Correlation between three-dimensional ultrasound features and pathological prognostic factors in breast cancer.
To investigate the correlation of three-dimensional (3D) ultrasound features with prognostic factors in invasive ductal carcinoma. Surgical resection specimens of 85 invasive ductal carcinomas of 85 women who had undergone 3D ultrasound were included. Morphology features and vascularization perfusion on 3D ultrasound were evaluated. Pathologic prognostic factors, including tumour size, histological grade, lymph node status, oestrogen and progesterone receptor status (ER, PR), c-erbB-2 and p53 expression, and microvessel density (MVD) were determined. Correlations of 3D ultrasound features and prognostic factors were analysed. The retraction pattern in the coronal plane had a significant value as an independent predictor of a small tumour size (P = 0.014), a lower histological grade (P = 0.009) and positive ER or PR expression status (P = 0.001, 0.044). The retraction pattern with a hyperechoic ring only existed in low-grade and ER-positive tumours. The presence of the hyperechoic ring strengthened the ability of the retraction pattern to predict a good prognosis of breast cancer. The increased intra-tumour vascularization index (VI, the mean tumour vascularity) reflected a higher histological grade (P = 0.025) and had a positive correlation with MVD (r = 0.530, P = 0.001). The retraction pattern and histogram indices of VI provided by 3D ultrasound may be useful in predicting prognostic information about breast cancer. Three-dimensional ultrasound can potentially provide prognostic evaluation of breast cancer. The retraction pattern and hyperechoic ring in the coronal plane suggest good prognosis. The increased intra-tumour vascularization index reflects a higher histological grade. The intra-tumour vascularization index is positively correlated with microvessel density.


Pregnant women's expectations about pain intensity during childbirth and their attitudes towards pain management: Findings from an Icelandic national study.
Pregnant women expect childbirth to be painful. However, little is known about their expectations of the intensity of pain in childbirth (EIPC) and their attitudes to pain management. The design was a cross-sectional survey, with self-reported questionnaires used to collect data from low-risk pregnant women (N = 1111) early in pregnancy at 26 of the largest primary health care centres in Iceland. This consecutive national sample was stratified by residency. The mean score for the EIPC was 5.58 (SD = 1.38) measured on a 7 point scale. The strongest predictors of a high EIPC score were: negative attitude to the impending childbirth (OR = 2.39), low manifestation of a sense of security (OR = 1.80), and a positive attitude to pain management with medication (OR = 1.63). Women living outside the capital area were less likely to have a high EIPC (OR = 0.68). Most women (77%) had a positive attitude towards pain management without medication and 35% had a positive attitude to pain management with medication. The study detected multiple predictors of women's EIPC and attitude to pain management. Early and throughout pregnancy, midwives and health care professionals need to address these predictors in order to assist women to prepare themselves for the pain of labour.


The Treatment Strategy for Skull Base Reconstruction for Anterior Cranial Fossa Intra- and Extracranial Tumors.
Anterior cranial fossa intra- and extracranial tumors arise from the anterior cranial fossa and invade the orbit and nose. Anterior cranial fossa tumor resection and skull base reconstruction are challenging for neurosurgeons due to the complex anatomy, leakage of cerebrospinal fluid, and critical neurovasculature involvement. The authors report a case series of cranio-orbital communicating tumors and cranionasal-orbital communicating tumors. All patients underwent a modified Derome approach or transfrontal basal approach, and all tumor resections were satisfactory. Skull base reconstruction for small defects (<1.5 cm) can be performed with autogenous fascia, muscle, and fat. Large defects (≥1.5 cm) require autogenous fascia, muscle, and fat combined with osseous reconstruction (autogenous bone, titanium mesh, and polyetheretherketone). The techniques and treatments were successful, and only 1 patient experienced mild cerebrospinal fluid leak but no intracranial infection, pneumocrania or intracranial hemorrhage. Additionally, long-term follow-up demonstrated that the outcomes remain favorable. According to a literature review, this technique might be an alternative strategy for treating anterior cranial fossa intra- and extracranial tumors, and better skull base reconstruction can prevent many postoperative complications.


Molecular and Genetic Bases of Inhibition of Tick-Borne Encephalitis Virus Replication by Eprosartan and Ribavirin.
The antiviral activity of eprosartan (compound selected in silico) towards highly and low-virulent strains of tick-borne encephalitis virus was compared in vitro with activity of ribavirin. Study of the cytopathogenic activity of the virus on SPEV cells by ELISA, IFAT, and PCR showed similar results: both substances (eprosartan and ribavirin) promoted elimination of tick-borne encephalitis virus. Ribavirin exhibited intracellular inhibition towards both strains: the selectivity index for highly virulent Dal'negorsk strain was 160, for low-virulent Primorye-437 strain - 113. Eprosartan inhibited intracellular replication of Dal'negorsk strain (13.7) and less so that of Primorye-437 strain (2.9). The efficiency of virtual screening of the ligand (eprosartan) was demonstrated for highly virulent, but not low virulent tick-borne encephalitis strain.


New and Investigational Agents for Irritable Bowel Syndrome.
Irritable bowel syndrome (IBS) affects about 15 % of the US population and results in significant morbidity and health care costs. There remains a significant unmet need for effective treatments particularly for the pain component of IBS and other functional gastrointestinal disorders (FGIDs). Progress made in our understanding of pathophysiological mechanisms such as the role of altered bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and secretory properties of the gut has led to advancements in therapeutic armamentarium for IBS. This review discusses the new drugs for constipation and diarrhea-predominant IBS subtypes that have been tested or have been under investigation over the last 3-4 years. Overall, there is a promising pipeline of investigational drugs for the future treatment of IBS and related FGIDs.


Using the FpXylBH2•SMe2 reagent for the regioselective synthesis of cyclic bis(alkenyl)boranes.
The reactive borane reagent FpXylBH2•SMe2 was prepared from 1,4-bis(trifluoromethyl)benzene by treatment with n-BuLi, followed by H3B·SMe2 and subsequent removal of hydride. It undergoes a regioselective hydroboration reaction with 1,2-bis(trimethylsilylethynyl)benzene to give the "dimeric" product 13a featuring a conjugated 14-membered core heterocyclic structure that contains a pair of FpXylB units.


Optical and mechanical properties of conventional, milled and 3D-printed denture teeth.
Investigate the effect of various liquids on the optical properties and Vickers hardness of conventional, milled and 3D-printed denture teeth. Six different types of denture teeth (Maxillary anteriors of three different conventional teeth, Vivodent DCL, SR Phonares II, Vita Physiodens; milled teeth, IvotionDent; and two different 3D-printed teeth, Asiga DentaTooth and NextDent C&B MFH) were investigated (total n = 336). The labial surface of each specimen was prepared to a dimension of 10 × 5 × 3mm. Specimens were immersed in artificial saliva, coffee, red wine and denture cleaner with artificial aging to simulate denture use of 12 and 24 months in vivo. Measurements of translucency parameter (TP), shade change (ΔE), surface roughness (Ra) and Vickers hardness (VHN) were conducted at baseline and after artificial aging while immersed in the liquids at each timeframe. Data were statistically analysed by ANOVA and post-hoc test (SPSS Ver 27). Surfaces of specimens were analysed under scanning electron microscopy (SEM). Milled teeth had the highest overall translucency parameter (5.33 ± 0.76-7.3 ± 0.99). All materials had statistically significant change in translucency parameter and shade after 24 months simulated aging (p < 0.05), especially the milled and 3D-printed teeth (p < 0.01). Surface roughness of all materials were under plaque accumulation threshold Ra = 0.2 μm. At baseline, Vita Physiodens teeth (PMMA with microfillers) demonstrated the highest hardness (33.99 kgf/mm2±3.7), whereas both 3D-printed materials exhibited the lowest hardness (13.27 kgf/mm2±0.36-18.13 kgf/mm2±0.93). Artificial saliva, red wine and denture cleaner had a statistically significant impact (p < 0.05) on hardness of all materials (12.1 kgf/mm2±1.17-30.77 kgf/mm2±2.98). Milled teeth exhibited the best optical properties (highest overall translucency parameter and lowest shade change). Milled teeth were also the only material that showed colour change (ΔE values) within clinically acceptable limits. Denture cleaner had the most impact on optical and mechanical properties of all materials. Surface roughness and hardness of 3D-printed teeth had the most change after artificial aging.


The reversibility of phenytoin-induced IgA deficiency.
Phenytoin has been shown to induce serum IgA deficiency in patients with epilepsy. We have followed 37 phenytoin-treated patients with reduced serum IgA concentrations for 2-7 years. All anti-epileptic drug treatment was withdrawn in 8 patients. Phenytoin was substituted by other anti-epileptic drugs in 13 patients. Sixteen patients received phenytoin unchanged. The mean serum IgA concentration increased from 0.14 g/l to 0.71 g/l in the patients off drug treatment, and from 0.20 g/l to 0.84 g/l in the patients changing to other drugs. The mean IgA concentration increased from 0.21 g/l to 0.37 g/l in the patients with phenytoin unchanged, due to the increase of the IgA levels in a few patients who initially showed a slightly depressed IgA concentration. The overall increase of IgA concentrations was significant. When tested separately in each patient group, the difference was significant for the patients off all drugs, and for those changing from phenytoin to other drugs. The IgM concentration increased significantly when all patients were considered together. This was due to the increase of IgM in the patients no longer receiving phenytoin therapy. Withdrawal of phenytoin did not influence the IgG concentrations.


The value of Coronary Artery computed Tomography as the first-line anatomical test for stable patients with indications for invasive angiography due to suspected Coronary Artery Disease: CAT-CAD randomized trial.
The aim of this prospective, randomized trial was to evaluate whether the use of coronary computed tomography angiography (CCTA) as the first-line anatomical test in patients with suspected significant coronary artery disease (CAD) may reduce the number of coronary invasive angiographies (ICA), and expand the use of CCTA in patients currently diagnosed invasively. 120 patients (age:60.6 ± 7.9 years, 35% female) with indications to ICA were randomized 1:1 to undergo CCTA versus direct ICA. Outcomes were evaluated during the diagnostic and therapeutic periods. The number of invasively examined patients was reduced by 64.4% in the CCTA group as compared to the direct ICA group (21vs59,p < 0.0001). The number of patients with ICAs not followed by coronary intervention was reduced by 88.1% with the CCTA strategy (5vs42,p < 0.0001). Over the diagnostic and therapeutic course there were no significant differences regarding the median volume of contrast (CCTA 80.3 ml[65.0-165.0] vs ICA 90.0 ml[55.0-100.0], p = 0.099), while a non-significant trend towards higher radiation dose in the CCTA group was observed (9.9 mSv[7.0-22.1] vs 9.4 mSv[5.2-14.0], p = 0.05). There were no acute cardiovascular events. CCTA may hypothetically act as an effective 'gatekeeper' to the catheterization laboratory in the diagnosis of stable patients with current indications for ICA. This strategy may result in non-invasive, outpatient-based triage of two thirds of individuals without actionable CAD, obviating unnecessary invasive examinations. However, the longer follow-up is indispensable. CLINICALTRIALS. NCT02591992.


Big data-based urban greenness in Chinese megalopolises and possible contribution to air quality control.
Urban greenness is essential for people's daily lives, while its contribution to air quality control is unclear. In this study, Streetview big data of urban greenness and air quality data (Air Quality Index, PM2.5, PM10, SO2, NO2, O3, CO) from 206 monitoring stations from 27 provincial capital cities in China were analyzed. The national averages for the sky, ground and middle-level (shrub and short trees) view greenness were 5.4%, 5.5%, and 15.4%, respectively, and the sky:ground:middle ratio was 2:2:6. Street-view/bird-view greenness ratio averaged at 1.1. Large inter-city variations were observed in all the greenness parameters, and the weak associations between all street-view parameters and bird-eye greenspace percentage (21%-73%) indicate their representatives of different aspects of green infrastructures. All air quality parameters were higher in winter than in summer, except O3. Over 90% of air quality variation could be explained by socioeconomics and geoclimates, suggesting that air quality control in China should first reduce efflux from social economics, while geoclimatic-oriented ventilation facilitation design is also critical. For different air quality components, greenness had most significant associations with NO2, O3 and CO, and street-view/bird-view ratio was the most powerful indicator of all greenness parameters. Pooled-data analysis at national level showed that street-view greenness was responsible for 2.3% of the air quality variations in the summer and 3.6% in the winter; however, when separated into different regions (North-South China; East-West China), the explaining power increased up to 16.2%. Increased NO2 was accompanied with decreased O3, indicating NO titration effect. The higher O3 aligned with the higher street-view greenness, showing the greenness-related precursor risk for O3 pollution. Our study manifested that big internet data could identify the association of greenness and air pollution from street view scale, which can favor urban greenness management and evaluation in other regions where street-view data are available.


Oncogenic transformation of rat lung epitheloid cells by SV 40 DNA and restriction enzyme fragments.
Rat epitheloid lung cells were transformed with various preparations of SV40 dna using the Ca2+-precipitation technique. The amount of SV40 genetic information integrated into transformed clones was evaluated by DNA-DNA renaturation kinetics. The growth properties on plastic and in soft-agar were examined, as well as the ability to induce tumors in syngeneic new-born animals or in adult nude mice. One particular transformed line, which had received the Hpa II/BamH I A (59 per cent) fragment, was found to contain about 3 integrated copies of this fragment per cell and no significant amount of the Hpa II/BamH I B (41 per cent) fragment. This line which grew to high saturation densities and efficiently formed clones in low serum on plastic, produced tumors in both syngeneic rats and nude mice. Thus the Hpa II/BamH I A fragment, which mainly includes early viral information, was sufficient to impart these properties to rat epitheloid lung cells.


Transverse myelitis and hepatitis in varicella.
We describe a case with several grave complications of varicella rarely encountered in previously healthy young individuals.


Astonishing diversity of natural surfactants: 3. Carotenoid glycosides and isoprenoid glycolipids.
Carotenoid glycosides and isoprenoid glycolipids are of great interest, especially for the medicinal, pharmaceutical, food, cosmetic, flavor, and fragrance industries. These biologically active natural surfactants have good prospects for the future chemical preparation of compounds useful as antimicrobial, antibacterial, and antitumor agents, or in industry. More than 300 unusual natural surfactants are described in this review article, including their chemical structures and biological activities.


Treatment of Neuroendocrine Liver Metastases.
Neuroendocrine tumors are rare and slow-growing malignancies that commonly metastasize to the liver, resulting hormonal syndromes and death from liver failure. Surgical consultation and liver debulking are key components in management. Traditional surgical resection guidelines do not apply to these tumors as with other cancers. Surgical resection has shown survival benefit even in the event of an incomplete resection. Ablation may be used as an adjunct to resection or in patients who are not candidates for resection. Asymptomatic patients with high-volume disease do as well with intra-arterial therapy as with surgery.


A new method for the enzyme cytochemical staining of individual cells with the use of a polyacrylamide carrier.
A new method for enzyme cytochemical studies on individual cells is developed. Cells are incorporated in the matrix of a thin film of transparent polyacrylamide prior to incubation in a cytochemical medium. Five different kinds of individual cells, i.e. isolated rat hepatocytes, isolated mouse oocytes, cultivated human fibroblasts, rat thymocytes and human blood cells are used for testing the applicability of this method for the cytochemical demonstration of glucose-6-phosphate dehydrogenase with tetranitro BT. The incorporation technique solves at least some of the problems occurring with enzyme cytochemistry on single cells. The morphology of the cell is very well preserved, the formazan precipitation due to enzyme activity occurs entirely within the cell cytoplasm, the nothing dehydrogenase activity can be kept very low and the loss of cells is completely prevented with all cell types used.


Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia.
N-methyl-d-aspartate glutamate receptor (NMDAR) hypofunction is implicated in the impaired neuroplasticity and cognitive impairments associated with schizophrenia (CIAS). We hypothesized that enhancing NMDAR function by inhibiting the glycine transporter-1 (GLYT1) would improve neuroplasticity and thereby augment benefits of non-pharmacological cognitive training (CT) strategies. This study examined whether co-administration of a GLYT1 inhibitor and computerized CT would have synergistic effects on CIAS. Stable outpatients with schizophrenia participated in this double-blind, placebo-controlled, within-subject, crossover augmentation study. Participants received placebo or GLYT1 inhibitor (PF-03463275) for two 5-week periods separated by 2 weeks of washout. PF-03463275 doses (40 or 60 mg twice daily) were selected to produce high GLYT1 occupancy. To limit pharmacodynamic variability, only cytochrome P450 2D6 extensive metabolizers were included. Medication adherence was confirmed daily. Participants received 4 weeks of CT in each treatment period. Cognitive performance (MATRICS Consensus Cognitive Battery) and psychotic symptoms (Positive and Negative Syndrome Scale) were assessed in each period. 71 participants were randomized. PF-03463275 in combination with CT was feasible, safe, and well-tolerated at the doses prescribed but did not produce greater improvement in CIAS compared to CT alone. PF-03463275 was not associated with improved CT learning parameters. Participation in CT was associated with improvement in MCCB scores.


Prevalence of malnutrition among Samoan children aged 5 to 11 years in 2019-2020.
Globally, rapid economic development, urbanisation, and nutrition transitions have led to rising levels of malnutrition in all forms. The study objective was to document the prevalence of overweight/obesity, underweight, stunting, and anaemia among Samoan children in 2019-2020. Children from the Ola Tuputupua'e "Growing Up" in Samoa study at ages 5-11 years with complete physical assessments were included. Overweight/obesity, underweight, and stunting were classified using World Health Organisation Z-scores for body mass index-for-age (BMIZ> +1), weight-for-age (WAZ< -2SD), and height-for-age (HAZ< -2SD), respectively. Anaemia was defined as haemoglobin concentration <11.5 g/dL. Prevalence was compared by child age, sex, and census region of residence (representing urbanicity and exposure to nutrition transition) using Wilcoxon two-sample, Chi-square, or Fisher's exact tests. The prevalence of overweight/obesity, underweight, stunting, and anaemia was 36.2%, 0.5%, 1.6%, and 31.6%, respectively. Overweight/obesity in children was positively associated with age and highly prevalent in periurban and urban regions. While children living in the rural region with the lowest exposure to nutrition transition had the highest prevalence of mild-to-moderate stunting, anaemia prevalence was lower compared to those in the urban region. No sex differences in malnutrition were observed. Moderate-to-high levels of overweight/obesity and anaemia call for comprehensive intervention strategies.


Management of complications of ligament injuries of the wrist.
Despite advances in understanding the anatomy and biomechanics of wrist motion, intrinsic carpal ligament injuries are difficult to diagnose and treat. Even when an accurate diagnosis is made, there is no consensus on the most appropriate and reliable treatment. Injury predisposes to a progressive decline in wrist function and a predictable pattern of degenerative arthritis. To prevent inadequate outcomes, many treatment options exist, all having inherent benefits and complications. This article reviews the complications of intrinsic carpal ligament injuries and complications of their treatment. Methods to prevent and principles to manage the complications are discussed.


Laparoscopic abdominoperineal resection and anterior resection with curative intent for carcinoma of the rectum.
Within a 5-year period, 380 rectal carcinoma patients undergoing laparoscopic abdominoperineal excision or laparoscopic anterior resection were recruited to a multicenter study by 23 institutions in Germany and Austria. This study was initiated by the Laparoscopic Colorectal Surgery Study Group. One hundred forty-nine patients (39.2%) underwent abdominoperineal resection (APR), and 231 patients (60.8%) were treated by anterior resection (AR). The mean operating time was 208 min, and the conversion rate was 6.1%. Intraoperative complications, mostly vascular or bowel injuries, were observed in 22 patients (5.8%). Overall, a total of 257 postoperative complications and problems occurred in 143 patients, resulting in a morbidity rate of 37.6%. In the AR group, the anastomotic leakage rate increased as the distance of the tumor from the anal verge decreased. The perioperative mortality rate was low (6/1.6%). Most of the patients received a high transsection of the inferior mesenteric artery with radical lymph node dissection (342/90.0%); the mean number of recovered lymph nodes was 13.0, with considerable variation among the individual institutions. Intraoperative tumor cell spillage was reported in 12 patients (3.2%). Sufficient follow-up findings are available for 288 (77%) patients. To date, 19 patients have sustained a local recurrence (6.6%), and 30 (10.4%) have developed distant metastases. Within the (admittedly limited) mean follow-up of 24.8 months, the overall survival rate is 86.6%, the disease-free survival (freedom from both local recurrence and distant metastases) rate is 62.4% for APR, with the corresponding rates for AR being 71.7 and 54.8%, respectively, as established by the Kaplan-Meier function. These data show no alarmingly high recurrence rates at this time. In principle, laparoscopic anterior resection with curative intent generates considerably more reservations than laparoscopic abdominoperineal resection, which is technically much easier to perform.


Alpha-fetoprotein suppresses experimental allergic encephalomyelitis.
Experimental allergic encephalomyelitis (EAE), induced in guinea pigs by immunization with myelin basic protein (MBP) or whole CNS homogenate was successfully treated, as well as partially prevented, by daily administration of fetal alpha-fetoprotein (alpha FP). alpha FP which is produced in high quantities during pregnancy can inhibit both the cell-mediated immune response to MBP and the binding of MBP antibody to the antigen in vitro. It has a non-specific immunosuppressive effect on both the cellular and humoral responses. It is suggested that the ability of alpha FP to suppress an experimental autoimmune disease, as presented in this model of EAE, indicates that clinical remissions of human autoimmune disease during pregnancy may be attributed to the effect of this natural substance.


Drought-induced disturbance of carbohydrate metabolism in anthers and male abortion of two Gossypium hirsutum cultivars differing in drought tolerance.
Cotton pollen abortion, under drought stress, was closely associated with changes in anther carbohydrate metabolism, and pollen abortion rate due to drought was higher in drought-sensitive cultivars than drought-tolerant cultivars. Cotton reproductive failure under drought stress is intrinsically connected with altered male fertility, however, studies investigating the effect of drought stress on cotton male fertility are nonexistent. Thus, a drought stress experiment was conducted with two cotton cultivars, differing in drought tolerance, to study pollen fertility and anthers' physiology. Results indicated that drought stress reduced pollen fertility of both cultivars due to decreases in anther starch and adenosine triphosphate (ATP) synthesis. Lower assimilate supply capacity in conjunction with impaired activities of ADP-glucose pyrophosphorylase and soluble starch synthase were the main reasons for the decreased starch levels in drought-stressed anthers. The decreased activities of sucrose synthetase and acid invertase were responsible for the higher sucrose level in drought-stressed anthers than well-watered anthers and the changing trend of sucrose was intensified by the decreased expressions of sucrose synthase genes (GhSusA, GhSusB, GhSusD) and acid invertase genes (GhINV1, GhINV2). However, despite sucrose degradation being limited in drought-stressed anthers, glucose level was higher in droughted anthers than well-watered ones, and that might be attributed to the down-regulated respiration since decreased anther ATP levels were detected in drought-stressed plants. Furthermore, compared to the drought-tolerant cultivar, pollen fertility was more suppressed by drought stress for the drought-sensitive cultivar, and that was attributed to the larger decrease in starch and ATP contents.


STK33 Phosphorylates Fibrous Sheath Protein AKAP3/4 to Regulate Sperm Flagella Assembly in Spermiogenesis.
Spermatogenesis defects are important for male infertility; however, the etiology and pathogenesis are still unknown. Herein, we identified two loss-of-function mutations of STK33 in seven individuals with non-obstructive azoospermia. Further functional studies of these frameshift and nonsense mutations revealed that Stk33-/KI male mice were sterile, and Stk33-/KI sperm were abnormal with defects in the mitochondrial sheath, fibrous sheath, outer dense fiber, and axoneme. Stk33KI/KI male mice were subfertile and had oligoasthenozoospermia. Differential phosphoproteomic analysis and in vitro kinase assay identified novel phosphorylation substrates of STK33, fibrous sheath components A-kinase anchoring protein 3 and A-kinase anchoring protein 4, whose expression levels decreased in testis after deletion of Stk33. STK33 regulated the phosphorylation of A-kinase anchoring protein 3/4, affected the assembly of fibrous sheath in the sperm, and played an essential role in spermiogenesis and male infertility.


Preparation, physicochemical characterization, and in vitro starch digestibility on complex of Euryale ferox kernel starch with ferulic acid and quercetin.
The objective of the current research was to analyze the physicochemical, structural, and in vitro starch digestibility of Euryale ferox kernel starch (EFKS) in complexation with ferulic acid (FA) and quercetin (QR). XRD results have shown that FA and QR were attached to starch resulting crystalline complexes. SEM image showed a smooth, compact structure, indicating FA and QR assist in the reorganization of starch molecules. The 1H NMR spectra of starch-polyphenols complexes showed multiple additional peaks between 6.00 and 9.00 ppm due to the benzene ring and phenolic hydroxyl groups imparted from polyphenols. The shifting and emergence of the characteristic peak observed in the DSC thermogram confirmed that polyphenols were successfully attached to starch. Complexation alters colors, reduced swelling power, and increased the solubility of the complexes. Following the complexation of FA and QR, the content of resistant starch exhibited a significant rise, escalating from 7.69 % (control sample) to 49.39 % (10 % FA) and 54.68 % (10 % QR). This led to a notable reduction in the predicted glycemic index (pGI).The higher resistant starch in the complex is attributed due to the combined effects of the reordered structure of the complexes and the inhibitory activity of polyphenols against starch digestive enzymes. Therefore, EFKS-FA and EFKS-QR complex can be used as a functional ingredient for a low glycemic index food.


O(6)-methylguanine-DNA methyltransferase in glioma therapy: promise and problems.
Gliomas are the most frequent adult primary brain tumor, and are invariably fatal. The most common diagnosis glioblastoma multiforme (GBM) afflicts 12,500 new patients in the U.S. annually, and has a median survival of approximately one year when treated with the current standard of care. Alkylating agents have long been central in the chemotherapy of GBM and other gliomas. The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT), the principal human activity that removes cytotoxic O(6)-alkylguanine adducts from DNA, promotes resistance to anti-glioma alkylators, including temozolomide and BCNU, in GBM cell lines and xenografts. Moreover, MGMT expression assessed by immunohistochemistry, biochemical activity or promoter CpG methylation status is associated with the response of GBM to alkylator-based therapies, providing evidence that MGMT promotes clinical resistance to alkylating agents. These observations suggest a role for MGMT in directing adjuvant therapy of GBM and other gliomas. Promoter methylation status is the most clinically tractable measure of MGMT, and there is considerable enthusiasm for exploring its utility as a marker to assign therapy to individual patients. Here, we provide an overview of the biochemical, genetic and biological characteristics of MGMT as they relate to glioma therapy. We consider current methods to assess MGMT expression and discuss their utility as predictors of treatment response. Particular emphasis is given to promoter methylation status and the methodological and conceptual impediments that limit its use to direct treatment. We conclude by considering approaches that may improve the utility of MGMT methylation status in planning optimal therapies tailored to individual patients.


Health literacy and functional health status among older adults.
Individuals with limited health literacy have less health knowledge, worse self-management skills, lower use of preventive services, and higher hospitalization rates. We evaluated the association between health literacy, self-reported physical and mental health functioning, and health-related activity limitations among new Medicare managed care enrollees. A cross-sectional survey of 2923 enrollees was conducted in Cleveland, Ohio; Houston, Tex; Tampa, Fla; and Fort Lauderdale-Miami, Fla. Health literacy was measured using the short form of the Test of Functional Health Literacy in Adults. We used outcome measures that included scores on the physical and mental health functioning subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey, difficulties with instrumental activities of daily living and activities of daily living, and limitations because of physical health and pain. After adjusting for the prevalence of chronic conditions, health risk behaviors, and sociodemographic characteristics, individuals with inadequate health literacy had worse physical function (67.7 vs 78.0, P<.001) and mental health (76.2 vs 84.0, P<.001) than individuals with adequate health literacy. Individuals with inadequate health literacy were more likely to report difficulties with instrumental activities of daily living (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.74-2.92) and activities of daily living (OR, 2.83; 95% CI, 1.62-4.96), limitations in activity because of physical health (OR, 1.79; 95% CI, 1.39-2.32), fewer accomplishments because of physical health (OR, 1.90; 95% CI, 1.48-2.45), and pain that interferes with normal work activities (OR, 2.01; 95% CI, 1.46-2.77). Among community-dwelling older adults, inadequate health literacy was independently associated with poorer physical and mental health.


Potentiation of d-tubocurarine (d-Tc) neuromuscular blockade in cats by lithium chloride.
I.v. infusion of LiCl at 1.0 mEq/0.25 ml/min produced significant decrease in plasma Na+ from 158 +/- 4.5 mEq/l (p less than 0.025) and in Ca2+ from 7.8 +/- 0.34 to 6.8 +/- 0.24 mg% (p less than 0.01) with insignificant increase in K+. No significant changes in plasma electrolytes were observed on infusion of NaCl. The d-Tc induced neuromuscular blockade in Li Cl infused animals was significantly greater than that in Na Cl infused ones.


Lignans from the root of Valeriana jatamansi and their biological evaluation.
Investigation on the chemical components of Valeriana jatamansi Jones (Caprifoliaceae), a new lignan with pyran-ring, dipsalignan G (1), along with eight known compounds (2-9) were isolated. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HR-ESI-MS spectroscopic data. Additionally, possible biosynthetic pathway of 1 was proposed. Finally, biological evaluation results showed that 8 had significant scavenging ability to ABTS and DPPH free radicals, with IC50 values of 1.35 ± 0.01 and 2.94 ± 0.01 μg/ml, respectively.


Anticoagulant selection influences flow cytometric determination of CD11b upregulation in vivo and ex vivo.
We recently devised three-colour flow cytometric assay for evaluating expression of CD11b on neutrophils and monocytes in circulation. Artefactual upregulation of CD11b ex vivo was minimized by cooling blood samples on ice. In this communication we further characterize the method in terms of different anticoagulants. EDTA was less optimal than ACD or heparin because (i) saturating concentrations of CD11b antibody (clone D12) were not achieved with resting cells; (ii) CD11b fluorescence intensity of synovial fluid cells, i.e., in vivo activated cells expressing CD11b at high levels, was significantly lower in EDTA plasma, and (iii) EDTA mediated more cell damage at 37 degrees C, as determined by PI staining. The fluorescence data suggested that D12 antibody binding was dependent on divalent cations. Saturating concentrations in the presence of EDTA in medium were easily obtained with synovial fluid cells and peripheral blood phagocytes activated with chemotactic peptide FMLP, suggesting that cell activation decreased cation concentrations required for D12 antibody binding. Using another CD11b antibody (2MPL19c), whose binding proved to be cation independent, it was shown that CD11b upregulation was not affected by EDTA. ACD was superior to heparin and phenylalanylprolylarginyl chloromethyl ketone (PPACK), a thrombin inhibitor, because cell counts were significantly lower in heparinized samples in cold, and in PPACK-anticoagulated samples treated with LPS at 37 degrees C. Kinetics of L-selectin shedding was similar in heparin and ACD, suggesting that cell loss did not derive from differences in cell activation. In comparison of buffy coat cell assay and whole blood assay, neutrophil CD11b expression was similar but background fluorescence was significantly higher in whole blood preparations. This implies that nonspecific antibody binding may occur more in whole blood assay, whereas in the buffy coat cell assay, sample manipulation procedures may slightly increase CD11b antibody binding, but not control antibody binding. Finally, it was confirmed that warming from 0 degrees C, but not from room temperature, to 37 degrees C increased CD11b expression significantly on neutrophils, and it was further shown that monocytes undergo similar changes. Cooling did not upregulate CD11b, and completely prevented LPS-induced upregulation. In conclusion, the results support use of ACD in evaluating CD11b expression; if EDTA is used, it is important to make sure that binding of CD11b antibody selected does not require presence of divalent cations in medium.


[16S approximately 23S rDNA internal transcribed spacer sequence analysis and its application in mycobacterial identification].
To study the applicability of the 16S approximately 23S rDNA internal transcribed spacer (ITS) sequences in mycobacterial identification. The 16S approximately 23S rDNA ITS sequences of 22 mycobacterial species (30 reference strains and 16 clinical isolates) were determined by PCR-direct sequencing. The sequences determined by this study and those reported in Genbank were analysed by Clustal program (MegAlign Package [Windows Version 4.01]; DNASTAR, Madison, Wis). The percentage similarity of sequence pairs was calculated and a cluster analysis dendrogram was constructed by PHYLIP package. The 16S approximately 23S rDNA ITS sequences among mycobacterial species had highly polymorphism except that Mycobacterium tuberculosis complex (MTC) sequences were highly consistent. The similarity between sequence pairs was 30.4% to 86.5%. Mycobacterial species could be isolated by cluster analysis dendrogram. The results showed that sequence analysis of the 16S approximately 23S rDNA ITS can differentiate MTC from nontuberculous mycobacteria (NTM) and identify NTM at species level. 16S approximately 23S rDNA ITS sequences can be used as target genes in mycobacterial identification.


Clinical correlates and heritability of cystatin C (from the Framingham Offspring Study).
Cystatin C (CysC) is associated with cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined the clinical correlates and heritability of CysC and determined if associations between CVD risk factors and CysC differed by CKD status. Among Framingham Heart Study offspring (examined from 1998-2001, n = 3,241, mean age 61 years, 54% women), the 95(th) percentile cut-point was developed for CysC in a healthy subset (n = 779) after excluding participants with diabetes, hypertension, low high-density lipoproteins, obesity, smoking, high triglycerides, prevalent CVD, and CKD (as defined by glomerular filtration rate <60 mL/min per 1.73 m(2)). Multivariable logistic regression was used to evaluate the association between CVD risk factors and high CysC (CysC > or =95(th) percentile cut-point). In a family-based subset (n = 1,188), we estimated CysC heritability using the variance-components method. The cut-point for high CysC was 1.07 mg/L. Age, hypertension treatment, low diastolic blood pressure, body mass index, low high-density lipoprotein cholesterol, and smoking were associated with high CysC in multivariable models. These factors and estimated glomerular filtration rate (egFR) explained 39.2% of CysC variability (R(2)). Excluding CKD did not materially change associations. Multivariable-adjusted heritability for CysC was 0.35 (p <0.001). In conclusion, high CysC is associated with CVD risk factors even in the absence of CKD. The strong associations between CysC and CVD risk factors may partially explain why CysC is a strong predictor of incident CVD.


The value of NLR versus MLR in the short-term prognostic assessment of HBV-related acute-on-chronic liver failure.
Systemic inflammation is associated with the development and progression of hepatitis B-associated acute-on-chronic liver failure (HBV-ACLF). The neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic biomarker in patients with HBV-ACLF. However, the role of the monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in multiple diseases is rarely mentioned in HBV-ACLF. We included a total of 347 patients with HBV-ACLF who met the definition of the Chinese Guidelines for the Diagnosis and Treatment of Liver Failure (2018 edition). Among them, 275 cases were included retrospectively, and 72 cases were collected prospectively. Clinical characteristics and laboratory examination data were collected from medical records within 24 h after diagnosis to calculate MLR and NLR levels, and lymphocyte subpopulation counts were collected in prospectively included patients. Of the 347 patients with HBV-ACLF, 128 patients in the non-surviving group had a mean age of 48.87 ± 12.89 years; 219 patients in the survival group had a mean age of 44.80 ± 11.80 years and a combined 90-day mortality rate of 36.9%. The median MLR was higher in the non-survivors than in the survivors (0.690 vs 0.497, P < 0.001). MLR values were significantly associated with 90-day mortality in HBV-ACLF (OR 6.738; 95% CI 3.188-14.240, P < 0.001). The AUC for the predictive power of the combined MLR and NLR analysis for HBV-ACLF was 0.694, and the calculated MLR threshold was 4.495. In addition, in the analysis of peripheral blood lymphocyte subsets in HBV-ACLF, a significant decrease in the number of circulating lymphocytes was found in HBV-ACLF patients in the non-surviving group (P < 0.001), with a predominant decrease in the number of CD8 + T cells and no significant difference in the number of CD4 + T cells, B cells or NK cells. Increased MLR values are associated with 90-day mortality in patients with HBV-ACLF, and the MLR may serve as a potential prognostic indicator for patients with HBV-ACLF. Decreased CD8 + T-cell counts may be associated with poor survival in patients with HBV-ACLF.


Duration of the seminiferous epithelial cycle in the mature guinea pig: influence of unilateral orchiectomy.
The effect of unilateral orchiectomy on the seminiferous epithelial cycle in the mature guinea pig was studied. No significant change in the cycle duration was found. Thus, the previously reported hyperplasia of the contralateral testis is due to an increased number of cells entering the maturation process rather than to an acceleration of the cycle of seminiferous epithelium.


Characteristics of infertile women in the United States and their use of infertility services.
National estimates of demographic characteristics are shown for infertile women compared with those who were fecund, women with primary versus secondary infertility, and infertile women who had, and had not, sought infertility services. Overall, 30% of infertile women had primary infertility, and 70% had secondary infertility. Women with primary infertility were twice as likely to seek services as women with secondary infertility. Many demographic characteristics of women with secondary infertility who sought services differed from those of women who had not sought services. There were fewer differences among women with primary infertility. These findings have implications for the generalizability of results from clinic-based studies and suggest that more research is needed on the barriers to service among infertile couples.


Activation of a p53-mediated apoptotic pathway in quiescent lymphocytes after the inhibition of DNA repair by fludarabine.
The inhibition of UV-initiated DNA repair by 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A), the nucleoside of fludarabine, induces apoptosis in quiescent human lymphocytes. The sensing and signaling mechanisms after DNA repair inhibition by F-ara-A are unknown. The purpose of this study was 2-fold: (a) determine the importance of the inhibition of DNA repair processes for F-ara-A cytotoxicity and (b) identify the apoptotic signaling mechanism(s) that respond to DNA repair inhibition by F-ara-A. Lymphocytes were treated with F-ara-A to accumulate the active triphosphate metabolite and subsequently DNA repair was activated by UV irradiation. Cell viability was quantitated with respect to the treatments alone and in combination to evaluate the actions of F-ara-A inhibition of DNA repair on p53 status and Fas death receptor ligand expression and function. Preincubation of lymphocytes with 3 micro M F-ara-A inhibited DNA repair initiated by 2 J/m(2) UV and induced greater than additive apoptosis after 24 h. After equivalent repair inhibition with 0.1 micro M aphidicolin, there was apparently lesser p53 activation and significantly less apoptosis in irradiated lymphocytes than after 3 micro M F-ara-A. Blocking the incorporation of F-ara-A nucleotide into repairing DNA using 30 micro M aphidicolin lowered the apoptotic response to that observed with aphidicolin and UV. p53 serine 15 phosphorylation and protein accumulation were detected 2 h after treatment. Fas and Fas ligand mRNA expression and protein levels increased significantly after repair inhibition. Neutralizing antibodies against Fas or Fas ligand significantly reduced apoptosis. These results suggest that inhibition of UV-induced DNA repair by F-ara-A is critical for cytotoxicity and that induction of apoptosis may be conducted by a p53-mediated signaling mechanism to the Fas death pathway.


Corrections.
Ravimohan S, Tamuhla N, Steenhoff AP, et al. Immunological profiling of tuberculosis-associated immune reconstitution inflammatory syndrome and non-immune reconstitution inflammatory syndrome death in HIV-infected adults with pulmonary tuberculosis starting antiretroviral therapy: a prospective observational cohort study. Lancet Infect Dis 2015; published online Feb 9. http://dx.doi.org/10.1016/S1473-3099(15)70008-3— In figure 1B of this Article, the marker and line for MCP-1 had been moved up and were consequently missing from the MCP-1 row, and the square for eotaxin was not in line with the marker. This figure has been corrected as of Feb 11, 2015, and the printed Article will be correct.


RORs in autoimmune disease.
The retinoic acid receptor-related orphan receptor (ROR) subfamily of nuclear receptors are transcription factors involved in the maintenance of circadian rhythm and are essential for proper immune function. The T cell-specific isoform, RORγt, is required for T helper 17 cells (TH17) development and it has been implicated in the pathogenesis of autoimmune diseases including multiple sclerosis and rheumatoid arthritis. Thus, pharmacological repression of RORγt may provide a strategy for therapeutic intervention in autoimmune disorders. This chapter provides a summary of the current status for target validation and development of new chemical entities targeting RORγt.


Characteristics and outcomes of primary interposition vascular grafts in free flap breast reconstruction.
There is paucity of data on primary interposition vascular grafts (IVG) use in microsurgery. Our study examines the characteristics, indications and outcomes of IVG in free flap breast reconstruction. All cases of breast reconstruction with free flaps between January 2013 and June 2018 were examined and cases with primary IVG were included. Data were collected on patient, flap and graft characteristics, indications and outcomes. A total of 76 IVG, specifically 65 vein grafts and 11 arterial grafts, were used for 49 (of 1547) flaps in 48 (of 1346) cases. Of these, 52 grafts were primarily used to lengthen the pedicle and aid flap inset and 24 grafts to augment venous flow; 49 grafts were harvested from the flap harvest site, 7 from the anastomosis recipient site and 20 from a separate site. Of the total, 16.7% (8/49 flaps) required salvage procedures - seven cases for venous congestion and one for ischaemic compromise - in comparison to 4.3% in cases without IVG (65/1498) (p<0.0001). Out of 49 IVG flaps, three (6.1%) failed in comparison to 1.7% (26/1498), where IVG flaps were not used (p<0.05). Two were transverse upper gracilis flaps with vessel calibre mismatch, and one lumbar artery perforator (LAP) flap with past infected implant and failed deep inferior epigastric artery (DIEP). We present the largest number of primary vascular grafts for free flap breast reconstruction in the literature. Primary IVG were used for at-risk flaps and had a success rate of 93.9%. This shows that IVG are a viable option to prevent venous congestion and lengthen the pedicle to aid inset and shaping; they are associated with higher complication rates bearing in mind the high-risk profile of the flaps these are used for.


The influence of the muscarinic agonist RS 86 on the cortisol system.
To test the assumption that activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is mediated by cholinergic neurons, the cortisol response to the administration of the muscarinic agonist RS 86 was investigated in 12 healthy volunteers. In addition, prolactin and growth hormone secretion patterns were assessed. No significant increase in plasma cortisol or growth hormone was observed after the administration of 1.5 and 3.0 mg RS 86, respectively. However, there was a slight increase in prolactin serum concentration after 3.0 mg RS 86. As RS 86, when used in the same dose range, causes a shortening of rapid eye movement (REM) latency and displays antimanic properties, it is unlikely that a reduced dosage of RS 86 in itself accounts for the lack of stimulation of the HPA axis. If one assumes that in humans the stimulation of the HPA axis is under cholinergic control, then the failure of RS 86 to increase cortisol might be attributable to the fact that different subtypes of muscarinic neurons, for which RS 86 is not a full agonist, are involved, or else nicotinic neurons are implicated in the activation of the HPA axis.


Construction of a cyanobacterium synthesizing cyclopropane fatty acids.
Microalgae have received much attention as a next-generation source of biomass energy. However, most of the fatty acids (FAs) from microalgae are multiply unsaturated; thus, the biofuels derived from them are fluid, but vulnerable to oxidation. In this study, we attempted to synthesize cyclopropane FAs in the cyanobacterium Synechocystis sp. PCC 6803 by expressing the cfa gene for cyclopropane FA synthase from Escherichia coli with the aim of producing FAs that are fluid and stable in response to oxidization. We successfully synthesized cyclopropane FAs in Synechocystis with a yield of ~30% of total FAs. Growth of the transformants was altered, particularly at low temperatures, but photosynthesis and respiration were not significantly affected. C16:1(∆9) synthesis in the desA(-)/desD(-) strain by expression of the desC2 gene for sn-2 specific ∆9 desaturase positively affected growth at low temperatures via promotion of various cellular processes, with the exceptions of photosynthesis and respiration. Estimation of the apparent activities of desaturases suggested that some acyl-lipid desaturases might recognize the lipid side chain.


A review of the pangenome: how it affects our understanding of genomic variation, selection and breeding in domestic animals?
As large-scale genomic studies have progressed, it has been revealed that a single reference genome pattern cannot represent genetic diversity at the species level. While domestic animals tend to have complex routes of origin and migration, suggesting a possible omission of some population-specific sequences in the current reference genome. Conversely, the pangenome is a collection of all DNA sequences of a species that contains sequences shared by all individuals (core genome) and is also able to display sequence information unique to each individual (variable genome). The progress of pangenome research in humans, plants and domestic animals has proved that the missing genetic components and the identification of large structural variants (SVs) can be explored through pangenomic studies. Many individual specific sequences have been shown to be related to biological adaptability, phenotype and important economic traits. The maturity of technologies and methods such as third-generation sequencing, Telomere-to-telomere genomes, graphic genomes, and reference-free assembly will further promote the development of pangenome. In the future, pangenome combined with long-read data and multi-omics will help to resolve large SVs and their relationship with the main economic traits of interest in domesticated animals, providing better insights into animal domestication, evolution and breeding. In this review, we mainly discuss how pangenome analysis reveals genetic variations in domestic animals (sheep, cattle, pigs, chickens) and their impacts on phenotypes and how this can contribute to the understanding of species diversity. Additionally, we also go through potential issues and the future perspectives of pangenome research in livestock and poultry.


Improved insulin sensitivity and metabolic flexibility in ghrelin receptor knockout mice.
Stimulation of the ghrelin receptor (GhrR) by ghrelin results in a variety of metabolic changes including increased food intake, fat storage and insulin resistance. Loss of ghrelin signaling is protective against diet-induced obesity, suggesting that ghrelin plays a significant homeostatic role in conditions of metabolic stress. We examined glycemic control in GhrR -/- mice fed a high-fat diet, and used indirect calorimetry to assess fuel substrate usage and energy expenditure. GhrR -/- mice fed a high-fat diet had several measures of greater insulin sensitivity, including: lower fasted blood glucose and plasma insulin, lower %Hb(A1c), lower insulin levels during glucose tolerance tests, and improved performance in hyperinsulinemic-euglycemic and hyperglycemic clamp studies. GhrR -/- mice fed a high-fat diet did not develop hepatic steatosis and had lower total cholesterol, relative to controls. Furthermore, GhrR -/- mice demonstrated a lower intestinal triglyceride secretion rate of dietary lipid. GhrR -/- mice have higher respiratory quotients (RQ), indicating a preference for carbohydrate as fuel. The range of RQ values was wider in GhrR -/- mice, indicating greater metabolic flexibility and insulin sensitivity in these animals. We therefore propose that loss of ghrelin signaling promotes insulin sensitivity and metabolic flexibility, and protects against several fatty diet-induced features of metabolic syndrome due to convergent changes in the intake, absorption and utilization of energy.


In silico evaluation of drugs used in treatment of oral lichen planus.
Oral lichen planus (OLP) is a chronic T cell-mediated, immunological, mucocutaneous disease with a number of genes and inflammatory mediators implicated in its pathogenesis. Heart shock protein 70 and the proinflammatory mediator TNFα have been predominantly involved in the etiopathogenesis of oral lichen planus. In this study, the action of 27 commonly used drugs for treating OLP at HSP70 and TNFα were evaluated by molecular docking using Maestro Schrodinger version 10.1. X-ray crystallographic structures of the target proteins, that is, Heat Shock Protein 70 (PDB Code: 6FDT) and tumor necrosis factor alpha-1 (PDB Code: 1TNF) were obtained from Protein Data Bank (PDB). The structures of the ligands (27 drugs) were obtained from PubChem in.sdf format. Using Ligprep, pre-processing of the ligands was done. Extra-precision docking was performed with the prepared protein and the ligands. With respect to HSP70, the highest dock score (-4.768) and glide score (-4.818) were seen with hydroxychloroquine (HCQ), followed by epigallocatechin gallate (green tea), methotrexate, and curcumin. The highest dock (-9.525) and glide score (-9.584) in TNFα were seen in with epigallocatechin gallate, followed by HCQ, dapsone, and methotrexate. The results of the study tend to explain the clinical use of HCQ in recalcitrant and severe cases, as well as the anti-inflammatory property of epigallocatechin gallate. The results of the study open ventures for exploring the in silico behavior of drugs for effective pathological management.


Membrane remodelling in bacteria.
In bacteria the ability to remodel membrane underpins basic cell processes such as growth, and more sophisticated adaptations like inter-cell crosstalk, organelle specialisation, and pathogenesis. Here, selected examples of membrane remodelling in bacteria are presented and the diverse mechanisms for inducing membrane fission, fusion, and curvature discussed. Compared to eukaryotes, relatively few curvature-inducing proteins have been characterised so far. Whilst it is likely that many such proteins remain to be discovered, it also reflects the importance of alternative membrane remodelling strategies in bacteria where passive mechanisms for generating curvature are utilised.


Pharmacokinetics of pirprofen in young volunteers and elderly patients.
Plasma concentrations of pirprofen were measured in 11 elderly arthritic patients and 6 healthy young volunteers at the beginning and end of 8 days treatment with 400 mg doses twice daily. The mean ages of the two groups were 74.5 and 21.8 years, respectively. There were no statistically significant differences in peak concentrations, times to peak, areas under the curve or terminal elimination half-lives between the groups after single dosing. Repeated dosing increased plasma drug concentrations in both groups but the extent was as predicted from the single dose data. Again there were no statistically significant differences between the groups, although pre-dosing plasma concentrations were higher in the elderly compared with the young individuals. The results of this relatively small study suggest that advancing age and arthritic disease appear to have little influence on the pharmacokinetics of pirprofen and no modification in the dosage recommendation in elderly patients without overt renal or hepatic impairment is indicated.


MCM3AP and POMP Mutations Cause a DNA-Repair and DNA-Damage-Signaling Defect in an Immunodeficient Child.
Immunodeficiency patients with DNA repair defects exhibit radiosensitivity and proneness to leukemia/lymphoma formation. Though progress has been made in identifying the underlying mutations, in most patients the genetic basis is unknown. Two de novo mutated candidate genes, MCM3AP encoding germinal center-associated nuclear protein (GANP) and POMP encoding proteasome maturation protein (POMP), were identified by whole-exome sequencing (WES) and confirmed by Sanger sequencing in a child with complex phenotype displaying immunodeficiency, genomic instability, skin changes, and myelodysplasia. GANP was previously described to promote B-cell maturation by nuclear targeting of activation-induced cytidine deaminase (AID) and to control AID-dependent hyperrecombination. POMP is required for 20S proteasome assembly and, thus, for efficient NF-κB signaling. Patient-derived cells were characterized by impaired homologous recombination, moderate radio- and cross-linker sensitivity associated with accumulation of damage, impaired DNA damage-induced NF-κB signaling, and reduced nuclear AID levels. Complementation by wild-type (WT)-GANP normalized DNA repair and WT-POMP rescued defective NF-κB signaling. In conclusion, we identified for the first time mutations in MCM3AP and POMP in an immunodeficiency patient. These mutations lead to cooperative effects on DNA recombination and damage signaling. Digenic/polygenic mutations may constitute a novel genetic basis in immunodeficiency patients with DNA repair defects.


The systematic review and meta-analysis of free flap safety in the elderly patients.
Prolonged mean life expectancy gives rise to a more populated and older patient group. With increasing number of cases during the past decades, older patients are regarded as candidates for microsurgical interventions. Whether advanced patient age is an independent risk factor for microsurgical reconstruction is still an ongoing matter of debate. The Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, CINAHL and EMBASE databases were screened for combination of the key words "elderly", "geriatric", "advanced age", "free flap", "microsurgery", free tissue transfer" by using time limits between 1989 and 2015. According to results of the meta-analysis, there was no significant difference in the flap success rates(P =.39, CI = 0.848 to 2.329) and surgical complication rates (P = .83, CI = 0.792 to 1.163) between the young and elderly patient groups. However, the systemic complication rates(P = .02, CI = 1.468 to 3.572), preoperative ASA scores(P < .0001, CI = 0.342 to 1.078), and mortality rates (P = .03, CI = 2.636 to 9.055) were found to be significantly higher in the elderly patients. Although an increased rate of systemic complications and mortality has been associated with advanced age, our study results showed no significant difference between the flap success rates and surgical complications. A successful reduction in systemic complications would bring the risk level of reconstructive microsurgical interventions of the elderly patient group to the level of the young patient group. © 2017 Wiley Periodicals, Inc. Microsurgery 37:442-450, 2017.


Freeze-fracture studies on the giant axon and ensheathing Schwann cells of the squid.
The giant axons and encompassing sheaths from the stellar nerves of the squids Sepioteuthis sepioidea and Loligo forbesi have been analysed by freeze-fracture. The axolemma exhibits many intramembranous particles (IMPs) that fracture onto the cytoplasmic membrane half-leaflet (P-face); the larger IMPs may be aggregated into clusters. Axoplasmic subsurface cisternae are found beneath this membrane. Clustered or aligned arrays of P-face IMPs are also found on the membranes of the Schwann cells that intimately encapsulate the giant axons as well as 'capitate' projections of Schwann cells into the axons. When adjacent Schwann cells abut directly against one another, aligned E-face IMPs are found along the fracture plane of the upturning membranes. These E-face alignments of IMPs have complementary furrows on the Schwann cell membranes which exhibit no complementary structure on the axolemma as they represent the clefts between adjacent glial cells. The other Schwann cell membranes exhibit P-face dimples and E-face (extracellular membrane half-leaflet) protuberances which may reflect endo- or exocytotic activity; alternatively they may represent caveolae. Comparable structures are occasionally observed at axo-glial interfaces. However, those in the Schwann cell membrane could be part of the transverse tubular lattice system which also exists in adaxonal glia. Beyond the Schwann cells, layers of endoneurial cells (fibrocytes) are interleaved by collagen-filled spaces. These cells exhibit extensive cross-fractured intracellular invaginations as well as inpushings of the extracellular matrix material. Their membranes exhibit a large number of IMPs.


The educational community and its knowledge and perceptions of native and invasive alien species.
Environmental education seeks to foster an appreciation for nature and the impact of humans on it while introducing citizens to scientific thinking. Biological invasions affect different aspects of life on earth and mandate urgent management actions. Education and public awareness are strongly recommended for successful prevention and management of invasive alien species (IAS). This work presents a study on knowledge and perception of the educational community of Argentina about native species and IAS. We designed an on-line semi-structured questionnaire to examine perception of the environment, recognition of native species and IAS and awareness about biological invasions. Educators recognised an important number of biotic components, mostly represented by trees, birds and mammals. Recognition of native species and IAS, and awareness of biological invasions were different between NST (Natural Science Teachers) and non-NST. Respondents had different performances when they were exposed to recognising native species though written names or photographs. Out of 532 respondents, 56% knew what biological invasions are, 21% answered "Maybe" and 23% had never heard about them. We need to foster capacity-building and encourage a two-way communication between educators and scientists, formally and informally, to engage the participation of the whole society in recognition, prevention and management of IAS.


Pneumonia virus of mice: severe respiratory infection in a natural host.
Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to human and bovine respiratory syncytial viruses. Among the prominent features of this infection, robust replication of PVM takes place in bronchial epithelial cells in response to a minimal virus inoculum. Virus replication in situ results in local production of proinflammatory cytokines (MIP-1alpha, MIP-2, MCP-1 and IFNgamma) and granulocyte recruitment to the lung. If left unchecked, PVM infection and the ensuing inflammatory response ultimately lead to pulmonary edema, respiratory compromise and death. In this review, we consider the recent studies using the PVM model that have provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. We also highlight several works that have elucidated acquired immune responses to this pathogen, including T cell responses and the development of humoral immunity. Finally, we consider several immunomodulatory strategies that have been used successfully to reduce morbidity and mortality when administered to PVM-infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe respiratory virus infections in human subjects.


Facilitatory and inhibitory modulation by endogenous adenosine of noradrenaline release in the epididymal portion of rat vas deferens.
The present study aimed at determining the modulation by adenosine of the release of noradrenaline in the epididymal portion of the rat vas deferens. The tissues were treated with pargyline and perifused in the presence of desipramine and yohimbine. Up to four periods of electrical stimulation were applied (5 Hz, 9 min). The A1-adenosine receptor selective agonist R-N6-phenylisopropyladenosine (R-PIA; 100-900 nmol.l-1) reduced, whereas the A2A-receptor selective agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30 nmol.l-1) increased the electrically-evoked noradrenaline overflow in a concentration-dependent manner. The nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA; 30-300 nmol.l-1) reduced noradrenaline overflow, but the effect did not depend on the concentration. Adenosine deaminase at the concentration of 0.5 mu.ml-1 decreased but at that of 2.0 mu.ml-1 increased noradrenaline overflow. The inhibitors of adenosine uptake, S-(4-nitrobenzyl)-6-thioinosine (NBTI; 50 nmol.l-1) and dipyridamole (3 mumol.l-1), increased the electrically-evoked noradrenaline overflow. The A1-adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 20 nmol.l-1) caused an increase whereas the A2-adenosine receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine (DMPX; 0.1 mumol.l-1) caused a decrease. NBTI (50 nmol.l-1), partially antagonized the effect of both DPCPX (20 nmol.l-1) and DMPX (0.1 mumol.l-1).(ABSTRACT TRUNCATED AT 250 WORDS)


Fabrication of cross-linked chitosan beads grafted by polyethylenimine for efficient adsorption of diclofenac sodium from water.
Diclofenac sodium (DS) is an emerging contaminant that is toxic and remains at high concentrations in natural aquatic environments. The aim of this study was to fabricate a novel spherical polymeric adsorbent composed of cross-linked chitosan beads grafted by polyethylenimine (PEI) to remove DS from water. The adsorbents were thoroughly characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, elemental analyses, and X-ray photoelectron spectroscopy. A cross-linking step was expected to enhance adsorption. The experimental data obtained from a series of adsorption experiments were fit well by the Langmuir isotherm model and pseudo-second-order model. The epichlorohydrin-PEI adsorbent (EPCS@PEI) showed a maximum adsorption capacity of 253.32 mg/g and removal efficiency of nearly 100% for the DS in the initial 50 mg/L solution. Therefore, EPCS@PEI is proposed as a potential adsorbent for DS removal, where these initial findings are expected to promote further design and fabrication of effective adsorbents for practical applications.


A systematic review of the safety information contained within the Summaries of Product Characteristics of medications licensed in the United Kingdom for Attention Deficit Hyperactivity Disorder. how does the safety prescribing advice compare with national guidance?
The safety of paediatric medications is paramount and contraindications provide clear pragmatic advice. Further advice may be accessed through Summaries of Product Characteristics (SPCs) and relevant national guidelines. The SPC can be considered the ultimate independent guideline and is regularly updated. In 2008, the authors undertook a systematic review of the SPC contraindications of medications licensed in the United Kingdom (UK) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). At that time, there were fewer contraindications reported in the SPC for atomoxetine than methylphenidate and the specific contraindications varied considerably amongst methylphenidate formulations. In 2009, the European Medicines Agency (EMA) mandated harmonisation of methylphenidate SPCs. Between September and November 2011, there were three changes to the atomoxetine SPC that resulted in revised prescribing information. In addition, Clinical Guidance has also been produced by the National Institute for Health and Clinical Excellence (NICE) (2008), the Scottish Intercollegiate Guidelines Network (SIGN) (2009) and the British National Formulary for Children (BNFC). An updated systematic review of the Contraindications sections of the SPCs of all medications currently licensed for treatment of ADHD in the UK was undertaken and independent statements regarding contraindications and relevant warnings and precautions were then compared with UK national guidance with the aim of assessing any disparity and potential areas of confusion for prescribers. As of November 2011, there were seven medications available in the UK for the treatment of ADHD. There are 15 contraindications for most formulations of methylphenidate, 14 for dexamfetamine and 5 for atomoxetine. Significant differences exist between the SPCs and national guidance part due to the ongoing reactive process of amending the former as new information becomes known. In addition, recommendations are made outside UK SPC licensed indications and a significant contraindication for methylphenidate (suicidal behaviours) is missing from both the NICE and SIGN guidelines. Particular disparity exists relating to monitoring for suicidal and psychiatric side effects. The BNFC has not yet been updated in line with the European Union (EU) Directive on methylphenidate; it does not include any contraindications for atomoxetine but describes contraindications for methylphenidate that are no longer in the SPC. Clinicians seeking prescribing advice from critical independent sources of data, such as SPCs and national guidelines, may be confused by the disparity that exists. There are major differences between guidelines and SPCs and neither should be referred to in isolation. The SPC represents the most relevant source of safety data to aid prescribing of medications for ADHD as they present the most current safety data in line with increased exposure. National guidelines may need more regular updates.


Integrating traditional indigenous medicine and western biomedicine into health systems: a review of Nicaraguan health policies and miskitu health services.
Throughout the world, indigenous peoples have advocated for the right to retain their cultural beliefs and traditional medicine practices. In 2007, the more than 370 million people representing 5000 distinct groups throughout the world received global recognition with the adoption of the United Nations Declaration on the Rights of Indigenous Peoples (UNDRIP). UNDRIP Article 24 affirms the rights of indigenous peoples to their traditional medicines and health practices, and to all social and health services. Although not a legally binding agreement, UNDRIP encourages nation states to comply and implement measures to support and uphold its provisions. Within the context of indigenous health and human rights, Nicaragua serves as a unique case study for examining implementation of UNDRIP Article 24 provisions due to the changes in the Nicaraguan Constitution that strive for the overarching goal of affirming an equal right to health for all Nicaraguans and supporting the integration of traditional medicine and biomedicine at a national and regional level. To explore this subject further, we conducted a review of the policy impact of UNDRIP on health services accessible to the Miskitu indigenous peoples of the North Atlantic Autonomous Region (RAAN). We found that although measures to create therapeutic cooperation are woven into Nicaraguan health plans at the national and regional level, in practice, the delivery of integrated health services has been implemented with varying results. Our review suggests that the method of policy implementation and efforts to foster intercultural collaborative approaches involving respectful community engagement are important factors when attempting to assess the effectiveness of UNDRIP implementation into national health policy and promoting traditional medicine access. In response, more study and close monitoring of legislation that acts to implement or align with UNDRIP Article 24 is necessary to ensure adequate promotion and access to traditional medicines and health services for indigenous populations in Nicaragua and beyond.


Effectiveness of polyvalent bacterial lysate for pediatric asthma control: a retrospective propensity score-matched cohort study.
Previous studies showed bacterial lysates were effective for pediatric asthma. However, evidence of polyvalent bacterial lysate Qipian is lacking. In this real-world retrospective cohort study, data of children with asthma, aged six months to 14 years old, attending to Jiangxi Provincial Children's Hospital from January 2021 to April 2022, prescribed routine treatment for asthma plus Qipian (Qipian group) or not (control group) were extracted. To minimize the impact of confounders on the outcomes, baseline characteristics were utilized to perform propensity score matching through a multivariable logistic regression model. After matching, asthma control, exacerbation, etc. were compared. Totally, 795 patients were included (337 in the Qipian group and 458 in the control group), with 278 pairs (556 patients) matched. Most baseline characteristics were well-balanced. The proportion of males were 68.3% and 70.1% in the two groups. The Qipian group favored better asthma control, with more "controlled" [3-month: 257 (92.4%) vs. 240 (86.3%); 6-month: 246 (88.5%) vs. 235 (84.5%)], and fewer "poorly/very poorly controlled" patients, compared with the control group (P=0.004 and 0.025, respectively). Patients in the Qipian group had lower risks of exacerbation. Incidence rate ratios (IRR) for any exacerbation were 0.56 [95% confidence interval (CI): 0.33 to 0.93] in the 3-month period and 0.83 (95% CI: 0.55 to 1.26) in the 6-month period. IRR for severe exacerbations were 0.09 (95% CI: 0.01 to 0.71) in the 3-month period and 0.20 (95% CI: 0.06 to 0.70) in the 6-month period (compared to the control group). Qipian significantly reduced the cumulative dose of short-acting beta-agonist (3-month: 3.22±10.37 vs. 8.08±16.71 mg; P<0.001; 6-month: 6.56±16.23 vs. 11.81±24.41 mg; P=0.002). There was no difference in incidences of respiratory tract infection or fever due to respiratory tract infection between the two groups. Numbers of antibacterial agent prescription were fewer in the Qipian group compared to the control group (3-month: 0.67±1.16 vs. 1.04±1.45; P=0.001; 6-month: 1.14±1.69 vs. 1.51±2.12; P=0.023). According to this retrospective study, Qipian may be effective for improved pediatric asthma control. Safety profile and mechanisms of action of Qipian need further investigation. Further randomized controlled trials are warranted to confirm our results.


Advanced HIV Disease at Enrolment in HIV Care: Trends and Associated Factors over a Ten Year Period in Cambodia.
Early HIV diagnosis and enrolment in care is needed to achieve early antiretroviral treatment (ART) initiation. Studies on HIV disease stage at enrolment in care from Asian countries are limited. We evaluated trends in and factors associated with late HIV disease presentation over a ten-year period in the largest ART center in Cambodia. We conducted a retrospective analysis of program data including all ARV-naïve adults (> 18 years old) enrolling into HIV care from March 2003-December 2013 in a non-governmental hospital in Phnom Penh, Cambodia. We calculated the proportion presenting with advanced stage HIV disease (WHO clinical stage IV or CD4 cell count <100 cells/μL) and the probability of ART initiation by six months after enrolment. Factors associated with late presentation were determined using multivariate logistic regression. From 2003-2013, a total of 5642 HIV-infected patients enrolled in HIV care. The proportion of late presenters decreased from 67% in 2003 to 44% in 2009 and 41% in 2013; a temporary increase to 52% occurred in 2011 coinciding with logistical/budgetary constraints at the national program level. Median CD4 counts increased from 32 cells/μL (IQR 11-127) in 2003 to 239 cells/μL (IQR 63-291) in 2013. Older age and male sex were associated with late presentation across the ten-year period. The probability of ART initiation by six months after enrolment increased from 22.6% in 2003-2006 to 79.9% in 2011-2013. Although a gradual improvement was observed over time, a large proportion of patients still enroll late, particularly older or male patients. Interventions to achieve early HIV testing and efficient linkage to care are warranted.


Probing Depth and Peri-implant Health as Related to Buccal and Lingual Bone Thickness Around Dental Implants: An Experimental Study.
A retrospective chart review was conducted of CBCT images captured between November 2019 and April 2021 on patients who underwent dental implant placement and had a periodontal charting. The buccal and lingual bone thickness around the implants was measured as an average of three measurements taken from the buccal and lingual aspects of implants. Implants with peri-implantitis were placed in Group 1, and implants with peri-implant mucositis or good peri-implant health were placed in Group 2. Wilcoxon rank sum test was used to compare the differences between the bone thicknesses of the groups. In total, 93 CBCT radiographs were screened, and 15 CBCT images with both an implant and corresponding periodontal charting were analyzed. Of the 15 implants examined, 5 presented with peri-implantitis (33%), 1 with peri-implant mucositis, and 9 with good peri-implant health. Within the limitations of this study, buccal bone thickness averaging ≥ 1.10 mm or midlingual probing depths ≤ 3.4 mm correlates with a more favorable peri-implant response. Larger studies are needed to substantiate these findings.


Exploitation of capsule system for colon targeted drug delivery of biopolymer-based microparticles: in vivo and in vitro applications.
The current study was to improve and control aceclofenac delivery prepared as biopolymer-based microparticles for effective colon-targeted drug delivery using modified gelatin capsules (MGCs) at different time intervals developed in two batches (C1 and C2). Microparticles were formulated with extracted mucuna gum using liquid paraffin oil (AC.LPO) and soybean oil (AC.SO) and evaluated in vitro for physicochemical performance and in vivo in rats. Encapsulation efficiency ranges from 54.48 ± 0.21% to 82.83 ± 0.22% for AC.LPO and 52.64 ± 0.11% to 80.36 ± 0.22% for AC.SO. SEM showed oblong and irregular shapes with porous and cracked surfaces. DSC showed low enthalpy and a very broad endothermic peak depicting high amorphous property. Delayed drug release was observed in the upper gastrointestinal tract with sustained release depicted in the lower gastrointestinal tract (GIT) using 3 and 9-h batch C1 of MGCs. AC.SO exhibited significantly (p < 0.05) higher anti-inflammatory activity (86%) than AC.LPO (77%). Hence, aceclofenac colon delivery could be improved and controlled using biopolymer-based colon-targeted microparticles delivered with MGCs.


Aging of perennial cells and organ parts according to the programmed aging paradigm.
If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.


Comparison of the elastolytic effects of human leukocyte elastase and porcine pancreatic elastase.
Porcine and bovine elastins were digested by human leukocyte elastase and porcine pancreatic elastase. The enzymes showed similarities in the extent to which they digested elastin and the pattern and quantitative distribution of N-terminal amino acids in the digests. However, fingerprints of the digests showed differences between the products of leukocyte elastase and pancreatic elastase. Each enzyme produced its characteristic fingerprint irrespective of whether the elastin substrate was obtained from ligament, pleura or lung parenchyma. The enzymes also digested tropoelastin differently. The results suggest that leukocyte elastase and pancreatic elastase should not be considered interchangeable in experimental models of tissue injury.


Protein-driven biomineralization: Comparing silica formation in grass silica cells to other biomineralization processes.
Biomineralization is a common strategy adopted by organisms to support their body structure. Plants practice significant silicon and calcium based biomineralization in which silicon is deposited as silica in cell walls and intracellularly in various cell-types, while calcium is deposited mostly as calcium oxalate in vacuoles of specialized cells. In this review, we compare cellular processes leading to protein-dependent mineralization in plants, diatoms and sponges (phylum Porifera). The mechanisms of biomineralization in these organisms are inherently different. The composite silica structure in diatoms forms inside the cytoplasm in a membrane bound vesicle, which after maturation is exocytosed to the cell surface. In sponges, separate vesicles with the mineral precursor (silicic acid), an inorganic template, and organic molecules, fuse together and are extruded to the extracellular space. In plants, calcium oxalate mineral precipitates in vacuolar crystal chambers containing a protein matrix which is never exocytosed. Silica deposition in grass silica cells takes place outside the cell membrane when the cells secrete the mineralizing protein into the apoplasm rich with silicic acid (the mineral precursor molecules). Our review infers that the organism complexity and precursor reactivity (calcium and oxalate versus silicic acid) are main driving forces for the evolution of varied mineralization mechanisms.


Neuro-rehabilitation--a challenge for neurosurgeons in the century 21st concepts and visions of the WFNS-Committee on neurosurgical rehabilitation.
Patients with severe brain, spinal cord and peripheral nerve lesions today survive surgery. This, however, is quite often achieved at the burden of disabilities. Neuro-rehabilitation could improve significantly patient's quality of life (QoL). Formed in 1997, the WFNS Committee supports all efforts regarding personal and regional activities, teaching, research, recommendations, guidelines, and practical application to improve neurosurgeon's quality management within the spectrum of rehabilitation around the world. Neuro-rehabilitation became part of the scientific programmes at the 11th EANS, 10th AANS, ICRAN 1999, and now 12th WFNS congresses. The first international conference on Neurosurgical Rehabilitation took place in D--Münster, 2000. The WFNS Committee can influence neurosurgeons to take over the challenge of neuro-rehabilitation to improve patient's outcome in respect to ICIDH-2 WHO classification. Delegates of all neurosurgical societies are kindly invited to join us.


Neurodevelopmental implications of the use of sedation and analgesia in neonates.
Laboratory studies have shown that general anesthetics may cause accelerated apoptosis and other adverse morphologic changes in neurons of the developing brain. The mechanism may be related to the neuronal quiescence or inactivity associated with anesthetic exposure. Few data exist on how brief anesthetic exposure may affect neurodevelopment in the newborn. Good evidence however shows that untreated pain and stress have an adverse effect on neurodevelopment, and therefore, at this stage, providing effective analgesia, sedation, and anesthesia would seem to be more important than concern over neurotoxicity.


A Lifetime Prevalence of Comorbidity Between Bipolar Affective Disorder and Anxiety Disorders: A Meta-analysis of 52 Interview-based Studies of Psychiatric Population.
Bipolar affective disorder has a high rate of comorbidity with a multitude of psychiatric disorders and medical conditions. Among all the potential comorbidities, co-existing anxiety disorders stand out due to their high prevalence. To determine the lifetime prevalence of comorbid anxiety disorders in bipolar affective disorder under the care of psychiatric services through systematic review and meta-analysis. Random effects meta-analyses were used to calculate the lifetime prevalence of comorbid generalised anxiety disorder, panic disorder, social anxiety disorder, specific phobia, agoraphobia, obsessive compulsive disorder and posttraumatic stress disorder in bipolar affective disorder. 52 studies were included in the meta-analysis. The rate of lifetime comorbidity was as follows: panic disorder 16.8% (95% CI 13.7-20.1), generalised anxiety disorder 14.4% (95% CI 10.8-18.3), social anxiety disorder13.3% (95% CI 10.1-16.9), post-traumatic stress disorder 10.8% (95% CI 7.3-14.9), specific phobia 10.8% (95% CI 8.2-13.7), obsessive compulsive disorder 10.7% (95% CI 8.7-13.0) and agoraphobia 7.8% (95% CI 5.2-11.0). The lifetime prevalence of any anxiety disorders in bipolar disorder was 42.7%. Our results suggest a high rate of lifetime concurrent anxiety disorders in bipolar disorder. The diagnostic issues at the interface are particularly difficult because of the substantial symptom overlap. The treatment of co-existing conditions has clinically remained challenging.


High levels of IgG3 anti ICB2-5 in Plasmodium vivax-infected individuals who did not develop symptoms.
Plasmodium vivax has the potential to infect 2.85 billion individuals worldwide. Nevertheless, the limited number of studies investigating the immune status of individuals living in malaria-endemic areas, as well as the lack of reports investigating serological markers associated with clinical protection, has hampered development of vaccines for P. vivax. It was previously demonstrated that naturally total IgG against the N-terminus of P. vivax merozoite surface protein 1 (Pv-MSP1) was associated with reduced risk of malarial infection. Immune response against Pv-MSP1 (N-terminus) of 313 residents of the Rio Pardo rural settlement (Amazonas State, Brazil) was evaluated in a cross-sectional and longitudinal follow up over two months (on site) wherein gold standard diagnosis by thick blood smear and rRNA gene-based nested real-time PCR were used to discriminate symptomless Plasmodium vivax-infected individuals who did not develop clinical symptoms during a 2-months from those uninfected ones or who have had acute malaria. The acquisition of antibodies against Pv-MSP1 was also evaluated as survival analysis by prospective study over a year collecting information of new malaria infections in surveillance database. The majority of P. vivax-infected individuals (52-67%) showed immune recognition of the N-terminus of Pv-MSP1. Interesting data on infected individuals who have not developed symptoms, total IgG levels against the N-terminus Pv-MSP1 were age-dependent and the IgG3 levels were significantly higher than levels of subjects had acute malaria or those uninfected ones. The total IgG anti ICB2-5 was detected to be an important factor of protection against new malaria vivax attacks in survival analysis in a prospective survey (p = 0.029). The study findings illustrate the importance of IgG3 associated to 2-months of symptomless in P. vivax infected individuals and open perspectives for the rationale of malaria vaccine designs capable to sustain high levels of IgG3 against polymorphic malaria antigens.


Missed irradiation of cellular blood components for vulnerable patients: Insights from 10 years of SHOT data.
Irradiation of cellular blood components is recommended for patients at risk of transfusion-associated graft-vs-host disease (TA-GvHD). Prestorage leucodepletion (LD) of blood components is standard in the UK since 1999. Analysis of 10 years' reports from UK national hemovigilance scheme, Serious Hazards of Transfusion (2010-2019), where patients failed to receive irradiated components when indicated according to British Society for Haematology guidelines (2011). There were 956 incidents of failure to receive irradiated components all due to errors. One hundred and seventy two incidents were excluded from analysis, 125 of 172 (72.7%) because of missing essential information. No cases of TA-GvHD were reported in this cohort. The 784 patients received 2809 components (number unknown for 67 incidents). Most failures occurred in patients treated with purine analogues (365) or alemtuzumab (69), or with a history of Hodgkin lymphoma (HL) (192). Together these make up 626 of 784 (79.9%). Poor communication is an important cause of errors. Leucodepletion appears to reduce the risk for TA-GvHD. None of 12 cases of TA-GvHD reported to SHOT prior to introduction of LD occurred in patients with conditions recommended for irradiated components by current guidelines. Irradiation indefinitely for all stages of HL is not based on good evidence and is a difficult guideline to follow. Further research on long-term immune function in HL is required. Variation between different national guidelines reflects the very limited evidence.


Socioeconomic status and infant nighttime sleep across the second year of life: The moderating role of infant attachment security.
This study examined socioeconomic status (SES) and attachment security as predictors of infant nighttime sleep during the second year. Participants included 128 mothers (86% White) with infants (48.4% boys). Data collection took place between April, 2009 and February, 2014. At 12, 18, and 24 months, infant sleep was assessed via actigraphy and daily diaries, and attachment with the Attachment Q-Set. SES indicators included income-to-needs ratios and education. Lower SES predicted greater variability in sleep duration and later sleep timing only for less secure infants. Less secure attachment was associated with poorer sleep at both between- and within-person levels, especially when infants were 12 months of age. Results emphasize the complex interactive effects of environmental and relational factors on infant sleep.


Experimental and theoretical studies on formation and degradation of chloro organic compounds.
Studies on oxidation of tert-butyl ethers in the presence of chloride ions proved that acid medium favoured formation of chloro organic compounds. 1,2-Dichloro-2-methylpropane, 3-chloro-2-chloromethylpropene were identified among the reaction products. Presence of these compounds was identified both in the case when methyl-tert-butyl ether (MTBE) and ethyl-tert-butyl ether (ETBE) were subjected to reaction. Reaction products were analysed by gas chromatography method with application of -FID, -MS and -AED detectors. On the basis of experimental data, the path of tert-butyl ethers conversion to dichloro products was proposed. It was found that the identified chloro derivatives could be formed both by ionic and radical reactions. In order to confirm this thesis for the proposed scheme of reaction, the theoretical calculations of molecular simulation of the reaction paths were performed.


Anatomical landmarks in anterior fontanelle ultrasonography.
Real time ultrasound via the anterior fontanelle in infants is a frequent examination. Six coronal and three sagittal planes are defined and described. These give consistent landmarks with which normal and abnormal anatomy can be correlated. The anatomy was confirmed by cutting and correlating autopsy brains at the same angulation.


Impact of Type 1 Diabetes Mellitus on Skeletal Integrity and Strength in Adolescents as Assessed by HRpQCT.
Adults with type 1 diabetes mellitus (T1DM) are at risk of premature osteoporosis and fractures. The onset of T1DM typically starts during childhood and adolescence. Thus, the effects of DM on the skeleton may be established during this period. Studies in children with T1DM primarily use DXA with conflicting results. We present the first study in adolescents assessing the impact of T1DM on skeletal microstructure and strength using HRpQCT. We recruited 22 patients aged 12 to 16 years with T1DM who were matched by age, gender, and pubertal stage with healthy controls. Paired t tests were applied to assess differences in cortical and trabecular microarchitecture measurements from HRpQCT, and skeletal strength from HRpQCT-derived microfinite element analysis. Subtotal body, lumbar, and pelvic parameters were assessed using DXA. There was no significant difference in subtotal body, lumbar spine, and pelvic BMD between T1DM and control pairs. However, tibial trabecular thickness was lower (-0.005 mm; 95% CI, -0.01 to -0.001; p = 0.029) and trabecular loading was lower at the distal radius (ratio of the load taken by the trabecular bone in relation to the total load at the distal end (Tb.F/TF) distal: -6.2; 95% CI, -12.4 to -0.03; p = 0.049), and distal and proximal tibia (Tb.F/TF distal: -5.2, 95% CI, -9.2 to -1.2; p = 0.013; and Tb.F/TF proximal: -5.0, 95% CI, -9.8 to -0.1; p = 0.047) in T1DM patients. A subanalysis of radial data of participants with duration of T1DM of at least 2 years and their matched controls demonstrated a reduced trabecular bone number (-0.15, 95% CI, -0.26 to -0.04; p = 0.012), increased trabecular separation (0.041 mm, 95% CI, 0.009-0.072; p = 0.015), an increased trabecular inhomogeneity (0.018, 95% CI, 0.003-0.034; p = 0.021). Regression models demonstrated a reduction in tibial stiffness (-0.877 kN/mm; p = 0.03) and tibial failure load (-0.044 kN; p = 0.03) with higher HbA1C. Thus, in adolescents with T1DM, detrimental changes are seen in tibial and radial microarchitecture and tibial and radial strength before changes in DXA occur and may result from poor diabetic control. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.