Diffusion-weighted imaging uncovers likely sources of processing-speed deficits in schizophrenia.

Schizophrenia, a devastating psychiatric illness with onset in the late teens to early 20s, is thought to involve disrupted brain connectivity. Functional and structural disconnections of cortical networks may underlie various cognitive deficits, including a substantial reduction in the speed of information processing in schizophrenia patients compared with controls. Myelinated white matter supports the speed of electrical signal transmission in the brain. To examine possible neuroanatomical sources of cognitive deficits, we used a comprehensive diffusion-weighted imaging (DWI) protocol and characterized the white matter diffusion signals using diffusion kurtosis imaging (DKI) and permeability-diffusivity imaging (PDI) in patients (n = 74), their nonill siblings (n = 41), and healthy controls (n = 113). Diffusion parameters that showed significant patient-control differences also explained the patient-control differences in processing speed. This association was also found for the nonill siblings of the patients. The association was specific to processing-speed abnormality but not specific to working memory abnormality or psychiatric symptoms. Our findings show that advanced diffusion MRI in white matter may capture microstructural connectivity patterns and mechanisms that govern the association between a core neurocognitive measure-processing speed-and neurobiological deficits in schizophrenia that are detectable with in vivo brain scans. These non-Gaussian diffusion white matter metrics are promising surrogate imaging markers for modeling cognitive deficits and perhaps, guiding treatment development in schizophrenia.

The common genetic influence over processing speed and white matter microstructure: Evidence from the Old Order Amish and Human Connectome Projects.

Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p<0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p<0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior.

Heritability of complex white matter diffusion traits assessed in a population isolate.

INTRODUCTION: Diffusion weighted imaging (DWI) methods can noninvasively ascertain cerebral microstructure by examining pattern and directions of water diffusion in the brain. We calculated heritability for DWI parameters in cerebral white (WM) and gray matter (GM) to study the genetic contribution to the diffusion signals across tissue boundaries. METHODS: Using Old Order Amish (OOA) population isolate with large family pedigrees and high environmental homogeneity, we compared the heritability of measures derived from three representative DWI methods targeting the corpus callosum WM and cingulate gyrus GM: diffusion tensor imaging (DTI), the permeability-diffusivity (PD) model, and the neurite orientation dispersion and density imaging (NODDI) model. These successively more complex models represent the diffusion signal modeling using one, two, and three diffusion compartments, respectively. RESULTS: We replicated the high heritability of the DTI-based fractional anisotropy (h(2) = 0.67) and radial diffusivity (h(2) = 0.72) in WM. High heritability in both WM and GM tissues were observed for the permeability-diffusivity index from the PD model (h(2) = 0.64 and 0.84), and the neurite density from the NODDI model (h(2) = 0.70 and 0.55). The orientation dispersion index from the NODDI model was only significantly heritable in GM (h(2) = 0.68). CONCLUSION: DWI measures from multicompartmental models were significantly heritable in WM and GM. DWI can offer valuable phenotypes for genetic research; and genes thus identified may reveal mechanisms contributing to mental and neurological disorders in which diffusion imaging anomalies are consistently found. Hum Brain Mapp 37:525-535, 2016. © 2015 Wiley Periodicals, Inc.

Perioperative Adverse Outcome and Its Predictors After Emergency Laparotomy Among Sigmoid Volvulus Patients: Retrospective Follow-Up Study.

Background: Acute sigmoid volvulus is a surgical emergency with closed-loop obstruction of the colon that often requires emergency laparotomy, which is associated with a multitude of post-operative complications. Although sigmoid volvulus is the main cause of intestinal obstruction in Ethiopia, local studies of its management outcomes are limited. Objective: To assess the magnitude and predictors of adverse perioperative outcomes of emergency laparotomy for acute sigmoid volvulus in the Debre Markos Comprehensive Specialized Hospital (DMCSH), Amhara region, Ethiopia in 2023. Methods: This was a retrospective follow-up study. Descriptive statistics were used to measure perioperative outcomes and other study variables. Bivariable and multivariable logistic regression models were used to identify the predictors of adverse surgical outcomes. Associations were considered significant at p < 0.05 (95% confidence interval). Results: In total, 170 study participants were enrolled, with a response rate of 91.4%. Forty-nine patients (28.8%) developed perioperative adverse outcomes. Pneumonia (29 patients, 28.1%), surgical site infection (19 patients, 18.4%), and wound dehiscence (10 patients, 9.7%) were the most common complications. Pre-operative shock [AOR: 3.87 (95% CI: (1.22, 12.28))], pus or fecal matter contamination of the peritoneum [AOR: 4.43 (95% CI: (1.35, 14.47)], and a higher American Society of Anesthesiologists (ASA) score [AOR: 2.37 (95% CI: (1.05, 5.34))] were identified as predictors of perioperative adverse events. Conclusion: The perioperative adverse outcomes in this study were higher than those reported in Ethiopian national and global reports following emergency laparotomies. Hypotension at presentation, pus and/or fecal matter contamination of the peritoneum, and higher ASA scores are strong predictors of increased perioperative adverse outcomes. Therefore, healthcare providers and institutions involved in the delivery of emergency surgical care should emphasize the importance of early surgical intervention, adequate resuscitation, and patient monitoring to improve perioperative outcomes.

Microbiome and Colorectal Cancer Management.

Globally, colorectal cancer (CRC) is one of the most typical lethal cancers. One of the main factors for better outcomes in CRC management is the early detection of the disease. As an integral component of human metabolism and homeostasis, gut microbiome has recently been a subject of extensive research for its role in the pathogenesis, diagnosis, and treatment of CRC. Microbial dysbiosis (the decrease in beneficial gut flora and the increase of detrimental populations) leads to chronic inflammation and genetic alteration in the host cells, triggering and promoting CRC carcinogenesis. Identifying these microbial changes in depth would potentially isolate the pathogenic microbiota species and establish biomarker models for early detection of CRC. On the other hand, modifying these microbial changes would help formulate preventative and therapeutic strategies for CRC, developing a more precise CRC management plan according to each patient's microbial print. This essay explains gut microbiome composition, microbial changes (dysbiosis) in CRC carcinogenesis, the probability of creating microbiome-based CRC biomarkers, and potential microbiome-targeted treatment options.

White Matter Integrity in High-Altitude Pilots Exposed to Hypobaria.

INTRODUCTION: Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability. METHODS: There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values. RESULTS: Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots. DISCUSSION: Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes.McGuire SA, Boone GRE, Sherman PM, Tate DF, Wood JD, Patel B, Eskandar G, Wijtenburg SA, Rowland LM, Clarke GD, Grogan PM, Sladky JH, Kochunov PV. White matter integrity in high-altitude pilots exposed to hypobaria. Aerosp Med Hum Perform. 2016; 87(12):983-988.