Ex vivo human testes as a practical model to simulate ultrasound-guided testicular cell transplantation for human fertility restoration.

OBJECTIVE: To develop an ex vivo model to practice ultrasound-guided injection of cellular material into human seminiferous tubules to simulate testicular cell transplantation (TCT). DESIGN: Simulated TCT injections were performed in human testes removed during orchiectomy. The rete testis was the target site of injection. Successful retrograde infiltration of injected material into the lumen of the seminiferous tubules was detected using ultrasound and confirmed with histology. SETTING: Single academic surgical center. PATIENT(S): Adult patients undergoing orchiectomy for nononcologic indications. INTERVENTION(S): The testes were injected with sonographic contrast (Optison), methylene blue, and fluorescent-labeled cells. MAIN OUTCOME MEASURE(S): A characteristic streaming pattern of sonographic contrast in the testis was used to define sonographic success, and the presence of methylene blue and fluorescent-labeled cells within the seminiferous tubules confirmed histologic success. RESULT(S): We performed simulated TCT injections in 30 testes obtained from 16 patients undergoing orchiectomy. We were able to achieve sonographic success in 57% of injections and confirmed that sonographic success is correlated with histologic success. CONCLUSION(S): Testicular cell transplantation injections can be practiced using human testes. As there appears to be a learning curve associated with this procedure, developing this infrastructure to practice these skills is critical before implementation in patients.

Hospital complications and costs of spinal arteriovenous malformations in the United States from 2002-2014.

BACKGROUND: Spinal arteriovenous malformations (AVMs) are rare disease entities with significant morbidity if untreated. Risk factors of complications, hospitalization and costs-of-care remain in need of characterization. METHODS: Using the National Inpatient Sample years 2002-2014, adult subjects with spinal AVMs who underwent either laminectomy with lesion excision or endovascular embolization were extracted using ICD-9-CM diagnostic code 747.82. Predictors of inpatient complications, hospital length of stay (HLOS), and discharge home were evaluated using multivariable regression. Cost was evaluated using inflation-adjusted healthcare cost [charge*(cost/charge ratio)]. Mean differences (B), odds ratios (OR) and 95% CIs are reported. Significance was assessed at P<0.001. RESULTS: In 2546 weighted admissions, age was 54.4±16.5-years (laminectomy: 70.0%, embolization: 30.0%). Fifteen percent suffered inpatient complications. Cost of hospitalization was $ 41216±38511 and was elevated for subjects with complications ($67571±2636, vs. no complications: $36562±723, P<0.001). Increased costs for categories of complications ranged from $ 16525 (renal/urinary) to $62246 (thromboembolism). In surgical subjects, complications were more costly ($ 69761±2896, vs. no complications: 36520±809, P<0.001). On multivariable analysis, major/extreme disease severity and major/extreme mortality risk were associated with increased complications and HLOS (P<0.001). Elective admissions had shorter HLOS (B=-4.3-days, [-4.8, -3.8], P<0.001) and higher odds of discharge home (OR=2.6 [2.1-3.2], P<0.001). Laminectomy (vs. embolization) was associated with complications (OR=2.6, 95% CI [1.7-3.8], P<0.001), HLOS (B=3.4-days [2.9-4.0], P<0.001), and decreased discharge home (OR=0.3 [0.2-0.4], P<0.001). CONCLUSIONS: In spinal AVMs, high disease severity, non-elective admissions, and surgery are associated with complications, HLOS, and discharge to a non-home facility. Costs are elevated in patients suffering complications. Future studies are warranted.

Basal impulses: findings from the last twenty years on impulsivity and reward pathways using deep brain stimulation.

INTRODUCTION: Deep brain stimulation (DBS) is an important treatment modality for movement disorders. Its role in tasks and processes of higher cortical function continues to increase in importance and relevance. This systematic review investigates the impact of DBS on measures of impulsivity. EVIDENCE ACQUISITION: A total of 45 studies were collated from PubMed (30 prospective, 8 animal, 4 questionnaire-based, and 3 computational models), excluding case reports and review articles. Two areas extensively studied are the subthalamic nucleus (STN) and nucleus accumbens (NAc). EVIDENCE SYNTHESIS: While both are part of the basal ganglia, the STN and NAc have extensive connections to the prefrontal cortex, cingulate cortex, and limbic system. Therefore, understanding cause and treatment of impulsivity requires understanding motor pathways, learning, memory, and emotional processing. DBS of the STN and NAc shell can increase objective measures of impulsivity, as measured by reaction times or reward-based learning, independent from patient insight. The ability for DBS to treat impulse control disorders, and also cause and/or worsen impulsivity in Parkinson's disease, may be explained by the affected closely-related neuroanatomical areas with discrete and sometimes opposing functions. CONCLUSIONS: As newer, more refined DBS technology emerges, large-scale prospective studies specifically aimed at treatment of impulsivity disorders are needed.

Apolipoprotein E Epsilon 4 Genotype, Mild Traumatic Brain Injury, and the Development of Chronic Traumatic Encephalopathy.

The annual incidence of mild traumatic brain injury (MTBI) is 3.8 million in the USA with 10⁻15% experiencing persistent morbidity beyond one year. Chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by accumulation of hyperphosphorylated tau, can occur with repetitive MTBI. Risk factors for CTE are challenging to identify because injury mechanisms of MTBI are heterogeneous, clinical manifestations and management vary, and CTE is a postmortem diagnosis, making prospective studies difficult. There is growing interest in the genetic influence on head trauma and development of CTE. Apolipoprotein epsilon 4 (APOE-ε4) associates with many neurologic diseases, and consensus on the ε4 allele as a risk factor is lacking. This review investigates the influence of APOE-ε4 on MTBI and CTE. A comprehensive PubMed literature search (1966 to 12 June 2018) identified 24 unique reports on the topic (19 MTBI studies: 8 athletic, 5 military, 6 population-based; 5 CTE studies: 4 athletic and military, 1 leucotomy group). APOE-ε4 genotype is found to associate with outcomes in 4/8 athletic reports, 3/5 military reports, and 5/6 population-based reports following MTBI. Evidence on the association between APOE-ε4 and CTE from case series is equivocal. Refining modalities to aid CTE diagnosis in larger samples is needed in MTBI.

Caveolin1 Identifies a Specific Subpopulation of Cerebral Cortex Callosal Projection Neurons (CPN) Including Dual Projecting Cortical Callosal/Frontal Projection Neurons (CPN/FPN).

The neocortex is composed of many distinct subtypes of neurons that must form precise subtype-specific connections to enable the cortex to perform complex functions. Callosal projection neurons (CPN) are the broad population of commissural neurons that connect the cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes and connectivity is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We identify in mouse that the lipid-bound scaffolding domain protein Caveolin 1 (CAV1) is specifically expressed by a unique subpopulation of Layer V CPN that maintain dual ipsilateral frontal projections to premotor cortex. CAV1 is expressed by over 80% of these dual projecting callosal/frontal projection neurons (CPN/FPN), with expression peaking early postnatally as axonal and dendritic targets are being reached and refined. CAV1 is localized to the soma and dendrites of CPN/FPN, a unique population of neurons that shares information both between hemispheres and with premotor cortex, suggesting function during postmitotic development and refinement of these neurons, rather than in their specification. Consistent with this, we find that Cav1 function is not necessary for the early specification of CPN/FPN, or for projecting to their dual axonal targets. CPN subtype-specific expression of Cav1 identifies and characterizes a first molecular component that distinguishes this functionally unique projection neuron population, a population that expands in primates, and is prototypical of additional dual and higher-order projection neuron subtypes.