Freestanding crystalline oxide perovskites down to the monolayer limit.
Two-dimensional (2D) materials such as graphene and transition-metal dichalcogenides reveal the electronic phases that emerge when a bulk crystal is reduced to a monolayer1-4. Transition-metal oxide perovskites host a variety of correlated electronic phases5-12, so similar behaviour in monolayer materials based on transition-metal oxide perovskites would open the door to a rich spectrum of exotic 2D correlated phases that have not yet been explored. Here we report the fabrication of freestanding perovskite films with high crystalline quality almost down to a single unit cell. Using a recently developed method based on water-soluble Sr3Al2O6 as the sacrificial buffer layer13,14 we synthesize freestanding SrTiO3 and BiFeO3 ultrathin films by reactive molecular beam epitaxy and transfer them to diverse substrates, in particular crystalline silicon wafers and holey carbon films. We find that freestanding BiFeO3 films exhibit unexpected and giant tetragonality and polarization when approaching the 2D limit. Our results demonstrate the absence of a critical thickness for stabilizing the crystalline order in the freestanding ultrathin oxide films. The ability to synthesize and transfer crystalline freestanding perovskite films without any thickness limitation onto any desired substrate creates opportunities for research into 2D correlated phases and interfacial phenomena that have not previously been technically possible.


UHPLC-HRMS-Based Untargeted Lipidomics Reveal Mechanism of Antifungal Activity of Carvacrol against Aspergillus flavus.
Aspergillus flavus is a common contaminant in grain, oil and their products. Its metabolite aflatoxin B1 (AFB1) has been proved to be highly carcinogenic. Therefore, it is of great importance to find possible antifungal substances to inhibit the growth and toxin production of Aspergillus flavus. Carvacrol (CV) was reported as a potent antifungal monoterpene derived from plants. In this paper, the antifungal effects and mechanism of CV on Aspergillus flavus were investigated. CV was shown good inhibition on the growth of Aspergillus flavus and the production of AFB1. CV used in concentrations ranging from 0, 50, 100 and 200 μg/mL inhibited the germination of spores, mycelia growth and AFB1 production dose-dependently. To explore the antifungal mechanism of CV on Aspergillus flavus, we also detected the ergosterol content of Aspergillus flavus mycelia, employed Scanning Electron Microscopy (SEM) to observe mycelia morphology and utilized Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS) to explore the lipidome profiles of Aspergillus flavus. The results showed that the production of ergosterol of mycelia was reduced as the CV treatment concentration increased. SEM photographs demonstrated a rough surface and a reduction in the thickness of hyphae in Aspergillus flavus treated with CV (200 µg/mL). In positive ion mode, 21 lipids of Aspergillus flavus mycelium were downregulated, and 11 lipids were upregulated after treatment with 200-µg/mL CV. In negative ion mode, nine lipids of Aspergillus flavus mycelium were downregulated, and seven lipids upregulated after treatment with 200-µg/mL CV. In addition, the analysis of different lipid metabolic pathways between the control and 200-µg/mL CV-treated groups demonstrated that glycerophospholipid metabolism was the most enriched pathway related to CV treatment.


Toggled RNA aptamers against aminoglycosides allowing facile detection of antibiotics using gold nanoparticle assays.
We have used systematic evolution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers against aminoglycoside antibiotics. The SELEX rounds were toggled against four pairs of aminoglycosides with the goal of isolating reagents that recognize conserved structural features. The resulting aptamers bind both of their selection targets with nanomolar affinities. They also bind the less structurally related targets, although they show clear specificity for this class of antibiotics. We show that this lack of aminoglycoside specificity is a common property of aptamers previously selected against single compounds and described as "specific". Broad target specificity aptamers would be ideal for sensors detecting the entire class of aminoglycosides. We have used ligand-induced aggregation of gold-nanoparticles coated with our aptamers as a rapid and sensitive assay for these compounds. In contrast to DNA aptamers, unmodified RNA aptamers cannot be used as the recognition ligand in this assay, whereas 2'-fluoro-pyrimidine derivatives work reliably. We discuss the possible application of these reagents as sensors for drug residues and the challenges for understanding the structural basis of aminoglycoside-aptamer recognition highlighted by the SELEX results.


Non Electrocardiographic alterations in exercise testing in asymptomatic women. Associations with cardiovascular risk factors.
To estimate the prevalence of exercise testing alterations in middle-aged women without symptoms of heart disease and to verify the associations of functional capacity and heart rate behavior during and after exercise with cardiovascular risk factors. A cross-sectional study was conducted with 509 asymptomatic women aged between 46 and 65 years who underwent clinical evaluations and exercise testing (Bruce protocol). The heart rate behavior was evaluated by the maximal predicted heart rate achieved, chronotropic index and recovery heart rate. The mean age was 56.4±4.8 years, and 13.4% of the patients had a Framingham risk score above 10%. In the exercise treadmill testing, 58.0% presented one or more of the following alterations (listed in order of ascending prevalence): symptoms (angina, dyspnea, and dizziness), ST-segment depression, arrhythmia, reduction in recovery heart rate of ≤12 bpm at 1 minute, altered maximal predicted heart rate achieved, abnormal blood pressure, functional capacity deficiency, and altered chronotropic index. In the multivariate analysis, the following associations (odds ratio) were observed for these alterations: chronotropic index was associated with obesity (2.08) and smoking (4.47); maximal predicted heart rate achieved was associated with smoking (6.45); reduction in the recovery heart rate at 1 minute was associated with age (1.09) and obesity (2.78); functional capacity was associated with age (0.92), an overweight status (2.29) and obesity (6.51). More than half of middle-aged women without cardiovascular symptoms present alterations in one or more exercise testing parameters. Alterations in the functional capacity or heart rate behavior, as verified by exercise testing, are associated with age, smoking, an overweight status and obesity.


Cancer incidence in familial Mediterranean fever patients: a retrospective analysis from central Anatolia.
Although chronic inflammation has been associated with increased cancer risk in various disease including hepatitis or inflammatory bowel disease, a lower incidence of cancer has been reported recently in familial Mediterranean fever (FMF) which is an auto-inflammatory disease with persistent inflammation. We have assessed cancer incidence among FMF patients with or without amyloidosis to investigate this hypothesis. We performed a retrospective review of FMF patients, diagnosed and treated in Hacettepe University hospitals between 2001 and 2018. We identified patients from the hospital medical records using the ICD-10 code for FMF. We collected data on demographic and clinical features, drug history, the presence of amyloidosis and subsequent diagnosis of cancer. The expected cancer incidence was estimated using age- and gender-specific standardized incidence rates (SIRs) in comparison with the general Turkish population according to Turkish National Cancer Registry data at 2014. Total of 3899 FMF patients (120 patients had also amyloidosis) were included. Median age was 22 and 56% were females. Thirty-eight patients were diagnosed with cancer during 100,283 person-years of follow-up. The most common cancer was breast cancer in females (7/28 patients) and leukemia (2/10 patients) in males. The overall cancer incidence among patients with FMF was significantly lower in both males {SIR 0.42 [95% confidence interval; (CI) 0.21-0.75], p = 0.019} and females [SIR 065 (95% CI 0.44-0.93), p = 0.002]. The overall cancer incidence among patients with FMF and amyloidosis was [SIR 1.21 (95% CI 0.49-2.52), p = 0.73] without gender difference. Cancer incidence was significantly lower in FMF patients compared with the general Turkish population. We found no increased cancer incidence in FMF patients having amyloidosis. Possible underlying mechanisms need to be explained.


Prevention and treatment of deep venous thrombosis.
Postoperative venous thromboembolism (VTE) is a common cause of preventable patient morbidity and mortality. Hospitalized patients have multiple risk factors for VTE, which can exert a cumulative effect on the individual patient. Although effective thromboprophylactic measures are currently available, they are not commonly used for a number of reasons, in addition to heightened concern about increasing bleeding risk. Limited data are available characterizing the incidence of symptomatic VTE following major vascular surgery in the absence of thromboprophylactic therapy. Reported rates vary according to the type of surgery, type of prophylaxis used, and diagnostic modalities used for deep venous thrombosis (DVT) and pulmonary embolism (PE). Hospital-acquired DVT in the absence of thromboprophylaxis can occur in up to 40% of patients, occurring primarily in the proximal deep veins, which elevates the risk of PE. Risk factors for VTE in vascular surgery include limb ischemia, prolonged surgery duration, localized intraoperative trauma, and atherosclerosis. Advanced patient age is also a risk factor for VTE; however, the relationship between age and risk of VTE after surgery is complex and dependent on both the type of surgery and the underlying disease process. Evidence-based guidelines for venous thrombo-prophylaxis are now available; however, adoption of and compliance with these guidelines have lagged. Effective thrombo-prophylactic strategies exist and include both pharmacologic and nonpharmacologic approaches. For those surgical patients who develop a VTE, antithrombotic therapy remains the treatment of choice.


Association of language concordance and restraint use in adults receiving mechanical ventilation.
Clinician-patient language concordance improves patient outcomes in non-intensive care unit (ICU) settings. We sought to assess the association of ICU nurse-patient language concordance with delirium-related outcomes. We conducted a retrospective cohort study of adult English- or Spanish-speaking mechanically ventilated ICU patients admitted to ICUs at the University of Miami Hospital and Clinics (January 2021-September 2022). Our primary exposure was nurse-patient language concordance on each shift. We used mixed-effects multivariable regression to evaluate the association of language concordance with the primary outcome of restraint use, and secondary outcomes of agitation and identification of delirium, during each shift (with patient as a random effect). Our cohort included 4326 shifts (3380 [78.1%] with language concordance) from 548 patients and 157 nurses. Spanish language was preferred by 269 (49.1%) of patients. English-speaking patients tended to be younger (65 [53, 75] vs 73 [61, 83], p < 0.001) and of non-Hispanic ethnicity (55.5% vs 7.1%, p < 0.001). English-speakers had restraints ordered on fewer of their included shifts (0 [0, 3] vs 1 [0, 3], p = 0.005). After adjustment, the odds of restraint use on shifts with language concordance was significantly lower (odds ratio [OR, 95% confidence interval [CI]]: 0.50 [0.39-0.63], p < 0.001). Agitation (18.6% vs 25.2%; OR [95% CI]: 0.71 [0.55-0.92], p = 0.009) and delirium identification (34.5% vs 41.3%; OR [95% CI]: 0.54 [0.34-0.88], p = 0.014) were also less common. We identified a twofold reduction in the odds of restraint use among mechanically ventilated patients for language concordant nurse-patient dyads. Ensuring nurse-patient language concordance may improve ICU delirium, agitation, and restraint use.


The weeks before 100 persecutory delusions: the presence of many potential contributory causal factors.
The period before the formation of a persecutory delusion may provide causal insights. Patient accounts are invaluable in informing this understanding. To inform the understanding of delusion formation, we asked patients about the occurrence of potential causal factors - identified from a cognitive model - before delusion onset. A total of 100 patients with persecutory delusions completed a checklist about their subjective experiences in the weeks before belief onset. The checklist included items concerning worry, images, low self-esteem, poor sleep, mood dysregulation, dissociation, manic-type symptoms, aberrant salience, hallucinations, substance use and stressors. Time to reach certainty in the delusion was also assessed. Most commonly it took patients several months to reach delusion certainty (n = 30), although other patients took a few weeks (n = 24), years (n = 21), knew instantly (n = 17) or took a few days (n = 6). The most frequent experiences occurring before delusion onset were: low self-confidence (n = 84); excessive worry (n = 80); not feeling like normal self (n = 77); difficulties concentrating (n = 77); going over problems again and again (n = 75); being very negative about the self (n = 75); images of bad things happening (n = 75); and sleep problems (n = 75). The average number of experiences occurring was high (mean 23.5, s.d. = 8.7). The experiences clustered into six main types, with patients reporting an average of 5.4 (s.d. = 1.0) different types. Patients report numerous different experiences in the period before full persecutory delusion onset that could be contributory causal factors, consistent with a complex multifactorial view of delusion occurrence. This study, however, relied on retrospective self-report and could not determine causality. None.


Vax1 Plays an Indirect Role in the Etiology of Murine Cleft Palate.
Cleft lip with or without palate (CLP) and isolated cleft palate (CP) are common human developmental malformations with a complex etiology that reflects a failure of normal facial development. VAX1 encodes a homeobox-containing transcription factor identified as a candidate gene for CLP in human populations, with targeted deletion in mice associated with multiple anomalies, including disruption of the visual apparatus and basal forebrain, lobar holoprosencephaly, and CP. We have investigated Vax1 function during murine palatogenesis but found no evidence for a direct role in this process. Vax1 is not expressed in the developing palate and mutant palatal shelves elevate above the tongue, demonstrating morphology and proliferation indices indistinguishable from wild type. However, mutant mice did have a large midline cavity originating from the embryonic forebrain situated beneath the floor of the hypothalamus and extending through the nasal cavity to expand this region and prevent approximation of the palatal shelves. Interestingly, despite strong expression of Vax1 in ectoderm of the medial nasal processes, the upper lip remained intact in mutant mice. We found further evidence of disrupted craniofacial morphology in Vax1 mutants, including truncation of the midface associated with reduced cell proliferation in forebrain neuroectoderm and frontonasal mesenchyme. Sonic hedgehog (Shh) signal transduction was downregulated in the mutant forebrain, consistent with a role for Vax1 in mediating transduction of this pathway. However, Shh was also reduced in this region, suggestive of a Shh-Vax1 feedback loop during early development of the forebrain and a likely mechanism for the underlying lobar holoprosencephaly. Despite significant associations between VAX1 and human forms of CLP, we find no evidence of a direct role for this transcription factor in development of this region in a mutant mouse model.


A growth stimulus is needed for IGF-1 to induce skeletal muscle hypertrophy in vivo.
Here, we characterise new strains of normal and dystrophic (mdx) mice that overexpress Class 2 IGF-1 Ea in skeletal myofibres. We show that transgenic mice have increased muscle levels of IGF-1 (approximately 13-26 fold) and show striking muscle hypertrophy (approximately 24-56% increase in mass). Adult normal muscles were resistant to elevated IGF-1; they reached adult steady state and maintained the same mass from 3 to 12 months. By contrast, dystrophic muscles from mdx/IGF-1(C2:Ea) mice continued to increase in mass during adulthood. IGF-1 signalling was evident only in muscles that were growing as a result of normal postnatal development (23-day-old mice) or regenerating in response to endogenous necrosis (adult mdx mice). Increased phosphorylation of Akt at Ser473 was not evident in fasted normal adult transgenic muscles, but was 1.9-fold higher in fasted normal young transgenic muscles compared with age-matched wild-type controls and fourfold higher in fasted adult mdx/IGF-1(C2:Ea) compared with mdx muscles. Muscles of adult mdx/IGF-1(C2:Ea) mice showed higher p70(S6K)(Thr421/Ser424) phosphorylation and both young transgenic and adult mdx/IGF-1(C2:Ea) mice had higher phosphorylation of rpS6(Ser235/236). The level of mRNA encoding myogenin was increased in normal young (but not adult) transgenic muscles, indicating enhanced myogenic differentiation. These data demonstrate that elevated IGF-1 has a hypertrophic effect on skeletal muscle only in growth situations.


Disputes over the Divine: Introducing the Religion and Armed Conflict (RELAC) Data, 1975 to 2015.
This article introduces the Religion and Armed Conflict (RELAC) data, 1975 to 2015, which is a new data set suitable for analyzing the causes, dynamics, and resolution of religious conflicts. It contains information about key religious dimensions of conflicts: whether the issue at stake is religious, the actors' religious identity, and fine-grained data about the type and salience of religious claims. The article presents the major features of the data set and describes patterns and trends that shed new light on religious conflicts, for example, by demonstrating that conflicts over Islamist claims have become more prevalent. We also illustrate the utility of the data. For instance, we show that there is great variation in lethality across conflicts with different types of Islamist claims, thereby offering a more nuanced understanding of the deadliness of religious conflicts. RELAC should be a valuable resource for scholars, examining religious dimensions of intrastate armed conflicts.


Identifying Sustainable Population Segments Using a Multi-Domain Questionnaire: A Five Factor Sustainability Scale.
This study presents the creation of a measurement device to determine and define sustainability attitudes into identifiable sustainability segments. These segments were profiled with behavioral and sociodemographic data. Based on previous literature, key sustainability topics were identified from which a 31-item questionnaire was developed, the Five Factor Sustainability Scale (FFSS). With the FFSS, multiple domains of environmental sustainability can be assessed. We present results validating this measure using a factor-cluster segmentation approach in a nationally representative sample (N = 508). Five sustainability factors emerged: (1) sustainable spending, (2) sustainable skepticism, (3) sustainable responsibility, (4) sustainable support, and (5) sustainable mobility. A cluster analysis on this sample yielded four segments in which people were grouped according to their sustainable attitudes: (1) Convinced Sustainers, (2) Sustainable Wannabes, (3) Sustainable Non-Believers, and (4) Non-Sustainers. Results linking these segments to behavioral and demographic data show discernable differences between the segments, making the FFSS a valuable tool for future intervention studies aiming at sustainable behavior change.


Dietary supplementation with 2-deoxy-D-glucose improves cardiovascular and neuroendocrine stress adaptation in rats.
Dietary restriction and physical exercise can enhance stress resistance and reduce the risk of cardiovascular disease. We investigated the effects of dietary supplementation with 2-deoxy-d-glucose (2-DG), a glucose analog that limits glucose availability at the cellular level, on cardiovascular and neuroendocrine responses to stress in rats. Young adult male Sprague-Dawley rats were implanted with telemetry probes to monitor blood pressure (BP), heart rate, body temperature, and body movements. These variables were measured at designated times during a 6-mo period in rats fed control and 2-DG-supplemented (0.4% 2-DG, fed ad libitum on a schedule of 2 days on the diet and 1 day off the diet) diets during unperturbed conditions and during and after immobilization stress or cold-water swim stress. Rats fed the 2-DG diet exhibited significant reductions in resting BP, attenuated BP responses during stress, and accelerated recovery to baseline after stress. Plasma concentrations of ACTH and corticosterone were elevated under nonstress conditions in rats fed the 2-DG diet and exhibited differential responses to single (enhanced response) and multiple (reduced response) stress sessions compared with rats fed control rat chow ad libitum. The 2-DG diet improved glucose metabolism, as indicated by decreased concentrations of blood glucose and insulin under nonstress conditions, but glucose and insulin responses to stress were maintained. We conclude that improvements in some cardiovascular risk factors and stress adaptation in rats maintained on a 2-DG-supplemented diet are associated with reduced neuroendocrine responses to the stressors.


Effects of nicotine on ethanol-induced locomotor sensitization: A model of neuroadaptation.
Co-morbid use of nicotine-containing tobacco products and alcohol (ethanol) is prevalent in young adults initiating use and in alcohol dependent adults, suggesting that these drugs in combination may increase risk to develop dependence on one or both drugs. Neuroadaptations caused by repeated drug exposure are related to the development of drug dependence and vulnerability to relapse. Locomotor sensitization has been used as a behavioral measure used to detect changes in neural drug sensitivity that are thought to contribute to drug dependence and relapse. Locomotor sensitization was measured in the current studies to examine potential differences in the effects of nicotine and ethanol given alone and in combination. Baseline activity levels of DBA/2J mice were assessed on 2 days, then mice were treated for 10 days with saline, nicotine (1 or 2mg/kg of nicotine tartrate), ethanol (1 or 2g/kg), or nicotine plus ethanol and locomotor activity was assessed every third day. On the following day, all mice were challenged with ethanol to measure the expression of sensitization. Mice treated with both nicotine and ethanol exhibited greater stimulation than predicted from the combined independent effects of these drugs, consistent with our previously published results. The combined effects of nicotine and ethanol on locomotor sensitization were dependent on the dose of ethanol and whether testing was performed after the drugs were given together, or after challenge with ethanol alone. These results suggest that nicotine and ethanol in combination can have neuroadaptive effects that differ from the independent effects of these drugs.


Sequelae of septic arthritis of the hip in children: a new classification and a review of 41 hips.
The sequelae of septic arthritis of the hip in children are diverse and represent a complex problem. A classification of the deformities is important to plan treatment and to give prognostic information. The radiographic main classification used provides detailed information of the deformities, but it is complicated and not feasible to apply in young children. The authors developed a simple and reliable method of classification and present the results of a large series of patients. The authors reviewed 37 children with 41 hips with sequelae of septic arthritis of the hip. Twenty-four were male subjects, and 13 were female subjects. Twenty-five had the acute infection at the neonatal period, and 16 were aged between 1 month and 3 years. None of them received adequate treatment at the acute process: 20 hips were not treated, and the other 21 had delayed drainage (at least 5 days after the onset of the infection). The hips were classified into 2 groups on the basis of radiographic appearance. Hips with sequelae grade 1 were reduced hips, with femoral head preserved (1A) or absent (1B); hips grade 2 were dislocated hips, with the femoral head preserved (2A) or absent (2B). There were 10 hips with grade 1A, 11 with grade 1B, 3 with grade 2A, and 17 were grade 2B. We compared our material and results with those presented by Choi et al and also compared the reliability of both classification. The criteria for satisfactory results were stability, range of motion of 50 degrees or more of flexion, a flexion contraction below 20 degrees, and a painless hip. Our classification presented a greater concordance (25 of 41 hips against 7 in 41 for the Choi et al classification; P = 0.01). Thirty-seven hips were pain-free, and 4 had occasional pain. Thirty-seven hips had a satisfactory range of motion (90.2%). Stability was present in 29 hips (70.7%). Final results showed 24 hips classified as satisfactory and 17 as unsatisfactory. Our material and end results were comparable with those reported by Choi et al.Septic arthritis of the hip developed at the newborn period produced more severe sequelae. Hips with sequelae grade 1 have a good prognosis. Surgical procedures in these grades were necessary to correct acetabular dysplasia and improve congruency. Fifteen of 20 hips with sequelae grade 2 (unstable) underwent reconstruction. At a mean follow-up of 6.9 years (range, 2.7-11.3 years), satisfactory results were obtained in 8 of them. The classification we proposed showed to be simpler and more reliable than the classification proposed by Choi et al. It may be useful to guide treatment and prognosis. Longer follow-up is needed to assess the real benefit of the reconstruction for unstable hips.


[Diagnosis and surgical treatment results in neurovascular thoracic outlet compression syndrome].
A detailed study of 44 patients with the neuro-vascular compression syndrome of thoracic exit has established the diagnostic value of clinical and special methods of diagnosing the disease. The most frequent symptoms were pain in the anterior scalene muscle (ASM) during palpation (96%) and paresthesia in fingers (93%). Rheography, arteriography and phlebography of the upper extremities combined with the positional tests should be resorted to. In case of marked neurological symptoms the data on the nerve block of the ASM are informative. Surgical treatment was undertaken in 35 patients: resection of the I rib in 14 cases (in 4 resection combined with upper thoracic sympathectomy), resection of the ASM in 12, removal of the accessory cervical rib with scalenotomy in 5, decompressive vascular reconstructive operations in 10 patients with vascular complications. Good results were obtained in 32 patients. It is stressed that detailed examinations of patients with vaso-neurological symptoms in the upper extremity are important for timely diagnosis and surgery before the complications supervene.


Calving rate following fixed time insemination after a 12-day progesterone treatment in dairy cows, beef cows and heifers.
Farm trials were carried out to determine if cows and heifers could be inseminated on a fixed time basis following a 12-day treatment with progesterone coils and an injection of 5 mg oestradiol benzoate and 200 mg progesterone at the start of treatment. The retention rate of the coils was significantly higher (P less than 0.05) when a 5.5 cm diameter was used compared with a diameter of 7.0 cm. Calving rate was similar in treated cows bred at a detected oestrus, at 56 + 74 hours after treatment or at 56 hours after treatment and injection of 100 microgram gonadotrophin releasing hormone 20 hours previously and in control cows bred at oestrus. Fertility to the first repeat oestrus was also similar in treated and control cows. Significantly (P less than 0.05) more synchronised cows calved following fixed time AI compared with the calving rate in control cows inseminated for a 24-day experimental period. In beef suckler cows, calved at least 50 days, and dairy heifers weighing over 280 kg, calving rate was similar in treated animals bred at 56 and 74 hours after treatment compared to calving rate in control animals bred at oestrus.


The time interval between injection of nicotine and tremor initiation; a new index for evaluating nicotine efficacy in rodents.
Tremor is one of the effects of nicotine as a toxic substance, especially in animal models. The intensity and duration of tremors were used to evaluate the effect of nicotine on locomotor activity in laboratory animals. In our observations, the time interval between nicotine injection and the onset of tremor changed depending on the dose. Therefore, by increasing the dose of nicotine in rats, the time interval of tremor onset was also shortened. These results suggest that the time interval between nicotine injection and the onset of tremors can be used as a complementary index for better evaluation of nicotine-derived motor disturbances.


Topical Management of Enterocutaneous and Enteroatmospheric Fistulas: A Systematic Review.
Enterocutaneous (ECF) and enteroatmospheric (EAF) fistulas are associated with considerable morbidity and patient care challenges, including optimal topical management. A systematic literature review was conducted to identify topical management interventions used in ECF/EAF care and to explore the role of these interventions in fistula closure and long-term fistula management. A search of PubMed, the Cumulative Index of Nursing and Allied Health Literature, and Scopus was conducted to identify English-language articles published from January 2004 to January 2019. The keywords enterocutaneous fistula, enteroatmospheric fistula, negative pressure wound therapy, NPWT, vacuum-assisted closure, VAC, pouch or pouching, troughing, bridging, collection device, dressing, and wound care were used to identify all publications pertaining to the topical management of adult and mixed adult/pediatric patients with an ECF or EAF. Single-person case studies, exclusively pediatric studies, surgical treatment-based, and duplicate publications were excluded. Abstracts were screened for relevance to the research questions, and eligible publications were abstracted and categorized using The Oxford Centre for Evidence-Based Medicine Levels of Evidence. The Joanna Briggs Institute (JBI) critical appraisal checklist for case series was used to assess each article for risk of bias and methodological quality. Outcomes of interest included patient demographics, closure rates, fistula classification (type of fistula, fistula output, fistula origin), type of topical treatment, adverse events (pain, new fistula formation, fistula recurrence, mortality), follow-up, long-term management, perifistula skin protection, effluent management, dressing change frequency, and quality of life. Descriptive statistics were presented; no statistical analysis was performed. Of the 983 articles identified, 57 underwent critical appraisal using the JBI checklist for case series. Forty-two (42) did not meet the inclusion criteria, leaving 15, level IV, case-based publications (N = 410 patients). No randomized controlled trials were found. All studies included some form of negative pressure wound therapy. JBI results found that each study was at high risk of bias in more than 2 domains. Interventions were categorized as intubation, occlusion, or isolation of the fistula. Of the 559 fistulas treated, spontaneous closure was reported in 164 cases, with rates ranging from 0% to 100%. Adverse events to treatment included pain (n = 33 patients), new fistula formation (n = 12), and fistula recurrence (n = 1). Sepsis was the leading cause of mortality (n = 29), with reported rates ranging from 0% to 44%. Due to the high risk of study bias and low quality of evidence, the exact contribution of any one intervention could not be established. Results also suggest a high risk of publication bias, and patient-centered outcomes were reported in only 1 study. Although topical management might play a role in fistula closure, it is only as part of a comprehensive plan of care. Future research should focus on developing and using standardized reporting tools, classifications, and outcomes and include patient-centered outcomes such as acceptance, tolerability, pain, and quality of life relating to any one intervention. At this time, the evidence base for management recommendations is limited, suggesting that interventions should mainly be based on practical considerations such as resources and clinician skill.


The role of free flaps in the treatment of persistent scalp osteomyelitis.
To evaluate the efficacy of the combination of an extensive surgical debridement and simultaneous free flap repair in case of troublesome cranial osteomyelitis. Five patients with persistent, frontal bone osteomyelitis were treated with surgical debridement of the infected bone and reconstruction with a free flap. In all patients, osteomyelitis occurred after neurosurgical procedures and lasted from 1 to 7 years. A latissimus dorsi muscle flap with a split skin graft has been performed. No flap failure occurred and donor site morbidity was negligible. No signs of osteomyelitis or soft tissue infection were observed during the mean follow-up period of 3.2 years. Furthermore, the contour of the cranium could be preserved without a need for bone grafts or implants. In our experience, the combination of an extensive surgical debridement and a free flap transfer is demonstrated to be an effective treatment for "chronic" osteomyelitis of the cranium.


CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease.
The Epstein-Barr virus (EBV) latency C promoter drives expression of a family of viral proteins commonly targeted by CD8 cytotoxic T cells. These proteins are not generally expressed in African Burkitt's lymphoma and in EBV-associated Hodgkin's disease. The failure to express these proteins is almost certainly an important factor in the evasion of immunosurveillance by EBV-associated tumors. In a previous study, we have shown that transcriptional activation of the C promoter is inhibited by methylation of a particular CpG site upstream of the promoter that prevents binding of a cellular protein (CBF2), and we have shown that this and adjacent CpG sites are methylated in a Burkitt's lymphoma cell line. In the present study, we show that CpG sites in the CBF2 binding region are predominantly methylated in African Burkitt's lymphoma and in EBV-associated Hodgkin's disease. In addition, we present the first direct evidence that the C promoter is transcriptionally silent in Burkitt's lymphoma. In contrast, we show a complete absence of methylation in the CBF2 binding region in a case of reversible EBV-associated B-cell lymphoma arising in an immunocompromised patient whose tumor shows C promoter transcriptional activity. By inhibiting expression of highly antigenic viral proteins, methylation of transcriptional control sequences may veil the presence of virus in tumor tissue from CD8(+) cytotoxic T-cell immune surveillance and thus facilitate viral tumorigenesis.


Ratios of template responses as the basis of semivision.
The template model starts with a layer of receptors that in the case of vision are leaky detectors or counters of photons. In many animals, the ratio of the responses of a few spectral types is the basis of colour vision irrespective of intensity. Ratios of template responses are now introduced as the basis of form discrimination. In insects, the second-order neurons on the visual pathway appear to detect temporal contrast at the spatial resolution of the retina. At the next level, in the optic medulla, we find a large number of small local neurons in a column on each visual axis. The template theory is a hypothesis about how the above system functions. All possible combinations of positive, indeterminate or negative temporal contrast are considered, at two adjacent visual axes at two successive instants, giving 81 possible local templates. These templates are therefore phasic detectors of all the possible spatiotemporal contrast combinations. Some of the template responses indicate polarity of edge, flicker, or direction of motion and other abstracted features of the stimulus pattern with the maximum spatial and temporal resolution. The ratios of numbers of template responses, in higher fields at a higher level, yield quantitative measures of the qualities of edges independently of the number of edges, but taking ratios causes a corresponding loss of the spatiotemporal resolution and the pattern within each field. Templates respond to transients without computation, are readily modified or selected in evolution and can be simulated in artificial vision.


The response regulator PhoP of Yersinia pseudotuberculosis is important for replication in macrophages and for virulence.
Yersinia pestis and Yersinia pseudotuberculosis are closely related facultative intracellular pathogens. The response regulator PhoP was previously shown to be important for Y. pestis survival in macrophages and for virulence in a murine bubonic plague infection assay. Here the importance of PhoP for Y. pseudotuberculosis pathogenesis was investigated. Y. pseudotuberculosis phoP mutants were unable to replicate in low-Mg(2+) medium or in macrophages. phoP(+) Y. pseudotuberculosis strains initiated replication in macrophages after a lag period of approximately 5 h, as shown by fluorescence microscopy and viable count assays. Y. pseudotuberculosis phoP mutants died at a low rate in macrophages; there was no decrease in viability over the first 5 h of infection, and there was a 10-fold decrease in viability between 5 and 24 h of infection. Trafficking of phagosomes containing phoP(+) or phoP mutant Y. pseudotuberculosis was studied by using immunofluorescence microscopy and cathepsin D as a marker for lysosomes. Phagosomes containing phoP mutant Y. pseudotuberculosis acquired cathepsin D at a higher rate than phagosomes containing phoP(+) bacteria. However, the increased rate of marker acquisition for phagosomes containing mutant bacteria was only evident approximately 5 h after infection, suggesting that phoP mutants are able to retard phagosome maturation during the lag phase of intracellular growth. The results obtained with a Y. pestis phoP mutant were similar to those described above, except that the rates of intracellular killing and trafficking to cathepsin D-positive vacuoles were significantly higher. A Y. pseudotuberculosis phoP mutant was 100-fold less virulent than the wild-type strain in a murine intestinal infection model, suggesting that survival and replication in macrophages are important for Y. pseudotuberculosis pathogenesis.


Image quality versus statistical power.
We investigated whether SPET studies of neuroactivation might benefit from a similar approach used in PET; that is, increase the number of scans per task and accept poorer individual scan quality. Different study paradigms were simulated by varying the scanning parameters: (1) administered radiation activity per scan, (2) number of scans per task and (3) scan acquisition time. The maximum total dose received by each simulated subject remained the same. Areas of activation of varying signal strength were added to the scans using a customized graphics package. To establish the statistical benefits of a replication paradigm versus a non-replication paradigm, the datasets were analysed using SPM95 statistics software. This simulation was able to show that, when an SPM investigation is used for data analysis, study replication is more important than the individual image quality typically available from a high-performance SPET system.


Efficient decellularization of equine tendon with preserved biomechanical properties and cytocompatibility for human tendon surgery indications.
Chronic and acute tendon injuries are frequent afflictions, for which treatment is often long and unsatisfactory. When facing extended injuries, matrices and scaffolds with sufficient biomechanical properties are required for surgical repair and could additionally serve as supports for cellular therapies to improve healing. In this study, protocols of either commonly used detergents only (SDS 1%, Triton 1%, TBP 1%, and Tween-20 1%) or a combination of freeze/thaw (F/T) cycles with decellularization agents (NaCl 1M, ddH2 O) were evaluated for the decellularization of horse equine superficial digital flexor tendon (SDFT) for hand flexor or extensor tendon reconstruction. Decellularization efficiency was assessed microscopically by histological staining (HE, DAPI) and DNA quantification. Macroscopical structure and biomechanical integrity of the tendon matrices were further assessed by gross observation, histological staining (SR), and mechanical testing (ultimate strain and stress, Young's modulus, energy to failure) for select protocols. Decellularization with hypertonic NaCl 1M in association with F/T cycles produced the most robust tendon matrices, which were nontoxic after 10 days for subsequent recellularization with human fetal progenitor tendon cells (hFPTs). This standardized protocol uses a less aggressive decellularization agent than current practice, which allows subsequent reseeding with allogenic cells, therefore making them very suitable and bioengineered tendon matrices for human tendon reconstruction in the clinic.


A2B adenosine receptors protect against sepsis-induced mortality by dampening excessive inflammation.
Despite intensive research, efforts to reduce the mortality of septic patients have failed. Adenosine is a potent extracellular signaling molecule, and its levels are elevated in sepsis. Adenosine signals through G-protein-coupled receptors and can regulate the host's response to sepsis. In this study, we studied the role of A(2B) adenosine receptors in regulating the mortality and inflammatory response of mice following polymicrobial sepsis. Genetic deficiency of A(2B) receptors increased the mortality of mice suffering from cecal ligation and puncture-induced sepsis. The increased mortality of A(2B) knockout mice was associated with increased levels of inflammatory cytokines and chemokines and augmented NF-kappaB and p38 activation in the spleen, heart, and plasma in comparison with wild-type animals. In addition, A(2B) receptor knockout mice showed increased splenic apoptosis and phosphatase and tensin homolog activation and decreased Akt activation. Experiments using bone-marrow chimeras revealed that it is the lack of A(2B) receptors on nonhematopoietic cells that is primarily responsible for the increased inflammation of septic A(2B) receptor-deficient mice. These results indicate that A(2B) receptor activation may offer a new therapeutic approach for the management of sepsis.


Prediction of local ultimate strain and toughness of trabecular bone tissue by Raman material composition analysis.
Clinical studies indicate that bone mineral density correlates with fracture risk at the population level but does not correlate with individual fracture risk well. Current research aims to better understand the failure mechanism of bone and to identify key determinants of bone quality, thus improving fracture risk prediction. To get a better understanding of bone strength, it is important to analyze tissue-level properties not influenced by macro- or microarchitectural factors. The aim of this pilot study was to identify whether and to what extent material properties are correlated with mechanical properties at the tissue level. The influence of macro- or microarchitectural factors was excluded by testing individual trabeculae. Previously reported data of mechanical parameters measured in single trabeculae under tension and bending and its compositional properties measured by Raman spectroscopy was evaluated. Linear and multivariate regressions show that bone matrix quality but not quantity was significantly and independently correlated with the tissue-level ultimate strain and postyield work (r = 0.65-0.94). Principal component analysis extracted three independent components explaining 86% of the total variance, representing elastic, yield, and ultimate components according to the included mechanical parameters. Some matrix parameters were both included in the ultimate component, indicating that the variation in ultimate strain and postyield work could be largely explained by Raman-derived compositional parameters.


Transient neurological symptoms following spinal anesthesia for cesarean section.
Transient neurological symptoms (TNS) are defined as symmetrical bilateral pain in the back or buttocks or pain radiating to the lower extremities after recovery from spinal anesthesia. About 80-85% of cesarean sections are performed under spinal anesthesia in our centre. Our aim was to determine the incidence of TNS, risk factors and outcome of management in pregnant women undergoing cesarean section. Approval was obtained from the hospital ethic's committee, and consent from the patients. ASA 1 and 2 pregnant women undergoing cesarean section under spinal anesthesia formed the subjects of this prospective study. They were evaluated and pre-medicated by the attending anesthetists. Spinal anesthesia was performed at the L2-3 or L3-4 interspaces, using a 25G Quincke or 25G pencil point spinal needle with 0.5% heavy bupivacaine. The investigators interviewed the patients in the ward for three consecutive days, in order to identify those that developed TNS. One hundred and twenty consecutive patients were studied. TNS were documented in 12 (10%) patients. Backache was recorded in 8 patients (6.6%), pain in the thighs in 2 (1.7%) and pain in the buttocks in 2 (1.7%). Onset time of symptoms was recorded as 6-12 hrs in 5 (4.2%) patients, 12-24 hrs in 5 (4.2%) and 24-48 hrs in 2 (1.6%). The patients that developed TNS were managed accordingly with satisfactory outcome. A follow-up for all patients that receive spinal anesthesia for cesarean section should constitute a standard practice.


Identification of an ATPase activity associated with a 71-kilodalton polypeptide encoded in gene 1 of the human coronavirus 229E.
Human coronavirus 229E gene expression involves proteolytic processing of the gene 1-encoded polyproteins pp1a and pp1ab. In this study, we have detected a 71-kDa polypeptide in virus-infected cells that is released from pp1ab by the virus-encoded 3C-like proteinase and that has been predicted to contain both metal-binding and helicase domains. The polypeptide encompasses amino acids Ala-4996 to Gln-5592 of pp1ab and exhibits nucleic acid-stimulated ATPase activity when expressed as a fusion protein with the Escherichia coli maltose-binding protein. These data provide the first identification of a coronavirus open reading frame 1b-encoded enzymatic activity.


Interpretation of dose-response curves for luteinizing hormone release by gonadotropin-releasing hormone, related peptides, and leukotriene C4 according to a hormone/receptor/effector model.
The dose-response curves for pituitary luteinizing hormone (LH) release in response to gonadotropin-releasing hormone and its agonists are unusually broad. It appears, however, that these ligands bind to a single class of receptors. It is shown that these dose-response data can be explained by either of two models in which ligand-receptor complexes stimulate LH secretion by interacting with either of two different effector systems or by interacting with a single effector system but forming monomeric and dimeric active effector complexes. A combination of these two basic models can account for the very broad, biphasic dose-response curve reported for LH release in response to leukotriene C4.


Energy transduction on the nanosecond time scale: early structural events in a xanthopsin photocycle.
Photoactive yellow protein (PYP) is a member of the xanthopsin family of eubacterial blue-light photoreceptors. On absorption of light, PYP enters a photocycle that ultimately transduces the energy contained in a light signal into an altered biological response. Nanosecond time-resolved x-ray crystallography was used to determine the structure of the short-lived, red-shifted, intermediate state denoted [pR], which develops within 1 nanosecond after photoelectronic excitation of the chromophore of PYP by absorption of light. The resulting structural model demonstrates that the [pR] state possesses the cis conformation of the 4-hydroxyl cinnamic thioester chromophore, and that the process of trans to cis isomerization is accompanied by the specific formation of new hydrogen bonds that replace those broken upon excitation of the chromophore. Regions of flexibility that compose the chromophore-binding pocket serve to lower the activation energy barrier between the dark state, denoted pG, and [pR], and help initiate entrance into the photocycle. Direct structural evidence is provided for the initial processes of transduction of light energy, which ultimately translate into a physiological signal.


[Reduction-plasty of the breast in symmastia].
Medial confluence of the breasts, known as symmastia, has received little attention in plastic surgery literature. By reporting on one case, we present our surgical technique. The chosen method of the reduction mammoplasty is considered to be particularly important. Liposuction is integrated into the surgical procedure. Suggestions made by other authors are discussed.


Integration of Continuous Glucose Monitoring Data into an Electronic Health Record System: Single-Center Implementation.
Managing data from continuous glucose monitoring (CGM) systems presents challenges to health care provider teams that rely on the electronic health record (EHR) during patient visits. A method of integrating CGM data with the EHR that relies on the Dexcom API was developed by Northwestern Medicine and Dexcom to address these challenges. Here, we describe the data management steps and user interface of the integrated system. Providers can access patients' historical and latest daily CGM data in the form of modal day plots and stacked columns showing time in various glucose concentration ranges. The integration facilitates the acquisition, storage, analysis, and display of CGM data within an EHR system and may be appropriate for deployment in other health care facilities.


Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer.
Inhibition of phosphatidylinositol-3-kinase (PI3K) induces apoptosis when combined with estrogen deprivation in estrogen receptor (ER)-positive breast cancer. The aims of the present study were to identify effective PI3K pathway inhibitor and endocrine therapy combinations, to evaluate the effect of PI3K pathway mutations and estrogen dependency on tumor response, and to determine the relevance of PIK3CA mutation in recurrent disease. The PI3K catalytic subunit inhibitor BKM120, the mammalian target of rapamycin (mTOR) inhibitor RAD001 and the dual PI3K/mTOR inhibitor BGT226 were tested against ER-positive breast cancer cell lines before and after long-term estrogen deprivation (LTED). The impact of estradiol deprivation and the ER downregulator fulvestrant on PI3K pathway inhibitor-induced apoptosis was assessed. PIK3CA hotspot mutation analysis was performed in 51 recurrent or metastatic breast cancers and correlated with ER status and survival. Drug-induced apoptosis was most marked in short-term estrogen-deprived cells with PIK3CA mutation and phosphatase and tensin homolog loss. Apoptosis was most highly induced by BGT226, followed by BKM120, and then RAD001. Estradiol antagonized PI3K inhibitor-induced apoptosis following short-term estrogen deprivation, emphasizing a role for estrogen-deprivation therapy in promoting PI3K inhibitor activity in the first-line setting. ER-positive MCF7 LTED cells exhibited relative resistance to PI3K pathway inhibition that was reversed by fulvestrant. In contrast, T47D LTED cells exhibited ER loss and ER-independent PI3K agent sensitivity. PIK3CA mutation was prevalent in relapsed ER-positive disease (48%) and was associated with persistent ER positivity and a late relapse pattern. Estrogen deprivation increased the apoptotic effects of PI3K and dual PI3K/mTOR inhibitors in ER-positive disease, providing a rationale for PI3K/aromatase inhibitor combinations as first-line therapy. In LTED cells, differential effects on ER expression may be a relevant consideration. When ER was persistently expressed, fulvestrant strongly promoted PI3K drug activity. When ER was lost, PI3K inhibitor monotherapy was sufficient to induce high-level apoptosis. Although tumors with PIK3CA mutation had a late recurrence pattern, these mutations were common in metastatic disease and were most often associated with persistent ER expression. Targeting PIK3CA mutant tumors with a PI3K pathway inhibitor and fulvestrant is therefore a feasible strategy for aromatase-inhibitor-resistant ER-positive relapsed breast cancer.


Association of resistance to avian coccidiosis with single nucleotide polymorphisms in the zyxin gene.
Our previous genetic studies demonstrated that resistance to avian coccidiosis is linked with microsatellite markers LEI0071 and LEI0101 on chromosome 1. In this study, the associations between parameters of resistance to coccidiosis and single nucleotide polymorphisms (SNP) in 3 candidate genes located between LEI0071 and LEI0101 [zyxin, CD4, and tumor necrosis factor receptor super family 1A (TNFRSF1A)] were determined. The SNP were genotyped in 24 F(1) generation and 290 F(2) generation animals. No SNP were identified in the TNFRSF1A gene, whereas 10 were located in the zyxin gene and 4 in the CD4 gene. At various times following experimental infection of the F(2) generation with Eimeria maxima, BW, fecal oocyst shedding, and plasma levels of carotenoid, nitrite plus nitrate (NO(2)(-) + NO(3)(-)), and interferon-gamma (IFN-gamma) were measured as parameters of resistance. Single marker and haplotype-based tests were applied to determine the associations between the 14 SNP and the parameters of coccidiosis resistance. None of the CD4 SNP were correlated with disease resistance. However, by single marker association, several of the zyxin SNP were significantly associated with carotenoid or NO(2)(-) + NO(3)(-) concentrations. These were the SNP at nucleotide 149 associated with carotenoid at d 3 postinfection (PI), nucleotide 187 with carotenoid at d 6 and 9 PI, and nucleotide 159 with carotenoid between d 3 and 9 PI. In addition, the zyxin SNP at nucleotide 191 was significantly associated with increased levels of NO(2)(-) + NO(3)(-) at d 3 PI. By haplotype association, the zyxin SNP also were found to be highly associated with NO(2)(-) + NO(3)(-) at d 3 PI and increased IFN-gamma at d 6 PI. These results suggest that zyxin is a candidate gene potentially associated with increased resistance to experimental avian coccidiosis.


Nonmelanoma skin cancer in relation to ionizing radiation exposure among U.S. radiologic technologists.
Ionizing radiation (IR) is an established cause of nonmelanoma skin cancer, but there is uncertainty about the risk associated with chronic occupational exposure to IR and how it is influenced by ultraviolet radiation (UVR) exposure. We studied 1,355 incident cases with basal cell carcinoma (BCC) and 270 with squamous cell carcinoma (SCC) of the skin in a cohort of 65,304 U.S. white radiologic technologists who responded to the baseline questionnaire survey in 1983-1989 and the follow-up survey in 1994-1998. Cox's proportional-hazards model was used to estimate relative risks of BCC and SCC associated with surrogate measures of occupational exposure to IR and residential UVR exposure during childhood and adulthood, adjusted for potential confounders including pigmentation characteristics. Relative risks of BCC, but not of SCC, were elevated among technologists who first worked during the 1950s (RR = 1.42; 95% CI = 1.12-1.80), 1940s (RR = 2.04; 95% CI = 1.44-2.88) and before 1940 (RR = 2.16; 95% CI = 1.14-4.09), when IR exposures were high, compared to those who first worked after 1960 (p for trend < 0.01). The effect of year first worked on BCC risk was not modified by UVR exposure, but was significantly stronger among individuals with lighter compared to darker eye and hair color (p = 0.013 and 0.027, respectively). This study provides some evidence that chronic occupational exposure to IR at low to moderate levels can increase the risk of BCC, and that this risk may be modified by pigmentation characteristics.


The pull into wakefulness: How sociocultural categories intersect to shape sleep opportunity and sleep ability in Israel.
Prior studies have documented the existence of sleep disparities between social groups and have proposed possible reasons for these gaps. To extend these empirical findings, the current study elucidates whether and how intersections between sociocultural identities shape the lived experience and management of sleep and sheds light on the social factors that explain within-group heterogeneity. This article draws on semi-structured interviews with 66 employed Israelis, aged 40-60, conducted between February 2020 and February 2022. Participants were selected using a non-probability purposeful sampling design that sought to include individuals with a wide range of sociodemographic backgrounds in terms of gender, ethnonationality, socioeconomic status, religion, and religiosity as well as the quality of sleep. The analysis shows that intersections of gender, socioeconomic status, ethnonationality, religion, and religiosity prompt qualitatively different understandings, experiences, and management of sleep, in a way that affects both sleep opportunity and sleep ability. This study contributes to the scholarly understanding of the social determinants of sleep by highlighting the significance of the intersections of sociocultural identities for sleep health and implementing a nuanced socioecological approach to understanding within-group variability. The results call for the design of tailored interventions that consider the sociocultural context.


CopR, a Global Regulator of Transcription to Maintain Copper Homeostasis in Pyrococcus furiosus.
Although copper is in many cases an essential micronutrient for cellular life, higher concentrations are toxic. Therefore, all living cells have developed strategies to maintain copper homeostasis. In this manuscript, we have analyzed the transcriptome-wide response of Pyrococcus furiosus to increased copper concentrations and described the essential role of the putative copper-sensing metalloregulator CopR in the detoxification process. To this end, we employed biochemical and biophysical methods to characterize the role of CopR. Additionally, a copR knockout strain revealed an amplified sensitivity in comparison to the parental strain towards increased copper levels, which designates an essential role of CopR for copper homeostasis. To learn more about the CopR-regulated gene network, we performed differential gene expression and ChIP-seq analysis under normal and 20 μM copper-shock conditions. By integrating the transcriptome and genome-wide binding data, we found that CopR binds to the upstream regions of many copper-induced genes. Negative-stain transmission electron microscopy and 2D class averaging revealed an octameric assembly formed from a tetramer of dimers for CopR, similar to published crystal structures from the Lrp family. In conclusion, we propose a model for CopR-regulated transcription and highlight the regulatory network that enables Pyrococcus to respond to increased copper concentrations.


Sexual imprinting in human mate choice.
Animal and human studies have shown that individuals choose mates partly on the basis of similarity, a tendency referred to as homogamy. Several authors have suggested that a specific innate recognition mechanism, phenotypic matching, allows the organism to detect similar others by their resemblance to itself. However, several objections have been raised to this theory on both empirical and theoretical grounds. Here, we report that homogamy in humans is attained partly by sexual imprinting on the opposite-sex parent during childhood. We hypothesized that children fashion a mental model of their opposite-sex parent's phenotype that is used as a template for acquiring mates. To disentangle the effects of phenotypic matching and sexual imprinting, adopted daughters and their rearing families were examined. Judges found significant resemblance on facial traits between daughter's husband and her adoptive father. Furthermore, this effect may be modified by the quality of the father-daughter relationship during childhood. Daughters who received more emotional support from their adoptive father were more likely to choose mates similar to the father than those whose father provided a less positive emotional atmosphere.


S6K1 controls pancreatic β cell size independently of intrauterine growth restriction.
Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance. Here we found that S6K1 deficiency in mice also leads to decreased β cell growth, intrauterine growth restriction (IUGR), and impaired placental development. IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic β cell growth and the onset of T2DM later in life. However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore β cell size or insulin levels in S6K1-/- embryos, suggesting that loss of S6K1 leads to an intrinsic β cell lesion. Consistent with this hypothesis, reexpression of S6K1 in β cells of S6K1-/- mice restored embryonic β cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR. Together, these data suggest that a nutrient-mediated reduction in intrinsic β cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced β cell growth and eventual development of T2DM later in life.


Exclusive Breastfeeding Is Favorably Associated with Physical Fitness in Children.
Objective: To examine the potential association between exclusive breastfeeding and its duration on physical fitness (PF) components during childhood. Materials and Methods: A random sample of 5,125 dyads children and their mothers was evaluated. With the use of a standardized questionnaire, telephone interviews were carried out for the collection of maternal lifestyle factors (e.g., breastfeeding and its duration, etc.). Data from five PF tests (e.g., vertical jump, standing long jump, small ball throw, 30-m sprint, and 20-m shuttle run) were used to assess lower and upper body strength, speed, and cardiorespiratory fitness (CRF). Linear and logistic regression models were estimated and adjusted for children's body mass index (BMI) and birth weight, and parental factors (prepregnancy BMI, gestational weight gain, gestational age, pregnancy in vitro, parity before, and educational level). Results: Among boys, exclusive breastfeeding was favorably associated with CRF (b = 0.07), lower body strength (b = 0.41), upper body strength (b = 0.10), and speed (b = -0.11). Also, among girls, we found a favorable association between exclusive breastfeeding and CRF (b = 0.07), lower body strength (b = 0.47), upper body strength (b = 0.10), and speed (b = -0.11). All of the associations remained significant after adjusting for several potential confounders. With the exception of speed test in girls, children who were exclusively breastfed ≥6 months had 10-40% increased odds for average/high performances in PF tests in comparison with those who were breastfed <1 month. Conclusions: Exclusive breastfeeding ≥6 months had a favorable influence on PF test performances in childhood. It seems that exclusive breastfeeding could play a significant role in children's future health.


High mitochondrial sequence divergence in synanthropic flea species (Insecta: Siphonaptera) from Europe and the Mediterranean.
Adult fleas are haematophagous ectoparasites of warm-blooded vertebrates, particularly mammals. Among them, the cat flea (Ctenocephalides felis) and the human flea (Pulex irritans) have high veterinary-medical significance, owing to their cosmopolitan distribution and role in the transmission of important vector-borne pathogens. While the taxonomy of Ct. felis has been investigated on a morphological basis during the past decades, its molecular-phylogenetic analyses have been only recently conducted. This study expands the knowledge on Ct. felis from hitherto less studied geographical regions, and includes representatives from additional flea families, less investigated with molecular approaches. Fleas were collected in four countries of the Mediterranean Basin (Croatia, Italy, Malta and Israel), as well as in Hungary, from domestic and wild carnivores, rodents and humans. The DNA extracts of representative fleas (n = 148), belonging to ten species of eight genera, were used for PCR amplification of part of their cytochrome c oxidase subunits 1, 2 (cox1, cox2) and 18S rRNA genes, followed by sequencing and phylogenetic analyses. The majority (65.6%) of Ct. felis felis cox2 sequences showed 99.4-100% similarity to each other (haplogroup A), whereas those from Malta and Israel had 98.1-98.7% sequence similarity (haplogroup B), and a third sequence from Israel (haplotype C) had as low as 96.3% sequence similarity in comparison with a reference sequence from group "A". Except for the shape of the head, no consistent morphological differences (e.g. in chaetotaxy) were found between haplogroups "A" and "C". Haplotypes of Ct. canis were genetically more homogenous, with 99.6-100% sequence similarity to each other. However, when P. irritans collected from humans was compared to those from three species of wild carnivores, these only had 96.6% cox2 similarity. The mouse flea, Leptopsylla segnis and the northern rat flea, Nosopsyllus fasciatus were both shown to have haplotypes with low intraspecific cox2 similarities (96.2 and 94.4%, respectively). Taken together, differences between mitochondrial lineages within four flea species exceeded that observed between two Chaetopsylla spp. (which had 97.3% cox2 similarity). The topologies of cox1 and cox2 phylogenetic trees were in line with relevant sequence comparisons. Conversely, 18S rRNA gene analyses only resolved differences above the species level. Ctenocephalides felis felis, P. irritans, L. segnis and N. fasciatus were shown to have such a high level of mitochondrial gene heterogeneity, that the uniformity of these flea taxa should be reconsidered. Although the present results are limited (especially in the case of L. segnis and N. fasciatus), there appears to be no geographical or host restriction, which could explain the divergence of these genetic lineages.


Magnetic sphincter augmentation: considerations for use in Barrett's esophagus.
Barrett's esophagus (BE) occurs in 5-15% of patients with gastroesophageal reflux disease (GERD). While acid suppressive therapy is a critical component of BE management to minimize the risk of progression to esophageal adenocarcinoma, surgical control of mechanical reflux is sometimes necessary. Magnetic sphincter augmentation (MSA) is an increasingly utilized anti-reflux surgical therapy for GERD. While the use of MSA is listed as a precaution by the United States Food and Drug Administration, there are limited data showing effective BE regression with MSA. MSA offers several advantages in BE including effective reflux control, anti-reflux barrier restoration and reduced hiatal hernia recurrence. However, careful patient selection for MSA is necessary.


Identification and predicted sequence of a previously unrecognized small hydrophobic protein, SH, of the paramyxovirus simian virus 5.
A previously unrecognized gene (SH) has been identified on the virion RNA of the paramyxovirus simian virus 5 between the genes for the fusion protein and the hemagglutinin-neuraminidase. An SH mRNA of 292 nucleotides (plus polyadenylate residues), transcribed from the SH gene, has been identified. The SH mRNA contains a single open reading frame which encodes a polypeptide of 44 amino acids with a molecular weight of 5,012. The SH polypeptide is predicted to contain an extensive hydrophobic region. This protein has been identified in simian virus 5-infected cells, and it has been shown to be encoded by the SH mRNA by in vitro translation of size-fractionated mRNAs, hybrid-arrest translation, and hybrid-selection translation.


Correlation of histopathologic and bacteriologic changes with cytokine expression in an experimental murine model of bacteremic Staphylococcus aureus infection.
Staphylococcus aureus infections are often life threatening. Relatively little is known about the host response to these infections, in particular, the role played by cytokines. We established a mouse model of bacteremic S. aureus infection to correlate bacteriologic findings and pathologic changes with cytokine gene expression. Bacterial density in blood and tissue was highest at 1 h and minimal by 48 h. Despite the rapid clearance of bacteria, pathologic abnormalities and inflammatory cytokines were detected after clearance of the bacteria. The number of infiltrating inflammatory cells, as well as the size of inflammatory foci, increased with time. Interstitial accumulation of inflammatory cells and tissue damage, such as microabscesses, edema, and necrosis progressed following clearance of bacteria from the tissues. Levels of tumor necrosis factor and interleukin-1 protein in serum were detectable at 1 h and peaked at 4 h. Interleukin-6 protein expression showed different kinetics, with low levels detected at 1 h and increasing levels at 72 h postinfection. Tumor necrosis factor and the interleukins were expressed in inflammatory and noninflammatory cells in lung, liver, and heart tissues. Leukocytes in the infected tissues were highly reactive with antibodies to the three cytokines, suggesting that activated leukocytes are a major source of inflammatory cytokines after staphylococcal infection. Expression of interleukin-1 and interleukin-6 in tissue-specific cells and endothelial cells was also detected in infected tissues, indicating that cells other than leukocytes contribute to the elevated cytokine levels in this model. Once initiated, expression of inflammatory cytokines contributes to the pathogenesis of S. aureus disease.


[Is histopathology still the gold standard?]
In the diagnostic process, microscopical analysis is considered to be the gold standard in determining the presence and nature of a disease. In some cases, in particular in rare diseases and in precursor lesions in which pathological changes have not yet fully developed, histological assessment is subject to diagnostic uncertainty. This uncertainty may be further compounded by the increasing tendency to submit small biopsies which may only harbour part of a pathological process. Several strategies may be adopted to increase the precision of histological analysis. While it is reasonable to assume that these strategies will lead to improved performance, systematic research to confirm this assumption is lacking. It is important to be aware of the limitations of histopathological testing.


Constriction of endoplasmic reticulum tubules by the viral movement protein BMB2 is associated with local BMB2 anchorage at constriction sites.
Plant virus-encoded movement proteins (MPs) interact with endoplasmic reticulum (ER) membranes, the cytoskeleton, and plasmodesmata (PD) to mediate intracellular delivery of the virus genome to PD and its further transport through PD from infected to healthy cells. The Hibiscus green spot virus MP termed BMB2 has been shown to induce constrictions of ER tubules and to occur at highly curved membranes, thus showing properties similar to those of reticulons, a class of cellular proteins inducing membrane curvature and shaping the ER tubules. Consistent with this BMB2 function, mRFP-BMB2 localizes to discrete, constricted regions scattered along the ER tubules. Here, using BMB2-mRFP fusion protein as a BMB2 derivative with partially disabled functionality, we demonstrate that the focal localization of BMB2 to discrete sites along the ER tubules is insufficient to induce local tubule constrictions at these sites, suggesting that the formation of ER tubule constrictions represents a specific BMB2 function and is not simply a mechanistic consequence of its localization to the ER. The presented data suggest that the formation of ER-residing BMB2-containing distinct small aggregates, or protein platforms, can be uncoupled from BMB2-induced ER tubule constrictions, whereas the anchoring of platforms at particular ER sites appears to be linked to the constriction of ER tubules at these sites.


Water oxidation electrocatalysis using ruthenium coordination oligomers adsorbed on multiwalled carbon nanotubes.
Photoelectrochemical cells that utilize water as a source of electrons are one of the most attractive solutions for the replacement of fossil fuels by clean and sustainable solar fuels. To achieve this, heterogeneous water oxidation catalysis needs to be mastered and properly understood. The search continues for a catalyst that is stable at the surface of electro(photo)anodes and can efficiently perform this reaction at the desired neutral pH. Here, we show how oligomeric Ru complexes can be anchored on the surfaces of graphitic materials through CH-π interactions between the auxiliary ligands bonded to Ru and the hexagonal rings of the graphitic surfaces, providing control of their molecular coverage. These hybrid molecular materials behave as molecular electroanodes that catalyse water oxidation to dioxygen at pH 7 with high current densities. This strategy for the anchoring of molecular catalysts on graphitic surfaces can potentially be extended to other transition metals and other catalytic reactions.


Genome-wide association studies in lung disease.
Genome-wide association studies (GWAS) have provided new insights into the molecular mechanisms of lung function and lung diseases. GWAS, and studies that build upon their findings, will continue to provide evidence aimed at advancing understanding of lung disease. This paper summarises the key features of a GWAS, references some recent findings and discusses how the chest physician can interpret the validity and utility of future GWAS and related studies.


Communication and decision making about life-sustaining treatment: examining the experiences of resident physicians and seriously-ill hospitalized patients.
Despite evidence-based recommendations for communication and decision making about life-sustaining treatment, resident physicians' actual practice may vary. Few prior studies have examined these conversations qualitatively to uncover why ineffective communication styles may persist. To explore how discussions about life-sustaining treatment occur and examine the factors that influence physicians' communicative practices in hopes of providing novel insight into how these processes can be improved. PARTICIPANTS AND APPROACH: We conducted and recorded 56 qualitative semi-structured interviews with participants from 28 matched dyads of a resident physician and a hospitalized patient or their surrogate decision maker with whom cardiopulmonary resuscitation was discussed. Transcripts were analyzed and coded using the constant comparative method to develop themes. Resident physicians introduced decisions about resuscitation in a scripted, depersonalized and procedure-focused manner. Decision makers exhibited a poor understanding of the decision they were being asked to make and resident physicians often disagreed with the decision. Residents did not advocate for a particular course of action; however, the discussions of resuscitation were framed in ways that may have implicitly influenced decision making. Residents' communication practices may stem from their attempt to balance an informed choice model of decision making with their interest in providing appropriate care for the patient. Physicians' beliefs about mandatory autonomy may be an impediment to improving communication about patients' choices for life-sustaining treatment. Redefining the role of the physician will be necessary if a shared decision making model is to be adopted.


How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial.
The initial studies on nitrosoureas were performed >30 years ago. These drugs remain the standard chemotherapy for glioblastoma. However, because the criteria used to evaluate the activity of nitrosoureas in a neuro-oncologic setting have changed, new data on their activity are needed. The authors conducted a phase II study on 40 patients with recurrent glioblastoma following surgery and standard radiotherapy. They analyzed progression-free survival at 6 months (PFS-6), time to progression (TTP), response rate, and toxicity. Patients were treated with 80 mg/m2 carmustine on days 1 to 3, every 8 weeks for a maximum of six cycles. Median TTP was 13.3 weeks (95% CI, 10.26 to 16.86 weeks), and PFS-6 was 17.5% (95% CI, 8.9 to 34.3). Response to chemotherapy, age < or =40 years, and performance status > or =90 were significant prognostic factors for TTP; however, with multivariate analysis, only response to chemotherapy was significant. The major side effects were reversible hematologic and long-lasting hepatic and pulmonary toxicity. The activity of this BCNU regimen is comparable with that reported in the past and with the newest therapies, such as temozolomide. However, BCNU toxicity is high and recovery is slow, thus compromising the administration of further drugs in patients with progressive disease.


Aggregation-induced near-infrared emitting platinum(ii) terpyridyl complex: cellular characterisation and lysosome-specific localisation.
A novel near-infrared luminogen (TPE/TPY-Pt-PA/PEG) based on the terpyridyl Pt(ii) complex with a tetraphenylethene periphery is synthesised and characterised. It displays aggregation-induced emission with the formation of self-assembled nanostructures. The nanoparticles fabricated with TPE/TPY-Pt-PA/PEG show excellent biocompatibility with high specificity to lysosomes in HeLa cells.


Plant species richness belowground: higher richness and new patterns revealed by next-generation sequencing.
Variation in plant species richness has been described using only aboveground vegetation. The species richness of roots and rhizomes has never been compared with aboveground richness in natural plant communities. We made direct comparisons of grassland plant richness in identical volumes (0.1 × 0.1 × 0.1 m) above and below the soil surface, using conventional species identification to measure aboveground richness and 454 sequencing of the chloroplast trnL(UAA) intron to measure belowground richness. We described above- and belowground richness at multiple spatial scales (from a neighbourhood scale of centimetres to a community scale of hundreds of metres), and related variation in richness to soil fertility. Tests using reference material indicated that 454 sequencing captured patterns of species composition and abundance with acceptable accuracy. At neighbourhood scales, belowground richness was up to two times greater than aboveground richness. The relationship between above- and belowground richness was significantly different from linear: beyond a certain level of belowground richness, aboveground richness did not increase further. Belowground richness also exceeded that of aboveground at the community scale, indicating that some species are temporarily dormant and absent aboveground. Similar to other grassland studies, aboveground richness declined with increasing soil fertility; in contrast, the number of species found only belowground increased significantly with fertility. These results indicate that conventional aboveground studies of plant richness may overlook many coexisting species, and that belowground richness becomes relatively more important in conditions where aboveground richness decreases. Measuring plant belowground richness can considerably alter perceptions of biodiversity and its responses to natural and anthropogenic factors.


Protein kinase-A phosphorylates titin in human heart muscle and reduces myofibrillar passive tension.
Protein kinase-A (PKA) is activated during beta-adrenergic stimulation of the heart and is known to phosphorylate several sarcomeric proteins including the giant polypeptide titin. A PKA phosphorylation site on titin is located within the N2B-unique sequence, which is present in the elastic segment of the two major isoforms of cardiac titin, N2B and N2BA, but not in the skeletal-muscle isoforms of the N2A-type. In bovine and rat cardiomyocytes, PKA-mediated phosphorylation decreases passive tension (PT), an effect ascribed to titin phosphorylation. Whether titin is phosphorylated by PKA upon beta-adrenergic stimulation in human heart has not been shown to date. Here we report that PKA induces phosphorylation of N2B and N2BA titin isoforms, as well as a characteristic proteolytic fragment of titin, T2, in human donor hearts. The PKA-induced phosphorylation signals were stronger when myofilaments were first de-phosphorylated by protein phosphatase-1, suggesting inherent phosphorylation of titin in human heart. Titin phosphorylation was associated with a reduction in PT of skinned human cardiac strips; the relative decrease was higher at shorter than at longer physiological sarcomere lengths. The PKA-dependent PT drop was substantially larger when fibers were pre-treated with protein phosphatase-1, indicating that inherent phosphorylation of titin is important for the basal myocardial PT level. Mechanical measurements on isolated myofibrils from rat heart confirmed the PKA effect on passive stiffness and also showed a more pronounced effect in the presence of reducing agent, DTT. In contrast, PKA did not alter the PT of single skinned rat diaphragm muscle fibers; however, the kinase was still able to phosphorylate the skeletal N2A-titin isoform, which lacks the N2B-unique sequence. Thus, an additional phosphorylation site in titin may exist outside the cardiac N2B-unique sequence. We conclude that PKA mediates phosphorylation of titin in normal human myocardium. Titin phosphorylation lowers titin-based passive stiffness in heart but not in skeletal muscle.


Cholesterol interactions with fluid-phase phospholipids: effect on the lateral organization of the bilayer.
The lateral organization of lipids and proteins in cell membranes is recognized as an important factor in several cellular processes. Cholesterol is thought to function as a modulator of the lateral segregation of lipids into cholesterol-poor and cholesterol-rich domains. We investigated how the affinity of cholesterol for different phospholipids, as seen in cholesterol partitioning between methyl-beta-cyclodextrin and large unilamellar vesicles, was reflected in the lateral organization of lipids in complex bilayers. We especially wanted to determine how the low-T(m) lipid affected the lateral structure. Partition experiments showed that cholesterol had a higher affinity for N-oleoyl-sphingomyelin (OSM) than for palmitoyl-oleoyl-phosphatidylcholine (POPC) bilayers, but the highest preference was for N-palmitoyl-sphingomyelin (PSM)-containing bilayers. Partial phase diagrams of POPC/PSM/cholesterol and OSM/PSM/cholesterol bilayers at 23 degrees C and 37 degrees C were used to gain insight into the lateral organization of lipids in bilayers. Analysis of phase diagrams revealed that the phospholipid composition of cholesterol-poor and cholesterol-rich domains reflected the affinity that cholesterol exhibited toward bilayers composed of different lipids. Therefore, the determined affinity of cholesterol for different phospholipid bilayers was useful in predicting the cholesterol-induced lateral segregation of lipids in complex bilayers.


Lithium increases serotonin release and decreases serotonin receptors in the hippocampus.
The effects of long-term lithium administration on pre- and postsynaptic processes involved in serotonergic neurotransmission were measured in rat hippocampus and cerebral cortex. Long-term lithium administration increased both basal and potassium chloride-stimulated release of endogenous serotonin from the hippocampus but not from the cortex. Serotonergic receptor binding was reduced in the hippocampus but not in the cortex. These results suggest a mechanism by which lithium may stabilize serotonin neurotransmission.


Least-squares dynamic approximation method for evolution of uncertainty in initial conditions of dynamical systems.
We describe an approximation method to solve the probability density function transport equation, i.e., the Liouville equation, which is encountered in the evolution of uncertainty of the initial values of dynamical systems. A state-space based method is formulated using a least-squares technique that preserves the parabolic nature of the Liouville equation and is flexible in terms of accuracy of representation. This method is based on a global approximation in terms of analytical elementary functions with unknown parameters, whose evolution equations are determined by a global least-squares approximation. The realizability conditions of the probability density, i.e., the non-negativity and normalization conditions are enforced at all times. The method is successfully evaluated in a number of scenarios including the uncertainty evolution in a system governed by a Riccati equation and a particle moving in a fluid under the influence of Stokes drag force. The results obtained in our examples exhibit a reasonable good agreement when compared with the solution of the probability transport equation using the method of characteristics. The cost of the method is proportional to the cost of solving the deterministic system and the number of parameters used to approximate the probability density function, a feature that can make the present method very advantageous in comparison with other methods in problems involving a large number of dimensions.


N-Acyl Dibenzazepine Chemistry as Versatile Approach for Photoreversible Thiol-Ene Networks.
It is herein reported that a facile application of N-acyl dibenzazepine (ADBA) photochemistry for preparing photoreversible ADBA based thiol-ene networks. Crosslinking of the ADBA thiol-ene networks is successfully achieved by UV induced dimerization of ADBA groups at wavelengths above 300 nm while a subsequent deep UV exposure (λ = 250 nm) results in a well-defined cleavage of the crosslinks. The photochemical bonding and cleavage of the process has been determined and studied in detail by spectroscopic measurements.


Knowledge, attitudes and practices (KAP) towards rabies and free roaming dogs (FRD) in Panchkula district of north India: A cross-sectional study of urban residents.
Canine rabies is endemic in urban India. A questionnaire was administered to 204 residents of the urbanised municipality of Panchkula in north India to assess the influence of gender, age, family size, social status and dog ownership, over the knowledge, attitudes and practices (KAP) towards rabies control and free-roaming dogs (FRD) in their locality. Bivariate analyses revealed significant knowledge gaps regarding crucial information on the control and transmission of rabies. Multivariable logistic regression models found that the respondents with a high/middle socio-economic status were likely to be more knowledgeable than those from low socio-economic levels (OR 3.03, 95%CI 1.5-6.0, p = 0.001). Households with children ≤14 years of age were likely to be lacking in knowledge about rabies compared to households with older or no children (OR 0.5, 95%CI 0.3-0.9, p = 0.04). The attitudes and practices of the respondents towards rabies control was positive in households with a high/middle socio-economic status (OR 3.4, 95%CI 1.7-7.2, p = 0.0008) but poor in older (≥ 35 years) participants (OR 0.4, 95%CI 0.2-0.7, p = 0.001). It is concluded that rabies awareness campaigns should be developed and conducted to target sectors of the urban community such as those belonging to lower socio-economic sections and schools to improve the residents' knowledge and practices towards rabies. Educating dog owners about sterilising their pets is also recommended to alter the attitudes of the residents towards FRD population control.


Current concepts in primary hyperparathyroidism.
622 patients were operated on between 1966 and 1988. Urolithiasis was the most common presenting symptom (26%) but routine measurements of serum calcium led to detect 50% cases. At present, the disease is three times more frequent in women than in men. Estrogenic deprivation, neck irradiation (3.4%) and lithium therapy favor the occurrence of hyperparathyroidism (HPT); frequent association with goiter (19.8%), diabetes (8.3%) and multiple endocrine neoplasia (3.5%) has been noticed. Bone Gla protein concentrations correlate with calcium and HPT blood concentrations but do not reflect the severity of bone damage. Dual photon absorptiometry is now available for quantification and follow-up of bone demineralization, especially in asymptomatic forms of HPT.


Predictors of a favorable response to transforaminal injection of steroids in patients with lumbar radicular pain due to disc herniation.
Transforaminal injection of steroids (TFIS) is effective for some patients with lumbar radicular pain caused by disc herniation. Factors associated with better outcomes are unknown. To identify clinical and radiological features predictive of a favorable response to TFIS. Seventy-one patients with lumbar radicular pain caused by disc herniation were treated with TFIS as part of a previously reported, randomized, clinical trial. The clinical features analyzed were the presence of neurologic symptom, neurologic signs, and the duration of sciatica. Radiological features evaluated using magnetic resonance imaging (MRI) were the segmental level of the pathology, the location and morphological features of the disc herniation, the cross-sectional area of the disc herniation and its ratio to the cross-sectional area of the spinal canal, and the grade of nerve root compression. None of the clinical features was associated with successful outcome from treatment. The only radiological feature associated with successful outcome was the grade of nerve root compression. Of patients with low-grade root compression, 75% responded favorably to TFIS. Only 26% of patients with high-grade nerve root compression responded. These results indicate that TFIS is more often successful in patients without significant compression of the nerve root and, therefore, in whom an inflammatory basis for radicular pain is most likely. In such patients, a success rate of 75% renders TFIS an attractive alternative to surgery. In patients with significant compression of the nerve root, the likelihood of benefiting from TFIS is low. The success rate may be no more than that of a placebo effect, and surgery may be a more appropriate consideration.


aPIE: an angle calibration algorithm for reflection ptychography.
Reflection ptychography is a lensfree microscopy technique particularly promising in regions of the electromagnetic spectrum where imaging optics are inefficient or not available. This is the case in tabletop extreme ultraviolet microscopy and grazing incidence small angle x ray scattering experiments. Combining such experimental configurations with ptychography requires accurate knowledge of the relative tilt between the sample and the detector in non-coplanar scattering geometries. Here, we describe an algorithm for tilt estimation in reflection ptychography. The method is verified experimentally, enabling sample tilt determination within a fraction of a degree. Furthermore, the angle-estimation uncertainty and reconstruction quality are studied for both smooth and highly structured beams.


Recognition of the Possible miRNA-mRNA Controlling Network in Stroke by Bioinformatics Examination.
Based on the latest research of WHO, it has been revealed that more than 15 million people suffer from stroke every year worldwide. Of these 15 million people, 6 million succumb to death, and 5 million get permanently disabled. This is the prime reason for the substantial economic burden on all parts of the world. These data have been obtained from the GEO database, and the GEO2R tool was used to find out the differentially expressed miRNAs (DEMs) between the stroke and normal patients' blood. FunRich and miRNet were considered to find potential upstream transcription factors and downstream target genes of candidate EMRs. Next, we use GO annotation and KEGG pathway enrichment. Target genes were analyzed with the help of the R software. Then, the STRING database and Cytoscape software were used to conduct PPI and DEM-hub gene networks. Finally, GSE58294 was used to estimate the hub gene expressions. Six DEMs in total were selected out from GSE95204 and GSE117064 datasets. 663 DEMs' target genes were predicted, and NRF1, EGR1, MYC, YY1, E2F1, SP4, and SP1 were predicted as an upstream transcription factor for DEMs' target genes. Target genes of DEMs were primarily augmented in the PI3K-Akt signaling pathway and p53 signaling pathway. The network construction of DEM hygiene is potentially modulated by hsa-miR-3591-5p, hsa-miR-548as-3p, hsa-miR-206, and hsa-miR-4503 hub genes which were found among the top 10 of the hub genes. Among the top 10 hub genes, justification of CTNNB1, PTEN, ESR1, CCND1, KRAS, AKT1, CCND2, CDKN1B, and MYCN was constant with that in the GSE58294 dataset. In summary, our research first constructs the miRNA-mRNA network in stroke, which probably renders an awakening purview into the pathogenesis and cure of stroke.


Prevalence of antibodies against SARS-CoV-2 among pregnant women in Norway during the period December 2019 through December 2020.
We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence among pregnant women in Norway by including all women who were first trimester pregnant (n = 6520), each month from December 2019 through December 2020, in the catchment region of Norway's second-largest hospital. We used sera that had been frozen stored after compulsory testing for syphilis antibodies in antenatal care. The sera were analysed with the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Cobas e801). This immunoassay detects IgG/IgM against SARS-CoV-2 nucleocapsid antigen. Sera with equivocal or positive test results were retested with the Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorin), which detects IgG against the spike (S)1 and S2 protein on the SARS-CoV-2 virus. In total, 98 women (adjusted prevalence 1.7%) had SARS CoV-2 antibodies. The adjusted seroprevalence increased from 0.3% (1/445) in December 2019 to 5.7% (21/418) in December 2020. Out of the 98 seropositive women, 36 (36.7%) had serological signs of current SARS-CoV-2 infection at the time of serum sampling, and the incidence remained low during the study period. This study suggests that SARS CoV-2 was present in the first half of December 2019, 6 weeks before the first case was recognised in Norway. The low occurrence of SARS-CoV-2 infection during 2020, may be explained by high compliance to extensive preventive measures implemented early in the epidemic.


In situ AFM visualization of Li-O2 battery discharge products during redox cycling in an atmospherically controlled sample cell.
The in situ observation of electrochemical reactions is challenging due to a constantly changing electrode surface under highly sensitive conditions. This study reports the development of an in situ atomic force microscopy (AFM) technique for electrochemical systems, including the design, fabrication, and successful performance of a sealed AFM cell operating in a controlled atmosphere. Documentation of reversible physical processes on the cathode surface was performed on the example of a highly reactive lithium-oxygen battery system at different water concentrations in the solvent. The AFM data collected during the discharge-recharge cycles correlated well with the simultaneously recorded electrochemical data. We were able to capture the formation of discharge products from correlated electrical and topographical channels and measure the impact of the presence of water. The cell design permitted acquisition of electrochemical impedance spectroscopy, contributing information about electrical double layers under the system's controlled environment. This characterization method can be applied to a wide range of reactive surfaces undergoing transformations under carefully controlled conditions.


F0 timing in Kinyarwanda.
In Kinyarwanda (Bantu, Rwanda), a high tone can occur on either the first or the second mora of a syllable. A study of f0 timing in the language was undertaken to determine how such a contrast is realized phonetically, and how this realization is affected by phrase position, word position, and distance from a following high tone. The study also aimed to explore a reported effect of 'tone anticipation' (raising of pitch in a syllable before a high tone) in the language. The study found significant effects of the position of a tone within the syllable, its position within the phrase, and its position with respect to following high tones. Models of f0 timing in Kinyarwanda are proposed, demonstrating the role of moras in phonetic implementation of tone. These models clarify issues regarding the phonological representation of tones in Kinyarwanda, and the division between phonetic patterns and phonological ones.