Unemployed individuals contact GPs more frequently but report lower satisfaction: results of the population-based DEGS1 and the GPCare-1 patient survey.

Unemployment is associated with a variety of adverse health-related outcomes, yet little data on primary care services for this risk group exist. Using data from two surveys, we analyzed the frequency of GP contacts and patients' experiences with GPs comparing unemployed with employed individuals. Data of the German Health Interview and Examination Survey for Adults (DEGS1), a nationwide cross-sectional study (n = 8151), were analyzed regarding associations between employment status and the number of GP visits. The General Practice Care-1 study (GPCare-1), a cross-sectional questionnaire survey (n = 813), evaluated patients' communication with their GP. Data were collected from June to August 2020 in 12 teaching practices affiliated with our university. The statistical analysis included individuals of working age (18-64 years old) (DEGS1 n = 5659, GPCare-1 n = 587). In both studies, working age subpopulations were analyzed (DEGS1: n = 5659 of 8151, GPCare-1: n = 587 of 813). In DEGS1, the prevalence of unemployment was 6.5% (n = 372). Unemployed individuals had more GP contacts in the last 12 months (4.50 vs. 2.86, p < 0.001). In the GPCare-1 study, unemployed individuals (6.6%, n = 39) were significantly less satisfied with GP communication: enough space in consultations (42.9% vs. 60.3%, p = 0.043), feeling comfortable to address sensitive topics (44.1% vs. 65.9%, p = 0.010), problems taken very seriously by GP (48.6% vs. 70.6%, p = 0.007). Yet, they were more willing to accept GPs' help for psychosocial burdens (67.6% vs. 47.6%, p = 0.024). GPs should be aware that patients with unemployment wish more support to cope with their burdening situation.

Association between habitual snoring, middle ear disease, and speech problems in young children with non-syndromic cleft palate anomalies.

The purpose of this study was to investigate the association between habitual snoring (HS), middle ear disease (MED), and speech problems in children with cleft palate. This cross-sectional study included children aged 2.0-7.9 years with non-syndromic cleft palate anomalies. Parents completed the Pediatric Sleep Questionnaire and a questionnaire about MED. Audiograms and speech assessment were also conducted. Ninety-five children were enrolled; 15.2% of families reported HS, 97.6% MED, and 17.1% speech problems. HS (37.5% vs 10.3%, P = 0.007) and early episodes of MED (92.3% vs 58.2%, P = 0.021) were more likely to be reported for children with isolated cleft palate when compared to those with cleft lip and palate. Children with cleft lip and palate had a higher frequency of MED with effusion compared to those with Robin sequence (86.4% vs 57.1%, P = 0.049). The odds ratio for HS in children with ≥1 episode of MED in the last year was 7.37 (95% confidence interval 1.55-35.15, P = 0.012). There was a trend for children with speech problems reported by parents to have HS (30.8% vs 11.5%, P= 0.076). Anatomical factors play a role in the frequency of upper airway symptoms in children with cleft palate. A recent history of at least one episode of MED was associated with an increased frequency of HS.

An inorganic geochemical argument for coupled anaerobic oxidation of methane and iron reduction in marine sediments.

Here, we present results from sediments collected in the Argentine Basin, a non-steady state depositional marine system characterized by abundant oxidized iron within methane-rich layers due to sediment reworking followed by rapid deposition. Our comprehensive inorganic data set shows that iron reduction in these sulfate and sulfide-depleted sediments is best explained by a microbially mediated process-implicating anaerobic oxidation of methane coupled to iron reduction (Fe-AOM) as the most likely major mechanism. Although important in many modern marine environments, iron-driven AOM may not consume similar amounts of methane compared with sulfate-dependent AOM. Nevertheless, it may have broad impact on the deep biosphere and dominate both iron and methane cycling in sulfate-lean marine settings. Fe-AOM might have been particularly relevant in the Archean ocean, >2.5 billion years ago, known for its production and accumulation of iron oxides (in iron formations) in a biosphere likely replete with methane but low in sulfate. Methane at that time was a critical greenhouse gas capable of sustaining a habitable climate under relatively low solar luminosity, and relationships to iron cycling may have impacted if not dominated methane loss from the biosphere.

Fiber hypertrophy and increased oxidative capacity can occur simultaneously in pig glycolytic skeletal muscle.

An inverse relationship between skeletal muscle fiber cross-sectional area (CSA) and oxidative capacity suggests that muscle fibers hypertrophy at the expense of oxidative capacity. Therefore, our objective was to utilize pigs possessing mutations associated with increased oxidative capacity [AMP-activated protein kinase (AMPKγ3(R200Q))] or fiber hypertrophy [ryanodine receptor 1 (RyR1(R615C))] to determine if these events occur in parallel. Longissimus muscle was collected from wild-type (control), AMPKγ3(R200Q), RyR1(R615C), and AMPKγ3(R200Q)-RyR1(R615C) pigs. Regardless of AMPK genotype, RyR(R615C) increased fiber CSA by 35%. In contrast, AMPKγ3(R200Q) pig muscle exhibited greater citrate synthase and ß-hydroxyacyl CoA dehydrogenase activity. Isolated mitochondria from AMPKγ3(R200Q) muscle had greater maximal, ADP-stimulated oxygen consumption rate. Additionally, AMPKγ3(R200Q) muscle contained more (∼50%) of the mitochondrial proteins succinate dehydrogenase and cytochrome c oxidase and more mitochondrial DNA. Surprisingly, RyR1(R615C) increased mitochondrial proteins and DNA, but this was not associated with improved oxidative capacity, suggesting that altered energy metabolism in RyR1(R615C) muscle influences mitochondrial proliferation and protein turnover. Thus pigs that possess both AMPKγ3(R200Q) and RyR(R615C) exhibit increased muscle fiber CSA as well as greater oxidative capacity. Together, our findings support the notion that hypertrophy and enhanced oxidative capacity can occur simultaneously in skeletal muscle and suggest that the signaling mechanisms controlling these events are independently regulated.

Use of dietary supplementation with ß-guanidinopropionic acid to alter the muscle phosphagen system, postmortem metabolism, and pork quality.

Rate and extent of postmortem metabolism control pork quality development. Our objective was to evaluate the role of the phosphagen system (phosphocreatine, PCr; and creatine, Cr) on metabolism and pork quality. Muscle PCr and Cr were manipulated by feeding pigs the creatine analogue, ß-guanidinopropionic acid (ß-GPA). In experiment 1, pigs received standard (control) diet or ß-GPA supplemented (2%) diet (1 wk or 2 wk). Supplementation with ß-GPA (2 wk) decreased total Cr (PCr+Cr; P=0.02) and improved pork color (decreased reflectance, P=0.003); however, ß-GPA supplementation reduced growth performance (P=0.007). To separate effects of phosphagen system and growth, a second experiment was conducted with control, pair-fed, and 2 wk ß-GPA (1%) supplementation; pigs were also offered a control or ß-GPA supplemented flavored beverage. Neither treatment influenced pork quality. Immediately postmortem, ATP/ADP was higher in control compared to pair-fed (P<0.05); subsequently, ATP/ADP was similar among all groups. Loss of the phosphagen system may lead to adaptive changes that promote conservation of cellular ATP.

Exploring the unknowns involved in the transformation of muscle to meat.

Meat quality development, or the transformation of muscle to meat, involves a myriad of biochemical pathways that are largely well-studied in living muscle tissue. However, these pathways are less predictable when homeostatic ranges are violated. In addition, there is far less known about how various management or environmental stimuli impact these pathways, either by substrate load or altered cellular environment. Likewise, it is largely accepted that oxygen plays little to no role in the conversion of muscle to meat, as anaerobic metabolism predominates in the muscle tissue. Even so, the oxygen tension within the tissues does not fall precipitously at exsanguination. Therefore, transition to an anaerobic environment may impact energy metabolism postmortem. Antemortem handling, on the other hand, clearly impacts meat quality development, yet the exact mechanisms remain a mystery. In this paper, we will attempt to review those factors known to affect postmortem energy metabolism in muscle and explore those areas where additional work may be fruitful.

High glycolytic potential does not predict low ultimate pH in pork.

Extent of postmortem pH decline influences meat quality development. To better understand physiological determination of ultimate pH (pHu), we utilized female and castrated male pigs from a line whose selection index includes differentiated pHu. All genotypes of AMP-activated protein kinase γ3 subunit (AMPKγ3) V199I site were present. The mutant 199II genotype increased pHu, but only in castrated males. Genotype affected glycolytic potential (GP), but GP was weakly associated with pHu. A subset of animals was selected based on low (-Gly) and high (+Gly) residual glycogen content, and compared with AMPKγ3 200Q, which is associated with low pHu. Both +Gly and 200Q muscle contained glycolytic substrate at 24h; however, 200Q muscle generated low pHu and greater lactate compared to +Gly. Additionally,-Gly and +Gly groups exhibited similar pHu despite a large difference in GP. In conclusion, high GP does not appear to directly impact the extent of postmortem pH decline.

Standardization of surgical procedures for identifying best practices and training.

A taxonomy was developed a) to describe surgical procedures with sufficient detail to review differences among surgeons, b) to examine the relationship between individual technique and outcomes, c) to enable surgeons to standardize technique around best practices and d) to identify clinical-evidence-based key points of teaching and assessment for surgical training. Sixty-seven microvascular anastomoses were recorded through video cameras mounted in the dissecting microscope. A hierarchical task analysis was used to decompose the observed procedures into successive levels of detail. The results were then presented to individual and small groups of microvascular surgeons to help define steps and step attributes necessary to describe a procedure so that other surgeons can perform the procedure exactly the same way. Coincidently, it was found that because the surgeons' attention is confined to a very small field of view in which they can see only the veins and arteries and the ends of their instruments, they often have difficulty communicating with others in the operating room. Analyses of selected cases using the proposed taxonomy shows how subtle details are revealed that may affect outcomes, and indicate specific training needs. By comparing different methods and outcomes, it should be possible to identify best practices for given conditions.

Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms.

The mammalian pyruvate dehydrogenase complex (PDC) plays central and strategic roles in the control of the use of glucose-linked substrates as sources of oxidative energy or as precursors in the biosynthesis of fatty acids. The activity of this mitochondrial complex is regulated by the continuous operation of competing pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) reactions. The resulting interconversion cycle determines the fraction of active (nonphosphorylated) pyruvate dehydrogenase (E1) component. Tissue-specific and metabolic state-specific control is achieved by the selective expression and distinct regulatory properties of at least four PDK isozymes and two PDP isozymes. The PDK isoforms are members of a family of serine kinases that are not structurally related to cytoplasmic Ser/Thr/Tyr kinases. The catalytic subunits of the PDP isoforms are Mg2+-dependent members of the phosphatase 2C family that has binuclear metal-binding sites within the active site. The dihydrolipoyl acetyltransferase (E2) and the dihydrolipoyl dehydrogenase-binding protein (E3BP) are multidomain proteins that form the oligomeric core of the complex. One or more of their three lipoyl domains (two in E2) selectively bind each PDK and PDP1. These adaptive interactions predominantly influence the catalytic efficiencies and effector control of these regulatory enzymes. When fatty acids are the preferred source of acetyl-CoA and NADH, feedback inactivation of PDC is accomplished by the activity of certain kinase isoforms being stimulated upon preferentially binding a lipoyl domain containing a reductively acetylated lipoyl group. PDC activity is increased in Ca2+-sensitive tissues by elevating PDP1 activity via the Ca2+-dependent binding of PDP1 to a lipoyl domain of E2. During starvation, the irrecoverable loss of glucose carbons is restricted by minimizing PDC activity due to high kinase activity that results from the overexpression of specific kinase isoforms. Overexpression of the same PDK isoforms deleteriously hinders glucose consumption in unregulated diabetes.

Positive influence of the Delta32CCR5 allele on response to highly active antiretroviral therapy (HAART) in HIV-1 infected patients.

The heterozygous 32 base pair deletion of the chemokine receptor 5 (Delta32CCR5) has been associated with a more benign course of HIV-1-infection. To study the influence of Delta32CCR5 on the response to antiviral therapy we analyzed the presence of Delta32CCR5 by PCR in PBMC from 107 randomly selected HIV-1-infected patients treated with HAART for at least three months. 24 of 107 patients were heterozygous for Delta32CCR5 (22.4%). Before initiation of HAART Delta32CCR5 heterozygous patients (d/w) did not differ from homozygous CCR5 wild-type patients (w/w) regarding viral load and CD4 counts. After a median treatment time on HAART of 17.5 months (d/w, range 6-31 months, p = n.s.) or 19 months (w/w, range 3-33 months) all 24 patients (100%) with the Delta32CCR5 mutation, but only 58/83 patients (69.9%) with wild-type CCR5 showed a suppression of HIV-1-viremia below 500 copies/ml (p = 0.0020). Furthermore, 20/24 (83.3%) of the Delta32CCR5 heterozygous patients achieved CD4 counts above 200/microliter, but only 57/83 (68.7%) of the patients homozygous for CCR5 wild-type (p = 0.011). Our data indicate that the presence of heterozygous Delta32CCR5 is associated with a better response to HAART suggesting that therapeutic strategies targeting CCR5 could be of value for a sustained suppression of HIV-1 by HAART.

Marked differences between two isoforms of human pyruvate dehydrogenase kinase.

Pyruvate dehydrogenase kinase (PDK) isoforms 2 and 3 were produced via co-expression with the chaperonins GroEL and GroES and purified with high specific activities in affinity tag-free forms. By using human components, we have evaluated how binding to the lipoyl domains of the dihydrolipoyl acetyltransferase (E2) produces the predominant changes in the rates of phosphorylation of the pyruvate dehydrogenase (E1) component by PDK2 and PDK3. E2 assembles as a 60-mer via its C-terminal domain and has mobile connections to an E1-binding domain and then two lipoyl domains, L2 and L1 at the N terminus. PDK3 was activated 17-fold by E2; the majority of this activation was facilitated by the free L2 domain (half-maximal activation at 3.3 microm L2). The direct activation of PDK3 by the L2 domain resulted in a 12.8-fold increase in k(cat) along with about a 2-fold decrease in the K(m) of PDK3 for E1. PDK3 was poorly inhibited by pyruvate or dichloroacetate (DCA). PDK3 activity was stimulated upon reductive acetylation of L1 and L2 when full activation of PDK3 by E2 was avoided (e.g. using free lipoyl domains or ADP-inhibited E2-activated PDK3). In marked contrast, PDK2 was not responsive to free lipoyl domains, but the E2-60-mer enhanced PDK2 activity by 10-fold. E2 activation of PDK2 resulted in a greatly enhanced sensitivity to inhibition by pyruvate or DCA; pyruvate was effective at significantly lower levels than DCA. E2-activated PDK2 activity was stimulated >/=3-fold by reductive acetylation of E2; stimulated PDK2 retained high sensitivity to inhibition by ADP and DCA. Thus, PDK3 is directly activated by the L2 domain, and fully activated PDK3 is relatively insensitive to feed-forward (pyruvate) and feed-back (acetylating) effectors. PDK2 was activated only by assembled E2, and this activated state beget high responsiveness to those effectors.

A retrospective analysis of revision sphincter pharyngoplasty.

This retrospective study was undertaken to determine the revision rate for dynamic sphincter pharyngoplasty (DSP) at the University of Michigan Medical Center to analyze the determinants contributing to the need for revision pharyngoplasties, and ultimately to improve primary pharyngoplasty to avoid the need for revision. The records of 30 children with repaired palatal clefts who presented with velopharyngeal insufficiency and hypernasal speech, and who underwent DSP from January 1988 through July 1994 were reviewed. Clinical follow-up ranged from 6 to 48 months (mean, 20.2 months). Seven of the original 30 patients (23%) had persistent, moderate-to-severe hypernasality that required reoperation, while 1 patient (3%) demonstrated hyponasality requiring revision. Seven of 8 patients who underwent revision pharyngoplasty had acceptable speech after revision. Dehiscences, low-lying pharyngoplasty flaps, and end-to-end suturing of the flaps were the main determinants resulting in the need for revision. In our study, female gender and older age was associated with a higher success of primary operation.

Carpal tunnel syndrome: a case of median nerve injection injury and a safe and effective method for injecting the carpal tunnel.

The carpal tunnel syndrome is a compressive neuropathy of the median nerve at the wrist. The local injection of corticosteroid is an effective treatment modality in properly selected cases; however, this usually efficacious and safe procedure may result in serious complications if insufficient attention is paid to technique. A recent case of severe median nerve injury secondary to local steroid injection at the wrist prompted this report. We present a safe and effective method for injection of the carpal tunnel syndrome.

Industrial lead contamination of an Illinois wildlife refuge and indigenous small mammals.

Deer mice (Peromyscus maniculatus) were trapped from a sand prairie at various distances from an adjacent battery lead reclamation plant. Analysis of liver, kidney, and bone for lead concentrations showed an increase of tissue lead concentrations over controls to a distance of approximately 400 m. Soil and plant lead concentrations roughly correlated with the findings in deer mouse tissues. At higher tissue lead concentrations, acid-fast staining intranuclear inclusions within renal tubular epithelial cells were an occasional finding.