Heart rate variability is associated with glycemic status after controlling for components of the metabolic syndrome.
To evaluate the relationship between heart rate variability (HRV) and glycemic status after controlling for metabolic syndrome (MetS) in a healthy working cohort. A growing body of literature suggests that reduced HRV, a physiological marker of autonomic nervous system activity, is associated with various pathological conditions including glycemic disorders and cardiovascular diseases. The extent to which this association is confounded by other more traditional markers of cardiovascular risk, such as MetS, is unclear. We recruited 2441 study participants (age 17-65) employed at three sites of an airplane manufacturing plant in southern Germany. All subjects underwent medical examination, blood sampling, and 24-hour ambulatory heart rate recording while on their normal work routine. Indices of HRV were determined from readings made throughout the 24-hour examination period, those during either the day or night only as well as a night to day ratio. Pearson correlations and multivariate-adjusted partial correlation coefficients (PCCs) were calculated. Pearson correlations suggested inverse associations between HRV measurements and glycemic status (e.g. High frequency r=-0.07, p<0.001; SDNN r=-0.09, p<0.001). After multivariate adjustment of all other components of MetS (triglyceride, blood pressure, waist circumference, high density lipoproteins), medical and demographic variables, these associations persisted (e.g. High frequency PCC=-0.05, p<0.001; SDNN PCC=-0.06, p<0.001). We confirm a negative correlation between HRV and glycemic status that appeared to be almost linear in a large cohort of healthy workers. Importantly, we showed that this association was independent of potential confounders, especially all of the MetS components and inflammation.


[Intracardiac echocardiography and percutaneous closure of atrial septal defects in adults].
Today, the transcatheter treatment of atrial septal defects using an occluding device is a safe and effective therapeutic approach. Recently, intracardiac echocardiography has been developed as an alternative to transesophageal echocardiography for guiding these procedures. We describe our experience with intracardiac echocardiography during the percutaneous closure of atrial septal defects in adult patients. This retrospective study involved 52 patients with atrial septal defects (77% with an ostium secundum defect and 23% with patent foramen ovale) who underwent transcatheter closure using an Amplatzer device under intracardiac echocardiographic guidance and without the need for general anesthesia or orotracheal intubation. Clinical follow-up was carried out at 24 hours, and 6 and 12 months, and with transthoracic echocardiograhy at 24 hours and 6 months. The procedure was successful in 51 (98%) of the 52 patients. No serious complication was recorded. Three patients suffered paroxysmal atrial fibrillation in the following weeks, which resolved with medical treatment. At 6 months, echocardiographic examination confirmed that there was no residual shunting across the atrial septum in any patient. Intracardiac echocardiography provided accurate anatomical information about the atrial septum and other intracardiac structures. The technique's use during the transcatheter closure of atrial septal defects using an occluding device was straightforward. In addition, the procedure was less uncomfortable for patients than transesophageal echocardiography because there was no need for general anesthesia or orotracheal intubation.


5-Fluorouracil versus mitomycin C as adjuncts to conjunctival autograft in preventing pterygium recurrence.
To compare the efficacy of 5-fluorouracil (5-FU) with mitomycin C (MMC) in preventing pterygium recurrence when used as an adjuvant following pterygium excision with conjunctival autograft. Low-dose MMC combined with conjunctival autograft is an effective treatment for preventing recurrence following pterygium excision, but safety, cost, and availability limit its use in developing countries. There is a paucity of data on the efficacy of 5-FU when used in Africa as an adjuvant to conjunctival autograft following pterygium excision. This is a randomized controlled prospective trial using either 50 mg/ml 5-FU or 0.01% MMC. Eighty eyes of 80 subjects were studied. Forty-six subjects with a mean age 49.8 ± 13.8 years were treated with 5-FU (USD 13.0 per unit), while 34 patients with a mean age 51.9 ± 12.1 years were treated with MMC (USD 20.0 per unit). There was no significant difference in mean age between the two groups (p = 0.48). The ratio of male to female patients in both groups was similar at 0.92:1 for the 5-FU group and 1:1 for the MMC group (p = 0.85). Mean follow-up period was 35.2 ± 29.1 weeks. Recurrence rate in the 5-FU group was 8.7% compared to 11.8% in the MMC group (recurrence risk ratio = 0.71, 95% CI 0.17-3.1, p = 0.7). One patient from the MMC-treated group had corneoscleral melting. Other complications were mild and not sight threatening. In the prevention of pterygium recurrence, 5-FU appears to compare favorably with low-dose MMC when used as an adjuvant following pterygium excision and conjunctival autograft. Further studies are required to assess the long-term effect of using 5-FU in such cases.


Spontaneously active suppressive cells in canine peripheral blood.
The phenomenon of the unusually high spontaneous suppressive activity of cells in peripheral blood of dogs was analysed. The m/c (mitomycin C)-treated population of peripheral blood leucocytes (PBL) contained cells able to reduce the responsiveness of autologous cells by 48 +/- 15% (P less than 0.01) and their activity was not indomethacin dependent. Thoracic duct lymphocytes (TDL) did not reduce the response of PBL to PHA, neither did cell crowding. The supernatants from 24-h cultures of m/c-treated PBL did not affect the response to PHA, and parallelly precultured cells inhibited the proliferation of PBL to a lesser degree (24 +/- 9%) than the fresh cells (50 +/- 16%, P less than 0.05). Addition of m/c-treated polymorphonuclear cells at PMN to PBL ratios of 1:4 and 1:1 progressively inhibited PBL reactivity to PHA, from 29.5 +/- 3.5% to 68.5 +/- 9%, respectively, and the supernatants from 24-h cultures of PMN reduced the proliferation by 48 +/- 2.8%. The neutrophil-derived inhibitory factor(s) was non-cytotoxic and reduced the formation of blasts to 61.5 +/- 3.5% of the control values. These results indicate that dog PBL from Lymphoprep gradient contain a population of non-recirculating, short-lived, spontaneously suppressive cells, mainly PMN, which modulate T cell reactivity in vitro, suggesting that neutrophils may be able to exert a regulatory effect in vivo.


Effect of dietary chloride content on the elimination of bromide by dogs.
The effect of dietary chloride content (0.2, 0.4 and 1.3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg-1) was evaluated in normal beagles. Increasing the dietary chloride content from 0.2 to 1.3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 +/- 22 days to 24 +/- 7 days. The mean area under the concentration curve (AUC) for dogs fed 1.3 per cent chloride was significantly smaller than the AUC for dogs fed 0.2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (Cmax) or on the time (Tmax) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg-1 of bromide were significantly lower in dogs fed 1.3 per cent chloride (310 +/- 150 mg litre-1) than in dogs fed 0.2 per cent chloride (1950 +/- 1140 mg litre-1). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1.3 per cent chloride (43 +/- 13 mg kg-1) were almost twice as high as the dose estimated for dogs fed 0.4 per cent chloride (22 +/- 3 mg kg-1) and nearly three times as high as the dose estimated for dogs fed 0.2 per cent chloride (15 +/- 4 mg kg-1). These differences were statistically significant (P = 0.002).


Management of retropharyngeal lymph node metastasis in oral cancer.
Retropharyngeal lymph node (RPLN) metastasis is extremely rare, and prognosis is significantly poor in oral cancer. We retrospectively examined the management of RPLN metastases in oral cancer. A total of 1247 patients with oral cancer were treated at our department from January 2002 and December 2016. Among these patients, 374 (30%) had histologically positive lymph node metastases. Of these, 15 patients (1.2%) were diagnosed with RPLN metastases. We evaluated the diagnostic period, size, recurrence pattern, laterality, treatment, and therapeutic outcomes. The Kaplan-Meier method was used to determine overall survival (OS) among the RPLN metastasis group, cervical lymph node (CLN) metastases group, and treatment methods group for RPLN metastases. One patient had RPLN involvement at the initial treatment, and RPLN involvement in other patients was found subsequently. The mean duration in confirming RPLN metastases was 228 days (range, 50-867 days). Surgical therapy was performed in 5 patients, chemoradiotherapy in 7 patients, and best supported care (BSC) in 3 patients. The cumulative 5-year OS rate for the RPLN metastasis group (n = 15) was 38.1%, compared with the rate of 71.3% for the CLN group (n = 359). Regarding the therapeutic approach for RPLN metastases, OS rates were 80.0% (n = 5) in the surgical therapy group, 28.6% (n = 7) in the chemoradiotherapy group, and 0% (n = 3) in the BSC group. Early detection and surgical treatment of RPLN metastases are associated with increased survival rate in oral cancer.


Statistical equating with measures of oral reading fluency.
Recent research on curriculum-based measurement of oral reading fluency has revealed important issues in current passage development procedures, highlighting how dissimilar passages are problematic for monitoring student progress. The purpose of this paper is to describe statistical equating as an option for achieving equivalent scores across non-parallel reading passages. The psychometric and design properties of words-correct scores are examined, and the requirements of traditional equating methods are discussed. Simulated and empirical words-correct scores are used to demonstrate the steps in the equating process and the situations in which each method is most appropriate.


A least-squares algorithm for the equiform transformation from spatial marker co-ordinates.
The present paper describes an algorithm for estimating the translation vector and the rotation matrix of a moving body from noisy measurements on the spatial co-ordinates of at least three non-collinear markers. A sensitivity analysis of the estimated parameters and of the helical axis is presented in terms of characteristics of the marker distribution. The implementation of the proposed algorithm in a FORTRAN-subroutine is appended.


Universal screening for infant hearing impairment: simple, beneficial, and presently justified.
In a recent article, Bess and Paradise (Pediatrics 93 (1994) 330-334) rejected the recommendation of the National Institutes of Health that all infants be screened for hearing loss on being released from their birthing hospital. This article responds to their objections with data from the literature and operational newborn hearing screening programs. These data show that universal newborn hearing screening is practicable, effective, cost-efficient, and safe, and concludes that such programs should be implemented without further delay.


How Valid Is Tomographic Ultrasound Imaging in Diagnosing Levator and Anal Sphincter Trauma?
Three-/four-dimensional translabial ultrasound (US) is increasingly used to image the levator ani and anal sphincters, especially in the form of tomographic US. The aim of the study was to evaluate the validity of these published methods. This work was a retrospective analysis of datasets of 172 nulliparous women who attended 2 tertiary urogynecologic centers for symptoms of pelvic floor dysfunction between June 2012 and September 2016. All patients had a standardized interview, clinical examination, and 4-dimensional translabial US examination. An evaluation of volume data was performed by the first author, who was blinded against all clinical data, including parity. An assessment for levator avulsion and anal sphincter defects was performed using stored US volume data. Data sets of 162 and 153 nulliparous women were available for levator and anal sphincter assessments, respectively. On the assessment by the first author, a complete avulsion was diagnosed in 3 nulliparas. On a review by 2 senior authors, 1 was judged as positive and the other 2 as normal. On the sphincter assessment, 2 significant external anal sphincter defects were detected. On the review, 1 was judged as false-positive. The second was judged as highly abnormal by all authors. Therefore, 1 nullipara each was diagnosed with avulsion and a significant external anal sphincter defect. Published diagnostic criteria for levator avulsion and external anal sphincter trauma on tomographic US imaging are highly unlikely to result in false-positive findings. This finding supports the clinical validity of this method.


Hyperlipidemia: a novel etiologic factor in deep vein thrombosis.
The possible association of hyperlipidemia and deep vein thrombosis (DVT) was investigated in 59 consecutive patients. The incidence of hyperlipidemia, judged by the value of serum total cholesterol and triglyceride, was unexpectedly high (overall 59%, high total cholesterol alone 25%, high triglyceride alone 9%, combined 25%), as compared with 29% of the control (p < 0.001). The idiopathic DVT patients (without known etiologic factors) had a higher incidence of hypercholesterolemia (63%) than the normal subjects (20%, p = 0.0002). The idiopathic DVT patients showed higher total cholesterol level of 255 +/- 72 mg/dl than that of 194 +/- 36 in the control subjects (p < 0.0001). And 67% of the idiopathic DVT patients were hyperlipidemic. Thereby, hyperlipidemia may be an important etiologic factor in DVT, which has not been recognized previously. The low incidence of DVT in Asians may, thus, be attributable to their lower cholesterol level.


Nonylphenol photodegradation by novel ternary MIL-100(Fe)/ZnFe2O4/PCN composite under visible light irradiation via double charge transfer process.
Nonylphenol (NP) residues, as a typical endocrine disrupting chemical (EDC), frequently exist in sewage, surface water, groundwater and even drinking water, which poses a serious threat to human health due to its bioaccumulation. In order to remove NP, a series of MIL-100(Fe)/ZnFe2O4/flake-like porous carbon nitride (MIL/ZC) was synthesized through in-situ synthesis at room temperature. High performance of ternary MIL/ZC is used to degrade NP under visible light irradiation. The results show that 30MIL/ZC2 (20 wt.% ZnFe2O4) ternary composite had the best photocatalytic activity (99.84%) when the dosage was 30 mg. Further mechanism analysis shows that the excellent photocatalytic activity of 30MIL/ZC2 could be ascribed to the double charge transfer process between flake-like porous carbon nitride (PCN) and other catalysts in the ternary heterojunction, and the separation of photogenerated electron-hole pairs was more effective. In addition, the 30MIL/ZC2 also showed high stability after five cycles of the photodegradation reaction. Furthermore, the active substance (•O2-) was considered to be the main active substance in the NP degradation process. Based on the research results, the possible photocatalytic reaction mechanism of 30MIL/ZC2 ternary composite was proposed and discussed in detail.


The role of electron microscopy in the diagnosis of unusual peripheral lung tumors.
The ultrastructure of the lung provides a cytomorphologic basis for the identification of unusual pulmonary neoplasms or unusual histologic variants of more common pulmonary lesions. Comparison of tumor cells with bronchioloalveolar lining cells and with pleural components has aided in the diagnosis of a spindle cell variant of a peripheral neuroendocrine cell tumor (carcinoid) and a tumor composed of cells resembling bronchioloalveolar epithelium (sclerosing hemangioma of lung).


Identification of brain structures and blood vessels by conventional ultrasound in rats.
Ultrasound is a safe, non-invasive and affordable imaging technique for the visualization of internal structures and the measurement of blood velocity using Doppler imaging. However, despite all these advantages, no study has identified the structures of the rat brain using conventional ultrasound. A 13 MHz high frequency transducer was used to identify brain structures in the rat. The enlargement of the transcranial window was performed gradually using the ultrasound directly on the skin of the animal, then against the skull, then through a delimited craniotomy and finally through a complete craniotomy. Our results showed that ultrasound allowed the identification of cerebral ventricles and subarachnoid cisterns, as well as the analysis of real-time monitoring of cerebral blood flow in the main brain arteries of the rat. Ultrasound is a tool with the potential to identify brain structures and blood vessels. In contrast to MRI, transcranial ultrasound is a fast, non-invasive, well tolerated and low-cost method and can be done at the bedside. In the present study, we described an atlas of the main brain structures as well as the main vasculature in the rat using ultrasound. This technique could be applied in animal models of various neurological diseases.


Phosphorus fractions and the effect of pH on the phosphorus release of the sediments from different trophic areas in Taihu Lake, China.
The sediment characteristics, different phosphorus (P) fraction concentrations and the effect of pH on P release were investigated in a shallow eutrophic lake in China. The total phosphorus (TP) concentrations in the sediments ranged greatly from 420 to 3408 mg kg(-1) and inorganic P (IP) was the main P fraction. For the heavily eutrophic sediment, IP mainly consisted of NaOH-P; while for the mesotrophic sediments, IP mainly consisted of HCl-P. The rate of P release decreased as pH increased from 2 to 6. But it increased as pH increased from 8 to 12. It is suggested that high pH promoted the release of NaOH-P, and low pH promoted the release of HCl-P, and there was no P release occurring in the neutral condition.


Retinoic acid induces translocation of protein kinase C (PKC) and activation of nuclear PKC (nPKC) in rat splenocytes.
Retinoic acid (RA), a vitamin A metabolite, has marked effects on growth of normal and malignant cells; however, the exact mechanism of action remains unclear. The effect of two RA analogs, 13-cis-RA and all-trans-RA, on transmembrane signalling processes was investigated in rat splenocytes. Treatment of rat splenic cells with these retinoic acid analogs resulted in translocation of protein kinase C (PKC) from the cytosol to the membrane. Previous studies have described nuclear RA receptors (RARs and RXRs) for several species and the biologic activity of RA has been shown to be mediated by specific interaction with these nuclear receptors. Thus, activation of nuclear pool(s) of protein kinase C (nPKC) by RA analogs was also studied. Rat splenocyte nuclei pure by enzymatic and electron microscope criteria demonstrated a biphasic pattern of bell-shaped curves for both cis- and trans-RA with maximum statistically significant peak of phosphate incorporation into endogenous substrates at 10(-16) M cis-RA and 10(-16)-10(-17) M trans-RA. A monoclonal antibody to PKC and the PKC inhibitors, H-7, sphingosine, and staurosporine, blocked the RA-stimulated nuclear phosphorylation. The ability of RA to activate cell membrane PKC resulting in an increase in particulate PKC activity correlates well with the activation of nPKC since the particulate fraction would include nuclear enzyme systems. This ability of RA to activate nPKC and possibly affect the growth status of a cell may provide a missing link to our understanding of the cellular sites of action for this vitamin.


Trimester-Specific and Total Gestational Weight Gain in Two Consecutive Pregnancies.
This retrospective study aimed to characterize trimester-specific and total gestational weight gain (GWG) over the course of two consecutive pregnancies, as well as maternal determinants associated with interpregnancy weight change (IPWC) and excessive GWG in the second pregnancy. We analyzed the electronic medical records of women who delivered their first two consecutive infants at term between 2001 and 2017. Weight gain trajectories differed between the first and second pregnancy for the 1497 women included in this study, with lower second- and third-trimester weight gain in the second pregnancy. Respectively, 53% and 41% of women had excessive GWG in the first and second pregnancies, with a higher proportion of excessive GWG found in women with a higher body mass index (BMI). Most women (55%) experienced interpregnancy weight gain. Maternal determinants of IPWC were BMI before first pregnancy, first-trimester and total GWG in the first pregnancy, and interpregnancy interval (P < 0.0001). Maternal risk factors associated with excessive GWG in the second pregnancy were excessive total GWG in the first pregnancy (OR 6.23; 95% CI 4.67-8.32), interpregnancy weight gain (OR 1.58; 95% CI 1.19-2.09), and interpregnancy interval (OR 1.18; 95% CI 1.07-1.29) as well as BMI before the second pregnancy (OR 1.04, 95% CI 1.02-1.07). Weight gain trajectories differ between consecutive pregnancies. GWG in the first pregnancy is a key determinant for IPWC and GWG in the second pregnancy.


[A new image-processing system designed for densitometry and pattern analysis of microscopic specimen. Application to the automated recognition and counting of cells in the various phases of the mitotic cycle (author's transl)].
A new image analysing system, designed for microphotometric measurement and pattern recognition has been applied in the discrimination of cells from the various phases of the mitotic cycle. The data acquisition procedure is controlled by a programmable electronic unit and involves the combination of the shifting of the microscope moving stages and the scanning of the successive fields by a mechanical device. The data processing is achieved by a computer. The preliminary results we obtained have shown that such a system allows the automatic recognition and counting of the M, G1, S and G2 cells as also the G0 resting cells. The most useful parameters of the cell proliferation kinetics are thus obtained from a single specimen of a cell population.


Physical training under the influence of beta-blockade in rats. II. Effects on vascular reactivity.
Rats were treated by daily swimming or running exercises for 7 weeks. One group of rats was also trained under the influence of propranolol, while another group received daily propranolol injections only. The rat groups trained without beta blockade maintained a higher tail skin temperature when exposed to 5 degrees C after the 7-week training period. This phenomenon was not observable in the animals having received their training under the influence of beta-blockade. Both rat groups trained without beta-blockade showed increased vasodilatatory response to isoprenaline, as judged from a higher elevation of the tail skin temperature in response to the drug. This response was absent in the animal group having performed its training periods under the influence of propranolol. After the injection of phenylephrine the trained rats had a higher tail skin temperature than did the controls or propranolol-treated rats. The present results suggest an elevated sensitivity of beta 2-adrenoceptors and/or decreased sensitivity of alpha-adrenoceptors in trained rats. It is suggested that for the development of these changes repeated activation of the sympathetic nervous system by exercise periods is needed. That is why they are preventable if the training is performed under the influence of beta-blockade.


User fees, demand for children's health care and access across income groups: the Philippine case.
This paper examines the potential effects of user fees on the demand for child health care across income groups. A mixed/conditional logit model of provider choice is estimated using national data from the Philippines. The model explicitly allows for price elasticity to be dependent upon income. The results indicate that price plays a significant role in the demand for child health care and that medical care demand for poorer children is substantially more price sensitive than it is for richer children. The notion that user fees are regressive is therefore supported.


Synthesis, structural and magnetic studies of an isostructural family of mixed 3d/4f tetranuclear 'star' clusters.
DC magnetic studies on new 'star' clusters of formula [Mn(3)Ln(acac)(6)(tea)(2)][Mn(acac)(3)] (Ln = Gd (1) and Dy (2)) and [Fe(3)Ln(acac)(6)(tea)(2)] (Ln = Gd (3) and Dy (4)) show that all cases display weak coupling, with compounds 3 and 4 displaying ferromagnetic J(LnFe) coupling, 3 having a S = 11 ground state.


Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects.
The purpose of the present study was to examine 10-year cardiovascular morbidity and mortality in patients with newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic control subjects and to evaluate the effects of general risk factors, plasma insulin, urinary albumin excretion, lipoprotein abnormalities characteristic of Type 2 diabetes and the degree of hyperglycaemia in diabetic patients on cardiovascular mortality. Furthermore, the extent to which the above-mentioned factors could contribute to the excessive cardiovascular mortality observed in diabetic patients was examined. In the years 1979-1981, altogether 133 (70 men, 63 women) newly-diagnosed patients with Type 2 diabetes and 144 (62 men, 82 women) non-diabetic control subjects aged 45-64 years were studied. Both groups were re-examined in the years 1985-1986 and 1991-1992. The impact of different factors on cardiovascular mortality was examined by univariate analyses after adjustment for age and sex and by multiple logistic regression analyses. The age-standardized total and cardiovascular mortality rates were substantially higher in diabetic men (17.8 and 15.0%, total and cardiovascular mortality, respectively p = 0.06 and NS) and women (18.5 and 16.6%, p < 0.01 for both) than in non-diabetic control men (5.2% both total and cardiovascular mortality) and women (4.2 and 2.2%). Cardiovascular mortality was not related to the treatment modality (diet, oral drugs, insulin) at 5 years from diagnosis. Use of diuretics, beta-blocking agents or their combination at baseline did not make a significant contribution to cardiovascular mortality either. In multiple logistic regression analysis on diabetic patients, age, LDL triglycerides, smoking, blood glucose and ischaemic ECG at baseline had independent associations with cardiovascular mortality. Interestingly, urinary albumin excretion rate measured at 5-year examination also predicted 10-year cardiovascular mortality after adjustment for the effects of major risk factors including lipoprotein abnormalities, but its predictive power reduced to a nonsignificant level when the effect of plasma glucose was taken into account. The relative risk of cardiovascular mortality associated with diabetes was 8.2 after allowing for age alone, but it declined to 3.7 when all contributing factors from the baseline examination (except blood glucose) were taken into account. In conclusion, the present results indicate that LDL triglycerides and/or other changes in lipoprotein composition characteristic of Type 2 diabetes and manifesting as elevated serum triglycerides are atherogenic and they strongly predict increased cardiovascular mortality.(ABSTRACT TRUNCATED AT 400 WORDS)


Clinical features of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in patients with cancers.
The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH. All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined. Overall, 250 patients (median age 71 years; range 30-87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5-38.0; P = 0.0002) and ipilimumab-nivolumab combination therapy (OR 61.2; 95% CI 7.9-1275.3; P < 0.0001). Immune-mediated hepatotoxicity occurred in 9.5% of patients treated with ICIs. Appropriate therapeutic interventions are important to avoid affecting the patient's prognosis, and accurate diagnosis of IMH is essential for this purpose. The frequency of IMH varied according to the type of cancer and the drug used, and was significantly higher in patients with malignant melanoma and in patients given ipilimumab-nivolumab combination therapy.


Author Correction: Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope.
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20098-z.


Effects of central and peripheral injections of apelin on fluid intake and cardiovascular parameters in rats.
Previous studies have indicated that apelin, a novel peptide suggested to have some actions related to angiotensin peptides, has either a dipsogenic or an antidipsogenic effect and either increases or decreases blood pressure. The present study attempts to provide replication or understanding of these disparate effects. Neither central (lateral or third cerebral ventricle) nor peripheral (intravenous) administration of apelin induced water intake in sated rats, nor did it decrease water intake in deprived rats. It also had no effect on sodium appetite. Peripherally injected apelin had a hypotensive action in anesthetized rats, but had no consistent effect in awake, unrestrained rats. We conclude that apelin does not have reliable or robust effects on fluid intake or blood pressure in Sprague-Dawley rats under normal conditions, but discuss the possibility for a role of apelin in fluid homeostasis in selected physiological states.


When meaningless symbols become letters: neural activity change in learning new phonograms.
Left fusiform gyrus and left angular gyrus are considered to be respectively involved with visual form processing and associating visual and auditory (phonological) information in reading. However, there are a number of studies that fail to show the contribution of these regions in carrying out these aspects of reading. Considerable differences in the type of stimuli and tasks used in the various studies may account for the discrepancy in results. This functional magnetic resonance imaging (fMRI) study attempts to control aspects of experimental stimuli and tasks to specifically investigate brain regions involved with visual form processing and character-to-phonological (i.e., simple grapheme-to-phonological) conversion processing for single letters. Subjects performed a two-back identification task using known Japanese, and previously unknown Korean, and Thai phonograms before and after training on one of the unknown language orthographies. Japanese subjects learned either five Korean or five Thai phonograms. Brain regions related to visual form processing were assessed by comparing activity related to native (Japanese) phonograms with that of non-native (Korean and Thai) phonograms. There was no significant differential brain activity for visual form processing. Brain regions related to character-to-phonological conversion processing were assessed by comparing pre- and post-tests of trained non-native phonograms with that of native phonograms and non-trained non-native phonograms. Significant differential activation post-relative to pre-training exclusively for the trained non-native phonograms was found in left angular gyrus. In addition, psychophysiologic interaction (PPI) analysis revealed greater integration of left angular gyrus with primary visual cortex as well as with superior temporal gyrus for the trained phonograms post-relative to pre-training. The results suggest that left angular gyrus is involved with character-to-phonological conversion in letter perception.


The comparison of MTA, Geristore® and Amalgam with or without Bioglass as a matrix in sealing the furcal perforations (in vitro study).
The objective of this in vitro was to assess the sealing ability of MTA, Geristore®, and amalgam with and without Bioglass as a matrix used to repair furcation perforations in mandibular molars by using dye penetration. One hundred mandibular molars were randomly divided into six experimental groups. Five teeth with perforation were used as positive control while five teeth without perforation were used as negative control group. Furcal perforations were made in the teeth. Perforations were repaired with amalgam in group 1, amalgam and Bioglass in group 2, MTA in group 3, MTA and Bioglass in group 4, Geristore® in group 5, and Geristore® and Bioglass in group 6. All repairing materials were allowed to set for 72 h. Leakage at the repaired sites was then evaluated using dye penetration and clearing technique under stereomicroscope. The perforations repaired with MTA and Geristore® leaked significantly less than amalgam (p = 0.000). Bioglass reduced sealing ability of MTA and Geristore® significantly (p = 0.000, p = 0.019), while reduced the sealing ability of amalgam insignificantly (p = 0.78). MTA and Geristore® have shown acceptable sealing ability in furcal perforation in comparison to amalgam while Bioglass as a matrix beneath them has reduced their sealing ability.


Splitting of the 520-kilometer seismic discontinuity and chemical heterogeneity in the mantle.
Seismic studies indicate that beneath some regions the 520-kilometer seismic discontinuity in Earth's mantle splits into two separate discontinuities (at approximately 500 kilometers and approximately 560 kilometers). The discontinuity near 500 kilometers is most likely caused by the (Mg,Fe)2SiO4 beta-to-gamma phase transformation. We show that the formation of CaSiO3 perovskite from garnet can cause the deeper discontinuity, and by determining the temperature dependence for this reaction we demonstrate that regional variations in splitting of the discontinuity arise from variability in the calcium concentration of the mantle rather than from temperature changes. This discontinuity therefore is sensitive to large-scale chemical heterogeneity. Its occurrence and variability yield regional information on the fertility of the mantle or the proportion of recycled oceanic crust.


Stress echocardiography for left ventricular diastolic dysfunction detection in patients with non-severe chronic obstructive pulmonary disease: a cross-sectional study.
To assess whether the simultaneous performance of exercise stress echocardiography and cardio-pulmonary testing (ESE-CPET) may facilitate the timely diagnosis of subclinical left ventricular diastolic dysfunction (LVDD) in patients with non-severe chronic obstructive pulmonary disease (COPD), preserved left ventricular systolic function, and exertional dyspnea or exercise intolerance. This cross-sectional study, conducted between May 2017 and April 2018, involved 104 non-severe COPD patients with exertional dyspnea and preserved ejection fraction who underwent echocardiography before CPET and 1-2 minutes after peak exercise. Based on the peak E/e' ratio, patients were divided into the group with stress-induced LVDD - E/e'>15 and the group without stress-induced LVDD. We assessed the association between LVDD and the following CPET variables: minute ventilation, peak oxygen uptake (VO2), ventilatory efficiency, heart rate reserve, and blood pressure. During ESE-CPET, stress-induced LVDD occurred in 67/104 patients (64%). These patients had lower work load, peak VO2, O2 pulse, and minute ventilation (VE), and higher VE/VCO2 slope than patients without stress-induced LVDD (35.18±10.4 vs 37.01±11.11, P<0.05). None of the CPET variables correlated with E/e'. Combined ESE-CPET may distinguish masked LVDD in patients with non-severe COPD with exertional dyspnea and preserved left ventricular systolic function. None of the CPET variables was a predictor for subclinical LVDD.


Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data.
Over the past 20 years, combined treatment with radiotherapy and second-generation chemotherapy drugs was extensively studied in patients with locally advanced NSCLC and became the standard over radiotherapy alone in patients with good performance status. Radiosensitizing properties of cisplatin have been identified in the laboratory. Close temporal administration of cisplatin and radiation is mandatory for enhanced antitumor efficacy, but results in significant toxicity to normal tissues. Early clinical studies demonstrated that the concurrent administration of cisplatin during STD-RT was feasible, with acceptable esophageal toxicity, and had the potential of significantly improving locoregional control. Carboplatin administered concurrently with accelerated HFX-RT was responsible for a higher rate of esophageal toxicity. Further improvement in survival also requires an effective treatment of micro-metastatic disease through full-dose delivery of cytotoxic drugs and the addition of at least one more active drug in conjunction with cisplatin and radiotherapy to further improve locoregional control of the disease. In most clinical studies, etoposide was the second drug of choice because of its own radiosensitizing properties and possible synergy with cisplatin. In numerous phase II studies, concurrent radiotherapy and PE resulted in reproducible results in terms of local control (30%-40%), median survival (15-18 months), survival at 2 years (35%-40%), and survival at 5 years (25%-30%). In phase III studies, these results were shown to be superior to radiotherapy alone and to induction chemotherapy followed by STD-RT. The question of the potential benefit of HFX-RT combined with PE has been addressed in phase II and III studies. At this time, there is no firm evidence that concurrent chemotherapy with HFX-RT is superior to concurrent chemotherapy with STD-RT in terms of local control and survival. Only a significant benefit in terms of local control or survival would justify the significant increase of esophageal toxicity observed with HFX-RT, which remains the main limiting factor of concurrent chemoradiotherapy with PE. Studies on postinduction surgery after concurrent chemoradiotherapy have been of major interest, demonstrating that a complete pathologic response rate of 25% to 30% could be achieved with a relatively low dose of radiation (45 Gy) and that downstaging was a major determinant for improved long-term survival. Long-term survival after trimodality treatment, however, does not appear to be significantly different from what can be achieved with concurrent chemoradiotherapy alone in phase II studies. Whether postinduction surgery is beneficial to patients with histologically proved stage III (N2) and stage IIIB patients was the question addressed in a large, recently completed phase III intergroup trial and of which the results are eagerly awaited. Over the past 10 years, further progress in radiation technology has been accomplished through three-dimensional treatment planning, multileaf collimators, and electronic portal imaging devices, leading to high-precision conformal radiotherapy and dose escalation and (it is hoped) to improved local control. Intensity-modulated radiotherapy and respiratory gating remain to be evaluated. Accurate delineation of critical organs and pretreatment analysis of toxicity-predicting factors allow for better protection of normal intrathoracic tissues such as lung and esophagus and, it is hoped, will lead to a significant reduction in the incidence of radiation esophagitis and pneumonitis. Third-generation drugs such as taxanes, vinorelbine, and gemcitabine have demonstrated high response rates in NSCLC patients with favorable toxicity profiles. These drugs have also shown major radiosensitizing properties in the laboratory and in the clinical setting, often leading, however, to excessive radiosensitization and unacceptable normal tissue toxicities when administered at full dose concurrently with radiotherapy. Weekly administration of these drugs at reduced doses during a full course of conformational radiotherapy up to 70 Gy or more, however, resulted in encouraging results in several phase II studies, with median survival in excess of 20 months and 2- and 3-year survival rates near 50% and 40%, respectively. The respective benefits of either induction or consolidation full-dose chemotherapy with these drugs, before or after concurrent chemoradiotherapy with second- or third-generation chemotherapy, are presently being evaluated in phase III studies. As a result of improved survival and enhanced local control, most of these studies show a significant increase in the incidence of brain metastases. Because the brain is often the first site of relapse after concurrent chemoradiotherapy with or without surgery, the issue of prophylactic cranial irradiation is currently being addressed in a phase III trial.


Temporal lobectomy.
The indications for, and results of the author's personal series of 486 resective operations in epileptic patients are reviewed, together with the long term results of 286 patients undergoing temporal lobectomy. Almost 50% of such patients were seizure free when followed for two to thirty years.


A full-scale simulation approach for atom probe tomography.
A versatile approach for simulation of APT measurements is presented. The model is founded on a Voronoi cell partition of 3D space. The partition is used in dual role: First, the atomic structure of the field emitter is depicted in a one to one relationship by single Wigner-Seitz cells. Second, the construction of an adaptive tetrahedral mesh enables solving the Poisson equation on length scales covering seven orders of magnitude. Ion trajectories are computed in full-length comparable to experiments. Contrary to former simulation approaches the sequence of desorbing atoms is determined by field-induced polarization forces. Both results for cubic lattices in <001>, <011>, and <111> orientation are presented and the simulation of an APT measurement of a complex crystalline/amorphous layer structure is demonstrated. The example of a grain boundary addresses the new possibility of constructing models with structural defects. In this case, the simulation reveals strong artifacts in the reconstruction even if homogenous evaporation threshold is assumed.


Effects of the combined treatment of naloxone and indomethacin on catecholamines and behavior after intranigral lipopolysaccharide injection.
The present study examined effects of the combined administration of naloxone (NX) and indomethacin (IM) on nigrostriatal catecholamines and locomotor activity after intranigral lipopolysaccharide (LPS) injection in Sprague-Dawley rats. NX plus IM was given 3 days after LPS injection; it significantly (P < .05) reversed LPS inflammation on nigrostriatal dopamine (DA) and nigral serotonin (5-HT) and nigral homovanillic acid (HVA)/DA ratio and nigrostriatal 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio. It also tended to ameliorate the locomotor hyperactivity. However, NX plus IM given 30 min before LPS could not satisfactorily protect against LPS's damage both biochemically and behaviorally. These results reveal that NX plus IM may protect against LPS on DA, 5-HT, and motor function after LPS injection but not before. Thus it suggests that the combined treatment of NX and IM gives a potent therapy, but not prevention, of LPS-induced inflammation and also protect nigrostriatal dopaminergic and serotoninergic systems against LPS in rats.


Automated MALDI matrix coating system for multiple tissue samples for imaging mass spectrometry.
Uniform matrix deposition on tissue samples for matrix-assisted laser desorption/ionization (MALDI) is key for reproducible analyte ion signals. Current methods often result in nonhomogenous matrix deposition, and take time and effort to produce acceptable ion signals. Here we describe a fully-automated method for matrix deposition using an enclosed spray chamber and spray nozzle for matrix solution delivery. A commercial air-atomizing spray nozzle was modified and combined with solenoid controlled valves and a Programmable Logic Controller (PLC) to control and deliver the matrix solution. A spray chamber was employed to contain the nozzle, sample, and atomized matrix solution stream, and to prevent any interference from outside conditions as well as allow complete control of the sample environment. A gravity cup was filled with MALDI matrix solutions, including DHB in chloroform/methanol (50:50) at concentrations up to 60 mg/mL. Various samples (including rat brain tissue sections) were prepared using two deposition methods (spray chamber, inkjet). A linear ion trap equipped with an intermediate-pressure MALDI source was used for analyses. Optical microscopic examination showed a uniform coating of matrix crystals across the sample. Overall, the mass spectral images gathered from tissues coated using the spray chamber system were of better quality and more reproducible than from tissue specimens prepared by the inkjet deposition method.


Association Between SNPs in 1q32.2 and NSCL ± P in Han Chinese Population.
Non-syndromic cleft lip with or without cleft palate (NSCL ± P) is one of the most common birth malformations. Currently, numerous susceptibility SNPs have been reported by GWA studies, however, the replications of them among NSCL ± P from Han Chinese were very limited. In this study, we selected 16 SNPs around 1q32.2 based on the published GWA studies and replicated them among 302 trios with NSCL ± P from Han Chinese Population. The genotypic data was analyzed with FBAT, PLINK and R package. The study was conducted in a tertiary medical center. 302 patients with CL ± P and their parents. To ascertain the genetic variants in 1q32.2 in patients with CL ± P in Han Chinese Population. Blood samples were collected. We found T allele (Z = 4.26, p = 0.00002) and T/T homozygotes (Z = 4.4, p = 0.000011) at rs12063989 was significantly over-transmitted among non-syndromic cleft lip with or without cleft palate (NSCL ± P). We found rs12063989 exhibited significant association with the occurrence of NSCL ± P, which would provide new evidence for the future study in the etiology of NSCL ± P.


Reduction of incarcerated inguinal hernia in infants using caudal epidural anaesthesia.
Incarcerated inguinal hernias in infants are commonly encountered. Reduction with intravenous sedation using morphine and related drugs carries risks of apnoea and/or respiratory arrest, especially in small, ex-premature babies who have an increased incidence of incarceration and thus opiate use is best avoided. Caudal epidural anaesthesia is widely used as pre- and post-operative analgesia in elective inguinal herniotomy in infants. In this study we sought to determine if caudal epidural anaesthesia would allow reduction of an incarcerated inguinal hernia in the acute setting, thereby obviating the need for intravenous sedation. A retrospective review of 12 male infants, with irreducible, incarcerated inguinal hernias was done. Each hernia was successfully reduced with the help of caudal epidural anaesthesia. This group of babies was treated at The Royal Belfast Hospital for Sick Children. Twelve male infants were identified with an incarcerated inguinal hernia in whom attempted reduction, without sedation had failed. Using Bupivacaine (1 ml/kg 0.25%), placed into the caudal space, these hernias were successfully reduced non-operatively. Ages at presentation ranged from 2 to 17 weeks with a median gestational age of 36 weeks (range 29-39 weeks). Caudal epidural anaesthesia is a safe, feasible and effective method of achieving reduction of irreducible, incarcerated inguinal hernias. It is especially useful in low-birth weight, premature infants where intravenous opiate sedation is best avoided.


HDAC Inhibitor SAHA Alleviates Pyroptosis by up-regulating miR-340 to Inhibit NEK7 Signaling in Subarachnoid Hemorrhage.
Subarachnoid hemorrhage (SAH) is a cerebral hemorrhagic disease with a high disability and fatality rate. Cell pyroptosis is involved in the brain injury following SAH. Here, we explored the effect of HDAC inhibitor SAHA against cell pyroptosis after SAH. The rat SAH model was established by endovascular perforation and the rat microglia were treated with 25 μm oxyhemoglobin (OxyHb) for 24 h to mimic SAH model in vitro. Neurological score and brain edema were assessed in rat SAH model. TUNEL staining detected apoptosis. qRT-PCR and western blotting were employed to detect expression levels of miR-340, NEK7 and inflammatory cytokines. ELISA assay determined the secretion of IL-1β and IL-18 in rat serum and cell supernatant. A lactate dehydrogenase (LDH) kit measured the LDH activity in rat primary microglia. Microglia pyroptosis was detected by flow cytometry. RIP and dual luciferase reporter assays confirmed the binding relationship between miR-340 and NEK7. SAHA alleviated neurological dysfunction, inflammatory injury and microglia pyroptosis in SAH rats. SAHA suppressed LDH release, inflammatory factor expression and pyroptosis in microglia treated with OxyHb. Meanwhile, SAHA increased miR-340 expression and inhibited NEK7 level in vivo and in vitro SAH models. Further, miR-340 directly targeted NEK7 to inhibit the NLRP3 signaling pathway. Knockdown of miR-340 or overexpression of NEK7 reversed the suppressive effects of SAHA on microglia inflammation and pyroptosis. Additionally, knockdown of NEK7 impaired microglia inflammation and pyroptosis induced by miR-340 inhibitor. HDAC inhibitor SAHA ameliorates microglia pyroptosis in SAH through triggering miR-340 expression to suppress NEK7 signaling. This novel mechanism provides promise for SAHA in SAH treatment.


[Study of morbidity and Plasmodium species in the several geographic-climatic areas of Mauritania].
We studied the proportion of malaria-infected patients among febrile outpatients in nine health centres selected in relation to their geo-climatic location and the level of malaria transmission in order to establish a reliable database on malaria-associated morbidity and Plasmodium species in three epidemiological strata in Mauritania. Blood samples were collected from a total of 7368 febrile individuals (1603 in sahelian zone, 3023 in sahelian-saharan transition zone, and 2742 in Saharan zone) to examine thin and thick blood smears between August 2010 and July 2011. The proportion of malaria-infected patients was 9.1% (672/7368). Depending on the season, the proportion varied from 16.3% (494/3021), 5.5% (157/2850), to 1.4% (21/1497) during the humid season (July-October), cool dry season (December-March), and hot dry season (April-June), respectively. Febrile patients in the sahelian-Saharan transition zone were most affected by malaria, with 65.6% (441/672) smear-positive cases. P. vivax occurred most frequently (61.6%, 414/672). P. falciparum, P. ovale, and P. malariae accounted for 32.4% (218/672), 5.2% (35/672), and 0.8% (5/672) of smear-positive cases, respectively. These data may contribute to improving our knowledge on malaria in Mauritania, which may in turn help develop control strategies and improved monitoring in each geo-climatic zone.


Schistosoma mattheei infections in cattle: changes associated with season and age.
The Schistosoma mattheei egg output was monitored in 31 cattle over a 18-month period on a dairy farm near Lusaka (Zambia). The animals were kept on pasture with free access to two streams which were suitable for the intermediate host, Bulinus globosus. Individual faecal egg excretion reached an average peak of 130 eggs per gram, around 9 months after birth and decreased markedly before the age of 18 months. Average counts declined significantly with age, down to less than five eggs per gram in adult cows. A seasonal increase in B. globosus snails and S. mattheei transmission during the rainy season had no effect on the egg output of animals older than 18 months. Two calves and two adult cows were necropsied to compare fluke and tissue egg counts in young and old infections. There was a marked decline in tissue egg accumulation in older cows, in spite of an increase in the numbers of adult female flukes, as compared with young animals. A shift of egg accumulation from the large intestine towards the liver was also observed as infection progressed. It is concluded from the results of faecal egg counts that cattle reared under conditions of continuous challenge develop acquired resistance to S. mattheei infection within the first year following primary infection. Comparison of fluke and tissue egg counts in farm animals of different ages suggests the acquisition of an anti-fecundity effect as infection progresses.


A two-stage enzymatic method for determination of uric acid and hypoxanthine/xanthine.
A method is described by which plasma or serum concentrations of uric acid and hypoxanthine/xanthine may be determined in a two-step sequential method. The principle of the method is that hydrogen peroxide, liberated by the action of uricase and xanthine oxidase on their substrates, is coupled to the production of a coloured product.


Redox Dysregulation in Vascular Pathobiology.
Oxidation-reduction (redox) reactions comprise a subset of fundamental biochemical reactions found throughout biological systems. While redox reactions are involved in many normal cellular functions, excess oxidative potential, or oxidative stress, can lead to cellular dysfunction and injury. Multiple protective antioxidant systems have evolved to guard against the adverse consequences of oxidant stress and injury. These systems include low-molecular-weight antioxidants, such as the glutathione-glutathione disulfide redox couple; the thiol proteome, whose various oxidation states can serve as a global redox buffer; and antioxidant enzymes, such as the superoxide dismutases, catalase, peroxidredoxins, and the glutathione peroxidases. One example of an essential antioxidant enzyme whose deficiency contributes to pathobiology in the vasculature is glutathione peroxidase-3 (GPx-3), the principal antioxidant enzyme in the extracellular compartment. This enzyme catalyzes the reduction of hydrogen and lipid peroxides to water and lipid alcohols, respectively, and does so using reducing equivalents provided by glutathione. As a selenoprotein, it requires unique translational machinery for its expression, as well as adequate selenium stores; its primary site of synthesis is the renal tubule, although all nucleated cells can express low levels of the enzyme. We have previously demonstrated that a deficiency of GPx-3 leads to enhanced platelet activation, and is an independent risk factor for acute ischemic stroke in the young. We recently developed a GPx-3-deficient mouse model, and demonstrated endothelial dysfunction as well as increased platelet-dependent thrombosis in an acute ischemic stroke model. Importantly, platelet inhibitors or small-molecule superoxide and hydrogen peroxide scavengers greatly attenuated the size of the ischemic stroke and its functional consequences in this model. These data support the importance of GPx-3as a key antioxidant enzyme that functions to limit arterial thrombosis in the setting of increased oxidant stress and endothelial dysfunction. A second example of an essential antioxidant enzyme whose deficiency contributes to pathobiology in the vasculature is glutathione peroxidase-1 (GPx-1), a central intracellular antioxidant. In our efforts to uncover a mechanism for the oxidative stress of hyperhomocysteinemia, we found that elevated levels of this amino acid is associated with a decrease in the expression and activity of GPx-1 in endothelial cells. This change in expression was found to be post-translational, and we recently demonstrated that it is a consequence of hypomethylation of selenocysteine (Sec)-charged tRNA. This modification is essential for appropriate incorporation of Sec into the selenoprotein GPx-1's active site during translation. Changes in Sec-tRNA methylation are brought about by increased S-adenosylhomocysteine, which inhibits the methyltransferase required to methylate Sec-tRNA to the Um34 form. These data suggest a unique mechanism for impaired GPx-1 expression in hyperhomocysteinemic states that directly relates to impaired cellular methylation potential caused by increased S-adenosylhomocysteine accumulation.


A novel mutation Gly222Arg in PROS1 causing protein S deficiency in a patient with pulmonary embolism.
Thrombophilia is becoming a more frequently reported disorder these years. Hereditary protein S deficiency is one of the anticoagulant deficiencies that eventually results in thrombophilia. A 24-year-old male patient was suffering from unexplained thrombosis for the second time with a family history of deep venous thrombosis. Screening tests for anticoagulant proteins found the activity of protein S markedly lowered (5.0%). The patient was discharged after anticoagulation treatment. Four years later, the review still showed the activity of protein S in his plasma decreased (16.0%). Molecular genetic analysis revealed him homozygous for a missense mutation, c.664G>A, in the exon7 of PROS1. The mutation discovered here is the first mutation affecting the codon 222 of PROS1. This mutation results in the replacement of the glycine at the codon 222 of protein S with arginine, leading to a reduction of protein S function. The finding of this mutation may help with the understanding of the mechanism of protein S deficiency, especially in the Chinese population.


Cardiac tamponade: a rare but life-threatening complication of central venous catheters in children.
The widespread use of central venous catheters in the treatment of pediatric patients has caused an increased incidence of complications. A rare, but potentially fatal complication occurs when the heart is perforated by the catheter tip causing a cardiac tamponade. This perforation of the heart generally is associated with the insertion procedure, but may also occur after some time because of displacement of the catheter tip. The authors present three cases in which the placement of a central venous catheter resulted in lethal cardiac tamponade. Proper positioning of the catheter tip in the superior vena cava and a high index of suspicion are essential in preventing this serious complication. Contrast-enhanced chest x-ray after insertion of the catheter must be performed to ascertain a correct position of the tip.


Impurities contained in antifungal drug ketoconazole are potent activators of human aryl hydrocarbon receptor.
Antifungal drug ketoconazole is a mixture of (+)/(-) cis-enantiomers, which also contains several impurities. Ketoconazole was identified as an activator of aryl hydrocarbon receptor AhR by three independent research teams. In the current paper we demonstrate that impurities contained in ketoconazole preparations are strong activators of human AhR and inducers of CYP1A1. Impurity IMP-C had similar potency (EC50), but 10-15 times higher efficacy (magnitude of induction) towards AhR, comparing to (+)-ketoconazole, as revealed by gene reporter assay in AZ-AHR stably transfected cells. Impurities IMP-B and IMP-C, and in lesser extent IMP-E, induced a formation of AhR-DNA complex, as demonstrated by electromobility shift assay EMSA. Impurities IMP-C and IMP-E dose-dependently induced CYP1A1 mRNA after 24 h, and their effects were comparable to those by (+)-ketoconazole. The level of CYP1A1 protein in HepG2 cells was strongly increased by IMP-C after 48h. In conclusion, our data further elucidated molecular effects of ketoconazole towards AhR signaling pathway, with possible implications in ketoconazole role in skin chemoprevention and/or damage, involving AhR.


Effects of Installing Different Types of Cooling Fins on the Cold Side of a Thermoelectric Power Generation Device on the Thermal Efficiency and Exergy Efficiency of Power Cable Surface Waste Heat Recovery.
This study investigates the thermal efficiency and exergy efficiency of a thermoelectric power generation device for recovering power cable surface waste heat. Numerical simulations are conducted to analyze the impact of different types of cooling fins on the system's performance. The results demonstrate that the installation of cooling fins improves heat transfer efficiency and enhances the thermoelectric power generation device's output power. Among the various fin designs, the system equipped with cooling fins with 17 teeth exhibits the highest performance. These findings highlight the importance of fin design in optimizing the system's thermal efficiency and exergy efficiency. This study provides valuable insights for the development and improvement of thermoelectric power generation systems for power cable surface waste heat recovery applications.


Potential analgesic, anti-inflammatory and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut.
The hydroalcoholic extract of Areca catechu L. (ANE) nut was screened for its analgesic, anti-inflammatory and in vitro antioxidant potential. Three doses of ANE (250, 500 and 1000 mg/kg orally) were tested for analgesic and anti-inflammatory activities. Evaluation of analgesic activity of ANE was performed using hot plate and formalin test in mice. ANE showed maximum increase in hot plate reaction time (56.27%, p<0.01), while reduced the duration of licking/biting behaviors in first (39.45%, p<0.05) and second (92.71%, p<0.01) phases of the formalin test indicating significant analgesic activity. ANE reduced the paw edema considerably (86.79% inhibition after 24h, p<0.01) in dose-dependent manner compared to carrageenan-induced rat. In addition, in vitro antioxidant activity of ANE was investigated by total phenolic content (TPC) and hydrogen peroxide assay. The IC(50) observed in hydrogen peroxide assay was 83.14 μg/ml and TPC 120.56±21.09 mg QE/g. Altogether, these results suggest that the hydroalcoholic extract of Areca catechu could be considered as a potential analgesic, anti-inflammatory and antioxidant agent.


Transperitoneal Versus Retroperitoneal Robotic-Assisted Partial Nephrectomy in Patients with Obesity.
Introduction: We aim to compare transperitoneal (TP) and retroperitoneal (RP) robotic partial nephrectomy (RPN) in obese patients. Obesity and RP fat can complicate RPN, especially in the RP approach where working space is limited. Materials and Methods: Using a multi-institutional database, we analyzed 468 obese patients undergoing RPN for a renal mass (86 [18.38%] RP, 382 [81.62%] TP). Obesity was defined as body mass index ≥30 kg/m2*. A 1:1 propensity score matching was performed adjusting for age, previous abdominal surgery, tumor size, R.E.N.A.L nephrometry score, tumor location, surgical date, and participating centers. Baseline characteristics and perioperative and postoperative data were compared. Results: In the propensity score-matched cohort, 79 (50%) TP patients were matched with 79 (50%) RP patients. The RP group had more posterior tumors (67 [84.81%], RP versus 23 [29.11%], TP; P < .001), while the other baseline characteristics were comparable. Warm ischemia time (interquartile range; 15 [10, 12], RP versus 14 [10, 17] minutes, TP; P = .216), operative time (129 [116, 165], RP versus 130 [95, 180] minutes, TP; P = .687), estimated blood loss (50 [50, 100], RP versus 75 [50, 150] mL, TP; P = .129), length of stay (1 [1, 1], RP versus 1 [1, 2] day, TP; P = .319), and major complication rate (1 [1.27%], RP versus 3 [3.80%], TP; P = .620) were similar. No significant difference was observed in positive surgical margin rate and delta estimated glomerular filtration at follow-up. Conclusion: TP and RP RPN yielded similar perioperative and postoperative outcomes in obese patients. Obesity should not be a factor in determining optimal approach for RPN.


Optical coherence tomography findings in three patients with Werner syndrome.
Werner syndrome is a rare, autosomal recessive disorder characterised by premature aging. It is a typical hereditary progeroid syndrome that can be difficult to diagnose owing to its rarity and the similarity of some of its symptoms, such as juvenile cataracts, to other common ophthalmologic conditions. Early onset of bilateral cataracts is currently used as the ophthalmological feature for Werner syndrome; however, ophthalmologists often find performing a detailed examination of the medical history and genetic testing for Werner syndrome at the time of an ophthalmologic consultation challenging. If a unique ocular finding was observed on ocular examinations in cases of juvenile bilateral cataracts, we could consider Werner syndrome as a differential diagnosis. CASE PRESENTATION: We documented the cases of three patients with Werner syndrome in whom thinning of the retina in the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were observed using optical coherence tomography (OCT). Visual field tests revealed the loss of visual field mainly owing to glaucoma. The thinnig of the choroidal thickness (CT) in three patients was also observed using enhanced depth imaging (EDI)-OCT. Three patients have thinning of the RNFL, GCC, and choroidal thickness and the loss of visual field. These findings suggest the need for including Werner syndrome in the differential diagnosis when patients presenting with juvenile cataracts of unknown cause also show abnormal retinal and choroidal thinning in the OCT images.


Acute pseudotumoral hemicerebellitis: diagnosis and neurosurgical considerations of a rare entity.
Acute pseudotumoral hemicerebellitis is an exceptionally rare unilateral presentation of acute cerebellitis mimicking a tumor. It typically has a benign course without specific therapy; thus, recognizing this entity is important to avoid needless surgical intervention. MRI provides the key for diagnosis and usually reveals a diffusely swollen cerebellar hemisphere with no well-defined mass. Some patients will require neurosurgical assistance by means of ventriculostomy or posterior fossa decompression. We present a 17-year-old girl with pseudotumoral hemicerebellitis, review the available literature, and discuss the diagnosis and therapeutic dilemma from the neurosurgical perspective.


Measurement of cardiac output from a test-bolus injection in multislice computed tomography.
The aim of this study was to assess the feasibility of non-invasive determination of cardiac function from test-bolus data in multislice spiral computed tomography (MSCT). In 25 patients enhancement data gathered from a standardized test-bolus injection were analyzed. The test-bolus examination was performed prior to a retrospectively ECG-gated MSCT of the heart. A time-attenuation curve was obtained in the ascending aorta at the level of the pulmonary arteries. A gamma variate fit was applied to the curve in order to exclude recirculation and get pure first-pass data. Using the known amount of iodine injected, cardiac output (CO), and stroke volume (SV) were determined from integration of the fitted contrast enhancement curve using a reformation of the Stewart-Hamilton equation. Results were compared with CO and SV calculated from the geometric analysis of the retrospectively gated MSCT data using the ARGUS Software (Siemens, Forchheim, Germany). The CO and SV determined from test-bolus analysis and from geometric analysis correlated well with Pearson's correlation coefficients of 0.87 and 0.88, respectively. The standard deviation of the difference between both methods was 0.51 l/min for CO (8.6%) and 11.0 ml for SV (12.3%). Non-invasive quantification of CO seems to be feasible from a standard test-bolus injection. It provides valuable information on cardiac function without additional radiation or application of contrast material.


Polyethylene glycol-mediated infection with avian sarcoma viruses.
In this communication we report that fusion of viral and cellular membranes by polyethylene glycol is a convenient approach to overcoming genetically determined resistance to infection. Using this method, avian sarcoma virus-transformed mammalian cells have been produced which serve as useful model systems for the study of Rous sarcoma virus-specific tumor antigens.


Low molecular weight heparin inhibits tumor necrosis factor alpha-induced leukocyte rolling.
Heparins may exert several anti-inflammatory actions. This study investigated the impact of low molecular weight heparin (LMWH) on tumor necrosis factor (TNF)-alpha-provoked leukocyte rolling, adhesion and extravascular accumulation. Leukocyte-endothelium interactions and tissue accumulation of leukocytes were induced by TNF-alpha in Balb/c mice and analyzed by the use of intravital microscopy in the mouse cremaster muscle microcirculation. We observed that administration of 5000 units/kg of LMWH, but not 50 and 500 units/kg, markedly reduced TNF-alpha-induced leukocyte rolling, adhesion and tissue infiltration. Notably, when LMWH was given after TNF-alpha only leukocyte rolling was reduced and no effect was observed on firm adhesion of leukocytes. Taken together, these findings indicate that LMWH inhibits TNF-alpha-induced leukocyte accumulation by inhibiting the rolling adhesive interaction which may help explain the anti-inflammatory effects of LMWH.


An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome.
Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome.


Vessel Wall Imaging of Cerebrovascular Disorders.
High-resolution magnetic resonance vessel wall imaging (VWI) permits direct visualization of intracranial arterial wall pathology, providing diagnostic and prognostic information that is complementary to conventional imaging techniques. We highlight the most recent studies that have advanced the clinical application of VWI. VWI aids in distinguishing and diagnosing intracranial atherosclerotic disease (ICAD), intracranial dissections, central nervous system vasculitis, reversible cerebral vasoconstriction syndrome, and moyamoya disease. VWI may help predict recurrent stroke in ICAD, treatment effects in vasculitis, and disease progression in moyamoya. VWI also identifies ruptured intracranial aneurysms and may predict stability of unruptured aneurysms. Implementing VWI as an adjunctive imaging technique may permit earlier and noninvasive discrimination of rare vasculopathies. However the prognostic utility of VWI for more common cerebrovascular pathologies requires further validation.


The presence of H+ and Na(+)-translocating ATPases in Methanobacterium thermoautotrophicum and their possible function under alkaline conditions.
Two ATPases with different apparent molecular masses of approx. 500 kDa and 400 kDa were identified in the EDTA extract of the cell membranes of Methanobacterium thermoautotrophicum. Western blotting with polyclonal antiserum reactive with beta-subunit of mitochondrial ATPase from rat liver and yeast was used for further analysis of these ATPases. A strong crossreactivity with a single protein band with an apparent molecular weight of about 53 kDa (similar to beta-subunit of F-type ATPase from other sources) was found in protein extracts of whole cells of Methanobacterium thermoautotrophicum strains delta H and Marburg, as well as of Methanospirillum hungatei. This indicates the presence of F-type ATPase in methanogens. ATP synthesis driven by membrane potential which was generated by artificially-imposed delta pH in the presence of protonophorous uncoupler and sodium ions was stimulated by bafilomycin A1, an inhibitor of V- and A-type ATPases, as well as by harmaline, an inhibitor of Na+/H+ antiporter. These results indicate that cells of Methanobacterium thermoautotrophicum strain delta H contain the F-type ATP synthase which is Na(+)-translocating in addition to V- or A-type ATP synthase which is H(+)-translocating.


The nature of the clear zone around microtubules.
The clear zones seen around microtubules in transverse sections of nutritive tubes vary in size depending on whether a microtubule is bordered by ribosomes or by another microtubule. We consider that such a finding is not consistent with the current view, that the clear zone is maintained by microtubule-associated material. It can, however, be accounted for by an electrostatic repulsion between the surfaces of negatively charged microtubules and between microtubules and ribosomes which are also negatively charged. The experiments presented here, involving on the one hand the addition of cationic substances to microtubules and on the other the alteration in charge of the microtubules, support this hypothesis.


Management of transvaginal ultrasound-guided absolute ethanol sclerotherapy for ovarian endometriotic cysts.
Endometriosis and endometriotic ovarian cysts are common gynecologic diseases. Excision of the cyst wall by laparotomy or laparoscopy is the standard treatment for endometriotic ovarian cysts. However, some young patients with cysts would prefer not to have an abdominal incision. We reviewed and assessed the effectiveness of transvaginal ultrasound-guided ethanol sclerotherapy in these patients. Eighteen patients with endometriotic ovarian cysts underwent transvaginal ultrasound-guided aspiration and ethanol sclerotherapy using spinal anesthesia. The contents of the cysts were drained and sent for cytological examination. The cyst cavities were washed with absolute ethanol, and the cysts were then filled with absolute ethanol for 5 min. The patients were followed up with transvaginal ultrasonography. The transvaginal ethanol sclerotherapy was completed in all cases. The mean long diameter of the cysts was 50 mm (31-100 mm), and the mean operative duration was 22 min (8-45 min). Malignant cells were not isolated from the aspirated fluid in any case. There were no significant intra- or postoperative complications. Two patients (11.1%) had a recurrence at 3 and 32 months after ethanol sclerotherapy, respectively. Transvaginal ultrasound-guided absolute ethanol sclerotherapy is useful for ovarian endometriotic cysts, particularly in young patients or in patients who would like to become pregnant. However, careful selection based on ultrasonography or magnetic resonance imaging findings and the age of the patients is critical.


Nucleotide sequence of bacteriophage fd DNA.
The sequence of the 6,408 nucleotides of bacteriophage fd DNA has been determined. This allows to deduce the exact organisation of the filamentous phage genome and provides easy access to DNA segments of known structure and function.


Through the Looking-Glass: Reevaluating DHEA Metabolism Through HSD3B1 Genetics.
Dehydroepiandrosterone (DHEA) and DHEA sulfate together are abundant adrenal steroids whose physiological effects are mediated through their conversion to potent downstream androgens. 3β-Hydroxysteroid dehydrogenase isotype 1 (3βHSD1) facilitates the rate-limiting step of DHEA metabolism and gates the flux of substrate into the distal portion of the androgen synthesis pathway. Notably, a germline, missense-encoding change, HSD3B1(1245C), results in expression of 3βHSD1 protein that is resistant to degradation, yielding greater potent androgen production in the periphery. In contrast, HSD3B1(1245A) encodes 3βHSD1 protein that is easily degraded, limiting peripheral androgen synthesis. These adrenal-permissive (AP) and adrenal-restrictive (AR) alleles have recently been associated with divergent outcomes in androgen-sensitive disease states, underscoring the need to reevaluate DHEA metabolism using HSD3B1 genetics.


Neighborhood socioeconomic status and BMI differences by immigrant and legal status: evidence from Utah.
We build on recent work examining the BMI patterns of immigrants in the US by distinguishing between legal and undocumented immigrants. We find that undocumented women have relative odds of obesity that are about 10 percentage points higher than for legal immigrant women, and their relative odds of being overweight are about 40 percentage points higher. We also find that the odds of obesity and overweight status vary less across neighborhoods for undocumented women than for legal immigrant women. These patterns are not found among immigrant men: undocumented men have lower rates of obesity (by about 6 percentage points in terms of relative odds) and overweight (by about 12 percentage points) than do legal immigrant men, and there is little variation in the impact of neighborhood context across groups of men. We interpret these findings in terms of processes of acculturation among immigrant men and women.


TrMADS3, a new MADS-box gene, from a perennial species Taihangia rupestris (Rosaceae) is upregulated by cold and experiences seasonal fluctuation in expression level.
In many temperate perennial plants, floral transition is initiated in the first growth season but the development of flower is arrested during the winter to ensure production of mature flowers in the next spring. The molecular mechanisms of the process remain poorly understood with few well-characterized regulatory genes. Here, a MADS-box gene, named as TrMADS3, was isolated from the overwintering inflorescences of Taihangia rupestris, a temperate perennial in the rose family. Phylogenetic analysis reveals that TrMADS3 is more closely related to the homologs of the FLOWERING LOCUS C lineage than to any of the other MIKC-type MADS-box lineages known from Arabidopsis. The TrMADS3 transcripts are extensively distributed in inflorescences, roots, and leaves during the winter. In controlled conditions, the TrMADS3 expression level is upregulated by a chilling exposure for 1 to 2 weeks and remains high for a longer period of time in warm conditions after cold treatment. In situ hybridization reveals that TrMADS3 is predominantly expressed in the vegetative and reproductive meristems. Ectopic expression of TrMADS3 in Arabidopsis promotes seed germination on the media containing relatively high NaCl or mannitol concentrations. These data indicate that TrMADS3 in a perennial species might have its role in both vegetative and reproductive meristems in response to cold.


Dexamethasone treatment improves morphological and hematological parameters in chronic experimental schistosomiasis.
Schistosomiasis, a chronic disease with considerable social impact, is an important health problem in many countries. To investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic Schistosoma mansoni infection, we evaluated the effect of dexamethasone on histological, hematological, and biochemical parameters that reflect disease severity and morbidity. Animals treated from the first day or after 35 days of infection, were analyzed. In both groups, dexamethasone: (1) induced a decrease in the number of granulomas in hepatic tissue without affecting the alanine aminotransferase profile, (2) reduced splenomegaly and hepatomegaly associated with disease, and (3) improved hemoglobin concentration, hematocrit values and reduced the percentage of reticulocytes, preventing the development of anemia that occurs in the chronic phase of infection. These data suggest that treatment with dexamethasone results in a mild course of murine schistosomiasis and point to this drug as a promising agent to complement S. mansoni specific treatment.


A practical biphasic contrast media injection protocol strongly enhances the aorta and pulmonary artery simultaneously using a single CT angiography scan.
Enhancement profiles of the pulmonary artery (PA) and aorta differ when using computed tomography (CT) angiography. Our aim was to determine the optimal CT protocol for a one-time CT scan that assesses both blood vessels. We prospectively enrolled 101 cases of CT angiography in patients with suspected pulmonary embolism or aortic dissection from our center between 2018 and 2020. We also retrospectively collected the data of 40 patients who underwent traditional two-time CT scans between 2015 and 2018. Patients were divided into four groups: test bolus (TB) I, TB II, bolus-tracking (BT) I, and BT II. The enhancement of the PA and aorta, and the radiation doses used in the four groups were collected. Those who underwent two-time scans were classified into the traditional PA or aorta scan groups. Data were compared between the BT and traditional groups. The aortic enhancement was highest in BT II (294.78 ± 64.48 HU) followed BT I (285.18 ± 64.99 HU), TB II (186.58 ± 57.53 HU), and TB I (173.62 ± 69.70 HU). The radiation dose used was lowest in BT I (11.85 ± 5.55 mSv) and BT II (9.07 ± 3.44 mSv) compared with that used in the traditional groups (20.07 ± 7.78 mSv) and accounted for half of the traditional group (45.17-59.02%). The aortic enhancement was also highest in BT II (294.78 ± 64.48 HU) followed by BT I (285.18 ± 64.99 HU) when compared with that in the traditional aorta scan group (234.95 ± 94.18 HU). Our CT protocol with a BT technique allows for a lower radiation dose and better image quality of the PA and aorta than those obtained using traditional CT scans. NCT04832633, retrospectively registered in April 2021 to the clinical trial registry.


Antioxidant and antimicrobial effects of phenolic compounds extracts of Northeast Portugal honey.
Phenolic compounds of dark and clear honeys from Trás-os-Montes of Portugal were extracted with Amberlite XAD-2 and evaluated for their antioxidant and antimicrobial activities. The antioxidant effect was studied using the in vitro test capacity of scavenge the 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical and of reducing power of iron (III)/ferricyanide complex. The antimicrobial activity was screened using three Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, Staphylococcus lentus) and three Gram-negative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli). The results obtained from the partial identification of honey phenolic compounds by high-performance liquid chromatography with a diode array detector showed that p-hydroxibenzoic acid, cinnamic acid, naringenin, pinocembrin and chrysin are the phenolic compounds present in most of the samples analyzed. Antioxidant potential was dependent of honey extract concentration and the results showed that dark honey phenolic compounds had higher activity than the obtained from clear honey. In the biological assays, results showed that S. aureus were the most sensitive microrganisms and B. subtilis, S. lentus, K. pneumoniae and E. coli were each moderately sensitive to the antimicrobial activity of honey extracts. Nevertheless, no antimicrobial activity was observed in the test with P. aeruginosa.


Women over 50 who use alcohol and their engagement with primary and preventative health services: a narrative review using a systematic approach.
Women who are over 50 years are drinking alcohol in higher quantities and more frequently than in previous decades. Good engagement with primary care is crucial for women's physical and psychological health, particularly if they use alcohol. However, there is little known about the alcohol use of women over 50 and their use of primary care. A systematic search was conducted on six databases; CINAHL, Medline, PsycINFO, Academic Search Complete, EMBASE and Web of Science to identify literature on primary health care engagement of women 50 years and older (50+) who use alcohol. Titles and abstracts were reviewed and full texts were independently reviewed by two researchers. A narrative review, critical appraisal and synthesis of the eligible studies produced common themes and key findings. After excluding 3822 articles, 13 articles were deemed eligible for the review. For this age group (50+), findings were: 1) women who drink heavily were less likely than men to attend General Practitioners (GPs), moderate drinkers were more likely than abstainers to attend mammogram screening, 2) GPs were less likely to ask questions or discuss alcohol with women than with men, 3) GPs offered less advice on alcohol to women than to men, and 4) less women than men received alcohol screening from their GP. While women 50+ are drinking more, their alcohol use is underreported and insufficiently provided for in primary health. As women's life expectancy increases, improved GP engagement will benefit women's health and reduce future healthcare costs.


Evaluation of partial and total splenectomy in children with sickle cell disease using an Internet-based registry.
Clinical outcomes of children with sickle cell disease (SCD) who undergo total or partial splenectomy (PS) are poorly defined. The purpose of this retrospective study was to initiate an Internet-based registry to facilitate analysis of clinical outcomes for these children. We hypothesized that both surgical procedures would be well tolerated and would eliminate risk of splenic sequestration. We developed a web-based registry using the Research Electronic Data Capture (REDCap) platform. Children were included if they had SCD and underwent total splenectomy (TS) or PS between 2003 and 2010. Clinical outcomes were compared between cohorts, with follow-up to 1 year. Twenty-four children were included, TS (n = 15) and PS (n = 9). There were no differences in surgical time or intraoperative blood loss. The length of stay was longer after PS (4.1 ± 1.7 days) compared to TS, (2.4 ± 1.2 days, P = 0.02). Within 30 days of surgery, 2 (20%) patients had acute chest syndrome (ACS) following TS and 2 (15%) patients had ACS after PS. During 1-year follow-up, no patient in either cohort had recurrent splenic sequestration, venous thrombosis or overwhelming postsplenectomy sepsis. All children who were transfused preoperatively to prevent recurrent splenic sequestration successfully discontinued transfusions. Both TS and PS result in favorable hematologic outcomes and low risk of adverse events for children with SCD. A REDCap-based registry may facilitate data entry and analysis of clinical outcomes to allow for comparison between different types of splenectomy.


Increasing temperature during early spring increases winter wheat grain yield by advancing phenology and mitigating leaf senescence.
High temperature usually reduces wheat yield, especially at critical growth stages, such as anthesis and grain filling. However, effects of increasing temperature during wintering period on winter wheat growth and development are rarely reported. Hence, this three-year field experiment evaluated how artificial warming during early spring (wintering period) affects winter wheat. The warming treatment (WT) advanced the wheat reviving, jointing, anthesis, and maturity stages, but the average temperature in each growing stage reduced, thus extending the duration of tillering, spike differentiation, and grain filling. Concurrently, the leaf area index and biomass accumulation were obviously increased. Additionally, WT showed a lower leaf senescence rate compared with that of control (CK). Also, the photosynthesis rate and SPAD of WT were increased relative to CK. WT increased superoxide dismutase and peroxidase activities, and reduced malondialdehyde content in flag leaf during the grain filling stage, suggesting WT during early spring could delay leaf senescence after anthesis, which contributed to a high filling rate and long filling duration. Correspondingly, the final spike number, kernel number, and kernel weight of WT were significantly increased compared with CK. In the three seasons, grain yield was increased by 18.2%-37.5% in WT compared with CK. Results of this study provided a new viewpoint that increasing temperature could shorten the wintering period but extend the effective growth phase, and increase grain yield in winter wheat.


A randomized biomechanical study of zone II human flexor tendon repairs analyzed in an in vitro model.
To study the effect of dorsally placed flexor tendon repairs on human cadaver tendons, we used the Kessler, Strickland, Robertson, and modified Becker techniques. The strengths of the repairs were tested in a previously described human cadaveric curvilinear model. There were statistically significant increases in dorsal versus volar grasping strength with the Kessler repair (38 N vs 33 N) and the Robertson repair (51 N vs 43 N). There were no differences with the locking Strickland and modified Becker repairs. One may infer that the locking techniques are intrinsically tighter and may not be as susceptible to the different forces between the tensile and compressive surfaces of a dynamic flexor tendon.


Correction to: Non-communicable disease prevention policy process in five African countries.
After publication of the article [1], it was noticed that the title has erroneously included 'authors' in the end.


Impact of valve prosthesis-patient mismatch on short-term mortality after aortic valve replacement.
The prosthesis used for aortic valve replacement (AVR) can be too small in relation to body size, thus causing valve prosthesis-patient mismatch (PPM) and abnormally high transvalvular pressure gradients. This study examined if there is a relation between PPM and short-term mortality after operation. The indexed valve effective orifice area (EOA) was estimated for each type and size of prosthesis being implanted in 1266 consecutive patients and used to define PPM as not clinically significant if >0.85 cm2/m2, as moderate if >0.65 cm2/m2 and <or=0.85 cm2/m2, and as severe if <or=0.65 cm2/m2; it was correlated with 30-day mortality and compared with other relevant variables. Moderate or severe PPM was present in 38% of patients. Thirty-day mortality was 4.6% (58/1266 patients) and the strongest independent predictors in multivariate analysis were left ventricular ejection fraction <40% (P=0.007), infectious endocarditis (P=0.002), emergent/salvage operation (P=0.002), cardiopulmonary bypass time >120 minutes (P=0.001), and PPM (P=0.003). Relative risk of mortality was increased 2.1-fold (95% confidence interval, 1.2 to 3.7) in patients with moderate PPM and 11.4-fold (4.4 to 29.5) in those with severe PPM. Moreover, risk of mortality for every category of PPM was higher in patients with a left ventricular ejection fraction <40% as compared with >or=40% (nonsignificant PPM, 2.7 versus 1.0; moderate PPM, 7.1 versus 1.8; severe PPM, 77.1 versus 11.3). PPM is a strong and independent predictor of short-term mortality among patients undergoing AVR, and its impact is related both to its degree of severity and the status of left ventricular function. In contrast to other risk factors, moderate-severe PPM can be largely avoided with the use of a prospective strategy at the time of operation.


Design and Synthesis of the Beryllium-Free Deep-Ultraviolet Nonlinear Optical Material Ba₃(ZnB₅O₁₀)PO₄.
Access to the elusive deep-ultraviolet by direct second harmonic generation (SHG) enabled by a new beryllium-free zincoborate-phosphate crystal is reported. Ba3(ZnB5O10)PO4, exhibits large SHG responses at 1064 and 532 nm and a short 180 nm absorption edge. Centimeter-size crystals are grown, and quantum mechanical calculations demonstrate the key role played by ZnO4 tetrahedra in the enhanced optical responses.


Bone marrow mononuclear stem cell infusion improves biochemical parameters and scintigraphy in infants with biliary atresia.
To evaluate early postoperative results in a case controlled study following clinical use of stem cells in extrahepatic biliary atresia (EHBA). From July 2005 to March 2008, 30 cases of suspected EHBA were divided in two groups in an intervention study. Group A received autologous mononuclear bone marrow stem cells at the time of Kasai or after Kasai. In Group B, only Kasai was performed. Liver function tests on postoperative day 7 were compared. Serum bilirubin, clinical status, hepatic scintigraphy and survival at 6 months and 1 year were compared. Mean age was 136 (74-275) days in Group A and 99.7 (56-172) days in Group B. Preoperative values of serum bilirubin (SB), aspartate aminotransferase (AST), alanine aminotransferase and alkaline phosphatase (ALP) were comparable between the groups though there was significant difference in postoperative SB, AST and ALP (p = 0.014, 0.0041, 0.0005), with and without the use of stem cells. The median post stem cell SB was 6.9 (0.5-11.6) mg/dl in Group A versus 10.1 (5.6-26.3) mg/dl in Group B. Median SB at 6 months follow-up was 0.6 (0.5-5.4) mg/dl in Group A versus 7.6 (0.8-9.2) mg/dl in Group B (p = 0.028). There was a significant difference in episodes of cholangitis at 6 months postoperatively between the two groups (p = 0.024). Hepatic scans done at <3 months; >3 months follow-up showed prompt excretion in 80% (4/5); 85.7% (6/7) in Group A versus 20% (1/5); 50% (1/2) in Group B. Survival at 6; 12 months' follow-up was 45.5%; 27.3% in Group A versus 33.3%; 6.7% in Group B. Median postoperative survival was 181 (139,223) days in Group A versus 123 (65,181) days in Group B. Significant biochemical and scintigraphic improvement was noted following stem cell therapy in biliary atresia, probably attributable to anti-inflammatory action of stem cells.


Molecular selectivity design of mitogen-inducible gene-derived phosphopeptides between oncogenic HER kinases.
Mitogen-inducible gene (MIG) is a natural negative regulator of the oncogenic HER kinase signaling by binding at the activation interface of kinase domain to disrupt the kinase dimerization. In this study, we systematically examine the binding structures, dynamics and energetics of MIG region 2 to four HER kinases based on their crystal or modeled complex structures, and identify an 8-mer phosphopeptide segment pYpY from the core strand sequence of MIG region 2 as the binding hotspot of MIG protein to HER kinases. We demonstrate that the small pYpY phosphopeptide can partially restore the binding affinity of full-length MIG protein, but exhibit a moderate selectivity over different HER kinases (S = 2.3-fold). In addition, the two phosphotyrosine residues pTyr394 and pTyr395 play an essential role in MIG-HER binding; dephosphorylation of them would fully eliminate the binding capability. A machine evolution algorithm is used to optimize the wild-type pYpY phosphopeptide, aiming to simultaneously improve affinity for these kinases and to maximize the affinity gap between different kinases. Consequently, a population is computationally evolved as selective phosphopeptide candidates; the dissociation constants of four representatives with HER kinases are systematically determined using binding affinity analysis, from which their selectivity is derived. The designed pYpYp3 phosphopeptide possesses a high selectivity over different HER kinases (S = 4.8-fold) and satisfactory affinity profile to these kinase (KD = 140-1000 μM). Structural analysis observes that the global binding modes of pYpYp3 to different kinases are roughly consistent, but its local conformation may vary considerably, thus conferring specificity to the phosphopeptide.