The amygdala and related structures in the pathophysiology of autism

Autism is a neurodevelopmental disorder that is defined behaviorally by severe deficiencies in reciprocal social interaction, verbal and nonverbal communication, and restricted interests. The amygdala is involved in the regulation of social behaviors and may be an important site of pathology for the social dysfunction seen in autism. This review focuses on lesion, postmortem, and neuroimaging studies that investigate the amygdala and related structures in this disorder. Other brain regions potentially involved in the neuropathology of autism are also briefly discussed. Although supportive evidence exists for amygdala dysfunction in autism, the currently available data are inconsistent and additional research is needed.     

Laparoscopic vertical sleeve gastrectomy after open gastric banding in a patient with situs inversus totalis

While several equivalent alternatives are available in the bariatric algorithm, more recently the laparoscopic sleeve gastrectomy (SG) has been gaining traction as an effective means of weight loss in patients with morbid obesity. We present the case of a 39-year-old woman with situs inversus totalis, who was taken to the operating room for laparoscopic SG. The patient had previously undergone a failed open gastric banding procedure 20 months earlier. Awareness of the inherited condition before performing the operation allows for advanced planning and preparation. Subsequent modifications to the standard trocar placement help make the procedure more technically feasible. To our knowledge, this is the first published report of a laparoscopic SG after open gastric banding in a patient with situs inversus totalis. After encountering the initial disorientation, we believe experienced laparoscopic surgeons can perform this procedure successfully and safely.     

Ultrasound-guided placement of midline catheters in the surgical intensive care unit: a cost-effective proposal for timely central line removal

Background

The early removal of central intravenous (IV) catheters, as a means of reducing the incidence of central line–associated blood stream infections (CLABSI), remains a major health care initiative. However, attaining IV access in the surgical intensive care unit (SICU) can be quite difficult. We report the success of a novel, resident-driven program for the placement of ultrasound-guided midline catheters in critically ill patients.

Materials and methods

A prospective pilot study of 31 subjects admitted to the SICU from June to December 2011 was performed. Intermediate-length (20 cm) midline catheters were placed by trained housestaff, under ultrasound guidance, into the basilic or cephalic veins. Procedural details including time to cannulation, complications, and costs were recorded.

Results

Successful placement was achieved in 96.8% (n = 30), with a mean follow-up of 9.8 ± 5.6 (range 2–21) days. An average of 1.3 ± 0.7 (range 1–4) attempts with a median of 13.0 ± 14.5 (range 0.5–68) minutes was required for successful venous cannulation. The most common site was the basilic vein (n = 23). Only minor complications were encountered; three catheters leaked at the insertion site and one patient developed phlebitis. No CLABSI occurred. The total procedure cost was $87 per catheter for the SICU team compared with $1500 per catheter when performed by an interventional radiologist. During the study period, a total of 283 central line days were avoided with an estimated cost savings of $13,614.

Conclusions

Ultrasound-guided midline catheters placed by the housestaff are a cost-effective alternative for patients in the SICU with difficult IV access. Successful placement can help facilitate early central line removal and thus may reduce CLABSI rates.     

Ferroxitosis: A cell death from modulation of oxidative phosphorylation and PKM2-dependent glycolysis in melanoma

Reliance on glycolysis is a characteristic of malignancy, yet the development of resistance to BRAF inhibitors in melanoma is associated with gain of mitochondrial function. Concurrent attenuation of oxidative phosphorylation and HIF-1α/PKM2-dependent glycolysis promotes a non-apoptotic, iron- and oxygen-dependent cell death that we term ferroxitosis. The redox cycling agent menadione causes a robust increase in oxygen consumption, accompanied by significant loss of intracellular ATP and rapid cell death. Conversely, either hypoxic adaptation or iron chelation prevents menadione-induced ferroxitosis. Ectopic expression of K213Q HIF-1α mutant blunts the effects of menadione. However, knockdown of HIF-1α or PKM2 restores menadione-induced cytotoxicity in hypoxia. Similarly, exposure of melanoma cells to shikonin, a menadione analog and a potential PKM2 inhibitor, is sufficient to induce ferroxitosis under hypoxic conditions. Collectively, our findings reveal that ferroxitosis curtails metabolic plasticity in melanoma.