Spindle oscillations are generated in the dorsal thalamus and modulated by the thalamic reticular nucleus

Spindle waves occur during the early stage of slow wave sleep and are thought to arise in the thalamic reticular nucleus (TRN), causing inhibitory postsynaptic potential spindle-like oscillations in the dorsal thalamus that are propagated to the cortex. We have found that thalamocortical neurons exhibit membrane oscillations that have spindle frequencies, consist of excitatory postsynaptic potentials, and co-occur with electroencephalographic spindles. TRN lesioning prolonged oscillations in the medial geniculate body (MGB) and auditory cortex (AC). Injection of GABA~A~ antagonist into the MGB decreased oscillation frequency, while injection of GABA~B~ antagonist increased spindle oscillations in the MGB and cortex. Thus, spindles originate in the dorsal thalamus and TRN inhibitory inputs modulate this process, with fast inhibition facilitating the internal frequency and slow inhibition limiting spindle occurrence

Lung Cancer Decreased Sharply in First 5 Years After Smoking Cessation in Chinese Men

BackgroundThe rate of decline in lung cancer risk after smoking cessation among male population and the importance of the magnitude of the early decline were not sufficiently defined in the earlier studies. We evaluated the detailed duration-response relationship between years since smoking cessation and lung cancer risk across major histological types in a population-based case-referent study.MethodsWe recruited 1208 consecutive incident cases of primary lung cancer among Chinese males from the largest oncology center in Hong Kong during 2004–2006, and 1069 male community referents frequency-matched in 5-year age groups. We performed unconditional multiple logistic regression and generalized additive model incorporating smoothing spline to model the potential nonlinear effect of years since cessation on lung cancer.ResultsAll histological types of lung cancer were strongly associated with current smoking. We observed a rapidly decreasing odds ratio of lung cancer (>50%) across all major histological types of lung cancer (except for the large cell type) within the first 5 years of quitting; the odds ratio continued to decrease but at a slower rate in the subsequent years.ConclusionThe substantial benefits obtainable within a short period of 5 years' abstinence should convey an encouraging message to chronic smokers, clinicians, and public health workers

The repeat FIT (RFIT) study:Does repeating faecal immunochemical tests provide reassurance and improve colorectal cancer detection?

AimFaecal immunochemical tests (FIT) are highly sensitive for colorectal cancer (CRC) detection. Little evidence exists regarding repeat FIT. The repeat FIT (RFIT) study aimed to determine whether second and third FIT provide reassurance and improve CRC or significant bowel disease (SBD) identification.MethodsThis was a prospective observational study. Patients recruited from urgent referrals returned three FIT and underwent colonoscopy. Chi-square tests compared categorical data. Diagnostic accuracy variables (sensitivity/specificity/positive predictive value [PPV]/negative predictive value [NPV]) were calculated for one, two and three FIT (95% CI). Three negative FIT (<10 μg Hb/g of faeces [μg/g]) groups (one, two, three) were compared with positive groups (one or more FIT ≥10 μg/g). CRC and SBD detection rates were compared by strategy.ResultsA total of 460 patients (mean age: 66.8 years, 233 males and 227 females, 23 CRC, 80 SBD) were included in the study. For one, two and three negative FIT, CRC sensitivity remained static (95.7%); specificity (44.6%, 40.7% and 38.4%) and NPV decreased (99.5%, 99.4% and 99.4%). For SBD, sensitivity increased (78.8%, 83.8% and 86.3%), specificity decreased (47.4%, 43.7% and 41.6%) and NPV increased (91.4%, 92.7% and 93.5%). In one, two and three positive FIT groups, CRC detection was 8.3%,16.1% and 20.9%. CRC mean FIT was 150 μg/g, <6 μg/g for benign pathology.ConclusionsOne or more negative FIT increases the sensitivity for CRC/SBD. Repeating FIT provides greater differentiation of patients with and without CRC/SBD compared to single FIT but is associated with decreased specificity and PPV. Multiple negative FIT may offer reassurance; however, application of repeating FIT may be restricted given the associated increase in investigations S1

Are Current or Future Mesothelioma Epidemics in Hong Kong the Tragic Legacy of Uncontrolled Use of Asbestos in the Past?

BACKGROUND: Because of the long latent period of asbestos-related mesothelioma, investigators suggest that the high incidence of this disease will continue in the coming decades. OBJECTIVES: We describe the time trends of mesothelioma incidence and its relationship to historical consumption of asbestos in Hong Kong and project future trends of mesothelioma incidence. METHODS: We obtained local annual consumption of total asbestos for 1960-2006 (converted to kilograms per person per year). Age-standardized incidence rates (ASIRs) of mesothelioma were computed and depicted on graphs using the centered moving average method. Indirectly standardized rates were regressed on a transformation of consumption data that assumed that the latency between asbestos exposure and mesothelioma diagnosis followed a normal distribution with a mean ± SD of 42 ± 10.5 years. RESULTS: ASIRs for males started to increase substantially in 1994 and were highest in 2004; for females, ASIRs climbed in the 1980s and in the early 1990s but have fluctuated without obvious trends in recent years. The highest asbestos consumption level in Hong Kong was in 1960-1963 and then decreased sharply afterward. Using past asbestos consumption patterns, we predict that the mesothelioma incidence rate for males will peak in 2009, with the number of cases peaking in 2014, and then slowly decline in the coming decades. CONCLUSIONS: Hong Kong experienced an epidemic of mesothelioma from 2000 to 2006 that corresponded with the peak of local asbestos consumption in the early 1960s assuming an average latent period of 42 years. The incidence is anticipated to decline in the coming decades but may not decrease back to the background risk level (the risk unrelated to asbestos exposure)

Satin associated lower cancer risk and related mortaity in patients with heart failure

Aims Patients with heart failure (HF) have an increased risk of incident cancer. Data relating to the association of statin use with cancer risk and cancer-related mortality among patients with HF are sparse. Methods and results Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (n = 87 102) from 2003 to 2015. Inverse probability of treatment weighting was used to balance baseline covariates between statin nonusers (n = 50 926) with statin users (n = 36 176). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of cancer and cancer-related mortality associated with statin use. Of all eligible subjects, the mean age was 76.5 +/- 12.8 years, and 47.8% was male. Over a median follow-up of 4.1 years (interquartile range: 1.6-6.8), 11 052 (12.7%) were diagnosed with cancer. Statin use (vs. none) was associated with a 16% lower risk of cancer incidence [multivariable adjusted subdistribution hazard ratio (SHR) = 0.84; 95% confidence interval (CI), 0.80-0.89]. This inverse association with risk of cancer was duration dependent; as compared with short-term statin use (3 months to = 6 years of use. Ten-year cancer-related mortality was 3.8% among statin users and 5.2% among nonusers (absolute risk difference, -1.4 percentage points [95% CI, -1.6% to -1.2%]; adjusted SHR= 0.74; 95% CI, 0.67-0.81). Conclusion Our study suggests that statin use is associated with a significantly lower risk of incident cancer and cancer-related mortality in HF, an association that appears to be duration dependent. [GRAPHICS]

Heat transfer enhancement in a micro-channel cooling system using cylindrical vortex generators.

Three-dimensional conjugate heat transfer under laminar flow conditions within a micro-channel is analysed numerically to explore the impact of a new design of vortex generator positioned at intervals along the base of the channel. The vortex generators are cylindrical with quarter-circle and half-circle cross sections, with variants spanning the whole width of the channel or parts of the channel. Micro-channels with Reynolds number ranging from 100 to 2300 are subjected to a uniform heat flux relevant to microelectronics cooling. To ensure the accuracy of the results, validations against previous microchannel studies were conducted and found to be in good agreement, before the new vortex generators with radii up to 400 µm were analysed. Using a thermal-hydraulic performance parameter expressed in a new way, the VGs described here are shown to offer significant potential in combatting the challenges of heat transfer in the technological drive toward lower weight/smaller volume electrical and electronic devices

The Spill-Over Impact of the Novel Coronavirus-19 Pandemic on Medical Care and Disease Outcomes in Non-communicable Diseases: A Narrative Review

OBJECTIVES: The coronavirus-19 (COVID-19) pandemic has claimed more than 5 million lives worldwide by November 2021. Implementation of lockdown measures, reallocation of medical resources, compounded by the reluctance to seek help, makes it exceptionally challenging for people with non-communicable diseases (NCD) to manage their diseases. This review evaluates the spill-over impact of the COVID-19 pandemic on people with NCDs including cardiovascular diseases, cancer, diabetes mellitus, chronic respiratory disease, chronic kidney disease, dementia, mental health disorders, and musculoskeletal disorders. METHODS: Literature published in English was identified from PubMed and medRxiv from January 1, 2019 to November 30, 2020. A total of 119 articles were selected from 6,546 publications found. RESULTS: The reduction of in-person care, screening procedures, delays in diagnosis, treatment, and social distancing policies have unanimously led to undesirable impacts on both physical and psychological health of NCD patients. This is projected to contribute to more excess deaths in the future. CONCLUSION: The spill-over impact of COVID-19 on patients with NCD is just beginning to unravel, extra efforts must be taken for planning the resumption of NCD healthcare services post-pandemic

Contact X-ray Brachytherapy as a sole treatment in selected patients with early rectal cancer

Contact X-ray Brachytherapy as a sole treatment in selected patients with early rectal cancer Objective The standard management of early rectal cancer is surgical resection. Contact X-ray brachytherapy (CXB) is an alternative treatment for patients who are not suitable or refuse surgery and is usually combined with external beam radiation (EBRT) to treat possible lymphatic spread. We report clinical outcomes from a cohort of patients who, for various reasons, received CXB as the sole treatment for early rectal cancer. Methods From our Clatterbridge Cancer Centre database (2009-2019), we selected patients with early rectal adenocarcinoma (cT1-2, cN0, cM0) and small tumour size (≤ 3cm) who received CXB as their sole treatment. For tumours ≤ 3cm, three fractions of CXB are usually delivered initially and this is followed by EBRT for patients who have residual tumour after CXB. For selected patients with very early rectal cancer who achieved an initial clinical complete response (cCR) after CXB, we did not offer EBRT as the likelihood of lymphatic spread is <20%. In this cohort, we categorised patients into three groups based on their reasons for receiving CXB without EBRT: Group A: 12 patients who refused surgery (of whom 7 also refused EBRT); Group B: 10 patients who were not suitable for surgery due to advanced age and/or comorbidities, and Group C: 11 patients who had received previous pelvic EBRT for other conditions and were therefore not eligible for further EBRT. The CXB treatment regimen consisted of 30Gy/#, a total of 90Gy over 4 weeks and a further dose of 20Gy was added instead of EBRT for patients who still had small volume residual disease. We adopted a watch-and-wait policy for follow-up with endoscopy, digital rectal examination and MRI every 3 months in the first two years and 6-monthly in the third year. Local tumour control rate, disease-free survival, radiation toxicities and sphincter preservation were analysed. Results A total of 33 patients were included, with a median follow-up of 2.9 years [IQR:1.0-5.0]) and there were no significant differences between the groups in terms of age, gender, performance status, T stage or tumour size. The initial cCR was excellent in Groups A and B (both 100%), but was significantly reduced (55%) in Group C (p=0.002). Sustained local tumour control was 83% in Group A, 90% in Group B, and 45% in Group C (p=0.30). Group A had better 5-year disease-free and overall survival rates (82% and 67%) compared to Group B (75% and 52%), and Group C (59% and 18%). The main radiation toxicity was rectal bleeding (21%), but only 6% of all patients required argon beam therapy. The overall organ preservation rate was 94% and only two patients needed a subsequent stoma. Conclusion In patients with early small rectal cancers with no suspicious lymph node spread, who are not suitable for or refuse surgery, it is feasible to offer CXB as the sole definitive treatment without EBRT. No patients relapsed with nodal tumour recurrence and only one patient developed distant metastasis during follow-up