Posttraumatic Stress Disorder in Institutionalized World War II Veterans.
Relatively little is known about posttraumatic stress disorder (PTSD) in World War II (WWII) veterans, despite the significant number of studies on this problem in Vietnam veterans. The authors document the prevalence of PTSD and other psychiatric disorders and investigate the etiological correlates of the syndrome in elderly, institutionalized WWII veterans. Sixty-two cognitively intact subjects (mean age 74.2 years), residents in a veterans' long-term care facility, were assessed for past and present psychopathology. A second investigator, blind to patients' psychiatric status, determined the degree of combat exposure and administered a checklist of pre-war and wartime variables. The lifetime prevalence of PTSD was 23%. Of those veterans with PTSD, 57% experienced chronic symptoms. The lifetime prevalence of other diagnoses was also high, including 3 7% for major depression and 53% for alcohol abuse. There was a strong correlation between the severity of the combat stressor and the development of PTSD. Significant correlations between PTSD and some pre-war variables were also found: more family histories of alcohol abuse, more deaths of close family members in early life, and less likelihood of having held a job for more than 1 year prior to the war. PTSD in elderly, institutionalized WWII veterans is a common, serious problem that is often unrecognized.


Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study.
Thalassemia is the most common genetic disorder worldwide. Use of iron chelators has improved survival but endocrine complications have become more frequent. The frequency of hypothyroidism in Beta Thalassemia Major (BTM) children ranges from 6 to 30 %. Thyroid dysfunction mainly occurs by gland infiltration, chronic tissue hypoxia, free radical injury, and organ siderosis. (a) To evaluate the thyroid function status in chronically transfused children with BTM, in the first and second decade of life and (b) to study the influence of factors like duration and amount of blood transfusions, serum ferritin level, and iron chelation therapy on thyroid function. BTM children, 3 years old and above, on regular blood transfusions with serum ferritin > 1500 mcg/l were included in the study. Thyroid function and ferritin assessment was done using ELISA kits. Autoimmune thyroiditis was ruled out by antithyroid peroxidase and antithyroglobulin antibody testing. A study population of 83 children consisted of 49 boys (59%) and 34 girls (41%). 4.8% of the children had evidence of subclinical hypothyroidism. Among them two belonged to the first decade and the other two to the second decade of life. Mean TSH, FT4, and ferritin values among children with thyroid dysfunction were 6.38 ± 0.83 mIU/ml, 1.08 ± 0.45 ng/dl, and 3983.0±1698.30 ng/ml, respectively. The severity of thyroid dysfunction was statistically significantly associated with higher serum TSH values in children in the second decade of life with a p value = 0.001. No other significant correlation was found between oral chelation, amount and duration of blood transfusion, or serum ferritin levels. Subclinical hypothyroidism was the thyroid dysfunction observed in our study. Regular blood transfusions with adequate chelation may decrease incidence of thyroid dysfunction.


[Perinatal Dengue: A case Report].
Few reports are available about perinatal dengue, with controversial results in regards the risk of perinatal outcome. To report a case of perinatal dengue as a differential diagno sis with neonatal sepsis, which must be considered in endemic areas. Male newborn of a 23 year-old female, who presented a Non-Structural Protein 1 (NS1) antigen positive to dengue at 36 weeks of gestation and negative anti-dengue antibodies. At day six of the illness a healthy newborn was born. On the second day of life the neonate presented fever with no other pathological findings on the physical exam, associated with severe thrombocytopenia (17,900 platelets/uL), increased C-reactive protein, a positive NS1 antigen, and positive anti-dengue immunoglobulin G (IgG). He was treated with ampicillin and gentamicin according the Institution protocol of neonatal sepsis. The newborn showed clinical improvement, with hemodynamic stability and significant increase of platelets, receiving the medical discharge. Dengue in pregnancy produces the risk of adverse perinatal outcomes, particularly low birth weight and preterm delivery. Children of mothers diagnosed with dengue at the end of pregnancy should be observed closely with serial hemograms during child's first days of life, due to the high risk of vertical transmission.


Strain-Induced Spatial and Spectral Isolation of Quantum Emitters in Mono- and Bilayer WSe2.
Two-dimensional transition metal dichalcogenide semiconductors are intriguing hosts for quantum light sources due to their unique optoelectronic properties. Here, we report that strain gradients, either unintentionally induced or generated by substrate patterning, result in spatially and spectrally isolated quantum emitters in mono- and bilayer WSe2. By correlating localized excitons with localized strain variations, we show that the quantum emitter emission energy can be red-tuned up to a remarkable ∼170 meV. We probe the fine-structure, magneto-optics, and second-order coherence of a strained emitter. These results raise the prospect of strain-engineering quantum emitter properties and deterministically creating arrays of quantum emitters in two-dimensional semiconductors.


Office-related antibiotic prescribing for Medicaid-enrolled children.
Prudent antibiotic prescribing practices are essential to limiting antibiotic resistance. To assess the trend in percentage of office visits for acute respiratory infections (ARIs) linked with an antibiotic prescription. Retrospective analysis of Montana Medicaid billing claims data for each year, 1999 to 2010, was done. Participants included continuously enrolled children aged ≤14 years. Primary outcomes were ARI-related office visits and filled antibiotic prescriptions within 10 days of the office visit. Of the 873 244 office visits identified, 116 962 (13%) had an ARI as the primary diagnosis. Among ARI-related office visits, 64 250 (55%) were linked with an antibiotic prescription. From 1999 to 2010, the odds of ARI-related visits being linked with an antibiotic prescription did not change (odds ratio = 1.00; 95% confidence interval = 0.995-1.002). The percentage of ARI-related visits linked with an antibiotic prescription did not decrease from 1999 to 2010. Further efforts are needed to reduce antibiotic treatment for ARIs.


Autologous Splenocyte Reinfusion Improves Antibody-Mediated Immune Response to the 23-Valent Pneumococcal Polysaccharide-Based Vaccine in Splenectomized Mice.
Common clinical options, currently, for necessary splenectomy are vaccinations and antibiotic prophylaxis. However, despite these two adjuncts, there still occur numerous cases of overwhelming post-splenectomy infection. To examine whether reperfusion of critical splenic lymphocytes could boost immune response, we harvested splenic lymphocytes, reperfused the autologous lymphocytes, and then administered a pneumococcal vaccine (PNEUMOVAX®23, i.e., PPSV23) in splenectomized mice. We found that splenectomy impaired the immune response in the splenectomized group compared to the non-splenectomized group; the splenectomized group with lymphocyte reinfusion had a higher response to polysaccharide vaccination based on antibody titer than the splenectomized group without lymphocyte reinfusion. The sham group with the native spleen had the most elevated antibody titer against the PPSV23 polysaccharide antigen. This may be additive, resulting from contributions of the splenic structure, along with the phagocytic function of the spleen and its constituent cells affecting the antibody response. Reinfusion of splenic lymphocytes may enhance immunity without the complications associated with splenic fragment autotransplantation, which never gained acceptance. This technique is safe and simple since the splenic lymphocytes are autologous and, therefore, not self-reactive, and very similar to autologous blood transfusion. This concept may be beneficial in cases of unavoidable splenectomy, especially in pediatric cases.


Study of some properties of ABO test sera by using the method of phagocytosing erythrocytes treated with formaldehyde in vitro.
By using the method of phagocytosis of erythrocytes treated with formaldehyde against human test sera, an indirect conclusion on the quantity of IgG antibodies in the used sera could be made. Combined tests of 0, A1 and B blood group with erythrocytes treated with formaldehyde against test sera 0 (alpha + beta), A (beta) and B (alpha) and AB (0) sera from non-immunized and immunized with anatoxin from staphylococcus aureus donors were made. The strongest phagocytosis was observed when A1 and B erythrocytes with 0 (alpha + beta) sera and A1 erythrocytes with AB (0) sera from immunized with anatoxin donors were combined. A weaker phagocytosis took place when erythrocytes non-compatible with the AB0-system A1 and B were combined with the B (alpha) and A (beta) test sera, and the weakest--when erythrocytes compatible with the AB0 test sera diluted with an equal volume of saline and heated at 70 degree C for 10 minutes.


Induction of PC12 cell death, apoptosis, by a sialoglycopeptide from bovine brain.
The sialoglycopeptide from bovine brain inhibited the growth of PC12 cells in the presence of nerve growth factor. This inhibition was accompanied by DNA fragmentation showing a ladder pattern and changes in cell morphology leading to cytoplasmic condensation. These results suggest that the sialoglycopeptide induces PC12 cell apoptosis in the presence of nerve growth factor.


OPTIMIZING WEIGHTED ENSEMBLE SAMPLING OF STEADY STATES.
We propose parameter optimization techniques for weighted ensemble sampling of Markov chains in the steady-state regime. Weighted ensemble consists of replicas of a Markov chain, each carrying a weight, that are periodically resampled according to their weights inside of each of a number of bins that partition state space. We derive, from first principles, strategies for optimizing the choices of weighted ensemble parameters, in particular the choice of bins and the number of replicas to maintain in each bin. In a simple numerical example, we compare our new strategies with more traditional ones and with direct Monte Carlo.


Primary B cell lymphoma of the penis: successful treatment with organ preservation.
Malignant lymphoma uncommonly manifests in the genitourinary tract. Primary penile lymphoma is extremely rare. A 77-year-old male presented with primary malignant B-cell lymphoma of the penis with the chief complaint of a painless and itching nodule on the penile glans for more than 2 months. The pathologic examination with immunohistochemical stain of penile biopsy revealed malignant B cell lymphoma, mixed cellular type. The physical examination and the computed tomography scan of chest, abdomen, and pelvis showed no evidence of superficial, thoracic, abdominal, or pelvic lymphadenopathy. This case was treated with local excision and systemic chemotherapy with good cosmetic and functional results. There was absence of recurrence 16 months after therapy.


Metagrating-enabled Brewster's angle for arbitrary polarized electromagnetic waves and its manipulation.
Brewster effect has attracted extensive interests through microwave to optical regime. However, previous work mainly focused on the cases with single linear polarization. We demonstrate in this paper an equal Brewster's angle for both TE (transverse-electric) and TM (transverse-magnetic) waves. Tunable Brewster effect is furthermore achieved. For practical implementation of this effect, we propose an anisotropic metagrating composed of modified split ring resonators (MSRR) as a proof-of-concept in X-band. Measurement results of the manufactured prototypes validate our method. The proposed metagrating featuring Brewster's angle manipulation potentially paves the way for many applications throughout the spectrum, e.g., angular selectivity.


Heparin in coronary artery disease: new uses for an old drug.
The role of heparin in the treatment of coronary artery disease remains unclear. Although of benefit in unstable angina and the prevention of acute occlusion following angioplasty, its value as adjunctive therapy in myocardial infarction is limited. Further studies are needed to assess the effect of heparin on angioplasty restenosis and late venous graft occlusion.


Electrocardiogram-based deep learning model to screen peripartum cardiomyopathy.
Peripartum cardiomyopathy, one of the most fatal conditions during delivery, results in heart failure secondary to left ventricular systolic dysfunction. Left ventricular dysfunction can result in abnormalities in electrocardiography. However, the usefulness of electrocardiography in the identification of peripartum cardiomyopathy in pregnant women remains unclear. This study aimed to evaluate the effectiveness of a 12-lead electrocardiography-based artificial intelligence/machine learning-based software as a medical device for screening peripartum cardiomyopathy. This retrospective cohort study included pregnant women who underwent transthoracic echocardiography between a month before and 5 months after delivery and underwent 12-lead electrocardiography within 30 days of echocardiography between December 2011 and May 2022 at Seoul National University Hospital. The performance of 12-lead electrocardiography-based artificial intelligence/machine learning analysis (AiTiALVSD software; version 1.00.00, which was developed to screen for left ventricular systolic dysfunction in the general population) was evaluated for the identification of peripartum cardiomyopathy. In addition, the performance of another artificial intelligence/machine learning algorithm using only 1-lead electrocardiography to detect left ventricular systolic dysfunction was evaluated in identifying peripartum cardiomyopathy. The results were obtained under a 95% confidence interval and considered significant when P<.05. Among the 14,557 women who delivered during the study period, 204 (1.4%) underwent transthoracic echocardiography a month before and 5 months after delivery. Among them, 12 (5.8%) were diagnosed with peripartum cardiomyopathy. The results showed that AiTiALVSD for 12-lead electrocardiography was highly effective in detecting peripartum cardiomyopathy, with an area under the receiver operating characteristic of 0.979 (95% confidence interval, 0.953-1.000), an area under the precision-recall curve of 0.715 (95% confidence interval, 0.499-0.951), a sensitivity of 0.917 (95% confidence interval, 0.760-1.000), a specificity of 0.927 (95% confidence interval, 0.890-0.964), a positive predictive value of 0.440 (95% confidence interval, 0.245-0.635), and a negative predictive value of 0.994 (95% confidence interval, 0.983-1.000). In addition, a 1-lead (lead I) artificial intelligence/machine learning algorithm showed excellent performance; the area under the receiver operating characteristic, area under the precision-recall curve, sensitivity, specificity, positive predictive value, and negative predictive value were 0.944 (95% confidence interval, 0.895-0.993), 0.520 (95% confidence interval, 0.319-0.801), 0.833 (95% confidence interval, 0.622-1.000), 0.880 (95% confidence interval, 0.834-0.926), 0.303 (95% confidence interval, 0.146-0.460), and 0.988 (95% confidence interval, 0.972-1.000), respectively. The 12-lead electrocardiography-based artificial intelligence/machine learning-based software as a medical device (AiTiALVSD) and 1-lead algorithm are noninvasive and effective ways of identifying cardiomyopathies occurring during the peripartum period, and they could potentially be used as highly sensitive screening tools for peripartum cardiomyopathy.


Cystine content of legume seed proteins: estimation by determination of cysteine with 2-vinylquinoline, and relation to protein content and activity of cysteine synthase.
The cystine content of the protein of a number of different lines of legume seeds has been determined by the method of Krull et al. which selectively reacts cysteine residues of intact, reduced proteins with 2-vinylquinoline, giving an adduct with an absorption maximum at 318 nm. Some seed lines were found to have 3.5 times as much cysteine as the seed line with the lowest cysteine content, perhaps offering opportunities for improvement in the nutritional quality of bean seed proteins through breeding and selections. While no correlation between cysteine levels and protein content was observed, a positive correlation was found between the specific activity of the terminal enzyme of cysteine synthesis, cysteine synthase, and the cysteine content of seeds.


Characterization of a novel transgenic mouse tumor model for targeting HER2+ cancer stem cells.
HER2 is an oncogenic tumor-associated antigen overexpressed in 20-25% of breast cancers, which is associated with increased invasion, metastasis of the disease and resistance to therapy. Recent studies have further shown that HER2 can increase the population of breast cancer stem cells (BCSCs). However, there is currently no in vivo model for the study of HER2(+) BCSCs. In this study, we characterized a mouse breast cancer model for HER2(+) BCSCs. This was accomplished by inoculating mouse mammary tumor EO771 cells engineered with human wild-type HER2 (EO771E2) into C57BL/6 HER2 transgenic mice to test and confirm the stable human HER2 expression in the model. More importantly, we detected a subpopulation of EO771E2 cells with a high activity of aldehyde dehydrogenases (ALDH(high)). We demonstrated that the isolated ALDH(high) EO771E2 cells possessed key properties of BCSCs including enhanced tumorigenicity, generation of heterogeneous tumors and the capacity to self-renewal in vitro. In conclusion, the tumors formed in C57BL/6 HER2 transgenic mice with EO771E2 cell injection revealed stable and functional human HER2 expression. These tumors contain a subset of ALDH(high) cells which are small in number, but are enriched in cancer stem cells. This model is deemed to be useful for experiments aimed to develop novel treatments to target HER2(+) BCSCs.


IFN-γ +875 microsatellite polymorphism as a potential protection marker for leprosy patients from Amazonas state, Brazil.
Polymorphisms present in the first intron of IFN-γ may have an important role in the regulation of the immune response, which could have functional consequences for gene transcription. Leprosy patients are characterized by different immune responses in different clinical forms. We investigated a possible association of the +874 polymorphism and CA repeats present in the first intron of IFN-γ with susceptibility to leprosy and with the manifestation of the different clinical forms. Nucleotide sequencing was performed with samples from 108 leprosy patients and 113 controls subjects, as well as immunophenotyping of CD(4)(+), CD(8)(+) and CD(69)(+) T cells by flow cytometry. The data showed that there were no significant differences between patients and control subjects, as well as according classification of Ridley-Jopling. However, the A/A genotype was significantly increased in paucibacillary patients (p=0.028) and the microsatellite encoding 16 CA repeats were significantly associated with paucibacillary compared to multibacillary patients (p=0.019). Individuals homozygous for the +874 A allele, the mean level of CD(4)(+) and CD(69)(+) T cells was higher. Our data suggest that polymorphisms present in the first intron of IFN-γ are not associated with susceptibility to leprosy, nevertheless, the +874 polymorphism and the CA repeats number encoded in IFN-γ gene may be related to a higher cellular immune response in patients and are consistently more frequently detected in PB patients.


Ursolic acid-rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease.
Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 μg/mL; LC50 26.73 ± 1.2 μg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity.


Elevated antidepressant plasma levels after addition of fluoxetine.
Four patients treated with tricyclic antidepressants and one patient treated with trazodone all demonstrated marked increases in plasma levels of these drugs after the addition of fluoxetine. Such increases could increase adverse effects.


Laser ablation of cutaneous leg veins.
Patients presenting with lower-extremity telangiectasias, commonly known as spider veins, are a frequent presentation for vascular surgeons. The use of lasers in the treatment of lower-extremity spider veins has gained increased popularity during the past 5 years. This technology, driven by consumer demand, has been effective in treating vessels that are refractory to sclerotherapy treatment, vessels that arise from telangiectatic matting, and in patients who experience a phobia to needles. One laser wavelength per machine limits what the practitioner can do. That is, each type of vein responds best to a specific wavelength. Light skin is more forgiving to complications than dark skin. The devices are a complement to good sclerotherapy, not a substitute.


Molecular determinants for a cardiovascular collapse in anthrax.
Bacillus anthracis releases two bipartite proteins, lethal toxin and edema factor, that contribute significantly to the progression of anthrax-associated shock. As blocking the anthrax toxins prevents disease, the toxins are considered the main virulence factors of the bacterium. The anthrax bacterium and the anthrax toxins trigger multi-organ failure associated with enhanced vascular permeability, hemorrhage and cardiac dysfunction in animal challenge models. A recent study using mice that either lacked the anthrax toxin receptor in specific cells and corresponding mice expressing the receptor in specific cell types demonstrated that cardiovascular cells are critical for disease mediated by anthrax lethal toxin. These studies are consistent with involvement of the cardiovascular system, and with an increase of cardiac failure markers observed in human anthrax and in animal models using B. anthracis and anthrax toxins. This review discusses the current state of knowledge regarding the pathophysiology of anthrax and tries to provide a mechanistic model and molecular determinants for the circulatory shock in anthrax.


Assessment of the relationship between polysomnography parameters and plasma malondialdehyde levels in patients with obstructive sleep apnea.
The relationship of plasma malondialdehyde (MDA) with major parameters of PSG was investigated to find out if there was a correlation between these variables. Polysomnograms were done on a total of 37 adults who do not have a history of any systemic illness, smoking, and supplement use. Plasma MDA measurements and their relationship with PSG parameters were analyzed. The mean MDA concentrations in patients with lower AHI values were also lower than those in the patients with higher AHI (p < 0.001). Higher predominance of apnea in patients with similar AHI values, longer mean apnea durations, O2 saturation dips to < 90%, and higher ODI values predicted higher plasma MDA concentrations. Higher oxidative stress measurements predicted more severe clinical picture. These findings show that oxidative stress measurement with MDA may provide a simple tool to screen patients for OSA and help select them for PSG study appropriately, if indicated.


Maternal mental health modifies the association of food insecurity and early child development.
We examined the association between household food insecurity and early child development and whether or not maternal depression and anxiety modifies this association. The cross-sectional study included 468 mother-infant pairs recruited at primary health centers of the Federal District, Brazil. Mothers answered a questionnaire that evaluated early child development (outcome), household food insecurity (independent variable), maternal depression and trait anxiety (effect modifiers). Variables were collected with validated questionnaires for the Brazilian population. Pearson's χ2 test and logistic regression analyses were conducted. Infants who lived in a moderate or severe food insecure household had 2.52 times (95% confidence interval [CI] [1.13, 5.65]) the odds of having early child development delays compared with infants in secure households. Maternal depression and anxiety modified the strength of association between household food insecurity and early child development, which is an innovative finding. Among infants with depressed mothers, those experiencing mild (adjusted odds ratio [aOR] 3.33, 95% CI [1.17, 9.46]) and moderate/severe household food insecurity (aOR 10.13, 95% CI [2.18, 47.10]) had higher odds of having early child development delays, compared with infants in food secure households. Among infants with both anxious and depressed mothers, these associations were even stronger for mild (aOR 4.69, 95% CI [1.41, 15.59]) and moderate/severe household food insecurity (aOR 16.07, 95% CI [2.70, 95.66]). In conclusion, household food insecurity is a risk factor for early child development delays, and this association is modified by maternal depression and anxiety. Future studies should evaluate the impact of intervention packages that address maternal depression and anxiety and household food insecurity on preventing early child development delays.


Transferable capacity for gastrointestinal colonization in Enterococcus faecium in a mouse model.
A high level of gastrointestinal colonization frequently precedes invasive infection due to Enterococcus faecium. Factors other than antimicrobial resistance that promote gastrointestinal colonization by E. faecium have not been identified. We tested the ability of a colonization-proficient clinical E. faecium isolate (C68) to transfer colonizing ability to noncolonizing E. faecium recipient strains. Transconjugants derived from matings that used E. faecium D344SRF as a recipient strain colonized mouse gastrointestinal tracts in high numbers under selective pressure from clindamycin or vancomycin, compared with control strains that lacked DNA transferred from C68. We transferred DNA into a second recipient strain (E. faecium GE-1), which also colonized mice in significantly greater numbers under selective pressure from clindamycin, compared with a control strain. These results indicate that E. faecium clinical isolates express transmissible factors other than antimicrobial resistance that promote colonization of the mouse gastrointestinal tract.


Agranulocytosis Associated with Topiramate: A Case Report and Review of Published Cases.
A 41-year-old female presented to the hospital with sore throat and shortness of breath. She was hypoxic with an oxygen saturation of 87% in room air. Physical examination revealed swollen uvula with exudates. She had been started on topiramate for treatment of migraine few months ago. The dose of topiramate was increased to 100 mg twice daily 2 weeks ago. Complete blood count revealed an absolute neutrophil count (ANC) of 8 c/mm3. She was intubated and started on broad-spectrum antibiotics. She was transferred to our hospital on the fifth day of hospitalization. On arrival, her absolute neutrophil count was 10 c/mm3. Her agranulocytosis was attributed to topiramate after ruling out other possible causes. ANC improved after topiramate was stopped. ANC increased to 1000 after 5 days of stopping topiramate. We also reviewed published cases of topiramate-associated agranulocytosis. Agranulocytosis is a rare side effect of topiramate, and only 3 case reports have been published so far. In all cases, agranulocytosis developed after months of topiramate therapy and when dose was increased to 200 mg daily suggesting a dose-dependent effect. Next steps would be further research on the pathogenesis of agranulocytosis associated with topiramate and creation of registry for data synthesis.


Blood pressure percentiles in 22,051 German children and adolescents: The PEP Family Heart Study.
Strong associations between blood pressure (BP) and overweight raise the question whether overweight children (body mass index (BMI) ≥85th percentile) should be included in the normative database. Using the LMS (Lamda-Mu-Sigma) method, we developed age-, gender-, and height-adjusted percentile curves for systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the 50th, 85th, 90th, 95th, and 97th percentiles in 22,051 German youths (18,917 normal-weight, 1,938 overweight, and 1,196 obese) aged 3-18 years from yearly cross-sectional surveys of the PEP Family Heart Study Nuremberg. Among children, we found no gender differences for BP and BMI. Male adolescents are taller and heavier. The mean prevalence of hypertension and obesity is 7.3% and 5.2% among children and 7.2% and 5.8% among adolescents, respectively. The prevalence of elevated BP increased substantially by weight groups achieving 24.4% in obese females and 21.9% in obese males with odds ratios of 5.9 (95% confidence interval (CI): 5.1-7.5) and 4.3 (95% CI: 3.5-5.2), respectively. The shapes of the 10 LMS-smoothed SBP and DBP percentile curves differ substantially between gender and weight group. The normal-weight percentiles are nearly identical with the overall growth charts, but separate percentiles for overweight and obese youths provide considerably higher values, such as 148/91 vs. 136/86 mm Hg for a 17-year-old male and 136/91 vs. 123/81 mm Hg for female, respectively, at the 90th percentile. Because of substantially higher BP percentiles, separate databases for overweight and obese children and adolescents are strongly recommended.


Imaging of vascular soft tissue tumors.
Most tumors of the vascular system are benign, cutaneous or subcutaneous lesions that are usually readily diagnosed without significant differential diagnosis. On the other hand, lesions that arise in deep soft tissues have to be differentiated from malignant neoplasms. In these cases, further imaging work-up is necessary for local staging and planning therapy. Vascular lesions of intermediate malignancy and malignant vascular tumors are very rare and demonstrate nonspecific imaging findings. This manuscript aims to give a brief overview of vascular soft-tissue tumors and to discuss the imaging appearances.


Arthritis in children with familial Mediterranean fever.
The clinical spectrum of arthritis in 124 children with well-documented familial Mediterranean fever (FMF) was investigated in a retrospective study. Seven mutations in the FMF gene (MEFV) were also screened using restriction enzyme digestion and amplification refractory mutation system techniques in 110 patients. Mean age at the onset of FMF arthritis was 5.93+/-3.50 years, 75% of the patients being under 10 years of age. Arthritis in the lower extremities, upper extremities, and small joints of the hands and feet was noted in 122 (98%), 17 (14%), and 15 (12%) patients, respectively. Three patients had atypical arthritis involving temporomandibular, sacroiliac, and sternoclavicular joints. Although most of the arthritic attacks resolved within a few weeks, 12 (10%) patients developed protracted arthritis persisting for months. Amyloidosis was demonstrated in 17 (14%) patients who had not received colchicine treatment. Mutation analysis confirmed the diagnosis of FMF in 77 (62%) children. The clinical presentations of arthritis in FMF may be an important source of diagnostic confusion in FMF. Mutation analysis is of value in situations of diagnostic uncertainty.


17β-Hydroxywithanolides as Sensitizers of Renal Carcinoma Cells to Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) Mediated Apoptosis: Structure-Activity Relationships.
Renal cell carcinoma (RCC) is a cancer with poor prognosis, and the 5-year survival rate of patients with metastatic RCC is 5-10%. Consequently, treatment of metastatic RCC represents an unmet clinical need. Screening of a 50 000-member library of natural and synthetic compounds for sensitizers of RCC cells to TRAIL-mediated apoptosis led to identification of the 17β-hydroxywithanolide (17-BHW), withanolide E (1), as a promising lead. To explore structure-activity relationships, we obtained natural and semisynthetic withanolides 1, 2a, 2c, and 3-36 and compared their ability to sensitize TRAIL-mediated apoptosis in a panel of renal carcinoma cells. Our findings revealed that 17-BHWs with a α-oriented side chain are superior to known TRAIL-sensitizing withanolides belonging to withaferin A class with a β-oriented side chain and demonstrated that the 17-BHW scaffold can be modified to enhance sensitization of RCCs to TRAIL-mediated apoptosis, thereby assisting development of natural-product-inspired drugs to treat metastatic RCC.


Lymphatic mapping and sentinel node analysis: current concepts and applications.
Since the introduction of sentinel node biopsy in 1990 as a minimally invasive surgical technique for the diagnosis of melanoma lymphatic metastases, the number of applications has expanded. We review applications and the current status of sentinel node biopsy in melanoma, breast, colon, gastric, esophageal, head and neck, thyroid, and lung cancer. Variations on techniques specific to each organ are explained, and the current role of sentinel node biopsy in diagnosis and treatment is discussed.


Decreased sensitivity of platelets to prostacyclin in patients with diabetes mellitus.
In order to ascertain the platelet sensitivity to prostacyclin (PGI2) in patients with diabetes mellitus, we determined the percentage inhibition of platelet aggregation and platelet ATP secretion following PGI2 addition in an in vitro system. The percentage inhibition of platelet aggregation caused by PGI2 in final concentration of 1.25, 2.5, or 5.0 ng/ml was significantly lower in diabetics than in healthy controls. That of platelet ATP secretion by 1.25 or 2.5 ng/ml of PGI2 was also significantly lower in diabetics. These data suggested that in patients with diabetes mellitus, the decreased sensitivity of platelets to PGI2 will bring about hypercoagulability and may become one of the risk factors of diabetic microangiopathy in cooperation with lowered vascular PGI2 generation.


The Janus face of glial-derived S100B: beneficial and detrimental functions in the brain.
Glia play active and vital roles in the CNS, including regulation of brain development, maintenance of cellular homeostasis and reparative responses to acute and chronic neurologic insults. However, in pathological conditions, glial function may be dysregulated resulting in enhanced neuroinflammation and further neurologic injury. The fundamental concept that aberrant regulation of a normally beneficial process may instead result in pathology is exemplified by the properties of the glial-derived protein, S100B. In the developing brain and following acute glial activation in response to injury, S100B acts as a neurotrophic factor and neuronal survival protein. In contrast, overproduction of S100B by activated glia can lead to exacerbation of neuroinflammation and neuronal dysfunction. This duality of S100B actions, both reparative and degenerative, is consistent with the compelling clinical evidence of the association between increases in S100B levels and outcome following brain injury. S100B levels generally correlate with the severity of damage and may have predictive value for adverse neurological outcomes. The cumulative data support the potential of S100B as a biomarker for brain damage, implicate glial activation as a possible treatment target in acute and chronic CNS disorders, and highlight the dual role of glia in the reparative and pathologic responses to neurologic injury.


Changes in Defense Mechanisms in Mothers From Pregnancy to 2 Years Postpregnancy.
The objective of this study was to assess changes in maternal defensive functioning from the third trimester of pregnancy to 2 years postpregnancy. A community sample of at-risk mothers ( N = 84; non-White [61%], unmarried [67%], high school or less education [72%], and income less than $20,000 [50%]) were recruited for this longitudinal study. Mothers responded to a semistructured interview during pregnancy and at 2 years postpregnancy about the parent-infant relationship; interview transcripts were coded using the Defense Mechanism Rating Scale (DMRS). Results indicated a significant increase in both total defense mechanisms used and the relative percentage of immature defense mechanisms used over time. A significant decrease in the relative percentage of healthy/adaptive defenses was noted. When all seven levels of defenses of the DMRS were assessed, it was an increase in minor image-distorting defenses, mechanisms that supported vulnerable self-esteem, that accounted for most of the change in immature defenses. Stability coefficients of defense mechanisms were reported, with large effect sizes, for overall defensive functioning, and mature and immature defenses over a 2-year period. These findings lend support to the importance of assessing defense mechanisms to better understand stressful life transitions in mothers.


Problematic Internet use and daily difficulties among adolescents with school refusal behaviors: An observational cross-sectional analytical study.
Problematic Internet use (PIU) is common and likely to coexist with mental health problems among adolescents with school refusal behavior. To date, no study has revealed to what extent PIU relates to the daily burden compared with other mental health problems. This study has examined the association between daily difficulties and PIU among adolescents with school refusal behaviors.This cross-sectional study involved all first-visit patients, regardless of diagnosis, aged 10 to 18 years at 2 child/adolescent psychiatric outpatient clinics in Yokohama City, Japan, from April 2016 to March 2018. The Questionnaire-Children with Difficulties (QCD) were obtained from parents. Simultaneously, the severity of PIU was evaluated using the Internet Addiction Test and depressive and anxiety symptoms were evaluated using the Patient Health Questionnaire-9 and General Anxiety Disorder-7 scale in the 2 weeks before the first-visit. From 684 first-visit patients, 227 with school refusal behaviors were enrolled in the study.PIU was observed in 40% of adolescents with school refusal behaviors. The QCD scores among patients with PIU were significantly lower than those in patients without PIU. Linear regression analysis revealed relationships between PIU and lower QCD scores throughout the day (except at night) and the total score of the day, after controlling for confounders such as depressive and anxiety symptoms.In conclusion, among adolescents with school refusal behaviors, PIU may affect their parent-assessed daily difficulties particularly experienced throughout the day.


Plasminogen activator production by human retinal endothelial cells of nondiabetic and diabetic origin.
The authors examined the effect of insulin-like growth factor 1 (IGF 1), epidermal growth factor (EGF), and acidic fibroblast growth factor (AFGF) on the synthesis by human retinal endothelial cell (HREC) of plasminogen activators (PA; tissue-type [t-PA] and urokinase-type [u-PA]) and plasminogen activator inhibitor (PAI). Immunologic and functional assays for t-PA, u-PA, and PA1 were conducted with cell lines derived from three diabetics and three nondiabetic controls. Confluent HREC of nondiabetic origin did not respond to IGF I (100 ng/ml) with any change of t-PA antigen in the medium (10.7 +/- 1.1 ng/ml unstimulated versus 10.1 +/- 0.8 ng/ml) stimulated, P = not significant). Likewise AFGF and EGF caused no significant change of t-PA levels. Both IGF I and EGF caused a significant increase of t-PA from HREC of diabetic origin (9.6 +/- 0.8 ng/ml unstimulated versus 16.6 +/- 1.9 ng/ml IGF I-stimulated, P less than 0.001, and 14.6 +/- 2.7 ng/ml EGF-stimulated P less than 0.005). Supplementation of AFGF had no effect on HREC of diabetic origin. In confluent cultures, only small quantities of u-PA were detected. After wounding confluent cultures, u-PA activity was associated with cells migrating from the wound edges. Functional PA activity was also measured by chromogenic assay. Results further supported a predominance of t-PA activity being produced by confluent HREC in culture. These results suggest that modulation of PA production by HREC is influenced by exposure to growth factors, by the state of confluency, and the origin of the cells (diabetic vesus nondiabetic).


Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial.
Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease. However, there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia. We conducted a randomized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aiming for hemoglobin of > or =13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to <9 g/dL. The primary end point was a composite of doubling of creatinine, renal replacement, or death. Eighty-eight patients were randomized (early treatment N= 45, deferred treatment N= 43) and followed for a median of 22.5 months. During follow-up, 13 versus 23 patients reached the primary end point in the two arms, respectively (log-rank P= 0.0078). The relative hazard for reaching an end point was 0.42 (P= 0.012). Adjusting for baseline serum creatinine, the adjusted relative hazard was 0.37 (P= 0.004), while the risk increased 2.23-fold (P < 0.001) per 1 mg/dL higher creatinine at baseline. The benefit was similar regardless of the baseline hemoglobin and proteinuria. No patients had any severe adverse events. Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy.


Sense of Coherence (SOC) of Italian healthcare workers during the COVID-19 pandemic: analysis of associated factors.
The COVID-19 pandemic has posed significant challenges for healthcare workers worldwide, potentially affecting their sense of coherence (SOC) and overall well-being. This study aimed to identify factors associated with different levels of SOC among healthcare workers, exploring demographic characteristics, work-related factors, changes in relationships and social habits, and the overall well-being. A cross-sectional study was conducted among 628 healthcare workers. SOC scores were assessed using a standardized questionnaire. Statistical analyses were performed to identify associations between these factors and SOC. Healthcare workers had a lower average SOC score (mean: 57.1) compared to the national average in Italy (mean: 60.3). Younger age and shorter length of service were associated with a higher risk of low SOC (p < 0.0001). Healthcare workers in the northwestern regions of Italy had an increased risk of low SOC compared to their counterparts in the northeastern regions (p = 0.0336). Adverse pandemic-related experiences and worsening social relationships were also associated with a higher risk of low SOC (p < 0.0001). This study highlights the unique challenges and stressors faced by healthcare workers during the COVID-19 pandemic and their impact on SOC. Age, length of service, geographic location, and social status were significant factors influencing SOC levels. Targeted interventions are needed to enhance SOC and well-being, particularly for younger and newly employed healthcare workers. Strategies promoting social connections, work-life balance, and psychological support services are crucial to support healthcare workers' resilience and coping abilities.


Long-term changes in spirometry in occupational divers: a 10-25 year audit.
To determine whether long-term engagement in occupational diving causes significant changes in spirometric measurements. All divers with adequate spirometric records spanning at least 10 years were identified from the New Zealand occupational diver database. Changes in lung function over time were compared with normative values derived using published prediction equations. Any significant changes were tested for correlation with age, duration of occupational diving, gender, smoking history and body mass index (BMI). Spirometry data spanning periods of 10 to 25 years were analysed for 232 divers. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) declined with increasing duration of diving, but slightly less than predicted with increasing age, while peak expiratory flow (PEF) declined more than expected for age in longer-term divers. The changes in PEF were statistically significant, and correlated with duration of diving exposure, initial age and final BMI. Nevertheless, the changes were small and probably clinically insignificant. We compared changes in spirometric parameters over long periods of occupational diving with normative data and found no clinically significant differences that could be attributed to diving. We found no justification for routine spirometry in asymptomatic divers.


Estimating the relapse risk of Plasmodium vivax in Iran under national chemotherapy scheme using a novel method.
This study aimed to estimate the relapse risk of Plasmodium vivax under national chemotherapy scheme using a novel method, and assessed its pattern in Kahnooj, a malaria endemic area in Iran. The authors traced repeated episodes of malaria attack between 1994 and 2001 and then, estimated the risks of secondary attack of P. vivax, classified by the species in their primary attack. It is suggested that the difference between the secondary attack rate in those who were infected by P falciparum and P. vivax in their primary attack may estimate the P. vivax relapse rate indirectly. This method showed that the relapse risk of P. vivax with in one and two years after the primary attack were 16.8 and 24.5% respectively. The risks of relapse before three or after 18 months were very low. The relapse pattern of P. vivax was compatible with the dominant pattern in most of the temperate areas. In addition, the relapse risk was very close to the estimated relapse risks in clinical trials on anti-relapse drugs. Therefore, we concluded that the anti-relapse therapy in the study area was effective; also, this method may estimate the relapse risk of P. vivax accurately.


RoCoMAR: robots' controllable mobility aided routing and relay architecture for mobile sensor networks.
In a practical deployment, mobile sensor network (MSN) suffers from a low performance due to high node mobility, time-varying wireless channel properties, and obstacles between communicating nodes. In order to tackle the problem of low network performance and provide a desired end-to-end data transfer quality, in this paper we propose a novel ad hoc routing and relaying architecture, namely RoCoMAR (Robots' Controllable Mobility Aided Routing) that uses robotic nodes' controllable mobility. RoCoMAR repeatedly performs link reinforcement process with the objective of maximizing the network throughput, in which the link with the lowest quality on the path is identified and replaced with high quality links by placing a robotic node as a relay at an optimal position. The robotic node resigns as a relay if the objective is achieved or no more gain can be obtained with a new relay. Once placed as a relay, the robotic node performs adaptive link maintenance by adjusting its position according to the movements of regular nodes. The simulation results show that RoCoMAR outperforms existing ad hoc routing protocols for MSN in terms of network throughput and end-to-end delay.


The end of knight-errantry in GVHD studies.
In this issue of Blood, Bolaños-Meade et al reported the results of the randomized phase 3 study Blood and Marrow Transplant Clinical Trials Network (BMTCTN) 0802. It compared the addition of mycophenolate mofetil to steroids vs steroids/placebo to treat newly diagnosed acute graft-versus-host disease (GVHD). Unfortunately, it failed to show a significant difference in outcomes.


Suramin potently inhibits cGAMP synthase, cGAS, in THP1 cells to modulate IFN-β levels.
Persistent activation of STING pathway is the basis for several autoimmune diseases. STING is activated by cGAMP, which is produced by cGAS in the presence of DNA. Results/methodology: HPLC-based medium throughput screening for inhibitors of cGAS identified suramin as a potent inhibitor. Unlike other reported cGAS inhibitors, which bind to the ATP/GTP binding site, suramin displaced the bound DNA from cGAS. Addition of suramin to THP1 cells reduced the levels of IFN-β mRNA and protein. Suramin did not inhibit lipopolysaccharide- or Pam3CSK4-induced IL-6 mRNA expression. Suramin inhibits STING pathway via the inhibition of cGAS enzymatic activity. Suramin or analogs thereof that displace DNA from cGAS could be used as anti-inflammatory drugs.


Association of IgG4-related disease and systemic rheumatic disorders.
Autoimmune disorders can occur together especially in genetically predisposed individuals. We here aimed to assess the occurrence of IgG4-related disease (IgG4-RD) in association with other systemic immune-mediated conditions. We retrospectively analyzed the clinical records of patients with IgG4-RD followed at the IgG4-RD Clinic of San Raffaele Hospital (Milan, Italy) for pre-existing or concomitant immune-mediated disorders. IgG4-RD was diagnosed based on histological findings and on the 2011 Comprehensive Diagnostic criteria. Associated immune-mediated disorders were diagnosed based on available classification and/or diagnostic criteria. Two-hundred and thirty-four patients with a definitive diagnosis of IgG4-RD were included in this study. A pre-existing immune-mediated connective tissue disease was reported in 6/234 patients (3%): one case each of sarcoidosis, Takayasu arteritis (TA), eosinophilic granulomatosis with polyangitis (EGPA), and rheumatoid arthritis; and two cases of granulomatosis with polyangitis (GPA). Organs involved by IgG4-RD included the lungs, the pancreas, the peritoneum, lacrimal glands, meninges and orbits. Sarcoidosis, EGPA, and TA preceded the onset of IgG4-RD. GPA preceded IgG4-RD onset in one case and occurred simultaneously in the other case. Rheumatoid arthritis occurred together with IgG4-RD in one case. Our observation suggests that "secondary" IgG4-RD can present in the context of pre-existing systemic immune-mediated disorders and complicate systemic autoimmune diseases as well as chronic granulomatous conditions. Further studies are needed to define whether this peculiar clinical scenario is associated with different genetic backgrounds, pathological bases, and long-term outcomes.


Determination of the elimination half-life of Glyphosate and its main metabolite, AMPA, in chicken plasma.
Glyphosate-based herbicides (GBHs) are the most-used herbicides worldwide. Concerns about their toxicity and ecotoxicity have motivated scientists to assess their potential effects on animals, as well as their toxicokinetic parameters in rats and humans. However, to our knowledge, such data have not been produced for avian models. In this study, toxicokinetic parameters for glyphosate and AMPA were calculated after one unique dietary exposure (40 mg of glyphosate equivalent per kg) and one unique intravenous injection of a GBH, in hens and roosters respectively. Non compartmental analysis was used to show the evolution of glyphosate and AMPA plasma concentrations over time. After one unique intravenous injection of a glyphosate-based herbicide, glyphosate and AMPA were quickly eliminated from plasma and were poorly distributed (Vssglyphosate = 0.30 L/kg). Their terminal half-lives are 4.7 h and 8.10 h, respectively. After dietary exposure, glyphosate and AMPA followed a 6 h absorption phase followed by a 42 h elimination phase. They were poorly distributed (Vssglyphosate = 0.00562 L/kg), and their maximum concentrations (Cmax) were 21285 µg/L and 108 µg/L, respectively. Their terminal elimination half-lives were 8.94 h and 6.93 h, respectively. Taken together, this study provides new data on the elimination rate and approximate biological half-life range of glyphosate in birds.


Loss of D2 dopamine receptor function modulates cocaine-induced glutamatergic synaptic potentiation in the ventral tegmental area.
Potentiation of glutamate responses is a critical synaptic response to cocaine exposure in ventral tegmental area (VTA) neurons. However, the mechanism by which cocaine exposure promotes potentiation of NMDA receptors (NMDARs) and subsequently AMPA receptors (AMPARs) is not fully understood. In this study we demonstrate that repeated cocaine treatment causes loss of D2 dopamine receptor functional responses via interaction with lysosome-targeting G-protein-associated sorting protein1 (GASP1). We also show that the absence of D2 downregulation in GASP1-KO mice prevents cocaine-induced potentiation of NMDAR currents, elevation of the AMPA/NMDA ratio, and redistribution of NMDAR and AMPAR subunits to the membrane. As a pharmacological parallel, coadministration of the high-affinity D2 agonist, aripiprazole, reduces not only functional downregulation of D2s in response to cocaine but also potentiation of NMDAR and AMPAR responses in wild-type mice. Together these data suggest that functional loss of D2 receptors is a critical mechanism mediating cocaine-induced glutamate plasticity in VTA neurons.


Highly efficient method of Lithospermum erythrorhizon transformation using domestic Rhizobium rhizogenes strain A13.
Lithospermum erythrorhizon, a medicinal plant growing in Asian countries, produces shikonin derivatives that are lipophilic secondary metabolites. These red naphthoquinone pigments are traditionally used as a natural drug and a dye in East Asia. In intact L. erythrorhizon plants, shikonin derivatives are produced in the root epidermal cells and secreted into extracellular spaces. The biosynthetic pathway for shikonin derivatives remains incompletely understood and the secretion mechanisms are largely unknown. Understanding the molecular mechanisms underlying shikonin biosynthesis and transport in L. erythrorhizon cells requires functional analysis of candidate genes using transgenic plants. To date, however, standard transformation methods have not yet been established. This study describes an efficient method for L. erythrorhizon transformation using hairy roots by Rhizobium rhizogenes strain A13, present domestically in Japan. Hairy roots of L. erythrorhizon were generated from explants of the axenic shoots that were infected with R. rhizogenes strain A13. Integration into the genome was assessed by PCR amplifying a transgene encoding green fluorescent protein (GFP) and by monitoring GFP expression. This method enhanced transformation efficiency 50-70%. Although methods for the systematic stable transformation of L. erythrorhizon plants have not yet been reported, the method described in this study resulted in highly efficient stable transformation using hairy roots. This method enables the functional analysis of L. erythrorhizon genes.


Heterogeneity of hemolytic efficiency and isoelectric point of streptolysin O.
Using thin-layer agarose gel isoelectric focusing overlaid with thin-layer erythrocyte agar plates, we found that crude streptolysin O (SLO) consisted of a variety of hemolytic components with different isoelectric points (pIs) and that the distribution of pIs in crude SLO was different even in samples which were produced from a single strain of Streptococcus pyogenes under similar conditions. All of the hemolytic components in crude SLO were shown to have the properties of SLO with respect to their susceptibility to oxygen and anti-SLO serum and their molecular weight. The SLO components showed a single molecular weight of 64,000, but they exhibited various pIs ranging from pH 5.4 to 8.3, with major components showing a pI of 6 and/or 7.5. Further examination revealed the slope of the hemolytic titration curve to be dissimilar among the samples of crude SLO. Since the slope of the hemolytic titration curve of a component appears to be based on its hemolytic efficiency, the value of the slope was designated its hemolytic efficiency index. When SLO was purified by isoelectric focusing, the pI of the components was correlated with its hemolytic efficiency index; hemolytic components with lower pIs exhibited a lower hemolytic efficiency index. These results indicate that SLO consists of heterogeneous components with different pIs and suggest that the differences in hemolytic efficiency indices of SLO components are due to the different electrical charges of SLO molecules, which are related to their polymerization and affect hemolytic efficiency.


Predictive value of bleeding risk scores in elderly patients with atrial fibrillation and oral anticoagulation.
The predictive value of bleeding risk scores for atrial fibrillation in older patients is not as well known. The goal of this study was to evaluate the predictive value of HASBLED, ORBIT and ATRIA for major bleeding (MB) and intracranial hemorrhage (ICH) in patients ≥ 75 years with atrial fibrillation and oral anticoagulation (OAC). A retrospective unicenter study including patients ≥ 75 years with atrial fibrillation (AF) and OAC. A total of 7613 patients ≥ 75 years with AF and OAC included between 2014 and 2018 (registry: NCT04364516). We analyzed the discriminative value of HASBLED, ATRIA and ORBIT scores for bleeding endpoints (major bleeding as primary endpoint and intracerebral hemorrhage as secondary). Cox regression was used to predict major bleeding with each scale and also for searching other variables potentially predictor of major bleeding. Model discrimination was assessed using Harrell's C-statistic. Calibration was assessed with goodness-of-fit test proposed by Gronnesby and Borgan. During a mean follow up of 4.0 years (IQR: 2.4-5.7 years), 729 patients developed MB (2.61 per 100 patients/year) and 243 patients developed ICH (0.85 per 100 patients/year). Three scores showed a low discrimination for major bleeding, being ORBIT the best (HASBLED C statistic = 0.557; ATRIA C statistic = 0.568; ORBIT C statistic = 0.595) and also a low discrimination for ICH (HASBLED C statistic = 0.509; ATRIA C statistic = 0.522; ORBIT C statistic = 0.526). Among the variables that are part of the scores and other baseline characteristics, after multivariable adjustment only sex (male), dementia, prior admission for bleeding, anemia and liver disease were found as a predictors of MB. In older patients under oral anticoagulation with atrial fibrillation, the risk scores HASBLED, ATRIA and ORBIT showed a weak discrimination for major bleeding and intracranial hemorrhage. Therefore, other better alternatives should be evaluated for this purpose.


Incidence of osteonecrosis of the jaw in patients with bone metastases treated sequentially with bisphosphonates and denosumab.
Osteonecrosis of the jaw (ONJ) is a serious adverse event of bone resorption inhibitors (BRIs), such as bisphosphonates and denosumab. Bisphosphonates and denosumab inhibit osteoclast function through different pharmacological effects and bisphosphonates are retained in bone for several months to years. Sequential treatment with bisphosphonates and denosumab might lead to an overlapping treatment effect, due to the addition of the effect of denosumab on the residual bisphosphonate effect. Therefore, the aim of our study was to investigate if switching from denosumab to bisphosphonates is associated with a higher incidence of ONJ. We retrospectively reviewed records of patients with solid tumors and bone metastases treated with denosumab after prior treatment with bisphosphonates at the University Hospitals Leuven (sequential group). Patients treated with denosumab or bisphosphonates alone were used as control groups. We identified 110 patients sequentially treated with bisphosphonates and denosumab with a median total BRI exposure of 36 months (sequential group). Median bisphosphonates exposure was 16 months and median denosumab exposure was 13 months. About 299 patients were included in the bisphosphonates control group with a median bisphosphonate exposure 19 months. About 6.7% (20/299) of patients developed ONJ. About 240 patients were included in the denosumab control group with a median denosumab exposure 17.5 months. About 10.0% of patients (24/240) developed ONJ. In the sequential group, 15.5% of patients (17/110) developed ONJ. The incidence of ONJ was 1.8% (2/110), 6.3% (6/99), 4.9% (4/82), 5.6% (3/54), and 3.4% (1/29), respectively in the first, second, third, fourth, and fifth year of BRI exposure, an ONJ-incidence similar to ONJ-incidence in the denosumab control group. In a time-to-ONJ-analysis, the curves of the sequential group and the denosumab control group were overlapping. In the sequential group, most of the ONJs occurred in the first year of denosumab exposure and in a matched control group analysis, with correction for median BRI-exposure, ONJ cases tend to occur earlier in the sequential group compared to ONJ cases in the bisphosphonates group. Cancer patients with bone metastases treated with BRIs seem to have a slightly higher risk of ONJ early after switching from bisphosphonates to denosumab compared to patients remaining on bisphosphonates. Nevertheless, based on the global ONJ-incidence, the switch from bisphosphonates to denosumab can be considered as safe as an equivalent exposure to denosumab from the start on.


The gastrectomy cripple: results of jejunal loop interposition.
The use of an interposed antiperistaltic jejunal loop between the stomach and the duodenum in the treatment of severe postgastrectomy nutritional disorder is described in two patients. Both patients had a gratifying return of digestive comfort and a striking increase in weight after the interposition operation. Several aspects of operative technique are described. This procedure should be considered in any patient suffering from this disorder.


Osteopontin is proinflammatory in experimental autoimmune uveitis.
Osteopontin (OPN) has been implicated in inflammatory and wound-healing processes. Increased OPN mRNA levels have been reported in experimental autoimmune uveitis (EAU), but the function of OPN in the inflamed eye is unknown. The purpose of this study was to investigate the role of OPN in the pathogenesis of EAU. EAU was induced in OPN-null and wild-type (WT) mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). Immunofluorescence experiments were performed to identify OPN-positive cells in WT mice. Disease incidence, serum IRBP antibody levels, vitreous infiltrates, retinal granulomas, and lymphocyte proliferation were assessed in OPN-null and WT mice. To determine whether OPN could induce an EAU-like condition, purified OPN and OPN fragments were injected intraocularly into WT mice and vitreous infiltrates were characterized and quantified. In WT EAU-positive eyes, cell types with increased OPN immunoreactivity were identified as F4/80-positive macrophages/microglia and CD4-positive T cells. OPN-null mice manifested attenuated disease with decreased vitreous infiltrates, fewer granulomas, less lymphocyte proliferation, and lower serum IRBP antibody levels. Exogenous full-length OPN, as well as N- and C-terminal fragments, induced leukocyte infiltration and retinal folding, with some similarities to EAU. The results demonstrate that OPN is proinflammatory in EAU and may be important for recruitment and activation of leukocytes in retinal inflammation.


CT Intensity Distribution Curve (Histogram) Analysis of Patients Undergoing Antiangiogenic Therapy for Metastatic Renal Cell Carcinoma.
The purpose of this study was to evaluate the median versus mean attenuation obtained from histograms in the response assessment of renal cell carcinoma (RCC) target lesions in patients treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors. Imaging findings of 19 patients with RCC and treated with a VEGFR tyrosine kinase inhibitor that included a baseline study and at least two follow-up studies were retrospectively analyzed. Histograms of target lesions were created from ROI measurements, and mean and median lesion attenuation were obtained. Shift of mean and median was used to classify response of lesions between baseline CT and the first follow-up examination according to the Choi criteria; morphology, attenuation, size, and structure (MASS) criteria; and the Response Evaluation Criteria in Solid Tumors (RECIST). RECIST classification of the last follow-up CT examination was considered the reference standard. Among the 19 patients (six women, 13 men; mean age, 60 ± 8 [SD] years; body mass index, 24.5 ± 4.6 kg/m2), three (16%) had evidence of disease progression; nine (47%), partial response; and seven (37%), stable disease. Temporal change in the shape of the histograms from or to gaussian occurred in 11 of the 19 (58%) lesions, which accounted for a significant difference between mean (64.3 ± 38.5 HU) and median (71.0 ± 36.5 HU) lesion attenuation (p < 0.001). According to the shift of median for outcome analysis, the number of properly classified lesions increased from 12 of 19 (63%) to 13 of 19 (68%) for the Choi criteria and from 14 of 19 (74%) to 15 of 19 (79%) for the MASS criteria. Mean and median attenuation of RCC target lesions differed significantly. Use of shift of median rather than shift of mean increased the number of accurate classifications of lesions at the first follow-up CT examination.


A retrospective, descriptive study of sacral ulcer flap coverage in nonambulatory patients with hypoalbuminemia.
Deep sacral pressure ulcers in nonambulatory hospitalized patients often are managed using surgical flaps. Reports about the effects of protein status on postoperative healing are inconsistent but surgery often is delayed until serum albumin levels normalize. Considering these conflicting data and the potential effects of delayed closure, the protocol at a Philippine national university hospital was changed to allow for early surgical reconstruction of sacral ulcers in hypoalbuminemic nonambulatory patients. A retrospective chart review was conducted to evaluate clinical outcomes of 16 nonambulatory patients (10 men, 6 women; average age 54 years, range 18 to 74) with moderate to severe hypoalbuminemia who underwent flap surgery for coverage of their Stage III or Stage IV sacral ulcers within a protocol of interdisciplinary care. Outcomes measured included the number of surgeries needed for coverage and wound complications encountered. Patient average albumin level before flap coverage was 21 g/L (range: 8 to 30 g/L), average sacral ulcer size was 10 cm x 10 cm, patients underwent an average of 2.56 procedures to achieve coverage, and average follow-up period was 11.25 months (range: 3 to 33 months, SD +/- 10.4) after surgical closure. Of the 16 flaps, 15 (93.75%) were healed on final follow-up. Six patients (37.5%) had wound-related complications with more complications observed in the younger (<54 years old) patient group (r = 0.516; P = 0.039). Results suggest that with a system of interdisciplinary care and collaboration, sacral ulcer flap surgery can be performed in patients with moderate to severe hypoalbuminemia.


Cricothyroidotomy.
Cricothyroidotomy is a technique used to gain emergency access to the airway through the cricothyroid membrane. Although its use should be reserved for specific circumstances, the procedure is safe and can be performed rapidly. Knowledge of the anatomy of the anterior neck and a specific sequence for performing the cricothyroidotomy generally will result in a good success rate and acceptable complications.


Writing a philosophy of nursing?
Nurses in education and management settings are often required to write a philosophy for the facility. In this paper, the use of the concept of 'philosophy' in nursing education and nursing management is explored. The nature of philosophy is then outlined, with specific reference to its relationship with a special science such as nursing. In the light of this discussion, the real nature of the document that nursing authors call a 'philosophy' is discussed. The concepts of a life and world view and a mission statement are discussed in this regard. Specific proposals are then made for nurses in approaching the task of producing this planning document.


Studies on the proteins from the seeds of Croton tiglium and of Jatropha curcas. Toxic properties and inhibition of protein synthesis in vitro.
1. Proteins extracted from the seeds of the Euphorbiaceae croton tiglium and Jatropha curcas were separated into three major peaks (I,II,and III) by Sephadex chromatography. 2. The crude protein from both seeds and peaks I and II from Croton and peak I from Jatropha were toxic to mice, to different extents. 3. The crude protein and peak I and peak II from both seeds, inhibited protein synthesis by a reticulocyte lysate; maximum inhibition was exerted by peak II from both seeds. None of these preparations affected protein synthesis in vitro by Ehrlich ascites cells.


Antibody structure, instability, and formulation.
The number of therapeutic monoclonal antibody in development has increased tremendously over the last several years and this trend continues. At present there are more than 23 approved antibodies on the US market and an estimated 200 or more are in development. Although antibodies share certain structural similarities, development of commercially viable antibody pharmaceuticals has not been straightforward because of their unique and somewhat unpredictable solution behavior. This article reviews the structure and function of antibodies and the mechanisms of physical and chemical instabilities. Various aspects of formulation development have been examined to identify the critical attributes for the stabilization of antibodies.


Implementing a Mobile Health System to Integrate the Treatment of Addiction Into Primary Care: A Hybrid Implementation-Effectiveness Study.
Despite the near ubiquity of mobile phones, little research has been conducted on the implementation of mobile health (mHealth) apps to treat patients in primary care. Although primary care clinicians routinely treat chronic conditions such as asthma and diabetes, they rarely treat addiction, a common chronic condition. Instead, addiction is most often treated in the US health care system, if it is treated at all, in a separate behavioral health system. mHealth could help integrate addiction treatment in primary care. The objective of this paper was to report the effects of implementing an mHealth system for addiction in primary care on both patients and clinicians. In this implementation research trial, an evidence-based mHealth system named Seva was introduced sequentially over 36 months to a maximum of 100 patients with substance use disorders (SUDs) in each of three federally qualified health centers (FQHCs; primary care clinics that serve patients regardless of their ability to pay). This paper reports on patient and clinician outcomes organized according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. The outcomes according to the RE-AIM framework are as follows: Reach-Seva reached 8.31% (268/3226) of appropriate patients. Reach was limited by our ability to pay for phones and data plans for a maximum of 100 patients per clinic. Effectiveness-Patients who were given Seva had significant improvements in their risky drinking days (44% reduction, (0.7-1.25)/1.25, P=.04), illicit drug-use days (34% reduction, (2.14-3.22)/3.22, P=.01), quality of life, human immunodeficiency virus screening rates, and number of hospitalizations. Through Seva, patients also provided peer support to one another in ways that are novel in primary care settings. Adoption-Patients sustained high levels of Seva use-between 53% and 60% of the patients at the 3 sites accessed Seva during the last week of the 12-month implementation period. Among clinicians, use of the technology was less robust than use by patients, with only a handful of clinicians using Seva in each clinic and behavioral health providers making most referrals to Seva in 2 of the 3 clinics. Implementation-At 2 sites, implementation plans were realized successfully; they were delayed in the third. Maintenance-Use of Seva dropped when grant funding stopped paying for the mobile phones and data plans. Two of the 3 clinics wanted to maintain the use of Seva, but they struggled to find funding to support this. Implementing an mHealth system can improve care among primary care patients with SUDs, and patients using the system can support one another in their recovery. Among clinicians, however, implementation requires figuring out how information from the mHealth system will be used and making mHealth data available in the electronic health (eHealth) record. In addition, paying for an mHealth system remains a challenge.


Sacral neuromodulation for overactive bladder in women: do age and comorbidities make a difference?
To evaluate if age and comorbidities are associated with progression from trial phase to implantation of an implantable pulse generator in women with overactive bladder. This multisite retrospective cohort included women with overactive bladder with or without urinary incontinence who had a trial phase for sacral neuromodulation. The primary outcome was progression to implantation. A sub-analysis of implanted patients was performed for the outcome of additional therapies or "implant only" for the duration of follow-up. Multivariate logistic regression models including potential predictors of implantation and post-implantation addition of therapies were performed. At six academic institutions, 91% (785/864) of patients progressed to implantation. Post-implantation success was achieved by 69% (536/782) of patients at median follow-up of 2 (range 0.3 to 15) years. Odds of implantation [OR 0.73 (CI 0.61, 0.88)] and post-implantation success [OR 0.78 (CI 0.98, 0.97)] were lower with increasing decades of age. Medical comorbidities evaluated did not affect implantation rates or post-implant success. Most women have successful sacral neuromodulation trials despite older age and comorbidities. Higher decade of age has a negative effect on odds of implantation and is associated with addition of therapies post-implantation. Comorbidities assessed in this study did not affect implantation or addition of therapies post-implantation. Most women add therapies to improve efficacy post-implantation, and explantation rates are low.


Optimization of Ultrasound-Assisted Extraction of Antioxidant Polyphenols from the Seed Coats of Red Sword Bean (Canavalia gladiate (Jacq.) DC.).
The seed coat of red sword bean (Canavalia gladiata (Jacq.) DC.) is rich in antioxidant polyphenols. It is often discarded as a byproduct with the consumption of red sword bean, since it is very thick and not consumed by people. The aim of this study was to develop an ultrasound-assisted extraction method to extract natural antioxidants from the seed coats. The extraction process was optimized by using response surface methodology. After the single-factor experiments, three key factors, including ethanol concentration, liquid/solid ratio, and extraction time, were selected and their interactions were studied using a central composite design. The optimal extraction condition was 60.2% hydroethanol, a liquid/solid ratio of 29.3 mL/g, an extraction time of 18.4 min, an extraction temperature of 50 °C, and ultrasound power of 400 W. Under the optimal conditions, antioxidant activity of the extract was 755.98 ± 10.23 μmol Trolox/g dry weight (DW), much higher than that from maceration (558.77 ± 14.42 μmol Trolox/g DW) or Soxhlet extraction (479.81 ± 12.75 μmol Trolox/g DW). In addition, the main antioxidant compounds in the extract were identified and quantified by high-performance liquid chromatography-diode array detection-tandem mass spectrometry (HPLC-DAD-MS/MS). The concentrations of digalloyl hexoside, methyl gallate, gallic acid, trigalloyl hexoside, and digallic acid were 15.30 ± 0.98, 8.85 ± 0.51, 8.76 ± 0.36, 4.27 ± 0.21, and 2.89 ± 0.13 mg/g DW. This study provides an efficient and green extraction method for the extraction of natural antioxidants from the bean coat of red sword bean. The extract of antioxidants might be added into functional foods or nutraceuticals with potential beneficial functions.


Academic help-seeking behavior among student pharmacists.
Objectives. To identify factors associated with academic help-seeking behavior among student pharmacists at a public university.Methods. Semi-structured focus group interviews were conducted to explore in depth perceptions of facilitators of and barriers to the help-seeking behavior and academic achievement of student pharmacists who had received a D or F grade in any year. A 4-part survey instrument was developed and administered to all student pharmacists and included sections for (1) attitudes and academic help-seeking behavior, (2) health status, (3) demographics, and (4) open comments. A structural equation modeling approach was used to assess relationships among domains of interest.Results. Three student focus groups noted that helpfulness of faculty members and school administrators were 2 prominent facilitators of help-seeking behavior and academic achievement. Diminished quality of life caused by stress and depression was the primary barrier to help-seeking and achievement. Three hundred four (68.6%) student pharmacists completed the survey instrument. Academic help-seeking behavior was influenced mostly by perceived academic competence and perceived faculty helpfulness. In contrast, ambivalence and perception of help-seeking as threatening were 2 factors that were negatively associated with academic help-seeking behavior.Conclusions. Academic help-seeking behavior was positively related to greater perceived academic competence and positive relationships among student pharmacists and faculty members.


Predicting the risk of "permanent" nursing home residence: the role of community help as indicated by family helpers and prior living arrangements.
This study examines the difference between permanent and transitory residence in a nursing home with special emphasis on the extent to which the risk of a long nursing home stay is reduced by the availability of informal help in the community. Secondary data were used, taken from the National Long-Term Care Surveys of 1982 and 1984. The 1982 NLTCS samples disabled elderly living in the community. For these community dwellers, the 1984 NLTCS provides information on continued residence in the community and on their nursing home episodes between 1982 and 1984. METHOD OF ANALYSIS: The analysis is based on estimates from a multinomial logit regression with three explicit categories: persons with at least one long nursing home stay (n = 292), persons with only short stays (n = 227), and persons who died without ever having had a nursing home stay (n = 945). The implicit category: persons living in the community in 1984 without having had any nursing home stay (n = 3,368). This study demonstrates the systematic differences in the personal characteristics that predict the risk of long stays from those that predict short stays in a nursing home. Controlling for limitations in physical and cognitive functioning, the regression analysis shows that indicators of informal help in the community have a statistically significant and relatively large effect on the risk of long stays; but the effects of these indicators on the risk of short stays is numerically smaller and not statistically significant. Specifically, when the burden of caregiving is shared by a spouse and children, the risk of a long stay in a nursing home is reduced by 9.3 percentage points; in contrast, the risk is increased by 18 percentage points for childless elders who are living alone and by 45.8 percentage points for elders living with adults other than a spouse or children. The relatively strong effects of family helpers and living arrangements on the risk of long nursing home stays confirm the hypothesis that, after controlling for the effects of physical and cognitive functioning, adequate help in the community reduces the risk of permanent nursing home residence. But help in the community has no effect on the risk of short nursing home episodes because these episodes are likely to be extensions of acute hospital care. The findings provide essential information for designing a long-term care program because they suggest the magnitudes of the effects that such a program can have on reducing the risk of permanent nursing home residence.


Approach to the acute abdomen in pregnancy.
Numerous physiologic changes in pregnancy may affect the presentation of abdominal pain in pregnancy. A high index of suspicion must be used when evaluating a pregnant patient with abdominal pain. General anesthesia is considered safe in pregnancy. Intraoperative monitoring and tocolytics should be individualized. Laparoscopic surgery should be performed in the second trimester when possible and appears as safe as laparotomy. If indicated, diagnostic imaging should not be withheld from the pregnant patient. Appendectomy and cholecystectomy appear to be safe in pregnancy. The reported incidence of adnexal masses and fibroids in pregnancy may increase with increasing use of first-trimester ultrasound. Conservative management, with surgical management postpartum, appears reasonable in most cases.


[Clinical investigation of cerebral infarction following head and neck injury].
The diagnosis of cerebral infarction following head and neck injury is difficult because of the lucid interval, which causes high mortality and morbidity. We report six patients with cerebral infarction following head and neck injury, whom we treated from 1993 to 2005. Only one patient suffered from cerebral infarction following direct neck injury. At the time of injury three patients had prodromal symptoms and the others had no symptoms. Three patients were diagnosed with artery-to-artery embolism based on the dissection of the internal carotid artery in the neck, two patients, from the dissection of the vertebral artery in the neck, and one patient was diagnosed with Wallenberg's syndrome. The overall patient outcomes at discharge as measured by using the Glasgow Outcome Scale were as follows: moderately disabled in one, severely disabled in three, vegetative survival in one, and death in two patients. No patient had been administered a screening test for neck vessel injury, indicating the difficulty in diagnosis. Prodromal symptoms, due to not only direct but also indirect neck injuries indicate the possibility of neck vessels injury, and hence, we should develop a method that enables the early detection of lesions caused by neck vessel injury.


The proton motive force, acting on acidic residues, promotes translocation of amino-terminal domains of membrane proteins when the hydrophobicity of the translocation signal is low.
We have shown previously that the first transmembrane segment of leader peptidase can function to translocate the polar amino-terminal Pf3 domain across the membrane into the periplasm independently of the proton motive force (pmf) (Lee, J. I., Kuhn, A., and Dalbey, R. E. (1992) J. Biol. Chem. 267, 938-943). We now show that when the first transmembrane segment lacks a strong hydrophobic character, the pmf is required for translocation. In addition, we find that the amino-terminal acidic residue proximal to the transmembrane domain plays a critical role in pmf-dependent amino-terminal translocation. Moreover, the pmf is required to hold the amino-terminal domain in the periplasm to prevent it from slipping such that the amino terminus is no longer exposed to the periplasm. In all cases, translocation occurs under conditions in which the function of the Sec machinery is impaired. These studies show that the low hydrophobicity of the first apolar domain (the translocation signal) can be compensated for by a negative charge in the amino-terminal region, upon which the pmf acts.


The bruxism construct: From cut-off points to a continuum spectrum.
This commentary discusses the need to move on from the adoption of cut-off points for the definition of the presence/absence of bruxism and justifies the need to embrace an evaluation based on the continuum of jaw motor behaviours. Currently, the number of events per hour, as identified by polysomnography (PSG), is used to define the presence of sleep bruxism (SB). Whilst PSG still remains the indispensable equipment to study the neurophysiological correlates of SB, the scoring criteria based on a cut-off point are of questionable clinical usefulness for the study of oral health outcomes. For awake bruxism (AB), criteria for a definite diagnosis have never been proposed. Some goal-oriented strategies are proposed to identify bruxism behaviours that increase the risk of negative oral health outcomes (eg, tooth wear, muscle and/or temporomandibular joint [TMJ] pain, restorative complications). One possible strategy would embrace an improved knowledge on the epidemiology and natural variability of bruxism, even including study of the amount of PSG/SB and electromyography masticatory muscle activity (EMG/MMA) during sleep and the frequency/prevalence of bruxism behaviours during wakefulness that are needed to represent a risk factor for clinical consequences, if any. There should not be any preclusion about the diagnostic strategies to pursue that goal, and a combination of instrumental and non-instrumental approaches may even emerge as the best available option. Once data are available, large-scale, non-selected population samples representing the entire continuum of EMG/MMA activities are also needed, in the attempt to estimate untreated health risks in the population.


Clinicians guide for cue-based transition to oral feeding in preterm infants: An easy-to-use clinical guide.
This article aims to provide evidence to guide multidisciplinary clinical practitioners towards successful initiation and long-term maintenance of oral feeding in preterm infants, directed by the individual infant maturity. A comprehensive review of primary research, explorative work, existing guidelines, and evidence-based opinions regarding the transition to oral feeding in preterm infants was studied to compile this document. Current clinical hospital practices are described and challenged and the principles of cue-based feeding are explored. "Traditional" feeding regimes use criteria, such as the infant's weight, gestational age and being free of illness, and even caregiver intuition to initiate or delay oral feeding. However, these criteria could compromise the infant and increase anxiety levels and frustration for parents and caregivers. Cue-based feeding, opposed to volume-driven feeding, lead to improved feeding success, including increased weight gain, shorter hospital stay, fewer adverse events, without increasing staff workload while simultaneously improving parents' skills regarding infant feeding. Although research is available on cue-based feeding, an easy-to-use clinical guide for practitioners could not be found. A cue-based infant feeding regime, for clinical decision making on providing opportunities to support feeding success in preterm infants, is provided in this article as a framework for clinical reasoning. Cue-based feeding of preterm infants requires care providers who are trained in and sensitive to infant cues, to ensure optimal feeding success. An easy-to-use clinical guideline is presented for implementation by multidisciplinary team members. This evidence-based guideline aims to improve feeding outcomes for the newborn infant and to facilitate the tasks of nurses and caregivers.


[Evaluation of Direct and Indirect Expenditures for Management of Patients With Stable Ischemic Heart Disease After Stenting of Coronary Arteries].
Assessment of cost of management of patients during 1 year after stenting of coronary arteries has shown that priority should be given to active introduction into practical health care of technologies increasing duration of life and lowering probability of invalidization. We stress the need for evaluation of indirect expenditures on patients care because of their substantial share in the total cost. We also consider essential to elaborate measures of state regulation of medication supply irrespective of type of treatment for shifting expenditures from hospital to ambulatory sector and improvement of effectiveness of pharmacotherapy.


Regulation of cell-mediated immunologic reactivity to Moloney murine sarcoma virus-induced tumors. II. Nature of blocking and unblocking factors in serum.
Serum blocking factors, detected in sera of inbred CBA and BALB/c mice with progressing virus-induced tumors by their interference with leukocyte-adherence inhibition (LAI) with the use of syngeneic leukocytes, were found to be strain related: No blocking occurred with allogeneic leukocytes. Furthermore, the unblocking factors of regressor serum were also strain related: No unblocking of allogeneic progressor serum was observed. There was no requirement for H-2 compatibility between leukocytes and tumor cells from which the LAI-inducing antigen was obtained. Absorption of CBA blocking serum with anti-I-Jk antiserum (and with anti-Ik containing this antibody specificity) removed blocking activity; absorption of regressor serum did not reduce its unblocking activity. These observations indicated that certain blocking factors resembled other suppressor factors in possessing antigenic determinants coded by the I-J subregion of the major histocompatibility complex. Their strain restriction and antigen specificity suggested combination with reactive lymphocytes in blocking LAI. The properties of unblocking factors suggested they combine with blocking factors and resemble antiidiotypic antibodies.


Nucleic acids in human glioma treatment: innovative approaches and recent results.
Gliomas are the most common primary central nervous system tumors with a dismal prognosis. Despite recent advances in surgery, radiotherapy, and chemotherapy, current treatment regimens have a modest survival benefit. A crucial challenge is to deliver drugs effectively to invasive glioma cells residing in a sanctuary within the central nervous system. New therapies are essential, and oligonucleotide-based approaches, including antisense, microRNAs, small interfering RNAs, and nucleic acid aptamers, may provide a viable strategy. Thanks to their unique characteristics (low size, good affinity for the target, no immunogenicity, chemical structures that can be easily modified to improve their in vivo applications), these molecules may represent a valid alternative to antibodies particularly to overcome challenges presented by the blood-brain barrier. Here we will discuss recent results on the use of oligonucleotides that will hopefully provide new effective treatment for gliomas.


Tuning face perception with electrical stimulation of the fusiform gyrus.
The fusiform gyrus (FG) is an important node in the face processing network, but knowledge of its causal role in face perception is currently limited. Recent work demonstrated that high frequency stimulation applied to the FG distorts the perception of faces in human subjects (Parvizi et al. []: J Neurosci 32:14915-14920). However, the timing of this process in the FG relative to stimulus onset and the spatial extent of FG's role in face perception are unknown. Here, we investigate the causal role of the FG in face perception by applying precise, event-related electrical stimulation (ES) to higher order visual areas including the FG in six human subjects undergoing intracranial monitoring for epilepsy. We compared the effects of single brief (100 μs) electrical pulses to the FG and non-face-selective visual areas on the speed and accuracy of detecting distorted faces. Brief ES applied to face-selective sites did not affect accuracy but significantly increased the reaction time (RT) of detecting face distortions. Importantly, RT was altered only when ES was applied 100ms after visual onset and in face-selective but not place-selective sites. Furthermore, ES applied to face-selective areas decreased the amplitude of visual evoked potentials and high gamma power over this time window. Together, these results suggest that ES of face-selective regions within a critical time window induces a delay in face perception. These findings support a temporally and spatially specific causal role of face-selective areas and signify an important link between electrophysiology and behavior in face perception. Hum Brain Mapp 38:2830-2842, 2017. © 2017 Wiley Periodicals, Inc.


Spectral Analysis of Acceleration Data for Detection of Generalized Tonic-Clonic Seizures.
Generalized tonic-clonic seizures (GTCSs) can be underestimated and can also increase mortality rates. The monitoring devices used to detect GTCS events in daily life are very helpful for early intervention and precise estimation of seizure events. Several studies have introduced methods for GTCS detection using an accelerometer (ACM), electromyography, or electroencephalography. However, these studies need to be improved with respect to accuracy and user convenience. This study proposes the use of an ACM banded to the wrist and spectral analysis of ACM data to detect GTCS in daily life. The spectral weight function dependent on GTCS was used to compute a GTCS-correlated score that can effectively discriminate between GTCS and normal movement. Compared to the performance of the previous temporal method, which used a standard deviation method, the spectral analysis method resulted in better sensitivity and fewer false positive alerts. Finally, the spectral analysis method can be implemented in a GTCS monitoring device using an ACM and can provide early alerts to caregivers to prevent risks associated with GTCS.


Data evaluation of broiler chicken rearing and slaughter-An exploratory study.
To process and evaluate the data from broiler fattening and slaughtering, we investigated the production data of 107 straight run flocks of the commercial meat-type breed Ross 308 (Aviagen, EU). All flocks were raised and slaughtered in Germany and the average slaughter age was 37 days. The health outcomes of interest were mortality, average weight, and the slaughter results. First-week mortality, cumulative mortality, stocking density, flock size, season, production week of the parental flock, farm, antibiotic treatment, and the interaction between antibiotic treatment and season were considered as possible influencing factors. The average first-week mortality (FWM) and cumulative mortality percentages were 0.66 and 2.74%, respectively. First-week mortality was influenced by flock size, production week of the parental flock, and the interaction between antibiotic treatment and season, whereas cumulative mortality was influenced by antibiotic treatment, farm, and first-week mortality. The average weight (mean 2.30 kg) was influenced by season, stocking density, flock size, farm, and the interaction between antibiotic treatment and season. The condemnation rate was on average 1.48%, with the most common causes being deep dermatitis (mean 0.63%), ascites (mean 0.53%), and not suitable for production/general disease (mean 0.25%). Several factors influenced the causes of condemnation, with season being the most predominant one, followed by the interaction between antibiotic treatment and season, the antibiotic treatment alone, and stocking density.