Proton conductivity dependence on the surface polymer thickness of core-shell type nanoparticles in a proton exchange membrane.
The proton exchange membrane (PEM) is the main component that determines the performance of polymer electrolyte fuel cells. The construction of proton-conduction channels capable of fast proton conduction is an important topic in PEM research. In this study, we have developed poly(vinylphosphonic acid)-block-polystyrene (PVPA-b-PS)-coated core-shell type silica nanoparticles prepared by in situ polymerization and a core-shell type nanoparticle-filled PEM. In this system, two-dimensional (2D) proton-conduction channels have been constructed between PVPA and the surface of silica nanoparticles, and three-dimensional proton-conduction channels were constructed by connecting these 2D channels by filling with the core-shell type nanoparticles. The proton conductivities and activation energies of pelletized PVPA-coated core-shell type nanoparticles increased depending on the coated PVPA thickness. Additionally, pelletized PVPA-b-PS-coated silica nanoparticles showed a good proton conductivity of 1.3 × 10-2 S cm-1 at 80 °C and 95% RH. Also, the membrane state achieved 1.8 × 10-4 S cm-1 in a similar temperature and humidity environment. Although these proton conductivities were lower than those of PVPA, they have advantages such as low activation energy for proton conduction, suppression of swelling due to water absorption, and the ability to handle samples in powder form. Moreover, by using PS simultaneously, we succeeded in improving the stability of proton conductivity against changes in the temperature and humidity environment. Therefore, we have demonstrated a highly durable, tough but still enough high proton conductive material by polymer coating onto the surface of nanoparticles and also succeeded in constructing proton-conduction channels through the easy integration of core-shell type nanoparticles.


Electrokinetic sweeping of colloids at a reactive magnesium oxide interface.
Investigating the electrokinetic (EK) response in the vicinity of interfaces has regained interest due to the development of new membrane based processes for energy harvesting or soil depollution. However, the case of reactive interfaces, ubiquitous in these processes, remains scarcely explored. Here we experimentally investigate the EK response of a model interface between an aqueous electrolyte and a bulk MgO crystal surface (100), for different pH. For that purpose, we use a lab-scale non invasive method to monitor the zeta potential of the interface versus time, by confocal fluorescent particle tracking. An unexpected motion of the particles, repelled and then attracted again by the interface is observed. We attributed this motion to the surface reactivity, inducing ion concentration gradients perpendicular to the interface and subsequent diffusiophoresis of the charged particle. Accordingly, we could describe at a semi-quantitative level the particle dynamics by solving numerically the Poisson-Nernst-Planck equations to establish concentration profile in the system and subsequent diffusiophoretic motion. These experiments open the way to the characterization of both the EK response and the reaction rate in the vicinity of reactive interfaces.


Vitellogenin B2 gene in Xenopus laevis: isolation, in vitro transcription and relation to other vitellogenin genes.
The isolation of the four Xenopus laevis vitellogenin genes has been completed by the purification from a DNA library of the B2 gene together with its flanking sequences. The overlapping DNA fragments analyzed cover 34 kilobases. The B2 gene which has a length of 17.5 kilobases was characterized by heteroduplex and R-loop mapping in the electron microscope and by in vitro transcription in a HeLa whole-cell extract. Its structural organization is compared with that of the closely related B1 gene. The mRNA-coding sequence of about 6 kilobases is interrupted 34 times in the B1 gene and 33 times in the B2 gene. Sequence homology between the two genes was not only found in exons. In addition, 54% of the intron sequences as well as 63% and 48.5% respectively of the 5' and 3' flanking sequences, show enough homology to form stable duplexes. These findings are compared with earlier results obtained with the two other closely related members of the vitellogenin gene family, the A1 and the A2 genes.


Office-based opioid dependence treatment.
Opioid misuse and abuse occurring in association with the treatment of chronic non-cancer pain are not new phenomena, but their increasing prevalence in recent years is unprecedented. Advancements in pharmaceutical technologies have provided opioid-related drugs, which lack the pure mu agonist activity characteristic of the typical opioid congeners. This absent or altered mu receptor activity imparts an opioid receptor antagonistic or partial agonistic pharmacologic action, which serves to modulate the development of opioid-induced tolerance and physical dependence and facilitate detoxification and withdrawal from opioids. Opioid antagonists and partial agonists are being used in abuse deterrent strategy regimens to prevent opioid tolerance and the development of dependence, as well as in the management of opioid detoxification and treatment of withdrawal. The specific opioid antagonists and partial agonists used in these various therapeutic modalities will be the focus of this review. Evaluate the comparative therapeutic utility of opioid antagonists and partial agonists in preventing the development of opioid tolerance and treating opioid dependence, detoxification, and withdrawal. A primary focus is the use of opioid antagonists and partial agonists within an office-based practice. A narrative review of the current literature involving the therapeutic use of opioid antagonists and partial agonists in the management of opioid tolerance, dependence, detoxification, and withdrawal. A computerized literature search in the PubMed, EMBASE, BioMed, and Cochrane Library review databases from 2008 through 2010 was performed. This search included systematic and narrative reviews, prospective and retrospective studies, as well as cross-references from bibliographies of notable primary and review articles and abstracts from scientific meetings. US Food and Drug Administration records and pharmaceutical manufacturers' product literature were also used in the search. Opioid dependency, whether it results from the misuse or abuse of prescription or street drugs, continues to be a significant public health issue. Passage of DATA 2000 and US Food and Drug Administration approval of buprenorphine and buprenorphine/ naloxone has revolutionized opioid dependence therapy. The traditional addiction medicine therapy regimen of methadone maintenance, with its inherent legal limitations and restrictions, has been challenged by an office-based dependence practice with buprenorphine serving as a prominent therapeutic tool.


HIV Preexposure Prophylaxis Care Continuum Among Individuals Receiving Medication for Opioid Use Disorder, South Carolina, 2020-2021.
We implemented the HIV preexposure prophylaxis (PrEP) care continuum among individuals receiving medication for opioid use disorder (MOUD). We screened HIV-negative MOUD participants for PrEP eligibility by assessing injection drug use risk factors and sexual behaviors. Implementation of the PrEP care continuum was challenging; less than a third of MOUD participants were aware of PrEP, and very few initiated PrEP. Findings should promote the development of effective interventions to increase engagement in PrEP during MOUD treatment. (Am J Public Health. 2022;112(1):34-37. https://doi.org/10.2105/AJPH.2021.306566).


Psychosocial consequences of living kidney donation: a prospective multicentre study on health-related quality of life, donor-recipient relationships and regret.
Previous studies have indicated decreased health-related quality of life (HRQoL) shortly after kidney donation, returning to baseline in the longer term. However, a subgroup of donors experiences persistent HRQoL problems. To identify which HRQoL aspects are impacted most by the donation and to identify at-risk donors, more specific insight into psychosocial donation consequences is needed. The current study examined the HRQoL course, donor-perceived consequences of donation for donors, recipients and donor-recipient relationships, and regret up to 12 months post-donation in donors from seven Dutch transplantation centres. Kidney donor candidates (n = 588) completed self-report questionnaires early in the screening procedure, of which 361 (61%) donated their kidney. Data for 230 donors (64%) with complete assessments before donation and 6 and 12 months post-donation were analysed. Results indicated that donor physical HRQoL was comparable at all time points, except for an increase in fatigue that lasted up to 12 months post-donation. Mental HRQoL decreased at 6 months post-donation, but returned to baseline at 12 months. Donors reported large improvements in recipient's functioning and a smaller influence of the recipient's kidney disease or transplantation on the donor's life over time. A subgroup experienced negative donation consequences with 14% experiencing regret 12 months post-donation. Predictors of regret were more negative health perceptions and worse social functioning 6 months post-donation. The strongest baseline predictors of higher fatigue levels after donation were more pre-donation fatigue, worse general physical functioning and a younger age. Future research should examine predictors of HRQoL after donation to improve screening and to provide potential interventions in at-risk donors.


The Adjunctive Value of Diffusion Weighted Imaging in Diagnosis and Follow Up of Uterovaginal Diffuse B-cell Lymphoma: A Case Report and Literature Review.
Lymphoma of the female gynecologic tract is extremely rare. Typically, lymphoma is managed nonsurgically unlike other non-lymphomatous malignant tumors raising the importance of differentiation between both entities. We describe the Magnetic Resonance Imaging (MRI) features of a case of uterovaginal diffuse large B-cell lymphoma in a 50-year-old postmenopausal woman emphasizing Diffusion-Weighted Imaging (DWI) as a diagnostic and follow up tool. We reviewed the literature regarding the diagnostic methods for female genital lymphoma. Forty-five cases, including our patient, were reviewed with an age range from 22 to 85 years. Vaginal bleeding was the most common presentation. The diagnosis was established by Papanicolaou smear, cervical biopsy (25/45), endometrial biopsy (6/45), vaginal biopsy (2/45), pelvic mass biopsy (2/45), iliac LN biopsy (1/45) and surgical diagnosis (8/45). Diffuse Large B-Cell Lymphomas (DLBCL) constitute the vast majority of the cases (82%). The uterine cervix was involved at diagnosis in the majority of these cases (68%), while the uterine body (42%) and vagina (28%) were less involved. Pelvic lymphadenopathy was found in 15 cases, while extra genital lymphomatous infiltration in 13 cases. Sonographic findings were nonspecific, while CT provided excellent data about extra-genital involvement. Thirteen cases underwent pelvic MRI that displayed superior detection of disease extension and parametric involvement. Diffusion restriction was reported only in one case without quantitative analysis of ADC map. MRI shows unique features that differentiate uterovaginal lymphoma from the much more common carcinomas and discriminate post-operative changes from tumor recurrence. It exhibits a marked restricted diffusion pattern with lower ADC values than carcinomas and post-operative changes.


[Retroperitoneal fibrosis with eye-drops containing timolol].
Retroperitoneal fibrosis occurred in a 62-year-old man who had been treated during 4 years eye-drops containing timolol. The disease was diagnosed after a sudden episode of nephritic colic. The recovery was progressive and uneventful. No corticosteroid therapy was used. Six months later the patient remained free of symptoms. Although an idiopathic origin could not be excluded, the causal relationship with timolol treatment is likely due to the chronology of events and the lack of other causes.


Self-reported trait mindfulness and affective reactivity: a motivational approach using multiple psychophysiological measures.
As a form of attention, mindfulness is qualitatively receptive and non-reactive, and is thought to facilitate adaptive emotional responding. One suggested mechanism is that mindfulness facilitates disengagement from an affective stimulus and thereby decreases affective reactivity. However, mindfulness has been conceptualized as a state, intervention, and trait. Because evidence is mixed as to whether self-reported trait mindfulness decreases affective reactivity, we used a multi-method approach to study the relationship between individual differences in self-reported trait mindfulness and electrocortical, electrodermal, electromyographic, and self-reported responses to emotional pictures. Specifically, while participants (N = 51) passively viewed pleasant, neutral, and unpleasant IAPS pictures, we recorded high-density (128 channels) electrocortical, electrodermal, and electromyographic data to the pictures as well as to acoustic startle probes presented during the pictures. Afterwards, participants rated their subjective valence and arousal while viewing the pictures again. If trait mindfulness spontaneously reduces general emotional reactivity, then for individuals reporting high rather than low mindfulness, response differences between emotional and neutral pictures would show relatively decreased early posterior negativity (EPN) and late positive potential (LPP) amplitudes, decreased skin conductance responses, and decreased subjective ratings for valence and arousal. High mindfulness would also be associated with decreased emotional modulation of startle eyeblink and P3 amplitudes. Although results showed clear effects of emotion on the dependent measures, in general, mindfulness did not moderate these effects. For most measures, effect sizes were small with rather narrow confidence intervals. These data do not support the hypothesis that individual differences in self-reported trait mindfulness are related to spontaneous emotional responses during picture viewing.


Adrenal carcinosarcoma--a case report.
Carcinosarcoma of the adrenal gland is an extremely rare variant of adrenocortical carcinoma, characterized by a biphasic pattern of carcinoma and sarcoma-like components. We report a case of adrenal carcinosarcoma occurring in a 61-year-old Korean man who presented with right flank pain of one month duration radiating to the back and right iliac crest. The tumor measured 12 x 12 x 7 cm and adhered to the liver and right upper pole of the kidney. The carcinomatous component of the tumor showed polygonal cells in a broad anastomosing trabecular pattern with delicate slit-like vascular channels; the sarcomatous component showed uniform spindled cells in a fascicular pattern. Both the carcinomatous and sarcomatous portions of the tumor were positive for pan-cytokeratin, and vimentin stained only the sarcomatous areas.


An Exploratory Brief Head-To-Head Non-Inferiority Comparison of an Internet-Based and a Telephone-Delivered CBT Intervention for Adults with Depression.
Telephone-administered psychotherapy (tCBT) and internet-based treatments (iCBT) may overcome barriers to mental health treatment. TCBT has demonstrated efficacy similar to traditional psychotherapy, however, few studies have compared iCBT to efficacious interventions. This exploratory study examined the noninferiority of iCBT relative to tCBT. We also explored pretreatment moderators of outcome and assessed treatment dropout. As a secondary exploratory analysis of a 304-participant randomized noninferiority trial, we compared iCBT, the first level of a stepped-care intervention, with tCBT on depression outcome after 5 weeks of treatment (prior to stepping). Multiple linear regression models were fit to examine moderators of 5-week depression. Differences in dropout were examined using Kaplan-Meier survival analysis. After 5 weeks of treatment, both interventions significantly reduced depression severity. The effect size difference between the two interventions was d=0.004 [90% CI=-0.19 to 0.19]; the CI did not cross the non-inferiority margin. Pretreatment depression was significantly associated with depression at week 5. The relationship between cognitive strategy usefulness and depression at week 5 differed between interventions, controlling for pretreatment depression. There was no significant difference in dropout between interventions. Given the stepped-care trial design, iCBT and tCBT could not be compared at the end of treatment or follow-up. Analyses were exploratory and should be interpreted with caution. A large sample, powered for noninferiority, found iCBT no less efficacious than tCBT at reducing depression symptoms after five weeks of treatment.


Natural Language Processing for Adjudication of Heart Failure in a Multicenter Clinical Trial: A Secondary Analysis of a Randomized Clinical Trial.
The gold standard for outcome adjudication in clinical trials is medical record review by a physician clinical events committee (CEC), which requires substantial time and expertise. Automated adjudication of medical records by natural language processing (NLP) may offer a more resource-efficient alternative but this approach has not been validated in a multicenter setting. To externally validate the Community Care Cohort Project (C3PO) NLP model for heart failure (HF) hospitalization adjudication, which was previously developed and tested within one health care system, compared to gold-standard CEC adjudication in a multicenter clinical trial. This was a retrospective analysis of the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial, which compared 2 influenza vaccines in 5260 participants with cardiovascular disease at 157 sites in the US and Canada between September 2016 and January 2019. Analysis was performed from November 2022 to October 2023. Individual sites submitted medical records for each hospitalization. The central INVESTED CEC and the C3PO NLP model independently adjudicated whether the cause of hospitalization was HF using the prepared hospitalization dossier. The C3PO NLP model was fine-tuned (C3PO + INVESTED) and a de novo NLP model was trained using half the INVESTED hospitalizations. Concordance between the C3PO NLP model HF adjudication and the gold-standard INVESTED CEC adjudication was measured by raw agreement, κ, sensitivity, and specificity. The fine-tuned and de novo INVESTED NLP models were evaluated in an internal validation cohort not used for training. Among 4060 hospitalizations in 1973 patients (mean [SD] age, 66.4 [13.2] years; 514 [27.4%] female and 1432 [72.6%] male]), 1074 hospitalizations (26%) were adjudicated as HF by the CEC. There was good agreement between the C3PO NLP and CEC HF adjudications (raw agreement, 87% [95% CI, 86-88]; κ, 0.69 [95% CI, 0.66-0.72]). C3PO NLP model sensitivity was 94% (95% CI, 92-95) and specificity was 84% (95% CI, 83-85). The fine-tuned C3PO and de novo NLP models demonstrated agreement of 93% (95% CI, 92-94) and κ of 0.82 (95% CI, 0.77-0.86) and 0.83 (95% CI, 0.79-0.87), respectively, vs the CEC. CEC reviewer interrater reproducibility was 94% (95% CI, 93-95; κ, 0.85 [95% CI, 0.80-0.89]). The C3PO NLP model developed within 1 health care system identified HF events with good agreement relative to the gold-standard CEC in an external multicenter clinical trial. Fine-tuning the model improved agreement and approximated human reproducibility. Further study is needed to determine whether NLP will improve the efficiency of future multicenter clinical trials by identifying clinical events at scale.


Evaluation of a successful intervention for sustainability and effects in post research phase.
Promoting appropriate use of drugs is an essential element in achieving quality of health and medical cares for patients and the community, and also to minimize financial burden. The objective of this paper is to assess the successful intervention for sustainability and effects in post research phase. To address these problems, a variety of educational, managerial and regulatory strategies to improve prescribing have been tried in Nepal. When training is combined with a managerial intervention i.e. peer-group discussion, it results into improved changes in prescribing practices of paramedics in several practices. A prospective, three-way design study consisting of small group training, small group training followed by peer-group discussion and control was conducted in three regions of Nepal including one hill and two terai (plains) districts from each region. The study included all health post from the sampled districts, making 80 health posts the study population. The study revealed the effectiveness of the peer-group discussion approach in improving the prescribing practices. An assessment to identify the sustainability of the strategy and its effect within the district healthcare system after the completion of the research phase was undertaken. The study found that peer-group discussion was discontinued in all targeted districts and the improved practices were not sustained after the completion of the research. Various reasons have been found for not continuing the effective intervention.


Management of clinical stage I nonseminomatous germ cell tumors.
Therapeutic options for clinical stage I nonseminomatous germ cell tumor include active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND). Lymphovascular invasion (LVI) determines risk of recurrence, as those without LVI have 15% risk of relapse on surveillance while those with LVI have a 50% risk. This stratifies patients into high risk(LVI+) and low risk(LVI-) groups which direct treatment recommendations. Surveillance is preferred for those with low risk disease, and is an option for those with high risk disease, as at least half are over-treated with other options. Adjuvant chemotherapy is an option for all patients as it can eradicate micrometastatic disease and reduce recurrence by at least 90%. RPLND benefits patients with low volume retroperitoneal disease with a cure rate of RPLND alone at approximately 70%. All three treatment modalities have similar survival rates approaching 100% but differing potential morbidities, which, along with patient preferences and compliance, should guide treatment decisions.


Coffee consumption is not associated with the risk of gastric cancer: An updated systematic review and meta-analysis of prospective cohort studies.
The results from epidemiological studies on the relationship between coffee consumption and gastric cancer risk are inconsistent and inconclusive. Based on the previous studies, we hypothesized that coffee consumption was not associated with the risk of gastric cancer. We aimed to test this hypothesis by conducting a meta-analysis to systematically review and quantify the relationship between coffee consumption and the risk of gastric cancer. Relevant prospective cohort studies were identified by a search of PubMed and Embase up to March 2021. A total of 18 independent prospective cohorts from 15 studies involving 1,608,760 participants and 3898 gastric cancer cases were included in this meta-analysis. A nonsignificant association with a pooled relative risk (RR) of 1.11 (95% confidence interval [CI], 0.99-1.25) was shown between coffee intake and the risk of gastric cancer. The dose-response analysis also suggested no significant effect on the risk of gastric cancer per 1 cup/d increment in coffee consumption (RR = 1.00; 95% CI, 0.99-1.01). No nonlinear association of gastric cancer risk with coffee consumption was found (P for nonlinearity = .17). In the subgroup analyses, significantly increased risk of gastric cancer was detected in the studies conducted in the United States (RR = 1.28; 95% CI, 1.03-1.58). In conclusion, coffee consumption had no effect on the risk of gastric cancer. However, the effect of coffee intake on persons in the United States must be further evaluated by additional high-quality and large-scale cohort studies.


Mercury, selenium, and glutathione peroxidase in dental personnel.
Eighteen persons, dentists and nurses, with urinary mercury levels higher than the group median value of all dental personnel in the country of Västerbotten were compared with a group consisting of 15 persons with low urinary mercury levels working in the same clinics. A statistically significant difference between the high urinary mercury group and the low urinary mercury group could be seen in the plasma mercury level. In each group a statistically significant relation could be seen between the plasma mercury level and the total number of amalgam surfaces. The two groups did not differ with regard to the levels of plasma selenium and erythrocyte glutathione peroxidase, and no correlation between these two variables and the plasma mercury levels could be found. To evaluate organ functions, a large number of supplementary analyses were performed. These analyses did not indicate any influence on organ functions. Although the persons in the present study were occupationally exposed to mercury, none of the biologic variables analyzed seemed to be affected. Even among dental personnel who handle amalgam professionally the number of amalgam surfaces is a major contributory factor to the P-mercury level.


Giant malignant insulinoma which developed from a non-functioning pancreatic tumor over a long period of time.
Insulinomas are the most common hormone-producing pancreatic neuroendocrine tumors (NETs), which are usually benign, solitary and small. We describe herein a patient with a giant insulinoma (>10 cm in diameter) with concomitant thyroid tumor as detected by Somatostatin receptor scintigraphy (SRS). A 50-year-old man presented hypoglycemic symptoms 20 years after the first detection of a pancreatic tumor, which was ameliorated by administration of a somatostatin analogue, octreotide. SRS showed abnormal uptake by the insulinoma as well as by the thyroid tumor. RT-PCR and immunohistochemical study revealed abundant expression of somatostatin receptor (SSTR)-1, -2, and -5 in his insulinoma and SSTR-1 and -2 in his thyroid follicular neoplasm. This is a rare case of a slow-growing pancreatic well-differentiated neuroendocrine carcinoma over a long period of time to become a symptomatic giant insulinoma. Furthermore, SRS proves to be a useful tool for localization of insulinoma as well as concomitant thyroid neoplasm with predominant expression of SSTRs.


Clinical research into anesthetic neurotoxicity: does anesthesia cause neurological abnormalities in humans?
General anesthetics mitigate distress and exaggerated hemodynamic responses to pain and stressful stimulation, allowing surgery and diagnostic procedures to be performed worldwide in millions of children every year. Emerging studies, mainly carried out in early postnatal laboratory animals, demonstrate widespread neuronal elimination, alteration in neuronal circuitry, and long-term neurological disabilities following exposure to all commonly used sedatives and anesthetics. These findings have raised concerns among parents, anesthesiologists, neuroscientists, and government regulators about the safety of anesthetic drugs in children, especially infants. Accumulating evidence from epidemiological studies suggests an association between surgery with anesthesia in early childhood and subsequent behavioral and cognitive abnormalities. During the Fourth Pediatric Anesthesia NeuroDevelopmental Assessment (PANDA) symposium, a meeting attended by many stakeholders, the most recent findings in the field were presented and discussed. This review summarizes the current state of clinical research into the effects of anesthetic exposure in human brain development, addresses some of the difficulties in examining the phenomenon, and introduces the most recent clinical findings presented at the PANDA symposium. The unanimous consensus among participants was that additional preclinical and clinical research efforts are urgently required to address this important concern for child health.


Comparative analysis of the plant mRNA-destabilizing element, DST, in mammalian and tobacco cells.
The labile SAUR transcripts from higher plants contain a conserved DST sequence in their 3'-untranslated regions. Two copies of a DST sequence from soybean are sufficient to destabilize reporter transcripts in cultured tobacco cells whereas variants bearing mutations in the conserved ATAGAT or GTA regions are inactive. To investigate the potential for conserved recognition components in mammalian and plant cells, we examined the function of this instability determinant in mouse NIH3T3 fibroblasts and tobacco BY2 cells. In fibroblasts, a tetrameric DST element from soybean accelerated deadenylation and decay of a reporter transcript. However, a version mutated in the ATAGAT region was equally effective in this regard, and a tetrameric DST element from Arabidopsis was inactive. In contrast, the soybean DST element was more active as an mRNA instability element than the mutant version and the Arabidopsis element, when tested as tetramers in tobacco cells. Hence, the plant DST element is not recognized in animal cells with the same sequence requirements as in plant cells. Therefore, its mode of recognition appears to be plant-specific.


Mediastinal Metastasis of Breast Cancer Mimicking a Primary Mediastinal Tumor.
BACKGROUND Breast cancer is becoming a common disease in women. It progresses slowly and may recur after a long time. Therefore, when a tumor is found in the chest of a patient with a history of breast cancer, an immediate concern is whether it is a primary tumor or a metastatic tumor. However, mediastinal metastasis is extremely unlikely to occur before lung metastasis, and breast cancer is not likely to have a solitary mediastinal metastasis. Additionally, patients should not undergo invasive procedures unnecessarily, so careful consideration is required. CASE REPORT We present 2 cases. In case 1, a 48-year-old woman with a history of breast cancer had a mediastinal tumor. Based on imaging findings, cystic thymoma was suspected. Thoracoscopic intraoperative rapid biopsy showed a lymphocyte-predominant tumor tissue; therefore, the tumor was resected via a median sternotomy. The final pathological diagnosis was breast cancer metastasis. In case 2, a 47-year-old woman who underwent breast cancer resection 15 years earlier was referred for upper limb edema. Based on imaging findings, a left medial vein occlusion due to mediastinal tumor was diagnosed. Our experience in case 1 suggested that a biopsy alone should be performed first. A tumor biopsy was performed through a small transverse neck incision in case 2, and the final diagnosis was metastatic breast cancer of the mediastinum. CONCLUSIONS In patients with a suspected primary mediastinal tumor on imaging, the possibility of a metastatic tumor should be considered if they have a history of breast cancer, regardless of how long in the past it was.


HRCT imaging of pulmonary involvement in granulomatosis with polyangiitis and microscopic polyangiitis at disease onset and during follow-up.
The pulmonary involvement in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) is well known at disease onset but data during follow-up (after the induction regimen and when the first relapse occurs) are limited. Our goal was to analyze chest high-resolution computed tomography (HRCT) findings of (ANCA)-associated vasculitis patients. All consecutive unselected AAV patients over eighteen with positive ANCA status and with HRCT chest performed at the diagnosis were retrospectively enrolled between 2004 and 2019 at the Toulouse University Hospital (France). Two experienced pulmonologists and one expert respiratory radiologist reviewed independently HRCT chest scans. A total of 157 AAV patients were included in the study. Two-thirds of AAV patients had pulmonary involvement at diagnosis. Diffuse alveolar hemorrhage (DAH) was observed in 31.2 % of cases, nodules and masses in 18.5 %, bronchial airway involvement in 13.4 %, and interstitial involvement in 12.7 %. Following the induction regimen, chest HRCT scans over a two-year period demonstrated significant improvement in DAH and nodular manifestations, whereas bronchial airway involvement exhibited variability and half of cases of interstitial lung disease (ILD) had progressive course. Outcomes and survival rates are better for nodular and bronchial involvement. DAH was the most frequent cause of deaths. Progressive fibrotic changes in ILD over time could impact prognosis despite AAV remission. Employing a pattern-based approach with HRCT chest scans to assess lung involvement could be valuable in predicting treatment response, relapse, mortality, and could improved the management of AAV patients.


Neonatal ovarian cysts: therapeutic dilemma.
Seven cases of neonatal ovarian cysts that presented over the past seven years were studied. Complications included torsion and rupture and usually occurred in cysts more than 5 cm in diameter. Surgical removal, either oophorectomy or cystectomy, was the treatment of choice. Because even cystectomy results in loss of normal ovarian tissue, and because spontaneous regression of cysts less than 5 cm in diameter can occur, a more conservative approach is now proposed. Regular ultrasonography alone is recommended if the cysts are less than 5 cm in diameter, and aspiration of the cysts followed by regular ultrasonographs if the cysts are more than 5 cm in diameter. Operation should be reserved for recurrent cysts or for those with complications. Cysts diagnosed antenatally may be aspirated in utero if there are signs of thoracic compression.


Chondroitin sulfate, a major component of the perineuronal net, elicits inward currents, cell depolarization, and calcium transients by acting on AMPA and kainate receptors of hippocampal neurons.
Chondroitin sulfate (CS) proteoglycans (CSPGs) are the most abundant PGs of the brain extracellular matrix (ECM). Free CS could be released during ECM degradation and exert physiological functions; thus, we aimed to investigate the effects of CS on voltage- and current-clamped rat embryo hippocampal neurons in primary cultures. We found that CS elicited a whole-cell Na(+)-dependent inward current (ICS) that produced drastic cell depolarization, and a cytosolic calcium transient ([Ca(2+)]c). Those effects were similar to those elicited by α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainate, were completely blocked by NBQX and CNQX, were partially blocked by GYKI, and were unaffected by MK801 and D-APV. Furthermore, ICS and AMPA currents were similarly potentiated by cyclothiazide, a positive allosteric modulator of AMPA receptors. Because CSPGs have been attributed Ca(2) (+) -dependent roles, such as neural network development, axon pathfinding, plasticity and regeneration after CNS injury, CS action after ECM degradation could be contributing to the mediation of these effects through its interaction with AMPA and kainate receptors.


Disseminated Mycobacterium marinum infection and bacteremia in a child with severe combined immunodeficiency.
We report an unusual case of disseminated dermatitis, osteomyelitis, and bacteremia in an immunocompromised host. An infant presented with a pustular skin rash resembling chicken pox, but culture of a skin lesion yielded Mycobacterium marinum. Upon further evaluation, severe combined immunodeficiency was diagnosed. Radiographs of the hands and feet showed evidence of osteomyelitis. M. marinum was isolated from blood and synovial fluid. We recommend a high level of suspicion for this organism in immunocompromised hosts who have been exposed to fresh water or salt water, particularly those of aquaria. Drug susceptibility testing of serial clinical isolates from our patient revealed development of high-level resistance to isoniazid and rifampin during therapy. We believe that treatment of disseminated M. marinum infections should include combinations of antimycobacterial agents chosen on the basis of results of susceptibility testing done by an experienced laboratory, thereby limiting the emergence of drug resistance.


Nutrigenetics: bridging two worlds to understand type 2 diabetes.
The increasing global prevalence of type 2 diabetes mellitus (T2DM) is a major public health concern. Accumulating data provides strong evidence of the shared contribution of genetic and environmental factors to T2DM risk. Genome-wide association studies have hugely improved our understanding of the genetic basis of T2DM. However, it is obvious that genetics only partly account for an individuals' predisposition to T2DM. The dietary environment has changed remarkably over the last century. Examination of individual macronutrients and more recently of foods and dietary patterns is becoming increasingly important in terms of developing public health strategies. Nutrigenetics offers the potential to improve diet-related disease prevention and therapy, but is not without its own challenges. In this review we present evidence on the dietary environment and genetics as risk factors for T2DM and bridging the 2 disciplines we highlight some key gene-nutrient interactions.


Heat Loss Prevention (HeLP) in the delivery room: A randomized controlled trial of polyethylene occlusive skin wrapping in very preterm infants.
To determine if polyethylene occlusive skin wrapping of very preterm infants prevents heat loss after delivery better than conventional drying and to evaluate if any benefit is sustained after wrap removal. This was a randomized controlled trial of infants <28 weeks' gestation. The experimental group was wrapped from the neck down. Only the head was dried. Control infants were dried completely. Rectal temperatures were compared on admission to the neonatal intensive care unit immediately after wrap removal and 1 hour later. Of 55 infants randomly assigned (28 wrap, 27 control), 2 died in the delivery room and 53 completed the study. Wrapped infants had a higher mean rectal admission temperature, 36.5 degrees C (SD, 0.8 degrees C), compared with 35.6 degrees C (SD, 1.3 degrees C) in control infants ( P = .002). One hour later, mean rectal temperatures were similar in both groups (36.6 degrees C, SD, 0.7 degrees C vs 36.4 degrees C, SD, 0.9 degrees C, P = .4). Size at birth was an important determinant of heat loss: Mean rectal admission temperature increased by 0.21 degrees C (95% CI, 0.04 to 0.4) with each 100-g increase in birth weight. Polyethylene occlusive skin wrapping prevents rather than delays heat loss at delivery in very preterm infants.


Cellular action of arginine vasopressin in the isolated renal tubules of hypothyroid rats.
Hypothyroidism has been demonstrated to be associated with an impaired concentrating capacity and specific morphological changes in the thick ascending limbs. This study was performed to evaluate the cellular action of arginine vasopressin (AVP) in the isolated renal tubules from control (C) and hypothyroid (HT) rats. Hypothyroidism was induced by feeding aminotriazole for 4 wk. Urinary volume was higher in HT rats (C 13.5 +/- 0.9, HT 17.7 +/- 0.9 ml/24 h, P less than 0.005) and urinary osmolality was lower in HT rats (C 1,707 +/- 49, HT 1,229 +/- 35 mosmol/kgH2O, P less than 0.001). Plasma AVP levels were significantly higher in HT rats (C 1.93 +/- 0.59, HT 4.12 +2- 0.62 pg/ml, P less than 0.05), thus documenting AVP resistance. The adenylate cyclase response to AVP (10(-6) M) was significantly lower (P less than 0.02) in the medullary thick ascending limb of Henle's loop (mTALH) in HT (14.3 +/- 2.4 to 41.7 +/- 5.8 fm X 30 min-1 X mm-1, P less than 0.001) than in mTALH in C rats (14.4 +/- 2.8 to 110.1 +/- 24.9 fm X 30 min-1 X mm-1, P less than 0.001). In contrast, the adenylate cyclase response to AVP was not significantly different in collecting tubules of cortex, outer medulla, and inner medulla from C and HT rats, although a slight decrease in response to AVP was observed in cortical and outer medullary collecting tubules.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of 0.9, 3.6, and 7.2% NaCl for correction of experimentally induced hypochloremic, hypokalemic metabolic alkalosis in sheep.
Nine adult female sheep were each surgically fitted with an Ivan and Johnston reentrant cannula in the cranial part of the duodenum just distal to the pylorus. By diversion (loss) of abomasal outflow, this model has been shown to consistently induce hypochloremic, hypokalemic metabolic alkalosis, accompanied by hyponatremia and dehydration. Each sheep was subjected to 3 treatment trials, each preceded by a 24-hour prediversion period, and a diversion period during which a syndrome of hypochloremia (68 +/- 2 mEq/L), hypokalemia, hyponatremia, and metabolic alkalosis was induced. Development of this syndrome was attributable to losses of large amounts of acid and electrolytes in the abomasal effluent. Mean total electrolyte contents of the effluent were: Cl-, 650 +/- 27 mEq; Na+, 388 +/- 23 mEq; and K+, 123 +/- 12 mEq, with total volume loss ranging from 3.6 to 10.0 L of gastric contents and pH ranging from 3 to 5. Decreases in plasma electrolyte concentrations also can be attributed to decreased intake, because anorexia developed shortly after the onset of diversion. Electrolyte losses in urine during diversion were minimal for Cl- (mean +/- SEM, 12.0 +/- 5.1 mEq), but were greater for Na+ (124.2 +/- 14.5 mEq) and K+ (185.1 +/- 31.2 mEq). Treatments consisted of 0.9% NaCl (300 mosm/L), 3.6% NaCl (1,200 mosm/L), and 7.2% NaCl (2,400 mosm/L) administered over a 2-hour period, with the administered volume determined by the estimated total extracellular fluid Cl- deficit. Significant difference was not found among treatments, with all solutions resulting in return of clinicopathologic and physical variables to prediversion values within 12 hours of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Iliac artery stenting in patients with poor distal runoff: Influence of concomitant infrainguinal arterial reconstruction.
Inadequate infrainguinal runoff is considered an important risk factor for iliac stent failure. However, the influence of concomitant infrainguinal arterial reconstruction (CIAR) on iliac stent patency is unknown. This study evaluated the influence of CIAR on outcome of iliac angioplasty and stenting (IAS) in patients with poor distal runoff. Over 5 years (1996 to 2001), 68 IAS procedures (78 stents) were performed in 62 patients with poor distal runoff (angiographic runoff score >or=5). The SVS/AAVS reporting standards were followed to define outcome variables and risk factors. Data were analyzed with both univariate analysis (Kaplan-Meier method [K-M]) and regression analysis (Cox proportional hazards model). Indications for iliac artery stenting were disabling claudication (59%) and limb salvage (41%). Of the 68 procedures, IAS with CIAR was performed in 31 patients (46%), and IAS alone was performed in 37 patients (54%). Patients undergoing IAS with CIAR were older (P =.03) and had more extensive and multifocal iliac artery occlusive disease, with more TASC (TransAtlantic Inter-Society Consensus) type C lesions (P =.03), compared with patients undergoing IAS alone. No other significant differences in risk factors were noted. Runoff scores between patients undergoing IAS with CIAR and those undergoing IAS alone were not significantly different (median runoff scores, 6 [range, 5-8] and 7 [range, 5-9], respectively; P =.77). Primary stent patency rate at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, for patients undergoing IAS with CIAR, and was 76%, 66%, and 55%, respectively, for patients undergoing IAS. Univariate analysis revealed that primary stent patency rate was not significantly different between the 2 groups (K-M, log-rank test, P =.81). Primary graft patency rate for CIAR was 81%, 52%, and 46% at 1, 3, and 5 years, respectively. Performing CIAR did not affect primary iliac stent patency (relative risk, 1.1; 95% confidence interval, 0.49-2.47; P =.81). Overall, there was a trend toward improved limb salvage in patients undergoing IAS with CIAR, compared with those undergoing IAS alone (K-M, log rank test, P =.07). In patients undergoing IAS with poor distal runoff, CIAR does not improve iliac artery stent patency. Infrainguinal bypass procedures should therefore be reserved for patients who do not demonstrate clinical improvement and possibly for those with limb-threatening ischemia.


Persistence of aflatoxin during the fermentation of soy sauce.
Aflatoxin was produced by Aspergillus parasiticus NRRL 2999 but not by A. oryzae during fermentation of soy sauce. Little aflatoxin was degraded within 6 weeks unless Lactobacillus delbrueckii also was present.


Genetic regulation of gene expression during shoot development in Arabidopsis.
The genetic control of gene expression during shoot development in Arabidopsis thaliana was analyzed by combining quantitative trait loci (QTL) and microarray analysis. Using oligonucleotide array data from 30 recombinant inbred lines derived from a cross of Columbia and Landsberg erecta ecotypes, the Arabidopsis genome was scanned for marker-by-gene linkages or so-called expression QTL (eQTL). Single-feature polymorphisms (SFPs) associated with sequence disparities between ecotypes were purged from the data. SFPs may alter the hybridization efficiency between cDNAs from one ecotype with probes of another ecotype. In genome scans, five eQTL hot spots were found with significant marker-by-gene linkages. Two of the hot spots coincided with classical QTL conditioning shoot regeneration, suggesting that some of the heritable gene expression changes observed in this study are related to differences in shoot regeneration efficiency between ecotypes. Some of the most significant eQTL, particularly those at the shoot regeneration QTL sites, tended to show cis-chromosomal linkages in that the target genes were located at or near markers to which their expression was linked. However, many linkages of lesser significance showed expected "trans-effects," whereby a marker affects the expression of a target gene located elsewhere on the genome. Some of these eQTL were significantly linked to numerous genes throughout the genome, suggesting the occurrence of large groups of coregulated genes controlled by single markers.


Immunosuppressive effects of environmental stressors on immunological function in Pinctada imbricata.
This study assessed the effects of mechanical agitation, hypo-saline conditions, and exposure to the air on the Akoya pearl oyster, Pinctada imbricata, focusing specifically on the immunological activity of haemocytes. Both phagocytosis and phenoloxidase activity decreased significantly when oysters were exposed to all three stressors. Transient decreases were also evident in total haemocyte counts after mechanical stress and exposure to air, while significant increases in total haemocyte counts were evident after exposure to low salinity. Acid phosphatase activity increased significantly when oysters were exposed to air. The frequency of granulocytes in the haemolymph increased significantly when oysters were stressed by hypo-saline conditions, whilst the relative frequency of granulocytes did not differ significantly after mechanical agitation or exposure to air. The total protein content of haemolymph increased significantly when oysters were stressed by mechanical agitation and low salinity. These results suggest that fluctuations in environmental conditions affect circulating haemocytes and their cytochemistry, and that the different immunological parameters tested were influenced uniquely according to the type of stressor.


TREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features.
Nasu-Hakola disease (NHD) is a rare, autosomal recessive disorder characterized by skeletal and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia (bvFTD) and other early-onset dementias. Our patients were analyzed and the literature was reviewed to delineate neurological and neuroimaging findings suggestive of NHD. Fourteen patients carrying a pathogenic mutation in the TREM2 gene were found in our database. Demographic, clinical, laboratory and radiological data were retrieved and analyzed. The presenting clinical picture was behavioral changes with cognitive decline resembling bvFTD in all patients. The mean age was 37.1 ± 4.97 years and the mean duration of the disease was 8.9 ± 3.51 years. Only two patients had typical bone cysts. Seven patients had bilateral calcification of the basal ganglia in computed tomography of the brain. Magnetic resonance imaging of the brain revealed severe atrophy of the corpus callosum, enlargement of the ventricles, atrophy of the caudate nuclei and periventricular white matter changes in all patients. Symmetrical global atrophy of the brain mainly affecting frontoparietal and lateral temporal regions were observed in all cases, and 13 patients had atrophy of the hippocampus. Cerebrospinal fluid examination of 10 patients showed elevated protein levels in six and the presence of oligoclonal bands in four patients. A combination of white matter changes, enlarged ventricles, atrophy of the caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests NHD in patients with FTD syndrome. Molecular genetic analysis should be performed in suspected cases, and families should receive genetic counseling.


Value-Based Payments and Incentives to Improve Care: A Case Study of Patients with Type 2 Diabetes in Medicare Advantage.
To estimate the impact of increased glycated hemoglobin (A1C) monitoring and treatment intensification for patients with type 2 diabetes (T2D) on quality measures and reimbursement within the Medicare Advantage Star (MA Star) program. The primary endpoint was the share of patients with T2D with adequate A1C control (A1C ≤ 9%). We conducted a simulation of how increased A1C monitoring and treatment intensification affected this end point using data from the National Health and Nutrition Examination Survey and clinical trials. Using the estimated changes in measured A1C levels, we calculated corresponding changes in the plan-level A1C quality measure, overall star rating, and reimbursement. At baseline, 24.4% of patients with T2D in the average plan had poor A1C control. The share of plans receiving the highest A1C rating increased from 27% at baseline to 49.5% (increased monitoring), 36.2% (intensification), and 57.1% (joint implementation of both interventions). However, overall star ratings increased for only 3.6%, 1.3%, and 4.8% of plans, respectively, by intervention. Projected per-member per-year rebate increases under the MA Star program were $7.71 (monitoring), $2.66 (intensification), and $10.55 (joint implementation). The simulation showed that increased monitoring and treatment intensification would improve A1C levels; however, the resulting average increases in reimbursement would be small.


Ultranarrow Line Width Room-Temperature Single-Photon Source from Perovskite Quantum Dot Embedded in Optical Microcavity.
Ultranarrow bandwidth single-photon sources operating at room-temperature are of vital importance for viable optical quantum technologies at scale, including quantum key distribution, cloud-based quantum information processing networks, and quantum metrology. Here we show a room-temperature ultranarrow bandwidth single-photon source generating single-mode photons at a rate of 5 MHz based on an inorganic CsPbI3 perovskite quantum dot embedded in a tunable open-access optical microcavity. When coupled to an optical cavity mode, the quantum dot room-temperature emission becomes single-mode, and the spectrum narrows down to just ∼1 nm. The low numerical aperture of the optical cavities enables efficient collection of high-purity single-mode single-photon emission at room-temperature, offering promising performance for photonic and quantum technology applications. We measure 94% pure single-photon emission in a single-mode under pulsed and continuous-wave (CW) excitation.


Liquid biopsy biomarkers to guide immunotherapy in breast cancer.
Immune checkpoint inhibitors (ICIs) therapy has emerged as a promising treatment strategy for breast cancer (BC). However, current reliance on immunohistochemical (IHC) detection of PD-L1 expression alone has limited predictive capability, resulting in suboptimal efficacy of ICIs for some BC patients. Hence, developing novel predictive biomarkers is indispensable to enhance patient selection for immunotherapy. In this context, utilizing liquid biopsy (LB) can provide supplementary or alternative value to PD-L1 IHC testing for identifying patients most likely to benefit from immunotherapy and exhibit favorable responses. This review discusses the predictive and prognostic value of LB in breast cancer immunotherapy, as well as its limitations and future directions. We aim to promote the individualization and precision of immunotherapy in BC by elucidating the role of LB in clinical practice.


Analysis of Pseudomonas aeruginosa clinical isolates for possible variations within the virulence genes exotoxin A and exoenzyme S.
We have previously characterized several Pseudomonas aeruginosa isolates that were obtained from patients with tracheal, urinary tract, or wound infections (A. H. Hamood, J. A. Griswold, and C. M. Duhan, 1996, J. Surg. Res. 61: 425). Analysis of additional isolates showed that regardless of the isolation site, some isolates produced significantly higher or significantly lower levels of either exotoxin A or exoenzyme S proteins. These variations did not correlate with the mucoid phenotype of the isolates. One aim of this study was to determine if the variations in the level of exotoxin A or exoenzyme S are due to DNA rearrangements within either the toxA or the exoS gene. This was accomplished by Southern blot hybridization experiments using a toxA internal probe, a toxA upstream probe, or an exoS internal probe. Hybridization with the toxA internal probe produced a 0.8-kb hybridizing fragment, whereas hybridization with the exoS internal probe produced either a 2.0- or a 2.3-kb hybridizing fragment. Hybridization with the toxA upstream probe, however, produced hybridizing fragments of varying sizes, regardless of their isolation site. Isolates that showed a similar hybridization fragment with either the toxA upstream probe or the exoS internal probe produced variable levels of exotoxin A or exoenzyme S. These results suggest that: [1] specific location within the host has no effect on either the mucoid phenotype of the isolate or the level of exotoxin A or exoenzyme S produced by the isolates; [2] although restriction polymorphism exists within the toxA upstream region, both the toxA and the exoS structural genes are relatively conserved; and [3] variations in the level of exoenzyme S and exotoxin A produced by different isolates do not correlate with either the observed heterogeneity within the toxA upstream region or the mucoid phenotype of the isolates.


Regeneration and developmental enhancers are differentially compatible with minimal promoters.
Enhancers and promoters are cis-regulatory elements that control gene expression. Enhancers are activated in a cell type-, tissue-, and condition-specific manner to stimulate promoter function and transcription. Zebrafish have emerged as a powerful animal model for examining the activities of enhancers derived from various species through transgenic enhancer assays, in which an enhancer is coupled with a minimal promoter. However, the efficiency of minimal promoters and their compatibility with multiple developmental and regeneration enhancers have not been systematically tested in zebrafish. Thus, we assessed the efficiency of six minimal promoters and comprehensively interrogated the compatibility of the promoters with developmental and regeneration enhancers. We found that the fos minimal promoter and Drosophila synthetic core promoter (DSCP) yielded high rates of leaky expression that may complicate the interpretation of enhancer assays. Notably, the adenovirus E1b promoter, the zebrafish lepb 0.8-kb (P0.8) and lepb 2-kb (P2) promoters, and a new zebrafish synthetic promoter (ZSP) that combines elements of the E1b and P0.8 promoters drove little or no ectopic expression, making them suitable for transgenic assays. We also found significant differences in compatibility among specific combinations of promoters and enhancers, indicating the importance of promoters as key regulatory elements determining the specificity of gene expression. Our study provides guidelines for transgenic enhancer assays in zebrafish to aid in the discovery of functional enhancers regulating development and regeneration.


[Magnetic resonance tomographic findings in esophageal cancer].
The value of MRT and CT for staging and for determining operability of carcinoma of the oesophagus was assessed in 20 patients with histologically confirmed diagnoses. Both methods are limited in this respect. In some cases magnetic resonance provides more accurate concerning the extent of the tumour; this, however, is true only for lesions in the upper and middle thirds of the oesophagus. Where tumours of the distal third of the oesophagus are concerned, and particularly in those extending into the fundus of the stomach, CT is clearly superior. Both methods are of limited value in assessing the depth of tumour penetration, infiltration of neighbouring organs and involvement of regional lymph nodes.


An objective function for radiation treatment optimization based on local biological measures.
The implementation of biological optimization of radiation treatment plans is impeded by both computational and modelling problems. We derive an objective function from basic model assumptions which includes the normal tissue constraints as interior penalty functions. For organs that are composed of parallel subunits, a mean response model is proposed which leads to constraints similar to dose-volume constraints. This objective function is convex in the case when no parallel organs lie in the treatment volume. Otherwise, an argument is given to show that a number of local minima may exist which are near degenerate to the global minimum. Thus, together with the measure quality of the objective function, highly efficient gradient algorithms can be used. The number of essential biological model parameters could be reduced to a minimum. However, if the optimization constraints are given as TCP/NTCP values, Lagrange multiplier updates have to be performed by invoking comprehensive biological models.


Treating acute colonic diverticulitis with extraluminal pericolic air: An Acute Care Surgery in the Netherlands (ACCSENT) multicenter retrospective cohort study.
Owing to improved quality of computed tomography, a new category of complicated acute diverticulitis, including patients with pericolic air but without abscess formation, can be defined (Hinchey 1a). Recent studies question whether this new category of acute diverticulitis could be treated as uncomplicated cases. The aim of our study is to report on the clinical course of acute diverticulitis Hinchey 1a in current clinical practice. For this multicenter retrospective cohort study, patients presenting at the emergency department with Hinchey 1a acute diverticulitis as demonstrated by computed tomography scan, were identified. The primary outcome measure was successful conservative treatment with observation alone, antibiotics, and/or hospital admission. Readmissions, percutaneous drainage of abscesses, and emergency operations were considered as failure. Between October 2016 and October 2018, 1,199 patients were clinically suspected for acute diverticulitis, of whom 101 (8.4%) were radiologically diagnosed to have type 1a acute diverticulitis (average age 57 (±13) years, 45% female) and started with conservative treatment. This was successful in 86 (85%) patients. One of the 15 unsuccessfully treated patients (1%) received percutaneous drainage of an abdominal abscess. Surgery was required in 9 cases (9%) after a median time of 6 days (range, 3 to 69 days). Although a difference in the volume of extraluminal air on computed tomography scan was found, this was not shown to be a risk factor for the clinical course. Patients with type 1a acute diverticulitis can be treated successfully by conservative therapy in the majority of cases (85%). More research is required to define predictive factors for successful conservative management.


Hypothermia-related deaths--Georgia, January 1996-December 1997, and United States, 1979-1995.
Although hypothermia-related deaths are prevalent during the winter in states that have moderately cold (e.g., Illinois, New York, and Pennsylvania) to severely cold (e.g., Alaska and North Dakota) winters and in states with mountainous or desert terrain (e.g., Arizona, Montana, and New Mexico), hypothermia-related deaths also occur in states with milder climates (e.g., Georgia, Mississippi, and South Carolina), where weather systems can cause rapid changes in temperature. This report summarizes three hypothermia-related deaths in Fulton County, Georgia, representing persons in the highest risk groups for hypothermia; and summarizes hypothermia-related deaths in Georgia during January 1996-December 1997 and in the United States during 1979-1995.


Ecosystem-bedrock interaction changes nutrient compartmentalization during early oxidative weathering.
Ecosystem-bedrock interactions power the biogeochemical cycles of Earth's shallow crust, supporting life, stimulating substrate transformation, and spurring evolutionary innovation. While oxidative processes have dominated half of terrestrial history, the relative contribution of the biosphere and its chemical fingerprints on Earth's developing regolith are still poorly constrained. Here, we report results from a two-year incipient weathering experiment. We found that the mass release and compartmentalization of major elements during weathering of granite, rhyolite, schist and basalt was rock-specific and regulated by ecosystem components. A tight interplay between physiological needs of different biota, mineral dissolution rates, and substrate nutrient availability resulted in intricate elemental distribution patterns. Biota accelerated CO2 mineralization over abiotic controls as ecosystem complexity increased, and significantly modified the stoichiometry of mobilized elements. Microbial and fungal components inhibited element leaching (23.4% and 7%), while plants increased leaching and biomass retention by 63.4%. All biota left comparable biosignatures in the dissolved weathering products. Nevertheless, the magnitude and allocation of weathered fractions under abiotic and biotic treatments provide quantitative evidence for the role of major biosphere components in the evolution of upper continental crust, presenting critical information for large-scale biogeochemical models and for the search for stable in situ biosignatures beyond Earth.


Maintaining labour epidural analgesia: what is the best option?
The intensity of labour pain is influenced by a multitude of factors. In this article, we discuss recent advances in the administration of labour epidural analgesia which have been targeted at creating a more satisfactory birthing experience for the parturient while safeguarding maternal and fetal well being. Induction of analgesia by the combined spinal epidural technique provides rapid onset of profound analgesia with minimal motor blockade, although the impact of the technique on overall maternal satisfaction with analgesia is equivocal. Patient-controlled epidural analgesia has gained acceptance among clinicians and parturients alike, and research has been focused on elucidating the optimal patient-controlled epidural analgesia programme settings. Results from laboratory and clinical studies suggest that intermittent epidural boluses may produce a more uniform block than a continuous basal infusion. Attempts have been made to incorporate background automated intermittent boluses into a patient-controlled epidural analgesia programme, with encouraging results. Computer-integrated patient-controlled epidural analgesia is a novel system that records the history of the patient's analgesic requirement over the past hour and increases its basal infusion rate proportionally to the number of demand-boluses made. The computer-integrated patient-controlled epidural analgesia programme appears to reduce the incidence of breakthrough pain without increasing drug consumption or side effects. Recent advances in medical technology have equipped us with many novel drug delivery modalities, which will enable us to customize a suitable analgesic regimen for each parturient.


The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol.
Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan-Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged ≥6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of <20 × 10(9)/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23.2 months. Death occurred in 69 of 343 patients (20.1 %). The major causes of death were infection and relapse. None of the patients died of drug-related toxicity. The ALL-BFM 95 protocol was applied successfully in these two centers. In developing countries in which minimal residual disease cannot be monitored, this protocol can still be used with high survival rates.


Neuronal ceroid lipofuscinosis. Diagnosis by semithin plastic-embedded sections of peripheral blood lymphocytes from a patient with a normal blood smear.
Neuronal ceroid lipofuscinosis is an important diagnostic consideration in a school-aged child with progressive blindness. Neurologic symptoms and signs may appear late, and the retinopathy is not specific. Ultrastructural abnormalities have been demonstrated in many body tissues, but skin has been claimed to be the most reliable. Light and electron microscopic examinations of WBCs have also been helpful in several instances. In the case reported, the skin biopsy specimen and light microscopy of a peripheral blood buffy coat failed to disclose diagnostic changes. Examination of semithin sections of plastic-embedded peripheral blood provided the answer.


The Isometric Midthigh Pull in Basketball: An Effective Predictor of Sprint and Jump Performance in Male, Adolescent Players.
To examine correlations between peak force and impulse measures attained during the isometric midthigh pull (IMTP) and basketball-specific sprint and jump tests. Male, adolescent basketball players (N = 24) completed a battery of basketball-specific performance tests. Testing consisted of the IMTP (absolute and normalized peak force and impulse at 100 and 250 ms); 20-m sprint (time across 5, 10, and 20 m); countermovement jump (CMJ; absolute and normalized peak force and jump height); standing long jump (distance); and repeated lateral bound (distance). Correlation and regression analyses were conducted between IMTP measures and other attributes. An almost perfect correlation was evident between absolute peak force attained during the IMTP and CMJ (r = .94, R2 = 56%, P < .05). Moderate to very large correlations (P < .05) were observed between IMTP normalized peak force and 5-m sprint time (r = -.44, R2 = 19%), 10-m sprint time (r = -.45, R2 = 20%), absolute (r = .57, R2 = 33%), normalized (r = .86, R2 = 73%) CMJ peak force, and standing long-jump distance (r = .51, R2 = 26%). Moderate to very large correlations were evident between impulse measures during the IMTP and 5-m sprint time (100 ms, r = -.40, R2 = 16%, P > .05) and CMJ absolute peak force (100 ms, r = .73, R2 = 54%; 250 ms, r = .68, R2 = 47%; P < .05). The IMTP may be used to assess maximal and rapid force expression important across a range of basketball-specific movements.


Access and care issues in urban urgent care clinic patients.
Although primary care should be the cornerstone of medical practice, inappropriate use of urgent care for non-urgent patients is a growing problem that has significant economic and healthcare consequences. The characteristics of patients who choose the urgent care setting, as well as the reasoning behind their decisions, is not well established. The purpose of this study was to determine the motivation behind, and characteristics of, adult patients who choose to access health care in our urgent care clinic. The relevance of understanding the motivation driving this patient population is especially pertinent given recent trends towards universal healthcare and the unclear impact it may have on the demands of urgent care. We conducted a cross-sectional survey of patients seeking care at an urgent care clinic (UCC) within a large acute care safety-net urban hospital over a six-week period. Survey data included demographics, social and economic information, reasons that patients chose a UCC, previous primary care exposure, reasons for delaying care, and preventive care needs. A total of 1, 006 patients were randomly surveyed. Twenty-five percent of patients identified Spanish as their preferred language. Fifty-four percent of patients reported choosing the UCC due to not having to make an appointment, 51.2% because it was convenient, 43.9% because of same day test results, 42.7% because of ability to get same-day medications and 15.1% because co-payment was not mandatory. Lack of a regular physician was reported by 67.9% of patients and 57.2% lacked a regular source of care. Patients reported delaying access to care for a variety of reasons. Despite a common belief that patients seek care in the urgent care setting primarily for economic reasons, this study suggests that patients choose the urgent care setting based largely on convenience and more timely care. This information is especially applicable to the potential increase in urgent care volume in a universal healthcare system. Additionally, this study adds to the body of literature supporting the important role of timely primary care in healthcare maintenance.


Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage.
Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH). To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption. Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption. Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment. Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome. Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%). Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies. clinicaltrials.gov Identifier: NCT01829581.


Outcomes of Adrenalectomy and the Aldosteronoma Resolution Score in the Black and Hispanic Population.
Outcomes after adrenalectomy in patients with primary aldosteronism (PA) are variable. The aldosteronoma resolution score (ARS) uses preoperative variables to calculate a score that identifies those patients that are more likely to have resolution of hypertension after adrenalectomy. We aim to determine the efficacy of adrenalectomy and whether the ARS accurately predicts clinical success in a Black and Hispanic population. We reviewed patients who underwent adrenalectomy for PA from 2004 to 2018 at two academic centers treating primarily Hispanic and Black patients. Postoperative outcomes were evaluated based on the primary aldosteronism surgical outcome consensus criterion. Retrospectively, the accuracy of ARS was determined by a receiver operating characteristic curve and the area under the curve (AUC). Forty-three Hispanic and 10 Black patients underwent adrenalectomy for PA. Twenty-two patients (41.5%) had complete clinical success. Variables associated with complete clinical success in the univariate analysis were female gender (p = 0.026), younger age (p = 0.001), lower preoperative aldosterone (p = 0.035), lower preoperative systolic blood pressure (p = 0.001), fewer number of preoperative antihypertensive medications (p = 0.007) and a higher ARS (p = 0.003). On multivariate analysis, only fewer number of preoperative antihypertensive medications was independently associated with complete clinical success (p = 0.026). The AUC of the ARS was 0.746. The rate of clinical success from adrenalectomy is good for Hispanic and Black patients with PA. Our analysis shows that the ARS is an accurate test of clinical success in Hispanic and Black patients. The ARS may be utilized preoperatively to frame expectations after adrenalectomy in these populations.


Mitochondrial DNA phylogeny and the reconstruction of the population history of a species: the case of the European anchovy (Engraulis encrasicolus).
Analysis of mitochondrial DNA restriction fragment length polymorphism in European anchovy (Engraulis encrasicolus) revealed a large number of mitotypes that form two distinct clusters (phylads). Phylad A consists of one common mitotype and many rare secondary mitotypes that are one mutational step removed from the main type. Nucleotide diversity and number of homoplasious changes are low. Phylad B has a complex pattern of mitotype connectedness, high nucleotide diversity, and a large number of homoplasious changes. It is suggested that the two phylads evolved in isolation from each other and that present coexistence is the result of a secondary contact. Moreover, phylad A has a "star" phylogeny, which suggests that it has evolved in a population that experienced a drastic bottleneck followed by an explosion of size. Phylad A is practically the only phylad present in the Black Sea, with its frequency dropping to 85% in the northern Aegean, and to 40% in the rest of Mediterranean and the Bay of Biscay. The Black Sea is, therefore, the most likely place of origin of phylad A. Molecular data are consistent with a population bottleneck in the Black Sea during the last glaciation event and a subsequent exit of phylad A with the outflow into the Aegean following the ice melting. Phylogenetic analysis of anchovy mtDNA provides a reconstruction of population history in the Mediterranean, which is consistent with the geological information.


Liposarcoma of the pleural cavity: clinical and pathologic features of 4 cases with a review of the literature.
Primary liposarcomas of the pleura are extremely rare malignancies, and relatively few reports appear in the world literature. We compiled a small series of 4 cases of primary pleural liposarcoma from the files of the Armed Forces Institute of Pathology (Washington, DC) and compared the histopathologic and clinical features of these 4 cases with those of 9 previously published cases. Our investigation included the case studies of 9 men and 4 women, aged 19 to 80 years (average, 49 years). Histologic subtypes in the 9 cases with available information included 5 myxoid liposarcomas, 1 well-differentiated liposarcoma, and 3 liposarcomas with mixtures of histologic types. Surgical resection with or without chemotherapy appeared to be the most common form of treatment, although radiation therapy was used in some cases and seemed beneficial. Survival information was available for 11 cases; 4 patients died of disease at 7, 9, 12, and 19 months; 1 died of heart failure 2 days after presentation; 1 died of unknown causes 16 months after presentation; and 3 patients were alive without tumor at 5, 16, and 66 months after diagnosis. One patient had local recurrence at 2 years. A second surgical resection in this patient failed, and he died of disease 9 years after initial presentation. A second patient experienced recurrence at 4 years and was free of disease 4 years after the second surgical resection. Primary pleural liposarcomas occur predominantly in older men, and the myxoid histologic subtype is the most common. Radiographic or surgical evaluation is important to distinguish primary pleural liposarcoma from chest wall or mediastinal sarcomas, as well as metastases from other sites. Although further investigation is needed, evidence from the cases reviewed here indicates that surgical resection with adjuvant radiation therapy may benefit patients with primary pleural liposarcoma.


c-myc and c-myb protein degradation: effect of metabolic inhibitors and heat shock.
The proteins encoded by both viral and cellular forms of the c-myc oncogene have been previously demonstrated to have exceptionally short in vivo half-lives. In this paper we report a comparative study on the parameters affecting turnover of nuclear oncoproteins c-myc, c-myb, and the rapidly metabolized cytoplasmic enzyme ornithine decarboxylase. The degradation of all three proteins required metabolic energy, did not result in production of cleavage intermediates, and did not involve lysosomes or ubiquitin. A five- to eightfold increase in the half-life of c-myc proteins, and a twofold increase in the half-life of c-myb proteins was detected after heat-shock treatment at 46 degrees C. In contrast, heat shock had no effect on the turnover of ornithine decarboxylase. Heat shock also had the effect of increasing the rate of c-myc protein synthesis twofold, whereas c-myb protein synthesis was decreased nearly fourfold. The increased stability and synthesis of c-myc proteins led to an overall increase in the total level of c-myc proteins in response to heat-shock treatment. Furthermore, treatments which reduced c-myc and c-myb protein turnover, such as heat shock and exposure to inhibitors of metabolic energy production, resulted in reduced detergent solubility of both proteins. The recovery from heat shock, as measured by increased turnover and solubility, was energy dependent and considerably more rapid in thermotolerant cells.


Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhuman primate hypothalamic-pituitary-adrenal axis and noradrenergic function.
The search for novel anxiolytics and antidepressants has focused on compounds with the potential to reduce excessive hypothalamic-pituitary-adrenal (HPA) axis activity. L-glutamate, an excitatory neurotransmitter ubiquitously present within the central nervous system, conceivably plays an important role in activating the neural sites involved in stress modulation. Deactivation of the HPA axis by glutamatergic neurotransmission modulation may represent a novel therapeutic approach. Accordingly, the acute intravenous effects of the novel metabotropic (mGlu2/3) agonist LY354740 were tested on bonnet macaques (Macaca radiata) undergoing acute infusions of yohimbine, a noradrenergic stimulant. Dependent measures were the magnitude of the increase of plasma cortisol and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) customarily elicited by yohimbine. Next, the effects of 6 weeks of chronic oral administration of LY354740 on baseline (postcapture) plasma cortisol and MHPG levels in comparison to the identical measure in untreated controls were assessed. Subjects chronically treated with LY354740 received yohimbine infusions which were compared to yohimbine infusions and saline infusions in non-LY354740-treated subjects. Preliminary evidence supports the view that acute LY354740 infusion resulted in a marked diminution of yohimbine-induced stress response, as manifest by a substantial attenuation of cortisol and MHPG response observed in comparison to the saline-treated yohimbine condition. Chronic oral administration of LY354740 led to postcapture baseline cortisol levels which were markedly reduced (approximately 50 percent) in comparison to untreated control subjects; however, there were no significant parallel differences in MHPG levels. Yohimbine infusions elicited an increase in cortisol and MHPG levels in both LY354740-treated and non-LY354740-treated subjects, in comparison to declines in cortisol values observed following vehicle infusions (group X time interaction; P<.0001). Chronic LY354740-treated subjects failed to achieve cortisol levels comparable in range to those of untreated subjects primarily because of their low baseline cortisol levels. In contrast, despite equivalent baselines, yohimbine-induced MHPG values were increased overall in the chronically treated group compared to the saline and yohimbine-alone groups. Thus, LY354740 markedly reduced the acute corticoid and noradrenergic response elicited by yohimbine infusion. Chronic administration of LY354740 appears to present a safe and effective mechanism to markedly down-modulate the HPA axis while retaining noradrenergic responsivity.


The place of hybrid therapies with drugs to supplement nonpharmacological therapies in atrial fibrillation.
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, and its prevalence continues to rise as the aged population increases. Comparative studies of rhythm control and rate control have been equivocal; however, the benefits of rhythm control may have been offset by the limitations of antiarrhythmic drugs. More recently, nonpharmacological therapies have emerged that provide hope of more effective rhythm control. Catheter ablation techniques have gained favour with high success rates in specialized centers, although these techniques are not without complications and require considerable expertise. Pacing therapies designed to reduce harmful right ventricular pacing and increase physiological pacing have shown benefit in AF patients with bradycardia. Despite this progress, no single modality confers benefit for all patients. Strategies to combine these treatment modalities in a hybrid approach has shown increasing promise for subgroups of AF patients.


Quantitative studies of the flora of the nasal vestibule in relation to nasal carriage of Staphylococcus aureus.
Aerobic and anaerobic bacterial flora and yeast flora of the nasal vestibule were studied quantitatively in eight persons who were persistent, transient or non-carriers of Staphylococcus aureus. The nasal flora of all the subjects consisted of lipophilic and non-lipophilic aerobic diphtheroids, propionibacteria and different staphylococcal species. Other micro-organisms, such as Pityrosporum and Candida, micrococci, streptococci and coliforms were found only occasionally. The presence of S. aureus was related to diminished numbers of other staphylococcal strains and of propionibacteria.


Neural correlates of emotion processing comparing antidepressants and exogenous oxytocin in postpartum depressed women: An exploratory study.
Despite common use of antidepressants to treat postpartum depression, little is known about the impact of antidepressant use on postpartum brain activity. Additionally, although oxytocin has been investigated as a potential treatment for postpartum depression, the interaction between antidepressants and exogenous oxytocin on brain activity is unknown. We explored postpartum depressed women's neural activation in areas identified as important to emotion and reward processing and potentially, antidepressant response: the amygdala, nucleus accumbens and ventral tegmental area. We conducted a secondary analysis of a functional imaging study of response to sexual, crying infant and smiling infant images in 23 postpartum depressed women with infants under six months (11 women taking antidepressants, 12 unmedicated). Participants were randomized to receive a single dose of oxytocin or placebo nasal spray. There was significantly higher amygdala activation to sexual stimuli than either neutral or infant-related stimuli among women taking antidepressants or receiving oxytocin nasal spray. Among unmedicated women receiving placebo, amygdala activation was similar across stimuli types. There were no significant effects of antidepressants nor oxytocin nasal spray on reward area processing (i.e., in the nucleus accumbens or ventral tegmental area). Among postpartum women who remain depressed, there may be significant interactions between the effects of antidepressant use and exogenous oxytocin on neural activity associated with processing emotional information. Observed effect sizes were moderate to large, strongly suggesting the need for further replication with a larger sample.


Through a Window, Brightly: A Review of Selected Nanofabricated Thin-Film Platforms for Spectroscopy, Imaging, and Detection.
We present a review of the use of selected nanofabricated thin films to deliver a host of capabilities and insights spanning bioanalytical and biophysical chemistry, materials science, and fundamental molecular-level research. We discuss approaches where thin films have been vital, enabling experimental studies using a variety of optical spectroscopies across the visible and infrared spectral range, electron microscopies, and related techniques such as electron energy loss spectroscopy, X-ray photoelectron spectroscopy, and single molecule sensing. We anchor this broad discussion by highlighting two particularly exciting exemplars: a thin-walled nanofluidic sample cell concept that has advanced the discovery horizons of ultrafast spectroscopy and of electron microscopy investigations of in-liquid samples; and a unique class of thin-film-based nanofluidic devices, designed around a nanopore, with expansive prospects for single molecule sensing. Free-standing, low-stress silicon nitride membranes are a canonical structural element for these applications, and we elucidate the fabrication and resulting features-including mechanical stability, optical properties, X-ray and electron scattering properties, and chemical nature-of this material in this format. We also outline design and performance principles and include a discussion of underlying material preparations and properties suitable for understanding the use of alternative thin-film materials such as graphene.


The quest for indicators of paroxysmal atrial fibrillation in sinus rhythm - the DETECT AF trial.
Background: Atrial fibrillation (AF) is related to an increased stroke risk. At present, differentiation between patients with paroxysmal AF (pAF) and without is only possible during AF episodes and not during sinus rhythm. If AF could be diagnosed more quickly and reliably, anticoagulation therapy may be administered and prevent from cardioembolic strokes. The DETECT AF trial evaluated the hypothesis that propagation of electric activities in patients with pAF differs from propagation in healthy atria and that this can be detected with a three-dimensional electrocardiogram in patients during sinus rhythm. Methods: We conducted a case-control study including patients with a history of pAF and a control group with no history of AF. Vectorcardiographic beat-to-beat variability of atrial activation in sinus rhythm was tested and compared between the two groups. Results: One hundred and eight patients with a history of pAF in sinus rhythm and 121 controls in sinus rhythm were included. With a combination of specific vectorcardiographic beat-to-beat variability parameters discrimination between the two groups was possible with a specificity of 82% and a sensitivity of 71% (p≤.01). Using heart rate independent parameters, both specificity and sensitivity were reduced to 70%. Conclusions: Analysis of atrial vectorcardiographic beat-to-beat variability indicates that atrial conduction variability in patients with pAF differs from patients without AF and may be used as an indicator to estimate the risk for pAF in patients during sinus rhythm. Further studies to investigate the potential of this parameter are needed. Clinical trial registration number: NCT02270112.


Efficacy of dendritic cell generation for clinical use: recovery and purity of monocytes and mature dendritic cells after immunomagnetic sorting or adherence selection of CD14+ starting populations.
Immunotherapy with monocyte-derived dendritic cells (Mo-DCs) is applied to an increasing number of patients requiring large-scale production of clinical-grade dendritic cells with standardized Mo-DC generation protocols. In many countries, e.g., in Germany, Mo-DCs are legally considered medicinal products, which must be produced under Good Manufacturing Practice (GMP) conditions by an institution holding an official production license. Plastic adherence, immunomagnetic selection of CD14(+) monocytes and depletion of CD2(+) and CD19(+) cells are used to enrich monocytes for Mo-DC culture. The latter two have received approval of the European Union (CE). However, enrichment by plastic adherence is well-established and commonly used for clinical and research Mo-DC applications. The various plastic materials, nevertheless, have not been officially approved for monocyte selection for clinical use. In the present study therefore, we compared three methods for enrichment of CD14(+) monocytes with regard to efficiency of enrichment, yield of monocyte-derived functional mature dendritic cells, cost effectiveness, and handling. We demonstrate that CD14 selection and CD2 and CD19 depletion yield similar results regarding purity of mature DEs MoDCs (97-99% vs. 64-97%) and their immunostimulatory capacity. However, cell preparations cultured after CD14 selection possessed 91% to 97% CD14(+) cells, whereas CD2-/and DC19-depleted preparations contained only 8% to 57% CD14(+) cells. Thus, positive selection requires smaller culture volumes to generate equal numbers of Mo-DCs. Both methods gave better results than plastic adherence. In conclusion, of the techniques examined, CD14 selection of monocytes gave the best results regarding reproducibility, yield, and purity of the resulting monocytes and mature Mo-DCs.


Reexamining the evidence for inpatient glucose control: new recommendations for glycemic targets.
To review the risks of hyperglycemia in hospitalized patients, data supporting the benefits of treating hyperglycemia, and recommendations from the 2009 American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on the management of inpatient hyperglycemia. Inpatient hyperglycemia is common, costly, and associated with poor clinical outcomes in many disease states. Despite inconsistencies in clinical trial results, good glucose management in the hospital remains important. Target blood glucose concentrations (BGs) were recently modified to somewhat higher values with the expectation that the benefit of treatment will persist with a lower risk of hypoglycemia, which is itself another marker of poor outcome in critically and non-critically ill patients. In the intensive care unit (ICU), the threshold to start treatment is a BG of <or=180 mg/dL. I.V. insulin is the treatment of choice in critically ill patients because of its rapid onset and offset of action. Once i.v. insulin is started, the BG should be maintained between 140 and 180 mg/ dL; a lower BG target (110-140 mg/dL) may be appropriate in selected patients. Targets of <110 mg/dL or >180 mg/dL are no longer recommended. In non-critically ill patients, premeal BG targets are <140 mg/dL; random BGs of <180 mg/dL are recommended. Scheduled subcutaneous insulin is the treatment of choice for hyperglycemia in non-critically ill patients; use of sliding-scale insulin is strongly discouraged. To avoid hypoglycemia, insulin regimens should be reassessed if BG falls to <100 mg/dL. Poor glycemic control in the hospital setting is a quality-of-care, safety, and cost issue. Safe and effective strategies to implement optimal glycemic control require multidisciplinary involvement. Insulin given i.v. in the ICU or subcutaneously on an as-scheduled regimen in other parts of the hospital is the treatment of choice.


Cognitive performance during senescence in untreated congenital isolated GH deficiency.
Individuals with untreated isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene from Itabaianinha Brazil have increased insulin sensitivity, normal life expectancy, and an extended healthspan, i.e., the period of life free from disabilities. We hypothesize that their prolonged healthspan is accompanied by a delayed cognitive decline in senescence. To test this hypothesis, we have administered the Literacy Independent Cognitive Assessment (LICA) to 15 IGHD individuals aged over 50 years and 15 controls matched by age, sex, years of education, and percentage of illiteracy. All individuals were negative for HIV and syphilis serology, and there were no differences in serum levels of folate, vitamin B12 and TSH between the 2 groups, while free T4 was higher in the IGHD group. IGHD subjects had a higher total LICA score than controls, 215 (22.7) vs. 204.2 (18.1), without reaching statistical significance. Scores of memory, visuoconstruction, language and calculation were similar between the two groups, with better attention [9.5 (1.4) vs. 8.3 (1.1), p= 0.01], and executive function [38.3 (4.8) vs. 35.1 (2.5), p= 0.03] scores in IGHD. MANCOVA revealed that group (but no age) had a significant effect on the LICA variables (partial eta squared of 0.455, power of 0.812, p= 0.02). This effect is verified on attention (partial eta squared 0.216, power of 0.749, p= 0.01) and executive function (partial eta squared 0.154, power of 0.570, p= 0.03. In conclusion, IGHD in senescence is associated with similar total cognitive performance, but better attention and executive function than controls.