Human SII and posterior insula differently encode thermal laser stimuli

The SII area and the posterior insular region are both activated by thermal stimuli in functional imaging studies. However, controversy remains as to a possible differential encoding of thermal intensity by each of these 2 contiguous areas. Using CO(2) laser stimulations, we analyzed the modifications induced by increasing thermal energy on evoked potentials recorded with electrodes implanted within SII and posterior insula in patients referred for presurgical evaluation of epilepsy. Although increasing stimulus intensities enhanced both SII and insular responses, the "dynamics" of their respective amplitude changes were different. SII responses were able to encode gradually the intensity of stimuli from sensory threshold up to a level next to pain threshold but tended to show a ceiling effect for higher painful intensities. In contrast, the posterior insular cortex failed to detect nonnoxious laser pulses but reliably encoded stimulus intensity variations at painful levels, without showing saturation effects for intensities above pain threshold. According to these results, one can assume that insular cortex could be more involved in the triggering of affective recognition of, and motor reaction to, noxious stimuli, whereas SII would be more dedicated to finer-grain discrimination of stimulus intensity, from nonpainful to painful levels.     

Inner experience of pain: imagination of pain while viewing images showing painful events forms subjective pain representation in human brain

Pain is an unpleasant sensation, and at the same time, it is always subjective and affective. Ten healthy subjects viewed 3 counterbalanced blocks of images from the International Affective Picture System: images showing painful events and those evoking emotions of fear and rest. They were instructed to imagine pain in their own body while viewing each image showing a painful event (the imagination of pain). Using functional magnetic resonance imaging, we compared cerebral hemodynamic responses during the imagination of pain with those to emotions of fear and rest. The results show that the imagination of pain is associated with increased activity in several brain regions involved in the pain-related neural network, notably the anterior cingulate cortex (ACC), right anterior insula, cerebellum, posterior parietal cortex, and secondary somatosensory cortex region, whereas increased activity in the ACC and amygdala is associated with the viewing of images evoking fear. Our results indicate that the imagination of pain even without physical injury engages the cortical representations of the pain-related neural network more specifically than emotions of fear and rest; it also engages the common representation (i.e., in ACC) between the imagination of pain and the emotion of fear.     

El estado inmunológico-inflamatorio-nutricional predice los resultados oncológicos tras la cistectomía radical por carcinoma urotelial de vejiga

ObjectiveTo perform the first investigation of the role of immune-inflammatory-nutritional status (INS) on oncological outcomes in patients undergoing open radical cystectomy (ORC) for urothelial carcinoma (UC).Materials and methodsThe records of consecutive patients who underwent ORC for non-metastatic bladder cancer between 2009 and 2020 were retrospectively analyzed. Neoadjuvant chemotherapy, non-urothelial tumor biology, and absence of oncological follow-up were exclusion criteria. Systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) values were calculated and optimal cut-off values for these were used to designate four subgroups: «high SII-high PNI», «low SII-high PNI», «low SII-low PNI», and «high SII-low PNI». The low SII-high PNI INS group had best overall survival (OS) rate while the remainder were included in non-favorable INS group. Survival curves were constructed, and a multivariate Cox regression model was used for OS and recurrence-free survival (RFS).ResultsAfter exclusions, the final cohort size was 173 patients. The mean age was 64.31 ± 8.35 and median follow-up was 21 (IQR: 9-58) months. Optimal cut-off values for SII and PNI were 1216 and 47, respectively. The favorable INS group (low SII-high PNI, n = 89) had the best OS rate (62.9%). Multivariate Cox regression analysis indicated that non-favorable INS (n = 84) was a worse independent prognostic factor for OS (HR: 1.509, 95% CI: 1.104-3.145, P=.001) and RFS (HR: 1.285; 95% CI: 1.009-1.636, P=.042).ConclusionPreoperative assessment of INS may be a useful prognostic panel for OS and RFS in patients who had ORC for UC.     

Development and technology transfer of Haemophilus influenzae type b conjugate vaccines for developing countries

This paper describes the development of a Haemophilus influenzae type b (Hib) conjugate vaccine at the National Institute for Public Health and the Environment/Netherlands Vaccine Institute (RIVM/NVI, Bilthoven, The Netherlands), and the subsequent transfer of its production process to manufacturers in developing countries. In 1998, at the outset of the project, the majority of the world's children were not immunized against Hib because of the high price and limited supply of the conjugate vaccines, due partly to the fact that local manufacturers in developing countries did not master the Hib conjugate production technology. To address this problem, the RIVM/NVI has developed a robust Hib conjugate vaccine production process based on a proven model, and transferred this technology to several partners in India, Indonesia, Korea and China. As a result, emerging manufacturers in developing countries acquired modern technologies previously unavailable to them. This has in turn facilitated their approach to producing other conjugate vaccines. As an additional spin-off from the project, a World Health Organization (WHO) Hib quality control (QC) course was designed and conducted at the RIVM/NVI, resulting in an increased regulatory capacity for conjugate vaccines in developing countries at the National Regulatory Authority (NRA) level. For the local populations, this has translated into an increased and sustainable supply of affordable Hib conjugate-containing combination vaccines. During the course of this project, developing countries have demonstrated their ability to produce large quantities of high-quality modern vaccines after a successful transfer of the technology.     

Age-related changes across the primary and secondary somatosensory areas: An analysis of neuromagnetic oscillatory activities

ObjectiveAge-related changes are well documented in the primary somatosensory cortex (SI). Based on previous somatosensory evoked potential studies, the amplitude of N20 typically increases with age probably due to cortical disinhibition. However, less is known about age-related change in the secondary somatosensory cortex (SII). The current study quantified age-related changes across SI and SII mainly based on oscillatory activity indices measured with magnetoencephalography.MethodsWe recorded somatosensory evoked magnetic fields (SEFs) to right median nerve stimulation in healthy young and old subjects and assessed major SEF components. Then, we evaluated the phase-locking factor (PLF) for local field synchrony on neural oscillations and the weighted phase-lag index (wPLI) for cortico-cortical synchrony between SI and SII.ResultsPLF was significantly increased in SI along with the increased amplitude of N20m in the old subjects. PLF was also increased in SII associated with a shortened peak latency of SEFs. wPLI analysis revealed the increased coherent activity between SI and SII.ConclusionsOur results suggest that the functional coupling between SI and SII is influenced by the cortical disinhibition due to normal aging.SignificanceWe provide the first electrophysiological evidence for age-related changes in oscillatory neural activities across the somatosensory areas.     

基于PNI、SII、CAR的列线图模型对肝移植术后腹腔感染的预测价值

目的  探讨原位肝移植术后发生腹腔感染的危险因素。方法  回顾性分析284例原位肝移植受者的临床资料,根据术后是否发生腹腔感染分为感染组(51例)和非感染组(233例)。采用单因素和多因素logistic回归分析腹腔感染的危险因素,构建列线图预测模型并评估模型预测效果,分析连续性变量对腹腔感染的预测价值。结果  284例受者中,51例发生腹腔感染,发生率为18.0%。术前有糖尿病[比值比(OR)2.66,95%可信区间(CI)1.13~6.14,P=0.013]、手术时间长(OR 1.98,95%CI 1.03~3.57,P=0.038)、预后营养指数(PNI)低(OR 2.18,95%CI 1.06~4.44,P=0.023)、全身免疫炎症指数(SII)高(OR 2.21,95%CI 1.06~4.78,P=0.012)、C-反应蛋白/白蛋白比值(CAR)高(OR 1.90,95%CI 1.05~3.49,P=0.029)是肝移植术后腹腔感染的独立危险因素。列线图模型预测肝移植术后腹腔感染的曲线下面积(AUC)为0.761,且模型标准,一致性较好。CAR、PNI、SII均为肝移植术后腹腔感染的预测因子(均为P < 0.05),AUC分别为0.648、0.611和0.648,临界值分别为2.75、43.15和564.50。结论  CAR、SII、PNI是肝移植术后腹腔感染的预测因子,基于PNI、SII、CAR构建的列线图模型可有效预测肝移植术后腹腔感染的发生。     

外周血炎性标志物在甲状腺癌中的应用进展

甲状腺癌是内分泌系统最常见的恶性肿瘤,近年来其发病率在世界范围内呈上升趋势,虽然总体治愈率高,但局部复发或远处转移也较常见,另有部分患者因肿瘤组织分化低,疾病进展较快而死亡.免疫反应和炎症反应在肿瘤的发生、发展中起着重要的作用,研究表明外周血中某些炎性细胞的数目及其比值是恶性肿瘤的重要预后因子,如血小板、中性粒细胞、淋...     

The connections of cortical somatosensory areas I and II with separate nuclei in the ventroposterior thalamus in the raccoon

The thalamocortical afferents to cortical somatosensory areas I (SI) and II (SII) were investigated in the raccoon using the horseradish peroxidase technique. The purpose of this study was to determine if the cell bodies of origin for thalamocortical afferents to these cortical regions were localized in the same or different nuclei in the ventroposterior region of the thalamus. Horseradish peroxidase was injected into subdivisions of SI or SII and after post-injection survival periods of 12-72 hours the horseradish peroxidase in the tissue was reacted with the chromogens dihydrochlorobenzidine or tetramethylbenzidine in the presence of hydrogen peroxide. The results show that SI and SII receive projections from neurons in separate and distinct nuclei in the ventroposterior thalamus. Following injections into subdivisions of area I, a topographical distribution of retrogradely-labelled cell bodies was observed in the ventrobasal complex. Following injections of horseradish peroxidase into subdivisions of area II, a topographical distribution of labelled cell bodies was observed in the ventroposterior inferior nucleus. No labelled cell bodies were observed in the ventrobasal complex. The thalamocortical connections of somatosensory cortices I and II in raccoon are compared with those in other animals and it is suggested that these two cortical areas may be involved in differential processing of tactile information.     

Brain mechanism of itch in atopic dermatitis and its possible alteration through non-invasive treatments

Atopic dermatitis (AD) is a common chronic skin disease that is characterized by intense pruritus and has high impairment of quality of life. AD is often described as “the itch that rashes, rather than the rash that itches”. Several studies suggest that mechanisms of central modulation play an important role in the development and maintenance of chronic itch. Therefore, treating the neurosensory aspects of itch is an important part in the management of chronic itch. However, little attention has been paid to the role of the central nervous system in the processing of itch in AD. Targeting itch-related anatomical structures in the brain with non-invasive treatments such as psychological interventions and transcranial Direct Current Stimulation (tDCS) could have an antipruritic effect in AD. Therefore, in this review article, we discuss the current progress in brain imaging research of itch, as well as the efficacy of non-invasive interventions for itch relief in this patient group.     

A comparative study to evaluate the safety and immunogenicity of two lots of Haemophilus influenzae type-B conjugate vaccine manufactured at different scales

Objective

To compare the immunogenicity and safety of two different lots of SII Haemophilus influenzae type-B-tetanus toxoid conjugate (SII HibP_RO) vaccine manufactured at different scales when given in 3-dose schedule.

Design

Phase IV, open label, comparative, randomized parallel group study.

Setting

Shirdi Sai Baba Hospital, Vadu Budruk, Pune and Pediatrics Department of King Edward Memorial Hospital Research Centre, Pune.

Subjects

204 normal healthy infants of age 6-8 weeks at the time of first vaccination.

Methods

The eligible subjects received 3 doses of 0.5 ml of SII HibP_RO vaccine of either lot depending upon randomization number, intramuscularly in right thigh in the EPI schedule of 6, 10 and 14 weeks. They also received concomitantly DTP-HB vaccine intramuscularly on left thigh and Oral Polio vaccine (OPV). Solicited reactions were captured for 7 days following each vaccination; the events beyond 7 days till day 28 were captured as unsolicited adverse events. Serious Adverse Events (SAEs) were looked for throughout the subject participation. Blood samples were collected at baseline (before the first dose) and one month after the third dose for anti-PRP (polyribosylribitol phosphate) antibodies.

Results

In both groups, more than 98% subjects achieved short-term seroprotection (anti-PRP ≥ 0.15 μg/ml) after 3 doses. The long-term seroprotection (anti-PRP ≥ 1 μg/ml) was 87% and 80% in infants receiving lot manufactured at industrial scale and small scale respectively. Short and long term seroprotection and GMTs increased significantly as compared to baseline in both the groups. Overall local pain (52% and 58%), redness (30% and 41%), swelling (34% and 44%), fever (6% and 6%) and irritability (52% and 50%) were reported in infants receiving lot manufactured at industrial scale and small scale respectively. Majority of the reactions were mild and resoled without any sequelae. Four SAEs, none of them causally related to the study vaccine, occurred during study.

Conclusion

SII HibP_RO vaccines manufactured in small and industrial scale are equally immunogenic, safe and confer adequate seroprotection to infants of 6-14 weeks of age. Scaling up production process has not affected the safety and immune response in the target population.