Intranasal nerve growth factor for prevention and recovery of the outcomes of traumatic brain injury

Traumatic brain injury is one of the main causes of mortality and disability worldwide.Traumatic brain injury is characterized by a primary injury directly induced by the impact,which progresses into a secondary injury that leads to cellular and metabolic damages,starting in the first few hours and days after primary mechanical injury.To date,traumatic brain injury is not targetable by therapies aimed at preventing and/or limiting the outcomes of secondary damage but only by palliative therapies.Nerve growth factor is a neurotrophin targeting neuronal and non-neuronal cells,potentially useful in preventing/limiting the outcomes of secondary damage in traumatic brain injury.This potential has further increased in the last two decades since the possibility of reaching neurotrophin targets in the brain through its intranasal delivery has been exploited.Indeed,molecules intranasally delivered to the brain parenchyma may easily bypass the blood-brain barrier and reach their therapeutic targets in the brain,with favorable kinetics,dynamics,and safety profile.In the first part of this review,we aimed to report the traumatic brain injury-induced dysfunctional mechanisms that may benefit from nerve growth factor treatment.In the second part,we then exposed the experimental evidence relating to the action of nerve growth factor(both in vitro and in vivo,after administration routes other than intranasal)on some of these mechanisms.In the last part of the work,we,therefore,discussed the few manuscripts that analyze the effects of treatment with nerve growth factor,intranasally delivered to the brain parenchyma,on the outcomes of traumatic brain injury.

Molecular identity, expression and functional analysis of interleukin-1α and its isoforms in rat testis

Interleukin-1α (IL-1α) is a proinflammatory cytokine that has also been found to act as a paracrine mediator involved in the regulation of testicular functions. The present review provides an overview of the role of IL 1α in testicular physiology. Bioactive IL-1α isolated from adult rat testis was found to consist of three distinct immunoreactive protein species with apparent sizes of 45, 24 and 19 kDa. These isoforms showed bioactivity in a thymocyte proliferation and steroidogenesis assays with different biopotencies. The background of the molecular heterogeneity and processing, secretion and regulation of the isoforms of testicular IL-1α are discussed. All three isoforms have been found to be secreted into the testis tubular lumen and interstitial space. We have provided evidence that IL-1α is a paracrine factor that may be of importance in, e.g., the regulation of Leydig cell steroidogenesis. Pathophysiologically, testicular IL-1α may contribute to testicular relapse of acute lymphocytic leukemia in boys.

Long-term implications of fetal growth restriction

Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.

Differentiation induced by physiological and pharmacological stimuli leads to increased antigenicity of human neuroblastoma cells

同情的 neuronal 区别与 neuroblastoma (NB ) 的有利预后被联系，早童年的最普通的颅外的稳固的肿瘤。区别代理人在 NB 治疗的临床的协议证明了有用，但是因为唯一的治疗不是足够的在病人导致肿瘤消除，使用他们。因此，互补途径例如免疫疗法，被保证。这里，我们证明 NB 房间线和前 vivo 的那区别孤立肿瘤房间响应生理或药理学刺激与增加的 antigenicity 的获得被联系。这是增加了表面专业的表示表明组织亲和性一级建筑群和 ICAM-1 分子并且由细胞毒素的 T 淋巴细胞(CTL ) 和生来的杀手(NK ) 翻译成 NB 房间的增加的敏感到细胞溶解房间。后者是由形式免疫者 conjugates 的区分的房间的提高的能力的 paralleled 并且把 granzyme B 的增加的数量绑在房间表面。 Wedemonstrate ，第一次那不管使用的刺激，在 NB 的区别状态与由细胞毒素的淋巴细胞启用肿瘤房间的更多的有效消除并且在 NB 病人作为一条辅助途径为导致区别的代理人和免疫疗法的联合申请铺平道路的增加的肿瘤 antigenicity 被联系。

This pain drives me crazy:Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome

BACKGROUND Interstitial cystitis/bladder pain syndrome(IC/BPS)is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic,abdominal,and/or pelvic pain.Although the term cystitis suggests an inflammatory or infectious origin,no definite cause has been identified.It occurs in both sexes,but women are twice as much affected.AIM To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS.METHODS Hypothesizing that particular psychological characteristics could underpin IC/BPS,we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy:("interstitial cystitis"OR"bladder pain syndrome")AND("mood disorder"OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk).RESULTS On September 27,2023,the PubMed search produced 223 articles,CINAHL 62,and the combined PsycLIT/PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36.Search on ClinicalTrials.gov produced 14 studies,of which none had available data.Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS,i.e.63 articles spanning from 2000 to October 2023.These studies identified depression and anxiety problems in the IC/BPS population,along with sleep problems and the tendency to catastrophizing.CONCLUSION Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS.Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

Impact of the COVID-19 kindergarten closure on overweight and obesity among 3-to 7-year-old children

Background Knowledge on the impact of the temporary kindergarten closure policy under COVID-19 in 2020 on childhood overweight and obesity is inadequate.We aimed to examine differences in rates of overweight and obesity from 2018 to 2021 among kindergarten children aged 3–7 years.Methods Overweight was defined as body mass index(BMI)>1 standard deviation(SD)for age and sex,and obesity was defined as BMI>2 SD for age and sex.Generalized linear mixed modeling was used for analysis.Results A total of 44,884 children and 71,216 growth data points from all 57 public kindergartens in Jiading District,Shanghai,China were analyzed.The rates of obesity from 2018 to 2021 were 6.9%,6.6%,9.5%,and 7.3%in boys and 2.8%,2.8%,4.5%,and 3.1%in girls,respectively.The rates of overweight from 2018 to 2021 were 14.3%,14.3%,18.2%,and 15.3%in boys and 10.6%,10.9%,13.9%,and 11.6%in girls.The rates of obesity and overweight among kindergarten children in 2020 were significantly higher than those in 2018,2019,and 2021.Compared to 2020,the odds ratios of the obesity rate in 2018,2019,and 2021 were 0.67[95%confidence interval(CI)=0.58–0.77,P<0.001],0.72(95%CI=0.64–0.80,P<0.001)and 0.81(95%CI=0.72–0.92,P=0.001),respectively.The odds ratios of the overweight rate in 2018,2019,and 2021 were 0.75(95%CI=0.69–0.82,P<0.001),0.78(95%CI=0.72–0.84,P<0.001),and 0.89(95%CI=0.81–0.97,P=0.008),respectively,compared to 2020.Conclusions The rates of overweight and obesity significantly increased among kindergarten children in 2020 after the 5-month kindergarten closure.It was critical to provide guidance to caregivers on fostering a healthy lifestyle for children at home under public health emergencies.

Intrahepatic Cholangiocarcinoma and Thermal Ablation:Long-term Results of An Italian Retrospective Multicenter Study

Background and Aims: Despite resection being considered the treatment of choice for intrahepatic cholangiocarcinoma(ICC),percutaneous thermal ablation can be an alter-native treatment for patients unfit for surgery.Our aim was to compare long-term results of percutaneous sonographi-cally-guided radiofrequency ablation(RFA)with high-powered microwave ablation(MWSA)in treatment of ICC.Methods: Results of 71 ICC patients with 98 nodules treated with RFA(36 patients)or MWSA(35 patients)between January 2008 and June 2018 in 5 Interventional Ultrasound centers of Southern Italy were retrospectively reviewed.Cu-mulative overall survival curves were calculated with the Ka-plan-Meyer method and differences with the log-rank test.Eleven possible factors affecting survival were analyzed.Results: Overall survival of the entire series was 88%,65%,45%and 34%at 12,36,60 and 80 months,respec-tively.Patients treated with MWSA survived longer than pa-tients treated with RFA(p < 0.005).The MWSA group with ICC nodules ≤3 cm or nodules up to 4 cm survived longer than the RFA group(p < 0.0005).In patients with nodules>4 cm,no significant difference was found.Disease-free sur-vival and progression-free survival were better in the MWSA group compared to the RFA group(p < 0.005).Diameter of nodules and MWSA were independent factors predicting a better survival.No major complications were observed.Conclusions: MWSA is superior to RFA in treating ICC unfit for surgery,achieving better long-term survival in small(≤3 cm)ICC nodules as well as nodules up to 4 cm of neo-plastic tumors and should replace RFA.

Expanding the genetic landscape of Rett syndrome to include lysine acetyltransferase 6A(KAT6A)

Pathogenic variants in methyl-Cp G protein 2(MECP2;OMIM300005)result in an X-linked,severe,and progressive epigenetic disorder,Rett syndrome(RTT,OMIM:312750),that predominantly affects females(Rett,1966).Using Neul’s revised diagnostic criteria,affected individuals can be clinically classified as classic or atypical RTT(Neul et al.,2010).

PGP9.5免疫组化结果显示,与宫体相反妊娠期及分娩时人类宫颈神经分布无变化

Objective: To examine the occurrence of the general neuronal marker protein gene product 9.5 (PGP 9.5) in the human corpus (isthmus region) and the cervix uteri during pregnancy and parturition. Study design: Biopsies were taken from the upper edge of the hysterotomy during caesarean section (CS) at term (n = 5), in labor (n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 5). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostate sections were prepared for immunohistochemistry using polyclonal antibodies to PGP 9.5. Results: Nerve fibers displaying PGP 9.5 immunoreactivity were observed in all sections from the three groups examined. They were identified in muscle tissue, in the stroma, and around blood vessel walls. A 30- fold decline of immunoreactive nerve fibers was observed in the isthmus part of the corpus uteri at term compared to the non-pregnant. There were no significant differences between the immunoreactivity in the cervix uteri of the three groups. Conclusions: The innervation of the cervix uteri is dense and unaltered throughout pregnancy and labor. In contrast, the corpus is almost denervated. Further studies are needed to clarify the reason and the impact of these findings.

注意缺陷多动症症状与自尊心之间长期关联的前瞻性纵向孪生子研究

Aim: To study the long-term relationship between symptoms of Attention Deficit Hyperactivity Disorder and the developing self-esteem in a population-based sample of twins. Methods:The cohort is all twin pair families born in Sweden between May 1985 and December 1986. Wave 1 took place in 1994 when the twins were 8 years old and wave 2 in 1999 when the children were 13 years old. Inwave 1 and 2 the parents completed questionnaires regarding ADHD-symptoms about their children. In wave 2 the twins completed a questionnaire about self-esteem and Youth Self Report (YSR). ADHD-symptoms and self-esteem were analyzed in the total study group. Results:There was a long-term relationship between high scores of parental-reported ADHD-symptoms at 8 and 13 years of age and low scores in measures of self-reported self-esteem at 13 years of age. In the cotwin control method controlling for YSR internalizing problem, paired comparisons within the twin pairs revealed that a high score of ADHD-symptoms at age 8 was related to significantly lower scores at age 13 in the self-esteem.Conclusions: The long-term relationships between ADHD-symptoms and a low self-esteem in a population-based sample were confirmed by the co-twin analyses.

Contrast-enhanced ultrasound with sulphur-hexafluoride in diagnosis of early HCC in cirrhosis

Contrast-enhanced ultrasound(CEUS)with pure blood stream contrast agents allow the study of blood supply of focal liver lesions and especially of hepatocellular carcinoma(HCC)in cirrhosis.Its sensitivity and specificity in diagnosis of small tumors is very high.This review summarizes the recent results on CEUS with SonoVue,which is one of the second generation contrast agents,in the diagnosis of early HCC in cirrhosis emphasizing its increasing role in routine clinical practice.

Editorial on "Role of thermal ablation in the management of colorectal liver metastasis"

The last 30 years have shown the increasing role of Ablation in the treatment of malignant liver tumors. By the introduction of percutaneous ethanol injection (PEI) as first ablation tool for percutaneous treatment of hepatocellular carcinoma (HCC) in cirrhosis that firstly showed very high efficacy (1), several ablation techniques (mainly thermal) have been introduced in clinical practice aimed at destroying primary and secondary hepatic tumors as alternative or substitute tools to surgery. Radiofrequency ablation (RFA) was the first thermal technique that showed a good efficacy to ablate liver metastases (2). Among the secondary liver tumors, colorectal liver metastases (CRLM) represent the unique indication for ablation (2). Unlike HCC in cirrhosis where the role of RFA is well defined as first line therapy for HCC nodules < or equal to 2 cm or as alternative to surgery in 1-3 HCC nodules with the maximum diameter<3 cm (3), in the case of CRLM it is not possible to reproduce the same paradigm. Liver resection remains the standard of care for CRLM and the indications to ablation remain confined to nonresectable patients (4). The review article by Takahashi and Berber recently published in HBSN wells illustrates the current role of ablation in treatment of CRLM (5).