Detection and characteristics of retrograde P waves.
Clinical evaluation performed on an external prototype of a programmable VDD pacemaker showed a high risk of induction of pacemaker-mediated tachycardia. In these tests tachycardia was observed following magnet removal, premature atrial and ventricular complexes, myopotential oversensing, detection of electrical interference and other events. The high risk and poor predictability of pacemaker-mediated tachycardia suggest that VDD (or DDD) pacemakers should provide automatic means to control this kind of tachycardia without undue loss of the hemodynamic benefits which can be provided by these units.


A strategic approach to social accountability: Bwalo forums within the reproductive maternal and child health accountability ecosystem in Malawi.
The majority of documented social accountability initiatives to date have been 'tactical' in nature, employing single-tool, mostly community-based approaches. This article provides lessons from a 'strategic', multi-tool, multi-level social accountability project: UNICEF's 'Social Accountability for Every Woman Every Child' intervention in Malawi. The project targeted the national, district and community levels. Three Civil Society Organisations (CSOs) were engaged to carry out interventions using various tools to generate evidence and political advocacy at one or more levels. This article focuses on one of the social accountability methods - the bwalo forum (a meeting based on a traditional Malawian method of dialogue). A detailed political economy analysis was conducted by one of the co-authors using qualitative methods including interviews and group discussions. The authors conducted in-country consultations and analysed secondary data provided by the CSOs. The political economy analysis highlighted several ways in which CSO partners should modify their work plans to be more compatible with the project context. This included shifting the advocacy and support focus, as well as significantly expanding the bwalo forums. Bwalos were found to be an important platform for allowing citizens to engage with duty bearers at the community and district levels, and enabled a number of reproductive, maternal, newborn, child and adolescent health issues to be resolved at those levels. The project also enabled learning around participant responses as intermediate project outcomes. The project utilised various tools to gather data, elevate community voices, and facilitate engagement between citizen and state actors at the community, district and national levels. This provided the scaffolding for numerous issues to be resolved at the community or district levels, or referred to the national level. Bwalo forums were found to be highly effective as a space for inter-level engagement between citizens and state; however, as they were not embedded in existing local structures, their potential for sustainability and scalability was tenuous. A key strength of the project was the political economy analysis, which provided direction for partners to shape their interventions according to local and national realities and be sensitive to the barriers and drivers to positive action.


Non-linear finite element stress analysis of plastic deformation in Co-Cr wrought-wire clasps.
The purpose was to assess the influence of plastic deformation by bending on stress, flexibility and permanent deformation in wrought-wire clasps. A three-dimensional finite element model of a straight wire (120 mm in length and 1.0mm in diameter) was created. The non-linear stress-strain relationship of a commercial Co-Cr alloy straight wrought-wire, measured by means of tensile test (n = 5) was put into the program. Bending to an angle of 90 degrees or 120 degrees and subsequent unloading processes with spring back phenomenon, were simulated in the clasp shoulder and arm. The stress distributions were analyzed at loading and unloading. Thereafter, the clasp models were deflected outwardly 0.25, 0.50, and 0.75 mm at the clasp tip, to simulate the removal and insertion of a denture. Under the bending force, the maximum tensile stress was recorded at the outside surface of the bending corner; while after unloading, the maximum tensile stress appeared at the inside of the bending angle. By deflection of the clasp tip, this stress increased up to 203% of that before deflection. The change of stress by deflection was larger at the shoulder than at the arm. The load required for deflection was approximately 43% larger in the models with the arm angle of 120 degrees than those with an angle of 90 degrees . The results suggest that the permanent deformation of wrought-wire clasps is likely to initiate at the clasp shoulder, while clasp flexibility is dependent on the bending angle of the clasp arm.


Development of high efficiency silica coated β-cyclodextrin polymeric adsorbent for the removal of emerging contaminants of concern from water.
This article reports the removal of several emerging contaminants (ECs) from water using novel adsorbent comprising of β-cyclodextrin (β-CD) coated on silica. Fourteen different adsorbents were synthesized under different experimental conditions using two different crosslinking agents (hexamethylene diisocyanate (HMDI) and epichlorohydrin (EPI)) and co-polymers (glycidoxypropyl trimethoxysilane (GPTS) and aminopropyl triethoxysilane (APTES). The adsorption capacities of the synthesized adsorbents were initially evaluated using 17β-estradiol, perfluorooctanoic acid (PFOA), and bisphenol-A (BPA) as adsorbates. The adsorbent prepared by using HMDI as crosslinking agent with DMSO as solvent was observed to perform the best, and removed more than 90% of 17β-estradiol, PFOA, and BPA. Furthermore, the β-CD loading on the ECs removal was studied which showed that the adsorbate removal increases with increase in loading of β-CD on the substrate. The best adsorbent was resynthesized in seven batches and its performance was reproducible for the removal of ten steroid hormones. The adsorbent showed very good regeneration potential for four successive adsorption-regeneration cycles to remove steroid hormones and PFOA. A plausible mechanism of adsorption is proposed. The synthesized best adsorbent is characterized using FTIR, HR-TEM, TGA and nitrogen adsorption analysis. The TGA results showed that the adsorbent has thermal stability of upto 300°C.


Effect of hypothermia on intestinal adaptation and carcinogenesis in the rat.
Postoperative hyperplasia enhances experimental intestinal carcinogenesis, but the effects of nonsurgical adaptation are uncertain. The tropic and tumour-promoting potentials of moderate hypothermia were tested in two groups of male Sprague-Dawley rats housed at 10 degrees C for 30 weeks. One group (n = 10) received a 6-week course of azoxymethane (total dose 90 mg kg-1). The second group (n = 7) acted as hypothermic controls. Another 2 groups maintained at 22 degrees C received azoxymethane (n = 15) or served as normothermic controls (n = 15). Overall food intake was 42% higher in the hypothermic groups, yet at sacrifice mean body weight was 13% lower (P less than 0.01). Hypothermia and azoxymethane combined to produce the following increases in crypt cell production rate (CCPR), as determined stathmokinetically: duodenum 170%, jejunum 172%, ileum 74%, proximal colon 227% (P = 0.05-0.01). Independently hypothermia had no effect, but azoxymethane produced 76-156% increases in CCPR throughout the large intestine. Although hypothermia did not affect overall tumour yield, the mean diameter of proximal colonic tumours was increased by 65% (P less than 0.05). In rats receiving azoxymethane, hypothermia stimulates cell proliferation in the small bowel as well as in the proximal colon, where it has a correspondingly mild cocarcinogenic effect.


Green Easily Implemented Spectrophotometric Methods for Concurrent Determination of Ephedrine Hydrochloride and Naphazoline Nitrate in Nasal Preparations Containing Methylparaben.
Spectrophotometric resolution of a mixture of several drugs is considered a cheaper, simpler, and more versatile alternative compared to costly chromatographic instruments. The work aims to resolve the interfering spectra of ephedrine hydrochloride, naphazoline nitrate, and methylparaben in nasal preparations using smart spectrophotometric methods. In our work, derivative and dual-wavelength methods were combined to eliminate this interference, under the name of derivative dual-wavelength method. Other methods, namely successive derivative subtraction and chemometric analysis, were also able to eliminate this interference. The methods have proven their applicability as they follow the International Conference on Harmonization (ICH) requirements regarding repeatability, precision, accuracy, selectivity, and linearity. Eco-scale, GAPI, and AGREE tools were used to estimate the possible environmental effects of the methods. Acceptable results for repeatability, precision, accuracy, selectivity, and linearity were obtained. Limit of detection (LOD) values were 2.2 for ephedrine and 0.3 for naphazoline. The correlation coefficients were above 0.999. The methods were proven to be safe for application. The introduced methods are cheap and easily implemented compared to chromatographic techniques. They can be used in purity-checking of raw material and estimation of concentrations in market formulations. The replacement of the published chromatographic techniques with our developed methods is useful when needing to save money, effort, and time. The three components of a decongestant nasal preparation were determined using cheap, green, and versatile spectrophotometric methods that keep the advantages of chromatographic techniques, including accuracy, reproducibility, and selectivity.


Effects of ATP on calcium binding to synaptic plasma membrane.
The release of labeled norepinephrine from preloaded synaptosomes requires the presence of potassium and calcium. ATP-dependent binding of calcium to synaptic plasma membranes (SPM) may provide a means of maintaining the cation in a readily available pool for the triggering of transmitter release. A high Ca-binding capacity was demonstrated in SPM. The Km for calcium is 5.5 X 10(-5) M. The dependence of the system on the gamma phosphate of ATP was demonstrated by an increase in Ca-binding with increasing ATP concentration and by competitive inhibition of binding by ADP and AMP. Magnesium is also required for ATP-dependent Ca-binding. The optimum pH for the Ca binding was 7.0. Pretreatment of SPM with phospholipase A2 lowered the binding capacity. Sulfhydryl groups are also critical for ATP-dependent Ca binding to occur. A model for ATP-dependent Ca-binding was proposed.


Asynchronous locking in metamaterials of fluids of light and sound.
Lattices of exciton-polariton condensates represent an attractive platform for the study and implementation of non-Hermitian bosonic quantum systems with strong non-linear interactions. The possibility to actuate on them with a time dependent drive could provide for example the means to induce resonant inter-level transitions, or to perform Floquet engineering or Landau-Zener-Stückelberg state preparation. Here, we introduce polaromechanical metamaterials, two-dimensional arrays of μm-sized traps confining zero-dimensional light-matter polariton fluids and GHz phonons. A strong exciton-mediated polariton-phonon interaction induces a time-dependent inter-site polariton coupling J(t) with remarkable consequences for the dynamics. When locally perturbed by continuous wave optical excitation, a mechanical self-oscillation sets-in and polaritons respond by locking the energy detuning between neighbor sites at integer multiples of the phonon energy, evidencing asynchronous locking involving the polariton and phonon fields. These results open the path for the coherent control of dissipative quantum light fluids with hypersound in a scalable platform.


Association of tumor necrosis factor-α gene promoter polymorphisms (-308G/A, -238G/A) with recurrent spontaneous abortion: a meta-analysis.
Tumor necrosis factor-α (TNF-α) gene promoter polymorphisms (-308G/A, -238G/A) have been associated with increased recurrent spontaneous abortion (RSA) risk, but the results of published articles are controversial. Hence, a meta-analysis was performed to assess the effect of TNF-α -308G/A, -238G/A polymorphisms on RSA risk. Heterogeneity testing and sensitivity analysis were performed using RevMan 5.0 software. Publication bias was assessed by the funnel plot method and modified Egger's linear regression test. In 12 studies for the TNF-α -308G/A polymorphism, the summary odds ratio (OR) with the corresponding 95% confidence interval (95% CI) was 1.04 (95% CI: 0.86, 1.26) under a fixed-effect model in the overall population. In 5 studies for the TNF-α -238G/A polymorphism, the summary OR with the corresponding 95% CI was 1.11 (95% CI: 0.60, 2.03) under a random-effect model in the overall population. We could not identify the sources of heterogeneity for TNF-α -238G/A. In addition, no evidence of publication bias was detected. The results of this meta-analysis indicate that TNF-α -308G/A, -238G/A polymorphisms are not significantly associated with the risk of RSA in the overall population. However, more convincing evidence is required to draw a solid conclusion on the relation between the TNF-α -238G/A polymorphism and the risk of RSA.


Vibrant Soundbridge implantation via a retrofacial approach in a patient with congenital aural atresia.
A method of Vibrant Soundbridge (VSB) placement to the round window (RW) via the retrofacial approach with preoperative evaluation of the relationship between the facial nerve (FN) and RW by 3D-CT reconstruction was proposed for the treatment of congenital aural atresia (CAA) patient. A fenestration to the mesotympanum was made mastoid portion of the FN. During the approach, part of the stapedial muscle was encountered and removed. The RW niche was identified, and the floating mass transducer was placed from an inferior approach into the RW niche. There were no intra-operative or post-operative surgical complications. The VSB placement to the RW via the retrofacial approach with partial removal of the stapedial muscle can be feasible alternative in CAA cases associated with an anteriorly and laterally positioned aberrant FN. Preoperative assessment using 3D CT may facilitate in assessing the feasibility of the approach and implantation of VSB.


Clinical and angiographic results of stenting for long coronary arterial atherosclerotic lesions.
A prospective registry of 187 patients who underwent percutaneous coronary angioplasty with attempted long NIR stent delivery was performed. A successful stent delivery was achieved in 93% of cases with a low rate of major cardiovascular events, and 6-month follow-up showed low rates of clinical events, new revascularization procedures, and angiographic restenosis.


Free boundary methods and non-scattering phenomena.
We study a question arising in inverse scattering theory: given a penetrable obstacle, does there exist an incident wave that does not scatter? We show that every penetrable obstacle with real-analytic boundary admits such an incident wave. At zero frequency, we use quadrature domains to show that there are also obstacles with inward cusps having this property. In the converse direction, under a nonvanishing condition for the incident wave, we show that there is a dichotomy for boundary points of any penetrable obstacle having this property: either the boundary is regular, or the complement of the obstacle has to be very thin near the point. These facts are proved by invoking results from the theory of free boundary problems.


Improved method for the simultaneous determination of proguanil and its metabolites by high-performance liquid chromatography and solid-phase extraction of 100-microl capillary blood samples dried on sampling paper.
An improved method is presented for the determination of proguanil, cycloguanil and 4-chlorophenylbiguanide in 100-microl capillary blood samples applied to sampling paper. This method also utilises a solid-phase extraction technique and high-performance liquid chromatography. Different kinds of sampling paper, such as ion-exchange and cellulose sampling paper were tested. The best elution recovery (70-80%) was obtained after treatment of cellulose sampling paper with a quaternary ammonium compound. The limit of determination was 50 nmol/l for cycloguanil and 4-chlorophenylbiguanide and 125 nmol/l for proguanil using 100 microl capillary blood. The stability of the analytes and elution performance from sampling paper was validated at different temperature and storage time. Venous blood and capillary blood concentrations of proguanil and metabolites were found to be similar.


Ultrasound of wrist and hand masses.
Ultrasound is a useful tool to investigate soft tissue masses in the wrist and hand. In most situations ultrasound helps distinguish between a cyst and a tissue mass. This article provides a simple clinical approach to the use of ultrasound imaging for the diagnosis and preoperative assessment of wrist and hand masses.


[Clinical and genetic characteristics of 12 cases of Loeys-Dietz syndrome].
To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.


Erectile dysfunction and Peyronie's disease diagnosis rates after penile fracture-a retrospective claims database cohort analysis.
Our objective was to analyze the rates of erectile dysfunction and Peyronie's disease following a penile fracture using a large, multi-institutional claims database. Inclusion criteria included men ages 15 or older with a diagnosis of penile fracture and any office visit within 5 years of the penile fracture. Exclusion criteria included prior erectile dysfunction, prescription of erectile aids, or penile prosthesis placement. Our primary outcome was the diagnosis of erectile dysfunction or prescription of phosphodiesterase-5 inhibitors within 5 years. A secondary analysis assessed rates of Peyronie's disease following penile fracture. 1242 men were identified with penile fracture and subsequently matched to men without penile fracture, resulting in equal cohorts of 1227 men. Men with a history of penile fracture were more likely to receive a diagnosis of erectile dysfunction or require phosphodiesterase-5 inhibitors (RR 3.18, 95% CI: 2.30-4.40). Men who did not undergo immediate repair had higher rates of erectile dysfunction or treatment (RR: 1.84, 95% CI: 1.22-2.78). Men over the age of 45 years who had a penile fracture were more likely to develop erectile dysfunction or treatment compared to men under 45 years (RR: 1.65, 95% CI: 1.14-2.39). Rates of Peyronie's disease were higher in men with a history of penile fracture (5.8% vs 0%, p < 0.0001). Rates of Peyronie's disease were lower if immediate repair of the fracture was performed (RR: 0.20, 95% CI: 0.10-0.41). Men over the age of 45 years with penile fracture were more likely to develop Peyronie's Disease within 5 years compared to men under the age of 45 years penile fracture (RR: 3.72, 95% CI: 1.94-7.16). Penile fracture increases the risk of both erectile dysfunction and Peyronie's disease, especially those treated with conservative measures or over the age of 45 years compared to patients under 45 years with a penile fracture.


Enhancement of the efficacy of erythromycin in multiple antibiotic-resistant gram-negative bacterial pathogens.
To improve the efficacy of erythromycin, a hydrophobic antibiotic, against multiple antibiotic-resistant gram-negative bacterial pathogens by enhancing their outer membrane permeability. Fifty-one nonrepeat gram-negative bacterial pathogens of various genera, resistant to multiple antibiotics, including erythromycin, were selected by disc agar diffusion tests. The amphiphilic cationic steroid antibiotic, Ceragenin CSA-13, a potent permeabilizer of bacterial outer membranes, reduced the minimum inhibitory concentration of erythromycin in 92% of the bacterial pathogens selected for the test, when supplemented with erythromycin. A synergistic effect of Ceragenin CSA-13 and erythromycin in combination was also observed. Spectrofluorimetric study confirmed that Ceragenin CSA-13 acts by depolarizing the bacterial outer membrane. The toxicity of Ceragenin CSA-13 was evaluated to be insignificant by measuring 'median lethal dose' (LD(50)) on mouse model. Ceragenin CSA-13 may be useful as an agent to make erythromycin effective against infections caused by multiple antibiotic resistant gram-negative bacteria. The outcome of the study suggests erythromycin-Ceragenin combination as a new approach to overcome the problem associated with the rapid emergence of multi-drug-resistant pathogens. The insignificant toxicity of Ceragenin CSA-13, as found, supports the possibility of the application of this compound for human therapeutics.


Sympathetic activity following paraventricular or ventromedial hypothalamic lesions in rats.
The present experiment was designed to measure the sympathetic firing rate of nerve filaments to interscapular brown adipose tissue in rats with acute and chronic lesions in the ventromedial hypothalamus or paraventricular nucleus. Female rats received injections of kainic acid into either the paraventricular nucleus or the ventromedial hypothalamus. The sympathetic activity was measured by recording the firing rate of nerve filaments to interscapular brown adipose tissue after mounting the filaments on silver wire electrodes connected to an amplifier and rate meter. In acute experiments performed 30 minutes after the lesion, the basal firing rate was reduced in both groups and was significantly lower in the VMH-lesioned rats than in those with PVN lesions. In the chronic experiment kainic acid was injected into the VMH or PVN and the sympathetic firing rate was measured 7 to 9 days later. Both lesioned groups gained more weight than controls, but the VMH-lesioned rats gained more weight than the PVN-lesioned rats. The basal firing rate of sympathetic nerve filaments in the VMH-lesioned rats was lower than in the other groups. There was no significant difference in the sympathetic activity between PVN-lesioned and control rats. These experiments support the hypothesis that lesions of the ventromedial hypothalamus reduce the sympathetic activity but that lesions in the paraventricular nucleus do not.


Diagnosis of postoperative pancreatic fistula.
Pancreatic fistula (PF) is a major source of morbidity after pancreatectomy. The International Study Group on Pancreatic Fistula (ISGPF) defines postoperative fistula by an amylase concentration in the abdominal drain of more than three times the serum value on day 3 or more after surgery. However, this definition fails to identify some clinical fistulas. This study examined the association between lipase measured in abdominal drainage fluid and PF. Amylase and lipase levels in the abdominal drain were measured 3 days after pancreatic resection. Grade B and C fistulas were classified as clinical fistulas, regardless of whether the measured amylase concentration was considered positive or negative. The PF group included patients with a clinical fistula and/or those with positive amylase according to the ISGPF definition. Sixty-five patients were included. The median level of lipase was higher in patients with positive amylase than in those with negative amylase: 12,176 versus 64 units/l (P < 0·001). The lipase level was 16,500 units/l in patients with a clinical fistula and 224 units/l in those without a clinical fistula (P = 0·001). Patients with a PF had a higher lipase concentration than those without: 7852 versus 64 units/l (P < 0·001). A lipase level higher than 500 units/l yielded a sensitivity of 88 per cent and a specificity of 75 per cent for PF. For clinical fistulas the sensitivity was 93 per cent and specificity 77 per cent when the threshold for lipase was 1000 units/l. Lipase concentration in the abdominal drain correlated with PF. A threshold of 1000 units/l yielded a high sensitivity and specificity for the diagnosis of clinical PF.


Radiosynthesis of (S)-[18F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors.
Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a [18F]-labelled analog of the highly affine and selective α3β4 ligand (S)-3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)quinuclidine ((S)-T1). (S)-[18F]T1 was synthesized from ethynyl-4-[18F]fluorobenzene ([18F]5) and (S)-azidoquinuclidine by click reaction. After a synthesis time of 130min (S)-[18F]T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of (S)-[18F]T1 in mice at 30min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of (S)-[18F]T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drug AT-1001. These findings make (S)-[18F]T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET.


The influence of climate change on food production and food safety.
Food security and food safety are two concepts related to food risks. The majority of studies regarding climate change and food risks are related to the security of food provision. The objective of this study was to review the current state of knowledge of the influence of climate change on food production and food safety. The literature search was carried out by specifying each area individually (crops, ranching, fishing, food safety, etc.), including the term "climate change" and other specific factors such as CO2, ozone, biotoxins, mortality, heat, etc.) The increase in carbon dioxide concentrations together with the increase in global temperatures theoretically produces greater yields in crops destined for human and animal consumption. However, the majority of studies have shown that crop yields are decreasing, due to the increase in the frequency of extreme weather events. Furthermore, these climate anomalies are irregularly distributed, with a greater impact on developing countries that have a lower capacity to address climate change. All of these factors result in greater uncertainty in terms of food provision and market speculation. An increase in average temperatures could lead to an increased risk of proliferation of micro-organisms that produce food-borne illnesses, such as salmonella and campylobacter. However, in developed countries with information systems that document the occurrence of these diseases over time, no clear trend has been determined, in part because of extensive food conservation controls.


Semi-IPN ionogel based on poly (ionic liquids)/xanthan gum for highly sensitive pressure sensor.
In this paper, a novel ionogel with semi-interpenetrating poly (ionic liquids)/xanthan gum (PIL/XG) polymer network (semi-IPN) was prepared by using a simple one-pot method. The structure and the pressure sensing performance have been systematically investigated. It was found that introducing a low content (0.3-3.1 wt%) of XG significantly promoted the mechanical performance of ionogels with little effect on the ionic conductivity. The optimized PIL/XG containing 2.2 wt% XG exhibited high compression strength (761.0 kPa) and ionic conductivity (0.63 S/m at 25 °C). Such ionogels showed a liner response (0-100 kPa) and high sensitivity value of 6.86 kPa-1 in a capacitive mode. Meanwhile, as a resistive sensor, PIL/XG exhibited a wide response range to dynamic pressure ranges with stable repeatability. Furthermore, this ionogel exhibited excellent bactericidal properties against both gram-positive bacteria and gram-negative bacteria. This research provides a potential approach for developing ionogels based on semi-IPN with pressure-sensitive and anti-bacterial properties.


DNA ploidy and its clinical implications in gastric cancer.
Biological characteristics of gastric cancer depend mostly on genetic alterations in the cancer cells of individuals. To precisely predict the biological behavior and clinical outcome of individual cancer, it may be important to clarify the DNA profiles of cancer cells in each case. We have reviewed the most important results of studies on DNA ploidy of gastric cancer published in the English literature during the last 2 decades. Gastric carcinoma with aneuploidy has been shown to have a high proliferative activity and a high metastatic or invasive potential, thus leading to a poor prognosis as compared to diploid tumors. Analyses of DNA ploidy in gastric cancer may provide clinically useful information on diagnostic, therapeutic, and prognostic aspects. Further investigations may be needed to clarify the relationship between chromosome instability and DNA ploidy.


Time constants of vestibular nuclei neurons in the goldfish: a model with ocular propioception.
A simple model of the vestibular-ocular reflex with a proprioceptive eye velocity feedback loop is used to simulate recent data on the vestibular responses of neurons in the vestibular nuclei of spinal goldfish. The data support the hypothesis that a proprioceptive feedback loop elongates the vestibular nucleus time constant to equal that of the slow phase eye movements of vestibular nystagmus.


Current and emerging molecular and epigenetic disease entities in acute myeloid leukemia and a critical assessment of their therapeutic modalities.
Acute myeloid leukemia (AML) is the most frequently diagnosed acute leukemia, and its incidence increases with age. Although the etiology of AML remains unknown, exposure to genotoxic agents or some prior hematologic disorders could lead to the development of this condition. The pathogenesis of AML involves the development of malignant transformation of hematopoietic stem cells that undergo successive genomic alterations, ultimately giving rise to a full-blown disease. From the disease biology perspective, AML is considered to be extremely complex with significant genetic, epigenetic, and phenotypic variations. Molecular and cytogenetic alterations in AML include mutations in those subsets of genes that are involved in normal cell proliferation, maturation and survival, thus posing significant challenge to targeting these pathways without attendant toxicity. In addition, multiple malignant cells co-exist in the majority of AML patients. Individual subclones are characterized by unique genetic and epigenetic abnormalities, which contribute to the differences in their response to treatment. As a result, despite a dramatic progress in our understanding of the pathobiology of AML, not much has changed in therapeutic approaches to treat AML in the past four decades. Dose and regimen modifications with improved supportive care have contributed to improved outcomes by reducing toxicity-related side effects. Several drug candidates are currently being developed, including targeted small-molecule inhibitors, cytotoxic chemotherapies, monoclonal antibodies and epigenetic drugs. This review summarizes the current state of affairs in the pathobiological and therapeutic aspects of AML.


Observed steric crowding at modest coverage requires a particular membrane-binding scheme or a complementary mechanism.
Membrane shape transitions, including fusion and fission, play an important role in many biological processes. It is therefore essential to understand mechanisms of "curvature generation," the mathematical quantification of membrane shape. Among the different mechanisms is the effect of steric pressure between proteins crowded on a surface. At a higher curvature, there is more space for the crowders and less steric pressure. Currently, the physical model of curvature induction by crowding views the proteins as being bound to the surface as a whole rather than to the underlying lipids. Here, we split the previously understood model into two pieces: first, the reduction in steric pressure due to reduced collisions between proteins, and second, the increased area available to the protein that is independent of other crowders. The cases are distinguished by how the crowder is attached to the membrane. When a protein is attached to a specific lipid, as is the case in a typical crowding experiment, one should not model its lateral entropy; this has already been accounted for by the underlying lipid. The Carnahan-Starling pressure includes this lateral entropy. The revised theory predicts that a purely entropic crowding mechanism is inconsistent with observations of reshaping at the lower range of surface coverage, suggesting that an additional mechanism is at play.


Shp1, a regulator of protein phosphatase 1 Glc7, has important roles in cell morphogenesis, cell cycle progression and DNA damage response in Candida albicans.
In yeast, the type 1 protein phosphatase (PP1) catalytic subunit Glc7 is involved in the regulation of multiple cellular processes and thought to achieve specificity through association with different regulatory subunits. Here, we report that the Glc7 regulator Shp1 plays important roles in cell morphogenesis, cell cycle progression and DNA damage response in Candida albicans. SHP1 deletion caused the formation of rod-shaped yeast cells with slow growth. Flow cytometry analysis revealed that shp1Δ cells showed a prolonged G(2)/M phase, which was rescued by deleting the spindle-checkpoint gene MAD2. Furthermore, shp1Δ cells were hypersensitive to heat and genotoxic stresses. Interestingly, depletion of Glc7 caused defects similar to the shp1Δ mutant such as arrest at G(2)/M transition; and the GLC7/glc7Δ heterozygous mutant exhibited increased sensitivity to genotoxic stresses, consistent with the recent finding that Saccharomyces cerevisiae Glc7 has a role in DNA damage response. We also show that Shp1 is required for the nuclear accumulation of Glc7, suggesting that Shp1 executes its cellular function partly by regulating Glc7 localization.


[Assessment of behavioral dependence with the Glover-Nilsson test in smoking cessation treatment].
To assess behavioral dependence using the Glover-Nilsson test and determine its association with successful smoking cessation. An analytical longitudinal study was carried out, the target population of which consisted of smokers who enrolled in a smoking cessation clinic for treatment. The following variables were examined: age, sex, nicotine dependence (Fagerström test), psychoactive drug use, prior attempts at quitting, and behavioral dependence measured with the Glover-Nilsson test. The most recent version of this test is an 11-item questionnaire which classifies behavioral dependence according to the scores obtained: mild (<12), moderate (12-22), severe (23-33), and very severe (>33). Successful cessation was defined as self-reported abstinence confirmed by measurement of expired CO level (< or =10 ppm). Results were expressed as means (SD) for quantitative variables and percentages and absolute frequencies for qualitative variables. The study population consisted of 167 smokers--89 men (53.3%) and 78 women (46.7%)--with a mean age of 43.5 (9.9) years, a nicotine dependence score (Fagerström test) of 6.5 (2.2) points, and a Glover-Nilsson score of 23.3 (6.6). Of the study population, 65.9% (n=110) had made previous attempts at quitting. Abstinence at 3 months was 55.1% (n=92). Differences between the sexes were found for age and previous attempts at quitting. Younger patients had higher scores on the Glover-Nilsson test and the Fagerström test and lower abstinence rates. Severe behavioral dependence can result in less successful cessation outcome. All aspects related to dependence must be assessed to help select the most adequate pharmacological and psychological treatment for results to be optimized.


The role of chlamydial antibodies in an in vitro fertilization program.
The reported incidence of antibodies to Chlamydia trachomatis in patients attending infertility clinics is at least 30%. It has been reported that chlamydial antibodies are associated with decreased pregnancy rates following in vitro fertilization (IVF). A study was performed to investigate the significance of chlamydial antibodies in an established IVF program. The results did not show a decreased pregnancy rate in the presence of chlamydial antibodies. Of the women achieving pregnancy, 41% were seropositive compared with 38% seropositivity in women who did not become pregnant. There was no apparent benefit of the use of prophylactic antibiotics. The results also suggested that past infection with C. trachomatis in men did not adversely affect semen analysis or fertilization.


Nutritive/non-nutritive sweeteners and high fat diet contribute to dysregulation of sweet taste receptors and metabolic derangements in oral, intestinal and central nervous tissues.
Overconsumption of non-nutritive sweeteners is associated with obesity, whereas the underlying mechanisms remain controversial. This study aimed to investigate the effects of long-term consumption of nutritive or non-nutritive sweeteners with or without high fat diet on sweet taste receptor expression in nutrient-sensing tissues and energy regulation dependent on sweet-sensing. 50 Male Sprague-Dawley rats (140-160 g) were assigned to 10 groups (n = 5/group). All received fructose at 2.5% or 10%, sucralose at 0.01% or 0.015% or water with a normal chow diet or high fat diet for 12 weeks. Food and drink intake were monitored daily. Oral glucose tolerance test and intraperitoneal glucose tolerance test were performed at week 10 and 11 respectively. Serum was obtained for measurement of biochemical parameters. Tongue, duodenum, jejunum, ileum, colon and hypothalamus were rapidly removed to assess gene expression. Long-term consumption of sweeteners impaired glucose tolerance, increased calorie intake and body weight. A significant upregulation of sweet taste receptor expression was observed in all the four intestinal segments in groups fed 0.01% sucralose or 0.015% sucralose, most strikingly in the ileum, accompanied by elevated serum glucagon-like peptide-1 levels and up-regulated expression of sodium-dependent glucose cotransporter 1 and glucose transporter 2. A significant down-regulation in the tongue and hypothalamus was observed in groups fed 10% fructose or 0.015% sucralose, with alterations in hypothalamic appetite signals. The presence of high fat diet differentially modulates sweet taste perception in nutrient-sensing tissues. Long-term consumption of whether nutritive sweeteners or non-nutritive sweeteners combined with high fat diet contribute to dysregulation of sweet taste receptor expression in oral, intestinal and central nervous tissues.


Functional and conformational properties of proteolytic enzyme-modified potato protein isolate.
Potato protein hydrolysates (PPHs) were preparedwith Alcalase on intact potato protein isolates (PPI), with differenthydrolysis times (0.5-4 h), and functional and conformational properties of resultant hydrolysates were investigated. The degree of hydrolysis changed during incubation. Peptide bond cleavage increased and hydrolysis progressed rapidly. Gel electrophoresis showed that, by increasing the hydrolysis time, peptides with an apparent molecular weight below 20 kDa increased. It also revealed that, among potato protein components, patatin was more sensitive to Alcalase® hydrolysis than protease inhibitors. Enzymatic hydrolysis significantly enhanced the solubility and foam capacity of PPHs, but impaired foam stability (P < 0.05). Limited enzymatic hydrolysates (0.5PPH) at the interface improved the emulsion activity and stability index. These emulsions also had the smallest z-average and polydispersity index and showed the highest zeta potential. Fourier-transform infrared spectrometry (FTIR) analysis indicated extensive disruption of hydrogen bonds in PPHs, besides augmentation of α-helices and β-turns, and a decline in the β-sheets in the secondary structure of the PPHs was shown. Potato protein isolate, especially 0.5PPH, has good functional and conformational properties. Overall, our results provide new insights into the use of potato protein hydrolysates as a functional food component in the food industry. © 2019 Society of Chemical Industry.


[Vitamin B6 deficiency caused by the use of levodopa].
There are indications that the use of levodopa/carbidopa can cause symptomatic vitamin B6 deficiency. However, this has only been described for patients who used the product in the form of an intestinal gel. We are describing 3 patients who developed vitamin B6 deficiency while using levodopa/carbidopa in tablet form. All 3 patients developed symptoms consistent with peripheral axonal polyneuropathy. The cases of our patients are providing support for the idea that oral use of levodopa/carbidopa can cause symptomatic vitamin B6 deficiency.


Parent reported barriers and facilitators towards cochlear implantation - A systematic review.
Early identification and intervention of hearing loss at a young age leads to long term benefits from language, communication, social, educational and financial aspects. Cochlear implantation is a widely recommended rehabilitation option for hearing loss. The process of cochlear implantation is a long one and the role played by parents is crucial. The present systematic review was carried out with the aim of identifying the different parent reported barriers towards cochlear implantation. PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus and Cochrane Library. Studies in parent reported barriers towards cochlear implantation screened and identified using 3 stages by 2 reviewers. Mixed Methods Appraisal Tool was used to carry out the quality appraisal of included studies. Outcome measures related to barriers and facilitators. Nineteen studies were identified and included in the present review which discussed the parent reported barriers based on themes such as service delivery, social issues, time related, device/surgery, financial, child related and others. The different factors that facilitated the process included availability of resources, finances, child related and parental. The present review was a novel attempt at exploring the different parent reported barriers towards cochlear implantation. The facilitators, which can be used to overcome these barriers, will be useful for making the process smoother.


Outcome prediction with serial neuron-specific enolase and machine learning in anoxic-ischaemic disorders of consciousness.
The continuation of life-sustaining therapy in critical care patients with anoxic-ischemic disorders of consciousness (AI-DOC) depends on prognostic tests such as serum neuron-specific enolase (NSE) concentration levels. To apply predictive models using machine learning methods to examine, one year after onset, the prognostic power of serial measurements of NSE in patients with AI-DOC. To compare the discriminative accuracy of this method to both standard single-day, absolute, and difference-between-days, relative NSE levels. Classification algorithms were implemented and K-nearest neighbours (KNN) imputation was used to avoid complete case elimination of patients with missing NSE values. Non-imputed measurements from Day 0 to Day 6 were used for single day and difference-between-days. The naive Bayes classifier on imputed serial NSE measurements returned an AUC of (0.81±0.07) for n=126 patients (100 poor outcome). This was greater than logistic regression (0.73±0.08) and all other classifiers. Naive Bayes gave a specificity and sensitivity of 96% and 49%, respectively, for an (uncalibrated) probability decision threshold of 90%. The maximum AUC for a single day was Day 3 (0.75) for a subset of n=79 (61 poor outcome) patients, and for differences between Day 1 and Day 4 (0.81) for a subset of n=46 (39 poor outcome) patients. Imputation avoided the elimination of patients with missing data and naive Bayes outperformed all other classifiers. Machine learning algorithms could detect automatically discriminatory features and the overall predictive power increased from standard methods due to the larger data set. Data analysis code is available under GNU at: https://github.com/emilymuller1991/outcome_prediction_nse.


Development and evaluation of a reverse dot blot assay for the simultaneous detection of six common Chinese G6PD mutations and one polymorphism.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited disorder worldwide including southern China. We developed and validated a reverse dot blot (RDB) assay for the rapid and simultaneous genotyping of six mutations (c.95A>G, c.871G>A, c.1004C>T, c.1024C>T, c.1376G>T and c.1388G>A), that were common mutations in the Chinese G6PD deficiency population, and one polymorphism (c.1311C>T). Reliable genotyping of wild-type and mutant genomic DNA samples was achieved by means of a test strip onto which allele-specific oligonucleotide probe lines are fixed in parallel. This method involves a multiplex PCR amplification of three fragments in the G6PD target sequence and a manual hybridization/detection protocol. The entire procedure starting from blood sampling to the identification of mutations requires less than 6 h. The diagnostic reliability of this reverse dot blot assay was evaluated on 207 pre-typed samples by using direct DNA sequence analysis in a blind study. The reverse dot blot typing was in complete concordance with the reference method. The reverse dot blot assay was proved to be a simple, rapid, highly accurate, and cost-effective method to identify common G6PD mutations in Chinese population.


Inflammation in the neoplasms of the adrenal gland: Is there a prognostic role? An immunohistochemical study.
Adrenal gland neoplasms are mostly benign. The differential diagnosis between adrenocortical adenoma and carcinoma relies on nine morphologic parameters (Weiss criteria) that are mostly subjective. Although rare, carcinomas represent an aggressive disease that require short time follow-up. For this reason, the diagnosis should be accurate. Neoplasms of the medulla are mostly represented by phaeochromocytomas, all potentially metastatic. Prognostic score systems (GAPP and PASS) have been implemented but not enough objective and useful in borderline cases. More objective parameters should be introduced. Little is known in literature on the inflammatory response in these tumors. Aim of our study was the definition (type, density and distribution) of inflammation in the adrenal neoplasms. Immunohistochemistry for CD45 (inflammatory cells), CD20 (B cells) and CD3 (T cells) antibodies was performed in 15 adrenocortical neoplasms and 17 phaeochromocytomas. A manual count of the signal was set for each marker, to establish the cellular type, their density (cells/mm2) and location within the tumor. Fisher's exact test was applied to assess the correlation between the immunoscore and clinico-pathologic parameters. The difference of cellular density between the three markers was statistically significant (p value = 0.0028), with highest values for CD45 and CD3. No differences were detected between the periphery and the center of the lesions. The most relevant finding was the detection of a higher immunoscore in adrenocortical adenomas, compared to carcinomas. Moreover, most of phaeochromocytomas showed high expression of inflammation, except the only metastatic case. The present study showed that inflammation could represent a valuable diagnostic and potential prognostic parameter, useful for the correct management of these lesions.


[Current status of the treatment of perforated duodenal ulcer].
A European study involving 15 major centres shows that the surgical treatment of a perforated duodenal ulcer depends closely upon the underlying condition and the operative risk. The latter is determined on the basis of the age of the subject, the time since the perforation, and the chronicity of the ulcer as well as the possible concomitant existence of severe medical pathology. In the optimal situation, preference is given to suture of the perforation and supraselective vagotomy. When general conditions are poor, the tendency is for a more simple approach such as simple suture or even the Taylor Wangensteen method. Type B II gastric resection remains indicated where there is associated bleeding or in the presence of large non-suturable ulcers which cannot be dealth with by a Rives-type patch of epiploon.


Chronic cholestasis, paucity of bile ducts, red cell aplasia, and the Stevens-Johnson syndrome. An ampicillin-associated case.
The unique case of severe chronic cholestasis with paucity of bile ducts accompanied by pure red cell aplasia and the Stevens-Johnson syndrome in a 35-year-old woman after ampicillin ingestion is presented. The patient improved gradually and is asymptomatic 4 years later. Sequential histological and clinical follow-up substantiate the course of her disease.


Interferon beta 1, an intermediate in the tumor necrosis factor alpha-induced increased MHC class I expression and an autocrine regulator of the constitutive MHC class I expression.
In conclusion, our observations indicate that the constitutive MHC class I expression is regulated by autocrine production of IFN-beta 1. TNF-alpha acts as an enhancer of the autocrine production of IFN-beta 1, and consequently as an enhancer of the MHC class I expression and viral protection.


The effect of sex on outcome of preterm infants - a population-based survey.
To provide comprehensive data on potential sex differences in maternal and neonatal characteristics, short-term morbidity and neurodevelopmental outcome within an entire geographically determined collective of infants born at a gestational age <32 weeks. Between 2003 and 2008, we prospectively enrolled all infants born in Tyrol at <32 weeks of gestation; the association between sex, and a wide set of pre- and postnatal factors, post-discharge morbidity and neurodevelopmental outcome was analysed. Girls less frequently suffered from early-onset sepsis than boys (p = 0.030). After adjustment for multiple corrections (Bonferroni's p = 0.003), no sex differences were seen within any maternal or neonatal parameter. Analysis of morbidity revealed a higher readmission rate in boys (p < 0.0001), which was primarily caused by a greater incidence of respiratory problems (p = 0.003). Boys did not show a greater adverse neurodevelopmental outcome at the age of 12 or 24 months. Parents of boys should be prepared for a potentially higher frequency of readmission after initial discharge, but our data currently give no reason for parents of boys to be disproportionately anxious about their neurodevelopmental outcome. Whether boys also enjoy a rosy prognosis for developmental outcome at school age remains to be elucidated.


Continuous noninvasive monitoring of arterial pressure using the vascular unloading technique in comparison to the invasive gold standard in elderly comorbid patients: A prospective observational study.
Elderly patients aged ≥65 years represent a growing population in the perioperative field, particularly orthopedic and vascular surgery. The higher degree of age-related or comorbid-dependent vascular alterations renders these patients at risk for hemodynamic complications and likely denote a possible limitation for modern, non-invasive arterial pressure monitoring devices. The aim was to compare vascular unloading technique-derived to invasive measurements of systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) in elderly perioperative patients. This prospective observational study included patients aged ≥65 years scheduled for orthopedic and patients ≥50 years with peripheral artery disease Fontaine stage ≥ II scheduled for vascular surgery, respectively. Invasive radial artery and non-invasive finger-cuff (Nexfin system) arterial pressures were recorded before and after induction of general anesthesia and during surgery. Correlation, Bland-Altman, and concordance analyses were performed. Measurements of arterial pressure were also compared during intraoperative hypotension (MAP <70 mm Hg) and hypertension (MAP >105 mm Hg). Sixty patients with orthopedic (N = 25, mean (SD) age 77 (5) years) and vascular surgery (N = 35, age 69 [10] years) were enrolled. Seven hundred data pairs of all patients were analysed and pooled bias and percentage error were: SAP: 14.43 mm Hg, 43.79%; DAP: -2.40 mm Hg, 53.78% and MAP: 1.73 mm Hg, 45.05%. Concordance rates were 84.01% for SAP, 77.87% for DAP, and 86.47% for MAP. Predefined criteria for interchangeability of absolute and trending values could neither be reached in the overall nor in the subgroup analyses orthopedic vs vascular surgery. During hypertension, percentage error was found to be lowest for all pressure values, still not reaching predefined criteria. Arterial pressure monitoring with the vascular unloading technique did not reach criteria of interchangeability for absolute and trending values. Nevertheless, the putatively beneficial use of noninvasive arterial pressure measurements should be further evaluated in the elderly perioperative patient.


Prosthetic replacement of a long segment of vein in the treatment of a lower limb injury.
A patient who sustained exceptionally severe damage to the main blood vessels and to the collateral circulation of his left lower limb is reported. The femoropopliteal vein was replaced by a Dacron prosthesis which remained patent for 6 weeks until an adequate collateral circulation was established.


The role of endogenous Na+, K(+)-adenosine triphosphatase inhibitory factor in the regulation of membrane fluidity of erythrocytes in essential hypertension.
To investigate the regulatory mechanisms of membrane functions in hypertension, we examined the relationship between endogenous Na+, K(+)-adenosine triphosphatase (ATPase) inhibitor (digitalis-like factor; DLF) and erythrocyte membrane fluidity in essential hypertension by means of an electron spin resonance (ESR) and spin labelling methods. Erythrocytes were obtained from patients with essential hypertension and normotensive subjects, and the ESR spectra for a fatty acid spin label agent (5-nitroxide stearate) incorporated into the erythrocyte membranes were studied. The DLF content in plasma was expressed as the inhibitory potency of dog kidney Na+, K(+)-ATPase activity in vitro. The values of outer hyperfine splitting and of order parameter in ESR spectra were significantly higher in hypertensive patients than in normotensive subjects. This finding shows that the erythrocyte membrane fluidity may be decreased in essential hypertension. The level of plasma DLF content was greater in hypertensive patients than in normotensive subjects and was significantly correlated with the decrease in erythrocyte membrane fluidity. These results suggest that the decrease in erythrocyte membrane fluidity may be partially dependent upon the increased plasma DLF content.


Relation between lipogranuloma formation and fibrosis, and the origin of brown pigments in lipogranuloma of the canine liver.
In a previous study we confirmed that canine hepatic lipogranuloma, defined as lesions consisting of small round cells which contain lipid vacuoles and brown pigments in their cytoplasm, was an assembly of Kupffer cells and/or macrophages, and that the cytoplasmic brown pigments in the lesions were hemosiderin and ceroid. However, the pathogenesis of the lesion remains unclear. Kupffer cells (resident macrophages) play a key role in hepatic fibrogenesis due to the production of cytokines including TGF-beta. In the present study, we have examined 52 canine liver samples (age: newborn - 14 years; 25 males and 27 females) and investigated the correlation between lipogranuloma formation and fibrosis as well as the origin of brown pigments of lipogranulomas. Lipogranulomas were detected histopathologically in 23 (44.2%) of the 52 liver samples. No significant correlation was found between the density of lipogranulomas and distribution of collagen type I/III in the liver. Pigmentation of lipogranulomas showed significant correlations with that on both hepatocytes and sinusoidal cells, indicating that pigments of lipogranuloma (hemosiderin and ceroid) might be derived from hepatocytes and Kupffer cells. Lipogranulomas are not a contributing factor in hepatic fibrosis, but might be a potential indicator of the accumulation of iron and lipid inside the liver.


Characterization of prolactin (PRL) and PRL receptor (PRLR) in Chinese soft-shelled turtle: Molecular identification, ligand-receptor interaction and tissue distribution.
Prolactin (PRL) plays crucial roles in many physiological and pathological processes through activating its specific membrane-anchored receptor (PRLR). Although this ligand-receptor pair has been extensively studied in mammals, birds and fishes, researches examining their significance is rather scarce in reptiles. Additionally, the interaction mechanism of PRL-PRLR has abortively understood across vertebrates, since two tandem repeated ligand-binding domains of PRLR have been identified in birds and few reptiles. To lay the foundation to clarify their roles and ligand-receptor interaction in reptiles, using Chinese soft-shelled turtle as model, the cDNAs containing open reading frame of PRL and PRLR were cloned. The cloned PRL consisted of 710 bp and encoded a precursor of 228 amino acid (-aa), while PRLR was 2658 bp in length and predicted to generate a 828-aa precursor. Furthermore, the recombinant PRL protein with high-purity was prepared from Escherichia coli (E. coli) strain Rosetta gamiB (DE3) by using cobalt resin. Using the 5 × STAT5-Luciferase reporter system, we found PRLR and PRLR-M2 (the PRLR-mutant lacking membrane-distal ligand-binding domain) could be dose-dependently activated by recombinant PRL, thereby triggering the intracellular JAK2-STAT5 signaling cascade, suggesting PRL-PRLR is functional in Chinese soft-shelled turtle, and the membrane-proximal ligand-binding domain of PRLR is the critical domain involving in PRL-binding. Quantitative real-time PCR revealed that PRL was predominantly and abundantly expressed in pituitary, while PRLR exhibited ubiquitous expression in all of the tissues examined. Collectively, our data indicate the PRL-PRLR pair may function in reptiles including Chinese soft-shelled turtle, in a way similar to that in birds.


Random-Reaction-Seed Method for Automated Identification of Neurite Elongation and Branching.
Conventional deterministic algorithms (i.e., skeletonization and edge-detection) lack robustness and sensitivity to reliably detect the neurite elongation and branching of low signal-to-noise-ratio microscopy images. Neurite outgrowth experiments produce an enormous number of images that require automated measurement; however, the tracking of neurites is easily lost in the automated process due to the intrinsic variability of neurites (either axon or dendrite) under stimuli. We have developed a stochastic random-reaction-seed (RRS) method to identify neurite elongation and branching accurately and automatically. The random-seeding algorithm of RRS is based on the hidden-Markov-model (HMM) to offer a robust enough way for tracing arbitrary neurite structures, while the reaction-seeding algorithm of RRS secures the efficiency of random seeding. It is noteworthy that RRS is capable of tracing a whole neurite branch by only one initial seed, so that RRS is proficient at quantifying extensive amounts of neurite outgrowth images with noisy background in microfluidic devices of biomedical engineering fields. The method also showed notable performance for reconstructing of net-like structures, and thus is expected to be proficient for biomedical feature extractions in a wide range of applications, such as retinal vessel segmentation and cell membrane profiling in spurious-edge-tissues.


Absence of the leaflets of the aortic valve in DiGeorge syndrome.
A newborn infant is described with complete absence of the leaflets of the aortic valve, interruption of the aortic arch and DiGeorge syndrome. This association has not previously been reported, nor has absence of the leaflets of the aortic valve without other features of left ventricular dysplasia. We discuss the possible influence of severe intra-uterine aortic regurgitation on development of the aortic arch.


Acute unilateral obstruction of ureter. Disparity in divided renal function calculated from 131I-hippuran and 99mTc-DTPA renography.
Fifteen patients with acute unilateral obstruction of ureter and 30 control patients were studied with simultaneous 131I-Hippuran and 99mTc-DTPA gamma camera renography. In severe outflow obstruction the relative function of the obstructed kidney was higher when calculated with Hippuran than with DTPA. No difference was found in the control subjects. This means that the glomerular filtration rate of an obstructed kidney may be relatively more reduced than the renal blood flow. Therefore, measurement of the single kidney fraction of total glomerular filtration rate has to be calculated with a glomerular filtered tracer, e.g., 99mTc-DTPA.


A review of the treatment of functional neurological disorder with intensive short-term dynamic psychotherapy.
The purpose of this article was to raise awareness of an under-recognized but well-supported treatment for Functional Neurological Disorders (FND) termed Intensive Short-term Dynamic Psychotherapy (ISTDP). There has been significant interest in the role of psychological mechanisms in FND onset and maintenance with specific evidence for maladaptive emotional processing. We outline how this supports the theoretical basis for ISTDP as an option in FND treatment and undertake a literature review of the current evidence base. We describe the application of ISTDP to FND illustrated through direct therapy transcripts. We conclude with reflections on the strengths and limitations of ISTDP as well as recommendations regarding future research.


Effect of Gender on Clinical Presentation of Tuberculosis (TB) and Age-Specific Risk of TB, and TB-Human Immunodeficiency Virus Coinfection.
Previous studies have shown gender differences in tuberculosis (TB) incidence; however, gender disparity has not been well documented across granular categorizations of anatomic sites affected by TB and in the presence of human immunodeficiency virus (HIV) coinfection, largely due to small sample size for less common TB clinical presentations and lack of detailed clinical data. The study population included TB cases aged ≥15 years (n = 41, 266) diagnosed in Harare, Zimbabwe. This cross-sectional study estimated male-to-female ratio (M/F ratio) for (1) age-specific TB incidence, (2) age-specific HIV prevalence among incident TB cases, and (3) 9 types of TB defined by affected anatomic site. Males were at a 53% higher risk of TB compared to females (risk ratio [RR] = 1.53; 95% confidence interval [CI], 1.12-2.09). Based on adjusted odds ratios (aORs) from multinomial logistic regression model, the odds of abdominal TB (aOR = 0.51; 95% CI, .39-.68), TB bones/joints/spine (aOR = 0.63; 95% CI, .45-.90), and "other" extrapulmonary TB sites (aOR = 0.69; 95% CI = .59-.81) versus pulmonary TB were lower among males compared to females. The risk of TB-HIV coinfection among males was 17% (RR = .83; 95% CI, .74-.93) and 8% (RR = 0.92; 95% CI, .88-.95) lower in the 15- to 24-year and 25- to 44-year age groups, respectively. This study revealed a nuanced role of gender across finer categorizations of TB, indicating the need for future research to delineate underlying mechanisms driving gender disparities in TB. The finding that women had a greater likelihood of severe forms of TB and TB-HIV coinfection compared to men has important implications for women's health in TB-HIV high-burden settings.


Self-reported visual function in healthy older people in Britain: an exploratory study of associations with age, sex, depression, education and income.
Tractable but undetected visual impairment in older people may be relatively common, particularly amongst the very old and in more deprived populations. Measurement of visual acuity is unlikely to be helpful in identifying this impairment, but targeted assessment of visual function may be beneficial. There is uncertainty about the defining characteristics of the target group. To explore factors associated with self-reported visual impairment in community dwelling older people. secondary cross sectional analysis of baseline data from a randomised controlled trial. three large group practices in outer London. older people aged 65 and over enrolled in a study of health risk appraisal. postal questionnaire using questions from the National Eye Institute Visual Function questionnaire. Moderate or extreme visual function loss occurred in 4 to 12% of community-dwelling older people in this population reporting less than excellent vision, depending on which aspect of visual function is considered. Visual function loss in this subgroup increases in prevalence with advancing age, but is not associated with female sex, low educational attainment or low income. It is associated with depressed mood. Questions about visual function identify a group of older people whose vision and mental state needs further investigation.


Being in control: a note on differences between caregiving and noncaregiving spouses.
Twenty-seven spouse caregivers of dementia patients and 33 noncaregiving (healthy) spouses, aged 54 to 90, described a stressful situation with their spouses and completed measures of perceived control and subjective well-being. Both groups were similar in their perceived lack of control over the spouse's behavior but differed in how control influenced positive affect. Perceived control over the spouse was negatively related to positive affect for the healthy couples but for caregivers it was positively related.


The first thieno[3,4-b]pyrazine based small molecular acceptor with a linear A2-A1-D-A1-A2 skeleton for fullerene-free organic solar cells with a high Voc of 1.05 V.
The first thieno[3,4-b]pyrazine (TP) based non-fullerene acceptor was synthesized and named as TP21, which shows a narrow band gap of 1.65 eV and a high-lying LUMO of -3.61 eV. Organic solar cells based on J61:TP21 realized a moderate power conversion efficiency (PCE) of 5.81% with a high open-circuit voltage (Voc) of 1.05 V.


Shifting Paradigms in Cardiovascular Therapeutic Strategies During the COVID-19 Era.
The coronavirus disease-19 (COVID-19) period have dictated a different approach to cardiac interventions at our medical institution. We prioritize emergent care geared toward lesser invasive approaches while minimizing hospitalization duration. This reflects upon coronary and structural/valvular cases altogether. Despite potential criticism of this approach, we believe it is the most appropriate therapeutic strategy for this unique period. Further investigation is needed to examine the external validity of our approach in other medical centers worldwide.


The association of standard Kt/V and surface area-normalized standard Kt/V with clinical outcomes in hemodialysis patients.
A previous study demonstrated that the surface area-normalized standard Kt/V (SAstdKt/V) was better associated with mortality than standard Kt/V (stdKt/V). This study investigates the association of SAstdKt/V and stdKt/V with mortality, anemia, and hypoalbuminemia in a larger patient cohort with a longer follow-up period. We included adult patients on thrice-weekly hemodialysis in the USRDS database and excluded amputated patients. StdKt/V and SAstdKt/V were calculated from the available single-pool Kt/V. Patients were categorized into five groups according to their stdKt/V and SAstdKt/V: <2.00, 2.00-2.19, 2.20-2.39, 2.40-2.59, and ≥2.60. Hazard ratios (HR) and odds ratios (OR) were calculated using Cox and logistic regression analysis respectively. There were 507,656 patients included in the analysis. The patients had a median age of 65.5 years with a median follow-up period of 2 years. Thirty-four percent died during follow-up. HRs for mortality progressively decreased as SAstdKt/V increased in both unadjusted and adjusted models. Unlike SAstdKt/V, HRs were the lowest in the categories with stdKt/V of 2.40-2.59 and they increased in the higher stdKt/V category. The adjusted HR for SAstdKt/V vs. stdKt/V were 0.68 vs. 0.62 in the category of 2.40-2.59, and 0.63 vs. 0.73 in the category of ≥2.60. The adjusted ORs for anemia progressively decreased as SAstdKt/V increased, whereas ORs decreased to the lowest in stdKt/V category 2.40-2.59 and increased in the ≥2.60 category. The adjusted ORs for hypoalbuminemia progressively decreased as SAstdKt/V and stdKt/V increased which were both 0.45 in 2.40-2.59 category and decreased to 0.29 and 0.42 in the ≥2.60 category. SAstdKt/V is better associated with mortality, anemia, and hypoalbuminemia than stdKt/V. SAstdKt/V is a better parameter in defining hemodialysis dosing which can be calculated by an available online tool. Further studies to determine the optimal SAstdKt/V dose required to achieve improved clinical outcomes with better cost-effectiveness are needed.


Comparison of the histopathological findings of patients with diabetic and idiopathic carpal tunnel syndrome.
This study is aimed to investigate whether there are any histopathological differences between diabetic and idiopathic carpal tunnel syndromes. The biopsy specimens were taken from transverse carpal ligament (TCL), tenosynovium adjacent to median nerve and epineurium of median nerve and evaluated in 47 patients (21 diabetic and 26 idiopathic) who were diagnosed with carpal tunnel syndrome (CTS) and treated surgically with open carpal tunnel release. Fibroblast proliferation, fibrosis, perivascular inflammation, oedema, vascular proliferation and vascular wall thickness were determined and scored in all specimens. There weren't any histopathological abnormalities in TCL specimens of both groups. Synovial hyperplasia, fibrosis and perivascular inflammation were not observed in tenosynovial analysis of both groups. Diabetic CTS patients, when compared with idiopathic CTS patients, had higher rates of synovial edema (idiopathic CTS 57 %, diabetic CTS 87 %), vascular proliferation (idiopathic CTS 30.8 %, diabetic CTS 90.5 %) and increased vascular wall thickness (idiopathic CTS 11.5 %, diabetic CTS 90.5 %). There was no oedema, fibrosis and perivascular inflammation of the epineurium in specimens of either group. But increases in vascular proliferation (idiopathic CTS 7.7 %, diabetic CTS 71.4 %) and vascular wall thickness (idiopathic CTS 3.8 %, diabetic CTS 71.4 %) was seen in the epineurium of diabetic patients and these differences were statistically significant (p < 0.05). Because of the severe synovial and epineurial histopathological abnormalities and inadequate neural regeneration capacity, surgical open carpal tunnel decompression should be planned earlier in diabetic CTS patients. Further studies should be considered to evaluate the histopathological features of diabetic CTS patients early in the course of the disease.


Initiation and tolerance of chemoprevention among women with high-risk breast lesions: the potential of low-dose tamoxifen.
High-risk lesions (HRLs) of the breast are an indication for chemoprevention, yet uptake is low, largely due to concerns about side effects. In 2019, low-dose (5 mg) tamoxifen was demonstrated to reduce breast cancer risk with improved tolerance. We describe chemoprevention uptake in an academic clinic before and after the introduction of low-dose tamoxifen. Females age ≥ 35 with HRLs who established care from April 2017 through January 2020 and eligible for chemoprevention were included. Rates of chemoprevention initiation before and after the introduction of low-dose tamoxifen (pre-2019 vs. post-2019) were compared with chi-squared tests. Logistic regression identified demographic and clinical factors associated with chemoprevention initiation. Kaplan-Meier methods determined the rates of discontinuation. Among 660 eligible females with HRLs, 22.7% initiated chemoprevention. Median time from first visit to chemoprevention initiation was 54 days (interquartile range (IQR): 0-209); 31.0% (46/150) started chemoprevention > 6 months after their initial visit. Chemoprevention uptake was not significantly different pre-2019 vs. post-2019 (21.2% vs. 26.3%, p = 0.16); however, post-2019, low-dose tamoxifen became the most popular option (41.5%, 34/82). On multivariable analyses, age and breast cancer family history were significantly associated with chemoprevention initiation. Discontinuation rates at 1 year were lowest for low-dose tamoxifen (6.7%) vs. tamoxifen 20 mg (15.0%), raloxifene (20.4%), or an aromatase inhibitor (20.0%). In this modern cohort, 22.7% of females with HRLs initiated chemoprevention with 31.0% initiating chemoprevention > 6 months after their first visit. Low-dose tamoxifen is now the most popular choice for chemoprevention, with low discontinuation rates at 1 year.


The break of earthquake asperities imaged by distributed acoustic sensing.
Rupture imaging of megathrust earthquakes with global seismic arrays revealed frequency-dependent rupture signatures1-4, but the role of high-frequency radiators remains unclear3-5. Similar observations of the more abundant crustal earthquakes could provide critical constraints but are rare without ultradense local arrays6,7. Here we use distributed acoustic sensing technology8,9 to image the high-frequency earthquake rupture radiators. By converting a 100-kilometre dark-fibre cable into a 10,000-channel seismic array, we image four high-frequency subevents for the 2021 Antelope Valley, California, moment-magnitude 6.0 earthquake. After comparing our results with long-period moment-release10,11 and dynamic rupture simulations, we suggest that the imaged subevents are due to the breaking of fault asperities-stronger spots or pins on the fault-that substantially modulate the overall rupture behaviour. An otherwise fading rupture propagation could be promoted by the breaking of fault asperities in a cascading sequence. This study highlights how we can use the extensive pre-existing fibre networks12 as high-frequency seismic antennas to systematically investigate the rupture process of regional moderate-sized earthquakes. Coupled with dynamic rupture modelling, it could improve our understanding of earthquake rupture dynamics.


Role of Thr199 residue in human β-carbonic anhydrase-II pH-dependent activity elucidated by microsecond simulation analysis.
Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to form bicarbonate, a reaction required for many functions such as carbon assimilation, pH acid-base homeostasis, respiration and photosynthesis via a zinc-hydroxide mechanism for carbon dioxide hydration. In earlier studies, it was revealed that Carbonic anhydrases are inactive at pH 7.5 and active at pH 8.4. This steep pH dependence for its activity led us to design this work to understand its mode of action at atomic level detail. In our microsecond simulation based analysis, it was revealed that the interaction between Glu106 and Thr199 plays a critically important role in its activity. Thr199 co-ordinated loop movement was observed to be acting as a lid, with 'open' and 'close' mechanism for substrate entry to the core of the catalytic site, where Zn-ion resides and executes its carbon dioxide hydration mechanism. On the other hand, decline in the total secondary structural elements percentage in the protein was observed in correspondence to the pH condition change. The α-helices between Thr125-Gly145 and Val150-Lys170 residues were especially noticed to be losing their structural integrity responsible for formation of dimer and tetramers. In conclusion, our analysis showed that the interaction between Glu106 and Thr199 is crucial for maintaining the structural integrity of the Thr199 coordinated loop, responsible for allowing substrate towards the catalytic site.Communicated by Ramaswamy H. Sarma.


Roadside soils show low plant available zinc and copper concentrations.
Vehicle combustion and component wear are a major source of metal contamination in the environment, which could be especially concerning where road ditches are actively farmed. The objective of this study was to assess how site variables, namely age, traffic (vehicles day(-1)), and percent carbon (%C) affect metal accumulation in roadside soils. A soil chronosequence was established with sites ranging from 3 to 37 years old and bioavailable, or mobile, concentrations of Zinc (Zn) and Copper (Cu) were measured along major highways in North Carolina using a Mehlich III extraction. Mobile Zn and Cu concentrations were low overall, and when results were scaled via literature values to "total metal", the results were still generally lower than previous roadside studies. This could indicate farming on lands near roads would pose a low plant toxicity risk. Zinc and Cu were not correlated with annual average traffic count, but were positively correlated with lifetime traffic load (the product of site age and traffic count). This study shows an often overlooked variable, site age, should be included when considering roadside pollution accumulation. Zinc and Cu were more strongly associated with %C, than traffic load. Because vehicle combustion is also a carbon source, it is not obvious whether the metals and carbon are simply co-accumulating or whether the soil carbon in roadside soils may facilitate previously overlooked roles in sequestering metals on-site.


Rhodamine-propargylic esters for detection of mitochondrial hydrogen sulfide in living cells.
Flow cytometric detection of mitochondrial H2S was achieved with propargylic esters of rhodamine B which selectively react with H2S via cationic rhodamine-moiety directed thiolysis of the propargylic esters to give nonfluorescent rhodamine thio-spirolactone.


Capillary pressure during and after incremental venous pressure elevation in man.
1. The relationship between capillary pressure and venous pressure was investigated during incremental venous pressure elevation in seven healthy volunteers. Pressure was measured simultaneously at the apex of finger nailfold capillaries and in the dorsal vein of the ipsilateral hand. Elevation of venous pressure was accomplished by inflation of a sphygmomanometer cuff around the upper arm. 2. As venous pressure rose, apical capillary pressure (Pc) approached venous pressure (Pv). For changes in Pv greater than 20 mmHg, the increment in Pc was invariably less than the increment in Pv. 3. Above a cuff pressure of 20 mmHg, capillary pulse pressure amplitude (CPPA) tended to decline. At 50 mmHg cuff pressure, CPPA was lower than at baseline for all subjects. At baseline, CPPA was 4.2 +/- 2.0 mmHg (mean +/- S.D.) and at 50 mmHg it was 2.3 +/- 1.1 mmHg (P = 0.02). 4. In the period between 1 and 6 min following cuff release, both Pc and CPPA were lower than at baseline. (At baseline, Pc was 16.1 +/- 2.3 mmHg and following cuff release it was 11.2 +/- 1.5 mmHg (P = 0.02). At baseline, CPPA was 4.2 +/- 2.0 mmHg and following cuff release it was 1.8 +/- 1.1 mmHg (P = 0.03).) 5. Estimated changes in the ratio of pre- to postcapillary resistance (Ra/Rv), using arterial blood pressure (Pa) measured in the contralateral arm, and taking (Pa-Pc)/(Pc-Pv) to approximate to Ra/Rv, closely mirrored changes in CPPA.(ABSTRACT TRUNCATED AT 250 WORDS)


[What big eyes you have!].
A 4-year-old girl presented to our department with a pain and symptom-free elevated intraocular pressure (IOP) of 44 mmHg in both eyes and with enlarged corneal diameters. Megalocornea, buphthalmos and anterior megalophthalmos were discussed as differential diagnoses. Due to age-related normal morphological, functional and electrophysiological results of the optic nerve head and a very deep anterior chamber, anterior megalophthalmos was diagnosed. No topical treatment was initiated and close ophthalmological surveillance control was recommended. To the best of our knowledge megalophthalmus anterior has not up to now been described as associated with a pathological sensitivity to minor changes in lid muscle tension causing a sudden increase of IOD.


Bilateral bone-marrow examinations in small-cell anaplastic carcinoma of the lung.
Bilateral bone-marrow examinations from the posterior iliac crests were routinely performed as a pretreatment staging procedure in 89 consecutive patients with small-cell anaplastic carcinoma of the lung. Bone-marrow involvement was found in 20 patients (22.5%), in 9 (10.1%) only on one side, and in 11 (12.4%) on both sides. Aspiration was found to be significantly superior to biopsy, being positive in 25 examinations as compared with 14 positive biopsies. Compared with unilateral bone-marrow examination the positive findings increased by approximately 30%. Bilateral bone-marrow examinations are recommended in patients in whom the detection of bone-marrow metastases will have therapeutic implications.


Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome.
Cystic fibrosis (CF) is an autosomal recessive disorder of Cl(-) and Na(+) transport. The vast majority of CF patients have deleterious mutations in an epithelial Cl(-) channel called the CF transmembrane conductance regulator (CFTR). In contrast, defects in the epithelial Na(+) channel (SCNN1) have been associated with phenotypes dominated by renal disease (systemic pseudohypoaldosteronism type I and Liddle syndrome). We report two non-classic CF patients without CFTR mutations who have novel deleterious mutations in the beta-subunits of SCNN1 in the absence of overt renal disease.


Dislocations after use of dual-mobility cups in cementless primary total hip arthroplasty: prospective multicentre series.
The purpose of this study was to investigate the incidence of dislocation and specific complications of the dual-mobility cup. The arthroplasties involved 167 hips in 165 patients; 51 hips (30.5%) were in men and 116 (69.4%) were in women. The active articulation E1® dual-mobility cup (Biomet, Warsaw, IN, USA) was used, and the surgical approach was posterolateral in 120 hips and anterolateral in 47 hips. Four (2.3%) dislocations were observed. Mean time of dislocation was 30.5 days post-operatively. Three incomplete reductions occurred during closed reduction. When comparing parameters between dislocation and no-dislocation groups, there were no differences in patient and surgical parameters. However, all dislocations occurred in patients with femoral neck fractures and in the posterolateral approach group. The incidence of dislocation in total hip arthroplasty (THA) using a dual-mobility cup was acceptable, and cup diameter of the dislocation group was substantially larger than that of no-dislocation group. Based on clinical outcomes of our study, we conclude that the dual-mobility cup is a reliable option in THA, and further studies are necessary.


HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. II. Verification of the algorithm and determination of the relative immunogenicity of amino acid triplet-defined epitopes.
HLAMatchmaker is a computer algorithm that assesses human leukocyte antigen (HLA) compatibility at the structural level by intralocus and interlocus comparisons of polymorphic amino acid triplets in antibody-accessible sequences of HLA class I molecules. This program permits the identification of mismatched HLA antigens that share all of their polymorphic triplets with the patient's HLA antigens and, therefore, could be considered fully compatible. The validity of this algorithm has been verified by analyzing the antibody specificity patterns of 127 well-characterized sera (panel reactive antibody [PRA] > 80%) that had been screened by direct complement-dependent and/or anti-human globulin augmented lymphocytotoxicity testing with large HLA-typed cell panels. A 2 x 2 table-based Chi-square analysis program was applied to determine positive and negative correlations between serum reactivity and the presence HLA triplets assigned from the HLA types in the cell panel. The results indicate that high PRA patients do not produce antibodies to shared triplets on mismatched HLA antigens. Moreover, this serum analysis has permitted the identification of triplets with different degrees of immunogenicity as indicated by the frequencies of positive and negative correlations of serum reactivity with the HLA-typed cell panel. Mismatching for triplets with low immunogenicity provides further opportunities for identifying donors with acceptable HLA mismatches for highly sensitized patients.


Introduction to a special section on Explaining Positive Adaptation of Immigrant and Minority Youth across Cultures.
This special section on "Explaining Positive Adaptation of Immigrant and Minority Youth across Cultures" is the result of an expert meeting organized by the Society for Research in Child Development (SRCD), the European Association of Developmental Psychology (EADP), and the European Association for Research on Adolescence (EARA). The aim of this special section was to bring together empirical studies and expert commentaries on a pressing topic of global importance, and to explore intersections between the fields of acculturation and positive youth development. From these contributions, several major challenges were identified. These included the need for greater attention to the strengths and adaptation of immigrant adolescents (i.e., to include a positive youth development framework in acculturation research and theory), the differentiation and intersections between acculturative processes and normative developmental challenges, the evolution acculturation theory, the need to better understand contact between multiple groups, the consideration of context-dependency and dynamic nature of acculturative processes.


ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure.
Premature ovarian failure (POF) is a complex and heterogeneous disorder that is influenced by multiple genetic components. Numerous candidate gene studies designed to identify POF susceptibility loci have been published, but most positive findings have not been confirmed in follow up studies. We sought to determine if sequence variants previously associated with age at natural menopause (AANM) or early menopause (EM) contribute as well to genetic susceptibility to POF. Our study was performed on 371 unrelated idiopathic women with POF and 800 women controls, all Chinese Han. Thirty six SNPs from previous genome-wide association studies (GWAS) responsible for AANM or EM and 3 additional SNPs in ESR1, and 2 additional SNPs in PTHB1 were tested using the Sequenom MassARRAY iPLEX platform for genotyping. Three SNPs - rs2278493 in HK3, rs2234693 in ESR1 and rs12611091 in BRSK1 - showed nominally significant association with POF. Thus, a plausible relationship could exist between ESR1, BRSK1, HK3 and POF. This largest association study undertaken to determine correlation between POF and AANM/EM revealed three significant SNPs (rs2278493, rs2234693, and rs12611091). All are associated with not only AAWM and EM but also POF. Insights into shared genetic susceptibility between POF and AANM/EM will provide novel entry points for unraveling genetic mechanism involved in ovarian reserve and oocyte aging processes.


Blocking of TRPV-1 in the parodontium relieves orthodontic pain by inhibiting the expression of TRPV-1 in the trigeminal ganglion during experimental tooth movement in rats.
Orthodontic pain has confused the orthodontics for a long time, and recent research demonstrated that transient receptor potential vanilloid type 1 (TRPV1) had crucial functions in transduction of painful stimuli. The present research investigated the analgesia effects of the blocking TRPV1 on orthodontic pain during experimental tooth movement. Under challenge with experimental tooth movement, the expression of TRPV1 in the parodontium was increased in a time-dependent and force-dependent manner. And treatment with selective TRPV1 antagonist AMG-9810 in the parodontium reduced the expression of TRPV1 in the trigeminal ganglion (TG) and decreased the secretion of IL-1β in the gingival crevicular fluid. Furthermore, AMG-9810 could relieve orthodontic pain arising from experimental tooth movement in rats. We suggest that TRPV1 both in the parodontium and trigeminal ganglion are involved in orthodontic pain, and TRPV1 in the parodontium influence on orthodontic pain through reducing the expression of TRPV1 in trigeminal ganglion. Our finding may help to develop strategies for relieving orthodontic pain after orthodontics.


Composite pulsed field gradients with refocused chemical shifts and short recovery time.
An improved self-compensating pulsed field gradient (PFG) technique that combines antiphase gradient pairs with broadband frequency-modulated 180 degrees pulses is proposed. The antiphase gradient pairs lead to superb system recovery. In addition, evolution under chemical shift and heteronuclear J coupling are refocused during the PFG, making it appear effectively instantaneous. This new approach makes it possible to obtain high-resolution phase-sensitive 2D spectra for the PFG version of many experiments such as COSY, DQF-COSY, and HSQC without adding extra compensating delays or pulses. While reasonable suppression of unwanted magnetization is achieved, this method also gives satisfactory retention of desired signals. As a bonus, the field-frequency lock is not perturbed during the experiments.


Undernutrition and elevated blood lead levels: effects on psychomotor development among Jamaican children.
We examined whether or not the effect of elevated blood lead levels on children's psychomotor development was modified by their nutritional status. Anthropometry, developmental quotients (DQs), blood lead levels and haemoglobin were measured in lead exposed and unexposed children with different levels of nutritional status. Social background and maternal height and verbal intelligence were also measured. Testers, anthropometrists and interviewers established reliabilities with a trainer before the study began. Children were from two suburban areas in Kingston, Jamaica. All measurements on the children were carried out at a research unit. Social background and maternal measurements were carried out at the children's homes. The exposed group comprised 58 children (3-6 years) attending the same preschool which was situated in a lead contaminated environment. The unexposed group comprised 53 children attending a nearby preschool without lead contamination. The exposed children had significantly higher blood lead levels and lower DQs, and their homes had poorer facilities than the unexposed children. The deficit in DQ was greater (10.6 points) among children with weight for height less than -1 SD (National Center for Health Statistics references) than among better nourished children (2 points). Undernourished children exposed to lead may have more serious developmental deficits than better nourished children.


Deoxygenation of nitrosoarene by N-heterocyclic carbene (NHC): an elusive Breslow-type intermediate bridging carbene and nitrene.
N-Heterocyclic carbene (NHC) activates and deoxygenates nitrosoarene (ArNO) to afford arylnitrene (ArN), thereby portraying a fundamental route connecting two 6e- species. A combination of spectroscopic and computational studies suggests that the interaction of ArNO with NHC affords a transient 2,2'-diamino imine-N-oxide as a key intermediate in ArNO deoxygenation.


Associations of physical activity, sedentary behavior and sleep duration with anxiety symptoms during pregnancy: An isotemporal substitution model.
Studies have evidenced the close relationships between movement behavior [physical activity (PA), sedentary behavior (SB), and sleep duration)] and anxiety. Capturing 24 h of these maternal movement behaviors during pregnancy is necessary to understand their relationships. In a cross-sectional study design, a total of 946 prenatal women filled Pregnancy Physical Activity Questionnaire-Chinese version, Pregnancy-Related Anxiety Questionnaire, and 7-item Generalised Anxiety Disorders scale between May 2020 and April 2021. An Isotemporal Substitution Model was used to estimate the per-hour effects of replacing one behavior. Replacing moderate-to-vigorous PA(MVPA), light PA (LPA), or SB with sleep could reduce both general and pregnancy-specific anxiety (LPA, B = -0.61∼-0.37, P ≤ 0.01; MVPA, B = -0.35, P = 0.03; SB, B = -0.45∼-0.34, P ≤ 0.01). Replacing SB with MVPA could reduce pregnancy-specific anxiety in the group without adequate sleep duration (SB, B = -0.62,95%CI = -1.13∼-0.17). As for the types of PA, replacing household, occupational or inactivity PA with transportation PA or sleep duration reduced general anxiety (household PA: B = -0.51, 95%CI = -0.73∼-0.29, P < 0.001; occupational PA: B = -0.48, 95%CI = -0.69∼-0.27, P < 0.001; inactivity: B = -0.45, 95%CI = -0.68∼-0.24, P < 0.001). Replacing household PA, occupational PA, or inactivity with transport PA was associated with improved general anxiety (household: B = -0.33, 95%CI = -0.64∼-0.03, P = 0.29; occupational PA: B = -0.31, 95%CI = -0.62∼-0.003, P = 0.35; inactivity: B = -0.28, 95%CI = -0.56∼-0.01, P = 0.33). A cross-sectional study design and self-reported measurement limits the reliability of study. Longer time spent in sleep and MVPA may mitigate the negative effects of SB on anxiety.


Significant variability in 10-year cumulative radiation exposure incurred on different surveillance regimens after surgery for pT1 renal cancers: yet another reason to standardize protocols?
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The topic of radiation safety has been hotly debated not only in the mainstream media, but also in the urological literature. Radiation exposure has been examined in urological diseases such as testicular cancer and urinary stone disease, with resultant recommendations for modifying surveillance imaging. Radiation risk with respect to surveillance regimens after RCC surgery has yet to be examined. We consider this largely to be a result of RCC typically affecting older patients in whom cumulative radiation exposure may be less of a consideration. However, current population data emphasize that RCC diagnosis and therapy have an increasing impact upon younger patients with a longer life expectancy after treatment. Therefore, radiation considerations in this cohort of patients may be significant. To determine the 10-year cumulative radiation exposure incurred on different surveillance imaging protocols after surgery for pT1 renal cell carcinoma (RCC). The PubMed database was queried for surveillance protocols after surgery for RCC. There were two index lesions that were selected: (i) pT1a 3 cm, Fuhrman 2, clear cell and (ii) pT1b 5 cm, Fuhrman 3, clear cell. Exposure for single-phase chest computed tomography (CT), abdominal CT and chest X-ray were 7, 8 and 0.1 mSV, respectively. Calculations assumed biphasic CT scans, negative surgical margins and an Eastern Cooperative Oncology Group status of ≤1. In total, 12 published surveillance regimens were identified. For the first lesion (pT1a, clear cell, Fuhrman 2), we observed significant variability in the proposed regimens, ranging from no imaging to several CT scans of both chest and abdomen. Cumulative incurred radiation exposure for this index patient was in the range 0-102 mSv (mean, 34 mSv). When considering the second tumour (pT1b, clear cell, Fuhrman 3), all studies recommended some form of follow-up imaging, although regimens once again varied from annual chest X-ray to multiple CT scans of chest and abdomen. Cumulative incurred radiation exposure in this scenario was in the range 0.5-450 mSv (mean, 89 mSV). Surveillance protocols after surgery for early-stage RCC result in widely divergent levels of radiation exposure. Such considerations are increasingly paramount given concerns of radiation-induced secondary malignancies and present another reason to standardize follow-up protocols.