Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa.

Individuals with anorexia nervosa (AN) restrict eating and become emaciated. They tend to have an aversion to foods rich in fat. Because epoxide hydrolase 2 (EPHX2) was identified as a novel AN susceptibility gene, and because its protein product, soluble epoxide hydrolase (sEH), converts bioactive epoxides of polyunsaturated fatty acid (PUFA) to the corresponding diols, lipidomic and metabolomic targets of EPHX2 were assessed to evaluate the biological functions of EPHX2 and their role in AN. Epoxide substrates of sEH and associated oxylipins were measured in ill AN, recovered AN and gender- and race-matched controls. PUFA and oxylipin markers were tested as potential biomarkers for AN. Oxylipin ratios were calculated as proxy markers of in vivo sEH activity. Several free- and total PUFAs were associated with AN diagnosis and with AN recovery. AN displayed elevated n-3 PUFAs and may differ from controls in PUFA elongation and desaturation processes. Cytochrome P450 pathway oxylipins from arachidonic acid, linoleic acid, alpha-linolenic acid and docosahexaenoic acid PUFAs are associated with AN diagnosis. The diol:epoxide ratios suggest the sEH activity is higher in AN compared with controls. Multivariate analysis illustrates normalization of lipidomic profiles in recovered ANs. EPHX2 influences AN risk through in vivo interaction with dietary PUFAs. PUFA composition and concentrations as well as sEH activity may contribute to the pathogenesis and prognosis of AN. Our data support the involvement of EPHX2-associated lipidomic and oxylipin dysregulations in AN, and reveal their potential as biomarkers to assess responsiveness to future intervention or treatment.

Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa.

Anorexia nervosa (AN) is a complex psychiatric disorder with high morbidity and mortality rates. While many individuals make full recoveries, up to a third of patients develop a chronic, treatment-resistant form of the illness that leads to a premature death in 15-20% of those affected. There have been few advances in treatment, both in terms of psychological or pharmacologic treatment over the last 30 years. Food aversion is commonly cited by patients with AN as a barrier to normalizing eating and weight. Our group has a keen interest in examining factors that might allow this to be addressed, thus improving treatment outcomes through personalized dietary plans or nutritional supplementation related to underlying genetic status. We demonstrated that polyunsaturated fatty acids (PUFAs)-derived bioactive lipids (eicosanoids) are implicated in not only the risk of AN, but also with its comorbid psychopathology. Of interest, the differential postprandial omega 6-derived eicosanoid shift observed in AN highlights the possibility that the metabolism of PUFAs is an important mechanism underlying the profound food version, contributing to pathological food restriction in AN. A concise knowledge of the relationships among PUFAs, eicosanoids, and AN clinical course and psychopathology could be the key to developing personalized nutritional rehabilitative treatments for those suffering from AN. This paper provides a comprehensive overview of the literature on PUFAs in AN. We also selectively reviewed the clinical benefits PUFA treatments exert in other psychiatric diseases, on weight and appetite regulation, and for resolution of inflammation, all of which are relevant in the disease course and outcome of AN. We propose that personalized PUFA formulation be developed and tested as a novel adjunctive treatment for patients with AN. We hypothesize that with personalized PUFA formulation, food aversion and anxiety about eating will decrease while mood, dietary behavior, and weight restoration will improve in AN, leading to improvements in the overall treatment outcome.

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

Treatment of axillary osmidrosis: a comparison between subcutaneous laser and superficial liposuction curettage.

BACKGROUND: Axillary osmidrosis can lead to personal and social problems, particularly in Asian culture. Superficial liposuction with curettage and subcutaneous laser are surgical intervention commonly used for osmidrosis. OBJECTIVE: Retrospectively, we compared the effectiveness and complications between superficial liposuction with curettage and subcutaneous laser in an Asian population. METHODS: Totally, 66 and 19 patients receiving subcutaneous laser and superficial liposuction with curettage (LC) were recruited. The effectiveness of treatment was assessed by patients subjectively. Recurrence rate of osmidrosis and complications were also evaluated. RESULTS: 95% of patients showed good-to-excellent improvement in LC group and only 30% of patients showing good-to-excellent results in laser group (P < 0.01). Binary logistic regression revealed that the odds ratio of LC was 53.288 (P = 0.006) for >50% improvement in osmidrosis. The recurrence rate was not significantly different (P = 0.139), however, the duration to recurrence of osmidrosis was significantly longer in LC group (P < 0.01). The complication rate was 31% in LC group and 6% in laser group (P < 0.01). CONCLUSION: Superficial liposuction with curettage provides more effective treatment with higher complication rates and is possibly suitable for severe patients. For mild-to-moderate osmidrosis, or preferring a better cosmetic result or short recovery, subcutaneous laser could be applied.

Streptococcus agalactiae infective endocarditis with large vegetation in a patient with underlying protein S deficiency.

We present a case of a patient with underlying protein S deficiency who suffered from infective endocarditis with a large anterior mitral leaflet (AML) mass of approximately 4.5 cm in length. Intraoperative transesophageal echocardiography (TEE) revealed the mass at the AML base and a rupture of the posterior mitral leaflet chordae tendinae. The vegetation's large size may have been caused by one or more of three factors: location, underlying disease, and the microorganism causing infection. Patients with protein S deficiency are prone to thromboembolic events during cardiac surgery. Infective endocarditis caused by Streptococcus agalactiae usually has a poor prognosis, and, thus, early surgery is recommended.

Common origin of sterol biosynthesis points to a feeding strategy shift in Neoproterozoic animals.

Steranes preserved in sedimentary rocks serve as molecular fossils, which are thought to record the expansion of eukaryote life through the Neoproterozoic Era ( ~ 1000-541 Ma). Scientists hypothesize that ancient C27 steranes originated from cholesterol, the major sterol produced by living red algae and animals. Similarly, C28 and C29 steranes are thought to be derived from the sterols of prehistoric fungi, green algae, and other microbial eukaryotes. However, recent work on annelid worms-an advanced group of eumetazoan animals-shows that they are also capable of producing C28 and C29 sterols. In this paper, we explore the evolutionary history of the 24-C sterol methyltransferase (smt) gene in animals, which is required to make C28+ sterols. We find evidence that the smt gene was vertically inherited through animals, suggesting early eumetazoans were capable of C28+ sterol synthesis. Our molecular clock of the animal smt gene demonstrates that its diversification coincides with the rise of C28 and C29 steranes in the Neoproterozoic. This study supports the hypothesis that early eumetazoans were capable of making C28+ sterols and that many animal lineages independently abandoned its biosynthesis around the end-Neoproterozoic, coinciding with the rise of abundant eukaryotic prey.

Comparison of component separation technique, partition technique, and extended anterolateral thigh flap in complex abdominal wall closure.

PURPOSE: This study tries to compare three methods in complex abdominal wall reconstruction. METHODS: A retrospective review was conducted at a single medical center between December 2008 and May 2019. Forty-seven patients who received abdominal fascia repair were enrolled. The patients were divided into three groups: A [component separation technique (CST)], B (partition technique), and C [extended anterolateral thigh (ALT) flap]. All relevant patient information was collected. Statistical analysis including one-way analysis of variance, Chi-square test, and the receiver operating characteristic curve were used. RESULTS: There were no significant differences between the group results related to gender, age, BMI, follow-up, diabetes mellitus, tobacco, or short-, and long-term complications. However, there were significant differences in fascia defect size between groups (group A: 7.6 cm vs. group B: 10.76 cm vs. group C: 13.64 cm). The averaged operative time in group C (339.25 mins) was significantly longer than that in group A (145.40 mins) and B (152.37 mins). The hospitalization in group C (24.1 days) was significantly longer than that in group A (8.2 days) and B (10.3 days). The complication thresholds of group A and group B are 9.45 cm and 11.75 cm, respectively. CONCLUSION: This study suggests that extended ALT flap provides the largest fascia defect closure, followed orderly by partition technique and CST, but requires longer operative time and hospitalization. There are no significant differences in postoperative complications between three groups. A prospective study with indications based on these findings is suggested.

Phanerozoic radiation of ammonia oxidizing bacteria.

The modern nitrogen cycle consists of a web of microbially mediated redox transformations. Among the most crucial reactions in this cycle is the oxidation of ammonia to nitrite, an obligately aerobic process performed by a limited number of lineages of bacteria (AOB) and archaea (AOA). As this process has an absolute requirement for O2, the timing of its evolution-especially as it relates to the Great Oxygenation Event ~ 2.3 billion years ago-remains contested and is pivotal to our understanding of nutrient cycles. To estimate the antiquity of bacterial ammonia oxidation, we performed phylogenetic and molecular clock analyses of AOB. Surprisingly, bacterial ammonia oxidation appears quite young, with crown group clades having originated during Neoproterozoic time (or later) with major radiations occurring during Paleozoic time. These results place the evolution of AOB broadly coincident with the pervasive oxygenation of the deep ocean. The late evolution AOB challenges earlier interpretations of the ancient nitrogen isotope record, predicts a more substantial role for AOA during Precambrian time, and may have implications for understanding of the size and structure of the biogeochemical nitrogen cycle through geologic time.

Priority allocation of pandemic influenza vaccines in Australia - Recommendations of 3 community juries.

BACKGROUND: Pandemic planning has historically been oriented to respond to an influenza virus, with vaccination strategy being a key focus. As the current COVID-19 pandemic plays out, the Australian government is closely monitoring progress towards development of SARS-CoV2 vaccines as a definitive intervention. However, as in any pandemic, initial supply will likely be exceeded by demand due to limited manufacturing output. METHODS: We convened community juries in three Australian locations in 2019 to assess public acceptability and perceived legitimacy of influenza pandemic vaccination distribution strategies. Preparatory work included literature reviews on pandemic vaccine allocation strategies and on vaccine allocation ethics, and simulation modelling studies. We assumed vaccine would be provided to predefined priority groups. Jurors were then asked to recommend one of two strategies for distributing remaining early doses of vaccine: directly vaccinate people at higher risk of adverse outcomes from influenza; or indirectly protect the general population by vaccinating primary school students, who are most likely to spread infection. RESULTS: Thirty-four participants of diverse backgrounds and ages were recruited through random digit dialling and topic-blinded social media advertising. Juries heard evidence and arguments supporting different vaccine distribution strategies, and questioned expert presenters. All three community juries supported prioritising school children for influenza vaccination (aiming for indirect protection), one by 10-2 majority and two by consensus. Justifications included that indirect protection benefits more people and is likely to be more publicly acceptable. CONCLUSIONS: In the context of an influenza pandemic, informed citizens were not opposed to prioritising groups at higher risks of adverse outcomes, but if resources and epidemiological conditions allow, achieving population benefits should be a strategic priority. These insights may inform future SARS-CoV-2 vaccination strategies.

Spin-phonon coupling effects in antiferromagnetic Cr2O3 nanoparticles.

In the present work we use Raman microscopy to investigate the size effect of spin-phonon coupling in antiferromagnetic Cr2O3 nanoparticles. The peculiarities of the dependency of the phonon wave number on temperature (with a relatively weak peak at 293 cm(-1)) can be attributed to the spin-phonon coupling. The variation with temperature of the spin-phonon mode develops when the antiferromagnetic state is near the ordering temperature of the Cr spins. The observations can be reasonably well interpreted by describing the order parameter. A shift in frequency is caused by a strong spin-phonon interaction in Cr2O3. The obtained s-ph coefficients are found to be consistent with the strain, where raising the strain results in weakening of the s-ph coupling.

Feasibility of pedicled anterolateral thigh flap with tensor fascia lata and vastus lateralis for difficult abdominal wall closure.

PURPOSE: Long-term follow-up for pedicled anterolateral thigh (ALT) flap with vastus lateralis and tensor fascia lata for complex abdominal wall reconstruction is rarely reported. This study aimed to evaluate the feasibility of extended pedicled ALT flap. METHODS: This retrospective review was conducted at a single medical center between 2011 and 2018. A total of 35 patients with complex abdominal wall defects reconstructed with partition (n = 20) or pedicled ALT flap (n = 15) were enrolled. Data on gender, age, fascial defect size, operation time, hospital days, follow-up duration, and complications were obtained. Mann-Whitney test evaluated the differences in continuous data, and Chi-square test analyzed categorical data. RESULTS: The partition technique was associated with 10.15 cm (range 8-14 cm) mean defect size, 146 min average operation time, 13.5 hospital days, and 95.42 months of mean follow-up duration. Short- and long-term complications were observed in seven (35%) and six (30%) cases, respectively. The pedicled ALT flap technique was associated with 13.4 cm (range 10.6-16 cm), 342.86 min average operation time, 22.33 hospital days, and 69.4 months of mean follow-up duration. Short- and long-term complications were observed in six (40%) and five (33%) cases, respectively. Significant differences in defect size, operative time, hospital days, and donor-site skin graft loss (p < 0.05) were observed between the groups. CONCLUSIONS: Extended pedicled ALT flap is a reliable option for complex abdominal wall reconstruction. Compared with the partition technique group, the extended pedicled ALT group had closure of larger fascia defects. However, it was associated with a higher risk of donor-site skin graft loss and longer operative time and hospital days.

Common genetic variants in the chromogranin A promoter alter autonomic activity and blood pressure.

Chromogranin A (CHGA) is stored and released from the same secretory vesicles that contain catecholamines in chromaffin cells and noradrenergic neurons. We had previously identified common genetic variants at the CHGA locus in several human populations. Here we focus on whether inter-individual variants in the promoter region are of physiological significance. A common haplotype, CGATA (Hap-B), blunted the blood pressure response to cold stress and the effect exhibited molecular heterosis with the greatest blood pressure change found in Hap-A/Hap-B heterozygotes. Homozygosity for three minor alleles with peak effects within the haplotype predicted lower stress-induced blood pressure changes. The G-462A variant predicted resting blood pressure in the population with higher pressures occurring in heterozygotes (heterosis). Using cells transfected with CHGA promoter-luciferase reporter constructs, the Hap-B haplotype had decreased luciferase expression compared to the TTGTC (Hap-A) haplotype under both basal conditions and after activation by pre-ganglionic stimuli. The G-462A variant altered a COUP-TF transcriptional control motif. The two alleles in transfected promoters differed in basal activity and in the responses to COUP-II-TF transactivation and to retinoic acid. In vitro findings of molecular heterosis were also noted with the transfected CHGA promoter wherein the diploid combination of the two G-462A alleles gave rise to higher luciferase expression than either allele in isolation. Our results suggest that common genetic variants in the CHGA promoter may regulate heritable changes in blood pressure.

Physiological and morphological properties of, and effect of substance P on, neurons in the A7 catecholamine cell group in rats.

The A7 catecholamine cell group consists of noradrenergic (NAergic) neurons that project to the dorsal horn of the spinal cord. Here, we characterized their morphology and physiology properties and tested the effect of substance P (Sub-P) on them, since the results of many morphological studies suggest that A7 neurons are densely innervated by Sub-P-releasing terminals from nuclei involved in the descending inhibitory system, such as the lateral hypothalamus and periaqueductal gray area. Whole cell recordings were made from neurons located approximately 200 microm rostral to the trigeminal motor nucleus (the presumed A7 area) in sagittal brainstem slices from rats aged 7-10 days. After recording, the neurons were injected with biocytin and immunostained with antibody against dopamine-beta-hydroxylase (DBH). DBH-immunoreactive (ir) cells were presumed to be NAergic neurons. They had a large somata diameter ( approximately 20 microm) and relatively simple dendritic branching patterns. They fired action potentials (AP) spontaneously with or without blockade of synaptic inputs, and had similar properties to those of NAergic neurons in other areas, including the existence of calcium channel-mediated APs and a voltage-dependent delay in initiation of the AP (an indicator of the existence of A-type potassium currents) and an ability to be hyperpolarized by norepinephrine. Furthermore, in all DBH-ir neurons tested, Sub-P caused depolarization of the membrane potential and an increase in neuronal firing rate by acting on neurokinin-1 receptors. Non-DBH-ir neurons with a smaller somata size were also found in the A7 area. These showed great diversity in firing patterns and about half were depolarized by Sub-P. Morphological examination suggested that the non-DBH-ir neurons form contacts with DBH-ir neurons. These results provide the first description of the intrinsic regulation of membrane properties of, and the excitatory effect of Sub-P on, A7 area neurons, which play an important role in pain regulation.

Minimally modified low-density lipoprotein induces monocyte adhesion to endothelial connecting segment-1 by activating beta1 integrin.

We have shown previously that treatment of human aortic endothelial cells (HAECs) with minimally modified low-density lipoprotein (MM-LDL) induces monocyte but not neutrophil binding. This monocyte binding was not mediated by endothelial E-selectin, P-selectin, vascular cell adhesion molecule-I, or intercellular adhesion molecule-I, suggesting an alternative monocyte-specific adhesion molecule. We now show that moncytic alpha4beta1 integrins mediate binding to MM-LDL-treated endothelial cells. We present data suggesting that the expression of the connecting segment-1 (CS-1) domain of fibronectin (FN) is induced on the apical surface of HAEC by MM-LDL and is the endothelial alpha4beta1 ligand in MM-LDL-treated cells. Although the levels of CS-1 mRNA and protein were not increased, we show that MM-LDL treatment causes deposition of FN on the apical surface by activation of beta1integrins, particularly those associated with alpha5 integrins. Activation of beta1 by antibody 8A2 also induced CS-1-mediated monocyte binding. Confocal microscopy demonstrated the activated beta1 and CS-1colocalize in concentrated filamentous patches on the apical surface of HAEC. Both anti-CS-1 and an antibody to activated beta1 showed increased staining on the luminal endothelium of human coronary lesions with active monocyte entry. These results suggest the importance of these integrin ligand interactions in human atherosclerosis.

Pastoral power in HIV prevention: Converging rationalities of care in Christian and medical practices in Papua New Guinea.

In his conceptualisation of pastoral power, Michel Foucault argues that modern healthcare practices derive a specific power technique from pastors of the early Christian church. As experts in a position of authority, pastors practise the care of others through implicitly guiding them towards thoughts and actions that effect self-care, and towards a predefined realm of acceptable conduct, thus having a regulatory effect. This qualitative study of healthcare workers from two Christian faith-based organisations in Papua New Guinea examines the pastoral rationalities of HIV prevention practices which draw together globally circulated modern medical knowledge and Christian teachings in sexual morality for implicit social regulation. Community-based HIV awareness education, voluntary counselling and testing services, mobile outreach, and economic empowerment programs are standardised by promoting behavioural choice and individual responsibility for health. Through pastoral rationalities of care, healthcare practices become part of the social production of negative differences, and condemn those who become ill due to perceived immorality. This emphasis assumes that all individuals are equal in their ability to make behavioural choices, and downplays social inequality and structural drivers of HIV risk that are outside individual control. Given healthcare workers' recognition of the structural drivers of HIV, yet the lack of language and practical strategies to address these issues, political commitment is needed to enhance structural competency among HIV prevention programs and healthcare workers.

Crown group Oxyphotobacteria postdate the rise of oxygen.

The rise of oxygen ca. 2.3 billion years ago (Ga) is the most distinct environmental transition in Earth history. This event was enabled by the evolution of oxygenic photosynthesis in the ancestors of Cyanobacteria. However, long-standing questions concern the evolutionary timing of this metabolism, with conflicting answers spanning more than one billion years. Recently, knowledge of the Cyanobacteria phylum has expanded with the discovery of non-photosynthetic members, including a closely related sister group termed Melainabacteria, with the known oxygenic phototrophs restricted to a clade recently designated Oxyphotobacteria. By integrating genomic data from the Melainabacteria, cross-calibrated Bayesian relaxed molecular clock analyses show that crown group Oxyphotobacteria evolved ca. 2.0 billion years ago (Ga), well after the rise of atmospheric dioxygen. We further estimate the divergence between Oxyphotobacteria and Melainabacteria ca. 2.5-2.6 Ga, which-if oxygenic photosynthesis is an evolutionary synapomorphy of the Oxyphotobacteria-marks an upper limit for the origin of oxygenic photosynthesis. Together, these results are consistent with the hypothesis that oxygenic photosynthesis evolved relatively close in time to the rise of oxygen.

Acceleration of hepatobiliary excretion by lemon juice on 99mTc-tetrofosmin cardiac SPECT.

BACKGROUND: We sought to determine whether drinking lemon juice reduces extra-cardiac activity and improves image quality on (99m)Tc-tetrafosmin myocardial single photon emission computed tomography (SPECT). METHODS: Eighty male patients were enrolled in this study and divided into four groups with 20 patients in each group. Each patient received 259-333 MBq tetrofosmin. Ten minutes after injection no action was taken for group 1 (G1), patients in group 2 (G2) each drank 250 ml of water, patients in group 3 (G3) each drank 250 ml of whole milk, and patients in group 4 (G4) each drank 250 ml diluted lemon juice. Myocardial perfusion imaging without attenuation correction was performed after a 1 day rest-stress protocol. Both rest and stress images were aligned at corresponding slices for comparison. Interfering activity was determined visually on reconstructed images, and the heart-to-liver (H/L) ratios were calculated with planar images at 25-30 min and at 45-50 min. RESULTS: Interfering activity was seen in 80% of G1, 70% of G2, 60% of G3, and 35% of G4 (G4 vs. G1, P=0.006) on rest images, and in 70% of G1, 60% of G2, 55% of G3, and 30% of G4 (G4 vs. G1, P=0.014) on stress images at 25-30 min. It was also observed in 60% of G1, 50% of G2, 45% of G3, and 15% of G4 (G4 vs. G1, P=0.006) on rest images, and in 50% of G1, 45% of G2, 40% of G3, and 10% of G4 (G4 vs. G1, P=0.011) on stress images at 45-50 min. The mean H/L ratios of rest images were 0.47+/-0.13 for G1, 0.71+/-0.17 for G2, 0.65+/-0.12 for G3, and 0.93+/-0.23 for G4 at 25-30 min, and 0.63+/-0.14 for G1, 0.73+/-0.14 for G2, 0.85+/-0.25 for G3, and 1.15+/-0.25 for G4 at 45-50 min. On stress images, they were 0.49+/-0.11 for G1, 0.74+/-0.16 for G2, 0.69+/-0.11 for G3, and 0.98+/-0.22 for G4 at 25-30 min, and 0.66+/-0.15 for G1, 0.77+/-0.11 for G2, 0.89+/-0.26 for G3, and 1.21+/-0.19 for G4 at 45-50 min. CONCLUSION: Drinking 250 ml of diluted lemon juice accelerates the transit of tetrofosmin through the liver parenchyma and improves image quality on (99m)Tc-tetrafosmin myocardial SPECT.

Hydrophobicities of the nucleic acid bases: distribution coefficients from water to cyclohexane.

To establish an experimental scale of hydrophobicities for the nucleic acid bases, comparable with a scale developed earlier for amino acid side-chains, these bases and their parent compounds (purine and pyrimidin-2-one) were converted to n-butylated and tetrahydrofurylated derivatives that are appreciably soluble in cyclohexane, a truly non-polar solvent that dissolves negligible water at saturation. Distribution measurements between neutral aqueous solution and cyclohexane, at varying solute concentrations, showed no evidence of self-association of the solute in either solvent, and the possibility of specific entrainment of water by solutes entering cyclohexane was ruled out by the results of experiments with tritiated water. In both the n-butyl and tetrahydrofuryl series, the bases span a range of approximately 5.3 kcal mol-1 in their free energies of transfer from water to cyclohexane, and are arranged in the following rank, in order of decreasing hydrophobicity: purine>thymine>adenine>uracil>pyrimidin-2-one>hypoxanthine>/=cytosine >/=guanine. In both series of pyrimidin-2-ones, hydrophobicity decreases with introduction of an amino substituent, but addition of an exocyclic keto group results in a modest enhancement of hydrophobicity; and free energies of transfer are relatively insensitive to the position of N-alkyl substitution. In both series of purines, hydrophobicity decreases with the introduction of exocyclic amino and keto groups, the keto group having the greater effect; and free energies of transfer vary substantially depending on the position of N-alkyl substitution. Several additional compounds were examined to test recent predictions based on SM5.4/A, a quantum mechanical self-consistent-field solvation model; and that model was found to yield values in reasonable agreement with the experimental results.

Difficult abdominal wall closure: component separation versus partition technique.

BACKGROUND: Partition technique and component separation techniques are natural methods of fascia-fascia closure. We present our experiences and research the differences between the two techniques. METHODS: From January 2006 to August 2013, 41 patients with complex abdominal wall defects reconstructed with partition (N = 18) or component separation technique (N = 23) alone were enrolled into this study. The related data including gender, age, size of defect, operation time, hospital stay, duration of follow-up, comorbidities, body mass index (BMI) and complications were collected. Nonparametric Mann-Whitney test was used to evaluate the differences between the two groups in continuous data; Chi-square test was used to assess the categorical data. RESULTS: The mean defect size of patients with partition technique (N = 18) was 12.55 cm (range 8.2-18.9 cm) with 148.63 min for average operation time, 8.66 days for hospital stay, and 28.8 months for mean follow-up. There were nine cases with postoperative complications (three cases with skin and soft tissue necrosis; two cases with fascia dehiscence; and three cases with wound infection). One case with fascia dehiscence suffered from pneumonia simultaneously. Four cases received secondary operation (fascia repair and split-thickness skin graft), and the other four cases healed spontaneously with mild wound debridement. The mean defect size of the patients with component separation (N = 23) technique was 9.45 cm (range 5.7-12.6 cm) with 143.27 min for average operation time, 7.43 days for hospital stay, and 34.33 months for mean follow-up. One case with skin and soft tissue necrosis underwent reconstruction with split-thickness skin graft and debridement. Two cases with wound infection healed spontaneously with mild wound debridement. There were no significant differences in gender, age, operation time, hospital stay, duration of follow-up, comorbidities, BMI and long-term postoperative complications between the two groups, except for size of defect and short-term postoperative complications. CONCLUSIONS: The partition technique could close larger abdominal fascia defects than component separation technique, but simultaneously run the higher opportunities for short-term postoperative complications.

Design and structural analysis of an engineered thermostable chicken lysozyme.

A hyperstable (hs) variant of chicken egg-white lysozyme with enhanced thermal (delta Tm approximately +10.5 degrees C) and chemical (delta Cm for guanidine hydrochloride denaturation = +1.3 M) stabilities relative to wild-type (WT) was constructed by combining several individual stabilizing substitutions. The free energy difference between the native and denatured states of the hs variant is 3.1 (GdnHCl, 25 degrees C) to 4.0 (differential scanning calorimetry, 74 degrees C) kcal mol-1 greater than that of WT. The specific activity of the hs variant is 2.5-fold greater than that of WT. The choice of mutations came from diverse sources: (1) The I55L/S91T core construct with delta Tm = 3.3 degrees C from WT was available from the accompanying study (Shih P, Holland DR, Kirsch JF, 1995, Protein Sci 4:2050-2062). (2) The A31V mutation was suggested by the better atomic packing in the human lysozyme structure where the Ala 31 equivalent is Leu. (3) The H15L and R114H substitutions were selected on the basis of sequence comparisons with pheasant lysozymes that are more stable than the chicken enzyme. (4) The D101S variant was identified from a screen of mutants previously prepared in this laboratory. The effects of the individual mutations on stability are cumulative and nearly additive.