Spigelian hernia: a multi-site review of operative outcomes of surgical repair in the adult population.

PURPOSE: Spigelian hernias arise at the linear semilunaris and account for approximately 1-2% of abdominal hernias. The aetiology is due to a defect of the aponeurosis of the transverse abdominis and when discovered, management is surgical intervention. The aim of this study was to observe operative outcomes for open and minimally invasive repair. METHODS: A retrospective chart review was conducted at two hospitals in Townsville, The Townsville University Hospital and The Mater Private Hospital over a 10-year period (2010 to 2020). A surgical database search (ORMIS & IEMR) was performed at both locations using key search terms, including "spigelian hernia", "laparoscopic", "open". Descriptive statistics were utilised to analyse patient factors and operative outcomes in the public and private setting. RESULTS: 43 cases of Spigelian hernias (25 female, 18 male) were reported over the study period. The average age was 66. There were 36 elective cases and 7 emergency cases. A laparoscopic approach was the preferred method of repair, occurring in 74% of cases. Of these cases, the predominant hernial content was fat only. 65% of cases had a history of prior abdominal surgery unrelated to the "Spigelian belt" location. Complications occurred in 19% of cases. Other variables, such as ethnicity, smoking status, defect size, predisposing factors and recurrence rate, were analysed and did not yield statistical significance. CONCLUSION: Although a small sample size, the data suggest there is no statistically significant difference between operative outcomes, complication rate and predisposing factors between open and minimally invasive case groups.

Diagnoses associated with the greatest years of potential life lost for in-hospital deaths in the United States, 1988-2010.

OBJECTIVE: Premature mortality is a public health concern that can be quantified as years of potential life lost (YPLL). Studying premature mortality from in-hospital mortality can help guide hospital initiatives and resource allocation. This paper identified the diagnosis categories associated with in-hospital deaths that account for the highest YPLL and their trends over time. STUDY DESIGN: Retrospective review of the Nationwide Inpatient Sample (NIS), 1988-2010. METHODS: Using the NIS, YPLL on patients hospitalized in the United States from 1988 to 2010 was calculated. Hospitalizations were categorized by related principal diagnoses using the Healthcare Cost and Utilization Project (HCUP) single-level Clinical Classification Software (CCS) definitions. RESULTS: Between 1988 and 2010, total in-hospital estimated mortality of 20,154,186 people accounted for 198,417,257 YPLL (9.84 YPLL per in-hospital mortality; 8,626,837 estimated annual mean YPLL). The ten highest YPLL diagnosis categories accounted for 51% of the overall YPLL. The liveborn disease category (i.e., in-hospital live births) was the most common principal diagnosis and accounted for the highest YPLL at 1,070,053. The septicemia category accounted for the second highest YPLL at 548,922. The highest in-hospital mortality rate (20.8%) was associated with adult respiratory failure/insufficiency/arrest. The highest estimated in-hospital annual mean deaths occurred in patients with pneumonia at 69,134. For all in-hospital mortality, the inflation adjusted total in-hospital charges per YPLL was highest for acute myocardial infarction at $9292 per YPLL. CONCLUSIONS: Using YPLL, a framework has been provided to compare the impact of premature in-hospital mortality from dissimilar diseases. The methodology and results may be used to help guide further investigation of hospital quality initiatives and resource allocation.

Distribution of NBCn2 (SLC4A10) splice variants in mouse brain.

The five known Na-coupled HCO(3)(-) transporters (NCBTs) of the solute carrier 4 (SLC4) family play important roles in pH regulation and transepithelial HCO(3)(-) transport. Nearly all of the NCBTs have multiple splice variants. One particular NCBT, the electroneutral Na/HCO(3)(-) cotransporter NBCn2 (SLC4A10), which is predominantly expressed in brain, has three known splice variants-NBCn2-A, -B, and -C-as well as a potential variant-D. It is important to know the tissue-specific expression of the splice variants for understanding the physiological roles of NBCn2 in central nervous system. In the present study, we developed three novel rabbit polyclonal antibodies against NBCn2: (1) anti-ABCD, which recognizes all four variants; (2) anti-BD, which recognizes NBCn2-B and -D; (3) anti-CD, which recognizes NBCn2-C and -D. By western blotting, we examined the expression and distribution of NBCn2 splice variants in five brain regions: cerebral cortex, subcortex, cerebellum, hippocampus, and medulla. The expression pattern revealed with anti-ABCD is distinct from those revealed with anti-BD and anti-CD. Moreover, by using immunoprecipitation in combination with western blotting, we demonstrate that NBCn2-D does indeed exist and that it is predominantly expressed in subcortex, to a lesser extent in medulla, but at very low levels in cortex, cerebellum, and hippocampus. NBCn2-A may be the dominant variant in mouse brain as a whole, and may also dominate in cerebral cortex, cerebellum, and hippocampus. Immunohistochemistry with anti-ABCD shows that NBCn2 is highly expressed in choroid plexus, cortex, molecular layer of cerebellum, hippocampus, and some specific regions of the brainstem.

A missense mutation in the non-neural G-protein alpha-subunit isoforms modulates susceptibility to obesity.

OBJECTIVE: The Gnas transcription unit located within an imprinting region encodes several proteins, including the G-protein alpha-subunit, Gsalpha, its isoform XLalphas and their variant truncated neural forms GsalphaN1 and XLN1. Gsalpha and GsalphaN1 are expressed predominantly from the maternally derived allele in some tissues, whereas XLalphas and XLN1 are expressed exclusively from the paternally derived allele. The relative contribution of full-length Gsalpha and XLalphas, and truncated forms GsalphaN1 and XLN1 to phenotype is unknown. The edematous-small point mutation (Oed-Sml) in exon 6 of Gnas lies downstream of GsalphaN1 and XLN1, but affects full-length Gsalpha and XLalphas, allowing us to address the role of full-length Gsalpha and XLalphas. The aim of this study was therefore to determine the metabolic phenotypes of Oed and Sml mice, and to correlate phenotypes with affected transcripts. METHODS: Mice were fed standard or high-fat diets and weighed regularly. Fat mass was determined by DEXA analysis. Indirect calorimetry was used to measure metabolic rate. Glucose was measured in tolerance tests and biochemical parameters in fasted plasma samples. Histological analysis of fat and liver was carried out post mortem. RESULTS: Oed mice are obese on either diet and have a reduced metabolic rate. Sml mice are lean and are resistant to a high-fat diet and have an increased metabolic rate. CONCLUSION: Adult Oed and Sml mice have opposite metabolic phenotypes. On maternal inheritance, the obese Oed phenotype can be attributed to non-functional full-length Gsalpha. In contrast, on paternal inheritance, Sml mice were small and resistant to the development of obesity on a high-fat diet, effects that can be attributed to mutant XLalphas. Thus, the neural isoforms, GsalphaN1 and XLN1, do not appear to play a role in these metabolic phenotypes.

Expression and localization of Na-driven Cl-HCO(3)(-) exchanger (SLC4A8) in rodent CNS.

The Na(+)-driven Cl-HCO(3) exchanger (NDCBE or SLC4A8) is a member of the solute carrier 4 (SLC4) family of HCO(3)(-) transporters, which includes products of 10 genes with similar sequences. Most SLC4 members play important roles in regulating intracellular pH (pH(i)). Physiological studies suggest that NDCBE is a major pH(i) regulator in at least hippocampal (HC) pyramidal neurons. We generated a polyclonal rabbit antibody directed against the first 18 residues of the cytoplasmic N terminus (Nt) of human NDCBE. By Western blotting, the antibody distinguishes NDCBE-as a purified Nt peptide or a full-length transporter (expressed in Xenopus oocytes)-from other Na(+)-coupled HCO(3)(-) transporters. By Western blotting, the antiserum recognizes an approximately 135-kDa band in several brain regions of adult mice: the cerebral cortex (CX), subcortex (SCX), cerebellum (CB), and HC. In CX, PNGase F treatment reduces the molecular weight to approximately 116 kDa. By immunocytochemistry, affinity-purified (AP) NDCBE antibody stains the plasma membrane of neuron cell bodies and processes of rat HC neurons in primary culture as well as freshly dissociated mouse HC neurons. The AP antibody does not detect substantial NDCBE levels in freshly dissociated HC astrocytes, or astrocytes in HC or CB sections. By immunohistochemistry, the AP antibody recognizes high levels of NDCBE in neurons of CX, HC (including pyramidal neurons in Cornu Ammonis (CA)1-3 and dentate gyrus), substantial nigra, medulla, cerebellum (especially Purkinje and granular cells), and the basolateral membrane of fetal choroid plexus. Thus, NDCBE is in a position to contribute substantially to pH(i) regulation in multiple CNS neurons.

Use of a new polyclonal antibody to study the distribution and glycosylation of the sodium-coupled bicarbonate transporter NCBE in rodent brain.

NCBE (SLC4A10) is a member of the SLC4 family of bicarbonate transporters, several of which play important roles in intracellular-pH regulation and transepithelial HCO(3)(-) transport. Here we characterize a new antibody that was generated in rabbit against a fusion protein consisting of maltose-binding protein and the first 135 amino acids (aa) of the N-terminus of human NCBE. Western blotting--both of purified peptides representing the initial approximately 120 aa of the transporters and of full-length transporters expressed in Xenopus oocytes--demonstrated that the antibody is specific for NCBE versus the two most closely related proteins, NDCBE (SLC4A8) and NBCn1 (SLC4A7). Western blotting of tissue in four regions of adult mouse brain indicates that NCBE is expressed most abundantly in cerebral cortex (CX), cerebellum (CB) and hippocampus (HC), and less so in subcortex (SCX). NCBE protein was present in CX, CB, and HC microdissected to avoid choroid plexus. Immunocytochemistry shows that NCBE is present at the basolateral membrane of embryonic day 18 (E18) fetal and adult choroid plexus. NCBE protein is present by Western blot and immunocytochemistry in cultured and freshly dissociated HC neurons but not astrocytes. By Western blot, nearly all NCBE in mouse and rat brain is highly N-glycosylated (approximately 150 kDa). PNGase F reduces the molecular weight (MW) of natural NCBE in mouse brain or human NCBE expressed in oocytes to approximately the predicted MW of the unglycosylated protein. In oocytes, mutating any one of the three consensus N-glycosylation sites reduces glycosylation of the other two, and the triple mutant exhibits negligible functional expression.

Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets.

Acute inhibition of serotonergic (5-HT) neurons in the medullary raphé (MR) using a 5-HT(1A) receptor agonist had an age-dependent impact on the "CO(2) response" of piglets (33). Our present study explored the effect of chronic 5-HT neuron lesions in the MR and extra-raphé on the ventilatory response to hypercapnia and hypoxia in piglets, with possible implications on the role of 5-HT in the sudden infant death syndrome. We established four experimental groups. Group 1 (n = 11) did not undergo any treatment. Groups 2, 3, and 4 were injected with either vehicle or the neurotoxin 5,7-dihydroxytryptamine in the cisterna magna during the first week of life (group 2, n = 9; group 4, n = 11) or second week of life (group 3, n = 10). Ventilation was recorded in response to 5% CO(2) (all groups) and 12% O(2) (group 2) during wakefulness and sleep up to postnatal day 25. Surprisingly, the piglets did not reveal changes in their CO(2) sensitivity during early postnatal development. Overall, considerable lesions of 5-HT neurons (up to 65% decrease) in the MR and extra-raphé had no impact on the CO(2) response, regardless of injection time. Postlesion raphé plasticity could explain why we observed no effect. 5,7-Dihydroxytryptamine-treated males, however, did present a lower CO(2) response during sleep. Hypoxia significantly altered the frequency during sleep in lesioned piglets. Further studies are necessary to elucidate the role of plasticity, sex, and 5-HT abnormalities in sudden infant death syndrome.

Parallel evolution of the sexes? Effects of predation and habitat features on the size and shape of wild guppies.

Environmental gradients often lead to the parallel evolution of populations and species. To what extent do such gradients also lead to parallel evolution of the sexes? We used guppies (Poecilia reticulata) to examine the parallel and independent (sex-specific) aspects of population divergence in response to predation and habitat features. Geometric morphometrics was used to analyse size and shape variation for 1335 guppies from 27 to 31 sites sampled in each of 2 years. Body size showed strong parallel population divergence; both sexes were larger at sites with a more open canopy and with higher flow. Body shape showed a mixture of parallel and independent population divergence. The strongest and most consistent effects were (1) high-predation sites had males with smaller heads and deeper caudal peduncles, (2) open-canopy sites had females with smaller heads and more distended abdomens and (3) high-flow sites had males and females with smaller heads and deeper caudal peduncles.

A parvo-like virus in cultured redclaw crayfish Cherax quadricarinatus from Queensland, Australia.

In the summer of 1999/2000, an epizootic occurred in cultured juvenile redclaw crayfish Cherax quadricarinatus on one commercial crayfish farm in northern Queensland, Australia. Mortalities occurred over 4 wk, with up to 96% cumulative mortalities in 2 earthen ponds stocked with juveniles. The crayfish were weak, anorexic and lethargic. A transmission trial was conducted, using filtered, cell-free extract prepared from infected crayfish as inoculum. The disease was reproduced, with on-going mortalities occurring in inoculated crayfish over 55 d. Experimentally inoculated crayfish showed gross signs of malaise, anorexia and disorientation before dying. Two types of intranuclear inclusion bodies (INIBs) were seen in tissues of endodermal, ectodermal and mesodermal origin by light microscopy with haematoxylin and eosin (H&E) stained sections. 'Early'-stage INIBs were eosinophilic, rounded and located centrally within slightly enlarged nuclei while 'late'-stage INIBs were well-rounded and deeply basophilic. The gills, cuticular epithelium and epithelial cells of the foregut, midgut and hindgut were the most heavily infected tissues. By transmission electron microscopy, virions with an average diameter of 19.5 nm were seen within electron-dense granular inclusion bodies within enlarged nuclei of both naturally and experimentally infected crayfish. The size of the virions and cytopathology are consistent with characteristics of viruses in the Family Parvoviridae. This is the first reported case of mass mortality caused by a parvo-like virus infection in C. quadricarinatus.

Short communication: concentration of conjugated linoleic acid from milk fat with a continuous supercritical fluid processing system.

A continuous pilot-scale supercritical carbon dioxide system was utilized for the concentration of conjugated linoleic acids (cis-9, trans-11 C18:2) from anhydrous milk fat, which was separated into five fractions (S1 to S5) in the pressure and temperature range of 2.4 to 24.1 MPa (350 to 3500 psi) and 40 to 60 degrees C, respectively. The highest concentration of CLA attained showed an increase of about 89% and occurred in the raffinate fraction (S1) when the solvent to feed ratio was 65. This was followed by a gradual decrease in the concentration of this fatty acid from S2 to S5. This study shows the feasibility of selectively enhancing the CLA concentration in one of the fractions of milk fat with a benign solvent in a one-step process. Other unique attributes of the CLA-rich fraction are also listed.

Tablet and capsule hydrophilic matrices based on heterodisperse polysaccharides having porosity-independent in vitro release profiles.

The purpose of the study was to investigate the release-controlling action of a swellable hydrophilic material based on heterodisperse polysaccharides (HP) in relation to the initial pore structure of the formulations. HP-based granules were produced under carefully controlled conditions and compacted into matrix tablets having equivalent tablet thickness. Quantification of pore structure using mercury porosimetry showed that the tablets had substantially different pore volumes and pore size distributions. Dissolution studies demonstrated that release of a water-soluble model compound, benzamide, from swollen matrices was affected neither by total porosity nor median pore diameter of the initial dry matrix. To extend the concept of porosity-independent release further, HP-based formulations containing either diclofenac sodium or propranolol HCl were contained within hard gelatin capsules in the form of uncompacted granules. This produced a dosage form with a high intraparticulate porosity in the dry state. Equivalent weights of the same formulations were also compacted into tablets. The in vitro release profiles from matrix tablets compacted from any of the formulations did not differ significantly from release profiles obtained when the same materials were contained uncompacted in hard gelatin capsules.

Effect of cytoplasmic tail truncations on the activity of the M(2) ion channel of influenza A virus.

The M(2) protein of influenza A virus forms a proton channel that is required for viral replication. The M(2) ion channel is a homotetramer and has a 24-residue N-terminal extracellular domain, a 19-residue transmembrane domain, and a 54-residue cytoplasmic tail. We show here that the N-terminal methionine residue is cleaved from the mature protein. Translational stop codons were introduced into the M(2) cDNA at residues 46, 52, 62, 72, 77, 82, 87, and 92. The deletion mutants were designated truncx, according to the amino acid position that was changed to a stop codon. We studied the role of the cytoplasmic tail by measuring the ion channel activity (the current sensitive to the M(2)-specific inhibitor amantadine) of the cytoplasmic tail truncation mutants expressed in oocytes of Xenopus laevis. When their conductance was measured over time, mutants trunc72, trunc77, and trunc92 behaved comparably to wild-type M(2) protein (a decrease of only 4% over 30 min). In contrast, conductance decreased by 28% for trunc82, 27% for trunc62, and 81% for trunc52 channels. Complete closure of the channel could be observed in some cells for trunc62 and trunc52 within 30 min. These data suggest that a role of the cytoplasmic tail region of the M(2) ion channel is to stabilize the pore against premature closure while the ectodomain is exposed to low pH.

Processing of palindromes in neglect dyslexia.

We report an investigation into the processing of symmetrical lexical stimuli by a patient with moderate visual neglect. This subject's neglect dyslexia was significantly less pronounced when presented with symmetrical lexical stimuli (palindromes) than with matched non-symmetrical words. We discuss the hypothesis that symmetry facilitates processing.

Effect of intake of pasture on concentrations of conjugated linoleic acid in milk of lactating cows.

We examined the effect of intake of fresh pasture on concentrations of conjugated linoleic acid in milk fat. Sixteen Holstein cows were paired and divided into either the control group or the grazing group. The study involved initial, transition, and final periods. During the initial period, all cows consumed a total mixed diet. Cows in the control group were fed the total mixed diet throughout the study, and cows in the grazing group were gradually adjusted to a diet consisting of intensively managed pasture. Performance of cows in the grazing group was significantly reduced from that of cows in the control group during the final period (dry matter intake, 19% less; milk yield, 29.6 vs. 44.1 kg/d; and live weight, 40 kg less). During the initial period, when both groups were consuming a total mixed diet, concentrations of conjugated linoleic acid in milk fat were similar (X = 5.1 mg/g of milk fat). As the grazing group was gradually adjusted to pasture, concentrations of conjugated linoleic acid in milk gradually increased. During the final period, when cows in the grazing group were consuming a diet consisting of pasture only, conjugated linoleic acid concentrations in the milk fat were doubled (10.9 vs. 4.6 mg/g of milk fat). Furthermore, results showed the individual consistency of the milk fat content of conjugated linoleic acid over time but also demonstrated substantial variation among individual cows within treatment groups. Overall, this study indicated that the concentration of conjugated linoleic acid in milk fat is enhanced by dietary intake of fresh pasture.

Granulocyte-macrophage colony-stimulating factor rescues TF-1 leukemia cells from ionizing radiation-induced apoptosis through a pathway mediated by protein kinase Calpha.

Protein kinase C (PKC) activity has a recognized role in mediating apoptosis. However, the role of individual PKC isoforms in apoptosis is poorly defined. Therefore, we investigated the translocation of individual PKC isoforms during radiation-induced apoptosis with and without rescue from apoptosis by granulocyte-macrophage colony-stimulating factor (GM-CSF) in the human erythroleukemia cell line TF-1. PKCalpha was translocated from the particulate to cytosolic fraction of TF-1 cells within 5 minutes of treatment with apoptosis-inducing levels of ionizing radiation. However, this postirradiation translocation did not occur when cells were rescued from apoptosis by GM-CSF. Furthermore, treatment of cells with Gö 6976, an inhibitor of classical PKC isoforms, abrogated the rescue effect of GM-CSF. The calcium-independent novel PKC isoform, PKCalpha appeared to be degraded in both the particulate and cytosolic fractions of TF-1 cells after treatment with apoptosis-inducing levels of ionizing radiation in either the presence or absence of GM-CSF rescue. Levels of ceramide, a lipid mediator of apoptosis, were measured at 2, 4, 8, 10, and 60 minutes after treatment with ionizing radiation and were substantially reduced in TF-1 cells rescued from apoptosis by GM-CSF compared with apoptotic TF-1 cells. The largest decrease in ceramide production seen was at 4 minutes postirradiation, with a 46% reduction in ceramide levels in TF-1 cells rescued from apoptosis by GM-CSF compared with those in apoptotic TF-1 cells. Because ceramide has been shown to affect PKCalpha subcellular distribution, these data implicate a role for ceramide in mediating the rapid postirradiation translocation and inhibition of PKCalpha in TF-1 cells not rescued from apoptosis by GM-CSF. Expression of the antiapoptotic protein Bcl-2 doubled in TF-1 cells rescued from apoptosis by GM-CSF, but did not increase in unrescued cells. Our findings suggest that activated PKCalpha and increased expression of Bcl-2 after gamma irradiation determine survival in TF-1 cells rescued from apoptosis with GM-CSF and that PKCalpha plays a role in mediating signals involved in sensing cellular damage and/or regulation of cell damage repair.

Dietary fatty acid sources affect conjugated linoleic acid concentrations in milk from lactating dairy cows.

Conjugated linoleic acid (CLA), a naturally occurring anticarcinogen found in dairy products, is an intermediary product of ruminal biohydrogenation of polyunsaturated fatty acids. Our objective was to determine the effect of different dietary oils, which vary in fatty acid composition, on CLA concentrations in milk from lactating dairy cows. Twelve Holstein cows were randomly assigned to a 3 x 3 Latin square design. Dietary treatments were the addition (53 g/kg dietary dry matter) of peanut oil (high oleic acid), sunflower oil (high linoleic acid) and linseed oil (high linolenic acid). Each treatment period was 2 wk, and milk samples were collected on the last 4 d of each period. Milk yield (34.2 +/- 1.3 kg/d) and milk fat (2.25 +/- 0.06%) were not different among treatments. Milk protein during the sunflower oil treatment (mean, 3.44% protein) was significantly higher (P < 0.01) than during the other treatments. Milk fat concentration of CLA during the sunflower oil treatment was significantly different from other treatments (P < 0.001) and approximately 500% greater than typically observed when cows consume traditional diets. CLA concentrations (mg/g of milk fat) were 13.3, 24.4 and 16.7 during peanut oil, sunflower oil and linseed oil treatment, respectively. CLA concentration in milk fat can be enhanced by the addition of polyunsaturated fatty acids to the diet, especially oils high in linoleic acid.

The Adolescent Behavior Checklist: development and initial psychometric properties of a self-report measure for adolescents with ADHD.

Developed and provided initial psychometric properties on an adolescent, self-report questionnaire for attention deficit hyperactivity disorder (ADHD). The Adolescent Behavior Checklist (ABC) consists of 44 items that measure ADHD core symptoms and associated difficulties (e.g., conduct problems, academic problems, and social deficits). A total of 909 adolescents between the ages of 11 and 17 served as the standardization sample. Results indicated that the ABC was internally consistent. Principal components analysis revealed six factors for the ABC: Conduct Problems, Impulsivity/Hyperactivity, Poor Work Habits, Inattention, Emotional Lability, and Social Problems. Significant gender and race differences were obtained for some ABC factor scores, and initial standardization data were established based on this information. Initial convergent and divergent validity of the ABC was supported by the correlations obtained between factor scores and the subscale scores on the Child Behavior Checklist and Youth Self-Report. Using an additional sample of 81 adolescents, the stability of ABC scores across a 2-week interval was found to be satisfactory. Initial evidence for discriminant validity was established by comparing ABC scores for a sample of adolescents diagnosed with ADHD to the normative sample.

Ion channels from synaptic vesicle membrane fragments reconstituted into lipid bilayers.

Cholinergic synaptic vesicles were isolated from the electric organ of Torpedo californica. Vesicle membrane proteins were reconstituted into planar lipid bilayers by the nystatin/ergosterol fusion technique. After fusion, a variety of ion channels were observed. Here we identify four channels and describe two of them in detail. The two channels share a conductance of 13 pS. The first is anion selective and strongly voltage dependent, with a 50% open probability at membrane potentials of -15 mV. The second channel is slightly cation selective and voltage independent. It has a high open probability and a subconductance state. A third channel has a conductance of 4-7 pS, similar to the subconductance state of the second channel. This channel is fairly nonselective and has gating kinetics different from those of the cation channel. Finally, an approximately 10-pS, slightly cation selective channel was also observed. The data indicate that there are one or two copies of each of the above channels in every synaptic vesicle, for a total of six channels per vesicle. These observations confirm the existence of ion channels in synaptic vesicle membranes. It is hypothesized that these channels are involved in vesicle recycling and filling.