Impaired decision-making and functional neuronal network activity in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with cognitive deficit but the exact neural mechanisms remain unclear. PURPOSE: To explore sequential brain activities using functional magnetic resonance imaging (fMRI) during the performance of a decision-making task, and to determine whether serum or clinical markers can reflect the involvement of the brain in SLE. SUBJECTS: Sixteen female SLE patients without overt clinical neuropsychiatric symptoms and 16 healthy controls were included. FIELD STRENGTH/SEQUENCE: 1.5T, T1 -weighted anatomic images, gradient-echo echo-planar imaging sequence, and 3D images. ASSESSMENT: The computer-based Iowa Gambling Task (IGT) for assessing decision-making was performed by SLE patients and 16 matched controls; brain activity was recorded via blood oxygen level-dependent (BOLD) fMRI. The amplitudes of the average BOLD responses were calculated for each individual subject, and activation data from fMRI experiments were compared between the two groups. STATISTICAL TESTS: Two-sample t-test; repeated-measures analysis of variance (ANOVA); linear regression analyses. RESULTS: Imaging revealed activity in a distributed network of brain regions in both groups, including the ventromedial prefrontal cortex (vmPFC), the orbitofrontal cortex (OFC), the dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC), the posterior cingulate cortex (PCC), and the striatum, as well as the insular, parietal, and occipital cortices. Compared to controls, SLE patients showed lower activation in a convergence zone and the limbic system, namely, the OFC, vmPFC, ACC, and PCC, but greater activation in memory, emotion, and behavior systems involving the dlPFC, the insular cortex and the striatum. Furthermore, brain activation in the vmPFC was positively correlated with IGT scores (r = 0.63, P < 0.001), but inversely related to disease activity (r = -0.57, P < 0.01). DATA CONCLUSION: The dynamics among the aforementioned neural systems (some hyperfunctioning, others hypofunctioning) may shed some light on the pathologic mechanisms underlying SLE without overt clinical neuropsychiatric symptoms. In addition, disease activity may potentially be used as an effective biomarker reflecting cerebral involvement in SLE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;48:1508-1517.

G protein-coupled estrogen receptor-protein kinase A-ERK-CREB signaling pathway is involved in the regulation of mouse gubernaculum testis cells by diethylstilbestrol.

The etiology of testicular dysgenesis syndrome is multifactorial and involves environmental factors, such as environmental estrogens. Several studies have shown that hormonal effects on the gubernaculum may affect testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernacular cells, but the underlying mechanisms remain elusive. In this study, we aimed to determine whether DES may regulate the function of gubernaculum testis cells by way of nongenomic effects mediated by G protein-coupled estrogen receptor (GPER). We used cultured mouse gubernacular testis cells to demonstrate that GPER is expressed in gubernaculum testis cells. Erk1/2 inhibitor PD98059, PKA inhibitor H89, and Src inhibitor PP2 relieved DES-induced inhibition of gubernaculum testis cell proliferation, but ER inhibitor ICI 182780 had no effects on DES-induced inhibition of gubernaculum testis cell proliferation. In addition, we found that DES induced the activation of CREB downstream of PKA, Src, and ERK1/2 in these cells. These data suggest that the effects of DES on mouse gubernaculum testis cells are mediated at least partially by GPER-protein kinase A-ERK-CREB signaling pathway.

[Diethylstilbestrol affects LGR8 expression in mouse gubernaculum testis].

OBJECTIVE: To investigate the impact of prenatal exposure to diethylstilbestrol (DES) on the specific receptor LGR8 of insulin-like factor 3 (INSL3) in the mouse gubernaculum testis, and that of exoestrogens on descensus testis in mice. METHODS: A total of 120 pregnant KM mice aged 8 to 10 weeks were assigned to a normal, a blank control and 4 DES groups of equal number, the blank controls injected subcutaneously with dimethyl sulfoxide plus normal saline, and the DES groups with DES at 0.1, 1, 10 and 100 microg/kg body weight, respectively, from embryonic day 9 (ED9) through ED17. Immunohistochemistry and RT-PCR were used to detect the expressions of LGR8 protein and mRNA in the gubernaculum testis of the ED18 fetuses and PND20 (postnatal day 20) offspring of the mice. RESULTS: Histological analysis showed that the gubernaculum testis of the ED18 fetuses were well developed in both the normal and control groups, with an inner mesenchymal core and muscular outer layer. In contrast, the gubernaculum testis were poorly developed in the experimental groups, morphologically abnormal and without visible dividing line between the mesenchymal tissue and the muscular outer layer. No obvious differences were found in the gubernaculum testis development of the neonates between the normal and experimental groups. Positive immunostaining was seen in the mesenchymal core and muscular outer layer, but mainly in the latter. The expression of LGR8 was weaker in the experimental groups than in the normal group (P < 0.05), but that of LGR8 mRNA was increased in the high-dose (10 and 100 microg/kg) DES groups (P < 0.05). No obvious mutations were observed in the PCR products in any of the experimental groups. CONCLUSION: Prenatal exposure to diethylstilbestrol affected the expression of LGR8 mRNA in the mouse gubernaculum testis, which suggests that diethylstilbestrol may induce cryptorchidism by interfering with the INSL3-LGR8 signaling system and consequently the development of the gubernaculum testis.

Risk factors for delayed intracranial hemorrhage secondary to ventriculoperitoneal shunt: A retrospective study.

BACKGROUND: Delayed intracranial hemorrhage (DICH), a potential complication of ventriculoperitoneal (VP) shunts, has been associated with high mortality, but its risk factors are still unclear. AIM: To investigate the risk factors of DICH after VP shunts. METHODS: We compared the demographic and clinical characteristics of DICH and non-DICH adult patients with VP shunts between January 2016 and December 2020. RESULTS: The 159 adult VP shunt patients were divided into 2 groups according to the development of DICH: the DICH group (n = 26) and the non-DICH group (n = 133). No statistically significant difference was found in age, sex, laboratory examination characteristics or preoperative modified Rankin Scale (mRS) score between the DICH and non-DICH groups (P > 0.05); however, a history of an external ventricular drain (EVD) [P = 0.045; odds ratio (OR): 2.814; 95%CI: 1.024-7.730] and postoperative brain edema around the catheter (P < 0.01; OR: 8.397; 95%CI: 3.043-23.171) were associated with a high risk of DICH. A comparison of preoperative mRS scores between the DICH group and the non-DICH group showed no significant difference (P = 0.553), while a significant difference was found in the postoperative mRS scores at the 3-mo follow-up visit (P = 0.024). CONCLUSION: A history of EVD and postoperative brain edema around the catheter are independent risk factors for DICH in VP shunt patients. DICH patients with a high mRS score are vulnerable to poor clinical outcomes.

[Progress in researches on 46, XY disorders of sexual development].

46, XY disorders of sexual development (46, XY DSD) are a group of complicated clinical conditions, which involve medical care, society, ethics and many other aspects. As chronic diseases, they necessitate long-term or even lifelong physical and mental follow-up and treatment. Early diagnosis and reasonable treatment could not only achieve appropriate development of the secondary sexual characteristics, but also effectively prevent gonadal malignancy. In recent years, environment pollution and other factors are contributing to the increasing incidence of 46, XY DSD all over the world. A deeper clinical insight into these disorders helps their earlier diagnosis and maximum improvement of prognosis. The etiology, new classification and treatment of 46, XY DSD are reviewed in this article.

Diagnosis and Treatment of Hypospadias With Megameatus Intact Prepuce.

Purpose: To evaluate the diagnosis and treatment methods of hypospadias with megameatus intact prepuce (MIP). Materials and Methods: A retrospective analysis was performed in 27 MIP children, 13 of whom underwent tubularized incised plate urethroplasty (TIP procedure), 7 underwent the Duplay procedure, 5 underwent the Mathieu procedure, 1 underwent meatal advancement and glanuloplasty (MAGPI procedure), and 1 underwent the glans approximation procedure (GAP). The patients were followed for 6-36 months to evaluate the surgical outcomes by the Pediatric Penile Perception Score (PPPS). Results: A total of 27 patients with a mean age of 8.12 ± 3.0 years were enrolled in this study, and 25 cases (25/27, 92.6%) were accidentally discovered during the first visit for phimosis. The patients had a formed urethra of 0.5 to 1.5 cm. Complications occurred in 4 of the 27 patients (14.81%): 2 patients with urethral fistula and 2 patients with meatal stenosis. One patient had a case of self-healed urethral fistula, and the remaining 3 patients underwent reoperation. The post-operative effect was satisfactory in all patients, and the urinary flow and stream during urination were normal. The overall average PPPS score of non-operative surgeons and parents was satisfactory. There were no significant differences in meatus appearance, glans appearance, skin appearance, and general appearance PPPS score among the Mathieu, TIP, and Duplay surgical procedures. Conclusions: MIP clinical manifestations are concealed and usually noted when circumcision is attempted. The suitable procedure for each patient should be tailored according to the anatomic features, and several techniques can be used with good functional and cosmetic results.

Peutz-Jeghers syndrome with intermittent upper intestinal obstruction: A case report and review of the literature.

RATIONALE: Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic syndrome characterized by a unique type of gastrointestinal hamartomatous polyp associated with oral and anal mucocutaneous pigmentations. Peutz-Jeghers polyps occur most numerously in the small intestine but frequently in the colon and stomach, only a few cases have been reported in the duodenum. PATIENT CONCERN: A further family history survey discovered 10 out of 14 members of the family (in 4 generations) had mucocutaneous pigmentations, but many of them were living in rural areas where they had no access to specialized medical services, so none were checked with endoscopy for polyps of hamartoma. DIAGNOSES: We report the case of a boy patient with mucocutaneous pigmentations over the lips, and a history of recurrent bouts of vomit and anemia over the preceding two years, no abdominal pain and mass. An upper gastrointestinal endoscopy revealed some small polyps in the stomach and multiple sessile polyps in the second part of the duodenum, but colonoscopy exam did not reveal any lesion. INTERVENTIONS: A double polypectomy and duodenum segmentary resection with end-to-end anastomosis was performed. Histopathology of the resected duodenum polyps indicated it to be a typical hamartomatous polyp. OUTCOMES: The child was under regular follow-up and recovered well. LESSONS: In this case, the patient was characteristic with pigmentations on his lips and intermittent upper intestinal obstruction (due to mass duodenal polyps), there are no definitive guidelines for the treatment to duodenal PJS hamartomatous polyp, each case requires tailor-made management.

Diagnosis and treatment of pediatric benign pneumoperitoneum: A case report series of 9 patients.

INTRODUCTION: Benign pneumoperitoneum (BPPT) is defined as asymptomatic free intraabdominal air or as pneumoperitoneum without peritonitis. Symptomatic free air requires surgical anagement, but management of asymptomatic pneumoperitoneum is controversial. In this study, we investigate the diagnosis and treatment of BPPT in children. CLINICAL FINDINGS: The clinical data of 9 pediatric patients with BPPT who were admitted to our hospital from January 2000 to January 2015 were retrospectively analyzed to summarize the diagnosis and treatment. Overall, 9 cases were included with 8 males and 1 female, aged from 4 days to 4 years. Among them there were 6 newborns (including 1 premature infant). Patients were all admitted to hospital with the major clinical symptom of abdominal distension, including 2 cases accompanied by tachypnea, 2 cases with vomiting, 1 case with diarrhea, and 2 cases with fever. No previous constipation or obstructive defecation existed. Six newborns had meconium defecation within 24 hours after birth. Physical examination revealed all patients with relaxed abdominal wall except 1 patient with abdominal distension had slight muscle stiffness and hyperactive bowel sounds. Abdominal X-ray suggested free air under the diaphragm in all cases. INTERVENTIONS/OUTCOMES: All patients except for one case of laparotomy were conservatively treated and cured with fasting, infection prevention, rehydration, abdominocentesis, and close observation. Nine cases of patients were all discharged with no death occurrence. After discharge follow-up of 7 months to 6 years was conducted. There was no recurrence of similar symptoms, and children were in good growth and development. CONCLUSION: The diagnosis of BPPT mainly relies on clinical symptoms in patient, careful abdominal examination, abdominal X-ray combined with abdominocentesis, and the exclusion of gastrointestinal perforation for confirmation. Conservative treatment can cure the disease. Attention should be paid to distinguish with surgical pneumoperitoneum to avoid unnecessary surgical exploration.

Decision-making in primary onset middle-age type 2 diabetes mellitus: a BOLD-fMRI study.

Although type 2 diabetes mellitus (T2DM) is a well-recognized risk factor for dementia, the neural mechanisms that underlying cognitive impairment in T2DM remain unclear. We used functional magnetic resonance imaging (fMRI) during a computerized version of the Iowa Gambling Task to investigate the neural basis of decision making at the initial onset stage of T2DM. Eighteen newly diagnosed middle-aged T2DM patients, with no previous diabetic treatment history, and 18 matched controls were recruited. Results indicated that T2DM patients made more disadvantageous decisions than controls. Compared to healthy subjects, T2DM patients showed decreased activation in the ventral medial prefrontal cortex (VMPFC), orbitofrontal cortex (OFC) and anterior cingulate cortex, and increased activity in the dorsolateral prefrontal cortex, posterior cingulate cortex, insula and occipital lobes. IGT performance positively correlated with changes in brain activation in the VMPFC and OFC in both groups. Moreover, poor glycemic control was associated with decision-making function both in behavioral and brain activity in the VMPFC and OFC in patients. Conclusively, T2DM patients may suffer from weaknesses in their prefrontal cortex functions that lead to poorer decision-making under ambiguity, at least as assessed by the IGT.

Spatial Working Memory Impairment in Patients with Non-neuropsychiatric Systemic Lupus Erythematosus: A Blood-oxygen-level Dependent Functional Magnetic Resonance Imaging Study.

OBJECTIVE: Using ethology and functional magnetic resonance imaging (fMRI) to explore mild cognitive dysfunction and spatial working memory (WM) impairment in patients with systemic lupus erythematosus (SLE) without overt neuropsychiatric symptoms (non-NPSLE) and to study whether any clinical biomarkers could serve as predictors of brain dysfunction in this disease. METHODS: Eighteen non-NPSLE patients and 18 matched subjects were all tested using the Montreal cognitive assessment scale test and scanned using blood-oxygen-level dependent fMRI while performing the n-back task to investigate the activation intensity of some cognition-related areas. RESULTS: Ethology results showed that non-NPSLE patients had mild cognitive dysfunction and memory dysfunction (p < 0.05). The fMRI scan confirmed a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), premotor area, parietal lobe, and supplementary motor area (SMA)/anterior cingulate cortex (ACC) that was activated during the n-back task, with right hemisphere dominance. However, only the right SMA/ACC showed a load effect in the non-NPSLE group; the activation intensity of most WM-related brain areas for the non-NPSLE group was lower than for the control group under 3 memory loads. Further, we found that the activation intensity of some cognition-related areas, including the bilateral caudate nucleus/insula and hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. An inverse correlation existed between individual activation intensity and disease duration. CONCLUSION: Non-NPSLE-related brain damage with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial WM and mild cognitive dysfunction. Patients with longer disease duration would be expected to exhibit increased central nervous system damage.