Matters of size: Roles of hyaluronan in CNS aging and disease

Involvement of extracellular matrix (ECM) components in aging and age-related neurodegeneration is not well understood. The role of hyaluronan (HA), a major extracellular matrix glycosaminoglycan, in malignancy and inflammation is gaining new understanding. In particular, the differential biological effects of high molecular weight (HMW-HA) and low molecular weight hyaluronan (LMW-HA), and the mechanism behind such differences are being uncovered. Tightly regulated in the brain, HA can have diverse effects on cellular development, growth and degeneration. In this review, we summarize the homeostasis and signaling of HA in healthy tissue, discuss its distribution and ontogeny in the central nervous system (CNS), summarize evidence for its involvement in age-related neurodegeneration and Alzheimer Disease (AD), and assess the potential of HA as a therapeutic target in the CNS.     

Gaslighting in alleged assault ascertained as Munchausen syndrome transcending to malingering in highly counterintuitive self inflicted acid burns

A factitious disorder leading to the self-infliction of highly counter-intuitive burns was diagnosed in a middle-aged female. The injuries were otherwise alleged to have been sustained by assault inflicted upon her by an unknown person. The case was diagnosed by medico-legal interpretation of injuries, in spite of a highly deceptive and concocted history by the patient and her husband. The entity was unique in being associated with magnificent primary, secondary and tertiary gains. The exploitation of the morbid sequel to malinger by the patient, and the involvement of the husband for the prolongation of the illness of his wife for financial gains as gaslighting was highly unusual. The self-infliction of injuries over hands is seen in factitious disorder. However, a combination of a guarded self-immersion of the hands and feet in a corrosive by an illiterate female, followed by malingering to earn livelihood is unprecedented in factitious disorders. The delayed presentation which required amputation of all the limbs to save the life of the patient is a glaring highlight of this case.     

The role of urease in the acid stress response and fimbriae expression in Klebsiella pneumoniae CG43

Background/purposeTwo urease operons were identified in Klebsiella pneumoniae CG43, ure-1 and ure-2. This study investigates whether a differential regulation of the expression of ure-1 and ure-2 exists and how urease activity influences the acid stress response and expression of type 1 and type 3 fimbriae.MethodsThe ureA1 and ureA2 gene specific deletion mutants were constructed. Promoter activity was assessed using a LacZ reporter system. The sensitivity to acid stress was determined by assessing the survival after pH 2.5 treatment. The influence on type 1 and type 3 fimbriae expression was assessed using western blotting and mannose-sensitive yeast agglutination and biofilm formation assay, respectively.ResultsBacterial growth analysis in mM9-U or modified Stuart broth revealed that ure-1 was the principal urease system, and ure-2 had a negative effect on ure-1 activity. Deletion of the fur or nac gene had no apparent effect on the activity of P_ure1, P_ure2-1, and P_ure2-2. The P_ure2-2 activity was enhanced by deletion of the hns gene. ureA1 deletion increased acid stress sensitivity, whereas the deleting effect of ureA2 was notable without hns. Deletion of ureA1 or ureA2 significantly induced the expression of type 1 fimbriae but decreased MrkA production and biofilm formation.Conclusionure-1 is the primary expression system in K. pneumoniae CG43, while ure-2 is active in the absence of hns. Impairment of urease activity increases the sensitivity to acid stress, and the accumulation of urea induces the expression of type 1 fimbriae but represses type 3 fimbriae expression.     

难治性胃食管反流病临证研究

难治性胃食管反流病是临床疑难病,症状反复,缠绵难愈,治疗棘手。中医药治疗“反酸”“吞酸”证历久源远,充分挖掘古籍,深研病机,提炼治法,发挥中医药特色,对治疗本病意义深远。     

Complete recovery of filler-induced visual loss following subcutaneous hyaluronidase injection

The rise in popularity of hyaluronic acid (HA) dermal filler injection has caused an exceptional increase in the number of cases of reported irreversible blindness. Here, we reported a case of ischemic optic neuropathy and ophthalmoplegia following subcutaneous HA filler injection with complete visual recovery. A 31-year-old Chinese woman presented with sudden onset of right monocular visual impairment associated with diplopia. Patient had received a hyaluronic acid-containing ?ller injection for nasal dorsum augmentation twelve hours prior to presentation. Visual acuity of the right eye was counting finger. A right relative afferent pupillary defect was demonstrated with ophthalmoplegia. Humphrey visual field test disclosed a right inferior altitudinal field defect with impairment of colour vision. Computed tomography of the orbit revealed mild enlargement of the right medial and inferior recti muscles. Our patient showed a tremendous improvement of vision after a subcutaneous hyaluronidase injection with complete visual recovery within 2 weeks.     

Rhinofilling with hyaluronic acid thought as a cartilage graft

IntroductionThere is great demand for nonsurgical aesthetic procedures. In this case series, the authors describe their stepwise technique of injecting hyaluronic acid (HA) into the nose to yield pleasing, stable results.Case seriesA total of 148 patients underwent minimally invasive rhinoplasty by injection of HA filler. Anatomic contraindications for the procedure were a large dorsal hump, extreme tip projection, or excessive nasal deviation. HA injections were made in a specific order to reshape and stabilize the nose; the surgical plan was conceptually similar to placement of cartilage grafts. Patients indicated their satisfaction with the surgical results on a visual analog scale. Immediately after the procedure, all patients had transient redness and slight swelling at the injection site; this resolved spontaneously by 24 h posttreatment. Vascular impairment developed in 1 patient and was managed with hyaluronidase. In general, patients expressed a high level of satisfaction. Thirty-two patients returned for a “touch-up” filler injection 1 year posttreatment.DiscussionNasal reshaping by HA injection can be carried out quickly, safely, and effectively with minimal patient discomfort or downtime. Care must be given to select patients who are indicated for this procedure, and meticulous pretreatment planning is necessary.     

深圳地区HBV核酸检测反应性献血者两种归队模式风险评估研究

目的评估HBV核酸检测反应性献血者归队风险,为采供血机构制定献血者归队策略提供依据。方法对ELISA双试剂无反应性、HBV核酸检测反应性献血者进行跟踪检测。每次间隔3个月以上,两次直接静脉采样。归队后再跟踪两次以上献血检测结果。两家血站分别按无门槛自愿原则与增加献血10次以上要求进行采样,并对两种模式归队结果进行比对。结果无门槛自愿归队模式归队前检测3例酶免检测阴转阳(15.79%);增加献血次数门槛归队模式归队成功率88.46%;两种归队模式成功归队后再次出现不合格情况分别为20.00%、13.04%,统计无差异,但归队后人均年献血次数有较大差别。结论酶免检测无反应性而HBV核酸检测反应性被屏蔽献血者无门槛归队模式存在窗口期感染风险。建议将多次献血或固定献血、首次出现酶免检测无反应性而HBV核酸检测反应性被屏蔽的献血者列入归队目标人群。仅以HBsAg+HBV DNA作为HBV核酸检测反应性献血者的归队评价指标存在较大风险,应考虑增加化学发光法等补充试验。     

Inhibitory Role of Gamma-Aminobutyric Receptors in Paraventricular Nucleus on Ejaculatory Responses in Rats

BackgroundAlthough abnormal sympathetic nerve system (SNS) activity has been demonstrated in the pathogenesis of ejaculation disorders, few data are available on its underlying mechanism.AimTo investigate whether differences in ejaculatory behavior of rats were associated with the state of SNS activity and gamma-aminobutyric (GABA) receptor expressions in the paraventricular nucleus (PVN) of the hypothalamus and the effects of GABA receptors in the PVN on ejaculatory behavior.MethodsBased on ejaculatory performance, Sprague-Dawley rats were divided into “sluggish,” “normal,” and “rapid” ejaculators. PVN microinjection was performed to evaluate the role of GABA receptors on sexual behavior.OutcomesThe outcomes include differences in expression and distribution of GABA receptors and norepinephrine level among the 3 groups and changes in copulation behavior parameters after PVN microinjection.ResultsCompared with “normal” rats, the “rapid” group ejaculated more times with shorter latency (P < .001, P < .001) and had lower expression and distribution of both GABA-A and GABA-B receptors, while the opposed results appeared in the “sluggish” group. The norepinephrine level was successively increased among “sluggish,” “normal,” and “rapid” rats (P < .001) and correlated with ejaculation frequency (r = 0.896, P < .001) and ejaculation latency (r = −0.835, P < .001). In addition, bilateral microinjection of the GABA-A and GABA-B receptor agonist (isoguvacine and baclofen) into the PVN both significantly prolonged the intromission latency and inhibited ejaculation, which could be blocked by antagonist gabazine and CGP-35348, respectively. Vigabatrin, the GABA-transaminase inhibitor, caused a significantly reduced ejaculation frequency and extended ejaculation latency in rats, which could be offset by simultaneous injections of gabazine and CGP-35348.Clinical ImplicationsOur findings provide new understanding about GABA receptors in the PVN on sexual behavior and enhance the comprehension of neurobiological mechanisms involved in premature ejaculation.Strengths & LimitationsOur results have indicated that GABA receptors in the PVN may inhibit ejaculation through restraining the activity of SNS. However, our study did not analyze the changes of GABA receptors in other brain areas, which needs further study.ConclusionEjaculation behaviors in male rats are associated with SNS activity and could be regulated by GABA receptors in the PVN, which may be of assistance in the treatment of ejaculation disorders in the future.Zhang QJ, Yang BB, Yang J, et al. Inhibitory Role of Gamma-Aminobutyric Receptors in Paraventricular Nucleus on Ejaculatory Responses in Rats. J Sex Med 2020;17:614–622.