from 9.96 to 168.16 micromol, with a median of 36.93 micromol. The levels were significantly elevated as compared with the control group (5.16 micromol, P < 0.05). The median NO level in patients with poor-grade SAH was 67.14 micromol as compared with 27.42 micromol in patients with good-grade hemorrhage (P < 0.05). No correlation was seen between CSF NO levels and middle cerebral artery velocities. The median NO level was 33.2 micromol in patients with a poor outcome as compared with 30.25 micromol in patients with a good outcome (P > 0.05). CONCLUSION: This study showed that NO levels are elevated after spontaneous SAH, and the degree of elevation is higher in patients with poor-grade SAH.

Giant aneurysm treated by bilateral cervical carotid artery to proximal middle cerebral artery bypass and balloon embolisation: a case report.

The authors describe a case of a 59 year-old Chinese lady with a history of spontaneous left caroticocavernous fistula in 1988 treated by left internal carotid artery clipping and muscle embolisation. She subsequently presented with a subarachnoid haemorrhage in November 1997 secondary to rupture of an unclippable giant right internal carotid artery aneurysm. This was treated satisfactorily with bilateral cervical carotid artery to proximal middle cerebral artery bypass followed by balloon occlusion. Postoperatively, the patient has no neurological deficit and CT angiogram shows good patency of both grafts 6 months after surgery.

Non-traumatic spontaneous acute epidural haematoma -- report of two cases and review of the literature.

Epidural haematomas are usually associated with preceding head trauma. The entity of non-traumatic spontaneous acute epidural haematoma is rare and most commonly occurs in the presence of infectious disease. It can also occur in the presence of coagulopathy, vascular malformations of the dura mater and haemorrhagic tumours. Sickle cell disease, systemic lupus erythematosus, open heart surgery and haemodialysis have also been implicated as causative factors. The authors report two cases of spontaneous epidural haematomas (one of unknown aetiology and one from a coagulation disorder) and discuss the aetiological agents involved in this rarely described condition.

Simple, at-site detection of diethylene glycol/ethylene glycol contamination of glycerin and glycerin-based raw materials by thin-layer chromatography.

This paper describes a rapid, inexpensive thin-layer chromatographic (TLC) method that separates diethylene glycol (DEG) from glycerin and other glycols. Studies with collaborating laboratories of the World Health Organization have shown that about 6% DEG in glycerin and about 2% DEG in acetaminophen (paracetamol) elixirs may be detected by direct visual inspection of the developed TLC sheets. Staining the sheet permits detection of DEG at less than 0.1%. The method costs less than $1.00 per test and takes 20 min by visual inspection, longer when staining is required. The visual method can be performed without laboratory facilities by personnel having little previous training. Samples testing positive by the visual method can be submitted to a laboratory for confirmation and quantitation of DEG.

Clinics in diagnostic imaging (89). Infantile hepatosplenic haemangioendotheliomas.

The ultrasonographical and computed tomography findings of a six-month-old female infant with haemangioendotheliomas of the liver and spleen are described. The splenic lesion had an unusual ultrasonographical appearance of a well-defined isoechoic mass with a hypoechoic rim. Diagnosis was confirmed by histological examination of the hepatic biopsy specimen. Hepatosplenic lesions in the first year of life may be due to a variety of pathological processes. It is important to include haemangioendotheliomas in the differential diagnosis of hepatosplenic masses in an infant.

Myocardial infarction with angiographically normal coronary arteries.

Acute myocardial infarction without obstruction of the coronary arteries is uncommon. The clinical course of a 32 year old patient with documented acute inferior and anterior wall infarctions is described. Selective coronary arteriography performed 23 months later revealed no obstruction of the coronary arteries angiographically. Probable pathologic mechanism are discussed.

Post-partum cardiomyopathy.

A report is presented of a patient who developed signs of cardiac failure 6 weeks after the birth of her fourth child. Detailed cardiac investigation indicated the diagnosis to be post-partum cardiomyopathy, a condition more commonly encountered in Negro women and comparatively rare in this country. The aetiology and mode of presentation are discussed.