Psychosocial and physical correlates of survival and recurrence in patients with head and neck carcinoma: results of a 6-year longitudinal study.
Studies that have examined correlations between psychosocial factors and survival in cancer patients do not permit any definitive conclusions. To the authors' knowledge, to date no study has examined the relation between medical as well as quality of life variables and survival in head and neck carcinoma patients. The current study focused on the complex interactions among psychosocial, medical, behavioral, and demographic variables as they relate to prognosis in these patients. A total of 133 consecutive head and neck carcinoma patients were included in a prospective study at pretreatment. In addition to clinical variables, psychosocial and physical functioning was assessed by means of a self-report questionnaire. During the observation period 57 patients died whereas 76 were still alive at 6 years after treatment. Results of the multivariate survival analysis indicated that patients without head and neck metastasis had a better prognosis than patients with positive cervical lymph nodes. Pretreatment smoking showed a negative correlation with overall survival. Patients who were more physically self-efficacious (i.e., higher perceived physical abilities) were more likely to survive and less likely to develop a recurrence. In addition, patients who expressed intense psychosocial complaints prior to treatment had a better prognosis than had those who did not express such negative feelings. The current findings linking physical self-efficacy and prognosis are promising, but clinical trials are necessary to examine the direct and indirect mediational pathways of the variables that underlie physical efficacy and influence survival and recurrence. Also, the negative correlation between pretreatment smoking and survival suggests a need for increased efforts to address smoking in newly diagnosed patients.


Characterization of GUCA1A-associated dominant cone/cone-rod dystrophy: low prevalence among Japanese patients with inherited retinal dystrophies.
GUCA1A gene variants are associated with autosomal dominant (AD) cone dystrophy (COD) and cone-rod dystrophy (CORD). GUCA1A-associated AD-COD/CORD has never been reported in the Japanese population. The purpose of this study was to investigate clinical and genetic features of GUCA1A-associated AD-COD/CORD from a large Japanese cohort. We identified 8 variants [c.C50_80del (p.E17VfsX22), c.T124A (p.F42I), c.C204G (p.D68E), c.C238A (p.L80I), c.T295A (p.Y99N), c.A296C (p.Y99S), c.C451T (p.L151F), and c.A551G (p.Q184R)] in 14 families from our whole exome sequencing database composed of 1385 patients with inherited retinal diseases (IRDs) from 1192 families. Three variants (p.Y99N, p.Y99S, and p.L151F), which are located on/around EF-hand domains 3 and 4, were confirmed as "pathogenic", whereas the other five variants, which did not co-segregate with IRDs, were considered "non-pathogenic". Ophthalmic findings of 9 patients from 3 families with the pathogenic variants showed central visual impairment from early to middle-age onset and progressive macular atrophy. Electroretinography revealed severely decreased or non-recordable cone responses, whereas rod responses were highly variable, ranging from nearly normal to non-recordable. Our results indicate that the three pathogenic variants, two of which were novel, underlie AD-COD/CORD with progressive retinal atrophy, and the prevalence (0.25%, 3/1192 families) of GUCA1A-associated IRDs may be low among Japanese patients.


Large-scale identification of genes important for apical growth in Saccharomyces cerevisiae by directed allele replacement technology (DART) screening.
In Saccharomyces cerevisiae, apical bud growth occurs for a brief period in G1 when the deposition of membrane and cell wall is restricted to the tip of the growing bud. To identify genes important for apical bud growth, we have utilized a novel transposon-based mutagenesis system termed DART (Directed Allele Replacement Technology) that allows the rapid transfer of defined insertion alleles into any strain background. A total of 4,810 insertion alleles affecting 1,392 different yeast genes were transferred into a cdc34-2 mutant strain that arrests in the apical growth phase when grown at the restrictive temperature of 37 degrees C. We identified 29 insertion alleles, containing mutations in 17 different genes ( SMY1, SPA2, PAN1, SLA1, SLA2, CBK1, SEC22, FAB1, VPS36, VID22, RAS2, ECM33, OPI3, API1/YDR372c, API2/YDR525w, API3/YKR020w, and API4/YNL051w), which alter the elongated bud morphology of cdc34-2 cells arrested in the apical growth phase. Upon treatment with mating pheromone at 25 degrees C, cells containing insertion alleles affecting ten of these genes ( SMY1, SPA2, PAN1, SLA1, SLA2, CBK1, FAB1, VPS36, VID22, and API2/YDR525w) form abnormal mating projections. Additionally, cells containing insertion alleles affecting SEC22, RAS2, API1/YDR372c, API3/YKR020w,and API4/YNL051display severe mating projection formation defects at the elevated temperature of 37 degrees C. DART mutagenesis has many advantages over traditional mutagenesis methods and will be a useful tool for dissecting gene networks important for biological processes.


Incomplete fractures associated with penetrating trauma: etiology, appearance, and natural history.
Patient charts and radiographs of 12 patients noted to have an incomplete fracture due to a penetrating injury were reviewed to evaluate the natural history of these fractures. One cortical chip fracture was due to a stab wound; the remainder were due to low-energy handguns. Morphologically, two patterns existed: drill hole fractures through the central metaphyseal region of long tubular bones, and divot fractures of the margins of long bone metaphyses and flat bones. Drill hole fractures and divot fractures complicated by fracture line extension required a weight bearing cast or functional brace while healing. The chip fracture and uncomplicated divot fractures were managed symptomatically. Chip, drill hole, and divot fractures followed a benign course and healed by formation of cortical bone along the defect rim.


Prognostic significance of QRS distortion and frontal QRS-T angle in patients with ST-elevation myocardial infarction.
QRS distortion (G3I) and frontal QRS-T angle (fQRS-T angle) are both electrocardiographic (ECG) signs of ongoing ischemia and depolarization-repolarization heterogeneity, which always occur in patients with ST-segment elevation acute myocardial infarction (STEMI). We retrospectively collected 592 STEMI patients who underwent coronary angiography and follow-up for 42 months. 1. We divided the patients into two groups according to whether they had G3I on admission, compared the differences in examination data and endpoint events between these two groups. 2. Group patients according to whether the endpoint events happened in hospital, at 12 and 42 months, compare whether there is a difference in fQRS-T angle at the same time point, and find out the predictive cutoff value of all-cause death. 3. Combined G3I and fQRS-T angle together to enhance the predictive value. G3I and fQRS-T angle are both independent risk factors for all-cause death in STEMI patients within 12 months (G3I P = 0.014, fQRS-T angle P < 0.001) and within 42 months (P < 0.001). The cutoff values of fQRS-T angle for predicting all-cause death are 66.5° at 12 months and 90.5° at 42 months. When G3I and fQRS-T angle are combined used to predict the mortality, the specificity is significantly improved, but the sensitivity decreased. G3I and fQRS-T angles are valuable in the prognostic assessment of STEMI patients, especially when combined. These findings help clinicians to identify high-risk patients early for more aggressive treatment.


Separation of malignant plasma cells from the bone marrow of patients with myelomatosis.
Complement-mediated lysis of bone marrow cells from patients with myelomatosis using a rabbit antiserum raised against normal peripheral blood mononuclear cells was found to greatly enrich the abnormal plasma cells. Cellular morphology was good and the cells were able to synthesize and secrete paraprotein. This was found to be a quick and useful method of preparing myeloma plasma cells for further studies of their metabolic properties.


Preparation of passive bilayer liposomes.
In studies of in-membrane molecular interactions, need may arise for a matrix that cannot itself interact, except hydrophobically, with the reactants. Such a bilayer matrix should, ideally, consist of only a hydrophobic zone without ionic outer layers and without hydrogen belts (the membrane strata containing CO and OH groups). However, because of the necessity of anchoring the bilayer to its aqueous surroundings, there must be polar substituents. Hydrophilic ether groups in the form of polyoxyethylenes can provide nearly sufficient anchoring and yet not confer unwanted reactivity to the membrane since they are only very weak H-bond acceptors. The stability of the bilayer is ensured by the presence of a few percent of an amphiphile (which may be the substrate to be studied, e.g. a phospholipid) or by a free polyethylene hydroxy group far remote from the original hydrogen belt region. Our most impermeable liposomes consisted of O-methylcholesterol/O-methoxyethoxyethoxyethylcholesterol; the most readily prepared liposomes were made from O-methylcholesterol and hydroxy(ethoxy)4dodecane (Brij 30) or Triton.


Strongyloides stercoralis mesenteric lymphadenopathy: clue to the etiopathogenesis of intestinal pseudo-obstruction in HIV-infected patients.
Mesenteric lymph node involvement in Strongyloides stercoralis hyperinfective states, described as an autopsy finding, remains a relatively poorly recognized and possibly underreported, antemortem phenomenon. Furthermore, the occurrence of S stercoralis mesenteric lymphadenopathy as a tocsin of bowel strongyloidiasis and the clue to the cause of intestinal pseudo-obstruction are undescribed. We report S stercoralis mesenteric lymphadenopathy and intestinal pseudo-obstruction in 5 HIV seropositive male patients, 21 to 42 years, who presented with abdominal pain and variable vomiting, diarrhea, and constipation. All were pale, pyrexial, and emaciated with abdominal distension. The preoperative diagnosis was intestinal obstruction. Poor clinical response on conservative therapy necessitated laparotomy. Dilated small bowel loops, ascites, and mesenteric lymphadenopathy were consistently noted; a diagnosis of pseudo-obstruction due to underlying tuberculosis or lymphoma was made. The mesenteric lymph nodes were biopsied. The pertinent nodal features were a dense infiltrate of eosinophils, eosinophil microabscesses and degranulation, a focal Splendore-Hoeppli phenomenon, and randomly disposed, but elusive, S stercoralis filariform larvae. Clinical deterioration confirmed intestinal complications at repeat laparotomy. Intestinal resections were performed in 4 patients; histopathologic appraisal confirmed intestinal strongyloidiasis. All patients died within 3 to 7 days after surgery. Heightened awareness of S stercoralis mesenteric lymphadenopathy as a sentinel of intestinal strongyloidiasis and etiopathogenetic clue of intestinal pseudo-obstruction may allow timely diagnosis and medical treatment and avoidance of further surgery, potentially reducing the long-term morbidity associated with S stercoralis hyperinfection.


Polymers and Composites Derived from Castor Oil as Sustainable Materials and Degradable Biomaterials: Current Status and Emerging Trends.
Recent years have seen rapid growth in utilizing vegetable oils to derive a wide variety of polymers to replace petroleum-based polymers for minimizing environmental impact. Nonedible castor oil (CO) can be extracted from castor plants that grow easily, even in an arid land. CO is a promising source for developing several polymers such as polyurethanes, polyesters, polyamides, and epoxy-polymers. Several synthesis routes have been developed, and distinct properties of polymers have been studied for industrial applications. Furthermore, fillers and fibers, including nanomaterials, have been incorporated in these polymers for enhancing their physical, thermal, and mechanical properties. This review highlights the development of CO-based polymers and their composites with attractive properties for industrial and biomedical applications. Recent advancements in CO-based polymers and their composites are presented along with a discussion on future opportunities for further developments in diverse applications.


Hierarchically organized behavior and its neural foundations: a reinforcement learning perspective.
Research on human and animal behavior has long emphasized its hierarchical structure-the divisibility of ongoing behavior into discrete tasks, which are comprised of subtask sequences, which in turn are built of simple actions. The hierarchical structure of behavior has also been of enduring interest within neuroscience, where it has been widely considered to reflect prefrontal cortical functions. In this paper, we reexamine behavioral hierarchy and its neural substrates from the point of view of recent developments in computational reinforcement learning. Specifically, we consider a set of approaches known collectively as hierarchical reinforcement learning, which extend the reinforcement learning paradigm by allowing the learning agent to aggregate actions into reusable subroutines or skills. A close look at the components of hierarchical reinforcement learning suggests how they might map onto neural structures, in particular regions within the dorsolateral and orbital prefrontal cortex. It also suggests specific ways in which hierarchical reinforcement learning might provide a complement to existing psychological models of hierarchically structured behavior. A particularly important question that hierarchical reinforcement learning brings to the fore is that of how learning identifies new action routines that are likely to provide useful building blocks in solving a wide range of future problems. Here and at many other points, hierarchical reinforcement learning offers an appealing framework for investigating the computational and neural underpinnings of hierarchically structured behavior.


Closing the gap between electron and X-ray crystallography.
The development of a proper refinement algorithm that takes into account dynamical scattering guarantees, for electron crystallography, results approaching X-rays in terms of precision, accuracy and reliability. The combination of such dynamical refinement and electron diffraction tomography establishes a complete pathway for the structure characterization of single sub-micrometric crystals.


The effect of the experimental antitumor agent caracemide on brain choline acetyltransferase.
Caracemide was found to inhibit choline acetyltransferase (CAT) from rat brain. A concentration of 0.5 mM caracemide inhibited the enzyme by 93%, whereas a degradation product from caracemide, N-(methylcarbamoyloxy)acetamide, produced only a 50% inhibition. Two other degradation products, N-(methyl-carbamoyloxy)-N'-methylurea and N-hydroxy-N'-methylurea, lacked any inhibitory activity. With bovine brain CAT, caracemide showed noncompetitive inhibition with the substrate choline, Km 337 microM, Ki240 microM, Vmax 2.83 nmol acetylcholine formed/min/mg protein and mixed inhibition with the substrate acetyl-CoA, Km 21 microM, Ki 146 microM, Vmax 3.85 nmol acetylcholine formed/min/mg protein.


Association between vasoactive-inotropic score and mortality in pediatric septic shock.
To assess the association between Vasoactive Inotrope Score (vis) and mortality in children with fluid-refractory septic shock. A retrospective chart review of 71 children (age 1 mo-16y) admitted with fluid-refractory septic shock in pediatric intensive care unit during a two year period was done. We divided our cohort into two groups viz High vasoactive inotrope score (Group-H) and Low-vasoactive inotrope score (Group-L) based on a cut-off value of 20. 73% of the children were in Group-L. The mortality rate was 44% and 100% in Group L and Group H, respectively. High inotropic score in children with septic shock is associated with high mortality rate.


Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as melena with long-term survival: A case report and review of literature.
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary intestinal T-cell lymphoma, previously known as enteropathy-associated T-cell lymphoma type II. MEITL is an aggressive T-cell lymphoma with a poor prognosis and high mortality rate. The known major complications of MEITL are intestinal perforation and obstruction. Here, we present a case of MEITL that was diagnosed following upper gastrointestinal bleeding from an ulcerative duodenal lesion, with recurrence-free survival for 5 years. A 68-year-old female was admitted to our hospital with melena and mild anemia. An urgent esophagogastroduodenoscopy (EGD) revealed bleeding from an ulcerative lesion in the transverse part of the duodenum, for which hemostatic treatment was performed. MEITL was diagnosed following repeated biopsies of the lesion, and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy was administered. She achieved complete remission after eight full cycles of CHOP therapy. At the last follow-up examination, EGD revealed a scarred ulcer and 18Fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography showed no abnormal FDG accumulation. The patient has been in complete remission for 68 mo after initial diagnosis. To rule out MEITL, it is important to carefully perform histological examination when bleeding from a duodenal ulcer is observed.


Reversal of insulin-induced negative cooperativity by monoclonal antibodies that stabilize the slowly dissociating ("Ksuper") state of the insulin receptor.
Two monoclonal antibodies to the insulin receptor, MA-5 and MA-20, unlike other monoclonal antibodies, do not mimick the accelerating effect of insulin on the dissociation of 125I-insulin from the receptors (negative cooperativity). On the contrary, MA-5 and MA-20 markedly slow down the dissociation rate. We show now that MA-5 and MA-20 are potent antagonists of the negative cooperativity induced by insulin, and reverse the insulin-induced acceleration whether added simultaneously with insulin or after insulin. The reversal of the insulin-induced acceleration is almost immediate. These data strengthen the concept therefore that the insulin-receptor complex has access to alternative conformational states that can be stabilized by ligand-induced site-site interactions.


Isolation of model soluble immune complexes in the fluid phase by monoclonal anti-IgG-ferritin antibodies.
Ferritin conjugates of monoclonal IgG anti-human gamma chain (anti-IgG-F) were reacted with soluble heat aggregates of IgG (A-IgG) and with soluble DNA-anti-DNA complexes to increase the S rate of the model soluble immune complexes (ICx) and thus facilitate isolation of ICx in the fluid phase and provide an immunochemical marker for subsequent ultrastructural analysis. A-IgG appeared as globular or curvilinear structures with individual IgG molecules arranged in a random fashion. The technique appears promising for characterization of other soluble ICx.


Prognostic Performance of Right Ventricular Global Longitudinal Strain Measurements in Patients With Ebstein Anomaly.
There are limited data on the prognostic role of right ventricular global longitudinal strain (RVGLS) in patients with Ebstein anomaly. This study sought to assess the relationship between RVGLS and mortality and to compare prognostic performance of RVGLS with conventional echocardiographic indices of right ventricular (RV) systolic function. This study identified adults with Ebstein anomaly with echocardiographic assessment of RV systolic function (RVGLS, RV fractional area change [RVFAC], RV tissue Doppler systolic velocity [RV s'], and tricuspid annular plane systolic excursion [TAPSE]) from 2003 to 2020. For ease of presentation, RVGLS was modeled as absolute values (ie, without the negative sign). Of 620 patients (median age 37 years; men 261 [42%]), the mean absolute RVGLS, RVFAC, RV s', and TAPSE were 18% ± 5%, 32% ± 9%, 14 ± 6 cm/s, and 22 ± 8 mm, respectively. There were correlations between absolute RVGLS and RVFAC (r = 0.71; P < 0.001), between absolute RVGLS and RV s' (r = 0.41; P = 0.03), and between absolute RVGLS and TAPSE (r = 0.44; P = 0.002). Of 620 patients, 47 (8%) died during follow-up, and 34 of these deaths were cardiovascular. Absolute RVGLS was independently associated with all-cause mortality (adjusted HR: 0.94; 95% CI: 0.92-0.96 per unit increase) and cardiovascular mortality (adjusted HR: 0.92; 95% CI: 0.90-0.94 per unit increase). Absolute RVGLS had superior prognostic power (ie, ability to predict mortality) as compared with RVFAC, RV s', or TAPSE. These data support the use of RVGLS for risk stratification in Ebstein anomaly, and further studies are required to assess how interventions may affect different patients according to risk stratification.


The febrile morbidity score as a predictor of febrile morbidity following cesarean section.
The study comprised 150 women delivered by cesarean section. Each patient was given a score of 0, 1 or 2 for each of the following risk factors; parity, body weight, hemoglobin level, duration of labor and duration of rupture of membranes. No antibiotics were given before, during or after the operation. Postoperatively, the cases were observed for the occurrence of febrile morbidity. It was found that out of the 150 cases, 60 (40%) developed febrile morbidity. The minimal threshold score of these patients was found to be 5. No case in the afebrile group (90 cases) had this score. Also, the mean febrile morbidity score (FMS) of the morbid cases was 6.37 +/- 0.87 compared with 3.16 +/- 0.78 among the nonmorbid cases (P less than 0.001). The febrile morbidity score is valuable in predicting the occurrence of febrile morbidity following cesarean section.


Advantages of using a mercury coated, micro-wire, electrode in adsorptive cathodic stripping voltammetry.
A mercury coated, gold, micro-wire electrode is used here for the determination of iron in seawater by catalytic cathodic stripping voltammetry (CSV) with a limit of detection of 0.1 nM Fe at a 60s adsorption time. It was found that the electrode surface is stable for extended periods of analyses (at least five days) and that it is reactivated by briefly (2s) applying a negative potential prior to each scan. Advantages of this electrode over mercury drop electrodes are that metallic mercury use is eliminated and that it can be readily used for flow analysis. This is demonstrated here by the determination of iron in seawater by continuous flow analysis. It is likely that this method can be extended to other elements. Experiments using bismuth coated, carbon fibre, electrodes showed that the bismuth catalyses the oxidation of the important oxidants bromate and hydrogen peroxide, which makes it impossible to use bismuth based electrodes for catalytic CSV involving these oxidants. For this reason mercury coated electrodes retain a major advantage for catalytic voltammetric analyses.


The influence of perceived stress and musculoskeletal pain on work performance and work ability in Swedish health care workers.
To evaluate the influence of perceived stress and musculoskeletal ache/pain, separately and in combination, at baseline, on self-rated work ability and work performance at two-year follow-up. Survey data were collected with a 2-year interval. Health care workers participating at both waves were included. Inclusion criteria were good self-reported work ability and unchanged self-rated work performance at baseline, resulting in 770 participants; 617 women and 153 men. Musculoskeletal pain was assessed using the question "How often do you experience pain in joints and muscles, including the neck and low back?", perceived stress with a modified version of a single item from the QPS-Nordic questionnaire, work performance by the question "Have your work performance changed during the preceding 12 months?" and work ability by a single item from the work ability index. Associations between baseline data and the two outcomes at follow-up were analysed by means of the log binomial model and expressed as risk ratios (RR) with 95% confidence intervals (CI). A combination of frequent musculoskeletal pain and perceived stress constituted the highest risk for reporting decreased work performance (RR 1.7; CI 1.28-2.32) and reduced work ability (RR 1.7; CI 1.27-2.30) at follow-up. Separately, frequent pain, but not stress, was clearly associated with both outcomes. The results imply that proactive workplace interventions in order to maintain high work performance and good work ability should include measures to promote musculoskeletal well-being for the employees and measures, both individual and organizational, to minimize the risk of persistent stress reactions.


Insulin and neurodegenerative disease: shared and specific mechanisms.
Insulin has functions in the brain and dysregulation of these functions may contribute to the expression of late-life neurodegenerative disease. We provide a brief summary of research on the influence of insulin on normal brain function. We then review evidence that perturbation of this role may contribute to the symptoms and pathogenesis of various neurodegenerative disorders, such as Alzheimer's disease, vascular dementia, Parkinson's disease, and Huntington's disease. We conclude by considering whether insulin dysregulation contributes to neurodegenerative disorders through disease-specific or general mechanisms.


Heterogeneity of the osteocyte lacuno-canalicular network architecture and material characteristics across different tissue types in healing bone.
Various tissue types, including fibrous connective tissue, bone marrow, cartilage, woven and lamellar bone, coexist in healing bone. Similar to most bone tissue type, healing bone contains a lacuno-canalicular network (LCN) housing osteocytes. These cells are known to orchestrate bone remodeling in healthy bone by sensing mechanical strains and translating them into biochemical signals. The structure of the LCN is hypothesized to influence mineralization processes. Hence, the aim of the present study was to visualize and match spatial variations in the LCN topology with mineral characteristics, within and at the interfaces of the different tissue types that comprise healing bone. We applied a correlative multi-method approach to visualize the LCN architecture and quantify mineral particle size and orientation within healing femoral bone in a mouse osteotomy model (26 weeks old C57BL/6 mice). This approach revealed structural differences across several length scales during endochondral ossification within the following regions: calcified cartilage, bony callus, cortical bone and a transition zone between the cortical and callus region analyzed 21 days after the osteotomy. In this transition zone, we observed a continuous convergence of mineral characteristics and osteocyte lacunae shape as well as discontinuities in the lacunae volume and LCN connectivity. The bony callus exhibits a 34% higher lacunae number density and 40% larger lacunar volume compared to cortical bone. The presented correlations between LCN architecture and mineral characteristics improves our understanding of how bone develops during healing and may indicate a contribution of osteocytes to bone (re)modeling.


[Experimental induced pancreatic carcinoma after choledochojejunostomy (author's transl)].
The pancreatic carcinogen DHPN (dihydroxypropylnitrosamin) was administered to Syrian golden hamsters. By intragastric administration more pancreatic carcinomas in the head of the gland were induced than by subcutaneous injections. After choledochojejunostomy the incidence of carcinomas was only 5--7% and the lesions were similar in multiplicity and distribution without relationship to the way of administration. The importance of biliary reflux in pancreatic tumor induction is discussed and the role of bile concerning the preferred localisation of the tumors in the head of the pancreas.


The combination of IL-21 and IFN-alpha boosts STAT3 activation, cytotoxicity and experimental tumor therapy.
For decades cytokines such as type I interferons and IL-2 have been used in immunotherapy against cancer, viral hepatitis, and autoimmune diseases such as multiple sclerosis. However, the therapeutic use of cytokines has been hampered by their pleiotropic effects on target-cells. Thus, cytokines such as IFN-alpha and IL-2 have multiple and severe side effects. Accordingly, they are generally used at sub-optimal doses, which limit their clinical efficacy. Here we hypothesized that a combination of IFN-alpha and IL-21, a novel cytokine of the IL-2 family with anti-cancer effects, will increase the anti-cancer efficacy at sub-optimal cytokine doses. We show that the combined stimulation of target-cells with IFN-alpha and IL-21 triggers an increased STAT3 activation whereas the activation of other STATs including STAT1/2 is unaffected. In parallel, the combined stimulation with IFN-alpha and IL-21 triggers a selective increase in MHC class I expression and NK- and CD8(+) T-cell-mediated cytotoxicity. In an experimental in vivo model of renal carcinoma, the combined treatment of IFN-alpha and IL-21 also produces a significant anti-cancer effect as judged by an inhibition of tumor growth and an increased survival. Taken together our data show that the combined use of IFN-alpha and IL-21 boosts STAT3 signaling, cytotoxicity, and anti-tumor efficacy, suggesting that a combinatorial therapeutic use of these cytokines may benefit cancer patients.


Arthroscopic repair of posterior instability and reverse humeral glenohumeral ligament avulsion lesions.
Posterior glenohumeral subluxation is not as uncommon as once believed. Unidirectional instability as a result of a traumatic event or the primary direction of multidirectional instability as a result of overuse can lead to recurrent involuntary subluxations. Failure of the posterior restraints can occur at the glenoid labral attachment, mid-capsule, and laterally, as in a RHAGL avulsion. Soft tissue reattachment to bone is by way of suture anchors. This may occur at the glenoid medially or laterally along the humeral head insertion (RHAGL lesion). Capsular plication and superior shift can obliterate the capsular pouch. Additional labral lesions superiorly and anteriorly are repaired to centralize the humeral head and reduce the possibility of subcoracoid and subacromial impingement. Recurrence rates are reduced with symmetric repairs that address multiple lesions that are not always seen with a unidirectional open approach. Capsular tears, detachments, and the rotator capsular interval are reduced with minimal alterations in range of motion. Immobilization is combined with intermittent range of motion exercises. Protective scapular and rotator strengthening is a prerequisite before return to strenuous activities. Surgical repair followed by a well monitored rehabilitation protocol can return most individuals back to sport and vocation.


Rotavirus activates MLKL-mediated host cellular necroptosis concomitantly with apoptosis to facilitate dissemination of viral progeny.
Reprogramming the host cellular environment is an obligatory facet of viral pathogens to foster their replication and perpetuation. One of such reprogramming events is the dynamic cross-talk between viruses and host cellular death signaling pathways. Rotaviruses (RVs) have been reported to develop multiple mechanisms to induce apoptotic programmed cell death for maximizing viral spread and pathogenicity. However, the importance of non-apoptotic programmed death events has remained elusive in context of RV infection. Here, we report that RV-induced apoptosis accompanies another non-apoptotic mode of programmed cell death pathway called necroptosis to promote host cellular demise at late phase of infection. Phosphorylation of mixed lineage kinase domain-like (MLKL) protein indicative of necroptosis was observed to concur with caspase-cleavage (apoptotic marker) beyond 6 hr of RV infection. Subsequent studies demonstrated phosphorylated-MLKL to oligomerize and to translocate to plasma membrane in RV infected cells, resulting in loss of plasma membrane integrity and release of alarmin molecules e.g., high mobility group box protein 1 (HMGB1) in the extracellular media. Moreover, inhibiting caspase-cleavage and apoptosis could not fully rescue virus-induced cell death but rather potentiated the necroptotic trigger. Interestingly, preventing both apoptosis and necroptosis by small molecules significantly rescued virus-induced host cytopathy by inhibiting viral dissemination.


Knockdown of TTC9 inhibits the proliferation, migration and invasion, but induces the apoptosis of lung adenocarcinoma cells.
Lung adenocarcinoma (LUAD) is one of the most commonly diagnosed subtypes of lung cancer, and one of the deadliest cancers. Tetratricopeptide repeat domain 9A (TTC9) is upregulated and has played an oncogenic role in some malignant tumors. However, the expression and role of TTC9 has not yet been elucidated in LUAD. Here, we investigated the expression profiles, biological functions and potential molecular mechanism of the TTC9 gene in LUAD. TTC9 expression was significantly overexpressed in LUAD tissues compared with that in normal lung tissues. TTC9 expression was closely correlated with gender, lymph node metastasis, and survival status in the TCGA-LUAD cohort. Subsequent cellular function assays demonstrated that knockdown of TTC9 promoted PC9 cell apoptosis and inhibited cell proliferation, migration and invasion, leading to cell cycle arrest in G2 phase. Moreover, inhibition of TTC9 suppressed the tumorigenicity of PC9 cells in nude mice. TTC9 might serve as oncogene in LUAD through cancer-related signaling pathways including p38 MAPK pathway. The expression of TTC9 gene might be modulated by DNA copy number variant and DNA methylation. TTC9 was significantly associated with tumor immune infiltration patterns. Accordingly, TTC9 may be a novel therapeutic target for the treatment of LUAD.


Antibody- and aptamer-free SERS substrate for ultrasensitive and anti-interference detection of SARS-CoV-2 spike protein in untreated saliva.
Sensitive and anti-interference detection of targeted signal(s) in body fluids is one of the paramount tasks in biosensing. Overcoming the complication and high cost of antibody/aptamer-modification, surface-enhanced Raman spectroscopy (SERS) based on antibody/aptamer-free (AAF) substrates has shown great promise, yet with rather limited detection sensitivity. Herein, we report ultrasensitive and anti-interference detection of SARS-CoV-2 spike protein in untreated saliva by an AAF SERS substrate, applying the evanescent field induced by the high-order waveguide modes of well-defined nanorods for SERS for the first time. A detection limit of 3.6 × 10-17 M and 1.6 × 10-16 M are obtained in phosphate buffered saline and untreated saliva, respectively; the detection limits are three orders of magnitude improved than the best records from AAF substrates. This work unlocks an exciting path to design AAF SERS substrates for ultrasensitive biosensing, not limited to detection of viral antigens.


Correction: A Web-Based Prostate Cancer-Specific Holistic Needs Assessment (CHAT-P): Multimethod Study From Concept to Clinical Practice.
[This corrects the article DOI: 10.2196/32153.].


Using patient perspectives to inform communication training materials for health care professionals discussing BRCA mutation testing.
As demand for genetic testing grows and a wide range of health care professionals (HCPs) are potentially involved in discussions about testing and delivering results, we developed an educational package to help HCPs with these conversations. To inform the content of training materials, we conducted interviews with 11 women four of whom had BRCA1 and seven with BRCA2 mutations. Five women had or were currently receiving breast cancer treatment. Ages ranged from 38 to 77 years. Interviews were audio-recorded, transcribed verbatim and analysed using the Framework approach to thematic analysis. We identified 18 themes and 12 subthemes across the interviews, encompassed by six overarching themes: risk, decision-making, information and understanding, communication and improvement, accessing the system: process and frustration, emotional and social drivers. The findings informed the didactic components of an educational communication workshop and a summary document for attendees. Qualitative interviews provide an important way of incorporating the patient perspective into communication training materials for HCPs by highlighting key issues that matter most to the patient.


Surgical History and Outcomes in Trisomy 13 and 18: A Thirty-year Review.
Patients with Trisomy 13(T13) and 18(T18) have many comorbidities that may require surgical intervention. However, surgical care and outcomes are not well described, making patient selection and family counseling difficult. Here the surgical history and outcomes of T13/ T18 patients are explored. A retrospective review of patients with T13 or T18 born between 1990 and 2020 and cared for at a tertiary children's hospital (Riley Hospital for Children, Indianapolis IN) was conducted, excluding those with insufficient records. Primary outcomes of interest were rates of mortality overall and after surgery. Factors that could predict mortality outcomes were also assessed. One-hundred-seventeen patients were included, with 65% T18 and 35% T13. More than half of patients(65%) had four or more comorbidities. Most deaths occurred by three months at median 42.0 days. Variants of classic trisomies (mosaicism, translocation, partial duplication; p = 0.001), higher birth weight(p = 0.002), and higher gestational age(p = 0.01) were associated with lower overall mortality, while cardiac(p = 0.002) disease was associated with higher mortality. Over half(n = 64) underwent surgery at median age 65 days at time of first procedure. The most common surgical procedures were general surgical. Median survival times were longer in surgical rather than nonsurgical patients(p<0.001). Variant trisomy genetics(p = 0.002) was associated with lower mortality after surgery, while general surgical comorbidities(p = 0.02), particularly tracheoesophageal fistula/esophageal atresia(p = 0.02), were associated with increased mortality after surgery. Trisomy 13 and 18 patients have vast surgical needs. Variant trisomy was associated with lower mortality after surgery while general surgical comorbidities were associated with increased mortality after surgery. Those who survived to undergo surgery survived longer overall. III.


Treatment of saline wastewater by a sequencing batch reactor with emphasis on aerobic granule formation.
The formation and characteristics of aerobic granules in a sequencing batch reactor (SBR), designed to treat saline wastewater, have been investigated in this study. Granule structure was determined using scanning electron microscope (SEM), and polymerase chain reaction (PCR). Granules formed in the reactors were grouped into light brown granules and black granules that looked 'fluffy'. The first group was more dense than the second group and consequently had a higher settling velocity. The densities of the first and the second group were 0.056 and 0.035 g/ml, respectively. While the corresponding settling velocity were 1.35 and 0.97 cm/s, respectively. The kinetic coefficients K(s), k(d), k and Y in saline substrate (10 g NaCl/l) were estimated to be 195 mg s COD/l, 0.025 g VSS/g VSS d, 2.29 g s COD/g VSS d and 0.45 mg VSS/mg s COD, respectively. Analysis of granules using 16S rDNA sequences showed that the dominant microbial species was Klebsiella oxitoca. Minerals and the protozoan community in saline substrate facilitated the formation of granules. It was concluded that the fluffy granules are a variation of the light brown granules which are resistant to salt.


False claims of victimization: a historical illustration of a contemporary problem.
In this article, a false claim of victimization made by a man in his late 20s during a 17th-century outbreak of mass allegations of Satanic abuse is described and discussed in relation to contemporary issues with relevance to psychiatry and applied mental health.


Decreased microsomal triglyceride transfer protein activity contributes to initiation of alcoholic liver steatosis in rats.
To elucidate the role of microsomal triglyceride transfer protein (MTP) in the pathogenesis of alcoholic fatty liver, the effects of ethanol on MTP activity and gene expression were investigated. Male Sprague-Dawley rats fed an ethanol-containing liquid diet for 37 days, respectively, showed 2.9- and 4.9-fold increases in hepatic cholesterol and triglyceride content in comparison with rats fed an isocaloric ethanol-free diet (P<0.01). Furthermore, a significant decrease in MTP activity and mRNA expression (by 27 and 58%, respectively) was observed after ethanol administration. Intravenous injection of human recombinant hepatocyte growth factor (hrHGF) on each of the last 7 days markedly suppressed ethanol-induced lipid accumulation in the liver. This inhibition of fatty change by hrHGF was accompanied by recovery of MTP activity and gene expression. No inhibitory effect of hrHGF on ethanol-induced acyl-CoA synthetase activation was observed. Experiments using human hepatoma-derived HepG2 cells indicated a direct positive effect of hrHGF on MTP gene expression as well as apolipoprotein B secretion. These results suggest that reduced MTP activity is crucial to development of alcoholic fatty liver, while promotion of MTP activity by HGF might serve as a therapeutic measure against alcoholic liver steatosis.


Ameliorating effect of polyherbal formulation (Febrojith) on acute and chronic inflammatory model via inhibiting inflammation and oxidative stress.
Inflammation is a complex biological response of the tissue to noxious stimuli, which causes several debilitating inflammatory disorders. Currently, various conventional medicines are available, but their consumption causes adverse effects, hence researchers focused on alternatives like medical herbs from natural sources, as one of the most promising sources of therapeutic agents for inflammation. Febrojith is a well-known traditional Ayurvedic formulation obtained from the treasures of Ayurveda with a unique blend of herbs that are used effectively in preventing and combating a broad spectrum of infections, fevers, and also enhancing immunity for many years. However, its anti-inflammatory, efficacy and underlying mechanism remained unexplored. In the present study, we investigated the chemical characterization and in vivo anti-inflammatory efficacy of Febrojith (FB) on acute and chronic inflammatory models via inhibiting inflammation and oxidative stress. FB was analyzed for chemical characterization & its phytoconstituents by UV-Vis spectrum, FT-IR, and GC-MS analysis. The anti-inflammatory activity of FB was studied on carrageenan-induced acute and adjuvant-induced chronic experimental models. The inflammatory cytokines and mediators were measured using the ELISA & Colorimetry techniques. Histopathology and cytology of paw tissue and synovium were analyzed by H&E and Papanicolau's (PAP)-staining methods. 100 mg/kg bwt was found to be a potent dose from the carrageenan model and evaluated its effect in the adjuvant-induced chronic arthritic model. In the chronic model, 84% of edema inhibition was observed at the dose of 100 mg/kg bwt. Moreover, the supplementation of FB was shown to significantly (p ≤ 0.05) decrease the TBARS level and activity of myeloperoxidase in the paw tissue. In addition, adjuvant-induced production of various pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, PGE2, NO and COX-2 were suppressed in inflamed rats subjected to FB supplementation. It also revealed that FB supplementation significantly (p ≤ 0.05) reduced the haematological markers. From the histopathology and cytological analysis, we found a reduction in the edema formation, and infiltration of inflammatory cells after the supplementation of FB. In conclusion, FB might be used as an effective and potent drug against inflammation.


Effect of 1 H-NMR serum lipoproteins on immunotherapy response in advanced triple-negative breast cancer patients.
We previously reported the results of a phase II trial of anti-PD-1 antibody plus anti-vascular endothelial growth factor receptor 2 inhibitors and eribulin in heavily pretreated advanced triple-negative breast cancer with a favorable objective response rate (ORR) of 37.0% (NCT04303741). Here we report updated survival outcomes and serum metabolite changes of the study. Proton nuclear magnetic resonance spectroscopy was used to detect metabolite dynamics and explore biomarkers for response. We found that treatment-sensitive patients had higher very low-density lipoprotein-related metabolite expression at baseline. A lipid proteomics model consisting of six metabolites predicted ORR and progression-free survival at 6 months with area under the receiver operating characteristic curves of 0.88 and 0.87, respectively. Serum asparagine and sarcosine concentrations were significantly higher after treatment in treatment-resistant patients. In conclusion, we constructed a model consisting of six metabolites to identify patients who benefit more from the triplet treatment, and asparagine and sarcosine may be associated with treatment resistance.


Occurrence, ecological risk assessment, and spatio-temporal variation of polychlorinated biphenyls (PCBs) in water and sediments along River Ravi and its northern tributaries, Pakistan.
Ecological risk assessment, spatio-temporal variation, and source apportionment of polychlorinated biphenyls (PCBs) were studied in surface sediments and water from River Ravi and its three northern tributaries (Nullah Deg, Nullah Basantar, and Nullah Bein) in Pakistan. In total, 35 PCB congeners were analyzed along 27 sampling stations in pre-monsoon and post-monsoon seasons. The ∑35PCB concentration ranged from 1.06 to 95.76 ng/g (dw) in sediments and 1.94 to 11.66 ng/L in water samples, with hexa-CBs and tetra-CBs as most dominant homologs in sediments and water matrixes, respectively. The ∑8DL-PCB levels were 0.33-22.13 ng/g (dw) and 0.16-1.95 ng/L in sediments and water samples, respectively. The WHO-toxic equivalent values were ranged from 1.18 × 10-6 to 0.012 ng/L and 1.8 × 10-6 to 0.031 ng/g in water and sediments matrixes, respectively. The ecological risk assessment indicates considerable potential ecological risk during pre-monsoon season ([Formula: see text] = 95.17) and moderate potential ecological risk during post-monsoon season ([Formula: see text] = 49.11). The industrial and urban releases were recognized as key ongoing sources for high PCB levels in environment. Therefore, we recommend more freshwater ecological studies to be conducted in the study area and firm regulatory initiatives are required to be taken in debt to the Stockholm Convention, 2001 to cop up with PCB contamination on emergency basis.


Flow diversion for posterior circulation aneurysms: a multicenter retrospective study.
The prevalence of intracranial aneurysms is approximately 3% worldwide. Posterior circulation (PC) aneurysms have a higher risk of treatment complications than anterior circulation aneurysms. Improving the survival rate and quality of life of patients with PC aneurysms remains one of the most important issues in the field. Flow diverter (FD) treatment of PC aneurysms remains controversial. We aimed to investigate the effects of FD treatment and analyze differences among different application methods or aneurysm types in PC aneurysms. This is a multicenter retrospective study. Patients with PC aneurysms treated with the pipeline embolization device (PED) or Tubridge embolization device (TED) between 2015 and 2020 in five neurovascular centers were retrospectively enrolled. The primary outcomes were major perioperative complication, clinical outcome, and aneurysm occlusion rates. Univariable and multivariable logistic regression analyses were used to determine the risk factors of each outcome. In total, 252 aneurysms were included. Major perioperative complication, favorable clinical outcome, and complete occlusion rates were 7.5%, 91.0%, and 79.1%, respectively. Compared with other types of aneurysms, dissecting aneurysms had the best clinical outcome and highest occlusion rate. Both clinical and angiographic outcomes were independently associated with the aneurysm location at the basilar artery. Aneurysm size was not associated with any outcome. TED had similar clinical and angiographic outcomes compared with PED but more perioperative major complications. Tandem treatment and coiling assistance may have poorer clinical outcomes but similar occlusion rates. Single- and multiple-stent treatments had similar outcomes. FD treatment of PC aneurysms achieved favorable clinical outcomes and long-term aneurysm occlusion rates with acceptable perioperative complication rates, especially in dissecting and non-basilar artery aneurysms. There was no additional improvement in outcomes with coiling assistance, multi-stent application, or tandem treatment. Therefore, the use of PC aneurysms should be carefully considered.


5-Hydroxymethylcytosine: generation, fate, and genomic distribution.
5-Methylcytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) in mammalian cells by the ten-eleven translocation (Tet) family of dioxygenases. While 5mC has been extensively studied, we have just started to understand the distribution and function of 5hmC in mammalian genomes. Despite the fact that this new epigenetic mark has only been discovered three years ago, exciting progress has been made in understanding its generation, fate, and genomic distribution. In this review we discuss these progresses as well as the recent advance in the single-base resolution mapping of 5hmC.


Ciliary neurotrophic factor-immunoreactivity in olfactory sensory neurons.
Ciliary neurotrophic factor (CNTF) has been implicated in processes of neuroprotection, axonal regeneration and synaptogenesis in the lesioned CNS. In the olfactory system, which is characterized by particularly robust neuroplasticity throughout life, the concentration of CNTF is high even under physiological conditions. In the present study, the cellular localization of CNTF-immunoreactivity was studied in the rat and mouse olfactory epithelium. In both species, individual olfactory sensory neurons (ONs) displayed intense CNTF-immunoreactivity. The number of CNTF-ir ONs varied interindividually in rats and was lower in mice than in rats. In olfactory epithelia of mice expressing beta-galactosidase under control of the CNTF promoter, cells of the ON layer were immunoreactive for the reporter protein. CNTF-ir ONs were olfactory marker protein-positive and growth associated protein 43-negative. CNTF-ir ONs lacked apoptotic markers, and the number of specifically labeled ONs was apparently unchanged after light chemical lesioning of the epithelium, indicating that CNTF-immunoreactivity was not associated with ON death. Electron microscopy of CNTF-ir ON axons in innervated olfactory bulb glomeruli documented that they formed typical ON axonal synapses with target neurons. Three dimensional reconstructions of bulb pairs showed a striking similarity of the positions of glomeruli innervated by CNTF-ir ON axons in left and right bulbs of individual animals and interindividually. The number of innervated glomeruli differed interindividually in rats and was lower in mice than in rats. The results show that in rodents CNTF-immunoreactivity occurs in a subset of mature, functionally competent ONs. The localization of target glomeruli suggests that CNTF-immunoreactivity may be associated with the expression and/or activation of specific olfactory receptor proteins.


A framework to estimate the environmentally attainable intake of dairy cows in constraining environments.
Most intake models for dairy cows have been developed to make predictions under normal conditions, in which animals can meet their nutritional requirements. To estimate intake under constraining conditions, i.e. when intake is defined by the environment and not by the animal's requirements, it is necessary to develop models that take into account environmentally driven effects. The aim of this work was to develop a framework to represent the links between environmental variables (food quality and quantity, as well as ambient temperature, season, and farm type) and intake. The framework integrates time as the major constraint on intake and proposes the environmentally attainable intake (EAI) as the product of the Eating Rate (ER) and the Eating Time (ET). ER is the maximum sustainable rate (gr DM/min) at which animals bite the food, and ET is the daily time (min/d) that animals have to eat. The architecture of the framework is easily extensible to add constraints such as predation pressure, reproductive costs, competition, parasitism, or diseases. Data from grazing and indoor dairy farms were used to test the usability of the framework. The results show that a time use-based framework is a reliable approach to estimate intake considering environmental variables with minimum use of animals' characteristics. In conclusion, a high-level framework of feeding behaviour, that captures the main underlying mechanisms of intake in constrained environments, can be used to predict the EAI and the effects of the environment on animal performance.


Individual Hearing Outcomes in Cochlear Implant Users Influence Social Engagement and Listening Behavior in Everyday Life.
The goal of this study was to assess the listening behavior and social engagement of cochlear implant (CI) users and normal-hearing (NH) adults in daily life and relate these actions to objective hearing outcomes. Ecological momentary assessments (EMAs) collected using a smartphone app were used to probe patterns of listening behavior in CI users and age-matched NH adults to detect differences in social engagement and listening behavior in daily life. Participants completed very short surveys every 2 hr to provide snapshots of typical, everyday listening and socializing, as well as longer, reflective surveys at the end of the day to assess listening strategies and coping behavior. Speech perception testing, with accompanying ratings of task difficulty, was also performed in a lab setting to uncover possible correlations between objective and subjective listening behavior. Comparisons between speech intelligibility testing and EMA responses showed poorer performing CI users spending more time at home and less time conversing with others than higher performing CI users and their NH peers. Perception of listening difficulty was also very different for CI users and NH listeners, with CI users reporting little difficulty despite poor speech perception performance. However, both CI users and NH listeners spent most of their time in listening environments they considered "not difficult." CI users also reported using several compensatory listening strategies, such as visual cues, whereas NH listeners did not. Overall, the data indicate systematic differences between how individual CI users and NH adults navigate and manipulate listening and social environments in everyday life.


A low-cost robotic hand prosthesis with apparent haptic sense controlled by electroencephalographic signals.
One of the biggest problems faced by amputees is obtaining a suitable low-cost prosthesis. To address this problem, the design and implementation of a transradial prosthesis controlled by electroencephalographic (EEG) signals was carried out. This prosthesis is an alternative to prostheses using electromyographic (EMG) signals, which are very complex and exhausting for the patient to execute. We collected EEG signal data using the Emotiv Insight Headset, which were then processed to control the movement of the prosthesis, known as the Zero Arm. Additionally, we incorporated Machine Learning algorithms to classify different types of objects and shapes. The prosthesis also features a haptic feedback system, which simulates the function of mechanoreceptors in the skin, providing the user with a sense of touch when using the prosthesis. Our research has yielded a viable and cost-effective prosthetic limb. We utilized 3D printing and easily obtainable servomotors and controllers, making the prosthesis affordable and accessible. Performance tests of the Zero Arm prosthesis have yielded promising results. The prosthesis demonstrated an average success rate of 86.67% across various tasks, indicating its reliability and effectiveness. Additionally, the prosthesis has an average recognition rate of 70% for different types of objects, a noteworthy accomplishment.


Impact of diabetes status and related factors on COVID-19-associated hospitalization: A nationwide retrospective cohort study of 116,370 adults with SARS-CoV-2 infection.
We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D. We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection. In 116,370 adults (>=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased risk for hospitalization included diabetes, male sex, public health insurance, decreased body mass index (BMI; <25.0-29.9 kg/m2), increased BMI (>25.0-29.9 kg/m2), vitamin D deficiency/insufficiency, and Elixhauser comorbidity score. After further adjustment for concurrent hyperglycemia and acidosis in those with diabetes, hospitalization risk was substantially higher in T1D than T2D and in those with low vitamin D and elevated hemoglobin A1c (HbA1c). The higher hospitalization risk in T1D versus T2D warrants further investigation. Modifiable risk factors such as vitamin D deficiency/insufficiency, BMI, and elevated HbA1c may serve as prognostic indicators for COVID-19-related hospitalization in adults with diabetes.


Lower 3H-imipramine binding in platelets from untreated depressed patients compared to healthy controls.
3H-Imipramine binding in platelets was measured in 63 severely depressed hospitalized patients, who had been drug free (with the exception of moderate doses of benzodiazepines) for at least 1 month, and in 53 healthy control subjects of comparable age and sex distribution. Bmax of 3H-imipramine binding was significantly lower in the depressed subjects (1012 +/- SD 295 vs. 1123 +/- SD 178 fmole/mg protein). Depressed patients who had attempted suicide by violent means tended to have higher Bmax than nonviolent attempters.


Anemia is associated with severe illness in COVID-19: A retrospective cohort study.
Anemia commonly aggravates the severity of respiratory diseases, whereas thus far, few studies have elucidated the impact of anemia on coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the clinical characteristics of patients with anemia, and to further explore the relationship between anemia and the severity of COVID-19. In this single-center, retrospective, observational study, a total of 222 confirmed patients admitted to Wuhan Ninth Hospital from 1 December 2019 to 20 March 2020 were recruited, including 79 patients with anemia and 143 patients without anemia. Clinical characteristics, laboratory findings, disease progression and prognosis were collected and analyzed. Risk factors associated with the severe illness in COVID-19 were established by univariable and multivariable logistic regression models. In our cohort, compared to patients without anemia, patients with anemia were more likely to have one or more comorbidities and severe COVID-19 illness. More patients demonstrated elevated levels of C-reactive protein (CRP), procalcitonin (PCT) and creatinine in anemia group. Levels of erythrocyte sedimentation rate, D-dimer, myoglobin, T-pro brain natriuretic peptide (T-pro-BNP) and urea nitrogen in patients with anemia were significantly higher than those without. In addition, the proportion of patients with dyspnea, elevated CRP, and PCT was positively associated with the severity of anemia. The odd ratio of anemia related to the severe condition of COVID-19 was 3.47 (95% confidence interval [CI]: 1.02-11.75; P = .046) and 3.77 (95% CI: 1.33-10.71; P = .013) after adjustment for baseline date and laboratory indices, respectively. Anemia is an independent risk factor associated with the severe illness of COVID-19, and healthcare professionals should be more sensitive to the hemoglobin levels of COVID-19 patients on admission. Awareness of anemia as a risk factor for COVID-19 was of great significance.


Canine mast cell tumors.
Mast cell tumors (MCTs) are common in the dog, occurring most frequently in the skin and subcutaneous tissues. Their biologic behavior can be quite variable, with approximately 50% being malignant. Although clinical features and histologic grading can help determine the likelihood of malignancy, it is difficult to predict the biologic behavior of an individual tumor. Consequently, all MCTs should be considered potentially malignant. Wide surgical excision is the most common therapy for canine MCTs, although approximately 50% recur locally. Nonresectable or recurrent MCTs can be treated with radiation and/or chemotherapy. Chemotherapy is also used in the treatment of metastatic MCTs, and it may be helpful in preventing the recurrence and/or metastasis of undifferentiated tumors.


Transport of Molecular Cargo by Interaction with Virus-Like Particle RNA.
Virus-like particles (VLPs) derived from Leviviridae virions contain substantial amounts of cellular and plasmid-derived RNA. This encapsidated polynucleotide serves as a reservoir for the efficient binding of the intercalating dye thiazole orange (TO). Polyethylene glycol (PEG) molecules and oligopeptides of varying length, end-functionalized with TO, were loaded into VLPs up to approximately 50 % of the mass of the capsid protein (hundreds to thousands of cargo molecules per particle, depending on size). The kinetics of TO-PEG binding included a significant entropic cost for the reptation of long chains through the capsid pores. Cargo molecules were released over periods of 20-120 hours following simple reversible first-order kinetics in most cases. These observations define a simple general method for the noncovalent packaging, and subsequent release, of functional molecules inside nucleoprotein nanocages in a manner independent of modifications to the capsid protein.


Real-World Safety and Clinical Outcomes of Macitentan in Asian Patients with Pulmonary Arterial Hypertension: A Prospective Multicenter Study.
Macitentan is approved for treating pulmonary arterial hypertension. However, the real-world evidence of macitentan use is limited. Therefore, we evaluated the safety and clinical outcomes of macitentan use in clinical practice under a post-marketing surveillance. Patients with pulmonary arterial hypertension receiving macitentan treatment were prospectively and consecutively enrolled from 2014 to 2020 at 50 medical centers in Korea. Safety and clinical outcomes were monitored from baseline to the nearest timepoint of 24 weeks after macitentan initiation. The adverse events and adverse drug reactions were identified. Changes in the World Health Organization functional class were assessed as the primary clinical outcome, which was used to estimate the final effectiveness (both improved and maintained). Factors associated with safety and final effectiveness were identified. Among 474 patients enrolled in the study, 467 and 440 were included in the safety and clinical outcome analyses, respectively. Dyspnea, nasopharyngitis, and worsening pulmonary arterial hypertension were the most frequent adverse events with incidences of 5%, 3%, and 3%, respectively. The final effectiveness rate was 93%. Older age (adjusted odds ratio [aOR] = 1.021, p = 0.003) and higher level (III vs II) of baseline World Health Organization functional class (aOR = 1.784; p = 0.022) were significantly associated with a higher adverse event occurrence. Younger age (aOR = 0.947; p = 0.001) and shorter disease duration (aOR = 0.991; p = 0.010) were significantly associated with positive final effectiveness. This real-world study demonstrated the safety and clinical outcomes of macitentan use in Korean patients with pulmonary arterial hypertension. Macitentan was well tolerated and significantly effective with no new safety concerns during the 24 weeks.


Improvement of Methods for Safety Control of Microbial Producers and Food Produced Therewith.
The study substantiates the necessity to implement the algorithm of molecular-genetic assessment of biosafety of the genetically modified microorganisms (GMM) and to develop standardized methods to test the genetically modified strains producing enzymes, bioactive substances, and other products of microbial synthesis prior to their use in food industry. Analysis of microbial producers and related food products for the presence of GMM-associated DNA revealed high incidence of the marker genes amp and lacZ in enzyme preparations and in mycelium of industrial genetically modified producer of Aspergillus genus. The procedure of extraction of DNA from mycelium of mold fungi is optimized by including the stage of additional purification of the extracts, assessment of their purity by PCR with universal ITS primers, and determination of effective DNA concentration in the samples prior to conduction of the molecular genetic assay. For identification and genotyping of mold fungi (the biotechnological producers of enzyme preparations), the Sanger sequencing method was adapted. Using this modified method, we determined the species of five equivocally identified strains of Aspergillus genus. To identify the closely-related micromycetes of Ascomycota division, a genotyping algorithm was developed based on amplification of total DNA with expanded panel of primers and DNA sequencing by capillary electrophoresis.


The Application of Mixed Reality to Sentinel Lymph Node Biopsy in Breast Cancer.
To explore the value of mixed reality (MR) in sentinel lymph node biopsy (SLNB) in patients with breast cancer. A total of 300 patients with breast cancer who underwent SLNB enrolled and were randomly divided into two groups. In group A, only dye (an injection of methylene blue) was used to detect sentinel lymph nodes, while in group B MR was used for positioning in addition to dye. (MR localization method: Before the surgery, we built a 1:1 3D reconstruction model based on the patient's CT or MRI original data, and after the patient was injected with dye, we completed MR localization by overlapping the pre-marked image with the model.) RESULTS: During surgery, the detection time in group B was significantly shorter than in group A (3.62 ± 1.20 vs.7.87 ± 1.86; p < 0.001). At 1-month post-surgery follow-up, the incidence of pain in group B was lower than that in group A (2.70 vs. 8.28%, p = 0.036). The incidence of upper limb dysfunction was lower in group B than in group A (2.03 vs. 8.97%, p = 0.009). In terms of the incidence of pain, group B was better than group A (0.68 vs. 3.45%, p = 0.094). The satisfaction of the two groups was scored, and the results showed that group B was better than group A (4.04 ± 0.91 vs.3.32 ± 0.94, p < 0.001). The application of MR to SLNB in breast cancer can significantly reduce the detection time and the occurrence of complications and improve patient satisfaction.


Peptidase specificity from the substrate cleavage collection in the MEROPS database and a tool to measure cleavage site conservation.
One peptidase can usually be distinguished from another biochemically by its action on proteins, peptides and synthetic substrates. Since 1996, the MEROPS database (http://merops.sanger.ac.uk) has accumulated a collection of cleavages in substrates that now amounts to 66,615 cleavages. The total number of peptidases for which at least one cleavage is known is 1700 out of a total of 2457 different peptidases. This paper describes how the cleavages are obtained from the scientific literature, how they are annotated and how cleavages in peptides and proteins are cross-referenced to entries in the UniProt protein sequence database. The specificity profiles of 556 peptidases are shown for which ten or more substrate cleavages are known. However, it has been proposed that at least 40 cleavages in disparate proteins are required for specificity analysis to be meaningful, and only 163 peptidases (6.6%) fulfil this criterion. Also described are the various displays shown on the website to aid with the understanding of peptidase specificity, which are derived from the substrate cleavage collection. These displays include a logo, distribution matrix, and tables to summarize which amino acids or groups of amino acids are acceptable (or not acceptable) in each substrate binding pocket. For each protein substrate, there is a display to show how it is processed and degraded. Also described are tools on the website to help with the assessment of the physiological relevance of cleavages in a substrate. These tools rely on the hypothesis that a cleavage site that is conserved in orthologues is likely to be physiologically relevant, and alignments of substrate protein sequences are made utilizing the UniRef50 database, in which in each entry sequences are 50% or more identical. Conservation in this case means substitutions are permitted only if the amino acid is known to occupy the same substrate binding pocket from at least one other substrate cleaved by the same peptidase.


Tranexamic acid in primary total knee arthroplasty without tourniquet: a randomized, controlled trial of oral versus intravenous versus topical administration.
Abundant literature confirms that intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) reduces blood loss in total knee arthroplasty (TKA). Oral formulations of TXA exhibit profound cost-saving benefits. However, comparisons of the clinical efficacy among three different modalities of TXA administration have not been previously investigated in the setting of TKA with no closed suction drain and tourniquet. A total of 180 patients undergoing TKA were randomized to receive 2-g oral TXA 2 hours preoperatively, 20-mg/kg IV TXA 5 minutes prior to incision, or 2-g IA TXA. The primary outcome was 72-hour blood loss. Secondary outcomes were reductions in hemoglobin, the rate of transfusions, and adverse events. No significant differences were identified with regard to the mean 72-hour blood loss among the three groups (1003 mL in oral group, 1108 mL in IV group, and 1059 mL in IA group, respectively). Similarly, hemoglobin reduction was equivalent among the groups. Only one patient in IV group exhibited deep venous thrombosis. No difference was identified regarding transfusion rates. Oral TXA results in similar blood loss in TKA, with a profound cost-saving benefit, compared with the IA and IV formulations.


The geographical assignment of cancer units: patient accessibility as an optimal allocation problem.
The seminal report A Policy Framework for Commissioning Cancer Services provides the foundation for a major reorganisation of cancer service provision in England and Wales. One central recommendation of the report, the establishment of a tier of specialised cancer units in each Health Authority Region has raised the fundamental question of where those units are to be located. In particular, a declared objective of the report is for services to be planned to maximise their accessibility to patients. This paper demonstrates a classical method (location-allocation modelling) by which the accessibility criterion can be used to determine the optimal number, location and capacity of units for a given cancer site. The method is illustrated with reference to cervical cancer in Trent Health Authority Region. The implications of the method for the guidance of access-related decisions on the placement of cancer services are considered, and the wider relevance of the method to the organisation of service provision in other branches of medicine is suggested.


Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas.
Lung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC), which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient's prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK) factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. SGK1 is the most represented SGK member. By means of immunohistochemistry and quantitative real-time PCR, we determined SGK1 protein and mRNA expression in a cohort of 66 formalin-fixed, paraffin-embedded NSCLC surgical samples. All samples belonged to patients with a well-documented clinical history. mRNA expression was significantly higher in squamous cell carcinomas, and correlated with several clinical prognostic indicators, being elevated in high-grade tumors and in tumors with bigger size and worse clinical stage. No correlation was found between SGK1 protein expression and these clinical parameters. This explorative analysis of SGK1 expression in NSCLC samples highlights the potential role of this factor in NSCLC patients' prognosis. Moreover, the higher expression in the squamous cell carcinoma subtype opens new therapeutic possibilities in this NSCLC subtype by designing specific kinase inhibitors.


Physical state of water controls friction of gabbro-built faults.
Earthquakes often occur along faults in the presence of hot, pressurized water. Here we exploit a new experimental device to study friction in gabbro faults with water in vapor, liquid and supercritical states (water temperature and pressure up to 400 °C and 30 MPa, respectively). The experimental faults are sheared over slip velocities from 1 μm/s to 100 mm/s and slip distances up to 3 m (seismic deformation conditions). Here, we show with water in the vapor state, fault friction decreases with increasing slip distance and velocity. However, when water is in the liquid or supercritical state, friction decreases with slip distance, regardless of slip velocity. We propose that the formation of weak minerals, the chemical bonding properties of water and (elasto)hydrodynamic lubrication may explain the weakening behavior of the experimental faults. In nature, the transition of water from liquid or supercritical to vapor state can cause an abrupt increase in fault friction that can stop or delay the nucleation phase of an earthquake.


Dosimetric advantages and superior treatment delivery efficiency of RapidArc over conventional intensity-modulated radiotherapy in high-risk prostate cancer involving seminal vesicles and pelvic nodes.
To compare the dosimetry and treatment delivery efficiency of RapidArc with conventional intensity-modulated radiotherapy (IMRT) in the treatment of high-risk prostate cancer. Fifteen patients with high-risk localised prostate cancer were studied. Sequential treatment was used. The initial planning target volume (PTV-L) included the prostate, seminal vesicles and pelvic lymphatics, whereas the prostate boost PTV (PTV-P) included the prostate and seminal vesicles only. The total prescription dose was 76 Gy (44 Gy to PTV-L, 32 Gy to PTV-P; 2 Gy/fraction). Two separate planning techniques were generated for each patient: seven static-field IMRT versus two-arc RapidArc. Dose-volume parameters for the organs at risk, conformity index and homogeneity index for the PTVs, the calculated monitor units and treatment delivery time for both techniques were compared. RapidArc gave more conformal plans than IMRT for both PTVs. RapidArc gave a higher homogeneity index to the PTV-P and a similar homogeneity index to the PTV-L. The two techniques gave similar dosimetric results for the rectum, bladder and femoral heads. The mean dose (Dmean) and the maximum dose (Dmax) of the bowel space were reduced by 3.06 and 2.83%, respectively, with RapidArc. The V20 Gy, V30 Gy and V40 Gy for healthy tissues were reduced by 7.77, 14.25 and 17.55%, respectively, with RapidArc. The calculated treatment delivery time and monitor units were reduced by 74.09%/60.93% and 68.32%/48.06% for the PTV-L/PTV-P, respectively, with RapidArc. RapidArc is better than conventional IMRT in terms of dosimetry and delivery efficiency for high-risk prostate cancer.


Guidance on infection control and plume management with Laser and Energy-Based Devices taking into consideration COVID-19.
The COVID-19 pandemic has disrupted the practice of medicine. Dermatologic laser and energy-based device (EBD) treatments carry a potential risk for the transmission of SARS-CoV-2 both for the patient and the practitioner. These risks include close practitioner to patient proximity, the treatment of higher viral load areas such as the face, the potential for infective bioparticles being carried by generated plumes and aerosols, and the direct contact between device, practitioner and patient. SARS-CoV-2 is a highly infective respiratory pathogen transmitted by respiratory droplets, respiratory/mucosal secretions, medically generated aerosols and via its transfer from contaminated fomites. This requires a review of the appropriateness of infection control protocols in regard to dermatologic laser and energy-based device treatments. A critical evaluation of patient skin preparation including skin asepsis, device disinfection, laser and electrosurgical plume management and PPE in regard to SARS-CoV-2 was performed. The adherence to a high standard of skin preparation and asepsis, device disinfection, laser and electrosurgical plume and aerosol management and appropriate PPE should help mitigate or reduce some of the inherent treatment risks. Head and neck treatments along with aerosol and laser plume generating treatments likely carry greater risk. COVID-19 needs to be considered in the clinic set-up along with the planning, treatment and post-treatment care of patients utilising EBD procedures. Some of these treatment precautions are COVID-19 specific; however, most represent adherence to good infectious disease and established laser and EBD safety precautions.


Enantiomeric purity of naproxen by liquid chromatographic analysis of its diastereomeric octyl esters.
A sensitive and specific analytical method was developed to determine the enantiomeric purity of naproxen. A simple derivatization of naproxen with (S)-(+)-2-octanol proceeded quantitatively and gave a mixture of diastereomeric esters displaying baseline separation on liquid chromatography. The ratio of these esters was the same as the ratio of enantiomers present in naproxen samples assayed. Reproducibility of the method was excellent.


Quality of working life of cancer survivors: development of a cancer-specific questionnaire.
The aim of this study was to generate, and select quality of working life issues for the development of an initial version of the Quality of Working Life Questionnaire for Cancer Survivors (QWLQ-CS). Quality of working life issues were generated through focus groups with cancer survivors and oncological occupational physicians, and interviews with employers, supervisors, and organization officers. A selection of these quality of working life issues was made based on relevance and importance by conducting an online questionnaire among the cancer survivors and oncological occupational physicians. Researchers formulated the issues into items for the QWLQ-CS. A total of 24 cancer survivors, six oncological occupational physicians and 11 employers, supervisors, and organization officers participated. The 222 quality of working life issues identified through the focus groups, interviews, and literature were converted into an online questionnaire. Cancer survivors (N = 20) found 44 issues not relevant or important with respect to their quality of working life. The researchers reviewed the remaining 178 issues and formulated them into 102 items classified by five categories: work perception, job characteristics, the social structure and environment, organizational characteristics, and the effect of the disease and treatment. The initial version of the QWLQ-CS exists out of 102 items which cover the experiences and perceptions of cancer survivors in the work environment. All items were indicated by working cancer survivors as relevant and important. This initial version of the QWLQ-CS may increase awareness of the potential problems or emotional difficulties working cancer survivors face during the work continuation process.


The aging of Gomori's aldehyde-fuchsin: the nature of the chemical changes and the chemical structures of the coloured components.
The chemical nature of Gomori's aldehyde-fuchsin (GAF) prepared by the method of Mowry et al. (1980) was studied by monitoring the staining characteristics and various chemical properties of ripening GAF solutions. Hydrophilic-hydrophobic characteristics were assessed by reverse-phase thin-layer chromatography; overall molecular sizes, and also the sizes of the conjugated systems, were investigated using hydrophobic gel-filtration. Other properties monitored included the nuclear magnetic resonance and visible spectra, the apparent pH, and the amount of precipitation. It was concluded that for GAF prepared by the Mowry et al. procedure: i. The purple, strongly staining components arising in the first few days of aging are Schiff bases derived from Pararosanilin. ii. These Schiff bases are slowly transformed into a variety of N-ethylated derivatives, which are weakly or non-staining. In addition to these chemical transformations, the quality of staining was markedly influenced by the tendency of GAF to precipitate; as much as three quarters of the dye was sometimes lost in this way during the first few days or weeks.


Hepatoblastoma with multiple tumors in a school-aged child.
Clinicians need to consider hepatoblastoma in the differential even in school-aged children or adolescents presenting with multiple liver tumors.


Late Preterm Infants: Morbidities, Mortality, and Management Recommendations.
Infants born between 34 weeks 0 days and 36 weeks 6 days of gestation are termed late preterm. This group accounts for the majority of premature births in the United States, with rates increasing in each of the last 3 years. This increase is significant given their large number: nearly 280,000 in 2016 alone. Late preterm infants place a significant burden on the health care and education systems because of their increased risk of morbidities and mortality compared with more mature infants. This increased risk persists past the newborn period, leading to the need for continued health monitoring throughout life.


A method for selecting reference beam model of VMAT plans with three 6MV beam-matched linear accelerators during radiation oncology.
Our objective was to provide a method for selecting reference beam model and evaluating the dosimetric accuracy of volumetric modulated arc therapy (VMAT) plans delivered on three Elekta beam-matched linacs during radiation oncology. Beam data was measured on three beam-matched linacs including Synergy1, Synergy2 and VersaHD. For eighteen lung and esophagus cases, fifty-four plans were generated using VMAT technique with three linac beam models respectively for point dose measurement and three-dimensional dose measurement. Each VMAT plan was executed sequentially on three linacs respectively. Measurement results were compared with treatment planning system (TPS) calculation results for all VMAT plans. Among three beam-matched linacs, discrepancy in beam output factor, percentage depth dose at 5 cm, 10 cm, 20 cm depth and MLC leaf offset are all within 1% except 20 × 20 cm2 and 30 × 30 cm2 field sizes, and discrepancy in beam profile is all within 2%. With comparison between measurement result and TPS calculation result, the absolute dose deviations are within the range of ± 3%, and the gamma passing rates are all over 95% for all VMAT plans, which are within the tolerance of clinical acceptability. Compared with all plans delivered on Synegy1 and VersaHD, the point dose discrepancy between measured results and TPS calculated results for plans delivered on Synergy2 is smallest, and the gamma passing rate between measured results and TPS calculated results for plans delivered on Synergy2 is highest. The beam-matched linacs demonstrate good agreement between measurement result and TPS calculation result for VMAT plans. The method can be used for selecting reference beam model for VMAT plans.


Sex Differences in the Impact of Racial Discrimination on Mental Health Among Black Americans.
Greater racial discrimination is associated with poorer mental health among Black Americans; yet, there remains an incomplete understanding of sex differences in exposure to racial discrimination, and further, of how sex differences in coping with racial discrimination may heighten or diminish risk for poorer mental health. Black men may experience greater exposure to both structural and communal forms of racial discrimination, whereas Black women may face both a wider range of potential sources, as well as encounter greater variability in the subjective experience of racial discrimination. For both Black women and men, racial discrimination may be similarly associated with maladaptive coping strategies (i.e., emotional eating, rumination) that also are linked to poorer mental health; however, emerging findings suggest that mindfulness may partially buffer these deleterious effects. Overall, the recent literature reveals mixed findings with respect to sex differences in the experience and negative mental health impact of racial discrimination. Despite this heterogeneity, evidence documents sex differences in the settings, type, and qualitative experience of racial discrimination among Black Americans. Additionally, growing evidence indicating that racial discrimination is associated with physiological markers of stress reactivity and psychopathology risk further bolsters its characterization as a unique form of chronic stress among Black Americans and other minority groups in the USA.


Inhibition of neuronal nitric oxide synthase and soluble guanylate cyclase prevents depression-like behaviour in rats exposed to chronic unpredictable mild stress.
Depression is the most common psychiatric disorder. It is well established that endogenous nitric oxide (NO) contributes to chronic unpredictable mild stress (CUMS)-induced depression. The aim of this study was to investigate brain-derived neurotropic factor (BDNF) expression in CUMS-induced depression-like behaviour in rats. Rats were exposed to CUMS for 5 weeks. A specific and selective nNOS inhibitor, 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg/day, i.p.), and a specific soluble guanylate cyclase (sGC) inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 mg/kg/day, i.p.), were administered during CUMS. The forced swimming test (FST) was used to assess despair and sucrose consumption, and sucrose preference test was used to assess anhedonia that are the main symptoms of the depression. We show that both 3-Br-7-NI and ODQ administration during CUMS suppressed CUMS-induced, depression-like behavioural changes, including reduced sucrose preference, body-weight and locomotor activity as well as increased immobility time in the FST. CUMS also significantly decreased BDNF protein levels in the CA1 and CA3 regions of the hippocampus, which was reversed by 3-Br-7-NI and ODQ administration. Our findings suggest a novel role for nNOS and sGC-cGMP in the development of the CUMS model of depression.


Travel behaviour of patients with haemophilia.
We aimed to identify socio-demographic, or illness-specific variables, influencing travel behaviour of haemophilic patients. A standardised questionnaire was sent to more than 2000 members of two German Haemophilia associations. Multivariable logistic regression with the outcomes frequent (at least two journeys per year) and long-haul travel (outside of Europe) was applied separately on adult patients and patients younger than 18 years. Among 345 adults, high education level, living in a partnership or travelling alone was significantly associated with frequent travel with odds ratios (ORs)/95%-confidence intervals (95%-CI) of 3.10/1.72-5.80, 1.99/1.10-3.62 and 1.73/1.01-3.62, respectively. High education level and self-application of clotting factors were significant variables for long-haul travel (OR/95%-CI: 2.45/1.43-4.26 and 3.25/1.33-8.52, respectively). Among 144 non-adults, a younger age or performing permanent prophylactic treatment was significantly associated with a lower likelihood for long-haul travel (OR/95%-CI: 0.51/0.22-0.95 and 0.10/0.01-0.65, respectively). Longer awareness of the disease increased the likelihood for long-haul travel (OR/95%-CI: 1.06/1.01-1.14). High education level and self-application of clotting factors influence travel intensity of adult patients most strikingly. Parents of very young patients on permanent prophylactic treatment might need special education to facilitate holiday travel for these families.


Atrial electrophysiologic remodeling: another vicious circle?
With few exceptions, acquired heart disease is the result of gradual changes in the heart, progressing during several months or years. This also includes certain cardiac arrhythmias, as for instance atrial fibrillation (AF). In spite of the important role of slowly progressing pathologic processes, most of our knowledge about mechanisms of cardiac arrhythmias is based on acute experiments. Only recently, the attention also is more focused on long-term adaptation processes like cardiac memory, electrical remodeling, and tachycardia-induced cardiomyopathy. In experimental animal models, it has been shown that AF induces a vicious circle of electrophysiologic and structural changes that inevitably leads to "domestication" of the arrhythmia ("AF begets AF"). In this article, the studies on AF-induced electrophysiologic and cellular remodeling are discussed.


Management of acquired rectourinary fistulas: how often and when is permanent fecal or urinary diversion necessary?
The objective of this study was to evaluate our experience in the management of acquired rectourinary fistulas at our tertiary center. Eighteen patients with fistulas treated from 1999 to 2004 were retrospectively reviewed for demographics, etiology of the fistulas, treatment, and outcome. The median age of the group was 69 years. Sixteen patients had fistulas that were malignant-associated. One patient died from tumor progression before any surgical therapy. The remaining 17 patients underwent surgical treatment of the fistula with a median of one procedure per patient. Eight patients had excision with permanent diversion, two had excision with repair/reconstructive procedures, and seven had repair surgical procedures. Initial surgical management was successful for 13 (76 percent) patients. Reoperation resulted in a final success rate of 100 percent. The rates of permanent fecal, urinary, and fecal plus urinary diversion in the malignant associated fistula group were 5.8, 47, and 5.8 percent, respectively. The median follow-up for all patients was 9.5 months. There were no procedure-related mortalities and five (29 percent) patients had significant surgical-related morbidity. Our data suggest that surgical treatment for acquired rectourinary fistulas can successfully avoid permanent fecal and/or urinary diversion in a large number of patients if locally curative cancer treatment can be achieved.


The influence of iliotibial tract thickness on clinical outcomes in women with patellofemoral pain.
The assessment of iliotibial tract thickness by ultrasonography may help identify a key, previously unexplored factor that may contribute directly to the homeostasis imbalance of the femoropatellar joint in people with patellofemoral pain (PFP). To compare the iliotibial tract thickness of people with PFP and asymptomatic people; and to correlate the iliotibial tract thickness with self-reported pain and function of people with PFP. Eighty women, separated into two groups: PFP group (n = 40) and control group consisting of asymptomatic participants (CG; n = 40). The participants answered the Anterior Knee Pain Scale (AKPS) questionnaire, to identify the self-reported knee function; they evaluated the pain in millimeters by the Visual Analog Scale for pain (VAS). For the imaging evaluation, an ultrasound was used, with a linear transducer at the distal portion of the iliotibial tract (coronal plane), with the participants positioned in dorsal decubitus, with 20° of knee flexion. The iliotibial band was visualized in its long axis, and three sequential images were recorded between the lateral femoral condyle and the lateral tibial condyle. The measurements were normalized and correlated. The groups had no differences (P > 0.001) between participants for: age/weight/height/IMC. Participants in the PFP group had moderate levels of pain (58 + 2.1 mm), considerable self-reported functional limitation (d = 3.05) and greater iliotibial tract thickness compared with the CG (d = 2.41). The iliotibial tract of women diagnosed with PFP have greater thickness compared with asymptomatic women. There was no association between iliotibial tract thickness and subjective measures of pain and function.


Controlled moisture permeability of thermoplastic starch/polylactic acid/poly butylene adipate-co-terephthalate film for the autolysis of straw mushroom Volvariella volvacea.
Straw mushrooms are prone to autolyze, leading to a high requirement of environmental humidity. In this work, thermoplastic starch/polylactic acid/poly (butylene adipate-co-terephthalate) (TPS/PLA/PBAT) film was produced by extrusion. The moisture permeability of the film was controlled by adjusting the content of TPS, which could be expected to further control humidity of the microenvironment in the package. Results revealed that the water vapor transmission rate of the film linearly increased from 612.31 g/m2·24 h to 1082.50 g/m2·24 h with the increase in the TPS concentration. The TPS/PLA/PBAT film with 30 wt% TPS showed the strongest inhibition on the autolysis of straw mushrooms compared with other groups, effectively delaying the increase in the free water, soluble solid content, rate of weight loss, and polyphenol oxidase of straw mushrooms and extending the shelf life of straw mushrooms from 24 h to 72 h.


Organizational climate and self-efficacy as predictors of staff strain in caring for dementia residents: A mediation model.
To date, no research has investigated how the organizational climate of aged care influences the self-efficacy of staff in caring for residents with dementia, or, how self-efficacy is associated with the strain experienced by staff. This study sought to investigate the extent to which the self-efficacy of aged care staff mediates the association between organizational climate variables (such as autonomy, trusting and supportive workplace relations, and the recognition of competence and ability, and perceptions of workplace pressure) and staff strain. A cross-sectional survey design was implemented in which 255 residential aged care staff recruited across aged care facilities in Melbourne, Australia. Staff completed self-report measures of organizational climate, self-efficacy, and strains in caring for residents with dementia. Indirect effects analyses using bootstrapping indicated that self-efficacy of staff mediated the association between the organizational climate variables of autonomy, trust, support, pressure, and staff strain. The findings of this study emphasize that the aged care sector needs to target organizational climate variables that enhance the self-efficacy of staff, and that this in turn, can help ameliorate the strain experienced by staff caring for residents experiencing dementia.