Is chest X-ray screening for lung cancer in smokers cost-effective? Evidence from a population-based study in Italy.
After implementation of the PREDICA annual chest X-ray (CXR) screening program in smokers in the general practice setting of Varese-Italy a significant reduction in lung cancer-specific mortality (18 %) was observed. The objective of this study covering July 1997 through December 2006 was to estimate the cost-effectiveness of this intervention. We examined detailed information on lung cancer (LC) cases that occurred among smokers invited to be screened in the PREDICA study (Invitation-to-screening Group, n = 5815 subjects) to estimate costs and quality-adjusted life-years (QALYs) from LC diagnosis until death. The control group consisted of 156 screening-eligible smokers from the same area, uninvited and unscreened, who developed LC and were treated by usual care. We calculated the incremental net monetary benefit (INMB) by comparing LC management in screening participants (n = 1244 subjects) and in the Invitation-to-screening group versus control group. The average number of QALYs since LC diagnosis was 1.7, 1.49 and 1.07, respectively, in screening participants, the invitation-to-screening group, and the control group. The average total cost (screening + management) per LC case was higher in screening participants (€17,516) and the Invitation-to-screening Group (€16,167) than in the control group (€15,503). Assuming a maximum willingness to pay of €30,000/QALY, we found that the intervention was cost-effective with high probability: 79 % for screening participation (screening participants vs. control group) and 95 % for invitation-to-screening (invitation-to-screening group vs. control group). Based on the PREDICA study, annual CXR screening of high-risk smokers in a general practice setting has high probability of being cost-effective with a maximum willingness to pay of €30,000/QALY.


Kinetics of enzyme-coenzyme interactions by NMR spectroscopy.
The kinetics for the binding of coenzymes to H4 and M4 lactate dehydrogenase from chicken were investigated by nuclear magnetic resonance spectroscopy. With detailed computer analysis, some kinetic parameters were extracted from the chemical shifts and the linewidth of the observed coenzyme resonances at various enzyme/coenzyme ratios and temperatures. The results of the analysis indicated that the dissociation rates of coenzymes from the enzyme/coenzyme complexes are slower with the H4 isozyme than those involving the M4 isozyme. The lifetimes for the NAD+-enzyme complexes are on the order of 1 msec while those for the NADH-enzyme complexes are on the order of 10 ms (at room temperature). Much shorter transverse relaxation times of the coenzyme resonances were observed in NADH-enzyme complexes than those in the NAD+-enzyme complexes. The calculated kinetic constants are in good agreement with the previous studies by stopped-flow and temperature jump methods. A generalized NMR kinetic treatment for the binding of small molecules to a macromolecule is presented.


Functional maturation of left and right atrial systolic and diastolic performance in infants, children, and adolescents.
Left atrial (LA) function is an important modulator of left ventricular filling and has a prognostic role in adult heart failure, but pediatric data are limited. The aim of this study was to characterize the normal LA and right atrial (RA) strain (ε) and strain rate (SR) in infants and children. Atrial ε and SR were prospectively investigated in 153 subjects using two-dimensional speckle-tracking echocardiography. High-frame rate, three-beat captures of LA (15-segment model; two-chamber, three-chamber, and four-chamber views) and RA (six-segment model; four-chamber view) were analyzed (Vivid 7, EchoPAC BT11). LA and RA segmental and global peak positive ε (εPos) and negative ε (εNeg) and peak positive SR, early negative SR, and late negative SR were measured. Linear and nonlinear regressions of ε and SR were performed with age and heart rate. Relationships of ε and SR with ventricular inflow Doppler and myocardial tissue Doppler indices were explored. The age range was 3 days to 20 years, and body surface area range from 0.17 to 2.3 m(2) for the study cohort. Mean global LA εPos, LA εNeg, RA εPos, and RA εNeg were 28 ± 9%, -16 ± 6%, 23 ± 9%, and -15 ± 6%, respectively. Positive correlations were found for global atrial εPos and εNeg with age (P < .001). A marked rate of changes in ε and SR was seen in the first year of life, reaching normal adult values by adolescence. Peak positive SR had a strong negative correlation with age, and early negative SR had a strong positive correlation with age (P < .001), while late negative SR was correlated nonlinearly. Heart rate and age both influenced all LA and RA ε and SR indices. Maturational changes in LA and RA ε and SR occur in normal children and are especially profound in infancy. Consequently, LA and RA performance indices must be interpreted in light of heart rate and age. Normal values and percentiles for atrial ε and SR reported here will provide a foundation for the study of pediatric atrial physiology and function in disease states.


5-Aminosalicylic acid concentration in mucosal interstitium of cat small and large intestine.
Uncertainty regarding the concentration of 5-ASA within the mucosal interstitium has been a major limitation of defining the protective mechanisms of 5-ASA in intestinal inflammation. Therefore, we measured the concentration of 5-ASA in intestinal lymph and venous plasma during luminal perfusion of the cat small and large intestine with 10 mM 5-ASA. Blood and lymph flows were measured in each segment. 5-ASA and N-acetyl-5-ASA were extracted from plasma and lymph and quantified using fluorescence spectroscopy. Luminal perfusion of the terminal ileum with 5-ASA resulted in the following concentration profile: intestinal venous plasma (143 +/- 30 micrograms/ml) much greater than lymph (43 +/- 17 micrograms/ml) = systemic arterial plasma (40 +/- 11 micrograms/ml). In the colon the local venous plasma concentration of 5-ASA was 20 +/- 6 micrograms/ml compared to 2.0 +/- 1.0 micrograms/ml in systemic arterial plasma. N-Acetyl-5-ASA was found to comprise less than 5% of the total metabolite concentration in both ileum and colon. We also found that 58% of luminal 5-ASA was absorbed per minute in the terminal ileum, whereas only 3%/min was absorbed from the colon. The results of this study suggest that: (1) the mucosal interstitial concentration of 5-ASA in the terminal ileum and colon are approximately 100 micrograms/ml (654 microM) and 20 micrograms/ml (164 microM), respectively; and (2) the rate of 5-ASA absorption in the terminal ileum is approximately seven times greater than that in the colon.


In situ architecture of the ER-mitochondria encounter structure.
The endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis that rely on lipid exchange via membrane contact sites1-3, but the underpinning mechanisms remain poorly understood. In yeast, tethering and lipid transfer between the two organelles is mediated by the endoplasmic reticulum-mitochondria encounter structure (ERMES), a four-subunit complex of unresolved stoichiometry and architecture4-6. Here we determined the molecular organization of ERMES within Saccharomyces cerevisiae cells using integrative structural biology by combining quantitative live imaging, cryo-correlative microscopy, subtomogram averaging and molecular modelling. We found that ERMES assembles into approximately 25 discrete bridge-like complexes distributed irregularly across a contact site. Each bridge consists of three synaptotagmin-like mitochondrial lipid binding protein domains oriented in a zig-zag arrangement. Our molecular model of ERMES reveals a pathway for lipids. These findings resolve the in situ supramolecular architecture of a major inter-organelle lipid transfer machinery and provide a basis for the mechanistic understanding of lipid fluxes in eukaryotic cells.


Clinical efficacy of arthroscopy combined with irrigation and drainage in the treatment of brucellosis of the hip.
To evaluate the short-term clinical efficacy of hip arthroscopy combined with catheter irrigation and drainage in the treatment of brucellosis of the hip. From 2015 to 2020, 11 patients with a diagnosis of brucellosis-induced unilateral hip joint arthritis were treated with arthroscopic debridement and lesion synovectomy. Catheterization was performed during the operation, and normal saline lavage was continued after the operation. A regimen of doxycycline plus rifampicin, plus a third-generation cephalosporin in cases of refractory infections, were used for three months. The rate of positive synovial bacterial culture during the operation was 91% (10/11). Postoperative pathological examination of 11 patients showed purulent arthritis; this result combined with the disease history led to the diagnosis of all patients with brucellosis of the hip. All patients were followed up for more than 24 months. From three months after surgery to the last follow-up, both ESR and CPR were within the normal range, but the VAS score decreased significantly (P < 0.05), and the mHHS and HOS-ADL scores increased significantly (P < 0.01). Compared with that on preoperative imaging, the measurement of the hip joint space on imaging at the last follow-up showed no significant change (P > 0.01). Arthroscopic treatment of brucellosis in the hip joint not only preserves the joint fluid and lesion tissue for a clear diagnosis but also allows thorough removal of the infected and injured tissue during surgery. Hip arthroscopy combined with postoperative tube irrigation and drainage is an effective method for the diagnosis and treatment of brucellosis in the hip joint.


Mannosylation of glycoproteins and dolichol derivatives in fibroblasts from patients with cystic fibrosis.
Increased incorporation of mannose into endogenous glycoprotein fractions has been found in whole cell lysates and crude membrane preparations of cultured skin fibroblasts from patients with cystic fibrosis (1.3-2.3-times normal) when GDP[14C]mannose served as the mannosyl donor. In contrast, the incorporation of mannose from GDPmannose into lipid fractions containing dolichol phosphate and dolichol pyrophosphate oligosaccharides as well as the incorporation of mannose from dolichol phospho[3H]mannose into both glycoproteins and dolichol derivatives were not significantly different among cell preparations from patients with cystic fibrosis and normal controls. Mannosyltransferase activity toward exogenous glycoproteins as well as the activities of soluble and membranous alpha-mannosidase and beta-mannosidase appeared to be normal and could not account for the observed differences. The altered incorporation of mannose into endogenous glycoprotein may reflect changes in glycosylation processes other than mannosylation.


Primary histiocytic sarcoma of the spleen associated with hemophagocytosis.
We report a patient with primary histiocytic sarcoma of the spleen associated with prominent hemophagocytosis. Although thrombocytopenia, probably due to hemophagocytosis, was refractory to corticosteroid therapy, the transfusion of platelets, and splenic irradiation, partial splenic embolization was effective and facilitated splenectomy for a diagnosis. The majority of the spleen showed necrosis, but viable neoplastic cells with pleomorphic nuclei and abundant cytoplasm, showing occasional erythrocytes or leukocytes, were still discernible. The neoplastic cells expressed CD68, lysozyme, and S-100 protein, and were negative for lymphoid, myeloid, and epithelial cell markers. CD163, a monocyte/macrophage-specific molecule, was positive in only some of them. Despite multiagent chemotherapy, the patient died of the disease, showing a rapidly progressive clinical course. Although the preoperative diagnosis of primary splenic histiocytic sarcoma is difficult, it has been confirmed in patients with splenomegaly of unknown etiology that clinicolaboratory features suggestive of hemophagocytosis may be important clues suggestive to the disease. CD163 expression by neoplastic cells could be confirmed only after careful observation, because the molecule may only be seen in some of the neoplastic cells.


Single-cell RNA-sequencing of stria vascularis cells in the adult Slc26a4-/- mouse.
The primary pathological alterations of Pendred syndrome are endolymphatic pH acidification and luminal enlargement of the inner ear. However, the molecular contributions of specific cell types remain poorly characterized. Therefore, we aimed to identify pH regulators in pendrin-expressing cells that may contribute to the homeostasis of endolymph pH and define the cellular pathogenic mechanisms that contribute to the dysregulation of cochlear endolymph pH in Slc26a4-/- mice. We used single-cell RNA sequencing to identify both Slc26a4-expressing cells and Kcnj10-expressing cells in wild-type (WT, Slc26a4+/+) and Slc26a4-/- mice. Bioinformatic analysis of expression data confirmed marker genes defining the different cell types of the stria vascularis. In addition, specific findings were confirmed at the protein level by immunofluorescence. We found that spindle cells, which express pendrin, contain extrinsic cellular components, a factor that enables cell-to-cell communication. In addition, the gene expression profile informed the pH of the spindle cells. Compared to WT, the transcriptional profiles in Slc26a4-/- mice showed downregulation of extracellular exosome-related genes in spindle cells. Immunofluorescence studies in spindle cells of Slc26a4-/- mice validated the increased expression of the exosome-related protein, annexin A1, and the clathrin-mediated endocytosis-related protein, adaptor protein 2. Overall, cell isolation of stria vascularis from WT and Slc26a4-/- samples combined with cell type-specific transcriptomic analyses revealed pH-dependent alternations in spindle cells and intermediate cells, inspiring further studies into the dysfunctional role of stria vascularis cells in SLC26A4-related hearing loss.


Enhanced photocatalytic toluene oxidation performance induced by two types of cooperative fluorine doping in polymeric carbon nitride with the first-principles calculations.
Fluorine atoms doping was reported in experiment to reduce the band gap, improve the oxidation potential of hole, and polarize the electron distribution of polymeric carbon nitride (PCN). However, the relationships between different types of F doping and the roles of F doping in electronic and optical properties remain elusive. In this work, we investigate several F doping types in PCN and analyze their different roles in electronic and optical properties with the first-principles calculations. The results show that two stable and cooperative F doping types are found, one is to form the C (sp3)-F bond (Fcorner type), and the other is F atom replacing amino group -NH2 (FN3 type) forming covalent C-F bond. The Fcorner doping reduces the energy level of valence-band maximum (VBM), causes excited electron-hole distribution polarized, and increases the hole distribution on F atoms, which strengthens the capacity of photocatalytic oxidation and improves the electron-hole separation efficiency, while FN3 type doping plays the roles of reducing the bandgap and improving the light absorption. In addition, under the synergistic action of two types of F doping, the adsorption energy of toluene on F-codoped PCN is greatly enhanced, improving the ability of photocatalytic activation of toluene. Our work develops a new understanding of F doping and reveals the roles of different types of F doping, providing a rationale for designing and regulating more efficient photocatalysts and improving the properties of photocatalytic toluene oxidation.


Effect of rotational malposition of the femoral component on knee stability kinematics after total knee arthroplasty.
Excessive external rotation of the femoral component can cause an abnormally tight popliteus tendon complex, which induces loss of rotational laxity of the knee in the late phase of knee flexion after total knee arthroplasty. This study evaluated the effect of popliteus tendon release on rotational and varus-valgus laxity of implanted knees with an excessively externally rotated femoral component. Rotational and varus-valgus laxity was measured with a knee kinematics testing device before and after total knee arthroplasty. External rotational positions of the femoral component of 5 degrees and 8 degrees were compared, and the effects of popliteus tendon release on rotational and varus-valgus laxity were evaluated. To further investigate this question, the effect of a conforming articular design was compared with that of a flat tibial surface. External rotational position of 5 degrees did not change rotational or varus-valgus laxity of the knee. With an 8 degrees external rotational position, however, external rotational laxity significantly decreased in knees with a conforming surface at angles of 30 degrees, 45 degrees, 60 degrees, and 90 degrees. After popliteus tendon release, external rotational laxity significantly improved at 90 degrees flexion and was identical to that of the normal knee. Internal rotational range was similar before and after popliteus tendon release. Popliteus tendon release did not affect the varus-valgus laxity (stability) with either articular surface.


Helping children and adolescents who lost a caregiver during the COVID-19 pandemic.
Between March 2020 and June of 2021, 140,000 children under 18 in the US lost a caregiver. Due to this sudden loss, their lives have been drastically impacted. This article presents interventions for this population's unique and stressful emotional trauma.


Physician-Modified Branched Double-Trunk Stent-Graft (PBDS) for Thoracoabdominal Aortic Aneurysm.
To describe the preliminary experience of using physician-modified, branched, double-trunk stent-grafts (PBDS) for treating thoracoabdominal aortic aneurysms (TAAA). Ten (10) patients with TAAA were included in the study from June 2017 to March 2020. The technical success, perioperative complications, re-intervention, and patency of branch arteries were assessed. The technical success rate was 100%. There were four type III endoleaks (40%) recorded in the perioperative period. The median follow-up was 13.4 months (range, 3-36 months). During follow-up, two renal stent-graft occlusions (2 of 37 visceral arteries reconstructed, 5.4%), one cerebral infarction (1 of 10, 10%) and one paraplegia (1 of 10, 10%) occurred. No aortic-related death was recorded. PBDS is useful in sealing TAAA and preventing visceral branches, providing an option for patients unsuited for open surgical repair. A larger sample size of patients is required to confirm the safety and effectiveness of this technique.


Evolutionary mechanisms underlying the diversification of nuclear factor of activated T cells across vertebrates.
The mechanisms of immunity linked to biological evolution are crucial for understanding animal morphogenesis, organogenesis, and biodiversity. The nuclear factor of activated T cells (NFAT) family consists of five members (NFATc1-c4, 5) with different functions in the immune system. However, the evolutionary dynamics of NFATs in vertebrates has not been explored. Herein, we investigated the origin and mechanisms underlying the diversification of NFATs by comparing the gene, transcript and protein sequences, and chromosome information. We defined an ancestral origin of NFATs during the bilaterian development, dated approximately 650 million years ago, where NFAT5 and NFATc1-c4 were derived independently. The conserved parallel evolution of NFATs in multiple species was probably attributed to their innate nature. Conversely, frequent gene duplications and chromosomal rearrangements in the recently evolved taxa have suggested their roles in the adaptive immune evolution. A significant correlation was observed between the chromosome rearrangements with gene duplications and the structural fixation changes in vertebrate NFATs, suggesting their role in NFAT diversification. Remarkably, a conserved gene structure around NFAT genes with vertebrate evolutionary-related breaking points indicated the inheritance of NFATs with their neighboring genes as a unit. The close relationship between NFAT diversification and vertebrate immune evolution was suggested.


A case of Marine Lenhart syndrome with Hashimoto's thyroiditis that mimicked thyroid carcinoma.
Marine Lenhart syndrome is a rare disease and causes refractory hyperthyroidism. So far, little evidence on the combination of both Marine Lenhart syndrome and Hashimoto's thyroiditis is available. We suspect that Marine Lenhart syndrome when combined with Hashimoto's thyroiditis might have its particular features, which are not exactly the same as those of the isolated Marine Lenhart syndrome. A 56-year-old middle-aged man presented with recurrent hyperthyroidism, and Graves' disease combined with Hashimoto's thyroiditis was considered. Radionuclide imaging showed a hot nodule, but ultrasonography suggested the possibility of malignancy with a category of 4B according to the Chinese-Thyroid Imaging-Reporting and Data System (C-TIRADS) model. Fine needle aspiration cytology (FNAC) revealed eosinophilic follicular lesions with papillary features, and prompted that papillary thyroid carcinoma could not be excluded. Partial thyroidectomy was performed and the nodule was proven to be benign by histopathology. The final diagnosis was atypical Marine Lenhart syndrome with Hashimoto's thyroiditis. Marine Lenhart syndrome combined with Hashimoto's thyroiditis has its particular characteristics, showing some signs mimicking malignancy. Limitations of ultrasonography and FNAC in diagnosis should be noted in these scenarios.


Impact of Contextual Factors on Interventions to Reduce Acute Care Transfers II Implementation and Hospital Readmission Rates.
Identify contextual and implementation factors impacting the effectiveness of an organizational-level intervention to reduce preventable hospital readmissions from affiliated skilled nursing facilities (SNFs). Observational study of the implementation of Interventions to Reduce Acute Care Transfers tools in 3 different cohorts. SNFs. SNFs belonging to 1 of 2 corporate entities and a group of independent SNFs that volunteered to participate in a Quality Improvement Organization (QIO) training program. Two groups of SNFs received INTERACT II training and technical assistance from corporate staff, and 1 group of SNFs received training from QIO staff. Thirty-day acute care hospital readmissions from Medicare fee-for-service claims, contextual factors using the Model for Understanding Success in Quality framework. All 3 cohorts were able to deliver the INTERACT training program to their constituent facilities through regional events as well as onsite technical assistance, but the impact on readmission rates varied. Facilities supported by the QIO and corporation A were able to achieve statistically significant reductions in 30-day readmission rates. A review of contextual factors found that although all cohorts were challenged by staff turnover and workload, corporation B facilities struggled with a less mature quality improvement (QI) culture and infrastructure. Both corporations demonstrated a strong corporate commitment to implementing INTERACT II, but differences in training strategies, QI culture, capacity, and competing pressures may have impacted the effectiveness of the training. Proactively addressing these factors may help long-term care organizations interested in reducing acute care readmission rates increase the likelihood of QI success.


Methamphetamine-induced dopaminergic hyperactivity is not accompanied with increase in tyrosine hydroxylase mRNA of the rat midbrain.
Tyrosine hydroxylase (TH) mRNA was measured in the midbrain of rats treated repeatedly with methamphetamine (MAP). Male Sprague-Dawley rats were daily injected with MAP (5 mg/kg, i.p., once daily) or saline for 14 days. Progressive augmentation was observed in MAP-induced stereotyped behaviors. After one week of abstinence, the rats were decapitated and the brains were prepared for either in situ hybridization using non-radioactive cRNA probes or Northern blot analysis using 32P-labeled cDNA probes. In situ hybridization showed that the signals of TH mRNA were localized to the dopaminergic perikarya in the midbrain and were reduced in MAP-treated animals compared to the controls. Northern blot analysis revealed that the level of TH mRNA in the midbrain of MAP-treated rats was decreased by 37% compared to the controls, which was close to the statistical significance (P = 0.053). These results indicate that the dopaminergic hyperactivity caused by repeated MAP treatment is not associated with enhanced transcription of the TH gene.


Diurnal neurobiological alterations after exposure to clozapine in first-episode schizophrenia patients.
Irregular circadian rhythm and some of its most characteristic symptoms are frequently observed in patients with schizophrenia. However, changes in the expression of clock genes or neuropeptides that are related to the regulation of circadian rhythm may influence the susceptibility to recurrence after antipsychotic treatment in schizophrenia, but this possibility has not been investigated. Blood samples were collected from 15 healthy male controls and 13 male schizophrenia patients at 4h intervals for 24h before and after treatment with clozapine for 8 weeks. The outcome measures included the relative expression of clock gene mRNA PERIOD1 (PER1), PERIOD2 (PER2), PERIOD3 (PER3) and the levels of plasma cortisol, orexin, and insulin. Compared with healthy controls, schizophrenia patients presented disruptions in diurnal rhythms of the expression of PER1, PER3, and NPAS2 and the release of orexin, accompanied by a delayed phase in the expression of PER2, decreases in PER3 and NPAS2 expression, and an increase in cortisol levels at baseline. Several of these disruptions (i.e., in PER1 and PER3 expression) persisted after 8 weeks of clozapine treatment, similar to the decreases in the 24-h expression of PER3 and NPAS2. Clozapine treatment for 8 weeks significantly decreased the 24-h levels of PER2 and increased the 24-h levels of insulin. These persistent neurobiological changes that occur after 8 weeks of clozapine treatment may contribute to the vulnerability to recurrence and efficacy of long-term maintenance treatment in schizophrenia.


Functional and Morphological Adaptations in the Heart of Children Aged 12-14 Years following Two Different Endurance Training Protocols.
This study investigated the cardiac functional and the morphological adaptations because of two endurance training protocols. Untrained children (N = 30, age: 12-14 years) were divided into three groups (N = 10/group). The first group did not perform any session (CONTROL), the second performed ventilatory threshold endurance training (VTT) for 12 weeks (2 sessions/week) at an intensity corresponding to the ventilatory threshold (VT) and the third (IT) performed two sessions per week at 120% of maximal oxygen uptake (VO2max). Two other sessions (30 min running at 55-65% of VO2max) per week were performed in VVT and IT. Echocardiograms (Left Ventricular end Diastolic Diameter, LVEDd; Left Ventricular end Diastolic Volume, LVEDV; Stroke Volume, SV; Ejection Fraction, EF; Posterior Wall Thickness of the Left Ventricle, PWTLV) and cardiopulmonary ergospirometry (VO2max, VT, velocity at VO2max (vVO2max), time in vVO2max until exhaustion (Tlim) was conducted before and after protocols. Significant increases were observed in both training groups in LVEDd (VTT = 5%; IT = 3.64%), in LVEDV (VTT = 23.7%; ITT = 13.6%), in SV (VTT = 25%; IT = 16.9%) but not in PWTLV and EF, after protocols. No differences were noted in the CONTROL group. VO2max and VT increased significantly in both training groups by approximately 9% after training. Our results indicate that intensity endurance training does not induce meaningful functional and morphological perturbations in the hearts of children.


Tick bites in healthy adults from western Norway: occurrence, risk factors, and outcomes.
The frequency of tick bites, risk factors, as well as simple outcome measures after tick bites in a healthy adult population (blood donors) from Sogn and Fjordane county situated at the western coast of Norway, was assessed. The study was based on cross-sectional data from blood donors at 4 different blood banks in the county during the period January to June 2010. Data on tick bites and potential risk factors were collected from 1213 blood donors using a questionnaire. Among participants, 65.7% had experienced tick bites during their life time, whereas 30% reported recent tick bites (during the latest 12 months). There were fewer tick bites in the eastern, inland part of the county, where the tick Ixodes ricinus is less prevalent compared to the western, coastal regions. The number of total and recent tick bites increased with the respondent's age, hours spent outdoors during summertime, educational level, ownership of domestic animals, and hunting. Women older than 50 years reported more bites than similarly aged men and younger females. Among bitten subjects, 22.7% reported ever having had a rash around a tick bite, whereas 12.7% had seen a medical doctor and 7.7% had received antibiotics owing to tick bite. Avoiding certain locations owing to a fear of tick bites was reported by 15.7% of all respondents, more women than men. In conclusion, tick bites are common in the western part of Norway. The risk of being bitten varies with age and outdoor activities, animal contact, and geography. The consequences in terms of disease seem modest.


Influence of type of mesh fixation in endoscopic totally extraperitoneal hernia repair (TEP) on long-term quality of life.
Laparoscopic total extraperitoneal mesh repair (TEP) of inguinal hernia has become well accepted with low recurrence and high patient satisfaction rates. However, inguinal pain has also been reported. Source of this pain has been suggested to be the fixation method, especially the use of tacks. Introduction of fibrin glue and absorbable tacks were suggested to lower chronic pain and inguinal discomfort rates. This study analyses the different methods of fixation. 201 patients were analysed. Primary end-points were patients' satisfaction, health-related quality of life, and specific inguinal conditions (e.g. pulling, swelling, troubles at coughing). Secondary endpoints were duration of operation, length of hospital stay, and material costs. Fibrin glue was used in 101 patients and tacks in 100 patients, in 21 of those absorbable tacks. Patients were fully satisfied with the results in more than 90%, irrespective of the fixation method. Health-related quality of life along the SF-12(®) questionnaire attested no differences. Inguinal pulling occurred significantly more often after fibrin glue (25.7 %) than after tack fixation (11 %; p = 0.026), whereas no differences in the other specific inguinal sensations occurred. Mesh fixation in TEP can be performed either by tacks or by fibrin glue with similar long-term results concerning satisfaction, health-related quality of life, and pain. No advantage of fibrin glue could be found, in fact, a higher percentage of patients had inguinal pulling and burning sensations after the use of fibrin glue. The use of absorbable tacks showed no advantage.


Studies On The Parasitic Helminths Of Korea: III. Nematodes And Cestodes Of Rodents.
A survey for nematode and cestode parasites of rodents in Korea has been carried out at the areas of Chulwon, Kumwha, Pochon, Paju and Chungpyong, Kyunggi-Do. A total of 300 rodents of seven species was examined, comprising of 219 A. agrarius, 33 R. norvegicus, 8 R. alexandrinus, 14 Mus musculus yamashinai, Microtus fortis pellceus, 21 Crocidura russula and a Cricetulus trition nester. The following fifteen species belonging to thirteen genera were identified. NEMATODA: Heterakis spumosa, Syphacia obvelata, Nippostrongylus muris, Protospirura muris, Capillaria hepatica, Capillaria sp., Heligmosomum sp., Heligmosomoides sp., Rictularia sp. and Gongylonema sp. CESTODA: Hymenolepis nana, Hymenolepis diminuta, Raillietina coreensis, Paranoplocephala sp. and Cysticercus fasciolaris(the larva of Taenia taeniaeformis).


Volume-Outcome Relationship of Resternotomy Coronary Artery Bypass Grafting.
We assessed volume-outcome relationships of resternotomy coronary artery bypass grafting (CABG). We studied 1,362,218 first-time CABG and 93,985 resternotomy CABG patients reported to The Society of Thoracic Surgeons Adult Cardiac Surgery Database between 2010 and 2019. Primary outcomes were in-hospital mortality and mortality and morbidity (M&M) rates calculated per hospital and per surgeon. Outcomes were compared across 6 total cardiac surgery volume categories. Multivariable generalized linear mixed-effects models were used considering continuous case volume as the main exposure, adjusting for patient characteristics and within-surgeon and hospital variation. We observed a decline in resternotomy CABG unadjusted mortality and M&M from the lowest to the highest case-volume categories (hospital-level mortality, 3.9% ± 0.6% to 3.3% ± 0.1%; M&M, 18.5% ± 1.1% to 15.7% ± 0.4%, P < .001; surgeon-level mortality, 4.1% ± 0.3% to 4.1% ± 1.3%; M&M, 18.5% ± 0.6% to 14.5% ± 2.2%, P < .001). Looking at outcomes vs continuous volume showed that beyond a minimum annual volume (hospital 200-300 cases; surgeon 100-150 cases, approximately), mortality and M&M rates did not further improve. Using individual-level data and adjusting for patient characteristics and clustering within surgeon and hospital, we found higher procedural volume was associated with improved surgeon-level outcomes (mortality adjusted odds ratio, 0.39/100 procedures; 95% CI, 0.24-0.61; M&M adjusted odds ratio, 0.37/100 procedures; 95% CI, 0.28-0.48; P < .001 for both). Hospital-level adjusted volume-outcomes associations were not statistically significant. We observed an inverse relationship between total cardiac case volume and resternotomy CABG outcomes at the surgeon level only, indicating that individual surgeon's experience, rather than institutional volume, is the key determinant.


Interprofessional education in nursing: The impact of collaboration between physical and mental health care professionals.
Interprofessional collaboration in the training of nursing and psychology students helps provide students of both disciplines with the ability and competences they need to best attend to their patients. This study implemented and analyzed a method for developing the competences of each discipline in a scenario of joint clinical simulation that incorporates mental and physical health simultaneously, and measured the caring ability of the participating students. Participants took a self-applied survey measuring their own caring ability. After, a clinical simulation was performed where nursing students performed clinical interviews on psychology students, who acted as standardized patients. Caring abilities were measured in the nursing students, and the psychology students implemented an intervention service measuring caring ability and brief - debrief simulation by coaching to nursing students. The results indicated that the self-applied questionnaire of caring ability resulted in scores significantly higher than what was measured by observers. The results contribute to the development of protocols, training and collaborative work practices in interprofessional education, which allow the scaling of these competences.


Myectomy versus anterior transposition for inferior oblique overaction.
Inferior oblique overaction can be either secondary (as a sequela of ipsilateral superior oblique palsy) or primary (commonly associated with horizontal strabismus). Superior oblique underaction often coexists with both primary and secondary inferior oblique overaction. This retrospective case series compares the efficacy of inferior oblique myectomy versus anterior transposition in improving inferior oblique overaction and superior oblique underaction in eyes with either primary or secondary inferior oblique overaction. One hundred twenty eyes of 81 patients were included in this retrospective case series, of which 20 had anterior transposition of the inferior oblique and 100 eyes underwent myectomy. Inferior oblique myectomy was compared with inferior oblique anterior transposition in improving inferior oblique overaction and superior oblique underaction in each diagnostic subgroup. Postoperative outcome was qualitatively and quantitatively assessed. Fisher's exact test was used to compare the outcomes. The quantitative improvement of function in terms of inferior oblique overaction and superior oblique underaction was analyzed by regression analysis. When postoperative inferior oblique overaction was considered, there was no statistically significant difference between myectomy and anterior transposition in both primary and secondary inferior oblique overaction. Myectomy was superior to anterior transposition in improving superior oblique underaction in both primary inferior oblique overaction (OR = 0.14; 95% CI, 0.015-1.45; p = 0.056) and secondary inferior oblique overaction (OR = 0; 95% CI, 0-0.027; p < 0.001). The quantitative improvement of function showed a significant difference between procedures for superior oblique underaction (t-test; p = 0.005; 95% CI, 0.25-1.3) but not inferior oblique overaction (t-test; p = 0.8; 95% CI, -0.67-0.54). This study demonstrates both inferior oblique myectomy and inferior oblique anterior transposition to be effective in correcting primary and secondary inferior oblique overaction. Myectomy is more effective in improving superior oblique underaction associated with both primary and secondary inferior oblique overaction. On this basis, we feel that inferior oblique myectomy has some advantage over anterior transposition in treating combined inferior oblique overaction and superior oblique underaction and can be considered the procedure of choice.


Climate Change as a Social Determinant of Health: An Interactive Case-Based Learning Activity.
Despite consensus on climate change's impact on humans, medical schools have not widely adopted inclusion of environmental topics into their mandatory curriculum. This educational activity explicitly addresses climate change as one of the environmental determinants of health (EDH). We developed a required, 1-hour module for all first-year medical students. This interactive, case-based, small-group activity was incorporated into a curriculum within an advising program but could be run independently. Before and after the session, participants completed evaluations assessing knowledge gains and attitude shifts. Of 183 first-year students, 155 completed both pre- and postmodule surveys. Participants' rating increased on the postmodule survey item "priority should be given to the discussion of EDH in medical education." The Wilcoxon signed rank test determined this difference in priority was statistically significant (p < .001). Reported strengths of this activity included the cases, informative content on EDH, the video, the discussion, and highlighted EDH resources. Suggested areas for improvement included more information on how to apply concepts to clinical contexts, guidance on how to engage in EDH concepts, and more discussion time. As a result of the module, students planned to engage in recycling, reduced consumption, advocacy, and changes to mode of transportation. Climate change remains the greatest global threat to human health, and future physicians must be equipped to educate patients and policymakers on the harms of environmental hazards. This brief yet effective module offers one approach to incorporating this topic into medical school curricula.


An anterior transversalis fascia repair for adult inguinal hernias.
During the eight year period from 1967 to 1975, 1,020 patients more than eighteen years old underwent 1,311 inguinal herniorrhaphies. Group I consisted of 723 inguinal herniorrhaphies in which either a Bassini or a Cooper's ligament repair was used. During a four to nine year follow-up period, the total recurrence rate was 11.5 per cent; the recurrence rate for the primary repair group was 7 per cent and for the recurrent group 32 per cent. The follow-up rate was 93.7 per cent. Group II consisted of 591 herniorrhaphies in which the repair was performed by an anterior transversalis fascia technic. During a two to five year follow-up period, the total recurrence rate was 2.7 per cent; 1.8 per cent for primary repairs and 8.0 per cent for recurrent hernias. The follow-up rate was 98 per cent (95 per cent by personal examination). Assuming that the recurrences in group II will occur with the same frequency as in group I, our projected four to nine year recurrence rate is 3.4 per cent. This suggests that the anterior transversalis fascia repair results in a lower recurrence rate than either the Bassini or Cooper's ligament repairs.


Pulmonary artery enlargement in schistosomiasis associated pulmonary arterial hypertension.
Schistosomiasis associated pulmonary arterial hypertension (Sch-PAH) might represent the most prevalent form of PAH worldwide. In Sch-PAH, the presence of aneurismal dilation of the pulmonary artery has been described, although it is still a matter of debate whether on average the pulmonary artery is more enlarged in Sc-PAH than IPAH. We retrospectively evaluated patients with IPAH (n = 25) and Sch-PAH (n = 22) who underwent computed tomography pulmonary angiogram and right heart catheterization. Sch-PAH patients were older and presented less severe hemodynamic profiles. Main pulmonary artery diameter (MPAD) was greater in Sch-PAH than IPAH (4.5 ± 1.8 vs 3.7 ± 1.1 cm, p = 0.018). For the same level of mean pulmonary artery pressure, the MPAD in Sch-PAH was 0.89 cm larger than in IPAH (Covariance model p = 0.02). This study demonstrated that pulmonary artery enlargement is more pronounced in Sch-PAH than IPAH, independently of mean pulmonary artery pressure level, suggesting that this is more likely a feature of Sch-PAH.


Malignant schwannoma with melanocytic and neuroepithelial differentiation in an infant with congenital giant melanocytic nevus: a complex neurocristopathy.
We describe an infant girl, born with a pigmented giant nevus, who developed a malignant schwannoma in the retroperitoneum at 16 months of age. At birth the nevus covered over 50% of her body and histologically was a compound nevus with extension into the deep dermis surrounding dermal appendages. The malignant schwannoma was biphasic with areas composed of spindle and round cells. Ultrastructurally, the majority of the tumor cells exhibited a Schwann cell phenotype, but neuroepithelial and melanocytic cells were identified as well. We believe that this constellation of findings represents a form of neurocristopathy. Neurocristopathy, as defined by Bolande (Hum Pathol 5:409-429, 1974), is a disease that results from aberrations in the migration, growth, or cytodifferentiation of neural crest tissues. These diseases may be simple (a singular pathologic process, usually localized) or complex (multiple neuroectodermal lesions). We report this case because the occurrence of retroperitoneal malignant schwannoma arising in a 16-month-old infant born with a pigmented giant nevus is unique, and may represent a previously undescribed form of a complex neurocristopathy.


Ultrasound-guided aspiration and ethanol sclerotherapy for treating endometrial cysts.
The authors sought to evaluate the effectiveness of ultrasound (US)-guided aspiration and ethanol sclerotherapy in treating endometrial cysts and adopt this procedure as an alternative to surgery. Fifty consecutive patients with an average age of 25.2 years [standard deviation (SD) 6.5; range 16-40 years) and US diagnosis of endometrial cyst who were pregnant or presenting with high anaesthesia risk, adhesions or who refused surgery underwent US-guided aspiration of a total of 54 endometrial cysts (40 with transabdominal approach and the remaining 14 with transvaginal approach) and ethanol sclerotherapy. The procedure was successful in all patients. Follow-up imaging was carried out at 12 h, 24 h, 15 days, 3 months, 6 months and 12 months. After 12 months, four patients (8%) showed recurrence, three of whom opted for a second session of US-guided aspiration and ethanol sclerotherapy. US-guided aspiration and sclerotherapy with 95% ethanol provides a valid alternative to surgery in treating endometrial cysts.


Lung anabolic activity in patients with chronic heart failure: potential implications for clinical practice.
The proteins in the lungs are in constant flux, undergoing degradation and resynthesis. We investigated pulmonary protein and amino acid metabolism, the biochemical basis of the remodeling process, in individuals with chronic heart failure receiving or not receiving β-blocker therapy with bisoprolol (BIS). Clinically stable rehabilitative patients with chronic heart failure, without metabolic diseases or liver/renal failure, and with a stable weight over the preceding 3 mo underwent right heart catheterization, and radial artery cannulation. Mixed central venous and arterial blood samples were drawn simultaneously to calculate the venous-arterial difference of amino acids (pulmonary uptake and release). Twenty-two patients on BIS therapy and eight not receiving BIS were analyzed. The two groups showed a net pulmonary protein synthesis (i.e., a positive value of phenylalanine [venous-arterial difference] × cardiac index product) and amino acid extraction, the rates of which were significantly lower in patients on BIS therapy. The two groups had pulmonary hypertension (mean pulmonary artery pressure >19 mmHg). Pulmonary vascular resistance was 57% higher in patients not receiving BIS than in those on BIS therapy (6.65 ± 2.90 versus 4.23 ± 1.49 mmHg/L · min⁻¹ · m⁻², P < 0.05). Pulmonary vascular resistance correlated positively with the pulmonary extraction of total essential amino acids (r = +0.4576, P = 0.01) and leucine (r = +0.5083, P = 0.004), the most important amino acid for protein synthesis. Patients with chronic heart failure have increased rates of amino acid extraction and pulmonary protein synthesis, suggesting, at least in part, an increased rate of lung remodeling. Therapy with BIS attenuates lung metabolic abnormalities.


Is there room for punctuated equilibrium in macroevolution?
The long-controversial theory of punctuated equilibrium (PE) asserts that speciation causes rapid evolution against a backdrop of stasis. PE is currently undergoing a resurgence driven by new developments in statistical methods. However, we argue that PE is actually a tangle of four unnecessarily conflated questions: (i) is evolution gradualistic or pulsed? (ii) does trait evolution occur mainly at speciation or within a lineage? (iii) are changes at speciation adaptive or neutral? and (iv) how important is species selection in shaping patterns of diversity? We discuss progress towards answering these four questions but argue that combining these conceptually distinct ideas under the single framework of PE is distracting and confusing, and more likely to hinder progress than to spur it.


Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells.
Treatment resistance in acute lymphoblastic leukemia (ALL) is often caused by defects in programmed cell death, e.g. by overexpression of Inhibitor of Apoptosis (IAP) proteins. Here, we report that small-molecule Smac mimetics (i.e. BV6, LCL161, birinapant) that neutralize x-linked IAP (XIAP), cellular IAP (cIAP)1 and cIAP2 cooperate with demethylating agents (i.e. 5-azacytidine (5AC) or 5-aza-2'-deoxycytidine (DAC)) to induce cell death in ALL cells. Molecular studies reveal that induction of cell death is preceded by BV6-mediated depletion of cIAP1 protein and involves tumor necrosis factor (TNF)α autocrine/paracrine signaling, since the TNFα-blocking antibody Enbrel significantly reduces BV6/5AC-induced cell death. While BV6/5AC cotreatment induces caspase-3 activation, the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) only partly rescues ALL cells from BV6/5AC-induced cell death. This indicates that BV6/5AC cotreatment engages non-apoptotic cell death upon caspase inhibition. Indeed, genetic silencing of key components of necroptosis such as Receptor-Interacting Protein (RIP)3 or mixed lineage kinase domain-like (MLKL) in parallel with administration of zVAD.fmk provides a significantly better protection against BV6/5AC-induced cell death compared to the use of zVAD.fmk alone. Similarly, concomitant administration of pharmacological inhibitors of necroptosis (i.e. necrostatin-1s, GSK'872, dabrafenib, NSA) together with zVAD.fmk is superior in rescuing cells from BV6/5AC-induced cell death compared to the use of zVAD.fmk alone. These findings demonstrate that in ALL cells BV6/5AC-induced cell death is mediated via both apoptotic and necroptotic pathways. Importantly, BV6/5AC cotreatment triggers necroptosis in ALL cells that are resistant to apoptosis due to caspase inhibition. This opens new perspectives to overcome apoptosis resistance with important implications for the development of new treatment strategies for ALL.


"Super hybrid tridentate ligands": 4-substituted-2-(1-butyl-1H-1,2,3-triazol-4-yl)-6-(1H-pyrazol-1-yl)pyridine ligands coordinated to Fe(ii) ions display above room temperature spin transitions.
A series of novel "super hybrid tridentate ligands" based on (2-(1-butyl-1H-1,2,3-triazol-4-yl)-6-(1H-pyrazol-1-yl)pyridine (tpp) derivatives were synthesized. Their Fe(ii) complexes display around (T(½) = 287 K) and above room temperature (T(½)≫ 375 K) spin transition temperatures.


Post-error slowing in anxiety and obsessive-compulsive disorders.
Altered brain response to errors in anxiety and obsessive-compulsive disorders (OCD) suggests cognitive control abnormalities across both types of illness, but behavioral metrics of cognitive control function have yet to be compared in patients selected from these different diagnostic categories. Thus, we examined post-error slowing (PES), a behavioral adjustment that typically occurs after a mistake, in children and adolescents with and without a primary anxiety disorder (N = 103 anxiety and N = 28 healthy controls) and adolescents and adults with and without OCD (N = 118 OCD and N = 60 healthy controls) using a go/no-go task. Primary analyses tested for differences in PES between diagnostic groups (anxiety, OCD, healthy), controlling for age, overall reaction time, and overall accuracy. Results indicated that patients with anxiety disorders exhibited more post-error slowing than both patients with OCD and healthy volunteers. In contrast, participants with OCD did not differ from healthy volunteers in post-error slowing. In subgroup analyses restricted to adolescent participants (ages 13-17 years), more post-error slowing was observed in the anxiety disorders group compared with either the OCD or healthy groups. These data suggest that excessive post-error slowing, an index of behavioral adjustment following errors, may uniquely characterize patients with anxiety disorders relative to healthy individuals and those with OCD.


A familial defect of neutrophil chemotaxis with asthma, eczema, and recurrent skin infections.
A defect in chemotaxis of peripheral blood polymorphonuclear leukocytes (PMN's) was demonstrated in both parents and three of four children in a single family afflicted with varying degrees of respiratory allergy, unusual onset of severe eczema in the first month of life, and recurrent bacterial skin infections. Of great interest was the identification of HLA-B12 at the B locus in all affected members but not in the unaffected child. The two children known since infancy to be most severely affected with eczema and recurrent infections are HLA identical and homozygous for HLA-B12. The child without eczema and infections had an intermediate cellular chemotactic defect most apparent on kinetic studies.


Tobramycin in the treatment of peritonitis.
Tobramycin is a new aminoglycosidic aminocyclitol antibiotic which has a broad spectrum of activity against aerobic and facultative Gram-negative bacilli. It is particularly effective against Pseudomonas aeruginosa, including some strains of this organism which are resistant to gentamicin. The newer aminoglycosidic aminocyclitol antibiotics all consist of a "backbone" of 2-deoxystreptamine, to which are attached several amino-containing sugar groups. These agents inhibit protein synthesis in bacteria at the level of the ribosome and are bactericidal although the precise mechanism by which they kill bacteria is still not known. There are a number of processes by which bacteria can become resistant to the action of the aminoglycosidic aminocyclitol antibiotics. Among these, the ability of bacteria to produce inactivating enzymes (usually mediated by R-factors or plasmids) appears to be the most important in current clinical isolates of bacteria. Aminoglycosidic aminocyclitol antibiotics which are resistant to these enzymes may have an enhanced spectrum of activity.


Resource limited and equilibrium models of populations.
The logistic equation has been used as the basis of two distinct models of population dynamics, a resource limited model and an equilibrium model. It is argued that although the two models are very different, the distinction between them has been obscured by the use of the same terminology for the parameters of both. It is further argued that the simple equilibrium model developed from the logistic equation has inconsistencies which make it untenable as a population model.


Protocol for diagnosis of seizure disorders in companion animals.
An algorism for diagnosis of the problem of seizures was used to develop a diagnostic plan. The plan was structured in stages for: (1) primary evaluation in the general practice and (2) specialized evaluation in difficult cases.


Gender and Racial Identity Moderate the Effects of Online and Offline Discrimination on Mental Health: Dismantling Systems of Racism and Oppression during Adolescence.
The present study highlights the growing need to examine Black youths' exposure to racial discrimination in online and offline contexts. Using a sample of 353 Black college students, findings indicate that high public regard moderates the positive association between online and offline racial discrimination and psychological consequences (i.e., depression, anxiety, and psychological well-being) among Black women. Additionally, racial centrality moderated the positive association between online and offline racial discrimination and mental health consequences regardless of gender. The findings highlight the importance of considering context, gender, and racial identity when examining the links between Black emerging adults' experiences of discrimination and mental health.


Evaluation of orbicularis oculi muscle stripping on the cosmetic outcome of upper lid blepharoplasty: a randomized, controlled study.
Many variations in the surgical treatment of upper eyelid blepharoplasty have been described, including orbicularis oculi muscle stripping. There is no evidence in the literature to support the efficacy of this technique in improving the aesthetic results of the procedure. To conduct a single-blind, randomized, controlled, split-face pilot study to evaluate the effects of orbicularis oculi muscle stripping on upper lid blepharoplasty. Ten subjects were randomized to receive upper lid blepharoplasty with orbicularis oculi muscle stripping on one side and skin-only blepharoplasty on the other. Patients and two blinded physicians evaluated the aesthetics of the eyelids at 1-, 3-, and 17-month follow-up visits. Blinded physician evaluation failed to show a difference in the overall cosmetic appearance of the eyelids between the control and treatment sides at any time point. Analysis of the composite of all patient scores showed a trend favoring the control side at 3 months (p = .28) and the treatment side at 17 months (p = .50), but neither difference was significant. Based on the data from this pilot study, orbicularis oculi muscle stripping appears to have no affect on the aesthetic outcome of upper lid blepharoplasty.


Dystroglycan Depletion Impairs Actin-Dependent Functions of Differentiated Kasumi-1 Cells.
Dystroglycan has recently been characterised in blood tissue cells, as part of the dystrophin glycoprotein complex involved in the differentiation process of neutrophils. In the present study we have investigated the role of dystroglycan in the human promyelocytic leukemic cell line Kasumi-1 differentiated to macrophage-like cells. We characterised the pattern expression and subcellular distribution of dystroglycans in non-differentiated and differentiated Kasumi-1 cells. Our results demonstrated by WB and flow cytometer assays that during the differentiation process to macrophages, dystroglycans were down-regulated; these results were confirmed with qRT-PCR assays. Additionally, depletion of dystroglycan by RNAi resulted in altered morphology and reduced properties of differentiated Kasumi-1 cells, including morphology, migration and phagocytic activities although secretion of IL-1β and expression of markers of differentiation are not altered. Our findings strongly implicate dystroglycan as a key membrane adhesion protein involved in actin-based structures during the differentiation process in Kasumi-1 cells.


Central inhibitory effects of relaxin on the milk ejection reflex of the rat depends upon the site of injection into the cerebroventricular system.
The effects of centrally administered porcine relaxin on the milk-ejection reflex were studied in anaesthetized, lactating rats. Injection of relaxin into either the lateral ventricles (10-1000 ng) or third ventricle (500 ng) of the brain significantly inhibited suckling-induced reflex milk-ejection. Following injection of relaxin into the third ventricle, the onset of inhibition was immediate and more profound compared to injection into the lateral ventricle, after which there was a delay to the onset of inhibition. Relaxin was without effect when injected into the fourth ventricle or cisterna magna, thus suggesting that the site of action was within the diencephalon and the mesencephalon. Because these effects were reversed by naloxone, the central inhibitory action of relaxin appears to be mediated through endogenous opioid peptides.


Longitudinal Self-Management and/or Transition Readiness per the TRxANSITION Index among Patients with Chronic Conditions in Pediatric or Adult Care Settings.
To evaluate the roles of key individual, family, and illness characteristics on the levels of and gains in longitudinal healthcare transition (HCT) readiness in the pediatric setting and/or self-management skills (SMS) in the adult-focused setting, we used a large dataset with longitudinal measurements from 2006 to 2015. This longitudinal observational study followed 566 adolescents and young adults with chronic conditions at University of North Carolina Hospitals. TRxANSITION Index measurements, which represent learning outcomes rather than health outcomes, were collected multiple times per patient and analyzed using a novel application of an education-based approach. Levels of and gains in HCT/SMS scores increased with age (P < .001) with smaller increases at older ages. Mastery of skills varied by age with self-management achieved after 20 years of age. Scores varied positively by father's education and negatively by mother's education and duration of diagnosis. Gains in scores further varied positively with private insurance and negatively with mother's education and duration of diagnosis. We found diminishing positive increases in HCT/SMS scores as patients become older and smaller levels of and gains in readiness among younger patients with more educated mothers. Risk factors for absolute level of HCT/SMS readiness and inadequate longitudinal gains are not always the same, which motivates a deeper understanding of this dynamic process through additional research. This information can guide providers to focus HCT/SMS preparation efforts on skills mastered at particular ages and to identify patients at risk for inadequate development of HCT/SMS skills.


Video-ambulatory EEG in a secondary care center: A retrospective evaluation of utility in the diagnosis of epileptic and nonepileptic seizures.
The development and optimization of protocols using simultaneous video recording alongside long-term electroencephalography (EEG), such as ambulatory EEG (AEEG), expanded the range of available techniques for the investigation of paroxysmal clinical events. In particular, video-AEEG has received increasing attention over the last few years because of its potential to further improve diagnostic utility in the differential diagnosis between epileptic and nonepileptic seizures. We retrospectively evaluated 88 video-AEEG studies in order to assess the diagnostic utility of video-AEEG in 87 patients consecutively referred to a neurophysiology department. Typical clinical events occurred during 55 studies (62.5%). In 26 of these, at least one event was also clearly seen on video recording, contributing to a confident diagnosis. Clinical events were classified according to three diagnostic categories: epileptic seizures (6 studies, 6.8%), physiologic nonepileptic events (13 studies, 14.8%), or psychogenic nonepileptic seizures (36 studies, 40.9%). Of the studies with an event not recorded on video, a confident diagnosis could be reached in 55.2% of cases. The main reason for unsuccessful video recording was failure to activate the camcorder by the patient or carer. We found an overall diagnostic utility of 67.0%, which confirms the findings of previous reports evaluating the diagnostic yield of AEEG. Implementation of video-AEEG protocols in a secondary care center appears to have high diagnostic utility, particularly for patients with psychogenic nonepileptic seizures. Our findings prompt further research into the potential applications of video-AEEG, in consideration of important implications for successful patient management and healthcare resource allocation.


Chromatin modifications and chromatin remodeling during DNA repair in budding yeast.
Double-strand breaks (DSBs) pose a serious threat to genome integrity. Eukaryotes from yeast to humans respond to DSB damage by activating a complex DNA damage response that includes imposing a block to cell cycle progression and the repair of the DSB by one of several pathways. Many of these processes are accompanied by alterations in chromosome and chromatin structure. In this review we focus on the checkpoint responses and DNA repair in the well-studied model organism, the budding yeast Saccharomyces cerevisiae.


The variant associations of aortic isthmic coarctation.
The term "coarctation" necessarily calls attention to a specific morphologic abnormality of the aortic isthmus. However, in this report, the author seeks to dispel the simplistic notion that coarctation is best characterized by isthmic obstruction, which is only 1 of an assemblage of abnormalities that include the proximal paracoarctation aorta, the distal paracoarctation aorta, the ascending aorta, the transverse aorta, the coronary arteries, the conduit arteries (radial, brachial, and carotid), the retinal vascular bed, dissecting aneurysms, cerebral aneurysms, vascular rings, systemic hypertension, and a decrease in left ventricular interpapillary muscle distance. Some of these abnormalities are secondary to the coarctation, such as collateral arteries and dissecting aneurysms. Others frequently or invariably coexist but are not secondary, such as bicuspid aortic valve and aneurysm of the circle of Willis. Still other abnormalities are seemingly contradictory, such as aneurysmal dilatation of the low-pressure distal paracoarctation aorta, while the high-pressure proximal segment does not dilate significantly. In conclusion, coarctation should be regarded as an assemblage of cardiovascular abnormalities rather than as isolated obstruction of the aortic isthmus.


Relation of the maximum temperature and relative humidity close to the insemination with the tropical milking criollo heifer's gestation in three seasons.
The high climatic variability of hot climates of the intertropical zone reduces cattle fertility. In dairy cows in temperates zones, the THI has been used to evaluate the temperature and relative humidity (RH) joint effect in reproduction, but its use is not recommended in all geographic zones; in hot climates, the maximum temperature (Tmax) can provide more convenient information than THI. The objective of this study was to determine the artificial insemination (AI) service seasons and their joint effect with the maximum temperature and relative humidity of the previous seven days, the service day, and posterior seven days to the AI in the tropical milking criollo (LT) heifer's gestation. Climatic data was used to define three seasons: hot-dry (HD), hot-humid (HH), and fresh-dry (FD), and 313 artificial insemination services from 176 heifers were analyzed over fourteen years. The seasons were determined by cluster analysis. Gestation at first service (GF) was analyzed with a logistic regression model and global gestation (GG) with a mixed linear generalized model. The Tmax of previous seven days insemination [Formula: see text] - 0.20 ± 0.09 (p ≤ 0.02) in HD (p ≤ 0.02) and RH of seven days posterior insemination [Formula: see text]= - 0.08 ± 0.04 (p ≤ 0.04) in HD (p ≤ 0.01) affected GF. No effect of the Tmax and RH on the service day was observed (p > 0.05). The highest GG probabilities were higher than 0.70 in HH and FD, making those seasons the most suitable for inseminating LT heifers.


Stereoselective degradation and thyroid endocrine disruption of lambda-cyhalothrin in lizards (Eremias argus) following oral exposure.
The disturbance of the thyroid system and elimination of chiral pyrethroid pesticides with respect to enantioselectivity in reptiles have so far received limited attention by research. In this study, bioaccumulation, thyroid gland lesions, thyroid hormone levels, and hypothalamus-pituitary-thyroid axis-related gene expression in male Eremias argus were investigated after three weeks oral administration of lambda-cyhalothrin (LCT) enantiomers. In the lizard liver, the concentration of LCT was negatively correlated with the metabolite-3-phenoxybenzoic acid (PBA) level during 21 days of exposure. (+)-LCT exposure induced a higher thyroid follicular epithelium height than (-)-LCT exposure. The thyroxine levels were increased in both treated groups while only (+)-LCT exposure induced a significant change in the triiodothyronine (T3) level. In addition, the expressions of hypothalamus-pituitary-thyroid axis-related genes including thyroid hormone receptors (trs), deiodinases (dios), uridinediphosphate glucuronosyltransferase (udp), and sulfotransferase (sult) were up-regulated after exposure to the two enantiomers. (+)-LCT treatment resulted in higher expression of trs and (-)-LCT exposure led to greater stimulation of dios in the liver, which indicated PBA-induced antagonism on thyroid hormone receptors and LCT-induced disruption of thyroxine (T4) deiodination. The results suggest the (-)-LCT exposure causes higher residual level in lizard liver while induces less disruption on lizard thyroid activity than (+)-LCT.


Age-dependent brain morphometry in Major Depressive disorder.
Major depressive disorder (MDD) is a complex disorder that affects nearly 264 million people worldwide. Structural brain abnormalities in multiple neuroanatomical networks have been implicated in the etiology of MDD, but the degree to which MDD affects brain structure during early to late adulthood is unclear. We examined morphometry of brain regions commonly implicated in MDD, including the amygdala, hippocampus, anterior cingulate gyrus, lateral orbitofrontal gyrus, subgenual cortex, and insular cortex subregions, from early to late adulthood. Harmonized measures for gray matter (GM) volume and cortical thickness of each region were estimated cross-sectionally for 305 healthy controls (CTLs) and 247 individuals with MDD (MDDs), collated from four research cohorts. We modeled the nonlinear associations of age with GM volume and cortical thickness using generalized additive modeling and tested for age-dependent group differences. Overall, all investigated regions exhibited smaller GM volume and thinner cortical measures with increasing age. Compared to age matched CTLs, MDDs had thicker cortices and greater GM volume from early adulthood until early middle age (average 35 years), but thinner cortices and smaller GM volume during and after middle age in the lateral orbital gyrus and all insular subregions. Deviations of the MDD and CTL models for both GM volume and cortical thickness in these regions started as early as age 18. The analyses revealed that brain morphometry differences between MDDs and CTLs are dependent on age and brain region. The significant age-by-group interactions in the lateral orbital frontal gyrus and insular subregions make these regions potential targets for future longitudinal studies of MDD.


Complementary and Integrative Medicine and Eating Disorders in Youth: Traditional Yoga, Virtual Reality, Light Therapy, Neurofeedback, Acupuncture, Energy Psychology Techniques, Art Therapies, and Spirituality.
Eating disorders (EDs) are a non-heterogeneous group of illnesses with significant physical and mental comorbidity and mortality associated with maladaptive coping. With the exception of lisdexamfetamine (Vyvanse) for binge eating disorder, no medications have been effective for the core symptoms of ED. ED requires a multimodal approach. Complementary and integrative medicine (CIM) can be helpful as an adjunct. The most promising CIM interventions are traditional yoga, virtual reality, eye movement desensitization and reprocessing, Music Therapy, and biofeedback/neurofeedback.


Prediction of relevant biomedical documents: a human microbiome case study.
Retrieving relevant biomedical literature has become increasingly difficult due to the large volume and rapid growth of biomedical publication. A query to a biomedical retrieval system often retrieves hundreds of results. Since the searcher will not likely consider all of these documents, ranking the documents is important. Ranking by recency, as PubMed does, takes into account only one factor indicating potential relevance. This study explores the use of the searcher's relevance feedback judgments to support relevance ranking based on features more general than recency. It was found that the researcher's relevance judgments could be used to accurately predict the relevance of additional documents: both using tenfold cross-validation and by training on publications from 2008-2010 and testing on documents from 2011. This case study has shown the promise for relevance feedback to improve biomedical document retrieval. A researcher's judgments as to which initially retrieved documents are relevant, or not, can be leveraged to predict additional relevant documents.


Prevalence of hepatitis E virus infection in children in the northeast of Spain.
The prevalence of immunoglobulin G (IgG) anti-hepatitis E virus (anti-HEV) antibodies was studied with a representative sample of 1,249 healthy children aged between 6 and 15 years. IgG anti-HEV antibodies were detected in 57 (4.6%) of the 1,249 samples analyzed, suggesting that some children are exposed to HEV in early childhood.


Vivid memory for 'everyday' pains.
A 2-part study in which memory for everyday pains was investigated is reported. The first part compared ratings of vivid, 'flashbulb' memories of pain and non-pain events. Memories of pain events were rated as having been more surprising, having induced more negative emotional change, and having provoked greater change in ongoing activity than their non-pain event counterparts. In the second part of the study the relationship between remembering the pain event, experiencing the pain and re-experiencing the sensory qualities was examined. No subject reported sensory re-experiencing and 41% of subjects were unable to recall the sensory quality of the pain experience memory. Elements of pain experience (recalled intensity, distress and sensory quality) were differentially associated with components of pain event memory. Distress was associated with the reported frequency with which the pain event was rehearsed and with ratings of emotional and activity change induced by the pain event. In contrast, ratings of the intensity and sensory quality of the pain were associated with the reported vividness of the pain event memory. It is concluded that memories of painful events are readily retrievable and that the memory for a pain event, the sensory and affective qualities of pain experience and somatosensory component of pain are separated in their encoding and/or retrieval. The possible mechanisms whereby pain memories are encoded and retrieved are discussed. The clinical implications of the data concerning how judgements of past pain are made and the possible role of memory in coping are also noted.


Surface sampling capillary electrophoresis-mass spectrometry for a direct chemical characterization of tissue and blood samples.
Capillary electrophoresis (CE) is a powerful separation tool for non-targeted analysis of chemically complex samples, such as blood, urine, and tissue. However, traditionally CE requires samples in solution for analysis, which limits information on analyte distribution and heterogeneity in tissue. The recent development of surface sampling CE-mass spectrometry (SS-CE-MS) brings these advantages of CE to solid samples and enables chemical mapping directly from the tissue surface without laborious sample preparation. Here, we describe developments of SS-CE-MS to increase reproducibility and stability for metabolite, lipid, and protein extraction from tissue sections and dried blood spots. Additionally, we report the first electrokinetic sequential sample injection for high throughput analysis. We foresee that the wide molecular coverage from a distinct tissue region in combination with higher throughput will provide novel information on biological function and dysfunction.


Isolation and characterization of phage AHP-1 and its combined effect with chloramphenicol to control Aeromonas hydrophila.
To develop an alternative bio-control measure for multi-drug resistant pathogenic Aeromonas hydrophila, which causes motile Aeromonas septicemia in fish, novel virulent phage (AHP-1) was isolated from carp tissues. Morphological analysis by transmission electron microscopy revealed that AHP-1 belongs to Myoviridae family. AHP-1 displayed 81% of moderate adsorption by 25 min, and latent period of 40 min with burst size of 97 PFU mL-1 at an optimal multiplicity of infection (MOI) 0.1. AHP-1 was stable over a broad range of pH (4-11), temperature (4-50 °C), and salinity (0.1-3.5%). Both time and MOI dependent in vitro A. hydrophila growth inhibition was observed with AHP-1. AHP-1 (10 MOI) showed higher growth inhibition against A. hydrophila than chloramphenicol (5 μg mL-1), and combined treatment was more promising than individuals. Immune gene expression analysis of zebrafish upon continuous bath exposure to AHP-1 resulted significantly higher (il-6 and sod-1) or slight induction (tnf-α, il1-β, il-10, and cxcl-8a) than controls at beginning of the phage exposure, but those lowered to basal level by day 12 post-phage exposure. It suggests no adverse immune responses have occurred for the AHP-1 dose that used, and have potential for the phage therapy. Further detailed in vivo studies are needed to confirm the protective efficacy of newly isolated AHP-1 against A. hydrophila infection.


Natural course of tympanic membrane pathology related to otitis media and ventilation tubes between ages 8 and 18 years.
To present the course of tympanic membrane pathology in childhood and young adulthood after otitis media (OM) in early life. Prospective follow-up study. Community study of a birth cohort. Three hundred fifty-eight subjects with a positive and negative history of OM (OM+ or OM-) or ventilation tube insertion (VT+ or VT-) derived from a birth cohort that had been followed-up from preschool to adult age. Standardized otomicroscopic examination performed at ages 8 and 18 years. Tympanic membrane abnormalities (i.e., tympanosclerosis, atrophy, atelectasis and retraction pockets of the pars tensa, and retraction of the pars flaccida). At the age of 8 years, tympanic membrane pathology was highly prevalent in the both OM+ subcohorts (OM+VT+, 92% and OM+VT-, 46%), whereas in the OM- ears (11%), tympanic membrane abnormalities were rare. In the subsequent 10-year period, many tympanic membrane abnormalities disappeared spontaneously, although the prevalence of tympanosclerosis remained substantial in the OM+VT+ cohort. The natural course of most tympanic membrane pathology associated with OM in early life is favorable over time, suggesting an intrinsic repair capacity of the tympanic membrane. Tympanosclerosis, the most prevalent sequelae of OM and treatment with VT, however, shows little tendency of resolution.


Relative contribution of multi-source water recharge to riparian wetlands along the lower Yellow River.
Rivers play a vital role in both the formation and maintenance of riparian wetland hydrology. However, few studies have focused on the response of water recharge of riparian wetlands to altered hydrological processes induced by water-sediment regulation practices. To fill this gap, our study investigated the contribution of multi-source water recharge of riparian wetlands in the lower Yellow River, as well as its influence both during and before the water-sediment regulation scheme of Xiaolangdi Dam. Our study is based on hydrochemistry and isotopic methods, using a Bayesian mixing model and artificial neutral network model. The results showed that riparian wetlands were fed by mixed sources, including groundwater, canals, the Yellow River, and precipitation. However, seasonal evaporation introduced additional variation, which affected the relative contribution of these sources across seasons. Among these sources, the Yellow River served as the main water source for recharging riparian wetlands, and its contribution varied both spatially and temporally (across seasons). Specifically, proximity of riparian wetlands was the primary factor explaining spatial variation in the contribution of Yellow River, while climatic (12.38%) and hydrological variabilities (87.62%) explained seasonal variation. Among these climatic and hydrological variables, suspended sediment content was the most important factor-with a relative contribution of 36.33%. By determining the contribution of the Yellow River to the recharge of riparian wetlands, our study has provided information which is beneficial to adaptive management of river-fed riparian wetlands, especially under the implementation of water-sediment regulation practices.


Scaling Family Voices and Engagement to Measure and Improve Systems Performance and Whole Child Health: Progress and Lessons from the Child and Adolescent Health Measurement Initiative.
The 1997 legislation authorizing the United States Child Health Insurance Program sparked progress to measure and publicly report on children's healthcare services quality and system performance. To meet the moment, the national Child and Adolescent Health Measurement Initiative (CAHMI) public-private collaboration was launched to put families at the center of defining, measuring and using healthcare performance information to drive improved services quality and outcomes. Since 1996 the CAHMI followed an intentional path of collaborative action to (1) articulate shared goals for child health and advance a comprehensive, life-course and outcomes-based healthcare performance measurement and reporting framework; (2) collaborate with families, providers, payers and government agencies to specify, validate and support national, state and local use of dozens of framework aligned measures; (3) create novel public-facing digital data query, collection and reporting tools that liberate data findings for use by families, providers, advocates, policymakers, the media and researchers (Data Resource Center, Well Visit Planner); and (4) generate field building research and systems change agendas and frameworks (Prioritizing Possibilities, Engagement In Action) to catalyze prevention, flourishing and healing centered, trauma-informed, whole child and family engaged approaches, integrated systems and supportive financing and policies. Lessons call for a restored, sustainable family and community engaged measurement infrastructure, public activation campaigns, and undeterred federal, state and systems leadership that implement policies to incentivize, resource, measure and remove barriers to integrated systems of care that scale family engagement to equitably promote whole child, youth and family well-being. Population health requires effective family engagement.


Methanogenesis from acetate by cell-free extracts of the thermophilic acetotrophic methanogen Methanothrix thermophila CALS-1
High rates of methanogenesis from acetate and ATP were observed from cell-free extracts of the thermophilic acetotrophic methanogen Methanothrix (Methanosaeta) thermophila strain CALS-1 when cultures were grown in a pH auxostat fed with acetic acid. Specific methanogenic activities ranged from 50-300 nmol min-1 (mg protein)-1, which was comparable to those for whole cells. In contrast to results with Methanosarcina spp., the reaction did not require high levels of H2 in the headspace. CO was inhibitory to methanogenesis from acetate. The inhibition by CO and the lack of effect of H2 on methanogenesis from acetate resemble previous results with whole cells of CALS-1. Protein concentrations in extracts > 5 mg/ml were required for good activity, and the optimum temperature for the methanogenesis was near 65° C. ATP was required in substrate quantities and was converted mainly to AMP. The maximum CH4/ATP stoichiometry obtained was near 1.0, consistent with acetate activation using an acetyl-CoA synthetase mechanism that converts ATP to AMP and pyrophosphate. Methanogenesis in extracts was inhibited by bromoethane sulfonate and cyanide, indicating the involvement of methylcoenzyme M methylreductase and a carbon monoxide dehydrogenase complex with methanogenesis from acetate. These results are consistent with acetyl-coenzyme A (CoA) as the form of activated acetate involved in methanogenesis from acetate in strain CALS-1, but no activity could be obtained from extracts using acetyl-CoA as a substrate.


Two bivariate geometrically defined reference regions with applications to male reproductive hormones and human growth.
Two conceptually simple two-dimensional reference charts are described. The charts are characterized analytically, but also by geometric properties that are easily communicated to subject-matter researchers--the users of such charts. For both charts, the proposed estimators are non-parametric, so no distributional assumptions are needed about the two-dimensional response. An important example that will serve to motivate and illustrate one of the charts is the study of the human reproductive hormones Inhibin B and FSH. A low Inhibin B concentration combined with a high FSH concentration is an indication that something may be wrong in the seminal cells which produce semen, and such measurements help in the process of distinguishing between different reasons for infertility. The aim in the study of the human reproductive hormones was to give a two-dimensional reference curve for the non-normally distributed hormone measurements while taking into account that some measurements were left-censored because of a detection limit in the assay used to measure the concentrations.


Patterns and predictors of hand functional recovery following pediatric burn injuries: Prospective cohort study.
To describe the pattern of hand functional recovery in the first six months following the discharge of children with burn injury, and to identify the predictors affecting this recovery. This was a prospective, comparative, follow-up cohort study in which hand functional outcome, was assessed during 9 months follow-up on 37 children with burn injuries involving the upper extremity with total body service area (TBSA<35%). Thirty-six matched healthy children were participated to compare the differences between children with burn and healthy children regarding the hand functional outcome. Hand function assessments included total active motion (TAM), grip strength and Jebsen Hand Function Test (JHFT) were conducted at hospital discharge, 3, and 6 months follow-up after discharge. We found a trend towards an increase in the TAM scores over time (P<0.001), and were excellent in 5.41%, at discharge and increased to 18.92% and 40.54% at 3 and 6-month following discharge. The hand grip strength and JHFT showed significant improvement over time after 6 months (P<0.001). Regression analysis revealed that time to surgery, engagement in rehabilitation services, hand dominance, age and TBSA were the predictors of hand functional recovery and accounted 74% for TAM, 0.79 and 0.86 for total JHFT scores and grip strength. the TAM, grip strength and JHFT were significantly improved after 3-month and these improvements were more evident at 6-month following discharge. Identification of the predictors may help therapists in the development of an effective rehabilitation programs.


Metagenomic analysis reveals enhanced biodiversity and composting efficiency of lignocellulosic waste by thermoacidophilic effective microorganism (tEM).
Composting is a microbiological process that converts organic waste into organic soil amendment. We reveal enhanced biodiversity and microbial population with subsequent enhancement of composting efficiency of lignocellulosic waste using thermoacidophilic effective microorganisms (tEM). Composting with tEM + shading (tEMA) or tEM without shading (tEMB) increased the average microbial population by 12.0% or 6.7%, respectively compared to non-tEM composting without shading/control (C). The biodiversity in tEMA or tEMB treated groups was increased by 34.7% or 43.7%, respectively, compared to C. The highest increase in population (31.7% and 9.4%) and diversity (91.2% and 91.6%) were observed in tEMA and tEMB at 30 d, respectively. Regarding microbial structure, the most dominant phylum shifted from Proteobacteria to Bacteroidetes during composting. From 60 to 120 d, tEM notably improved the average abundance of Firmicutes (mainly Bacillus) by 166.7% and 75.8% in tEMA and tEMB groups, respectively. The overall gradation rate of large compost granules (<2 mm) increased by 36.4% and 24.7%, following tEMA and tEMB treatment, respectively. The average rate of increase in bulk density was 42.6% or 33.3% by tEMA or tEMB, respectively, compared to C. We reveal the major differences in microbial structure, including a higher abundance of beneficial microbes like Bacillus in tEM treated composts. The study revealed that tEM could improve biodiversity and population of microbes, especially during thermophilic phase (above 45 °C), with a subsequent increase in composting rate, mineralization, and product quality. The results of this study are particularly invaluable in the areas of environmental conservation and organic agriculture.


Binding specificity of monoclonal antibodies towards the size variants of human growth hormone.
The expression of antigenic determinants on size variants of human growth hormone (hGH) has been investigated using monoclonal antibodies of distinct combining-site specificity. Monomeric, dimeric, trimeric and polymeric (very high-molecular-weight) forms of hGH were separated by gel filtration on Sephadex G-100, and their antigenic potency was determined quantitatively by competition with 125I-labelled hGH for binding to each of four different monoclonal antibodies. With three of these antibodies the potencies of monomeric, dimeric and trimeric hGH were not significantly different, and the polymeric material was 11-13% as potent as the monomer. However, using one antibody (NA 71) the antigenic potencies of dimeric and trimeric hGH were lower (30-50%) than that of the monomer, and the polymeric material was only about 5% as potent as the monomer. These results suggest that the determinant with which antibody NA 71 interacts is close to the site of interaction between hGH monomers and apparently partially 'masked' in dimers, trimers and polymeric hGH.


Adenovirus infection associated with central nervous system dysfunction in children.
Adenovirus is a common pathogen in the pediatric population. No reports systemically evaluated central nervous system (CNS) dysfunction associated with adenovirus. To describe the detailed clinical features of adenovirus-associated CNS dysfunction in children. Of 3298 children with a throat virus culture positive for adenovirus treated at a university-affiliated hospital, from January 2000 to June 2008, in northern Taiwan, medical charts were retrospectively reviewed and those with CNS dysfunction were included. 109 (3.3%) children had signs or symptoms of CNS dysfunction on admission. The median age was 3.6 years and 81 (76%) were less than 5 years of age. 64 (59%) were male. The most frequently cited CNS symptoms were seizure (64%), altered state of consciousness (13%), visual hallucination (9.3%) and lethargy (7.5%). The most common diagnoses included febrile seizure (48%), encephalitis (26%), afebrile seizure (11%) and meningitis/meningismus (8.3%). 31 (46%) of 67 patients receiving electroencephalogram examination had abnormal findings and 13 (36%) of 36 with image studies had abnormal findings. Ninety-nine (91%) children returned to normal health, 7 (6.4%) had a sequel of seizure disorder, and 3 (2.7%) had major sequelae and none died. Nine serotypes were identified, with three major serotypes (types 3, 2 and 1). CNS dysfunction was identified in 3.3% of children with adenoviral infection and most occurred in those <5 years old. The clinical prognosis seemed well. However, CNS dysfunction is a potentially serious complication of adenovirus infection in children.


Leishmania mexicana cell death achieved by Cleoserrata serrata (Jacq.) Iltis: Learning from Maya healers.
Aerial parts of Cleoserrata serrata (Jacq.) Iltis are widely used in South-Central Mexico to treat wounds and bacterial skin infections and in Panama by Kuna, Ngöbe-Buglé, and Teribe Indians for tropical warm baths and by Kunas in the form of "Ina kuamakalet" for snakebites. To evaluate the effect of Cleoserrata serrata extract on growth and viability of L. mexicana amastigotes and promastigotes in vitro, as well as on bacteria that usually co-infect skin ulcers. Cleoserrata serrata was collected in La Chontalpa, Tabasco, Mexico. The antiproliferative effect of the extract was tested on growth of Leishmania mexicana amastigotes and promastigotes in vitro, as well as on bacteria that usually co-infect skin ulcers. Our data show that Cleoserrata serrata significantly inhibits parasite growth (which was more important in infective amastigotes) and additionally inhibits growth of the co-infective bacteria Staphylococcus aureus and Pseudomonas aeruginosa. Confocal microscopy showed a leishmanicidal effect. We conclude that Cleoserrata serrata extract is potentially an optimal treatment alternative for patients with cutaneous leishmaniasis infected with Leishmania mexicana, since it controls both the parasite as well as bacterial co-infections. Furthermore, it can be applied topically. The precise metabolites responsible for the anti-Leishmania and anti-bacterial effects remain to be established.


Thermodynamic Analysis and Optimization of a Novel Power-Water Cogeneration System for Waste Heat Recovery of Gas Turbine.
A power-water cogeneration system based on a supercritical carbon dioxide Brayton cycle (SCBC) and reverse osmosis (RO) unit is proposed and analyzed in this paper to recover the waste heat of a gas turbine. In order to improve the system performance, the power generated by SCBC is used to drive the RO unit and the waste heat of SCBC is used to preheat the feed seawater of the RO unit. In particular, a dual-stage cooler is employed to elevate the preheating temperature as much as possible. The proposed system is simulated and discussed based on the detailed thermodynamic models. According to the results of parametric analysis, the exergy efficiency of SCBC first increases and then decreases as the turbine inlet temperature and split ratio increase. The performance of the RO unit is improved as the preheating temperature rises. Finally, an optimal exergy efficiency of 52.88% can be achieved according to the single-objective optimization results.


Use of hormonal contraceptives in perimenopause: A systematic review.
Hormonal contraceptives have been used in perimenopausal women to manage a variety of symptoms and prevent unintended pregnancy. However, it is unclear what contraceptive regimen is best for these women. To evaluate hormonal contraceptive methods in women experiencing perimenopause using two prespecified outcomes: perimenopausal symptom management and long-term effects. A literature search of PubMed and EMBASE databases was performed (January 1990 to October 2021) using search terms "perimenopause" and "contraception." Relevant full-text articles in English were included. Fifteen clinical articles were reviewed: Fourteen were internationally based, and one study was conducted in the United States. Nine articles evaluated symptom resolution, and six of these nine reported statistically significant changes in favor of treating perimenopausal women with hormonal contraceptives compared with no treatment. Seven studies evaluated long-term outcomes including bone loss and metabolic parameters, and six of these seven showed statistically significant improvements with hormonal contraceptives. Based on limited data and a lack of comparative studies, the use of a levonorgestrel intrauterine device with supplemental low-dose menopausal estrogen has positive results for the management of disruptive perimenopausal symptoms and long-term outcomes. Hormonal contraception in perimenopausal women improves symptom management and long-term outcomes if patients do not have contraindications. When selecting a contraceptive for women in perimenopause, clinicians and pharmacists need to address specific patient risk factors, symptom profiles, long-term risks and benefits, and patient preferences.


Follow-up after radical cystectomy based on patterns of tumour recurrence and its risk factors.
Following cystectomy, approximately 50% of patients will present tumour recurrence. A recurrence may be local, systemic or occur in the urethra or upper urinary tract. To analyse the characteristics, risk factors and outcomes of patients with tumour recurrence following cystectomy so as to subsequently propose a cancer follow-up protocol. Analysis of original articles and reviews related to tumour recurrence and follow-up after radical cystectomy for urothelial tumour. Articles were obtained from Pubmed searches. Systemic and local recurrences following cystectomy appear in 20%-35% and 5%-15% of cases, respectively. Some 80%-90% are diagnosed in the first 3 years, with the majority concentrated in the first 24 months. Common factors related to an increased risk of local and systemic recurrence are a pathologic stage ≥pT3, the presence of positive margins and the extension of the lymphadenectomy. The incidence of recurrence in the upper urinary tract and urethra is 2%-6% and 4%-6%, respectively. Both types of recurrence may appear late and share risk factors such as signs of multifocal disease, a history of non-muscle-invasive bladder cancer, multiplicity, presence of ISC, urinary tract tumours and prostatic urethral tumours. Tumours in the distal ureteral cystectomy specimen and tumours in the prostatic urethra are also risk factors related to the appearance of tumours in the urinary tract and urethra, respectively. Understanding the natural history of urothelial bladder carcinoma and the risk factors related to the appearance of tumour recurrence following cystectomy are essential for designing an appropriate follow-up protocol. The follow-up of patients with risk factors for local or systemic recurrence will achieve maximum efficiency during the first 3 years. The follow-up should be extended for patients with risk factors for presenting upper urinary tract or urethral tumours.


Safe design and maintenance of bone marrow transplant units: a narrative review.
Patients undergoing bone marrow transplantation or chemotherapy for cancer are profoundly immunosuppressed. They are at risk for both endogenous and exogenous infections and require enhanced protection from infection while in hospital. The aim of this narrative review was to determine the optimal design features of bone marrow transplant (BMT) units for reducing infection risk in these vulnerable patients. A literature search was performed on PubMed and other databases for documents published between January 2000 and October 2021. Keywords were: bone marrow transplant unit OR hematopoietic stem cell transplant unit OR haematology unit OR haemato-oncology unit AND design OR design guidelines OR design criteria OR ventilation specification OR HEPA filtration OR water outbreaks OR water system design. Guidelines and other papers pertaining to BMT unit design are discussed. Key design features identified from the literature to reduce infection risks include high efficiency particulate air filtration, positive-pressure ventilation, sufficient air changes and sealed rooms. The evidence for each of these parameters and other findings are discussed. We found no guidelines specific to water quality and control in BMT units. Guidelines on the various components of design were found, but no comprehensive guidance documents addressing all relevant aspects, such as ventilation, water, and other design features, were found. Literary publications and policy documents were combined and summarised to highlight key design features aimed at reducing infection risk in this vulnerable patient group. We propose the development of international guidance for the design of BMT units encompassing all components.