The course and branching pattern of pudendal nerve in fetus

The pudendal nerve is a considerably large branch of the sacral plexus. There are many articles in the literature concerning the pudendal nerve in adults, but as far as we know, there is none on the branching pattern and variations in pudendal nerve anatomy in fetus. This study investigates the pudendal nerve trunking with respect to the piriformis muscle in 25 formalin-fixed fetuses (50 sides of pelves, 15 females, 10 males), ranging from 20 to 37 weeks of gestation. We investigate pudendal nerve trunking in four types: Type I-a is defined as single-trunk with the inferior rectal nerve branching proximal to the dorsal nerve of penis/clitoris (38%), Type I-b is also single-trunk with the dorsal nerve of penis/clitoris branching proximal to the inferior rectal nerve (24%), Type II is double-trunk with medial trunk as an inferior rectal nerve (34%), and Type III is triple-trunk (4%). We measured the average diameter of the main trunk of pudendal nerve in Type I-a and I-b groups to be 0.98 +/- 0.33 mm. We also measured the average length of the pudendal nerve trunks before the dorsal nerve of penis/clitoris branch to be 7.35 +/- 3.50 mm. There was no significant statistical difference in the average length, diameter, number of trunks, and pudendal nerve variations between male and female and also right and left sides of the pelves. This first and detailed fetal study of pudendal nerve trunking with respect to the piriformis muscle would be useful for educational anatomy dissections and anatomical landmark definitions for relevant clinical procedures.     

Increase in Campylobacter jejuni invasion of intestinal epithelial cells under low-oxygen coculture conditions that reflect the in vivo environment

Campylobacter jejuni infection often results in bloody, inflammatory diarrhea, indicating bacterial disruption and invasion of the intestinal epithelium. While C. jejuni infection can be reproduced in vitro using intestinal epithelial cell (IEC) lines, low numbers of bacteria invading IECs do not reflect these clinical symptoms. Performing in vitro assays under atmospheric oxygen conditions neither is optimal for microaerophilic C. jejuni nor reflects the low-oxygen environment of the intestinal lumen. A vertical diffusion chamber (VDC) model system creates microaerobic conditions at the apical surface and aerobic conditions at the basolateral surface of cultured IECs, producing an in vitro system that closely mimics in vivo conditions in the human intestine. Ninefold increases in interacting and 80-fold increases in intracellular C. jejuni 11168H wild-type strain bacteria were observed after 24-h coculture with Caco-2 IECs in VDCs under microaerobic conditions at the apical surface, compared to results under aerobic conditions. Increased bacterial interaction was matched by an enhanced and directional host innate immune response, particularly an increased basolateral secretion of the proinflammatory chemokine interleukin-8 (IL-8). Analysis of the invasive ability of a nonmotile C. jejuni 11168H rpoN mutant in the VDC model system indicates that motility is an important factor in the early stages of bacterial invasion. The first report of the use of a VDC model system for studying the interactions of an invasive bacterial pathogen with IECs demonstrates the importance of performing such experiments under conditions that represent the in vivo situation and will allow novel insights into C. jejuni pathogenic mechanisms.     

Effect of Taurine on Brain 8-hydroxydeoxyguanosine and 3-nitrotyrosine Levels in Endotoxemia

Taurine is a sulfur-containing β-amino acid that is found in milimolar concentrations in most mammalian tissues and plasma. It was shown to have cytoprotective effects in many in vitro and in vivo studies and these actions are often attributed to an antioxidant mechanism. In this study, we aimed to investigate the effect of acute taurine administration on endotoxin-induced oxidative and nitrosative stress in brain. Fourty adult male guinea pigs were divided into four groups: control, taurine, endotoxemia, and endotoxemia + taurine. Taurine (300 mg/kg), lipopolysaccharide (LPS, 4 mg/kg), or taurine plus LPS was administered intraperitoneally. After 6 h of incubation, when highest blood levels of taurine and endotoxin were attained, the animals were killed and brain tissue samples were collected. 3-Nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHdG) and taurine levels were measured using high-performance liquid chromatography methods. LPS administration significantly increased 3-NT, 8-OHdG levels, and dramatically reduced taurine concentrations in brain tissue compared to control group. The groups in which taurine was administered alone or with LPS, contradiction to well-known antioxidant effect, taurine caused elevated concentrations of 3-NT and 8-OHdG compared to both control and endotoxemia groups. In conclusion, endotoxemia leads to tyrosine nitration and DNA base modification that can be assessed by 3-NT and 8-OHdG, respectively. Taurine did not exhibit any antioxidant effect; moreover, it may contribute to neuronal damage at this dose. Thus, we can suggest that lower dose of taurine administration may be benefial for neuronal protection or adversely taurine administration may have toxic effect at all doses.     

Comparison of quantitative susceptibility mapping methods on evaluating radiation-induced cerebral microbleeds and basal ganglia at 3T and 7T

Quantitative susceptibility mapping (QSM) has the potential for being a biomarker for various diseases because of its ability to measure tissue susceptibility related to iron deposition, myelin, and hemorrhage from the phase signal of a T₂*-weighted MRI. Despite its promise as a quantitative marker, QSM is faced with many challenges, including its dependence on preprocessing of the raw phase data, the relatively weak tissue signal, and the inherently ill posed relationship between the magnetic dipole and measured phase. The goal of this study was to evaluate the effects of background field removal and dipole inversion algorithms on noise characteristics, image uniformity, and structural contrast for cerebral microbleed (CMB) quantification at both 3T and 7T. We selected four widely used background phase removal and five dipole field inversion algorithms for QSM and applied them to volunteers and patients with CMBs, who were scanned at two different field strengths, with ground truth QSM reference calculated using multiple orientation scans. 7T MRI provided QSM images with lower noise than did 3T MRI. QSIP and VSHARP + iLSQR achieved the highest white matter homogeneity and vein contrast, with QSIP also providing the highest CMB contrast. Compared with ground truth COSMOS QSM images, overall good correlations between susceptibility values of dipole inversion algorithms and the COSMOS reference were observed in basal ganglia regions, with VSHARP + iLSQR achieving the susceptibility values most similar to COSMOS across all regions. This study can provide guidance for selecting the most appropriate QSM processing pipeline based on the application of interest and scanner field strength.     

Fracture mechanics of cortical bone tissue: a hierarchical perspective

The performance of bone tissue in the presence of flaws is a highly remarkable one. Bone tissue is the outcome of an adaptive evolutionary process; thus, insight into the mechanisms by which it fails would provide valuable information not only for development of mechanically superior biomimetic materials but also for development of treatment modalities to prevent debilitating bone fractures. Clinically, fractures of skeletal organs occur as a result of aging, disease, overuse, and trauma. Fracture mechanics, a sub-discipline of solid mechanics that investigates the performance of cracked materials, has been employed extensively in characterizing the mechanisms by which bone tissue fractures. At present the fracture mechanisms at the macroscale are better characterized than at the microscale. On the other hand, a mechanistic understanding of damage evolution at the submicroscopic scale is largely limited to postulations with little experimental insight. The challenge of skeletal fragility will be dealt with more efficiently with deeper understanding of the fracture process at each hierarchical size scale. The most recent review on this subject matter was a decade ago, and there have been numerous developments in the fracture mechanics of bone since then. This review recaps the existing literature with an emphasis on the hierarchical nature of the fracture process in bone, entailing the supramolecular, microscopic, and macroscopic scales.     

Effect of Formulation Variables on the Stability of a Live,Rotavirus (RV3-BB) Vaccine Candidate using in vitro Gastric Digestion Models to Mimic Oral Delivery

In this work, two different in vitro gastric digestion models were used to evaluate the stability of a live attenuated rotavirus vaccine candidate (RV3-BB) under conditions designed to mimic oral delivery in infants. First, a forced-degradation model was established at low pH to assess the buffering capacity of formulation excipients and to screen for RV3-BB stabilizers. Second, a sequential-addition model was implemented to examine RV3-BB stability under conditions more representative of oral administration to infants. RV3-BB rapidly inactivated at < pH 5.0 (37 °C, 1 h) as measured by an infectivity RT-qPCR assay. Pre-neutralization with varying volumes of infant formula (Enfamil®) or antacid (Mylanta®) conferred partial to full protection of RV3-BB. Excipients with sufficient buffering capacity to minimize acidic pH inactivation of RV3-BB were identified (e.g., succinate, acetate, adipate), however, they concomitantly destabilized RV3-BB in accelerated storage stability studies. Both effects were concentration dependent, thus excipient optimization was required to design candidate RV3-BB formulations which minimize acid-induced viral inactivation during oral delivery while not destabilizing the vaccine during long-term 2–8 °C storage. Finally, a statistical Design -of-Experiments (DOE) study examining RV3-BB stability in the in vitro sequential-addition model identified key formulation parameters likely affecting RV3-BB stability during in vivo oral delivery.